Endoscopic Palliation for Unresectable Pancreatic Carcinoma

0039-6109/95 $0.00

PANCREATIC NEOPLASMS

+ .20

ENDOSCOPIC PALLIATION FOR UNRESECTABLE PANCREATIC CARCINOMA David R. Lichtenstein, MD, and David L. Carr-Locke, MD, FRCP, FACG

Considerable progress has been made in understanding the pathogenesis, diagnosis, staging, and surgical and palliative nonsurgical treatments of pancreatic malignancy. A thorough appreciation of tumor biology and treatment options is important for managing individuals with pancreatic carcinoma. It is necessary to establish the patient's potential for cure based on lesion resectability and fitness for surgery. These tumors are biologically aggressive and typically present with locoregional or distant tumor spread, leaving palliative treatment to improve quality of life as the primary focus of therapy. Management of these patients requires a multidisciplinary team approach with input from the subspecialties of surgery, gastrointestinal endoscopy, oncology, and radiology. Prolonged biliary obstruction may result in malabsorption, progressive malnutrition, coagulopathy, pruritus, hepatocellular failure, renal dysfunction, and cholangitis favoring palliative biliary drainage to alleviate these disturbances. Nonsurgical techniques to restore bile duct patency are preferable to surgical alternatives in patients without other indications for operative therapy such as duodenal invasion by tumor, a complication that also may now be managed nonoperatively. Both endoscopic and percutaneous transhepatic radiologic approaches result in success rates equivalent to surgical biliary bypass procedures, with lower procedure-related morbidity and mortality, shorter initial hospital-

From the Division of Gastroenterology, Brigham and Women's Hospital; and Harvard Medical School, Boston, Massachusetts

SURGICAL CLINICS OF NORTH AMERICA VOLUME 75 • NUMBER 5 • OCTOBER 1995

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ization, and lower costs. Furthermore, endoscopic approaches offer advantages over the percutaneous techniques, with fewer procedure-related complications and better patient acceptance. The technique of biliary stent insertion for palliation of malignant obstructive jaundice was first described by Soehendra and ReyndersFrederix in 1980.83 The methodology and range of equipment currently available have been well standardized. Experience with endoprosthesis insertion suggests that, in centers performing it regularly, a technical success rate of at least 85% to 90% should be expected, with relief of jaundice and pruritus in over 80% of such individuals. Morbidity associated with stent insertion varies from 0 to 35%, but major morbidity remains well under 10%. ENDOSCOPIC METHODS FOR STENT PLACEMENT Indications and Efficacy

Prior to palliative stent placement, it is important to establish that the jaundice is the result of biliary obstruction and not secondary to intrahepatic metastatic disease. This can usually be assessed by hepatic imaging studies with computed tomography, ultrasonography, or magnetic resonance imaging. The second important question is whether alleviating jaundice is likely to provide true palliation to the patient. Many patients in the terminal stages of their illness are unlikely to benefit from aggressive measures, which under these circumstances may be considered inappropriate. Patients with compression of the second portion of the duodenum have been well served by a "double surgical bypass procedure" composed of a gastrojejunostomy and biliary-enteric anastomosis. Alternatively, those individuals with high operative risk may undergo biliary decompression followed by endoscopic placement of an expandable metallic stent within the duodenum. The most suitable palliative treatment for malignant biliary obstruction must be determined from an array of choices that include surgical, percutaneous, and endoscopic techniques. Provided that expertise is available and there is access to the papilla, endoscopic cholangiography is preferable to transhepatic biliary techniques. Endoscopic placement is less invasive and safer and provides additional information regarding assessment of the main papilla and pancreatic ductal system. Successful endoscopic insertion of a biliary endoprosthesis can be technically achieved in 80% to 90% of these patients,3, 5,15, 22, 32 with normalization of bilirubin in the overwhelming majority of cases (Table 1). Technical Considerations

The procedure required for endoscopic placement of a biliary endoprosthesis follows endoscopic retrograde cholangiopancreatography

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Table 1. RESULTS OF ENDOSCOPIC STENTING FOR CARCINOMA OF THE PANCREAS IN PATIENTS AT HIGH RISK FOR SURGERY

Number Mean age (years) Relief of jaundice Mortality (30 days) Mean survival (weeks) Duodenal obstruction Stent exchange

University of Amsterdam (32)

Middlesex Hospital (84)

Siegel (78)

221 71 87% 10% 26 7.5% 21%

99 76 88% 9% 25 6% 29.5%

311 73 89% 18% 18 0% 30%

(ERCP) and is performed under conscious sedation. Prior to the ERCP, prophylactic antibiotics are usually administered and coagulation defects are corrected with vitamin K and fresh frozen plasma. Both biliary tree and pancreatic duct should be evaluated to delineate the anatomy and the nature of the malignant process. Defining the location and length of the bile duct stricture is essential prior to endoprosthesis insertion, and the proximal biliary system is filled sufficiently to assess the proximal extent of stricturing and to exclude additional intrahepatic strictures. Following the diagnostic aspect of the ERCP, deep cannulation is attempted with the biliary catheter, that is, insertion of the biliary catheter across the papilla into the lumen of the bile duct. This occasionally requires the assistance of a guide wire or sphincterotome. Precut sphincterotomy with a needle knife or precut papillatome may be necessary in selected patients when deep cannulation cannot be achieved otherwise.71 Once deep cannulation has been accomplished, a 0.035 inch guide wire is manipulated across the stricture to the level of the right or left hepatic ducts. A stiff polyethylene inner catheter with radiopaque markers located 7 cm apart is then placed over the guide wire and the stent pushed over this inner catheter with a pusher device as a three-layer system (Fig. 1). The inner catheter and guide wire can then be withdrawn and the stent left in proper position. Endoscopic transpapillary wire-guided brush cytology, 20, 21, 92 needle aspiration,29 or forceps biops~7 may be used to obtain cytology specimens from the pancreatic or biliary duct strictures (Fig. 2). These techniques are performed under fluoroscopic guidance or less commonly under direct vision through peroral choledochoscopy.64 Compared with percutaneous fine-needle aspiration, these endoscopic techniques are less invasive, have similar diagnostic accuracy, carry no known risk for tumor dissemination, and can be performed at the time bf endoprosthesis placement. The specificity and positive predictive value for these techniques approach 100%, indicating that a positive specimen is virtually diagnostic of malignancy, obviating additional invasive diagnostic procedures. 20 However, their sensitivity is on average 60%; therefore, a negative result is not of sufficient negative predictive value to be helpful. The most common polyethylene stent configuration is a straight or

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Figure 1. A, ERCP study showing distal bile duct and pancreatic duct strictures "double duct sign" secondary to a malignant pancreatic head adenocarcinoma. B, Placement of a 10 Fr plastic endoprosthesis across a distal bile duct stricture.

Figure 2. ERCP study showing a cytology brush system within a distal bile duct stricture. The brush is located between the two distal radiopaque markers and is delivered through a plastic sheath, with its tip defined by a metal ring noted closest to the endoscope.

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curved stent with side flaps at each end to minimize the risk of proximal or distal stent migration. The stent length is measured between these flaps such that an excess margin of 1 to 2 cm is present at each end in anticipation of stent movement or tumor extension. The intent is to place the stent with the proximal flap located above the stricture and the distal flap just outside the papilla within the duodenal lumen. Endoscopic sphincterotomy is not generally required prior to stent insertion, but when performed, the associated risks of hemorrhage, pancreatitis, and perforation are appreciably lower than the corresponding risks of sphincterotomy performed for common duct stone removal, presumably owing to the shorter length of the incision. l l Following stent placement, patients are typically admitted for overnight observation. Serial outpatient liver function studies are obtained to confirm normalization of serum bilirubin, which falls at a variable rate. Confirmation of stent patency becomes important for persistently elevated liver function tests. Indirect assessment of stent patency can be obtained with plain abdominal radiography, which in the presence of a patent stent often shows air in the biliary tree; abdominal ultrasonography, which may show a reduction in proximal biliary ductal dilatation; and nuclear scintigraphy, which shows passage of radio tracer into the duodenum. However, the only reliable method to clarify stent position and patency is repeat ERCP. The main causes of endoscopic failure include inaccessibility of the ampulla due to prior surgery or tumor infiltration of the duodenum, inability to cannulate the common bile duct, and inability to pass a guide wire through the stricture, all now rare in expert centers.3 When endoscopic failure is the result of inability to gain deep cannulation of the bile duct, a combined percutaneous-endoscopic "rendezvous" stenting technique may be used. 27, 36, 91 A variety of methods have been described for this combined technique, but the most commonly used is a percutaneous drainage procedure followed by placement of a 400-cm guide wire through a catheter, across the stricture, and into the duodenum. Within the duodenum, the endoscopist places a snare around the tip of the guide wire and withdraws it up the endoscope channel, where it allows completion of the stenting procedure. The combined procedure requires percutaneous transhepatic passage of only a 5 Fr or 6 Fr catheter, theoretically reducing the complications of bleeding and bile leak compared with primary percutaneous stenting procedures, which typically required a 12 Fr or 13 Fr introducer for plastic stent placementY The recent development of expandable metallic stents with small-diameter delivery catheters appears to have reduced the risks of percutaneous stent placement, allowing for single-step insertion and effectively supplanting the need for combined procedures. Complications

Complications of stent placement can be divided into those acute prob_Iems related to the ERCP such as cholangitis, pancreatitis, and

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bile duct and duodenal perforation, and delayed complications directly related to stent placement, including cholecystitis,5o duodenal perforation,3,25 and stent migration,39 fracture,56 or occlusion. 59 Overall morbidity varies from 0 to 35%, depending partially on definitions of complications, but major procedure-related morbidity is well under 10%.1, 9,10,32,57,63,72,78 The 30-day post-procedure mortality varies from 10% to 20% and the median survival is only 6 months, largely depending on the status of the malignant process. lD, 32, 78, 84 Most endoscopic series report the development of duodenal obstruction from progressive pancreatic head tumor growth in 5% to 8% of individuals32,84 (Table 1). The most common and important early complication of endoprosthesis placement is the development of biliary tract infection. The use of prophylactic antibiotics to prevent cholangitis is widely practiced but controversial, as the timing, type, and efficacy of antibiotic therapy have not been thoroughly studied. Early cholangitis occurs in only a small percentage (2% to 3%) of patients with distal common bile duct strictures and principally in those endoscopic failures in which contrast is injected into an obstructed biliary tree, which is then unsuccessfully stented. 66 Purely diagnostic ERCP should be avoided in these obstructed patients owing to the high risk of infectious complications in the undrained biliary system. Some centers63 recommend pre-ERCP administration of prophylactic antibiotics in all obstructed patients, as no reliable preprocedural predictors of infection have been identified. Other centers argue for selective use of antibiotics following ERCP procedures that do not ac;hieve adequate drainage. A direct comparison of these two strategies has not been made. When cholangitis does develop, it is essential to provide timely drainage of obstructed ductal segments, which may require percutaneous transhepatic biliary intervention. Initial concern that biliary stents would lead to obstruction of the main pancreatic duct orifice has not been realized and does not justify performing a small sphincterotomy prior to stent placement. Likewise, the chance of obstructing a normal cystic duct with a stent is small. However, if the cystic duct origin is partially involved by tumor, the placement of a stent may rarely further compromise the lumen, leading to acute cholecystitis. 16, 50 Stent migration may occur in a proximal or distal direction with an incidence of approximately 5%.39 Factors responsible for stent migration are poorly characterized, but it appears to occur more frequently with stents of large diameter, with proximal bile duct strictures, and when sphincterotomy is performed to facilitate stent placement. 39 Rarely, distal stent migration has resulted in duodenal wall injury from mechanical stent tip trauma leading to hemorrhage or perforation.25, 54 Proximal migration of a biliary stent can be readily managed by a variety of adjuvant endoscopic techniques. 23,82 The major late complication of stent placement remains prosthesis occlusion and its clinical correlates of elevated liver function tests, recurrent jaundice, or cholangitis of varying severity. Patients must be forewarned of these signs and symptoms so that proper intervention can be applied in a timely fashion. Stent occlusion may occur from days

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to years after placement, with a mean of 6 to 8 months. 22 This occurs in a minority of such individuals because the majority die sooner from progression of their underlying pancreatic malignancy, translating into a need for stent exchange in 20% to 30% of surviving patients. The occurrence of plastic stent occlusion, with its serious principal complication of cholangitis, favors planned removal and replacement. This can usually be accomplished in an outpatient setting by repeat ERCP. The optimal time interval for stent exchange has not been determined, but exchange has been in practice performed at scheduled 3- to 6-month intervals. In a recent report by Frakes et al,22 occlusion rates of 10 Fr / 11.5 Fr stents at 3 and 6 months were 4.2% and 10.8%, respectively. The authors suggested the longer exchange interval of 6 months in order to avoid premature stent replacement, thereby minimizing patient discomfort and procedure related expenses. The variability of stent survival, however, and the difficulty in predicting occlusion in a given patient also support the alternative approach of close clinical follow-up with exchange of the stent at the earliest sign of occlusion. Endoscopic replacement of a clogged stent is usually technically simple and associated with resolution of symptoms. A variety of techniques are available for endoprosthesis removal and replacement. Small diameter (7 Fr) stents may be extracted with a snare or basket through the endoscope channel while maintaining a cannulating position. However, larger stents require adjuvant maneuvers for removal. Most commonly the stent is removed by grasping the intraduodenal segment with a snare or biliary basket and withdrawing it simultaneously with the endoscope from the patient. The original procedure is essentially repeated with recannulation and guide catheter insertion followed by new stent placement. This technique does not maintain access to the obstructed biliary system and may result in inability to recannulate the malignant stricture. Guide wire-assisted techniques have gained in popularity, as they allow removal of the occluded stent through the endoscope channel, obviating the need for endoscope withdrawal and reinsertion while maintaining endoscope positioning in the duodenum and access across the occluded bile duct. 4 , 58, 73, 81 The replaced stent should not automatically be assumed to be of the same length as that removed, and the same care and attention to insertion technique should be taken as on the first occasion. Light and electron microscopic studies of blocked stents have shown that the occluding material is composed of a matrix of bacterial cells surrounded by a fibrillar anionic extracellular product, termed bacterial "biofilm." Macroscopically, the material resembles biliary sludge or brown pigment stones. 26, 86, 93 It is most likely that bacterial attachment to the inner stent surface is the first step in the clogging process, followed by deposition of crystals of calcium bilirubinate, calcium palmitate, and cholesterol within the fibrillar organic proteinaceous material. This polysaccharide matrix protects the bacteria from the host defense mechanisms and from toxic substances such as antibiotics, biocides, and surfactants. Further bacterial multiplication leads to the formation of

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adherent microcolonies that eventually coalesce, resulting in progressive narrowing of the stent lumen and, ultimately, stent occlusion. 26, 86, 93 A variety of attempts to manipulate these processes are undergoing investigation but to date have resulted in little progress. Aspirin inhibits gallbladder and biliary mucus glycoprotein secretion in a dose-dependent fashion by blocking prostaglandin synthesis, theoretically inhibiting the formation of the glycoprotein layer on the wall of the stent. Coating or incorporation of antimicrobial substances into stents has been reported to reduce bacterial adherence and biofilm formation. In a single study, oral aspirin and the bactericidal antibiotic doxycycline both reduced the sludge content of biliary stents, but clinical endpoints of stent clogging were not assessed in the trial. 80 Stent surface modification with silver coating52 or the development of new polymers producing an ultrasmooth surface37,60 inhibit bacterial adherence in an in vitro system and have potential benefit in prolonging stent patency. Gallstone dissolution agents, mucolytic agents, and choleretic agents have also been ineffective in prolonging stent life in clinical practice, although encouraging in vitro effects have been demonstrated. 34,89 Several variables may affect stent occlusion: bile flow, bile composition, bacterial contamination, and endoprosthesis characteristics such as length, shape, design, position, size, number, and material. Efforts to prevent stent occlusion through modification of these variables have met with varied success. Leung et al51 have shown that the flow rates are substantially reduced by the pigtail configuration and sharply tapered ends, leading to the current stent design as either straight or curved stents with retention flaps on the upper and lower ends of the stent to prevent migration. Although flow rates are not affected by the presence of side holes at retention flaps,51 their presence may result in flow turbulence at these sites and thereby accelerate stent blockage. A recent, randomized study comparing stents with and without side holes was unable to substantiate this theoretical benefit. 88 Experimental data suggest that placement of the distal stent tip above the papilla may prolong stent life by reducing bacterial contamination, but this awaits verification in clinical practice. According to Poiseuille's law, a larger diameter stent provides greater flow through its lumen, leading to the notion that bigger is better. This has led to the development of larger stents that provide more rapid relief of jaundice and are associated with a lower risk of clogging and cholangitis. It is estimated that 10 Fr stents increase the flow by 170% compared with 8 Fr stents and flow capacity of 11.5 Fr stents is approximately twice that of 10 Fr stents. We prefer insertion of 10 Fr stents because they have resulted in longer stent patency than 7 Fr and 8 Fr stents,33, 67, 76, 77, 85 whereas the added increase in flow through polyethylene stents of 11.5 Fr or 12 Fr diameter does not translate into a clinically measurable difference in resolution of jaundice, stent clogging, or cholangitis. 59 A retrospective study comparing 10 Fr to 11.5 Fr stents found similar success rates in all measured parameters, including success of stent insertion (81% versus 77%), resolution of

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jaundice (85% versus 78%), complications, and stent patency (23 weeks versus 24 weeks).41 Metallic Stents In the search for a solution to the problem of plastic stent occlusion, larger-diameter expandable metallic stents have been developed by a number of manufacturers. All types were first deployed through the percutaneous transhepatic route38, 44, 48, 94 but have since been modified for endoscopic placement in order to avoid the risks and discomfort inherent in percutaneous placement. Some metallic stents have not yet been introduced in an endoscopically usable form in the United States, as is the case with the Strecker and Palmaz devices, while others are awaiting FDA approval. Two metallic stents are currently available as FDA-approved devices in the United States for placement through the duodenoscope, namely the Gianturco-Rosch Z-stent (Wilson-Cook Medical, Inc., Winston-Salem, NC) and the Wallstent (Schneider Stent, Inc., Minneapolis, MN). Neither requires balloon expansion. There is limited experience with the endoscopic Gianturco Z-stent, which is a self-expanding design consisting of stainless steel wire formed in a zigzag pattern into a closed ring. It is available as a single 12 Fr Teflon sheathed delivery system which achieves dimensions of 8 mm in diameter by 3 cm long when fully expanded. 42, 46, 74 Stent length can be increased by linking stent units in tandem to cover the necessary stricture length. The advantages of this device are its self-expanding nature, relative inexpense, and deployment at the site of positioning without shortening. The disadvantages, however, are the current suboptimal delivery system, the frequent need for multiple end-to-end placements in order to cover a long malignant stricture, and the theoretical disadvantage that the openstrut construction may allow early occlusion by tumor ingrowth. 35, 46, 48, 94 More experience has been gained with the Walls tent, which is a tubular superalloy of stainless steel mesh delivered in a collapsed form on an 8 Fr catheter system. When deployed, the Wallstent expands to a final diameter of 30 Fr and shortens to the designated length of 42, 68, or 90 mm as a result of its inherent expansile properties (Fig. 3). The system is passed over a 0.035-inch guide wire, and preliminary sphincterotomy and dilatation of the stricture are usually unnecessary. The prepared system is positioned across the malignant stricture with the aid of radiopaque markers on the delivery catheter. Controlled slow release of the Wallstent requires careful coordination between the end oscopist and assistant to maintain full control of the device. It is common to leave a short lengt~ of less than 10 mm of the stent exposed in the duodenal lumen after release if the stricture is distal in location as is the case with pancreatic cancer. Endoscopists must be aware of stent foreshortening by 30% that occurs following deployment (e.g., from 100 mm to 68 mm) as the stent diameter continues to expand to its final dimensions in the bile duct. Once fully deployed, Walls tents become

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Figure 3. ERCP deployment of a Wallstent across a distal CBD stricture showing A, appearance immediately after Wallstent release with delivery catheter within the stent lumen and B, following delivery system removal with partial expansion demonstrated by a waist in the distal portion of the Wallstent.

embedded in the wall of the bile duct and should be considered permanent, effectively eliminating the problem of stent migration. Initial studies of Wallstent placement were conducted in Europe and results reported in a total of 326 patients with malignant biliary obstruction. 2, 14, 30, 31, 48, 65 The patient population was representative of the usual spectrum of malignant biliary lesions, and technical success of implantation was high. Early procedural morbidity was very low, but unfortunately the large stent lumen did not entirely eliminate the problem of stent occlusion. Wallstent occlusion occurred by sludge deposition in only 2%, whereas tumor ingrowth or overgrowth occurred in 10% as a new problem not previously encountered with plastic stents. The theoretical advantages of the Wallstent over plastic stents are its ease of placement due to the smaller more flexible delivery system,

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superior initial bile drainage due to increased luminal diameter of 30 Fr versus 10 Fr for conventional stents, and prolonged stent patency translating into fewer endoscopic interventions, making it a cost-effective, safe alternative for palliation of malignant bile duct obstruction. These theoretical advantages for the metallic stents have now been confirmed through their evaluation in three prospective, randomized trials comparing them with conventional plastic stents?, 13, 45 The US Wallstent Study Group has conducted the largest of these trials in comparing the Wallstent to conventional 10 Fr biliary stents? Of the 182 patients randomized, 94 received Walls tents and 88 plastic stents with a 97% and 95% successful implantation rate, respectively. The range of tumors was similar to previous European and US open studies, with 47% and 51% of patients obstructed by pancreatic carcinoma in the two randomized groups. Complications within 30 days included 3% occluded plastic stents, no occluded Wallstents, and 7% deaths from underlying disease. Complications after 30 days were sludge occlusion of plastic stents in a further 25% and Wallstents in 5% but tumor ingrowth or overgrowth in the Wallstent group in 10%, making overall complication rates of 16% for Wallstents and 31 % for plastic stents (P<0.05). This advantage was observed irrespective of tumor site and was more marked for patients who had received previous plastic stents. Life-table analysis showed no difference in patient survival, but the mean time to stent occlusion was prolonged to 132 days for Wallstents and the probability of plastic stent occlusion was 2.8 times greater than for Wallstents. The implications of these findings are that there are significant clinical advantages for the Walls tent and, despite the higher initial expense of the device, a cost-benefit advantage results from the reduced need for subsequent intervention. Another prospective study from Holland13 randomized 105 patients to Wallstents (49 patients) and polyethylene stents (56 patients), resulting in a similar success rate of implantation (96% versus 95%), initial drainage efficacy, and early complications (12% versus 11%) with a comparable overall median survival of 149 days. The benefits of metallic stent therapy were the result of lower occlusion rate (33% versus 54%), prolonged Wallstent patency (273 versus 126 days), and a 28% reduction in endoscopic interventions in the metallic stent group, which the authors deduced had a significant impact on cost-effectiveness. The only other prospective trial45 included 62 patients randomized to receive plastic stents in 31 and metal stents in '31 placed endoscopically or by a combined percutaneous-endoscopic approach, with Walls tents placed in 70% and Strecker stents in 30%. This study showed a higher patency failure rate (11% versus 5%), a higher cholangitis rate (10% versus 3%), longer hospitalization (10 versus 3 days), and higher overall treatment costs associated with plastic stents. In summary, metallic stents are readily placed in distal CBD obstruction secondary to pancreatic malignancy with an incidence of acute complications similar to that for plastic endoprosthesis placement. It is important to assess the nature of a biliary stricture and its

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resectability prior to stent placement, as a metal stent must be considered permanent. Therefore, if there is doubt, a conventional polyethylene endoprosthesis should be placed and a metal stent implanted only when these factors are determined at the time of stent exchange. Although the initial fees for metallic stent placement are greater (plastic stents cost approximately $100 per kit whereas Wallstents cost approximately $1000 and Z-stents $450), the overall cost of palliative treatment with metallic stents is cost-effective based on the longer stent patency translating into a reduced need for repeat procedures and hospitalization. Tumor occlusion of metallic stents continues to be a problem. Unlike plastic stents, occluded metallic endoprostheses cqnnot be extracted and replaced. Recanalization of occluded metallic stents can be achieved with insertion of a second metallic or plastic endoprosthesis through the existing lumen of the occluded stentP Alternatively, contact thermal methods directly applied with diathermic I2 or hot-tip laser probes53 recanalize the stent but appear to carry an unnecessary risk of bleeding, ductal perforation, and stent fragmentation. IS The problem of tumor ingrowth may be overcome by the development of a silicone covering79 or the emergence of newer metallic stents that do not have an open framework,24 but additional problems may ensue, including stent migration and impairment of duct drainage from the pancreatic and cystic duct. Other uncommon complications of metallic stents include hemobilia and stent erosion through bowel wall. 49,62 Comparison with Surgical Palliation

Surgery should continue to be the first modality considered in patients with pancreatic malignancy because it is the only potential curative therapy. Patients, however, with clearly unresectable tumors or those considered unfit for surgery need palliation with options of endoscopic, percutaneo~s, or surgieal approaches. For malignant biliary obstruction, endoscopic stent placement compares well with surgical biliary drainage, which carries a high morbidity and mortality in elderly frail patients. 1, s, 9, 72 In two randomized studies involving 204 patients9 and 48 patients,72 respectively (Table 2); the procedural success rate and efficacy in relieving jaundice were comparable for both techniques at 90%. However, the length of hospital stay was shorter for the endoscopic group and the procedure-related morbidity and mortality were significantly lower. This initial benefit favoring an endoscopic approach was partially balanced by the subsequent need for more frequent hospital visits necessitated by stent occlusion, which occurred more often than enteric bypass failure. Only 6% of the patients in the stented group required a subsequent gastrojejunostomy for duodenal obstruction. Although the 30-day mortality rate was lower for the endoscopic approach, there was no significant difference· in median survival for the two groups. Cost analysis studies appear to favor the endoscopic approach,5 but patient and physician choice remains a major factor in the decision-

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Table 2. RANDOMIZED CONTROLLED TRIALS OF ENDOSCOPIC VERSUS SURGICAL PALLIATION IN MALIGNANT BILIARY OBSTRUCTION Middlesex (17) Endoscopy Patients Success (%) Complications (%) Mortality-procedure (%) Mortality-30 day (%) Duodenal obstruction (%) Initial hospital (days) Survival (weeks) Recurrent admissions (%) Stent exchange (%) Total hospital (days)

101 94 10' 3'

7' 6' 9' 21' 18' 33' Not indicated

Wessex (72)

Surgery

Endoscopy

Surgery

103 91 28 14 17 1 13 26 5 0

23 91 33 Not indicated 9 9' 5' 22 43' 43' 8'

25 92 56 20 4 13 8 12 0 13

'P
making process. The results from these studies should be re-interpreted in light of expandable metallic stent developments, which may further alter the balance in favor of the endoscopic approach owing to reduced stent clogging and its application for enteric obstruction, whereas developments in laparoscopic approaches to biliary-enteric anastomosis could alter the selection in favor of surgery?5 Theoretical considerations suggest that preoperative biliary drainage to reduce serum bilirubin levels and allow recovery of liver function and improve nutritional status may result in reduced perioperative morbidity and mortality. However, prospective randomized trials of preoperative percutaneous transhepatic drainage failed to show a lower overall operative morbidity or mortality, as any potential benefit of drainage was offset by procedural complications. 28 • 61. 68 Whether an endoscopic approach with a lower procedural complication rate would be of benefit has not been adequately studied and is unlikely to be assessed in the future owing to great strides made in operative technique already resulting in an operative mortality under 5%. Furthermore, it would be unethical not to place a stent at the time of ERCP in malignant biliary obstruction owing to the high risks of inducing cholangitis in an undrained biliary system. PALLIATION OF PAIN AND DUODENAL OBSTRUCTION

Proposed factors producing pain in pancreatic malignancy include neural tumor infiltration, increased parenchymal pressure secondary to pancreatic ductal obstruction, superimposed pancreatic inflammation, and distal common bile duct stenosis. Complete or partial main pancre-

II

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atic duct obstruction demonstrated on endoscopic pancreatography is a characteristic feature of pancreatic cancer. Little attention has been given to the association between these findings and the presence of "obstructive" pancreatic pain, namely episodic discomfort that is mealrelated or occurs in the context of recurrent acute pancreatitis. Analogous to the situation with chronic pancreatitis, main pancreatic duct obstruction with secondary proximal ductal hypertension and dilatation may be an important contributor to this pain. Limited experience with 5 or 7 Fr pancreatic stents placed across the malignant main pancreatic duct stricture (Fig. 4) in such patients has produced impressive alleviation of pain and is a promising method for palliation of this difficult aspect of management. Costamagna et al9 described eight such patients in which a pancreatic stent was inserted across the neoplastic stricture. All patients but one were free of pain within 48 hours of the endoscopic procedure and were able to discontinue narcotic analgesics. Six of the eight patients remained pain free, whereas two experienced painful relapse shortly before death. In a series totaling five patients, we similarly demonstrated success among those patients with an obstructive component to their pain. Therefore, endoscopic pancreatic stenting may be considered an effective alternative for palliation of pancreatic cancer in selected patients with "obstructive" pain not responding to analgesics. Effective palliation for obstructing luminal cancers in the upper gastrointestinal tract relieves intractable emesis and re-establishes the potential for oral nutrition while removing the need for parenteral

Figure 4. ERCP placement of a 7 Fr plastic stent across a malignant distal main pancreatic duct stricture for palliation of pain in a patient with prior placement of a biliary Wallstent.

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support in the context of a terminal illness. Gastric outlet obstruction from direct duodenal invasion by pancreatic cancer has traditionally been treated by surgical gastroenterostomy with complication rates as high as 20% to 30% reported. 70 Subsequent local recurrence with invasion of the gastroenterostomy, with or without pancreaticoduodenectomy, poses a problem for which repeat surgery is less desirable and gastric decompression via a percutaneous endoscopic gastrostomy (PEG) with jejunostomy feedings to provide drainage and nutritional support remains less than satisfactory.6 The recent application and modification of available biliary-type metallic stents with their refined delivery systems and larger stent diameters have stimulated interest in an alternative endoluminal approach. Initial experience with placement of these largediameter devices to re-establish luminal patency within the esophagus for malignant stenosis,19, 69 across the gastric outlet in patients with recurrent gastric carcinoma,9° and in malignant rectal or colonic stenoses87 has been encouraging. Kozarek et al46 have implanted a metallic Zstent in a patient with malignant afferent loop obstruction following pancreatoduodenectomy for pancreatic carcinoma and in the efferent limb of a Billroth II gastrojejunostomy after resection of a gastric cancer. Maetani et al55 describe a 78-year-old woman with pancreatic head carcinoma who underwent initial placement of a self-expanding Gianturco-Rosch Z-stent in the distal common bile duct for malignant biliary obstruction, and 9 months later, received an additional stent of 30 mm diameter in the descending duodenum to alleviate malignant stenosis. Keymling et al43 describe percutaneous Wallstent placement through a PEG across a duodenal stricture that resulted from an infiltrating pancreatic carcinoma. We have similarly placed specially designed Wallstents (16 mm diameter and 60 to 90 mm length) in four patients with malignant gastric outlet obstruction, two with obstructed gastrojejunostomies and two in the native duodenum across strictures resulting from pancreatic tumor infiltration (Fig, 5). There were no technical failures or procedure-related complications. Stent placement enabled all patients to resume enteral nutrition for the remainder of their survivaL Additional careful assessment of this new, yet promising approach is required to establish its proper place in the palliative management of malignant duodenal obstruction. Short- and long-term complication rates of bleeding, perforation, and stent occlusion need to be defined better. SUMMARY

Endoscopic stenting has revolutionized the palliation of malignant biliary obstruction. Individuals with biliary obstruction due to pancreatic malignancy are best managed by a team approach comprising individuals with expertise in oncology, surgery, endoscopy, and radiology. The clinical value of alleviating jaundice and associated symptoms of anorexia, pruritus, and malaise cannot be overestimated. These quality-oflife factors deserve more attention in future studies to define subgroups

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Figure 5. A, Upper GI series demonstrating a malignant duodenal stenosis (arrow) secondary to tumor infiltration from an underlying pancreatic head malignancy. Existing biliary Wallstent is present across distal CBD stricture with distal end located at proximal margin of duodenal narrowing. B, Placement of a Wallstent (16-mm luminal diameter) across the duodenal stricture (arrow) with patent biliary Wallstents (open arrow) denoted by the presence of intrahepatic pneumobilia.

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