Endoscopic therapy is recommended as the first-line therapy for painful chronic pancreatitis with an obstacle on the main pancreatic duct (MPD). The clinical response should be evaluated at 6 to 8 weeks. Calcified stones that obstruct the MPD are first treated by extracorporeal shockwave lithotripsy; dominant MPD strictures are optimally treated with a single, large, plastic stent that should be exchanged within 1 year even in asymptomatic patients. Pancreatic pseudocysts for which therapy is indicated and are within endoscopic reach should be treated by endoscopy.
Key points
- •
Endoscopic therapy is the first-line interventional therapy for painful chronic pancreatitis (CP) with an obstacle on the main pancreatic duct (MPD) and no locoregional complication.
- •
Calcified stones that obstruct the MPD are first treated by extracorporeal shockwave lithotripsy (ie, before or in place of ERCP).
- •
Dominant MPD strictures are treated with a single, large, plastic stent that should be exchanged within 1 year even in asymptomatic patients.
- •
In the case of unsatisfactory clinical response at 6–8 weeks, the patient’s case should be discussed in a multidisciplinary team.
- •
Treatment of pancreatic pseudocysts should be performed by endoscopy. Compared with surgery, results are better at short term and similar at long term.
Introduction
In chronic pancreatitis (CP), endoscopic therapy aims to provide pain relief and to treat local complications. Pain may be caused by multiple factors, including neuropathy, increased intraductal and parenchymal pancreatic pressure, pancreatic ischemia, and acute inflammation during a flare. Complications such as pseudocysts, strictures of the common bile duct (CBD), and pancreatic cancer may also cause pancreatic-type pain.
In the case of uncomplicated CP, most nonsurgical therapeutic interventions aim at relieving outflow obstruction of the main pancreatic duct (MPD). In a large multicenter study of endoscopic treatment of CP, MPD obstruction was caused by strictures (47% of the patients), stones (18%), or a combination of both (32%). Depending on the type of MPD obstruction, extracorporeal shockwave lithotripsy (ESWL), endoscopic retrograde cholangio-pancreatography (ERCP), or a combination of both may be used to restore MPD outflow. CP-related complications amenable to endoscopic treatment consist of pseudocysts and CBD strictures; in the multicenter study cited above, they were treated in 17% and 23% of patients, respectively.
The recommendations presented here are based on a Guideline that has recently been issued by the European Society of Gastrointestinal Endoscopy (ESGE). Importantly, they do not apply to patients with CP that is mild in severity at pancreatography as assessed by the Cambridge classification.
Introduction
In chronic pancreatitis (CP), endoscopic therapy aims to provide pain relief and to treat local complications. Pain may be caused by multiple factors, including neuropathy, increased intraductal and parenchymal pancreatic pressure, pancreatic ischemia, and acute inflammation during a flare. Complications such as pseudocysts, strictures of the common bile duct (CBD), and pancreatic cancer may also cause pancreatic-type pain.
In the case of uncomplicated CP, most nonsurgical therapeutic interventions aim at relieving outflow obstruction of the main pancreatic duct (MPD). In a large multicenter study of endoscopic treatment of CP, MPD obstruction was caused by strictures (47% of the patients), stones (18%), or a combination of both (32%). Depending on the type of MPD obstruction, extracorporeal shockwave lithotripsy (ESWL), endoscopic retrograde cholangio-pancreatography (ERCP), or a combination of both may be used to restore MPD outflow. CP-related complications amenable to endoscopic treatment consist of pseudocysts and CBD strictures; in the multicenter study cited above, they were treated in 17% and 23% of patients, respectively.
The recommendations presented here are based on a Guideline that has recently been issued by the European Society of Gastrointestinal Endoscopy (ESGE). Importantly, they do not apply to patients with CP that is mild in severity at pancreatography as assessed by the Cambridge classification.
Planning treatment
Differential Diagnosis and Local Disease Assessment
Before deciding on which treatment to apply, it is necessary to confirm the diagnosis of CP, to rule out the presence of a pancreatic cancer reasonably, and to assess the local anatomy.
The differential diagnosis of CP mostly includes intraductal papillary mucinous neoplasm (IPMN) and autoimmune pancreatitis:
- •
Approximately 10% of patients with IPMN are first inappropriately diagnosed with CP. Demographic and imaging data may help in making the correct diagnosis:
- ○
Patients with IPMN are more often women, are older, drink less alcohol, and smoke fewer cigarettes than those with CP ;
- ○
An MPD dilation without downstream stone or stricture evidenced at magnetic resonance cholangiopancreatography (MRCP) or endoscopic ultrasonography (EUS) is highly suggestive of IPMN;
- ○
Consensus guidelines for the management of IPMN have recently been updated.
- ○
- •
The diagnosis of autoimmune pancreatitis requires a combination of imaging, histopathology, serology (IgG 4 ), evaluation of other organ involvement, and response to steroids.
CP is one of the factors that increase the risk of pancreatic cancer. It is not a main cause of pancreatic cancer except in patients with the rare autosomal-dominant hereditary form of pancreatitis. Nevertheless, pancreatic cancer may be overlooked, in particular, at the time of the initial diagnosis of CP. Special attentiveness for pancreatic cancer should be paid in patients greater than 50 years, of female gender, of white race, those presenting with jaundice or exocrine insufficiency, as well as in the absence of pancreatic calcifications.
Assessment of the local anatomy is usually performed by a combination of computed tomographic (CT) scan without contrast medium injection (CT scan is the most sensitive examination for the detection of pancreatic calcifications and it allows broad assessment of the pancreatic parenchyma) and of MRCP (for assessing the pancreatic ducts, including MPD strictures and relevant anatomic variants such as pancreas divisum). Magnetic resonance and EUS may be superior to CT scan for the workup of pancreatic fluid collections because these techniques depict solid necrotic debris inside collections that may impede its effective drainage.
Choice of Treatment
Surgical and endoscopic interventions for the treatment of pain in CP have been compared in 2 randomized controlled trials (RCT). Criticisms of the nonsurgical treatment performed in these studies aside, these RCTs showed that surgery provides pain relief in more patients than endoscopic treatment but that complete pain relief is infrequent after surgical as well as endoscopic treatment. Hence, the ESGE recommended endoscopic therapy as the first-line therapy for painful uncomplicated CP because
- •
Surgery is not a “definitive” treatment of CP (except in the case of total pancreatectomy, with its long-term complications); pain eventually relapses following surgery in most patients. Total pancreatectomy with islet autotransplantation is an emerging option for definitive therapy, particularly in younger patients with aggressive hereditary pancreatitis such as that associated with mutations of the cationic trypsinogen gene (PRSS-1).
- •
Death is not exceptional after surgery, even in its least risky form (ie, MPD drainage; mortality, 0%–4%). Complications are extremely common after pancreatic resection for CP (20%–50%). In contrast, morbidity and mortality of nonsurgical interventions for CP are in the range of 3% to 9% and 0% to 0.5%, respectively, which is likely related to the relative protection against post-ERCP pancreatitis conferred by CP.
- •
Most patients present a satisfactory long-term outcome after nonsurgical treatment for CP. For example, in a selection of independent series ( Table 1 ), 59% to 79% of patients had no further pancreatic intervention during long-term (4–14 years) follow-up after nonsurgical intervention for CP.
Table 1
Long-term outcome after nonsurgical treatment of CP
First Author, Year
N
Follow-Up (mo)
Surgery (%)
Ongoing Endoscopic Treatment (%)
No Further Intervention (%)
Binmoeller et al, 1995
93
58
26
13
61
Rösch et al, 2002
1018
58
24
16
60
Delhaye et al, 2004
56
173
21
18
61
Tadenuma et al, 2005
70
75
1
20
79
Inui et al, 2005
555
44
4
—
—
Farnbacher et al, 2006
98
46
23
18
59
Adapted from Dumonceau JM, Delhaye M, Tringali A, et al. Endoscopic treatment of chronic pancreatitis: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline. Endoscopy 2012;44(8):784–800; with permission.
Therefore, in centers with both endoscopic and surgical expertise, a nonsurgical intervention is often proposed as a first-step procedure for the treatment of painful uncomplicated CP. Some factors that may help in the choice between the surgical and nonsurgical options are as follows:
- •
The location of obstructive calcifications in the head of the pancreas, a short disease duration, and a low frequency of pain attacks before a nonsurgical intervention predict a good clinical outcome.
- •
Conversely, if the lesions targeted by nonsurgical interventions are located in the pancreatic tail exclusively , pancreatic tail resection may be favored as a possible first-intent option. Nevertheless, it should be noted that patients with MPD obstruction located in both the head and the tail of the pancreas may have a favorable clinical outcome after relieving the MPD obstacle located in the head of the pancreas only.
- •
In the unusual cases where a pancreatic cancer cannot be reasonably excluded based on a detailed pretherapeutic workup, pancreatic resection may be performed as a diagnostic and therapeutic procedure (intraoperative needle aspiration is not adequate to exclude the presence of a cancer).
- •
The absence of MPD stricture predicts a good long-term outcome.
- •
Discontinuation of alcohol and tobacco during follow-up predicts a good outcome; help should be offered to the patients to succeed in this difficult task, independently of the treatment elected, and preferably before beginning treatment.
If nonsurgical treatment is elected, the clinical response should be evaluated at 6 to 8 weeks; if it seems unsatisfactory, the patient’s case should be discussed in a multidisciplinary team with endoscopists, surgeons, and radiologists and surgical options should be considered, in particular in patients with a predicted poor outcome following endoscopic therapy.
Management of pancreatic stones
Stones targeted by nonsurgical interventions for the treatment of PC are those that obstruct or are susceptible to obstruct the MPD. A significant exception to this general rule includes large stones that are located in a secondary duct and impede the communication between a pseudocyst and the MPD. Complete MPD stone clearance at initial ERCP predicts a good clinical outcome.
Infrequently, stones obstructing the MPD are not calcified. Such noncalcified stones are usually easy to extract at ERCP using a Dormia basket and/or a balloon following pancreatic sphincterotomy. Much more frequently, stones obstructing the MPD are calcified; such calcified stones can be cleared using ESWL alone, ERCP alone, a combination of ESWL plus ERCP, or medications. ESWL has become the core, first-line, therapy (except for stones smaller than 4 mm that are difficult to target at ESWL) because of the following:
- •
Endoscopic attempts at stone extraction using Dormia baskets without prior stone fragmentation have yielded unsatisfactory results in terms of both success rates (approximately 10%) and morbidity rates (3 times higher than those reported for biliary stones).
- •
Advanced intraductal lithotripsy techniques such as laser or electrohydraulic lithotripsy are not readily available in many endoscopy units; their use has been reported in small case series only and they have provided low success rates compared with ESWL. These techniques may be useful in the case of failed ESWL.
- •
Medications able to dissolve pancreatic stones are not approved for that use by health organizations. They have never been tested in comparative trials; treatment duration is long, and side effects may be significant.
On the contrary, ESWL is largely available because of its widespread use to treat urological stones and it has consistently been reported to be highly effective to fragment calcified MPD stones. MPD stones are successfully fragmented in approximately 90% of the cases. The material and the techniques of ESWL used to fragment MPD stones are critical to ensure such high success rates and less favorable results have been reported, particularly in low case-volume centers. A meta-analysis of 17 studies (total of 491 patients) showed that ESWL is useful to clear MPD stones and to decrease pain.
Performance of ESWL before endoscopic attempt at stone removal is independently associated with the success of MPD stone clearance. In practice, ESWL is always performed before ERCP to extract calcified MPD stones of significant size to avoid failure of stone extraction. After ESWL, successful MPD stone clearance is more likely for stones that are solitary or confined to the head of the pancreas.
ESWL may also be used alone to treat painful uncomplicated CP. Initial uncontrolled studies showed that stone fragments are spontaneously eliminated in the stools, through the intact pancreatic sphincter, in approximately 75% of patients subjected to ESWL alone; 78% of patients had long-term pain relief. Then, an RCT showed that, compared with ESWL combined with ERCP, ESWL alone provided a similar decrease in the MPD diameter and in the number of yearly pain attacks. The only significant differences between ESWL alone or combined with ERCP were a longer hospital stay and a higher treatment cost in the combination group (ESWL plus ERCP). Therefore, ESWL alone may be the preferred first-line intervention to treat painful uncomplicated CP, in particular, if no MPD stricture is evidenced at MRCP and if the center has expertise with pancreatic ESWL. Otherwise, endoscopic extraction of stone fragments is performed immediately after satisfactory stone fragmentation has been obtained.
Morbidity related to ESWL alone or combined with ERCP was reviewed based on 4 large (>100 patients) series: significant complications were reported in 104 of 1801 patients, including one death (morbidity and mortality: 5.8% and 0.05%, respectively). Complications related to the treatment of CP by ESWL alone were reported in 3 series that involved 165 patients ; the morbidity rate was 6.0%. For both ESWL alone or combined with ERCP, complications consisted of pancreatitis in most cases. Contraindications to ESWL are rarely encountered in patients with CP.
Management of MPD strictures
Temporary stent placement for a duration of at least 1 year has become the standard of care for the endoscopic treatment of dominant MPD strictures because repeated balloon dilation without stenting or MPD stenting for a short duration has been shown to be ineffective. The principles and technique of temporary MPD stricture dilation using stents is similar to those applied for benign biliary strictures. Technical points specific to MPD strictures are as follows:
- •
Pancreatic sphincterotomy always precedes stent insertion, contrary to what is performed for biliary stenting, carrying a 10% risk of post-ERCP pancreatitis but the flare is usually mild. Biliary sphincterotomy is associated with pancreatic sphincterotomy in specific cases only (ie, to facilitate catheterization of the MPD or to prevent cholangitis in patients who are at risk of this complication, including those with a bilirubin level ≥3 mg/dL, a diameter of the CBD ≥12 mm, or alkaline phosphatases >2 times the upper limit of normal values).
- •
Stricture dilation is performed before stenting in most cases because of the resilience of CP-related MPD strictures; bougies/balloons are used or, in most difficult cases, the Soehendra’s stent retriever.
The ESGE recommended treating dominant MPD stricture by inserting a single 10-French plastic stent, with stent exchange planned within 1 year even in asymptomatic patients to prevent complications related to long-standing pancreatic stent occlusion. Simultaneous placement of multiple, side-by-side, pancreatic stents is being applied more and more extensively, either at first treatment attempt or in patients with MPD strictures persisting after 12 months of single plastic stenting. At this time, all available options (eg, endoscopic placement of multiple simultaneous MPD stents, surgery) should be discussed in a multidisciplinary team.
The insertion of plastic stents in the MPD is technically successful in greater than 90% of attempted cases; it is followed by immediate and long-term pain relief in approximately 80% and 50% of the patients, respectively ( Table 2 ). Simultaneous insertion of multiple, side-by-side, MPD stents has been investigated in a single series of 19 patients, with encouraging results. This strategy might be particularly useful in patients (1) with MPD strictures persisting after 12 months of single plastic stenting and (2) with a pancreas divisum because this anatomy is associated with a more frequent relapse of MPD stricture and of pain after stent removal compared with a fused pancreas.
Related posts:
Advances in Pancreatic Endoscopy
Effective Endoscopic Management of Pancreatic Diseases
Role of Endoscopic Ultrasonography in the Diagnosis of Acute and Chronic Pancreatitis
Endoscopic Therapy for Acute Recurrent Pancreatitis
ERCP for Biliary Strictures Associated with Chronic Pancreatitis
Endoscopic Ultrasonography–Guided Drainage of the Pancreatic Duct
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
