Endoscopic technique for the management of pancreatitis and its complications

Best Practice & Research Clinical Gastroenterology Vol. 18, No. 1, pp. 155 –181, 2004 doi:10.1053/ybega.2004.413, available online at http://www.sciencedirect.com

10 Endoscopic technique for the management of pancreatitis and its complications Myriam Delhaye MD, PhD Clinical Director Department of Gastroenterology, Hoˆpital Universitaire Erasme, Universite Libre de Bruxelles, Route de Lennik 808, Brussels 1070, Belgium

Celso Matos

MD

Clinical Director Department of Radiology, Hoˆpital Universitaire Erasme, Universite Libre de Bruxelles, Route de Lennik, 808, Brussels 1070, Belgium

Jacques Devie`re*

MD, PHD

Chairman Department of Gastroenterology, Hoˆpital Universitaire Erasme, Universite Libre de Bruxelles, Route de Lennik 808, Brussels 1070, Belgium

Therapeutic endoscopy is now increasingly used to treat gallstone pancreatitis, acute pancreatitis of other aetiologies, chronic pancreatitis and complications associated with acute or chronic pancreatitis. This chapter is a brief review of the endoscopic interventions currently performed in patients with acute or chronic pancreatitis. These interventions include biliary and pancreatic endoscopic sphincterotomy at the major or minor papilla, stricture dilatation on the common bile duct or main pancreatic duct, stent placement in the biliary or pancreatic ducts, stone extraction with or without extracorporeal shock wave lithotripsy, and transmural or transpapillary drainage of pancreatic fluid collections. As most of the studies reported were uncontrolled and retrospective, uncertainties persist with regard to the best approaches for treating the patients concerned. Appropriate patient selection, adequate expertise, and a supporting multidisciplinary infrastructure are essential prerequisites of a high success rate in improving the clinical condition of these patients. Key words: acute pancreatitis; chronic pancreatitis; gallstone pancreatitis; idiopathic acute pancreatitis; pancreatic duct disruption; pancreatic fluid collection; endoscopic sphincterotomy; pancreatic stenting; biliary stenting; extracorporeal shockwave lithotripsy; pancreatic necrosis; pancreatic stones; pancreatic duct stricture; bile duct stricture; therapeutic endoscopy; transmural drainage; transpapillary drainage.

* Corresponding author. Tel.: þ32-2-555-3712; Fax: þ 32-2-555-4697. E-mail address: [email protected] (J. Devie`re). 1521-6918/04/$ - see front matter Q 2003 Elsevier Ltd. All rights reserved.

156 M. Delhaye, C. Matos and J. Devie`re

Acute pancreatitis (AP) is best defined as an acute inflammatory process of the pancreas that may involve peripancreatic tissues and/or remote organ systems1 and is distinguished from chronic pancreatitis (CP) by the absence of continuing inflammation, irreversible structural changes, and permanent impairment of exocrine and endocrine pancreatic function.2 The management of AP remains challenging; although most patients with mild AP have self-limited disease requiring only simple supportive measures, severe AP remains potentially fatal, with a mortality rate of 10 –20%.3 Factors that have reduced mortality from AP over the past 20 years include intensive care unit management and the early recognition and treatment of complications.4 The aims of endoscopic treatment in AP include: (1) treatment of the causal factor, and (2) the management of local complications such as organized pancreatic necrosis, ductal disruption, pseudocysts or abscesses. In CP, ductal hypertension due to an outflow obstruction caused by strictures and/or stones, and interstitial hypertension due to reduced parenchymal compliance secondary to fibrosis, which is associated with reduced pancreatic blood flow, may play an important role in the pathogenesis of the disease as well as in the aetiology of pain.5 The aims of therapeutic endoscopy in CP include: (1) pancreatic ductal drainage in patients with chronic pain or recurrent attacks of pancreatitis, and (2) the treatment of complications such as pseudocyst and biliary obstruction. This chapter reviews the current strategies for endoscopic management of AP and CP.

ACUTE PANCREATITIS Management of acute pancreatitis according to aetiology Gallstone-associated acute pancreatitis In Western countries, gallstones account for about half the cases of AP. They often occur during middle age or later, and are more common in women.6 The pathogenesis of AP is due to the transient obstruction of the main pancreatic duct (MPD) and/or possible biliary reflux in the MPD.7,8 There is experimental evidence that the severity of AP is proportional to the duration of pancreatic duct obstruction.8 This justifies the attempts to remove stones early in human gallstone pancreatitis. The following criteria are suggestive of gallstone pancreatitis: sudden pain with high hydrolase levels, high liver enzyme levels (the results of a meta-analysis suggested that ALT $ 3N, measured within 24 –48 hours of onset of symptoms was the most useful predictor of a biliary origin for pancreatitis (positive predictive value: 95%9), combined with the absence of other aetiological factors, and documentation of gallstones by ultrasonography. Most patients with gallstone-associated AP experience mild-to-moderate clinical disease; initially they can be treated conservatively, as the stone will spontaneously pass into the duodenum in more than 70% of cases.10 However, attacks will recur in 29– 67% of these patients if no treatment is instituted to correct the underlying biliary tract pathology.6,11,12 The average time from the first to the second attack of gallstone-induced pancreatitis was 108 days in one study.11 Therefore, in mild gallstone-associated AP, cholecystectomy should be recommended as soon as the patient has recovered, and ideally, during the same hospital stay (recommendation grade B: based on evidence from non-randomized clinical studies).13

Endoscopic technique in pancreatitis 157

Patients with retained common bile duct (CBD) stones for whom elective endoscopic sphincterotomy (ES) is indicated can be identified by early laboratory tests showing increased bilirubin . 1.35 mg/dl on hospital day 210 or any rise in serum pancreatic and liver enzymes during the first or second day of hospitalisation14. Among patients with a lower CBD stone probability, selection for ES may be possible by endoscopic ultrasonography (EUS)15 or magnetic resonance cholangiography (MRC)16 which can detect bile duct stones with little or no invasiveness. Between 1988 and 1997, endoscopic treatment of acute gallstone pancreatitis was compared to conservative management in four randomized controlled trials17 – 20 (Table 1). The designs of these trials differed as regards whether endoscopic retrograde cholangiopancreatography (ERCP) should be performed within 24 hours18,19 or 72 hours17 of admission, or within 72 hours of the onset of symptoms20, the proportion of severe AP cases and the criteria for severity assessment, the inclusion criteria (with or without patients with biliary obstruction or impacted bile duct stone at the papilla), the indications for ES (only in patients with stones in the CBD17,18,20 or in all patients randomized for endoscopic treatment19), and single-centre17 – 19 or multi-centre20 studies. Despite these differences, the authors of a meta-analysis21 found significantly lower morbidity and mortality rates among patients undergoing endoscopic treatment than among those treated ‘conventionally’. Early ERCP and ES therefore seem safe and beneficial in acute gallstone pancreatitis. The greatest benefit from ERCP/ES might be for patients with severe acute biliary pancreatitis17,18, although the findings of the Polish trial19 suggested that all patients, irrespective of the severity of their disease, would benefit from early endoscopic intervention. Note that this benefit was dramatically reduced when the interval between symptom onset and ES exceeded 72 hours19, thus raising the concept of the ‘therapeutic window’.22 The German trial20 was much criticized for various reasons: (1) the subgroups of patients most likely to benefit from endoscopic treatment were either excluded (patients with cholangitis or jaundice), or rarely included (patients with severe AP); (2) only three centres included $ 20 patients, while 19 centres contributed fewer than an average of two patients per year, possibly reflecting the few cases treated in some of the endoscopy centres participating in this trial, a factor known to affect the safety and success of endoscopic sphincterotomy23, and (3) it was not clear why more patients receiving early ERCP experienced respiratory failure and more severe complications than the other patients. In summary, despite the lack of clearly concordant results for these four trials, we favour early intervention (ERCP and ES within 24 hours of symptom onset) for all patients with severe attacks of gallstone pancreatitis as well as for patients with predicted mild pancreatitis who have biliary sepsis. Elective ES can be performed in patients with predicted mild pancreatitis who fail to improve within 48 hours of conservative therapy, who develop subsequent biliary symptoms suggestive of retained CBD stones and also in patients not fit to undergo cholecystectomy or who have already been cholecystectomized3,6,12,13,24,25 (Figure 1). Acute pancreatitis associated with congenital variants Pancreas divisum. Pancreas divisum (PD) is the most common congenital anatomic variant of the pancreas, as it occurs in 5 –10% of Caucasian individuals and results from the failure of dorsal and ventral pancreatic duct fusion during the 2nd month of fetal life.26

RCT Author (ref) design Neoptolemos et al17 Single-centre Fan et al18,a Single-centre Nowak et al19 Single-centre Fo¨lsch et al20 Multi-centre Sharma and Howden21,b Meta-analysis a b c d e

Number of patients

Morbidity (%)

ERCP/ ES

Conservative treatment

Time to ERCP (hours)

Severe AP (%)

59

62

72c

44

64

63

24c

46

178

102

24c

24

126

112

72d

460

374

–

ERCP/ ES

Mortality (%)

Conservative treatment

ERCP/ ES

Conservative treatment

12 61 17 54 12 25 74 51

0 4e 0 3e

0 18 0 18

14

Mild AP:12 Severe AP:24e Mild AP:18 Severe AP:13e Biliary sepsis:0e Mild AP:9e Severe AP:41e Total AP:46

1e 7e 11

5 33 6

30

Total AP:25e

38

5e

9

ERCP/ES ¼ endoscopic retrograde cholangiopancreatography/endoscopic sphincterotomy; AP ¼ acute pancreatitis; RCT ¼ randomized clinical trial. Patients with non-biliary pancreatitis excluded from the analysis. Patients with non-biliary pancreatitis from the Fan study included. Time to ERCP calculated from admission. Time to ERCP calculated from symptom onset. Significant.

158 M. Delhaye, C. Matos and J. Devie`re

Table 1. Gallstone-associated acute pancreatitis: early ERCP/ES versus conservative treatment.

Endoscopic technique in pancreatitis 159

Gallstone-associated AP

cholangitis, jaundice Predicted mild

improving no cholangitis, no jaundice no prediction of retained CBD stone

Predicted severe

early ERCP/ES

fail to improve within 48th Biliary symptoms suggesting CBD stones

unfit for cholecystectomy or already cholecystectomised

Elective ERCP/ES Stop

Lap. cholecystectomy + IOC during the same hospital stay

Stop

Lap. cholecystectomy delayed until resolution of inflammatory response and clinical recovery

If CBD stones present at IOC

next day ERCP/ES Figure 1. Recommended algorithm for the management of gallstone-associated acute pancreatitis. Early ERCP/ES (within 24 hours) should be performed in all cases of predicted severe pancreatitis , ), cholangitis or obstructive jaundice ( ) whether or not CBD stones are ( present. Elective ERCP/ES should be performed within 48–72 hours of admission in patients who fail improve ), who develop subsequent biliary symptoms suggesting after 48 hours of conservative therapy ( retained CBD stones ( ), and who are either unfit for cholecystectomy or already cholecyste), with or without visible stones in the CBD. Lap. cholecystectomy should be performed ctomised ( , ) but should be delayed until during the same hospital stay for predicted mild pancreatitis ( clinical recovery in predicted severe pancreatitis ( ) and in severe biliary sepsis ( ). If CBD stones are present at IOC during lap. cholecystectomy, ERCP/ES should be performed the next day. Patients unfit for cholecystectomy or already cholecystectomized should be followed-up clinically after early ( ) or elective ERCP/ES ( ). Further studies are required to define the possible role of magnetic resonance cholangiography or endoscopic ultrasonography in this approach. ERCP/ES ¼ endoscopic retrograde cholangiopancreatography; ES ¼ endoscopic sphincterotomy; CBD ¼ common bile duct; IOC ¼ intraoperative cholangiography; Lap. cholecystectomy ¼ laparoscopic cholecystectomy.

PD has been incriminated as a cause of idiopathic acute pancreatitis, as most of the pancreatic secretion must flow through the minor papilla27, but this incrimination is still controversial26 and recent investigations using dynamic magnetic resonance pancreatography after secretin injection (S-MRCP) suggested that among patients with

160 M. Delhaye, C. Matos and J. Devie`re

pancreatic pain or acute relapsing pancreatitis, the incidence of papillary obstruction, defined as persistent dilatation of the MPD after secretin stimulation, did not differ in PD patients and those with a conjugated anatomy.28 If treatment of symptomatic PD is proposed, it consists of minor papilla sphincterotomy and/or stenting of the dorsal duct.29 In six series including a total of 87 patients with PD and recurrent acute pancreatitis, this treatment led to an improvement of 76% of patients followed-up for 20 –29 months (reviewed in refs 29 and 30). Most pain relapses occurred within 6 months, due to restenosis of the minor papilla. Morbidity attributable to endoscopic treatment was higher in patients undergoing pancreatic stent insertion into normal dorsal ducts, and the resulting ductal changes, than in those undergoing minor papilla spincterotomy (44 versus 25%). Consequently, it was suggested that the period of stenting be limited to less than 2 months.31 Because of these poor results and the uncertainty about aetiological factors, the selection of patients with PD who might benefit from endoscopic therapy remains controversial. The presence of santorinicele (defined as focal cystic dilatation of the termination of the dorsal pancreatic duct at the minor papilla)32 might be helpful in identifying a subset of patients with PD who benefit from minor papilla sphincterotomy.33 In summary, a cautious conservative attitude to the treatment of symptomatic PD patients is necessary in view of the absence of strict selection criteria indicating which patients would benefit most from endoscopic therapy, the absence of agreement on the best therapeutic approach because of the lack of randomized trials designed to compare management strategies, and the unforeseeable complications resulting from the application of endoscopic procedures to the minor papilla. Other congenital variants. Acute pancreatitis was reported in up to 31% of patients with an anomalous pancreaticobiliary union (APBU)34, defined as a junction of the CBD and MPD outside the duodenal wall forming a common channel measuring more than 15 mm in length, a rare feature with a reported incidence of 1.5 – 3.2%.35 The pathogenesis of recurrent pancreatitis in cases of APBU has been associated with temporary occlusion of the pancreatic duct by stones, protein plugs, or sphincter of Oddi dysfunction36 leading to a rise in pancreaticobiliary intraductal pressure. Most of the AP cases reported were mild and resolved in a few days with conservative treatment. Sphincter ablation by ES may reduce the risk of recurrent pancreatitis associated with APBU.37 For choledochocele, a cystic dilatation of the intramural segment of the CBD38, endoscopic biliary sphincterotomy and removal of CBD stones is a currently accepted treatment with excellent long-term results.39 Acute idiopathic pancreatitis The incidence of acute pancreatitis considered as ‘idiopathic’ should be less than 20%.3 Aetiological assessment depends on three variables: age, the number and severity of episodes, and whether or not the gallbladder is in situ.40 In the case of a first attack, it is always important to rule out the possibility of a neoplasm, especially in patients older than 40, and also to screen for intraductal papillary mucinous tumours whose initial clinical symptom is AP in up to 60% of cases.41 Magnetic resonance (MR) imaging and possibly dynamic MR are probably the best examinations to propose in this case. Small CBD stones, sludge or microlithiasis may account for many cases of ‘idiopathic’ AP, as suggested by EUS studies42,43, especially when any change in transaminase levels is observed at about the time of the attack.40,44

Endoscopic technique in pancreatitis 161

There is also a category of patients with acute relapsing pancreatitis in whom none of these causes can be shown and whose condition is defined as ‘early chronic pancreatitis’ or ‘sphincter of Oddi dysfunction’.30,44 – 46 These two entities, which probably to some extent overlap, are distinguished according to the way in which they are diagnosed, namely, by imaging (S-MRCP has replaced ERCP)46, or sphincter of Oddi manometry, which is more popular in the U.S.A., but is associated with significant morbidity.45 At present, dual ES is considered as the treatment of choice for patients with structural or functional stenosis of the sphincter of Oddi.44 However, the risk of post-sphincterotomy pancreatitis is five times higher for this indication than for other indications.23 Placement of a transient pancreatic stent might reduce this risk when the accessory duct is not patent.47 The results of various endoscopic treatments (biliary or dual sphincterotomy, or pancreatic stenting) in non-divisum patients with prior unexplained AP have only been reported for small series with a limited follow-up and their analysis is difficult, given the differences in therapies and outcomes.40,44 About 70% of such patients improved after endoscopic therapy.40 The use of pancreatic duct stents in preventing attacks of pancreatitis in patients with recurrent acute idiopathic pancreatitis has been evaluated in only one prospective randomized trial.48 Patients randomized to stent placement experienced fewer episodes of pancreatitis during nearly 3 years of follow-up, but no studies designed to evaluate their prognosis after stent removal are available. Management of complications due to acute pancreatitis Pancreatic necrosis AP is complicated by parenchymal necrosis in about 20% of patients.49 Pancreatic necrosis is defined as a diffuse or focal area of nonviable pancreatic parenchyma, which typically is associated with peripancreatic fat necrosis.1 It is best defined as non-enhancing pancreatic parenchyma revealed by dynamic contrast-enhanced CT scan (CE-CT) within 48 –96 hours of symptom onset.50 There is increasing agreement that patients with sterile necrosis should be managed medically for as long as possible in the hope that the systemic inflammatory response syndrome will eventually resolve and that surgery will not be necessary (recommendation grade B in refs13 and 51 – 54). In this connection, it has indeed been demonstrated that mortality does not improve after surgical necrosectomy in patients with sterile necrosis. However, bacterial infection occurs in 40 – 70% of cases of necrotizing pancreatitis, and this incidence increases with the duration of the disease.49 At present, this infection rate tends to be lower, thanks to the early antibiotic prophylaxis given to these patients53 and the increasing use of enteral instead of parenteral nutrition in severe AP.55 Because it is impossible to distinguish clinically between severe sterile and infected necrosis, the procedure recommended is a CT-guided percutaneous fine-needle aspiration for Gram’s stain and culture in cases of persistent systemic toxicity and/or organ failure.51 If infection is documented, surgical debridement is the treatment of choice, although it carries a complication rate of 44%.53 When necrosis is collected and liquefied, endoscopic drainage with lavage to remove necrotic tissue may be proposed as an alternative in certain cases56,57 (Figure 2). For such drainage, MRI is preferable to CE-CT for differentiating between the solid and liquid components of pancreatic necrosis in the subacute setting (. 4 weeks after symptom onset)58 (Figure 3).

(S-MRCP) deterioration

(CE-CT/MRI) deterioration

Sterile

(CE-CT/MRI) symptomatic

Infected

Partial disruption

MRI organized necrosis No

Yes

Transpapillary pancreatic stent bridging the ductal disruption

surgical debridement endoscopic transmural drainage 1 or more 10F stent(s) nasocystic catheter(s) for lavage

(CE-CT/MRI)

Complete disruption

smouldering supportive care

Pancreatic abscess

ERCP / EUS

ERCP / EUS

CT-guided percutaneous FNA

Pseudocyst

Transmural drainage

Transpapillary drainage • cyst diameter < 6 cm • communicating with the MPD • located in the pancreas head/body • non-bulging

Transmural drainage • any diameter • with or without communication with the MPD • any location • bulging (or EUS-guided, for non bulging collections)

Figure 2. Management of complications due to acute pancreatitis. Pancreatic necrosis and pancreatic pseudocyst and abscess are best diagnosed by imaging procedures such as CE-CT or MRI, whereas S-MRCP is required to identify pancreatic duct disruption. In infected pancreatic necrosis confirmed by CT-guided percutaneous FNA, MRI should be performed to differentiate the solid and liquid components of pancreatic necrosis. In case of organized necrosis, defined as a partially encapsulated, well-defined collection of pancreatic juice and necrotic debris57, endoscopic transmural drainage with lavage to remove necrotic tissue may be proposed as an alternative to surgical debridement for certain patients. In partial main pancreatic duct disruption, endoscopic transpapillary pancreatic duct stenting bridging the disruption is associated with a favourable outcome, whereas in complete duct disruption associated with pseudocyst formation, endoscopic transmural drainage is the treatment of choice. For symptomatic pseudocyst or pancreatic abscess, transpapillary drainage can be performed if the pseudocyst is less than 6 cm in diameter, when it communicates with the MPD, when it is located in the head or body of the pancreas, and when the cyst does not bulge through the gastrointestinal wall. When both transmural and transpapillary drainage are technically feasible, transmural drainage is preferable. CE-CT ¼ contrast-enhanced CT scan; MRI ¼ magnetic resonance imaging; S-MRCP ¼ secretin-enhanced magnetic resonance cholangiopancreatography; FNA ¼ fine needle aspiration; ERCP ¼ endoscopic retrograde cholangiopancreatography; EUS ¼ endoscopic ultrasonography; MPD ¼ main pancreatic duct; 10 F ¼ 10 French.

162 M. Delhaye, C. Matos and J. Devie`re

Pancreatic duct disruption

Pancreatic necrosis

Endoscopic technique in pancreatitis 163

Figure 3. A 67-year-old man with acute gallstone pancreatitis was treated by ERCP, ES and removal of a CBD stone within 24 hours of symptom onset. (A) T2-weighted MRI at admission showed severe acute pancreatitis. (B and C) Six weeks from the onset, T2-weighted MRI (B) and contrast-enhanced CT (C) showed a large collection containing a few necrotic debris, and replacing most of the pancreas. (D–F) Transmural drainage of the infected pancreatic collection. A diathermic needle was used to perform a transgastric puncture perpendicular to the area of maximal bulging (D). After injection of contrast medium and insertion of a guide-wire (E), the puncture site was enlarged using a cystenterostome, and a double pigtail 4 cm10 F stent was placed in the collection (F). ERCP ¼ endoscopic retrograde cholangiopancreatography; ES ¼ endoscopic sphincterotomy; CBD ¼ common bile duct; MRI ¼ magnetic resonance imaging; CT ¼ computed tomography; 10 F ¼ 10 French.

164 M. Delhaye, C. Matos and J. Devie`re

Indications for non-surgical drainage include persistent abdominal pain and/or evidence of infection attributable to well-defined, organized and liquefied collections that persist for several weeks after acute necrotizing pancreatitis. Drainage includes transgastric and/or transduodenal stenting with placement of nasocystic catheters for lavage, which are left in position until the collection collapses.56,57 Technical and clinical success was reported for this indication in an average 70% of cases, thus avoiding surgery.57 However, complications occurred in 37% and consisted mainly of procedure-induced infection when endoscopic drainage of sterile necrosis was attempted.57 Percutaneous drainage can mostly be used as adjuvant therapy to endoscopic or surgical treatment of undrained peripheral collections. Its primary use should be avoided when pancreatic duct rupture is suspected, because it may favour the development of pancreatic fistulae. Pancreatic duct disruption Pancreatic duct disruption is defined as extravasation of contrast medium from the ductal system, as visualized by ERCP.59 Disruption may be characterized by the site of pancreatic duct disruption (head, genu, body or tail), the extent of this disruption, which may be partial (opacification of the proximal duct upstream of the leak) or complete (no visualization of the duct upstream of the leak, and loss of ductal continuity) and the associated complications (pseudocyst, pancreatic ascites, pleural effusions, or fistula inside the colon, small bowel or biliary system or outside the skin). Pancreatic duct leak does not occur in clinically mild AP60 but may be observed in 30 –50% of patients with severe pancreatic necrosis.60 – 62 Currently, S-MRCP is increasingly used as a non-invasive alternative to diagnostic ERCP63 and can reveal ductal rupture in the setting of severe AP (unpublished observations). As direct contrast medium injection into the pancreatic ductal system is not performed, it is not known whether such visualized rupture by S-MRCP requires immediate specific management. The treatment of ductal leaks associated with severe AP comprises conservative management designed to reduce pancreatic stimulation (nothing by mouth, total parenteral/enteral nutrition, and octreotide) and drainage of the MPD and of the associated collections. Most leaks can be safely managed without surgery.61,62,64 In partial duct disruption, endoscopic transpapillary pancreatic duct stent placement converts the normally high-pressure pancreatic duct into a low-pressure system, with preferential flow through the stent. A stent bridging the duct disruption, so that its proximal end was upstream of the disruption, was associated with resolution of the disruption in 92% of cases, compared to 50% when the stent was placed adjacent to the disruption, and 44% when a short stent was placed across the papilla.59 In multivariate analysis, only the bridging stent position remained correlated to a successful outcome, whereas the site and the extent of ductal disruption (partial or complete) did not differ significantly according to outcome.59 In complete disruption of the MPD combined with pseudocyst formation, endoscopic transmural drainage is the treatment of choice64 (Figures 2 and 3). Pseudocyst and abscess An acute pseudocyst is a collection of pancreatic juice enclosed by a wall of fibrous or granulation tissue formed after an attack of AP.1

Endoscopic technique in pancreatitis 165

Acute pseudocysts develop in 10 – 25% of patients with acute necrotizing pancreatitis and resolve spontaneously in 30– 50% of cases within 2 months of onset.50,51 There is no proven strategy to facilitate the resolution of a pancreatic pseudocyst. Asymptomatic pseudocysts require no specific treatment. The decision to drain is based chiefly on symptoms: severe abdominal pain, symptoms of biliary or gastric outlet obstruction and clinical signs suggesting infection of the pseudocyst (an infected acute pseudocyst is currently called a pancreatic abscess).1,3,65 Symptomatic pseudocysts can be decompressed by surgical, radiological or endoscopic methods.51 Percutaneous drainage is associated with lower morbidity and mortality than surgical drainage but requires a long drainage period, and cutaneous fistulas are likely to occur if the pseudocyst communicates with the MPD.66 Therefore endoscopic drainage is recommended as the treatment of choice and consists of cystogastrostomy or cystoduodenostomy with insertion of one or more stents (Figure 3). The stents are generally left in place until resolution is radiographically documented and may then be endoscopically removed.65 – 67 It is not known whether the stent(s) can be left in place for longer periods. In cases of communicating pseudocyst associated with complete ductal disruption, we currently favour long-term transmural stenting to keep the fistula through the digestive tract open. Endoscopic therapy, which was previously limited to collections overtly bulging into the gastrointestinal tract, has now become accessible to most collections thanks to therapeutic endoscopic ultrasonography.68,69

CHRONIC PANCREATITIS Chronic pancreatitis (CP) is a progressive disease for which there is no curative treatment. Therapeutic efforts have therefore concentrated on alleviating the severe pain associated with this condition. Interventional endoscopy has been increasingly used to treat CP over the last 20 years, with clinical results comparable to those of conventional surgery.70,71 However, unlike surgery, endoscopic therapy can be repeated in response to the recurrence of pain, and has a high clinical success rate close to that for the initial therapy.72 Moreover, age is not a risk factor for procedure-related morbidity, and the overall complication rate is low.73 Consequently, endoscopic management appears to be both a safe and successful alternative to surgery. Treatment should be initiated as soon as possible after CP diagnosis, because this reduces costs and increases the probability of long-term clinical benefit.72,74 Pancreatic ductal obstruction Pancreatic ductal obstruction may be due to the presence of intraductal obstructive stone(s), stricture(s) of the MPD, or both (Figure 4). In a multicentre study of more than 1000 patients with painful CP, these causes were, respectively, recorded in 18, 47 and 32% of cases.73 Obstructive pancreatic ductal stones Successful endoscopic stone extraction after endoscopic pancreatic sphincterotomy (EPS) depends on the size (# 10 mm), number (# 3) and pancreatic location (head/body) of the stones75, and may not be possible if strictures are present, or

166 M. Delhaye, C. Matos and J. Devie`re Figure 4. A 53-year-old alcoholic man presented with recurrent epigastric pain which had started 1 year previously and continuous pain the previous 2 weeks, weight loss, but not diabetes or steatorrhoea. Plain film centred on calcified pancreatic stones in the head of the pancreas before (A) and immediately after one session of ESWL (A’). Good fragmentation was obtained. Non-enhanced CT scan centred on the pancreatic head (B) and body (C) also showed typical calcified stones, mainly in the head of the pancreas. S-MRCP before ESWL (D) showed upstream dilatation of the MPD, above the ductal obstruction at the genu. Pancreatic exocrine function was preserved, as shown by normal duodenal filling after IV secretin administration. ESWL ¼ extracorporeal shock wave lithotripsy; CT ¼ computed tomography; S-MRCP ¼ secretin-enhanced magnetic resonance cholangiopancreatography; MPD ¼ main pancreatic duct; 10 F ¼ 10 French.

Endoscopic technique in pancreatitis 167

when the stones are impacted in the ductal wall. Since 1987, extracorporeal shock wave lithotripsy (ESWL), which allows millimetric fragmentation of pancreatic stones (Figure 4), has facilitated endoscopic extraction of MPD stones and is necessary in 36 –68% of patients with CP.72,76 – 78 The best fragmentation is obtained with a two-dimensional radiological targeting system and rapidly rising pressures of up to 500 –1000 bars within the focal area, under conscious sedation or general anaesthesia when ESWL and therapeutic ERCP are performed during the same session. If calcified stones are present, ESWL is now mostly performed as a first procedure, before therapeutic ERCP. Successful fragmentation was reported for a very high percentage of patients in most series, regardless of the shock wave system used72,76 – 83 (Table 2), but was lower in two series81,82 in which ultrasound only was used to locate the stones. Stone fragmentation should be accompanied by the relief of ductal obstruction, shown by a decrease in MPD diameter and by ductal clearance. In a multivariate analysis of 70 patients with CP, ESWL was classified as the best independent predictor of complete MPD clearance74, whereas the initial size or number of MPD stones did not correlate with complete clearance. In another study83, complete clearance of MPD stones was obtained spontaneously in 24/32 patients (75%) using ESWL only. Note that in this series, 22 patients had no pancreatic ductal stricture, only two presented with steatorrhoea, and the others had good residual exocrine function. This suggests that ESWL alone could be helpful in cases with a single impacted stone and no stricture. Therapeutic ERCP includes EPS as the first step in improving access to the pancreatic duct prior to pancreatic stone extraction. Biliary sphincterotomy is recommended in conjunction with EPS in cases of cholangitis or obstructive jaundice, when there is high-grade cholestasis (CBD diameter $ 12 mm and increased alkaline phosphatase $ 2N) or when it is technically necessary to improve access to the MPD.84 Table 2. Results of ESWL and/or endotherapy for severe chronic pancreatitis (selected series of more than 30 patients).

Author (ref) (year)

Complete Number Fragmentation clearance of patients (%) (%)

Complete or partial pain relief (%)

Need for Mean surgery follow-up (%) (months)

ESWL and endotherapy Delhaye et al (1992)76 Schneider et al (1994)79 Johanns et al (1996)80 Costamagna et al (1997)77 Adamek et al (1999)81 Brand et al (2000)82 Kozarek et al (2002)78 Farnbacher et al (2002)72

123 50 35 35 80 48 40 114

99 86 100 100 54 60 100 82

59 60 46 74 ND 44 ND 46

85 62 83 72 76 82 80 48% (complete)

8 12 14 3 10 4 20 13

14 20 23 27 40 7 29 29

ESWL alone Ohara et al (1996)83

32

100

75

86

3

44

ESWL ¼ extracorporeal shock wave lithotripsy; ref ¼ reference number; ND ¼ not determined.

168 M. Delhaye, C. Matos and J. Devie`re

EPS is performed after deep cannulation of the MPD by means of a standard pull-type sphincterotome threaded over a guidewire (Figure 5), using only pure cutting current to prevent damage to the pancreas and possible further development of stenosis.85 An alternative method has been proposed, consisting of the use of a needle knife to cut the pancreatic sphincter over a previously inserted pancreatic stent.86 However, in CP it is often very difficult to insert a stent before stone removal, which greatly limits the use of the needle knife technique. In case of dominant dorsal duct (i.e. complete or incomplete pancreas divisum or ansa pancreatica), the minor papilla is opened by a technique similar to that used for major papilla pancreatic sphincterotomy.87 The early complication rate of EPS appears to be lower in CP than in other indications, perhaps because of the periductal fibrosis and limited amounts of nearby acinar tissue associated with CP.86 Early complications occur in 4.2 – 16% of cases and include the exacerbation of mild pancreatitis (2.9 – 9%), bleeding (0 – 3.6%), cholangitis (3.6 – 4.3%) and in rare instances, perforation.74,86 Late stenosis of the sphincterotomy site was reported in one study to be as high as 14%86, probably due, according to the authors, to the relatively small incision used early in their experience, but perhaps also, in our opinion, to the blended current used to perform pancreatic sphincterotomy in that series. Clinical improvement, assessed by complete or partial pain relief, increase in body weight and improvement of exocrine function, was observed in 62 –86% of the patients in the largest reported series, during a mean follow-up ranging from 7 to 44 months (Table 2). Immediate pain relief was independently associated with MPD clearance74 whereas the independent predictors of pain relapse at long-term follow-up (46% after 2 years) were very frequent episodes of pain before treatment, long duration of disease before treatment, and the presence of a non-papillary stricture of the MPD.74 These findings suggest that treatment soon after the onset of CP also affects long-term outcome in a positive manner. After ESWL, complications such as organ damage or acute pancreatitis are rare (0– 12.5%), and overall morbidity is primarily due to associated endoscopic procedures. No mortality was reported in the largest published series.76 – 83 Stone recurrence was found in 48% of cases treated by ESWL at a mean follow-up of 7.4 months.72 Calculated stone-free survival time was 18.5 months. The technical and clinical success rates for treatment of recurrent stones were comparable to those of the initial treatment.72 The recommended algorithm for therapeutic approaches to patients with pancreatic stones is shown in Figure 6. Three variables should be considered: the stones, the MPD, and the pancreatic exocrine function. Small or radiolucent stones can be endoscopically retrieved after EPS, using conventional balloons or Dormia baskets (Figure 5(C)). For patients with calcified stones but without associated tight stricture and with good residual exocrine function, ESWL alone could be proposed as a possible first-line treatment, perhaps in the framework of a randomized trial (Dumonceau JM et al, personal communication, AGA meeting 2003), and endotherapy could be considered in cases where this approach is not successful. Pancreatic duct stricture(s) Strictures of the MPD may be a complication of a previously embedded stone or a consequence of acute inflammatory changes around the MPD.71 Ductal stricture is defined as high-grade narrowing that involves at least one of the following: (1) induction

Endoscopic technique in pancreatitis 169

Figure 5. Same patient as that shown in Figure 4, after ESWL. (A) ERCP showed a normal common bile duct, multiple intraductal pancreatic stones corresponding to the fragments of stones visible on the plain film, and dilatation of the MPD above the genu. (B) Endoscopic pancreatic sphincterotomy was performed after deep cannulation of the MPD by means of a standard pull-type sphincterotome threaded over a guidewire. (C) A Dormia basket was inserted along the guidewire and was used to remove stone fragments from the pancreatic duct. (D) Pancreatography through a 6 F nasopancreatic catheter showed no significant stricture of the MPD. ESWL ¼ extracorporeal shock wave lithotripsy; ERCP ¼ endoscopic retrograde cholangiopancreatography; MPD ¼ main pancreatic duct; 6 F ¼ 6 French.

170 M. Delhaye, C. Matos and J. Devie`re

Variable

Treatment

Stones small ∅ < 3 mm radiolucent

Endotherapy alone

calcified

MPD stricture

ESWL alone

Exocrine function good ESWL + endotherapy reduced Figure 6. Recommended algorithm for therapeutic approaches to patients with chronic pancreatitis ). For associated with ductal stones. Endotherapy alone is applicable to small or radiolucent stones ( patients with calcified stones, no MPD stricture, and good residual exocrine function, ESWL alone can be ). ESWL combined with endotherapy should be reserved for recommended as a first-line option ( cases in which pain relief is not obtained with ESWL alone ( ). MPD ¼ main pancreatic duct; ESWL ¼ extracorporeal shock wave lithotripsy; B ¼ diameter.

of upstream MPD dilatation ($ 6 mm in diameter), (2) prevention of contrast medium outflow beside a 6F nasopancreatic catheter and/or (3) pain during catheter perfusion with normal saline (1l/24 hours). Before pancreatic duct stent insertion, the duct stricture must be dilated, using either graduated 6-10 F Teflon bougies (Wilson-Cook Medical, Winston-Salem, NC, U.S.A.) or more effectively, 4 – 6 mm hydrostatic Maxforce balloon catheters (Microvasive, Boston Scientific International, Watertown, MA, U.S.A.) or again the Soehendra stent retriever (Wilson-Cook Medical, Winston-Salem, NC) which has a screw at its end that can be rotated to core a path through a high-grade stricture.88 The polyethylene stents used are those with the largest diameter that can traverse the stricture (8.5 or 10 F), as larger-bore stents have longer patency rates.89 Stent length is adapted to the anatomical features and location of the stricture. The possibility of inserting 2 or 3 8.5 F or 10 F stents into the MPD is currently under investigation in several centres to establish whether it can lengthen the interval between stent replacements (Figure 7). Before stent insertion into the MPD, attempts to exclude occult malignancy must be made. They should include brush cytology and screening for K-ras gene mutations, especially for patients without pancreatic calcification.90

Endoscopic technique in pancreatitis 171

Figure 7. A 57-year-old non-alcoholic woman presented with epigastric pain and weight loss. (A) Pancreatography showed distal stricture and upstream dilatation of the main pancreatic duct (MPD diameter: 6.3 mm). Side branches were massued and shortened, features typical of chronic pancreatitis. (B) Two polyethylene stents (one C loop 10 F and one straight 8.5 F) were implanted in the MPD to allow adequate drainage of pancreatic secretions. (C and D) MRCP before pancreatic duct stenting (C) and 7 months afterwards (D) showed a significant decrease in MPD diameter, and patency of the pancreatic stents. MPD ¼ main pancreatic duct; MRCP ¼ magnetic resonance cholangiopancreatography; F ¼ French.

172 M. Delhaye, C. Matos and J. Devie`re

During the past decade, the outcome of pancreatic duct stent placement was evaluated in four major series.71,91 – 93 Overall, successful stent placement was achieved in 96– 100% of CP patients. Immediate pain relief was recorded in 82%93 and 94%71, and at 6 months improvement was lasting in 74%.91,92 In the absence of early symptomatic improvement, the stent should be removed because ductal hypertension is not likely to be the cause of pancreatic pain, so that other causes can be considered. In this connection, the clinical results of pancreatic stenting are also a good predictive factor for the outcome of derivation surgery. In some cases, stents, even when clogged, may function like a wick around which pancreatic juice can drain.91 Our current strategy is to replace the stent when the patient becomes symptomatic, i.e. experiences recurrent abdominal pain or an acute bout of pancreatitis combined with recurrent MPD dilatation, shown by transabdominal ultrasound or S-MRCP. This strategy means that stent replacement is required after a mean period of 12 months (range: 2 – 38).71 Long-term pain relief is experienced by about two-thirds of patients after stenting.91 However, resolution of the stricture after stent removal was observed only in a minority of patients.71,93 Fortunately, stricture calibration is not a prerequisite for improvement of symptoms.92,93 For example, stents could be removed from 49 out of 93 patients (53%) after a mean period of 15.7 months, and 73% of these patients remained pain-free without a stent during a mean follow-up of 3.8 years.91 Long-term pain relief after pancreatic stenting was also found to be associated with a shorter history of symptomatic CP91, thus arguing in favour of early ductal drainage in CP patients. Besides clogging, stent migration can also occur either distally into the duodenum, or proximally into the MPD. In the latter case, endoscopic retrieval is sometimes technically difficult and is done with a rat-tooth forceps, baskets or balloon catheters.94 Duodenal wall injury has also been recorded as a complication caused by distal migration of a pancreatic stent.93 Concern has been expressed about potential stent-induced pancreatic ductal changes, mainly described when stents are placed in normal ducts.95 However, in patients with severe CP, any such changes are unlikely to have clinical consequences. Surgical procedures were performed in 12 –26% of cases after pancreatic stenting71,73,91 – 93, for the following reasons: (1) failure to respond to endoscopic treatment, (2) to cure complications in the form of pancreatic abscesses in a few patients91, and (3) in cases where despite clinical improvement after stenting, excessively frequent stent replacements were necessary during follow-up. In a recent large retrospective multicentre study including 996 patients, 599 (60%) had completed endoscopic pancreatic ductal drainage after a mean follow-up of 4.9 years, 159 (16%) were still having continuing endoscopic treatment (mostly with stents in situ), and 238 (24%) had undergone surgery.73 However, 10% of the patients who underwent surgical drainage continued with some form of endoscopic pancreatic therapy after surgery. Overall, on an intention-to-treat basis, two-thirds of the patients in this series with painful obstructive CP at initial presentation can be expected to be completely or nearly free of pain after 5 years, without needing surgery.73 No significant improvement in endocrine or exocrine pancreatic functions had been shown in this retrospective series. In summary, the following strategy can be proposed: when a pancreatic stricture is present, treatment begins with EPS, stricture dilatation and stone removal, followed by the placement of an initial 10 F pancreatic stent. The patient is followed-up clinically every 6 months on an out-patient basis, with plain films and US or S-MRCP performed at each visit. If the symptoms recur, the stent is replaced and this strategy is maintained

Endoscopic technique in pancreatitis 173

for at least 24 months. At that time, stents are removed, and clinical results assessed. If the improvement of symptoms persists, the patient is nevertheless kept under observation regardless of the radiological appearance of the ducts. If the symptoms recur after stent removal, the stent is replaced by one with the largest diameter possible or by 2/3 stents. Surgical drainage can also be considered, mainly for patients without surgical contraindications who are good responders to stent therapy. Complications Pseudocyst In the setting of CP, pseudocyst formation can follow acute exacerbation of pancreatitis, or can result from the rupture of a side branch of the MPD or of the MPD itself, thus allowing the gradual escape of pancreatic juice into the surrounding tissue. Ductal rupture is mostly secondary to downstream ductal obstruction due to stones, protein plugs or strictures.96 Pancreatic pseudocysts may complicate the course of CP in 20 –40% of cases, and less than 10% of these cases will resolve spontaneously.97 The cyst wall is composed of fibrous and granulation tissue and the cystic fluid is rich in amylase. The indications for pseudocyst drainage are the presence of symptoms, cyst enlargement, or complications. Cysts more than 4 cm in diameter located in the body or tail of the pancreas, or exhibiting extrapancreatic development, are likely to require drainage.98 Asymptomatic pseudocysts can safely be kept under observation provided they are carefully monitored and do not increase in size.99 Complications arising from pseudocyst include obstruction of any part of the gastrointestinal tract and biliary obstruction (, 10% of cases), vascular occlusion, the formation of a fistula in the pleural cavity, pericardium or adjacent viscera, spontaneous infection resulting in abscess formation (, 10%), digestion of an adjacent vessel with the development of a pseudoaneurysm, and free rupture in the peritoneal cavity (, 3%).96,99 Patient selection is of paramount importance for the exclusion of the possible presence of an acute fluid collection likely to resolve, of a cystic neoplasm (by cyst fluid analysis) and of an associated pseudo-aneurysm which occurs in about 10% of patients with pseudocysts.96 In the latter case, arterial embolization with radiological coils or gel foam must be done before cyst drainage is attempted.100 In the opinion of the authors of this chapter, S-MRCP is at present mandatory for the planning of pseudocyst drainage, in particular to determine the following: the size, number and location of the pseudocyst(s), the proportions of fluid and necrotic debris in the cystic content, the presence of associated ductal lesions, including downstream ductal obstruction or ductal rupture, the presence of a communication between the ductal system and the pseudocyst, and the presence of associated vascular lesions such as a pseudo-aneurysm or venous thrombosis, and assessment of the compression of adjacent organs (stomach, duodenum and CBD). Endoscopic treatment is currently recommended as the treatment of choice for pseudocyst drainage.101 Two major endoscopic routes are recommended: the transmural and transpapillary routes, which if necessary can be combined. The major limitations of transmural drainage were the requirements of a pseudocyst bulging into the stomach or duodenum, and close proximity of the pseudocyst to the gut lumen.102,103 However, the development of larger channel linear array echoendoscopes has rendered transmural drainage feasible, even when no pseudocyst bulging is detected at endoscopy, and when the gut lumen is more than 1 cm away from the pseudocyst.68,69 This has considerably broadened the indications for the endoscopic

174 M. Delhaye, C. Matos and J. Devie`re

approach to cystic fluid collections in CP, as 42 –45% of these collections were non-bulging.69,104 After drainage, a transmural stent is left in place to keep the fistula open. In our experience, these stents are not always removed, the strategy being to leave the stent in place, at least in all cases in which the presence of communication between the pseudocyst and the MPD has been demonstrated or suspected.69 Transpapillary drainage may be effective for the drainage of small, solitary, communicating pseudocysts (diameter: , 6 cm), which comprise 50– 60% of chronic pseudocysts and are located far from the gastric and duodenal wall, especially when they are combined with downstream ductal obstruction by stones or strictures.97,102,104 It is important to deal with such ductal stones or strictures because failure to relieve ductal obstruction may result in recurrence of the pseudocyst.96 Transpapillary drainage is not indicated for end pancreatic fistula, transsected duct syndrome or large pseudocysts with debris. For these conditions, transmural cystenterostomy should be the preferred method of drainage, possibly combined with transpapillary stent placement. When both transmural and transpapillary drainage are technically feasible, we currently favour transmural drainage because transpapillary drainage is dependent on stent patency. In the literature, technically successful pseudocyst drainage was achieved by endoscopic therapy in 80 – 95% of cases, with a recurrence rate of 10 –20%.57,96,101,104 In a review of published trials97, initial clinical resolution was observed in 104 out of 121 patients (86%) after transmural drainage and in 98 out of 117 (84%) after transpapillary drainage. Long-term success rates were reported in 75% of these cases during mean follow-ups of 9 –48 months after endoscopic cystenterostomy, and 15 – 37 months after transpapillary cyst drainage. Surgery was required in 11– 35% of cases, mainly for initial failure of the treatment or late pseudocyst recurrence.105 Today, this rate is clearly lower, thanks to the advent of EUS-guided cyst drainage. Complications of pseudocyst drainage procedures occur in about 10% of patients.96,97 The main complications reported after transmural drainage are bleeding and retroperitoneal leakage. Bleeding results from the rupture of an undetected pseudo-aneurysm or of a gastric wall vessel. Coil embolization by angiography of the bleeding vessel, or endoscopic coagulation at the puncture site using the cystenterostome usually succeeds in controlling this bleeding.96,100 Rupture of a pseudo-aneurysm often occurs several days after cyst drainage. In that case, angiography and transarterial embolization are clearly the first line diagnostic and therapeutic procedures to perform. Retroperitoneal leakage or pneumoperitoneum generally resolve spontaneously under antibiotic therapy.69 When such leakage occurs during treatment, cyst drainage has to be performed despite the leakage, to allow resolution of the pseudocyst and avoid peritoneal leakage of the cystic content. Additional percutaneous drainage for single loculation in the periphery of the cyst, or surgical drainage, may be required if the pseudocyst is multiloculated, large, or contains abundant necrotic debris, or if the patient develops systemic sepsis.96 Common bile duct stricture Intrapancreatic CBD stricture occurs in 3– 46% of patients with CP101 and is caused by fibrotic changes in the head of the pancreas or compression of the CBD by a pancreatic pseudocyst. CBD stricture is defined as a distal narrowing of the CBD with proximal dilatation of $ 12 mm above the stricture and delayed drainage of contrast medium into

Endoscopic technique in pancreatitis 175

the duodenum. In CP, characteristic CBD strictures mostly involve the long, regular, intrapancreatic stenosis or the short hour-glass stricture.106 Most CBD strictures in CP are not clinically significant and require no intervention. Biliary drainage is indicated in patients with cholangitis, jaundice, or increased alkaline phosphatase ($ 2N) persisting for 4 weeks or more and resulting from a CBD stricture. Its aim is to prevent long-term complications such as recurrent cholangitis and secondary biliary cirrhosis. The possible presence of a malignant stricture should always be ruled out by brush cytology, especially in asymmetrical stenosis. The initial treatment consists of stricture dilatation, usually with straight, single or multiple, large-bore polyethylene 10 F stents106, but this treatment has the drawback of being liable to cause rapid occlusion due to stent clogging, which may result in cholangitis. In our series107, stent clogging occurred in 42% of patients after a mean period of 6.5 months. Another cause of stent dysfunction is stent migration, reported in 15% of cases in four combined series106, i.e. much more frequently than in malignant stenosis. Although biliary stenting was technically successful in 100% of patients and led to the immediate clinical resolution of symptoms in all cases, it resulted in sustained benefit in only about 25% of cases (16 – 32%), 12 –46 months after stent removal.107 – 110 Consequently, surgical biliary bypass should be proposed for patients who are fit to undergo surgery and have persistent symptomatic strictures after at least 1 year of stenting. For patients with recurrent plastic biliary stent obstruction who are poor surgical candidates, placement of an expandable metallic stent may be a reasonable solution for obtaining long-term palliation.111,112

SUMMARY Thanks to the low invasiveness and safety of endoscopic therapy, it is now widely used as a first-line treatment for patients with acute or chronic pancreatitis. In gallstone pancreatitis, the results of four randomized controlled studies in which endoscopic treatment was compared to conservative management indicate that the use of ERCP/ES should depend on the predicted severity of the disease and on its biliary symptoms. In recurrent acute idiopathic pancreatitis, whether or not it is associated with congenital variants, including pancreas divisum, the selection of patients likely to benefit from endoscopic therapy remains controversial, as does the choice of the best treatment for these patients. Further studies are required to solve these problems. For first-line management of the complications of severe acute pancreatitis, the present trend is to favour a non-surgical approach. There is indeed increasing agreement that patients with sterile pancreatic necrosis should be managed conservatively, while patients with infected necrosis and clinical signs of sepsis should be treated by surgical or other methods of drainage, once the infected material has liquefied sufficiently. For patients who develop symptomatic fluid collections as a result of necrosis liquefaction, or ongoing ductal leak, or both, the treatments of choice include transpapillary stenting to bridge duct disruption, and endoscopic transmural drainage of adjacent collections. For patients with painful chronic pancreatitis, endoscopic therapy is now proposed as a first-line approach to the relief of main pancreatic duct obstruction by one or

176 M. Delhaye, C. Matos and J. Devie`re

several stones and/or strictures. The best results are obtained when endotherapy is performed early in the course of CP. After this treatment, about two-thirds of the patients concerned can be expected to become free of pain during the long-term follow-up. The complications of chronic pancreatitis are mainly the development of pseudocyst secondary to the downstream ductal obstruction, and biliary obstruction caused by fibrotic changes in the head of the pancreas. Successful endoscopic pseudocyst drainage is currently obtained in most patients, and carries a low complication rate. Biliary stenting is a safe and effective technique for the acute treatment of symptomatic bile duct stricture due to chronic pancreatitis, but permanent resolution is obtained in only 25% of cases. In conclusion, endoscopic management is now considered to be the preferred interventional treatment of acute and chronic pancreatitis, for patients selected on the basis of the anatomical changes caused by the diseases. This treatment is generally safe, minimally invasive, often effective for years, does not prevent further surgery, and can be repeated.

Practice points Acute pancreatitis † acute pancreatitis is a potentially fatal disease; it is severe in 20 – 25% of patients and still carries a mortality rate of almost 10% † severe pancreatitis is defined by early prognostic signs (Ranson’s criteria and the CT severity index), organ failure, local complications or clinical deterioration † for patients with severe gallstone pancreatitis or with jaundice or cholangitis associated with acute pancreatitis, the morbidity and mortality risks will be lower if urgent ERCP and endoscopic sphincterotomy (ES) are performed † patients with mild gallstone pancreatitis who fail to improve within 48 hours of conservative therapy, who display indirect evidence of retained common bile duct stones, who are unfit for further cholecystectomy, or who have already been cholecystectomized are also candidates for elective ERCP and ES † most of the congenital variants of the biliopancreatic ductal system, including pancreas divisum, are clinically irrelevant † there is no agreement regarding the selection of those patients with symptomatic pancreas divisum most likely to benefit from endoscopic therapy, or regarding the best treatment for such patients † patients with sterile pancreatic necrosis should be managed conservatively † fine-needle aspiration is the only reliable test for diagnosing infected necrosis † infected pancreatic necrosis in patients with clinical signs of sepsis is an indication for intervention, including surgical debridement or endoscopic drainage procedures † in partial disruption of the main pancreatic duct, endoscopic transpapillary pancreatic stent placement bridging the leakage is associated with a favourable outcome, whereas in complete duct disruption, endoscopic transmural drainage is the recommended treatment

Endoscopic technique in pancreatitis 177

Chronic pancreatitis † magnetic resonance imaging may be helpful in selecting the appropriate treatment of chronic pancreatitis and its complications † endotherapy is a reasonable alternative to surgery for the subgroup of patients with painful chronic pancreatitis who display the following features: W dilatation of the main pancreatic duct due to outflow obstruction by one or more strictures and/or stones W fluid collections resulting from downstream ductal obstruction or disruption of a pancreatic duct W obstruction of the common bile duct caused by fibrotic changes in the pancreas or compression by a pancreatic pseudocyst † definitive treatment can be expected in 66% of patients after completion of endoscopic pancreatic ductal drainage, in more than 75% after endoscopic drainage of pseudocyst, but in only 25% after biliary stenting

Research agenda † the role of EUS/MRC in the selection of patients for urgent or elective ES in the management of gallstone pancreatitis needs to be defined † in acute idiopathic recurrent pancreatitis, whether or not it is associated with anatomical variants, the patients most likely to benefit from endoscopic therapy, and the choice of the most reliable endoscopic technique for these patients, need to be defined by further prospective randomized studies † non-surgical management of infected necrosis by transmural endoscopic drainage should be compared to open surgery for efficacy, safety and costeffectiveness † controlled trials designed to compare the results of endoscopic, radiological, and surgical treatments are needed to determine the optimal management strategy in pancreatic duct disruption associated with pancreatic fluid collections † the technical and clinical results obtained after ESWL alone or ESWL plus endoscopic ductal drainage in chronic pancreatitis associated with ductal stones should be compared, to identify the best candidates for treatment by ESWL alone † methods of preventing the recurrence of MPD stones must be investigated

REFERENCES * 1. Bradley E. A clinically based classification system for acute pancreatitis. Archives of Surgery 1993; 128: 586 –590. 2. Cotton PB & Sarner M. International workshop on pancreatitis, cambridge, March 1993. In Gyr KE, Singer MV & Sarles H (eds) Pancreatitis, Concepts, and Classification. Amsterdam: Elsevier Science Publishers BV, 1983, pp 239 –241. 3. British Society of Gastroenterology, United Kingdom guidelines for the management of acute pancreatitis. Gut 1998; 42(supplement 2): S1– S13. 4. Bank S, Singh P, Pooran N & Stark B. Evaluation of factors that have reduced mortality from acute pancreatitis over the past 20 years. Journal of Clinical Gastroenterology 2002; 35: 50–60.

178 M. Delhaye, C. Matos and J. Devie`re 5. Karanjia ND & Reber HA. The cause and management of the pain of chronic pancreatitis. Gastroenterology Clinics of North America 1990; 19: 895–904. 6. Frakes JT. Biliary pancreatitis: a review. Journal of Clinical Gastroenterology 1999; 28: 97 –109. 7. Acosta JM & Ledesma CL. Gallstone migration as a cause of acute pancreatitis. New England Journal of Medicine 1974; 290: 484– 487. 8. Ru¨nzi M, Saluja A, Lerch MM et al. Early ductal decompression prevents the progression of biliary pancreatitis: an experimental study in the opossum. Gastroenterology 1993; 105: 157 –164. 9. Tenner S, Dubner H & Steinberg W. Predicting gallstone pancreatitis with laboratory parameters: a metaanalysis. American Journal of Gastroenterology 1994; 89: 1863–1866. 10. Chang L, Lo SK, Stabile BE et al. Gallstone pancreatitis: a prospective study on the incidence of cholangitis and clinical predictors of retained common bile duct stones. American Journal of Gastroenterology 1998; 93: 527–531. 11. Paloyen D, Simonirtz D & Skinner DB. The timing of biliary tract operations in patients with pancreatitis associated with gallstones. Surgery Gynecology and Obstetrics 1975; 141: 737–739. 12. Debette-Gratien M & Yahchouchy E. Management of acute biliary pancreatitis. Gastro-ente´rologie Clinique et Biologique 2001; 25: 1S225– 1S240. 13. Uhl W, Warshaw A, Imrie C et al. IAP guidelines for the surgical management of acute pancreatitis. Pancreatology 2002; 2: 565 –573. 14. Cohen ME, Slezak L, Wells CK et al. Prediction of bile duct stones and complications in gallstone pancreatitis using early laboratory trends. American Journal of Gastroenterology 2001; 96: 3305–3311. 15. Chak A, Hawes R, Cooper GS et al. Prospective assessment of the utility of EUS in the evaluation of gallstone pancreatitis. Gastrointestinal Endoscopy 1999; 49: 599–604. 16. Sica GT, Braver J, Cooney MJ et al. Comparison of endoscopic retrograde cholangiopancreatography with MR cholangiopancreatography in patients with pancreatitis. Radiology 1999; 210: 605–610. 17. Neoptolemos JP, Carr-Locke DL, London NJ et al. Controlled trial of urgent endoscopic retrograde cholangiopancreatography and endoscopic sphincterotomy versus conservative treatment for acute pancreatitis due to gallstones. Lancet 1988; ii: 979–983. 18. Fan ST, Lai ECS, Mok FPT et al. Early treatment of acute biliary pancreatitis by endoscopic papillotomy. New England Journal of Medicine 1993; 328: 228–232. 19. Nowak A, Nowakowska-Dulawa E, Marek TA & Rybicka J. Final results of the prospective, randomized, controlled study on endoscopic sphincterotomy versus conventional management in acute biliary pancreatitis. Gastroenterology 1995; 108(supplement): A380. 20. Fo¨lsch UR, Nitsche R, Lu¨dtke R et al. Early ERCP and papillotomy compared with conservative treatment for acute biliary pancreatitis. New England Journal of Medicine 1997; 336: 237–242. * 21. Sharma V & Howden C. Meta analysis of randomised controlled trials of endoscopic retrograde cholangiopancreatography and endoscopic sphincterotomy for the treatment of acute biliary pancreatitis. American Journal of Gastroenterology 1999; 94: 3211–3214. 22. Norman J. The role of cytokines in the pathogenesis of acute pancreatitis. American Journal of Surgery 1998; 175: 76– 83. * 23. Freeman ML, Nelson DB, Sherman S et al. Complications of endoscopic biliary sphincterotomy. New England Journal of Medicine 1996; 335: 909–918. 24. Soetikno RM & Carr-Locke DL. Endoscopic management of acute gallstone pancreatitis. Gastrointestinal Endoscopy Clinics of North America 1998; 8: 1–12. 25. Mergener K & Baillie J. Endoscopic treatment for acute biliary pancreatitis. When and in whom? Gastroenterology Clinics of North America 1999; 28: 601– 613. * 26. Delhaye M, Engelholm L & Cremer M. Pancreas divisum: congenital anatomic variant or anomaly? Contribution of endoscopic retrograde dorsal pancreatography. Gastroenterology 1985; 89: 951 –958. 27. Cotton PB. Congenital anomaly of pancreas divisum as cause of obstructive pain and pancreatitis. Gut 1980; 21: 105–114. 28. Matos C, Metens T, Devie`re J et al. Pancreas divisum: evaluation with secretin-enhanced magnetic resonance cholangiopancreatography. Gastrointestinal Endoscopy 2001; 53: 728 –733. 29. Cohen SA & Siegel JH. Pancreas divisum. Endoscopic therapy. Surgical Clinics of North America 2001; 81: 467–477. * 30. Somogyi L, Martin SP, Venkatesan T & Ulrich CD. Recurrent acute pancreatitis: An algorithmic approach to identification and elimination of inciting factors. Gastroenterology 2001; 120: 708–717. 31. Heyries L, Barthet M, Delvasto C et al. Long-term results of endoscopic management of pancreas divisum with recurrent acute pancreatitis. Gastrointestinal Endoscopy 2002; 55: 376 –381. 32. Eisen G, Schutz S, Metzler D et al. Santorinicele: new evidence for obstruction in pancreas divisum. Gastrointestinal Endoscopy 1994; 1: 73–76.

Endoscopic technique in pancreatitis 179 33. Costamagna G, Ingrosso M, Tringali A et al. Santorinicele and recurrent acute pancreatitis in pancreas divisum: diagnosis with dynamic secretin-stimulated magnetic resonance pancreatography and endoscopic treatment. Gastrointestinal Endoscopy 2000; 52: 262–267. 34. Guelrud M, Morera C, Rodriguez M et al. Sphincter of Oddi dysfunction in children with recurrent pancreatitis and anomalous pancreaticobiliary union: an etiologic concept. Gastrointestinal Endoscopy 1999; 50: 194–199. 35. Misra SP & Dwivedi M. Pancreaticobiliary ductal union. Gut 1990; 31: 1144–1149. 36. Sugiyama M, Atomi Y & Kuroda A. Pancreatic disorders associated with anomalous pancreaticobiliary junction. Surgery 1999; 126: 492–497. 37. Samavedy R, Sherman S & Lehman GA. Endoscopic therapy in anomalous pancreatobiliary duct junction. Gastrointestinal Endoscopy 1999; 50: 623 –627. 38. Greene FL, Brown JJ, Rubinstein P & Anderson MC. Choledochocele and recurrent pancreatitis. Diagnosis and surgical management. American Journal of Surgery 1985; 149: 306 –309. 39. Ladas SD, Katsogridakis I, Tassios P et al. Choledochocele, an overlooked diagnosis: report of 15 cases and review of 56 published reports from 1984 to 1992. Endoscopy 1995; 27: 233–239. 40. Tarnasky PR & Hawes RH. Endoscopic diagnosis and therapy of unexplained (idiopathic) acute pancreatitis. Gastrointestinal Endoscopy Clinics of North America 1998; 8: 13–37. 41. Azar C, Van de Stadt J, Rickaert F et al. Intraductal papillary mucinous tumours of the pancreas. Clinical and therapeutic issues in 32 patients. Gut 1996; 39: 457– 464. 42. Frossard JL, Sosa-Valencia L, Amouyal G et al. Usefulness of endoscopic ultrasonography in patients with ‘idiopathic’ acute pancreatitis. American Journal of Medicine 2000; 109: 196– 200. 43. Norton SA & Alderson D. Endoscopic ultrasonography in the evaluation of idiopathic acute pancreatitis. British Journal of Surgery 2000; 87: 1650–1655. 44. Levy MJ & Geenen JE. Idiopathic acute recurrent pancreatitis. American Journal of Gastroenterology 2001; 96: 2540–2555. 45. Sherman S, Troiano FP, Hawes RH et al. Frequency of abnormal sphincter of Oddi manometry compared with the clinical suspicion of sphincter of Oddi dysfunction. American Journal of Gastroenterology 1991; 86: 586–589. * 46. Matos C, Metens T, Devie`re J et al. Pancreatic duct: morphologic and functional evaluation with dynamic MR pancreatography after secretin stimulation. Radiology 1997; 203: 435–441. 47. Tarnasky P, Palesch Y, Cunningham J et al. Pancreatic stenting prevents pancreatitis after biliary sphincterotomy in patients with sphincter of Oddi dysfunction. Gastroenterology 1998; 115: 1518–1524. 48. Jacob L, Geenen JE, Catalano MF & Geenen DJ. Prevention of pancreatitis in patients with idiopathic recurrent pancreatitis: a prospective non blinded randomized study using endoscopic stents. Endoscopy 2001; 33: 559– 562. * 49. Beger H, Rau B, Mayer J et al. Natural course of acute pancreatitis. World Journal of Surgery 1997; 21: 130 –135. * 50. Balthazar EJ, Freeny PC & van Sonnenberg E. Imaging and intervention in acute pancreatitis. Radiology 1994; 193: 297–306. 51. Banks PA. Practice guidelines in acute pancreatitis. American Journal of Gastroenterology 1997; 92: 377– 386. 52. Dervenis C, Johnson CD, Bassi C et al. Diagnosis, objective assessment of severity, and management of acute pancreatitis.Santorini consensus Conference. International Journal of Pancreatology 1999; 25: 195–210. 53. Bu¨chler MW, Gloor B, Mu¨ller CA et al. Acute necrotizing pancreatitis: treatment strategy according to the status of infection. Annals of Surgery 2000; 232: 619–626. 54. Slim K & Pilleul F. Management of complicated acute pancreatitis: local complications. Gastro-ente´rologie Clinique et Biologique 2001; 25: 1S213– 1S224. 55. Lobo DN, Memon MA, Allison SP & Rowlands BJ. Evolution of nutritional support in acute pancreatitis. British Journal of Surgery 2000; 87: 695–707. 56. Baron TH, Thaggard WG, Morgan DE & Stanley RJ. Endoscopic therapy for organized pancreatic necrosis. Gastroenterology 1996; 111: 755–764. 57. Baron TH, Harewood GC, Morgan DE & Yates MR. Outcome differences after endoscopic drainage of pancreatic necrosis, acute pancreatic pseudocysts, and chronic pancreatic pseudocyst. Gastrointestinal Endoscopy 2002; 56: 7–17. 58. Morgan DE, Baron TH, Smith JK et al. Pancreatic fluid collections prior to intervention: evaluation with MR imaging compared with CT and US. Radiology 1997; 203: 773–778. 59. Telford JJ, Farrell JJ, Saltzman JR et al. Pancreatic stent placement for duct disruption. Gastrointestinal Endoscopy 2002; 56: 18–24. 60. Neoptolemos JP, London NJM & Carr-Locke DL. Assessment of main pancreatic duct integrity by endoscopic retrograde pancreatography in patients with acute pancreatitis. British Journal of Surgery 1993; 80: 94–99.

180 M. Delhaye, C. Matos and J. Devie`re 61. Uomo G, Molino D, Visconti M et al. The incidence of main pancreatic duct disruption in severe biliary pancreatitis. American Journal of Surgery 1998; 176: 49–52. 62. Lau ST, Simchuk EJ, Kozarek RA & Traverso LW. A pancreatic ductal leak should be sought to direct treatment in patients with acute pancreatitis. American Journal of Surgery 2001; 181: 411–415. 63. Fulcher AS & Turner MA. MR pancreatography: a useful tool for evaluating pancreatic disorders. Radiographics 1999; 19: 5 –24. 64. Devie`re J, Bueso H, Baize M et al. Complete disruption of the main pancreatic duct: endoscopic management. Gastrointestinal Endoscopy 1995; 42: 445–451. 65. Baron TH & Morgan DE. The diagnosis and management of fluid collections associated with pancreatitis. American Journal of Medicine 1997; 102: 555–563. 66. Wilson C. Management of the later complications of severe acute pancreatitis—pseudocyst, abscess and fistula. European Journal of Gastroenterology and Hepatology 1997; 9: 117– 121. 67. Park JJ, Kim SS, Koo YS et al. Definitive treatment of pancreatic abscess by endoscopic transmural drainage. Gastrointestinal Endoscopy 2002; 55: 256– 262. 68. Giovannini M, Pesenti C, Rolland AL et al. Endoscopic ultrasound-guided drainage of pancreatic pseudocysts or pancreatic abscesses using a therapeutic echoendoscope. Endoscopy 2001; 33: 473–477. 69. Sanchez Cortes E, Maalak A, Le Moine O et al. Endoscopic cystenterostomy of non-bulging pancreatic fluid collections. Gastrointestinal Endoscopy 2002; 56: 380– 386. 70. Bradley EL. Long-term results of pancreaticojejunostomy in patients with chronic pancreatitis. American Journal of Surgery 1987; 153: 207–213. 71. Cremer M, Devie`re J, Delhaye M et al. Stenting in severe chronic pancreatitis: Results of medium-term follow-up in seventy-six patients. Endoscopy 1991; 23: 171 –176. 72. Farnbacher MJ, Schoen C, Rabenstein T et al. Pancreatic duct stones in chronic pancreatitis: criteria for treatment intensity and success. Gastrointestinal Endoscopy 2002; 56: 501– 506. * 73. Ro¨sch T, Daniel S, Scholz M et al. Endoscopic treatment of chronic pancreatitis: a multicenter study of 1000 patients with long-term follow-up. Endoscopy 2002; 34: 765–771. 74. Dumonceau J-M, Devie`re J, Le Moine O et al. Endoscopic pancreatic drainage in chronic pancreatitis associated with ductal stones: long-term results. Gastrointestinal Endoscopy 1996; 43: 547–555. 75. Sherman S, Lehman GA, Hawes RH et al. Pancreatic ductal stones: frequency of successful endoscopic removal and improvement in symptoms. Gastrointestinal Endoscopy 1991; 37: 511– 517. 76. Delhaye M, Vandermeeren A, Baize M & Cremer M. Extracorporeal shock wave lithotripsy of pancreatic calculi. Gastroenterology 1992; 102: 610– 620. 77. Costamagna G, Gabbrielli A, Mutiagnani M et al. Extracorporeal shock wave lithotripsy of pancreatic stones in chronic pancreatitis: immediate and medium-term results. Gastrointestinal Endoscopy 1997; 46: 231–236. 78. Kozarek RA, Brandabur JJ, Ball TJ et al. Clinical outcomes in patients who undergo extracorporeal shockwave lithotripsy for chronic pancreatitis. Gastrointestinal Endoscopy 2002; 56: 496–500. 79. Schneider HT, May A, Benninger J et al. Piezoelectric shockwave lithotripsy of pancreatic duct stones. American Journal of Gastroenterology 1994; 89: 2042–2048. 80. Johanns W, Jakobeit C, Greiner L et al. Ultrasound-guided extracorporeal shock wave lithotripsy of pancreatic ductal stones: six years’ experience. Canadian Journal of Gastroenterology 1996; 10: 471–475. 81. Adamek HE, Jakobs R, Buttmann A et al. Long-term follow-up of patients with chronic pancreatitis and pancreatic stones treated with extracorporeal shock wave lithotripsy. Gut 1999; 45: 402–405. 82. Brand B, Kahl M, Sidhu S et al. Prospective evaluation of morphology, function, and quality of life after extracorporeal shockwave lithotripsy and endoscopic treatment of chronic calcific pancreatitis. American Journal of Gastroenterology 2000; 95: 3428–3438. 83. Ohara H, Hoshino M, Hayakawa T et al. Single application extracorporeal shock wave lithotripsy is the first choice for patients with pancreatic duct stones. American Journal of Gastroenterology 1996; 91: 1388–1394. 84. Kim MH, Myung SJ, Kim YS et al. Routine biliary sphincterotomy may not be indispensable for endoscopic pancreatic sphincterotomy. Endoscopy 1998; 30: 697–701. 85. Devie`re J, Delhaye M & Cremer M. Pancreatic duct stones management. Gastrointestinal Endoscopy Clinics of North America 1998; 8: 163–179. 86. Kozarek RA, Bael TJ & Patterson DJ. Endoscopic pancreatic duct sphincterotomy: indications, technique, and analysis of results. Gastrointestinal Endoscopy 1994; 40: 592–598. 87. Sherman S & Lehman GA. Endoscopic pancreatic sphincterotomy: techniques and complications. Gastrointestinal Endoscopy Clinics of North America 1998; 8: 115–124. 88. Binmoeller KF, Rathod VD & Soehendra N. Endoscopic therapy of pancreatic strictures. Gastrointestinal Endoscopy Clinics of North America 1998; 8: 125– 142.

Endoscopic technique in pancreatitis 181 89. Ikenberry SO, Sherman S, Hawes RH et al. The occlusion rate of pancreatic stents. Gastrointestinal Endoscopy 1994; 40: 611–613. 90. Arvanitakis M, Van Laethem J-L, Parma J et al. Predictive factors of development of pancreatic cancer in patients with chronic pancreatitis and K-ras gene mutation detected in pancreatic duct brushings. Gastroenterology 2002; 122: 652. 91. Binmoeller KF, Jue P, Seifert H et al. Endoscopic pancreatic stent drainage in chronic pancreatitis and a dominant stricture: long-term results. Endoscopy 1995; 27: 638–644. 92. Ponchon T, Bory R, Hedelins F et al. Endoscopic stenting for pain relief in chronic pancreatitis: results of a standardized protocol. Gastrointestinal Endoscoy 1995; 42: 452 –456. 93. Smits ME, Badiga SM, Rauws EAJ et al. Long-term results of pancreatic stents in chronic pancreatitis. Gastrointestinal Endoscopy 1995; 42: 461 –467. 94. Lahoti S, Catalano MF, Geenen JE et al. Endoscopic retrieval of proximally migrated biliary and pancreatic stents: experience of a large referral center. Gastrointestinal Endoscopy 1998; 47: 486 –491. 95. Kozarek RA. Pancreatic stents can induce ductal changes consistent with chronic pancreatitis. Gastrointestinal Endoscopy 1990; 36: 93 –95. 96. Howell DA, Elton E & Parsons WG. Endoscopic management of pseudocysts of the pancreas. Gastrointestinal Endoscopy Clinics of North America 1998; 8: 143–162. 97. Beckingham IJ, Krige JEJ, Bornman PC et al. Endoscopic management of pancreatic pseudocysts. British Journal of Surgery 1997; 84: 1638–1645. 98. Gouyon B, Levy P, Ruszniewski P et al. Predictive factors in the outcome of pseudocysts complicating alcoholic chronic pancreatitis. Gut 1997; 41: 821–825. 99. Pitchumoni CS & Agarwal N. Pancreatic pseudocysts. When and how should drainage be performed? Gastroenterology Clinics of North America 1999; 28: 615 –639. 100. Golzarian J, Nicaise N, Devie`re J et al. Transcatheter embolization of pseudoaneurysms complicating pancreatitis. Cardiovascular Interventional Radiology 1997; 20: 435– 440. * 101. ASGE Guidelines. Endoscopic therapy of chronic pancreatitis. Gastrointestinal Endoscopy 2000; 52: 843 –848. 102. Barthet M, Bugallo M, Moreira LS et al. Management of cysts and pseudocysts complicating chronic pancreatitis. A retrospective study of 143 patients. Gastroenterology and Clinical Biology 1993; 17: 270– 276. 103. Beckingham IJ, Krige JEJ, Bornman PC et al. Long-term outcome of endoscopic drainage of pancreatic pseudocysts. American Journal of Gastroenterology 1999; 94: 71–74. 104. Barthet M, Sahel J, Bodiou-Bertli C & Bernard JP. Endoscopic transpapillary drainage of pancreatic pseudocysts. Gastrointestinal Endoscopy 1995; 42: 208–213. 105. Vitale GC, Lawhon JC, Larson GM et al. Endoscopic drainage of the pancreatic pseudocyst. Surgery 1999; 126: 616 –623. 106. Ng C & Huibregtse K. The role of endoscopic therapy in chronic pancreatitis-induced common bile duct strictures. Gastrointestinal Endoscopy Clinics of North America 1998; 8: 181–193. 107. Devie`re J, Devaere S, Baize M et al. Endoscopic biliary drainage in chronic pancreatitis. Gastrointestinal Endoscopy 1990; 36: 96–100. 108. Barthet M, Bernard JP, Duval JL et al. Biliary stenting in benign biliary stenosis complicating chronic calcifying pancreatitis. Endoscopy 1994; 26: 569–572. 109. Smits ME, Rauws EAJ, van Gulik TM et al. Long-term results of endoscopic stenting and surgical drainage for biliary stricture due to chronic pancreatitis. British Journal of Surgery 1996; 83: 764– 768. 110. Farnbacher MJ, Rabenstein T, Ell C et al. Is endoscopic drainage of common bile duct stenoses in chronic pancreatitis up-to-date? American Journal of Gastroenterology 2000; 95: 1466–1471. 111. Devie`re J, Cremer M, Baize M et al. Management of common bile duct stricture caused by chronic pancreatitis with metal mesh self expandable stents. Gut 1994; 35: 122–126. 112. Menon K, Romagnuolo J & Barkun A. Expandable metal biliary stenting in patients with recurrent premature polyethylene stent occlusion. American Journal of Gastroenterology 2001; 96: 1435–1440.