13 Non-operative palliation of pancreatic cancer K. HUIBREGTSE
Pancreatic adenocarcinoma is the fifth leading cause of cancer death in the United States (Silverberg and Lubera, 1986). The incidence has increased in recent decades to around 10 per 100000 population in most of the Westernized countries. The median age at presentation lies between 65 and 70 years and 44% of men and 95% of women are older than 70 years of age at the time of registration (Allen-Mersh and Earlham, 1986). The disease has a very poor prognosis: 90% of patients are dead within one year of diagnosis and survival beyond five years is exceptional. Surgical resection of the tumour is the only possibility of cure but resectability rates are low (Andren-Sandberg and Ihse, 1983; Trede, 1985; Allen-Mersh and Earlham, 1986; Warshaw and Swanson, 1988) and the median survival after curative resection is 17 to 20 months (Connolly et al, 1987; Warshaw and Swanson, 1988). These dismal figures mean that the vast majority of patients with a pancreatic cancer can only be treated palliatively. Modern imaging techniques not only allow for accurate diagnosis but can usually indicate those patients in whom only palliation should be offered. Most patients initially present with pain and/or jaundice. Kalser et al (1985) found pain to be the presenting symptom in 79% of 393 patients and jaundice to be present in 50%. Jaundice alone gives little indication as to the stage of the disease. Of patients with a resectable lesion in the head of the pancreas, 84% presented with obstructive jaundice. More than 70% of patients will eventually develop jaundice in the course of the disease. Duodenal obstruction is a complication that mainly develops in the later stages of the disease. In a collected review of 3300 patients, Sarr and Cameron (1984) found that 13% of patients who had undergone palliative biliary diversion alone required re-operation for duodenal obstruction. Pain is best treated by analgesics or coeliac plexus block. Duodenal obstruction can only be treated by surgery. Obstructive jaundice can be treated surgically and non-surgically. In this chapter we shall concentrate on the non-surgical approaches. These modalities have been developed in the last two decades as a therapeutic application of the two available diagnostic techniques for direct cholangiography: percutaneous transhepatic cholangiography (PTHC) and endoscopic retrograde cholangiopancreatography (ERCP). Baillit+e’s
Clinical
Gastroenterology-
Vol. 4, No. 4, December 1990 ISBN 0-7020-147@2
995 Copyright @ 1990, by Baillitre Tindall All rights of reproduction in any form reserved
996
K. HUIBREGTSE
PERCUTANEOUS TECHNIQUES The first PTHC is generally attributed to Huard and Do-Xun-Hop, which was performed in 1937 (Wechsler and Wechsler, 1975). It is only in the past two decades that the percutaneous transhepatic route for diagnostic cholangiography has become a standard technique and that therapeutic techniques for biliary drainage have been developed (Pereiras et al, 1978; Burcharth, 1982; Ferrucci, 1982; Mueller et al, 1985).
Technique All percutaneous procedures start with puncture of the biliary tree with the flexible Chiba needle to obtain a cholangiogram. The examination is performed via the right lateral or anterior approach using local anaesthesia and intravenous sedation and analgesia. Once well-positioned a guide wire is inserted through the needle or, alternatively, an over-sheath. A pigtail catheter can then be introduced over the guide wire to obtain external drainage. If it is possible, the guide wire should be manoeuvred through the stricture and a pigtail catheter with multiple side holes is advanced into the duodenum to establish external-internal drainage. Most radiologists prefer not to place a stent at the first session, but rather to wait a few days for the catheter tract to mature. The stent can then be introduced with the help of a pusher tube over the guide wire which is re-inserted via the external-internal catheter. A pigtail catheter for external drainage is left in place for safety. This catheter can be removed a few days later when adequate functioning of the stent is confirmed radiologically.
Results and early complications The success rate for puncturing a dilated bile duct and providing external drainage should be close to 100%. The establishment of external-internal drainage is less successful, the success rates for percutaneous stent placement varying between 82% and 92% (Burcharth, 1982; Mueller et al, 1985). Major complications are about 3% in patients undergoing diagnostic fine-needle PTHC and increase to 7-23% when a drainage procedure is added (Harbin et al, 1980; Stambuk et al, 1983; Demas et al, 1984). The most frequent serious complication of transhepatic biliary drainage is sepsis which occurs in slightly over 10% of patients even with prophylactic antibiotics. Liver puncture usually results in some localized pain, presumably due to a small bile leak. Major bile leakage and haemorrhage from the puncture site, however, can also occur. Pneumothorax and pleural effusion may result from high punctures. The long-term complications of external drainage are considerable and their use should therefore be restricted. Although the severe loss of fluids and electrolytes giving rise to the 'bile-loss syndrome' can be prevented by re-infusion of bile via a nasogastric tube or a percutaneous endoscopic gastrostomy, such an approach is distressing. Because external tubes are a physical and psychological burden for the patient they should only be used temporarily as a step in the technique of stent placement.
NON-OPERATIVE PALLIATION
997
ENDOSCOPIC TECHNIQUES The first endoscopic cannulation of the ampulla of Vater was by McCune et al in 1968. Therapeutic biliary endoscopy started in 1974 with sphincterotomy and gallstone extraction. Nasobiliary drainage was subsequently developed to prevent stone impaction and post-ERCP cholangitis in patients with biliary strictures. In 1979 a method for inserting an endoscopic biliary endoprosthesis was first described (Soehendra and ReijndersFrederix, 1980), which has since been developed and refined into a standard treatment procedure (Huibregtse et al, 1981; Huibregtse and Tytgat, 1984; Cotton, 1984, 1986).
Technique Following a diagnostic ERCP a small sphincterotomy is often made to facilitate manipulation. A 6 Fr or 7 Fr catheter with an 0.035 inch guide wire is introduced into the distal common bile duct. The catheter and guide wire are manoeuvred through and above the malignant stricture. Over the catheter a 10 Fr or 12 Fr endoprosthesis is then inserted with the help of a pusher tube (Figures 1 and 2).
Figure I. The straight Amsterdam-type endoprosthesis with side-flaps and the ancillary equipment for insertion procedure.
998
K. HUIBREGTSE
Figure 2. Left: Stricture of the pancreatic duct and the distal common bile duct in pancreatic cancer ('double duct sign'). Right: Endoscopic stent inserted through the bile duct stricture.
Results and early complications Endoscopists with reasonable experience will expect to place stents successfully in about 90% of patients (see Table 1) (Huibregtse et al, 1986; Huibregtse, 1988; Siegel et al, 1986; Speer and Cotton, 1988; Dowsett et al, 1989a, b). Difficulties can arise when there is distortion or invasion of the Table 1. Results of endoscopic stents in patients with carcinoma of the
pancreas in two large series. University of Amsterdama Number of patients Mean age Successful drainage 30-day mortality Median survival Duodenal stenosis Stent blockage
632 71 years 87% 10.8% 5 months 9% 29%
a Coene (1990); b Dowsett et al (1989). NA = not available.
Middlesex Hospitalb 403 NA 85% 17% 4.5 months 5% 16%
999
NON-OPERATIVE PALLIATION
duodenum by tumour. In this situation not only is it difficult to identify the ampulla but also the risk of subsequent duodenal obstruction is high and surgical palliation is usually more appropriate. Immediate complications of attempted and successful stent placements are similar to those of other ERCP procedures including acute pancreatitis, bleeding and perforation. Acute cholangitis is only a problem when adequate drainage has not been achieved. Although it is possible to perforate the bile duct and even to enter the venous system with guide wires, serious problems do not usually ensue. PERCUTANEOUS OR ENDOSCOPIC ROUTE? In general the external and external-internal percutaneous drainage procedures are only used as temporary measures or before placement of a stent. The complication rate of the percutaneous route is higher than the endoscopic approach. Moreover, whilst a failed percutaneous procedure often leaves the patient with an undesirable external bile leak, a failed endoscopic procedure causes little if any harm. Only one randomized trial has compared the percutaneous and endoscopic methods of stent insertion (Speer et al, 1987). Seventy-five patients participated in this study between 1983 and 1985. The endoscopic method had a higher success rate for relief of jaundice and a lower complication and mortality rate (Table 2). This study, which was performed in a unit with comparable expertise and experience in both procedures, clearly showed the superiority of the endoscopic approach. Table 2. Endoscopic versus percutaneous endoprosthesis for the
treatment of obstructive jaundice (Speer et al, 1987).
Number attempted Successful drainage Complications 30-day mortality Median survival
Percutaneous stent
Endoscopic stent
36 61% 67% 33% 88 days
39 81%* 19% * 15%* 119 days
• Statistically significant.
It is now generally accepted that the endoscopic method should be attempted first. Most failures of endoscopic stent placement are due to failed cannulation of the ampulla or to failed passage of the guide wire through the stricture. The success rate can be improved by a combined radiological and endoscopic technique or 'rendez-vous' procedure first described by Mason and Cotton in 1981. C O M B I N E D PROCEDURE
In this technique, the radiologist first introduces an external-internal catheter and a guide wire is inserted through this catheter into the duodenum.
1000
K. HUIBREGTSE
The endoscopist then grasps this guide wire and pulls the guide wire through the instrumentation channel. Over this guide wire, catheters, papillotomes or endoprostheses can now be inserted endoscopically. The main idea behind this combined procedure is that a large percutaneous tract can be avoided so that the complication rate is less than for percutaneous stent insertion. One study of combined procedures in 53 malignant strictures showed a success rate of 80%, a procedure-related morbidity of 36% and a mortality of only 3%. Although this would seem to be a useful approach, prospective randomized studies comparing the percutaneous and combined procedures are lacking (Dowsett et al, 1989a). LONG-TERM COMPLICATIONS OF BILIARY STENTS The main long-term complication of biliary stents is occlusion by sludge which occurs in 20 to 40% of the patients. Clogging may occur from one week to over 15 months after placement, with mean of about 5 months. The patients with a clogged endoprosthesis present with a 'flu-like' syndrome, consisting of malaise, low-grade fever or disturbance of liver function. Unless the significance of these symptoms is recognized, jaundice and acute cholangitis will soon supervene. Immediate removal and replacement of the clogged endoprosthesis is indicated. Although brushing and irrigation of the clogged endoprosthesis is technically possible, this is rarely indicated as prompt re-obstruction of the endoprosthesis usually occurs. Endoscopic replacement of a clogged endoprosthesis is usually technically simple, especially if a sphincterotomy was performed at the time of initial insertion. Replacement is nearly always followed by resolution of the symptoms. Percutaneous replacement of a clogged endoprosthesis is also possible but carries at least the same complication rate as percutaneous stent placement alone. Occasionally when a percutaneous secondary approach is necessary a second endoprosthesis should be placed alongside the clogged one. A blocked endoprosthesis contains inspissated bile, calculous debris and proteinaceous material (Wosiewitz et al, 1985; Groen et al, 1987). Endoprostheses removed 2 months after insertion are usually covered with a layer of protein and this is especially prominent around the side flaps and side holes. This layer always contains bacteria even when antibiotics have been administered continuously. It is still not clear whether this layer is produced by bacteria or whether the proteins derive from bile (Leung et al, 1988; Speer et al, 1988). In all probability this layer is the first step in the clogging process. Despite many in vitro and in vivo investigations in order to overcome the clogging problem, including the use of endoprostheses made of different materials and endoprostheses without side holes or rough surfaces as well as gallstone dissolution agents, mucolytic agents and choleretic agents, no practical recommendations can yet be made. On the other hand, the results obtained with the new Wallstent endoprosthesis, which is a self-expanding metal stent, are most encouraging (Figure 3). The inside diameter of the fully expanded stent is one centimetre. In a recent multicentre evaluation, stent occlusion by biliary sludge
NON-OPERATIVE PALLIATION
1001
Figure 3. Metal self-expanding stent (Wallstent) introduced through bile duct stricture due to pancreatic cancer.
was seen in only two out of 103 patients who had been followed up for a median period of 5 months (Huibregtse et al, unpublished). Other late complications are unusual but include acute cholecystitis, migration of the endoprosthesis into the more proximal bile duct or into the duodenum and perforation by the endoprosthesis of the bile duct or the duodenum. Duodenal obstruction from direct tumour invasion occurs as a late complication as well but in less than 10% of collected series. This relatively low incidence is due to the appropriate selection of cases, those patients with impending duodenal obstruction being recommended for operative gastroenterostomy as well as operative biliary drainage at the time of initial stent placement. Prompt recognition of the late complications of
1002
K. HUIBREGTSE
stenting is essential in order to optimize the quality of life as well as avoiding unnecessary early death. SURGICAL OR NON-SURGICAL PALLIATION Surgery is clearly indicated in patients with small potentially resectable tumours and in those patients with impending or overt duodenal obstruction. On the other hand, elderly patients who are at high risk from surgery are best treated by the non-operative approach, preferably by endoscopic means if the expertise is available. There is, however, a large group of patients who fall between these extremes and the relative merits of surgical versus non-surgical palliation are difficult to define. The relatively low surgical mortality and shorter hospital stay of the non-surgically treated patients in comparison with those undergoing operative bypass have been used as arguments in favour of the endoscopic and radiological approaches. Against this has been the penalty of recurrent jaundice and the need for frequent stent changes as well as the subsequent development of duodenal obstruction. Comparison with surgical series may not be appropriate because of selection bias. Recently, however, there have been three prospective randomized trials which have partly clarified the situation (Shepherd et al, 1988; Dowsett et al, 1989c; Andersen et al, 1989) the largest of which is still ongoing (Dowsett et al, 1989c). It is apparent from the studies that the immediate mortality rate as well as the incidence of complications are significantly lower in the endoscopically treated patients (Table 3). The benefit of shorter initial hospital stay of the non-operatively treated groups is to some extent counterbalanced, but not entirely eliminated, by the need to re-admit for stent changes and surgically bypass cases for duodenal obstruction. Table 3. Results of three prospective randomized trials comparing endoscopic stenting with surgical bypass for obstructive jaundice.
Shepherd et al (1988) Stent Number of patients Successful drainage Complications 30-day mortality Duodenal bypass Recurrent jaundice Median survival (range)
Surgery
Andersen et al (1989) Stent
Surgery
Dowsett et al (1989c) Stent
Surgery
23
25
25
19
101
103
91% 22% 9%
92% 40% 20%
96% NA NA
84% NA NA
94% 10% 7%
91% 28%* 17%*
0%
0%
0%
0%
6%
1%*
17% 152 days (39-411)
2% 125 days (52-354)
28% 84 days (3-498)
16% 100 days (10-642)
18% 5 monthst
NA = not available;
* statistically significant;
t mean survival.
3%* 5 monthst
NON-OPERATIVE PALLIATION
1003
There is no difference in the long-term survival of patients irrespective of treatment. This indicates that the main gain is in the reduction of initial hospital stay and procedural mortality. The need to re-admit patients for further procedures is, however, distressing for patients and confirms the rationale for using surgical palliation from the outset in younger or fitter patients. The general conclusions from these studies need to be treated with some caution. The results apply to only those patients entered into these trials whilst the spectrum of cases in clinical practice is diverse. Moreover, studies formally examining the quality of life of the two respective types of treatment need to be undertaken (see Andersen et al, 1989). CONCLUSIONS Pancreatic adenocarcinoma is a disease of the elderly. More than 50% of patients are over 70 years at the time of onset. With increasing life expectancy it is expected that more elderly patients with pancreatic cancer will be seen, increasing the demand for non-surgical palliation. Further improvement of these techniques will take place and the problem of the late obstruction of the endoprostheses should ultimately be solved. Whilst the increasing choice and sophistication of techniques available is interesting, the complexity of the problems should not divert us from our main aim which is to provide the optimum care for these patients. Close collaboration is required between radiologists, surgeons and endoscopists not only for the development of further prospective trials seeking answers to specific questions but also to provide on a day-to-day basis the best individual treatment for those patients currently in our care. REFERENCES Allen-Mersh TG & Earlham ILl (1986) Pancreatic cancer in England and Wales; surgeons look at epidemiology. Annals of the Royal College of Surgeons of England 68: 154--158. Andersen JR, Sorensen SM, Kruse A & Rokkjaer M (1989) Randomised trial of endoscopic endoprosthesis versus operative bypass in malignant obstructive jaundice. Gut 30: 11321135. Andren-Sandberg A & Ihse I (1983) Factors influencing survival after total pancreatectomy in patients with pancreatic cancer. Annals of Surgery 198: 605-610. Burcharth F (1982) Nonsurgical drainage of the biliary tract. Seminars in Liver Disease 2: 75-85. Coene PPLO (1990) Endoscopic Biliary Stenting. Krips Repro, Meppel. Connolly MM, Dawson PJ, Michelassi F et al (1987) Survival in 1001 patients with carcinoma of the pancreas. Annals of Surgery 206: 397-400. Cotton PB (1984) Endoscopic methods for relief of malignant obstructive jaundice. World Journal of Surgery 6: 854-861. Cotton PB (1986) Endoscopic biliary stents, trick or treatment? Gastrointestinal Endoscopy 32: 364-365. Demas BE, Moss A A & Goldberg HI (1984) Computed tomographic diagnosis of complications of transhepatic cholangiography and percutaneous biliary drainage. Gastrointestinal Radiology 9: 219-222. Dowsett JR, Vaira D, Hatfield ARW et al (1989a). Endoscopic biliary therapy using the combined percutaneous and endoscopic technique. Gastroenterology 96: 1180--1186. Dowsett JR, Williams SJ, Hatfield ARW et al (1989b). Endoscopic management of low biliary
1004
K. HUIBREGTSE
obstruction due to unresectable primary pancreato-biliary malignancy: a review of 463 consecutive cases. Gastroenterology 96: A129. Dowsett JF, Russell RCG, Hatfield ARW et al (1989c) Malignant obstructive jaundice; a prospective randomized trial of surgery versus endoscopic stenting. Gastroenterology 96: A128. Ferrucci JT (1982) Percutaneous biliary drainage: technical and catheter related problems in 200 procedures. American Journal of Radiology 138: 17-23. Groen AK, Out T, Huibregtse K et al (1987) Characterization of the content of occluded biliary endoprosthesis. Endoscopy 19: 57-59. Harbin WP, Mueller PR & Ferrucci JT (1980) Transhepatic cholangiography: complications and use patterns of the fine needle technique. Radiology 135: 15-22. Huibregtse K (1988) Endoscopic biliary and pancreatic drainage. Stuttgart: George Thieme Vertag. Huibregtse K & Tytgat GNJ (1984) Endoscopic placement of biliary prostheses. In Salmon PR (ed.) Gastrointestinal Endoscopy. Advance in Diagnosis and Therapy, pp 219-231. London: Chapman and Hall. Huibregtse K, Haverkamp HJ & Tytgat GNJ (1981) Transpapillary positioning of a large 3.2 mm biliary endoprosthesis. Endoscopy 13: 217-219. Huibregtse K, Katon RM, Coene PP & Tytgat GNJ (1986) Endoscopic palliative treatment in pancreatic cancer. Gastrointestinal Endoscopy 32" 334-338. Kaiser MH, Barkin J & Maclntyre JM (1985) Pancreatic cancer. Assessment of prognosis by clinical presentation. Cancer 56: 397--402. Leung JWC, Ling TKW, Kung JLS & Vallence-Owen J (1988) The role of bacteria in the blockage of biliary stents. Gastrointestinal Endoscopy 34: 19--22. McCune WS, Shorb PE & Moscovitz H (1968) Endoscopic cannulation of the ampulla of Vater: a preliminary report. Annals of Surgery 167: 752-756. Mason RR & Cotton PB (1981) Combined duodenoscopic and transpapillary approach to stenosis of the papilla of Vater. British Journal of Radiology 54: 678. Mueller PR, Ferrucci JT, Teplich SK et al (1985) Biliary stent endoprosthesis: analysis of complications in 113 patients. Radiology 156: 637-639. Pereiras RV, Rheingold O J, Hutson D et al (1978) Relief of malignant obstructive jaundice by percutaneous insertion of a permanent prosthesis in the biliary tree. Annals of Internal Medicine 89: 589-593. Sarr MG & Cameron JL (1984) Surgical palliation of unresectable carcinoma of the pancreas. World Journal of Surgery 8: 906--918. Shepherd HA, Royle G, Ross APR, Diba A, Arthur M & Colin-Jones D (1988) Endoscopic biliary endoprosthesis in the palliation of malignant obstruction of the distal common bile duct: a randomised trial. British Journal of Surgery 75:1166-1168. Siegel JH &Snady H (1986) The significance of endoscopically placed prostheses in the management of biliary obstruction due to carcinoma of the pancreas: results of nonoperative decompression in 277 patients. American Journal of Gastroenterology 81: 634-641. Silverberg E & Lubera J (1986) Cancer statistics. Cancer 36: 9-25. Soehendra N & Reijnders-Frederix V (1980) Palliative bile duct drainage. A new endoscopic method of introducing a transpapillary drain. Endoscopy 12" 8--11. Speer AG & Cotton PB (1988) Endoscopic treatment of pancreatic cancer. International Journal of Pancreatology 3: 146--158. Speer AG, Cotton PB, Russell RCG et al (1987) Randomised trial of endoscopic versus percutaneous stent insertion in malignant obstructive jaundice. Lancet ii: 52-62. Speer AG, Cotton PB, Rode Jet al (1988) Biliary stent blockage with bacterial biofilm. Annals of Internal Medicine 108: 546-553. Stambuk EC, Pitt HA, Pais O, Mann LL, Lois JF & Gomes AS (1983) Percutaneous transhepatic cholangiography. Archives of Surgery 118: 1388-1394. Trede M (1985) The surgical treatment of pancreatic cancer. Surgery 97: 28-35. Warshaw AL & Swanson RS (1988) Pancreatic cancer in 1988. Annals of Surgery 208: 541-553. Wechsler RL & Wechsler L (1975) The first application of transhepatic cholangiography to the localization of liver or biliary tract pathology: Hanoi, 1937. American Journal of Digestive Diseases 20: 699-700. Wosiewitz V, Schrameyer B & Safrany L (1985) Biliary sludge: its role during bile duct drainage with an endoprosthesis. Gastroenterology 88: 1706.
Pancreatic adenocarcinoma is the fifth leading cause of cancer death in the United States (Silverberg and Lubera, 1986). The incidence has increased in recent decades to around 10 per 100000 population in most of the Westernized countries. The median age at presentation lies between 65 and 70 years and 44% of men and 95% of women are older than 70 years of age at the time of registration (Allen-Mersh and Earlham, 1986). The disease has a very poor prognosis: 90% of patients are dead within one year of diagnosis and survival beyond five years is exceptional. Surgical resection of the tumour is the only possibility of cure but resectability rates are low (Andren-Sandberg and Ihse, 1983; Trede, 1985; Allen-Mersh and Earlham, 1986; Warshaw and Swanson, 1988) and the median survival after curative resection is 17 to 20 months (Connolly et al, 1987; Warshaw and Swanson, 1988). These dismal figures mean that the vast majority of patients with a pancreatic cancer can only be treated palliatively. Modern imaging techniques not only allow for accurate diagnosis but can usually indicate those patients in whom only palliation should be offered. Most patients initially present with pain and/or jaundice. Kalser et al (1985) found pain to be the presenting symptom in 79% of 393 patients and jaundice to be present in 50%. Jaundice alone gives little indication as to the stage of the disease. Of patients with a resectable lesion in the head of the pancreas, 84% presented with obstructive jaundice. More than 70% of patients will eventually develop jaundice in the course of the disease. Duodenal obstruction is a complication that mainly develops in the later stages of the disease. In a collected review of 3300 patients, Sarr and Cameron (1984) found that 13% of patients who had undergone palliative biliary diversion alone required re-operation for duodenal obstruction. Pain is best treated by analgesics or coeliac plexus block. Duodenal obstruction can only be treated by surgery. Obstructive jaundice can be treated surgically and non-surgically. In this chapter we shall concentrate on the non-surgical approaches. These modalities have been developed in the last two decades as a therapeutic application of the two available diagnostic techniques for direct cholangiography: percutaneous transhepatic cholangiography (PTHC) and endoscopic retrograde cholangiopancreatography (ERCP). Baillit+e’s
Clinical
Gastroenterology-
Vol. 4, No. 4, December 1990 ISBN 0-7020-147@2
995 Copyright @ 1990, by Baillitre Tindall All rights of reproduction in any form reserved
996
K. HUIBREGTSE
PERCUTANEOUS TECHNIQUES The first PTHC is generally attributed to Huard and Do-Xun-Hop, which was performed in 1937 (Wechsler and Wechsler, 1975). It is only in the past two decades that the percutaneous transhepatic route for diagnostic cholangiography has become a standard technique and that therapeutic techniques for biliary drainage have been developed (Pereiras et al, 1978; Burcharth, 1982; Ferrucci, 1982; Mueller et al, 1985).
Technique All percutaneous procedures start with puncture of the biliary tree with the flexible Chiba needle to obtain a cholangiogram. The examination is performed via the right lateral or anterior approach using local anaesthesia and intravenous sedation and analgesia. Once well-positioned a guide wire is inserted through the needle or, alternatively, an over-sheath. A pigtail catheter can then be introduced over the guide wire to obtain external drainage. If it is possible, the guide wire should be manoeuvred through the stricture and a pigtail catheter with multiple side holes is advanced into the duodenum to establish external-internal drainage. Most radiologists prefer not to place a stent at the first session, but rather to wait a few days for the catheter tract to mature. The stent can then be introduced with the help of a pusher tube over the guide wire which is re-inserted via the external-internal catheter. A pigtail catheter for external drainage is left in place for safety. This catheter can be removed a few days later when adequate functioning of the stent is confirmed radiologically.
Results and early complications The success rate for puncturing a dilated bile duct and providing external drainage should be close to 100%. The establishment of external-internal drainage is less successful, the success rates for percutaneous stent placement varying between 82% and 92% (Burcharth, 1982; Mueller et al, 1985). Major complications are about 3% in patients undergoing diagnostic fine-needle PTHC and increase to 7-23% when a drainage procedure is added (Harbin et al, 1980; Stambuk et al, 1983; Demas et al, 1984). The most frequent serious complication of transhepatic biliary drainage is sepsis which occurs in slightly over 10% of patients even with prophylactic antibiotics. Liver puncture usually results in some localized pain, presumably due to a small bile leak. Major bile leakage and haemorrhage from the puncture site, however, can also occur. Pneumothorax and pleural effusion may result from high punctures. The long-term complications of external drainage are considerable and their use should therefore be restricted. Although the severe loss of fluids and electrolytes giving rise to the 'bile-loss syndrome' can be prevented by re-infusion of bile via a nasogastric tube or a percutaneous endoscopic gastrostomy, such an approach is distressing. Because external tubes are a physical and psychological burden for the patient they should only be used temporarily as a step in the technique of stent placement.
NON-OPERATIVE PALLIATION
997
ENDOSCOPIC TECHNIQUES The first endoscopic cannulation of the ampulla of Vater was by McCune et al in 1968. Therapeutic biliary endoscopy started in 1974 with sphincterotomy and gallstone extraction. Nasobiliary drainage was subsequently developed to prevent stone impaction and post-ERCP cholangitis in patients with biliary strictures. In 1979 a method for inserting an endoscopic biliary endoprosthesis was first described (Soehendra and ReijndersFrederix, 1980), which has since been developed and refined into a standard treatment procedure (Huibregtse et al, 1981; Huibregtse and Tytgat, 1984; Cotton, 1984, 1986).
Technique Following a diagnostic ERCP a small sphincterotomy is often made to facilitate manipulation. A 6 Fr or 7 Fr catheter with an 0.035 inch guide wire is introduced into the distal common bile duct. The catheter and guide wire are manoeuvred through and above the malignant stricture. Over the catheter a 10 Fr or 12 Fr endoprosthesis is then inserted with the help of a pusher tube (Figures 1 and 2).
Figure I. The straight Amsterdam-type endoprosthesis with side-flaps and the ancillary equipment for insertion procedure.
998
K. HUIBREGTSE
Figure 2. Left: Stricture of the pancreatic duct and the distal common bile duct in pancreatic cancer ('double duct sign'). Right: Endoscopic stent inserted through the bile duct stricture.
Results and early complications Endoscopists with reasonable experience will expect to place stents successfully in about 90% of patients (see Table 1) (Huibregtse et al, 1986; Huibregtse, 1988; Siegel et al, 1986; Speer and Cotton, 1988; Dowsett et al, 1989a, b). Difficulties can arise when there is distortion or invasion of the Table 1. Results of endoscopic stents in patients with carcinoma of the
pancreas in two large series. University of Amsterdama Number of patients Mean age Successful drainage 30-day mortality Median survival Duodenal stenosis Stent blockage
632 71 years 87% 10.8% 5 months 9% 29%
a Coene (1990); b Dowsett et al (1989). NA = not available.
Middlesex Hospitalb 403 NA 85% 17% 4.5 months 5% 16%
999
NON-OPERATIVE PALLIATION
duodenum by tumour. In this situation not only is it difficult to identify the ampulla but also the risk of subsequent duodenal obstruction is high and surgical palliation is usually more appropriate. Immediate complications of attempted and successful stent placements are similar to those of other ERCP procedures including acute pancreatitis, bleeding and perforation. Acute cholangitis is only a problem when adequate drainage has not been achieved. Although it is possible to perforate the bile duct and even to enter the venous system with guide wires, serious problems do not usually ensue. PERCUTANEOUS OR ENDOSCOPIC ROUTE? In general the external and external-internal percutaneous drainage procedures are only used as temporary measures or before placement of a stent. The complication rate of the percutaneous route is higher than the endoscopic approach. Moreover, whilst a failed percutaneous procedure often leaves the patient with an undesirable external bile leak, a failed endoscopic procedure causes little if any harm. Only one randomized trial has compared the percutaneous and endoscopic methods of stent insertion (Speer et al, 1987). Seventy-five patients participated in this study between 1983 and 1985. The endoscopic method had a higher success rate for relief of jaundice and a lower complication and mortality rate (Table 2). This study, which was performed in a unit with comparable expertise and experience in both procedures, clearly showed the superiority of the endoscopic approach. Table 2. Endoscopic versus percutaneous endoprosthesis for the
treatment of obstructive jaundice (Speer et al, 1987).
Number attempted Successful drainage Complications 30-day mortality Median survival
Percutaneous stent
Endoscopic stent
36 61% 67% 33% 88 days
39 81%* 19% * 15%* 119 days
• Statistically significant.
It is now generally accepted that the endoscopic method should be attempted first. Most failures of endoscopic stent placement are due to failed cannulation of the ampulla or to failed passage of the guide wire through the stricture. The success rate can be improved by a combined radiological and endoscopic technique or 'rendez-vous' procedure first described by Mason and Cotton in 1981. C O M B I N E D PROCEDURE
In this technique, the radiologist first introduces an external-internal catheter and a guide wire is inserted through this catheter into the duodenum.
1000
K. HUIBREGTSE
The endoscopist then grasps this guide wire and pulls the guide wire through the instrumentation channel. Over this guide wire, catheters, papillotomes or endoprostheses can now be inserted endoscopically. The main idea behind this combined procedure is that a large percutaneous tract can be avoided so that the complication rate is less than for percutaneous stent insertion. One study of combined procedures in 53 malignant strictures showed a success rate of 80%, a procedure-related morbidity of 36% and a mortality of only 3%. Although this would seem to be a useful approach, prospective randomized studies comparing the percutaneous and combined procedures are lacking (Dowsett et al, 1989a). LONG-TERM COMPLICATIONS OF BILIARY STENTS The main long-term complication of biliary stents is occlusion by sludge which occurs in 20 to 40% of the patients. Clogging may occur from one week to over 15 months after placement, with mean of about 5 months. The patients with a clogged endoprosthesis present with a 'flu-like' syndrome, consisting of malaise, low-grade fever or disturbance of liver function. Unless the significance of these symptoms is recognized, jaundice and acute cholangitis will soon supervene. Immediate removal and replacement of the clogged endoprosthesis is indicated. Although brushing and irrigation of the clogged endoprosthesis is technically possible, this is rarely indicated as prompt re-obstruction of the endoprosthesis usually occurs. Endoscopic replacement of a clogged endoprosthesis is usually technically simple, especially if a sphincterotomy was performed at the time of initial insertion. Replacement is nearly always followed by resolution of the symptoms. Percutaneous replacement of a clogged endoprosthesis is also possible but carries at least the same complication rate as percutaneous stent placement alone. Occasionally when a percutaneous secondary approach is necessary a second endoprosthesis should be placed alongside the clogged one. A blocked endoprosthesis contains inspissated bile, calculous debris and proteinaceous material (Wosiewitz et al, 1985; Groen et al, 1987). Endoprostheses removed 2 months after insertion are usually covered with a layer of protein and this is especially prominent around the side flaps and side holes. This layer always contains bacteria even when antibiotics have been administered continuously. It is still not clear whether this layer is produced by bacteria or whether the proteins derive from bile (Leung et al, 1988; Speer et al, 1988). In all probability this layer is the first step in the clogging process. Despite many in vitro and in vivo investigations in order to overcome the clogging problem, including the use of endoprostheses made of different materials and endoprostheses without side holes or rough surfaces as well as gallstone dissolution agents, mucolytic agents and choleretic agents, no practical recommendations can yet be made. On the other hand, the results obtained with the new Wallstent endoprosthesis, which is a self-expanding metal stent, are most encouraging (Figure 3). The inside diameter of the fully expanded stent is one centimetre. In a recent multicentre evaluation, stent occlusion by biliary sludge
NON-OPERATIVE PALLIATION
1001
Figure 3. Metal self-expanding stent (Wallstent) introduced through bile duct stricture due to pancreatic cancer.
was seen in only two out of 103 patients who had been followed up for a median period of 5 months (Huibregtse et al, unpublished). Other late complications are unusual but include acute cholecystitis, migration of the endoprosthesis into the more proximal bile duct or into the duodenum and perforation by the endoprosthesis of the bile duct or the duodenum. Duodenal obstruction from direct tumour invasion occurs as a late complication as well but in less than 10% of collected series. This relatively low incidence is due to the appropriate selection of cases, those patients with impending duodenal obstruction being recommended for operative gastroenterostomy as well as operative biliary drainage at the time of initial stent placement. Prompt recognition of the late complications of
1002
K. HUIBREGTSE
stenting is essential in order to optimize the quality of life as well as avoiding unnecessary early death. SURGICAL OR NON-SURGICAL PALLIATION Surgery is clearly indicated in patients with small potentially resectable tumours and in those patients with impending or overt duodenal obstruction. On the other hand, elderly patients who are at high risk from surgery are best treated by the non-operative approach, preferably by endoscopic means if the expertise is available. There is, however, a large group of patients who fall between these extremes and the relative merits of surgical versus non-surgical palliation are difficult to define. The relatively low surgical mortality and shorter hospital stay of the non-surgically treated patients in comparison with those undergoing operative bypass have been used as arguments in favour of the endoscopic and radiological approaches. Against this has been the penalty of recurrent jaundice and the need for frequent stent changes as well as the subsequent development of duodenal obstruction. Comparison with surgical series may not be appropriate because of selection bias. Recently, however, there have been three prospective randomized trials which have partly clarified the situation (Shepherd et al, 1988; Dowsett et al, 1989c; Andersen et al, 1989) the largest of which is still ongoing (Dowsett et al, 1989c). It is apparent from the studies that the immediate mortality rate as well as the incidence of complications are significantly lower in the endoscopically treated patients (Table 3). The benefit of shorter initial hospital stay of the non-operatively treated groups is to some extent counterbalanced, but not entirely eliminated, by the need to re-admit for stent changes and surgically bypass cases for duodenal obstruction. Table 3. Results of three prospective randomized trials comparing endoscopic stenting with surgical bypass for obstructive jaundice.
Shepherd et al (1988) Stent Number of patients Successful drainage Complications 30-day mortality Duodenal bypass Recurrent jaundice Median survival (range)
Surgery
Andersen et al (1989) Stent
Surgery
Dowsett et al (1989c) Stent
Surgery
23
25
25
19
101
103
91% 22% 9%
92% 40% 20%
96% NA NA
84% NA NA
94% 10% 7%
91% 28%* 17%*
0%
0%
0%
0%
6%
1%*
17% 152 days (39-411)
2% 125 days (52-354)
28% 84 days (3-498)
16% 100 days (10-642)
18% 5 monthst
NA = not available;
* statistically significant;
t mean survival.
3%* 5 monthst
NON-OPERATIVE PALLIATION
1003
There is no difference in the long-term survival of patients irrespective of treatment. This indicates that the main gain is in the reduction of initial hospital stay and procedural mortality. The need to re-admit patients for further procedures is, however, distressing for patients and confirms the rationale for using surgical palliation from the outset in younger or fitter patients. The general conclusions from these studies need to be treated with some caution. The results apply to only those patients entered into these trials whilst the spectrum of cases in clinical practice is diverse. Moreover, studies formally examining the quality of life of the two respective types of treatment need to be undertaken (see Andersen et al, 1989). CONCLUSIONS Pancreatic adenocarcinoma is a disease of the elderly. More than 50% of patients are over 70 years at the time of onset. With increasing life expectancy it is expected that more elderly patients with pancreatic cancer will be seen, increasing the demand for non-surgical palliation. Further improvement of these techniques will take place and the problem of the late obstruction of the endoprostheses should ultimately be solved. Whilst the increasing choice and sophistication of techniques available is interesting, the complexity of the problems should not divert us from our main aim which is to provide the optimum care for these patients. Close collaboration is required between radiologists, surgeons and endoscopists not only for the development of further prospective trials seeking answers to specific questions but also to provide on a day-to-day basis the best individual treatment for those patients currently in our care. REFERENCES Allen-Mersh TG & Earlham ILl (1986) Pancreatic cancer in England and Wales; surgeons look at epidemiology. Annals of the Royal College of Surgeons of England 68: 154--158. Andersen JR, Sorensen SM, Kruse A & Rokkjaer M (1989) Randomised trial of endoscopic endoprosthesis versus operative bypass in malignant obstructive jaundice. Gut 30: 11321135. Andren-Sandberg A & Ihse I (1983) Factors influencing survival after total pancreatectomy in patients with pancreatic cancer. Annals of Surgery 198: 605-610. Burcharth F (1982) Nonsurgical drainage of the biliary tract. Seminars in Liver Disease 2: 75-85. Coene PPLO (1990) Endoscopic Biliary Stenting. Krips Repro, Meppel. Connolly MM, Dawson PJ, Michelassi F et al (1987) Survival in 1001 patients with carcinoma of the pancreas. Annals of Surgery 206: 397-400. Cotton PB (1984) Endoscopic methods for relief of malignant obstructive jaundice. World Journal of Surgery 6: 854-861. Cotton PB (1986) Endoscopic biliary stents, trick or treatment? Gastrointestinal Endoscopy 32: 364-365. Demas BE, Moss A A & Goldberg HI (1984) Computed tomographic diagnosis of complications of transhepatic cholangiography and percutaneous biliary drainage. Gastrointestinal Radiology 9: 219-222. Dowsett JR, Vaira D, Hatfield ARW et al (1989a). Endoscopic biliary therapy using the combined percutaneous and endoscopic technique. Gastroenterology 96: 1180--1186. Dowsett JR, Williams SJ, Hatfield ARW et al (1989b). Endoscopic management of low biliary
1004
K. HUIBREGTSE
obstruction due to unresectable primary pancreato-biliary malignancy: a review of 463 consecutive cases. Gastroenterology 96: A129. Dowsett JF, Russell RCG, Hatfield ARW et al (1989c) Malignant obstructive jaundice; a prospective randomized trial of surgery versus endoscopic stenting. Gastroenterology 96: A128. Ferrucci JT (1982) Percutaneous biliary drainage: technical and catheter related problems in 200 procedures. American Journal of Radiology 138: 17-23. Groen AK, Out T, Huibregtse K et al (1987) Characterization of the content of occluded biliary endoprosthesis. Endoscopy 19: 57-59. Harbin WP, Mueller PR & Ferrucci JT (1980) Transhepatic cholangiography: complications and use patterns of the fine needle technique. Radiology 135: 15-22. Huibregtse K (1988) Endoscopic biliary and pancreatic drainage. Stuttgart: George Thieme Vertag. Huibregtse K & Tytgat GNJ (1984) Endoscopic placement of biliary prostheses. In Salmon PR (ed.) Gastrointestinal Endoscopy. Advance in Diagnosis and Therapy, pp 219-231. London: Chapman and Hall. Huibregtse K, Haverkamp HJ & Tytgat GNJ (1981) Transpapillary positioning of a large 3.2 mm biliary endoprosthesis. Endoscopy 13: 217-219. Huibregtse K, Katon RM, Coene PP & Tytgat GNJ (1986) Endoscopic palliative treatment in pancreatic cancer. Gastrointestinal Endoscopy 32" 334-338. Kaiser MH, Barkin J & Maclntyre JM (1985) Pancreatic cancer. Assessment of prognosis by clinical presentation. Cancer 56: 397--402. Leung JWC, Ling TKW, Kung JLS & Vallence-Owen J (1988) The role of bacteria in the blockage of biliary stents. Gastrointestinal Endoscopy 34: 19--22. McCune WS, Shorb PE & Moscovitz H (1968) Endoscopic cannulation of the ampulla of Vater: a preliminary report. Annals of Surgery 167: 752-756. Mason RR & Cotton PB (1981) Combined duodenoscopic and transpapillary approach to stenosis of the papilla of Vater. British Journal of Radiology 54: 678. Mueller PR, Ferrucci JT, Teplich SK et al (1985) Biliary stent endoprosthesis: analysis of complications in 113 patients. Radiology 156: 637-639. Pereiras RV, Rheingold O J, Hutson D et al (1978) Relief of malignant obstructive jaundice by percutaneous insertion of a permanent prosthesis in the biliary tree. Annals of Internal Medicine 89: 589-593. Sarr MG & Cameron JL (1984) Surgical palliation of unresectable carcinoma of the pancreas. World Journal of Surgery 8: 906--918. Shepherd HA, Royle G, Ross APR, Diba A, Arthur M & Colin-Jones D (1988) Endoscopic biliary endoprosthesis in the palliation of malignant obstruction of the distal common bile duct: a randomised trial. British Journal of Surgery 75:1166-1168. Siegel JH &Snady H (1986) The significance of endoscopically placed prostheses in the management of biliary obstruction due to carcinoma of the pancreas: results of nonoperative decompression in 277 patients. American Journal of Gastroenterology 81: 634-641. Silverberg E & Lubera J (1986) Cancer statistics. Cancer 36: 9-25. Soehendra N & Reijnders-Frederix V (1980) Palliative bile duct drainage. A new endoscopic method of introducing a transpapillary drain. Endoscopy 12" 8--11. Speer AG & Cotton PB (1988) Endoscopic treatment of pancreatic cancer. International Journal of Pancreatology 3: 146--158. Speer AG, Cotton PB, Russell RCG et al (1987) Randomised trial of endoscopic versus percutaneous stent insertion in malignant obstructive jaundice. Lancet ii: 52-62. Speer AG, Cotton PB, Rode Jet al (1988) Biliary stent blockage with bacterial biofilm. Annals of Internal Medicine 108: 546-553. Stambuk EC, Pitt HA, Pais O, Mann LL, Lois JF & Gomes AS (1983) Percutaneous transhepatic cholangiography. Archives of Surgery 118: 1388-1394. Trede M (1985) The surgical treatment of pancreatic cancer. Surgery 97: 28-35. Warshaw AL & Swanson RS (1988) Pancreatic cancer in 1988. Annals of Surgery 208: 541-553. Wechsler RL & Wechsler L (1975) The first application of transhepatic cholangiography to the localization of liver or biliary tract pathology: Hanoi, 1937. American Journal of Digestive Diseases 20: 699-700. Wosiewitz V, Schrameyer B & Safrany L (1985) Biliary sludge: its role during bile duct drainage with an endoprosthesis. Gastroenterology 88: 1706.
