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Endoscopic Therapy for Chronic Pancreatitis
THE PANCREAS REVISITED I: DIAGNOSTIC, CHRONIC PANCREATITIS
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ENDOSCOPIC THERAPY FOR CHRONIC PANCREATITIS Franklin E. Kasmin, MD, and Jerome H. Siegel, MD
Endoscopic management of chronic pancreatitis was first reported in 19778 with the performance of pancreatic sphincterotomy for relief of an impacted pancreatic ductal stone. Since then, pancreatic endoscopic therapy has become an important, albeit controversial, alternative therapy for patients with chronic pancreatitis not amenable to surgical management.27The development of pancreatic endoscopic therapy has been driven by clinicians' desire to provide a nonsurgical means of palliating some of the complications of chronic pancreatitis. Various pancreatic abnormalities, including stone disease, ductal strictures, fluid collections, and functional sphincter disorders, all can be treated endoscopically. Adjuvant therapy to the bile duct, in the case of pancreatitis-induced biliary strictures, and the stenting of the obstructed duodenum are also feasible endoscopically. The relief of pain is generally the most compelling reason for endoscopic management of chronic pancreatitis. As with surgical ductal decompression, the goal of endoscopic management of pain in chronic pancreatitis is ductal decompre~sion.~, 37 Endoscopic techniques, such as stenting or stone extraction, can reestablish pancreatic drainage and reduce ductal pressures while maintaining pancreatic secretory activity in a functional gland. Ductal obstruction in chronic pancreatitis occurs in several ways. Fibrotic strictures can occur as a result of recurrent acute episodes of pancreatitis. Stone disease can present as parenchymal calcification resulting in an extrinsic compression of the pancreatic duct or as intraductal stone disease. Periampullary and sphincteric disease can lead to ductal hypertension and recurrent episodes of acute pancreatitis. The goal of endoscopic therapy in each situation is the relief of obstruction by the removal of its cause, as in the case of stone extraction or sphincter ablation, or in the stenting of the pancreatic duct. From the Albert Einstein College of Medicine (FEK, JHS); the Department of Medicine (FEK), and Endoscopy (IHS), Division of Gastroenterology, Beth Israel Medical Center, New York, New York SURGICAL CLINICS OF NORTH AMERICA VOLUME 81 NUMBER 2 APRIL 2001
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THERAPY FOR STRICTURES
Fibrotic strictures can occur at any point along the pancreatic duct; however, in most patients who present with painful chronic pancreatitis, stricturing develops in the head, rather than the tail, of the gland. The approach to these strictures involves dilation and stenting to provide short- or long-term decompression (Fig. 1 ). Pancreatic endoscopic therapy generally begins with sphincterotomy of the pancreatic sphincter. This maneuver permits the introduction of endoscopic accessories, ensures repeated selective access to the duct, and enhances the flow of pancreatic juice. Pancreatic sphincterotomy can be performed alone or in combination with biliary sphincterotomy, and the decision to perform one or both sphincterotomies is based on the initial ease of access into the two ductal systems. Deep access into the pancreatic duct in chronic pancreatitis can be difficult. Although access to the pancreatic duct after sphincterotomy usually can be achieved de novo, further entry into the body or tail may require the use of a guidewire. This is especially true in the region of the stricture itself. Advances in guidewire technology make the negotiation of these strictures successful in most cases. Wires that use a hydrophilic coating and a floppy atraumatic tip are
Figure 1. A tight stricture (A) is dilated first with a catheter remover (C), after which a stent is placed (0).
(B)and then a screw-tip stent
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especially useful. The authors favor the use of a modified 7 F dilating catheter (Siegel-Cohen, Wilson Cook, Inc., Winston-Salem, NC) for introduction of the wire because this allows for stricture dilation and simplified guidewire exchange by virtue of its large inner diameter.30 Although the stricture usually can be traversed easily with a guidewire, the passage of the catheter over the guidewire and across the stricture is not always as easy. Difficult strictures may result from intense local fibrosis, extrinsic compression of the duct by parenchymal calcification, or an acute angulation of the duct. Techniques to assist the crossing of a stricture include the use of gradual catheter dilation; balloon dilation using an angioplasty balloon**;or the use of a coiled wire stent removal device, which acts as a screw or drill bit? This last technique is perhaps most attractive because the technique uses a cable with a screw tip to core its way across a stricture, disrupting ductal fibrosis and perhaps resulting in a more permanent strictureplasty than can be achieved with dilation by a balloon or catheter. After access to the duct has been achieved across a stricture, stent placement is performed to ensure postprocedural drainage. Polyethylene stents typically are used, and the appropriate stent length is tailored to the distance a stricture lies from the sphincter orifice. Stents are usually 5.0 or 7.0 F, but 8.5, 10.0, or 11.5 F drains also can be placed in patients with large-diameter ducts undergoing long-term stricture dilation. Stent design varies, but the authors prefer a C loop stent with a curl in the duodenum to prevent in-migration and an inner flap to prevent out-migration.Side holes are cut along the length of the stent to promote side branch drainage. Alternative methods of stent design include straight stents, which may promote flow of juice but be more apt to migrate into the duct, and Silastic stents, which may be less likely to irritate the pancreatic ductal m~cosa.’~ Drainage of pancreatic juice across a stricture is expected to result in a decrease in ductal pressures and a diminution in pain for patients in whom pain is related to obstruction. The reestablishment of ductal drainage also may result in an improvement in malabsorption; however, for these benefits to persist, the stent must remain patent. Unfortunately, stents have a limited life patency,I6 and stent occlusion can be expected after an average of 2 to 4 months. Plugs comprised of proteinaceous material and calcium stone debris form along the length of the stent and especially at the tip in the duodenum. Although a stent often can act as a ”wick,” permitting flow around its outer skin, occlusion may lead to recurrent pain or even a suppurative ductal process analogous to the infections seen with cholangitis and the occluded bile duct stent. Stricture dilation may occur with time when a stent has been left in place, so stent therapy in chronic pancreatitis may be carried out over a period of many months. The authors follow an algorithm that begins with a pancreatic sphincterotomy and the placement of an initial stent, usually 7 F because this is typically the largest stent that can be passed initially. Stricture dilation is carried out before stent placement with the 7 F Siegel-Cohen catheter or the screwtipped stent remover, if necessary. The patient returns within 4 months, at which time the stent is removed and the tightness of the stricture and drainage of contrast medium from the duct is assessed. If the stricture persists, further dilation and the passage of a larger stent, usually 8.5 F, are carried out. Additional sessions of endoscopic therapy are carried out if the stricture persists; the ultimate goal is to insert a 10 F stent (or larger) for several months to allow for maximum stricture dilation. All stents are ultimately removed at some point, and clinical results are assessed. If the patient’s symptoms remain improved, regardless of the radiologic appearance of the gland, the patient is observed and provided supplemental pancreatic enzymes, if necessary. If the patient has
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recurrence of symptoms following stent removal, the stent is replaced in the largest size possible, and the patient is referred for consideration of surgical drainage. In the event that a patient derives no relief from stent therapy, longterm pharmacologic pain management therapy is advised. The authors believe that the response to stent therapy predicts the response to surgical decompression and that patients who do not improve with endoscopic drainage are best managed medically or with resection. The results of stenting in patients with chronic pancreatitis and strictures are difficult to assess accurately because prospective randomized studies comparing surgical versus medical versus endoscopic alternatives exist. Binmoeller et a12 treated 93 patients having dominant strictures on ductography with serial dilation and stenting for pain relief. In this uncontrolled, retrospective study, partial or complete pain relief occurred in 74% of patients. Eighty-seven percent of patients continued to have pain relief when evaluated in follow-up at a mean of 4.9 years. Using a similar approach, Cremer et a17 reported symptom relief in 55% of patients at a mean follow-up of 2 years; however, almost half required ongoing stent therapy. Complications included clinically apparent stent occlusion in 20% and stent migration in 10% of patients. Ponchon et a121reported a standardized protocol of stricture dilation and stenting for 6 months. Stents were removed after the study period, and pain control was assessed. Seventy-four percent of patients had early relief of pain, and 52% remained substantially asymptomatic at 1-year follow-up. Complications of pancreatic stent therapy include acute events occurring after endoscopic retrograde cholangiopancreatography (ERCP) and complications that occur during the protracted course of therapy. Early complications include acute pancreatitis, bleeding, perforation, and fluid collection formation. In the authors’ series of 59 patients undergoing pancreatic sphincterotomy, the rate of acute pancreatitis was lo%, with a mean hospital stay of 3.7 days.17 The Ponchon series had a pancreatitis rate of 41%, perhaps because of the use of hydrostatic balloon dilation of the pancreatic duct. The authors’ impression is that manipulation of the pancreatic duct in patients with chronic pancreatitis is less likely to cause severe acute pancreatitis than is a similar manipulation in patients with healthy pancreatic ducts. Most episodes of acute post-ERCP pancreatitis clear quickly. Ductal changes from indwelling pancreatic stents are a troubling long-term consequence of endoscopic therapy for chronic pancreatitis.5,lo,18,32 Smith et a132 found that 80% of patients undergoing pancreatic stent therapy developed new morphologic changes on removal of the stent. These changes occurred in patients with healthy ducts and in those with prior chronic abnormalities and are concerning because the induced changes have the appearance of strictures seen in chronic pancreatitis. Fortunately, most changes are reversible, although 37% of patients had residual stent-related abnormalities at a mean follow-up of 6.4 months. The long-term clinical consequences of these ductal changes, if any, are unknown.
THERAPY FOR DUCTAL STONE DISEASE
Ductal stones can produce obstruction and pain.9,24, 25 Stones may be attached to the wall of the duct, lie within the parenchyma, or be free floating within the duct. Stone material can cause ductal obstruction, thereby causing pain (Fig. 2A). In the case of intraductal stones, the duct is obstructed by intrinsic
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Figure 2. A, A stone impacted in the pancreatic ductal orifice. Alcoholic pancreatitis with stone disease before (6)and after (C)endoscopic therapy. obstruction at the level of the pancreatic orifice or at the level of a ductal stricture. In the case of parenchymal stone disease, extrinsic compression of the main duct can occur because the concretions cause mass effect and local inflammatory changes. Therapeutic interventions aimed at relief of obstruction include (1) stenting to provide short- or long-term decompression and (2) stone extraction (Fig. 2B and C). Most often, pancreatic calculi form behind a duct stricture and the stricture is simultaneously treated. Initial therapy is with pancreatic sphincterotomy. This maneuver enhances pancreatic drainage and facilitates the extraction of stone material. The techniques required to remove a pancreatic stone are similar to that used for biliary stone extraction. A Dormia-type basket is used most commonly to engage the floating stone within the duct and attempt extraction. In the case of stones attached to the wall, the basket does not seem to spread its arms around the stone; instead, the basket remains collapsed as it passes by the stone. Stones may be quite soft and crumble during basket manipulation or, conversely, be quite rigid and densely calcified, remaining substantially intact. In some instances, a stone may be too large to deliver intact through the pancreatic orifice. In this situation, lithotripsy is used. Mechanical lithotripsy uses a standard wire basket that is forcefully drawn into a stiff cable housing after the stone is engaged. The action of the four basket wires retracting into the cable causes a slicing of the stone into four pieces that can be further crushed or removed with a standard basket. Additional small fragments may be removed with an occlusion balloon. Several commercially available mechanical lithotripters are designed as a dedicated unit, but a standard basket can be used for lithotripsy by advancing
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an appropriately sized cable over the disassembled basket after the stone is engaged within its arms. Hence, even if a standard basket has become imvacted wiuhk the duct around a large stone, ”emergency” lithotripsy can b’e performed.29 If a stone is heavily calcified and rigid, lithotripsy may not be successful. In this instance, the basket may remain engaged around the stone, or the stone may be impacted but the basket cannot be disengaged. Continued forceful withdrawal of the basket cables ultimately causes breakage of the wires holding the stone, and the cables then are removed from the endoscope. Residual basket wire pieces typically remain in the duct and usually can be removed with endoscopic grabbing forceps. Many patients have intraductal stones that cannot be removed by mechanical means and are not amenable to lithotripsy. If a stone is large or positioned tightly within the duct, room may be inadequate for a basket to spread its arms around the stone, making basket extraction or lithotripsy impossible. Finally, a stricture positioned between the papilla and the stone may make extraction of sizable fragments unlikely. In these situations, the use of extracorporeal shock wave lithotripsy (ESWL)9,24 can fracture stones into sufficiently small pieces to allow for more complete duct clearance. ESWL is carried out with the patient under intravenous sedation using an x-ray focused beam. Each session lasts approximately 1 hour and delivers approximately 3000 shocks per session. Multiple sessions often are needed to satisfactorily fragment the stones. When stones are radiolucent, a nasopancreatic drain usually is left in place so that contrast medium injection and guidance of the beam can be carried out at the time of ESWL. Subsequent ERCP is carried out, and extraction of stone material is attempted. Pancreatic stents can be placed if drainage is incomplete, and the need for further ESWL sessions is assessed. Stricture dilation is performed as needed to facilitate the removal of stone fragments. When this situation is encountered and multiple sessions are required, surgery seems quite reasonable. The results of clinical studies using endoscopic pancreatic stone extraction for treatment of chronic pancreatitis have been promising. In 1985, Schneider and Luxz5reported immediate pain relief in three of three patients undergoing pancreatic sphincterotomy and stone clearance. Delhaye et a19 found complete or partial pain relief in 75 of 88 patients with relapsing pancreatitis in whom ESWL and duct decompression were used. Cremer et all1 reported durable pain relief (2 years) in 54% of 70 patients who had undergone ductal drainage. The complete clearance of the duct, a decrease in the ductal diameter, and the use of ESWL were associated with long-term improvement. Smits et a133accomplished complete stone extraction in 39 of 53 patients with chronic pancreatitis and achieved complete pain relief in all but one patient. A combination of sphincterotomy, stent placement, mechanical lithotripsy, ESWL, and basket extraction was used. THERAPY FOR SPHINCTER DYSFUNCTION A hypertensive or stenotic sphincter is a theoretic cause for ductal hypertension in the biliary and pancreatic ductal systems.l2,20*34 In the patients undergoing cholecystectomy, sphincter hypertension can cause pain and sphincterotomy can be curative. Because ductal hypertension may be at least partially responsible for pain in patients with chronic pancreatitis, it is sensible to consider that lowering pancreatic ductal pressures may improve pain. Furthermore, it is con-
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ceivable that ductal hypertension, as a result of primary or secondary sphincter dysfunction, may be partially responsible for the occurrence of chronic pancreatitis in some patients. Patients with possible sphincter dysfunction are classified according to the presence of objective findings before the performance of sphincter of Oddi manometry. Those with presumed biliary dysfunction and pain are classified according to the presence or absence of duct dilation, delayed ductal drainage, and liver function test abnormalities. Type 1 patients have pain plus all three objective criteria; type 2 patients have pain plus one or two objective findings; and type 3 patients have pain only. Geenen et all3 originally put forth this classification system; it has been modified to classify patients with pancreatic sphincter dysfunction. Hyperamylasemia, more than 5-mm dilation of the pancreatic duct, and delay in drainage of the pancreatic duct beyond 8 minutes after endoscopic injection are the objective parameters used to classify patients in the ”modified Milwaukee” scale.12This classification system is most useful in patients who suffer recurrent attacks of pain; however, if sphincter dysfunction is responsible for recurrent attacks of acute pancreatitis, then chronic changes can be expected to ultimately occur. Sphincter of Oddi manometry is performed at the time of ERCP. A waterperfused catheter with three lumens typically is used. At the authors’ institution (Beth Israel), two lumens are used to measure sphincter pressures while the third central lumen is used for guidewire passage and pancreatic juice aspiration because aspiration of perfused liquid is associated with a decreased risk for post-ERCP pancreatitis.26The catheter is initially placed into the duodenum, where the luminal pressure is measured and used as baseline. The catheter is then advanced into the duct, and a slow pull-through across the sphincter is performed. If the mean level of relaxation across the sphincter is more than 40 mm Hg, then the basal sphincter pressure is considered elevated. Peak sphincter pressures and the frequency of contractions are thought to be less important. Sphincterotomy of the symptomatic hypertensive sphincter is the treatment of choice. Placement of a stent in the pancreatic duct is thought to be protective against severe pancreatitis. A thin 5 F stent with no internal flaps typically is used to intentionally allow stent out-migration. If migration does not occur, the stent is removed within 2 weeks, especially in patients with minimal ductal changes, to avoid further ductal damage. Sphincter dysfunction of the pancreatic sphincter may be common in chronic pancreatitis. Eversman et all2found that 21 of 39 patients with chronic pancreatitis who underwent sphincter of Oddi manometry had elevated basal sphincter pressures. Novis et alZofound that 21% of 33 patients with alcoholic pancreatitis had abnormal manometry. Tamasky et al” found that abnormal pancreatic sphincter manometric findings were more likely in patients with early chronic pancreatitis than in controls as assessed by endoscopic ultrasonography.Interestingly, Guelrud et all4 found that the topical application of rubbing alcohol onto the sphincter caused sphincter contraction. This finding may suggest that sphincter hypertension has a partial etiologic role in the pathogenesis of alcoholic pancreatitis. Finally, abnormal pancreatobiliary anatomy may cause dysfunction in emptying and be a causative factor in acute and chronic pancreatitis. A study of 18 patients= with abberrant perisphincter anatomy demonstrated a high rate of pancreatitis, acute and chronic, and a reduction in symptomatic attacks of pancreatitis after sphincterotomy in most patients. Sphincter dysfunction also is thought to have an important role in idiopathic acute recurrent pancreatitis. Several published studiesz2,35, 36 indicate that between 15% and 50% of patients with idiopathic pancreatitis may have pancreatic
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sphincter hypertension and that most of these patients have long-term relief after sphincterotomy.In the authors' experience, chronic pancreatitis that develops in these patients often requires resection to achieve durable relief despite endoscopic treatment of their pancreatic sphincter dysfunction. Early cases of acute relapsing pancreatitis caused by sphincter dysfunction are more amenable to sphincterotomy than more chronic cases. BlLlARY STRICTURES AND DUODENAL OBSTRUCTION
Secondary stricturing of the distal common bile duct caused by fibrotic changes in the head of the pancreas is a common complication of chronic pancreatitis. The stricture is usually long and smooth and can be distinguished from biliary obstruction caused by pancreatic cancer by virtue of its appearance on cholangiography. Proximal biliary dilation occurs gradually, ultimately leading to obstructive jaundice. Pain, if present, typically is related to fibrosing pancreatitis and not the biliary obstruction. Endoscopic drainage of the obstructed biliary tree is usually straightforward, with the placement of a straight Amsterdam plastic stent following the performance of biliary sphincterotomy. Stent occlusion is common and requires intermittent stent exchange. Dilation with catheter bougienage, or hydrostatic balloon dilation followed by the placement of single or multiple large bore stents, may result in an increase in the stricture lumen.6 The use of metallic expandable stents to palliate biliary obstruction in chronic pancreatitis is controversial because these stents are not removable and are prone to occlusion from biliary sludge.' The inner lumen of such stents is greater than that of the largest plastic stents (30 F vs. 12 F), and prolonged patency in comparison to plastic stents would be expected. In patients whose risk of surgical bypass is prohibitive, a metallic stent may be a reasonable approach for long-term palliation, but randomized trials are needed to prove the utility of this type of stent. Duodenal obstruction caused by inflammation, calcification, and fibrosis in the head of the pancreas occurs occasionally and is an indication for surgical bypass. In patients who are unfit for surgery, the placement of a luminal stent for the palliation of duodenal obstruction is feasible. Metallic, expandable stents are available for deployment in the tubular gut after bougienage to allow for placement by rather large (24-36 F) delivery devices. These stents have been used primarily in patients with advanced malignant disease and limited survival time, in whom palliation to allow for eating is not anticipated beyond several month^.^^,^^ Problems with these stents include angulation of the stent as it curves around the duodenal sweep. This results in a narrowed lumen, and provides a place for intermittent food impaction. In malignant disease, tumor growth is also a cause of stent occlusion. Like other metallic stents, these stents are not endoscopically removable and so are not recommended for most patients with chronic pancreatitis in whom long-term palliation is required. SUMMARY
Endoscopic therapy for chronic pancreatitis is feasible and effective in selected patients. The management of pain and ductal obstruction is most effective if reversal of the obstructive process-stricture or s t o n e i s successful and durable. Multiple endoscopic modalities are available, and new technologies will continue to advance the capabilities of therapeutic pancreatic endoscopists. Ad-
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junctive treatments, such as ESWL, enhance the success of these techniques. These varied therapies, although attractive and theoretically sensible, have not been compared in a randomized, controlled fashion with standard surgical therapies. In this sense, they remain experimental. Nonetheless, these techniques are widely applied in advanced endoscopy centers worldwide, and uncontrolled individual series are expected to continue to expound on and demonstrate the effectiveness of these minimally invasive interventions until randomized, prospective studies become available. References 1. Auroux J, Dumonceau JM, Deviere J, et al: A comparison of Wallstent and Diamond
metal stents for common bile duct (CBD) strictures caused by chronic pancreatitis [abstract]. Gastroenterology 1141785, 1998 2. Binmoeller KF, Jue P, Siefert H, et al: Endoscopic pancreatic stent drainage in pancreatitis and a dominant stricture: Long-term results. Endoscopy 27638-644, 1995 3. Bradley EL Pancreatic duct pressures in chronic pancreatitis. Am J Surg 1M313-316, 1982 4. Brand B, Thonke F, Obytz S, et al: Stent retriever for dilation of pancreatic and bile duct strictures. Endoscopy 31:142-145, 1999
5. Burdick JS, Geenen JE, Hogan WJ: Ductal morphologic changes due to pancreatic stent therapy: A randomized controlled study [abstract]. Am J Gastroenterol 87155, 1992 6. Catalan0 MF, Lahoti S, Geenen JE, et al: Treatment of symptomatic CBD strictures secondary to chronic pancreatitis: Comparison of single versus multiple, simultaneous endoscopic endoprosthesis [abstract]. Gastrointest Endosc 45:522,1997 7. Cremer M, Deviere J, Delhaye M, et al: Non-surgical management of severe chronic pancreatitis. Scand J Gastroenterol25(suppl 175):77-84, 1990 8. Cremer M [abstract]. Presented at the Third International Symposium on Endoscopy. Brussels, February 1977 9. Delhaye M, Vandermeeren A, Baize M, et al: Extracorporeal shock-wave lithotripsy of pancreatic calculi. Gastroenterology 102610420, 1992 10. Derfus GA, Geenen JE, Hogan WJ: Effects of endoscopic pancreatic duct stent placement in pancreatic ductal morphology [abstract]. Gastrointest Endosc 36206, 1990 11. Dumonceau JM, Deviere J, Le Moine 0, et al: Endoscopic pancreatic drainage in chronic pancreatitis associated with ductal stones: Long term results. Gastrointest Endosc 43:547-555, 1996 12. Eversman D, Fogel EL, Rusche M, et a1 Frequency of abnormal pancreatic and biliary sphincter manometry compared to clinical suspicion of sphincter dysfunction. Gastrointest Endosc 50:637-641, 1999 13. Geenen JH, Hogan WJ, Dodds WJ, et al: The efficacy of endoscopic sphincterotomy after cholecystectomy in patients with suspected sphincter of Oddi dysfunction. N Engl J Med 320:82-87, 1989 14. Guelrud M, Mendoza S, Rossiter G, et al: Effect of local instillation of alcohol on sphincter of Oddi activity: Combined ERCP and manometry study. Gastrointest Endosc 37428-432, 1991 15. Johlin FC, Pate1 RS, Brown BP: Silastic pancreatic "wedge stents": An alternative to polyethylene stents [abstract]. Gastrointest Endosc 45:537, 1997 16. Josephs M, Heier SK, Chan C, et al: Factors predicting pancreatic stent occlusion [abstract]. Gastrointest Endosc 45:538, 1997 17. Kasmin FE, Khan M, Cohen SA, et al: Endoscopic therapy of idiopathic pancreatitis [abstract]. Gastrointest Endosc 41:518, 1995 18. Kozarek RA: Pancreatic stents can induce chronic changes consistent with chronic pancreatitis. Gastrointest Endosc 3693-95, 1990 19. Nevitt AW, Vida F, Kozarek RA, et al: Expandable metallic prostheses for malignant obstructions of gastric outlet and proximal small bowel. Gastrointest Endosc 47271276, 1998
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20. Novis BH, Bomman PC, Girdwood AW, et al: Endoscopic manometry of the pancreatic duct and sphincter zone in patients with chronic pancreatitis. Dig Dis Sci 30525-228, 1985
21. Ponchon T, Bory RM, Hedelius F, et al: Endoscopic stenting for pain relief in chronic pancreatitis: Results of a standardized protocol. Gastrohitest Endosc 42:452456, 1995 22. Raddawi HM, Geenen JE, Hogan WJ, et al: Pressure measurements from biliary and pancreatic segments of the sphincter of Oddi: Comparison between patients with functional abdominal pain, biliary, or pancreatic disease. Dig Dis Sci 36:71-74, 1991 23. Samavedy R, Sherman S, Lehman G A Endoscopic therapy in anomalous pancreatobiliary duct junction. Gastrointest Endosc 50:623-627, 1999 24. Sauerbruch T, Holl J, Sackmann M, et al: Extracorporeal shock wave lithotripsy of pancreatic stones. Gut 30:140&1411, 1989 25. Schneider MU, Lux G Floating pancreatic duct concrements in chronic pancreatitis. Endoscopy 178-10,1985 26. Sherman S, Troiano FP, Hawes RH, et al: Sphincter of Oddi manometry: Decreased risk of clinical pancreatitis with the use of a modified aspirating catheter. Gastrointest Endosc 36:462466, 1990 27. Siegel JH: Pancreatic disorders: Inflammatory, congenital, and malignant. In Siegel JH (ed): Endoscopic Retrograde Cholangiopancreatography.New York, Raven Press, 1992, pp 123-174 28. Siegel JH: Cholangeopancreatoplasty:Hydrostatic dilatation of strictures of the biliary tree and pancreas. In Siegel JH (ed): Endoscopic Retrograde Cholangiopancreatography. New York, Raven Press, 1992, pp 364-395 29. Siegel JH. Stone extraction, lithotripsy, stents, and stones. In Siegel JH (ed): Endoscopic Retrograde Cholangiopancreatography. New York, Raven Press, 1992, pp 227-271 30. Siegel JH, Pullano W. Two new methods for selective bile duct cannulation and sphincterotomy. Gastrointest Endosc 33:438-440, 1987 31. Singer SB, Asch M: Metallic stents in the treatment of duodenal obstruction: Technical issues and results. Canadian Association of Radiologists Journal 51:121-129, 2000 32. Smith MT, Sherman S, Ikenberry SO, et al: Alterations in pancreatic ductal morphology following polyethylene pancreatic stent therapy. Gastrointest Endosc M268-275, 1996 33. Smits ME, Rauws EAJ, Tytgat GNJ, et al: Endoscopic treatment of pancreatic stones in patients with chronic pancreatitis. Gastrointest Endosc 43:556-560, 1996 34. Tamasky PR, Hoffman B, Aabakken L, et al: Sphincter of Oddi dysfunction is associated with chronic pancreatitis. Am J Gastroenterol92:11251129, 1997 35. Toouli J, Francesco VD, Saccone G, et a1 Division of the sphincter of Oddi for the treatment of dysfunction associated with chronic pancreatitis. Br J Surg 83:1205-1210, 1996 36. Venu RP, Geenen JE, Hogan WJ, et a1 Idiopathic recurrent pancreatitis: An approach to diagnosis and treatment. Dig Dis Sci 3456-60, 1989 37. Warshaw AL, Popp JW, Schapiro RH:Long-term patency, pancreatic function, and pain relief after lateral pancreaticojejunostomy for chronic pancreatitis. Gastroenterology 79289-293,1981
Address reprint requests to Franklin E. Kasmin, MD 60 East End Avenue New York, NY 10028
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ENDOSCOPIC THERAPY FOR CHRONIC PANCREATITIS Franklin E. Kasmin, MD, and Jerome H. Siegel, MD
Endoscopic management of chronic pancreatitis was first reported in 19778 with the performance of pancreatic sphincterotomy for relief of an impacted pancreatic ductal stone. Since then, pancreatic endoscopic therapy has become an important, albeit controversial, alternative therapy for patients with chronic pancreatitis not amenable to surgical management.27The development of pancreatic endoscopic therapy has been driven by clinicians' desire to provide a nonsurgical means of palliating some of the complications of chronic pancreatitis. Various pancreatic abnormalities, including stone disease, ductal strictures, fluid collections, and functional sphincter disorders, all can be treated endoscopically. Adjuvant therapy to the bile duct, in the case of pancreatitis-induced biliary strictures, and the stenting of the obstructed duodenum are also feasible endoscopically. The relief of pain is generally the most compelling reason for endoscopic management of chronic pancreatitis. As with surgical ductal decompression, the goal of endoscopic management of pain in chronic pancreatitis is ductal decompre~sion.~, 37 Endoscopic techniques, such as stenting or stone extraction, can reestablish pancreatic drainage and reduce ductal pressures while maintaining pancreatic secretory activity in a functional gland. Ductal obstruction in chronic pancreatitis occurs in several ways. Fibrotic strictures can occur as a result of recurrent acute episodes of pancreatitis. Stone disease can present as parenchymal calcification resulting in an extrinsic compression of the pancreatic duct or as intraductal stone disease. Periampullary and sphincteric disease can lead to ductal hypertension and recurrent episodes of acute pancreatitis. The goal of endoscopic therapy in each situation is the relief of obstruction by the removal of its cause, as in the case of stone extraction or sphincter ablation, or in the stenting of the pancreatic duct. From the Albert Einstein College of Medicine (FEK, JHS); the Department of Medicine (FEK), and Endoscopy (IHS), Division of Gastroenterology, Beth Israel Medical Center, New York, New York SURGICAL CLINICS OF NORTH AMERICA VOLUME 81 NUMBER 2 APRIL 2001
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THERAPY FOR STRICTURES
Fibrotic strictures can occur at any point along the pancreatic duct; however, in most patients who present with painful chronic pancreatitis, stricturing develops in the head, rather than the tail, of the gland. The approach to these strictures involves dilation and stenting to provide short- or long-term decompression (Fig. 1 ). Pancreatic endoscopic therapy generally begins with sphincterotomy of the pancreatic sphincter. This maneuver permits the introduction of endoscopic accessories, ensures repeated selective access to the duct, and enhances the flow of pancreatic juice. Pancreatic sphincterotomy can be performed alone or in combination with biliary sphincterotomy, and the decision to perform one or both sphincterotomies is based on the initial ease of access into the two ductal systems. Deep access into the pancreatic duct in chronic pancreatitis can be difficult. Although access to the pancreatic duct after sphincterotomy usually can be achieved de novo, further entry into the body or tail may require the use of a guidewire. This is especially true in the region of the stricture itself. Advances in guidewire technology make the negotiation of these strictures successful in most cases. Wires that use a hydrophilic coating and a floppy atraumatic tip are
Figure 1. A tight stricture (A) is dilated first with a catheter remover (C), after which a stent is placed (0).
(B)and then a screw-tip stent
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especially useful. The authors favor the use of a modified 7 F dilating catheter (Siegel-Cohen, Wilson Cook, Inc., Winston-Salem, NC) for introduction of the wire because this allows for stricture dilation and simplified guidewire exchange by virtue of its large inner diameter.30 Although the stricture usually can be traversed easily with a guidewire, the passage of the catheter over the guidewire and across the stricture is not always as easy. Difficult strictures may result from intense local fibrosis, extrinsic compression of the duct by parenchymal calcification, or an acute angulation of the duct. Techniques to assist the crossing of a stricture include the use of gradual catheter dilation; balloon dilation using an angioplasty balloon**;or the use of a coiled wire stent removal device, which acts as a screw or drill bit? This last technique is perhaps most attractive because the technique uses a cable with a screw tip to core its way across a stricture, disrupting ductal fibrosis and perhaps resulting in a more permanent strictureplasty than can be achieved with dilation by a balloon or catheter. After access to the duct has been achieved across a stricture, stent placement is performed to ensure postprocedural drainage. Polyethylene stents typically are used, and the appropriate stent length is tailored to the distance a stricture lies from the sphincter orifice. Stents are usually 5.0 or 7.0 F, but 8.5, 10.0, or 11.5 F drains also can be placed in patients with large-diameter ducts undergoing long-term stricture dilation. Stent design varies, but the authors prefer a C loop stent with a curl in the duodenum to prevent in-migration and an inner flap to prevent out-migration.Side holes are cut along the length of the stent to promote side branch drainage. Alternative methods of stent design include straight stents, which may promote flow of juice but be more apt to migrate into the duct, and Silastic stents, which may be less likely to irritate the pancreatic ductal m~cosa.’~ Drainage of pancreatic juice across a stricture is expected to result in a decrease in ductal pressures and a diminution in pain for patients in whom pain is related to obstruction. The reestablishment of ductal drainage also may result in an improvement in malabsorption; however, for these benefits to persist, the stent must remain patent. Unfortunately, stents have a limited life patency,I6 and stent occlusion can be expected after an average of 2 to 4 months. Plugs comprised of proteinaceous material and calcium stone debris form along the length of the stent and especially at the tip in the duodenum. Although a stent often can act as a ”wick,” permitting flow around its outer skin, occlusion may lead to recurrent pain or even a suppurative ductal process analogous to the infections seen with cholangitis and the occluded bile duct stent. Stricture dilation may occur with time when a stent has been left in place, so stent therapy in chronic pancreatitis may be carried out over a period of many months. The authors follow an algorithm that begins with a pancreatic sphincterotomy and the placement of an initial stent, usually 7 F because this is typically the largest stent that can be passed initially. Stricture dilation is carried out before stent placement with the 7 F Siegel-Cohen catheter or the screwtipped stent remover, if necessary. The patient returns within 4 months, at which time the stent is removed and the tightness of the stricture and drainage of contrast medium from the duct is assessed. If the stricture persists, further dilation and the passage of a larger stent, usually 8.5 F, are carried out. Additional sessions of endoscopic therapy are carried out if the stricture persists; the ultimate goal is to insert a 10 F stent (or larger) for several months to allow for maximum stricture dilation. All stents are ultimately removed at some point, and clinical results are assessed. If the patient’s symptoms remain improved, regardless of the radiologic appearance of the gland, the patient is observed and provided supplemental pancreatic enzymes, if necessary. If the patient has
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recurrence of symptoms following stent removal, the stent is replaced in the largest size possible, and the patient is referred for consideration of surgical drainage. In the event that a patient derives no relief from stent therapy, longterm pharmacologic pain management therapy is advised. The authors believe that the response to stent therapy predicts the response to surgical decompression and that patients who do not improve with endoscopic drainage are best managed medically or with resection. The results of stenting in patients with chronic pancreatitis and strictures are difficult to assess accurately because prospective randomized studies comparing surgical versus medical versus endoscopic alternatives exist. Binmoeller et a12 treated 93 patients having dominant strictures on ductography with serial dilation and stenting for pain relief. In this uncontrolled, retrospective study, partial or complete pain relief occurred in 74% of patients. Eighty-seven percent of patients continued to have pain relief when evaluated in follow-up at a mean of 4.9 years. Using a similar approach, Cremer et a17 reported symptom relief in 55% of patients at a mean follow-up of 2 years; however, almost half required ongoing stent therapy. Complications included clinically apparent stent occlusion in 20% and stent migration in 10% of patients. Ponchon et a121reported a standardized protocol of stricture dilation and stenting for 6 months. Stents were removed after the study period, and pain control was assessed. Seventy-four percent of patients had early relief of pain, and 52% remained substantially asymptomatic at 1-year follow-up. Complications of pancreatic stent therapy include acute events occurring after endoscopic retrograde cholangiopancreatography (ERCP) and complications that occur during the protracted course of therapy. Early complications include acute pancreatitis, bleeding, perforation, and fluid collection formation. In the authors’ series of 59 patients undergoing pancreatic sphincterotomy, the rate of acute pancreatitis was lo%, with a mean hospital stay of 3.7 days.17 The Ponchon series had a pancreatitis rate of 41%, perhaps because of the use of hydrostatic balloon dilation of the pancreatic duct. The authors’ impression is that manipulation of the pancreatic duct in patients with chronic pancreatitis is less likely to cause severe acute pancreatitis than is a similar manipulation in patients with healthy pancreatic ducts. Most episodes of acute post-ERCP pancreatitis clear quickly. Ductal changes from indwelling pancreatic stents are a troubling long-term consequence of endoscopic therapy for chronic pancreatitis.5,lo,18,32 Smith et a132 found that 80% of patients undergoing pancreatic stent therapy developed new morphologic changes on removal of the stent. These changes occurred in patients with healthy ducts and in those with prior chronic abnormalities and are concerning because the induced changes have the appearance of strictures seen in chronic pancreatitis. Fortunately, most changes are reversible, although 37% of patients had residual stent-related abnormalities at a mean follow-up of 6.4 months. The long-term clinical consequences of these ductal changes, if any, are unknown.
THERAPY FOR DUCTAL STONE DISEASE
Ductal stones can produce obstruction and pain.9,24, 25 Stones may be attached to the wall of the duct, lie within the parenchyma, or be free floating within the duct. Stone material can cause ductal obstruction, thereby causing pain (Fig. 2A). In the case of intraductal stones, the duct is obstructed by intrinsic
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Figure 2. A, A stone impacted in the pancreatic ductal orifice. Alcoholic pancreatitis with stone disease before (6)and after (C)endoscopic therapy. obstruction at the level of the pancreatic orifice or at the level of a ductal stricture. In the case of parenchymal stone disease, extrinsic compression of the main duct can occur because the concretions cause mass effect and local inflammatory changes. Therapeutic interventions aimed at relief of obstruction include (1) stenting to provide short- or long-term decompression and (2) stone extraction (Fig. 2B and C). Most often, pancreatic calculi form behind a duct stricture and the stricture is simultaneously treated. Initial therapy is with pancreatic sphincterotomy. This maneuver enhances pancreatic drainage and facilitates the extraction of stone material. The techniques required to remove a pancreatic stone are similar to that used for biliary stone extraction. A Dormia-type basket is used most commonly to engage the floating stone within the duct and attempt extraction. In the case of stones attached to the wall, the basket does not seem to spread its arms around the stone; instead, the basket remains collapsed as it passes by the stone. Stones may be quite soft and crumble during basket manipulation or, conversely, be quite rigid and densely calcified, remaining substantially intact. In some instances, a stone may be too large to deliver intact through the pancreatic orifice. In this situation, lithotripsy is used. Mechanical lithotripsy uses a standard wire basket that is forcefully drawn into a stiff cable housing after the stone is engaged. The action of the four basket wires retracting into the cable causes a slicing of the stone into four pieces that can be further crushed or removed with a standard basket. Additional small fragments may be removed with an occlusion balloon. Several commercially available mechanical lithotripters are designed as a dedicated unit, but a standard basket can be used for lithotripsy by advancing
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an appropriately sized cable over the disassembled basket after the stone is engaged within its arms. Hence, even if a standard basket has become imvacted wiuhk the duct around a large stone, ”emergency” lithotripsy can b’e performed.29 If a stone is heavily calcified and rigid, lithotripsy may not be successful. In this instance, the basket may remain engaged around the stone, or the stone may be impacted but the basket cannot be disengaged. Continued forceful withdrawal of the basket cables ultimately causes breakage of the wires holding the stone, and the cables then are removed from the endoscope. Residual basket wire pieces typically remain in the duct and usually can be removed with endoscopic grabbing forceps. Many patients have intraductal stones that cannot be removed by mechanical means and are not amenable to lithotripsy. If a stone is large or positioned tightly within the duct, room may be inadequate for a basket to spread its arms around the stone, making basket extraction or lithotripsy impossible. Finally, a stricture positioned between the papilla and the stone may make extraction of sizable fragments unlikely. In these situations, the use of extracorporeal shock wave lithotripsy (ESWL)9,24 can fracture stones into sufficiently small pieces to allow for more complete duct clearance. ESWL is carried out with the patient under intravenous sedation using an x-ray focused beam. Each session lasts approximately 1 hour and delivers approximately 3000 shocks per session. Multiple sessions often are needed to satisfactorily fragment the stones. When stones are radiolucent, a nasopancreatic drain usually is left in place so that contrast medium injection and guidance of the beam can be carried out at the time of ESWL. Subsequent ERCP is carried out, and extraction of stone material is attempted. Pancreatic stents can be placed if drainage is incomplete, and the need for further ESWL sessions is assessed. Stricture dilation is performed as needed to facilitate the removal of stone fragments. When this situation is encountered and multiple sessions are required, surgery seems quite reasonable. The results of clinical studies using endoscopic pancreatic stone extraction for treatment of chronic pancreatitis have been promising. In 1985, Schneider and Luxz5reported immediate pain relief in three of three patients undergoing pancreatic sphincterotomy and stone clearance. Delhaye et a19 found complete or partial pain relief in 75 of 88 patients with relapsing pancreatitis in whom ESWL and duct decompression were used. Cremer et all1 reported durable pain relief (2 years) in 54% of 70 patients who had undergone ductal drainage. The complete clearance of the duct, a decrease in the ductal diameter, and the use of ESWL were associated with long-term improvement. Smits et a133accomplished complete stone extraction in 39 of 53 patients with chronic pancreatitis and achieved complete pain relief in all but one patient. A combination of sphincterotomy, stent placement, mechanical lithotripsy, ESWL, and basket extraction was used. THERAPY FOR SPHINCTER DYSFUNCTION A hypertensive or stenotic sphincter is a theoretic cause for ductal hypertension in the biliary and pancreatic ductal systems.l2,20*34 In the patients undergoing cholecystectomy, sphincter hypertension can cause pain and sphincterotomy can be curative. Because ductal hypertension may be at least partially responsible for pain in patients with chronic pancreatitis, it is sensible to consider that lowering pancreatic ductal pressures may improve pain. Furthermore, it is con-
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ceivable that ductal hypertension, as a result of primary or secondary sphincter dysfunction, may be partially responsible for the occurrence of chronic pancreatitis in some patients. Patients with possible sphincter dysfunction are classified according to the presence of objective findings before the performance of sphincter of Oddi manometry. Those with presumed biliary dysfunction and pain are classified according to the presence or absence of duct dilation, delayed ductal drainage, and liver function test abnormalities. Type 1 patients have pain plus all three objective criteria; type 2 patients have pain plus one or two objective findings; and type 3 patients have pain only. Geenen et all3 originally put forth this classification system; it has been modified to classify patients with pancreatic sphincter dysfunction. Hyperamylasemia, more than 5-mm dilation of the pancreatic duct, and delay in drainage of the pancreatic duct beyond 8 minutes after endoscopic injection are the objective parameters used to classify patients in the ”modified Milwaukee” scale.12This classification system is most useful in patients who suffer recurrent attacks of pain; however, if sphincter dysfunction is responsible for recurrent attacks of acute pancreatitis, then chronic changes can be expected to ultimately occur. Sphincter of Oddi manometry is performed at the time of ERCP. A waterperfused catheter with three lumens typically is used. At the authors’ institution (Beth Israel), two lumens are used to measure sphincter pressures while the third central lumen is used for guidewire passage and pancreatic juice aspiration because aspiration of perfused liquid is associated with a decreased risk for post-ERCP pancreatitis.26The catheter is initially placed into the duodenum, where the luminal pressure is measured and used as baseline. The catheter is then advanced into the duct, and a slow pull-through across the sphincter is performed. If the mean level of relaxation across the sphincter is more than 40 mm Hg, then the basal sphincter pressure is considered elevated. Peak sphincter pressures and the frequency of contractions are thought to be less important. Sphincterotomy of the symptomatic hypertensive sphincter is the treatment of choice. Placement of a stent in the pancreatic duct is thought to be protective against severe pancreatitis. A thin 5 F stent with no internal flaps typically is used to intentionally allow stent out-migration. If migration does not occur, the stent is removed within 2 weeks, especially in patients with minimal ductal changes, to avoid further ductal damage. Sphincter dysfunction of the pancreatic sphincter may be common in chronic pancreatitis. Eversman et all2found that 21 of 39 patients with chronic pancreatitis who underwent sphincter of Oddi manometry had elevated basal sphincter pressures. Novis et alZofound that 21% of 33 patients with alcoholic pancreatitis had abnormal manometry. Tamasky et al” found that abnormal pancreatic sphincter manometric findings were more likely in patients with early chronic pancreatitis than in controls as assessed by endoscopic ultrasonography.Interestingly, Guelrud et all4 found that the topical application of rubbing alcohol onto the sphincter caused sphincter contraction. This finding may suggest that sphincter hypertension has a partial etiologic role in the pathogenesis of alcoholic pancreatitis. Finally, abnormal pancreatobiliary anatomy may cause dysfunction in emptying and be a causative factor in acute and chronic pancreatitis. A study of 18 patients= with abberrant perisphincter anatomy demonstrated a high rate of pancreatitis, acute and chronic, and a reduction in symptomatic attacks of pancreatitis after sphincterotomy in most patients. Sphincter dysfunction also is thought to have an important role in idiopathic acute recurrent pancreatitis. Several published studiesz2,35, 36 indicate that between 15% and 50% of patients with idiopathic pancreatitis may have pancreatic
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sphincter hypertension and that most of these patients have long-term relief after sphincterotomy.In the authors' experience, chronic pancreatitis that develops in these patients often requires resection to achieve durable relief despite endoscopic treatment of their pancreatic sphincter dysfunction. Early cases of acute relapsing pancreatitis caused by sphincter dysfunction are more amenable to sphincterotomy than more chronic cases. BlLlARY STRICTURES AND DUODENAL OBSTRUCTION
Secondary stricturing of the distal common bile duct caused by fibrotic changes in the head of the pancreas is a common complication of chronic pancreatitis. The stricture is usually long and smooth and can be distinguished from biliary obstruction caused by pancreatic cancer by virtue of its appearance on cholangiography. Proximal biliary dilation occurs gradually, ultimately leading to obstructive jaundice. Pain, if present, typically is related to fibrosing pancreatitis and not the biliary obstruction. Endoscopic drainage of the obstructed biliary tree is usually straightforward, with the placement of a straight Amsterdam plastic stent following the performance of biliary sphincterotomy. Stent occlusion is common and requires intermittent stent exchange. Dilation with catheter bougienage, or hydrostatic balloon dilation followed by the placement of single or multiple large bore stents, may result in an increase in the stricture lumen.6 The use of metallic expandable stents to palliate biliary obstruction in chronic pancreatitis is controversial because these stents are not removable and are prone to occlusion from biliary sludge.' The inner lumen of such stents is greater than that of the largest plastic stents (30 F vs. 12 F), and prolonged patency in comparison to plastic stents would be expected. In patients whose risk of surgical bypass is prohibitive, a metallic stent may be a reasonable approach for long-term palliation, but randomized trials are needed to prove the utility of this type of stent. Duodenal obstruction caused by inflammation, calcification, and fibrosis in the head of the pancreas occurs occasionally and is an indication for surgical bypass. In patients who are unfit for surgery, the placement of a luminal stent for the palliation of duodenal obstruction is feasible. Metallic, expandable stents are available for deployment in the tubular gut after bougienage to allow for placement by rather large (24-36 F) delivery devices. These stents have been used primarily in patients with advanced malignant disease and limited survival time, in whom palliation to allow for eating is not anticipated beyond several month^.^^,^^ Problems with these stents include angulation of the stent as it curves around the duodenal sweep. This results in a narrowed lumen, and provides a place for intermittent food impaction. In malignant disease, tumor growth is also a cause of stent occlusion. Like other metallic stents, these stents are not endoscopically removable and so are not recommended for most patients with chronic pancreatitis in whom long-term palliation is required. SUMMARY
Endoscopic therapy for chronic pancreatitis is feasible and effective in selected patients. The management of pain and ductal obstruction is most effective if reversal of the obstructive process-stricture or s t o n e i s successful and durable. Multiple endoscopic modalities are available, and new technologies will continue to advance the capabilities of therapeutic pancreatic endoscopists. Ad-
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junctive treatments, such as ESWL, enhance the success of these techniques. These varied therapies, although attractive and theoretically sensible, have not been compared in a randomized, controlled fashion with standard surgical therapies. In this sense, they remain experimental. Nonetheless, these techniques are widely applied in advanced endoscopy centers worldwide, and uncontrolled individual series are expected to continue to expound on and demonstrate the effectiveness of these minimally invasive interventions until randomized, prospective studies become available. References 1. Auroux J, Dumonceau JM, Deviere J, et al: A comparison of Wallstent and Diamond
metal stents for common bile duct (CBD) strictures caused by chronic pancreatitis [abstract]. Gastroenterology 1141785, 1998 2. Binmoeller KF, Jue P, Siefert H, et al: Endoscopic pancreatic stent drainage in pancreatitis and a dominant stricture: Long-term results. Endoscopy 27638-644, 1995 3. Bradley EL Pancreatic duct pressures in chronic pancreatitis. Am J Surg 1M313-316, 1982 4. Brand B, Thonke F, Obytz S, et al: Stent retriever for dilation of pancreatic and bile duct strictures. Endoscopy 31:142-145, 1999
5. Burdick JS, Geenen JE, Hogan WJ: Ductal morphologic changes due to pancreatic stent therapy: A randomized controlled study [abstract]. Am J Gastroenterol 87155, 1992 6. Catalan0 MF, Lahoti S, Geenen JE, et al: Treatment of symptomatic CBD strictures secondary to chronic pancreatitis: Comparison of single versus multiple, simultaneous endoscopic endoprosthesis [abstract]. Gastrointest Endosc 45:522,1997 7. Cremer M, Deviere J, Delhaye M, et al: Non-surgical management of severe chronic pancreatitis. Scand J Gastroenterol25(suppl 175):77-84, 1990 8. Cremer M [abstract]. Presented at the Third International Symposium on Endoscopy. Brussels, February 1977 9. Delhaye M, Vandermeeren A, Baize M, et al: Extracorporeal shock-wave lithotripsy of pancreatic calculi. Gastroenterology 102610420, 1992 10. Derfus GA, Geenen JE, Hogan WJ: Effects of endoscopic pancreatic duct stent placement in pancreatic ductal morphology [abstract]. Gastrointest Endosc 36206, 1990 11. Dumonceau JM, Deviere J, Le Moine 0, et al: Endoscopic pancreatic drainage in chronic pancreatitis associated with ductal stones: Long term results. Gastrointest Endosc 43:547-555, 1996 12. Eversman D, Fogel EL, Rusche M, et a1 Frequency of abnormal pancreatic and biliary sphincter manometry compared to clinical suspicion of sphincter dysfunction. Gastrointest Endosc 50:637-641, 1999 13. Geenen JH, Hogan WJ, Dodds WJ, et al: The efficacy of endoscopic sphincterotomy after cholecystectomy in patients with suspected sphincter of Oddi dysfunction. N Engl J Med 320:82-87, 1989 14. Guelrud M, Mendoza S, Rossiter G, et al: Effect of local instillation of alcohol on sphincter of Oddi activity: Combined ERCP and manometry study. Gastrointest Endosc 37428-432, 1991 15. Johlin FC, Pate1 RS, Brown BP: Silastic pancreatic "wedge stents": An alternative to polyethylene stents [abstract]. Gastrointest Endosc 45:537, 1997 16. Josephs M, Heier SK, Chan C, et al: Factors predicting pancreatic stent occlusion [abstract]. Gastrointest Endosc 45:538, 1997 17. Kasmin FE, Khan M, Cohen SA, et al: Endoscopic therapy of idiopathic pancreatitis [abstract]. Gastrointest Endosc 41:518, 1995 18. Kozarek RA: Pancreatic stents can induce chronic changes consistent with chronic pancreatitis. Gastrointest Endosc 3693-95, 1990 19. Nevitt AW, Vida F, Kozarek RA, et al: Expandable metallic prostheses for malignant obstructions of gastric outlet and proximal small bowel. Gastrointest Endosc 47271276, 1998
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20. Novis BH, Bomman PC, Girdwood AW, et al: Endoscopic manometry of the pancreatic duct and sphincter zone in patients with chronic pancreatitis. Dig Dis Sci 30525-228, 1985
21. Ponchon T, Bory RM, Hedelius F, et al: Endoscopic stenting for pain relief in chronic pancreatitis: Results of a standardized protocol. Gastrohitest Endosc 42:452456, 1995 22. Raddawi HM, Geenen JE, Hogan WJ, et al: Pressure measurements from biliary and pancreatic segments of the sphincter of Oddi: Comparison between patients with functional abdominal pain, biliary, or pancreatic disease. Dig Dis Sci 36:71-74, 1991 23. Samavedy R, Sherman S, Lehman G A Endoscopic therapy in anomalous pancreatobiliary duct junction. Gastrointest Endosc 50:623-627, 1999 24. Sauerbruch T, Holl J, Sackmann M, et al: Extracorporeal shock wave lithotripsy of pancreatic stones. Gut 30:140&1411, 1989 25. Schneider MU, Lux G Floating pancreatic duct concrements in chronic pancreatitis. Endoscopy 178-10,1985 26. Sherman S, Troiano FP, Hawes RH, et al: Sphincter of Oddi manometry: Decreased risk of clinical pancreatitis with the use of a modified aspirating catheter. Gastrointest Endosc 36:462466, 1990 27. Siegel JH: Pancreatic disorders: Inflammatory, congenital, and malignant. In Siegel JH (ed): Endoscopic Retrograde Cholangiopancreatography.New York, Raven Press, 1992, pp 123-174 28. Siegel JH: Cholangeopancreatoplasty:Hydrostatic dilatation of strictures of the biliary tree and pancreas. In Siegel JH (ed): Endoscopic Retrograde Cholangiopancreatography. New York, Raven Press, 1992, pp 364-395 29. Siegel JH. Stone extraction, lithotripsy, stents, and stones. In Siegel JH (ed): Endoscopic Retrograde Cholangiopancreatography. New York, Raven Press, 1992, pp 227-271 30. Siegel JH, Pullano W. Two new methods for selective bile duct cannulation and sphincterotomy. Gastrointest Endosc 33:438-440, 1987 31. Singer SB, Asch M: Metallic stents in the treatment of duodenal obstruction: Technical issues and results. Canadian Association of Radiologists Journal 51:121-129, 2000 32. Smith MT, Sherman S, Ikenberry SO, et al: Alterations in pancreatic ductal morphology following polyethylene pancreatic stent therapy. Gastrointest Endosc M268-275, 1996 33. Smits ME, Rauws EAJ, Tytgat GNJ, et al: Endoscopic treatment of pancreatic stones in patients with chronic pancreatitis. Gastrointest Endosc 43:556-560, 1996 34. Tamasky PR, Hoffman B, Aabakken L, et al: Sphincter of Oddi dysfunction is associated with chronic pancreatitis. Am J Gastroenterol92:11251129, 1997 35. Toouli J, Francesco VD, Saccone G, et a1 Division of the sphincter of Oddi for the treatment of dysfunction associated with chronic pancreatitis. Br J Surg 83:1205-1210, 1996 36. Venu RP, Geenen JE, Hogan WJ, et a1 Idiopathic recurrent pancreatitis: An approach to diagnosis and treatment. Dig Dis Sci 3456-60, 1989 37. Warshaw AL, Popp JW, Schapiro RH:Long-term patency, pancreatic function, and pain relief after lateral pancreaticojejunostomy for chronic pancreatitis. Gastroenterology 79289-293,1981
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