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© 2000 American Society for Clinical Oncology Preoperative Chemoradiation for Patients With Pancreatic Cancer: Toxicity of Endobiliary StentsFrom the Pancreatic Tumor Study Group, The University of Texas M.D. Anderson Cancer Center, Houston, TX. Address reprint requests to Peter W.T. Pisters, MD, Department of Surgical Oncology, Box 106, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030-4095; email ppisters{at}notes.mdacc.tmc.edu
PURPOSE: A recent multicenter study of preoperative chemoradiation and pancreaticoduodenectomy for localized pancreatic adenocarcinoma suggested that biliary stent–related complications are frequent and severe and may prevent the delivery of all components of multimodality therapy in many patients. The present study was designed to evaluate the rates of hepatic toxicity and biliary stent–related complications and to evaluate the impact of this morbidity on the delivery of preoperative chemoradiation for pancreatic cancer at a tertiary care cancer center. PATIENTS AND METHODS: Preoperative chemoradiation was used in 154 patients with resectable pancreatic adenocarcinoma (142 patients, 92%) or other periampullary tumors (12 patients, 8%). Patients were treated with preoperative fluorouracil (115 patients), paclitaxel (37 patients), or gemcitabine (two patients) plus concurrent rapid-fractionation (30 Gy; 123 patients) or standard-fractionation (50.4 Gy; 31 patients) radiation therapy. The incidences of hepatic toxicity and biliary stent–related complications were evaluated during chemoradiation and the immediate 3- to 4-week postchemoradiation preoperative period. RESULTS: Nonoperative biliary decompression was performed in 101 (66%) of 154 patients (endobiliary stent placement in 77 patients and percutaneous transhepatic catheter placement in 24 patients). Stent-related complications (occlusion or migration) occurred in 15 patients. Inpatient hospitalization for antibiotics and stent exchange was necessary in seven of 15 patients (median hospital stay, 3 days). No patient experienced uncontrolled biliary sepsis, hepatic abscess, or stent-related death. CONCLUSION: Preoperative chemoradiation for pancreatic cancer is associated with low rates of hepatic toxicity and biliary stent–related complications. The need for biliary decompression is not a clinically significant concern in the delivery of preoperative therapy to patients with localized pancreatic cancer.
PANCREATICODUODENECTOMY is the only known potentially curative treatment for pancreatic adenocarcinoma. Surgery alone results in a median survival of approximately 12 to 14 months.1,2 The addition of postoperative fluorouracil (5-FU)-based chemoradiation increases survival duration to 18 to 22 months.3-6 However, recent studies suggest that a minimum of 30% of patients who undergo pancreaticoduodenectomy do not receive intended postoperative therapy because of delayed recovery from surgery or surgery-related morbidity.4,5,7,8 Thus, to the extent that chemoradiation may improve survival duration, treatment sequencing that delivers chemoradiation postoperatively may be suboptimal because many patients will not receive all intended treatment components. In contrast, preoperative chemoradiation allows all patients who undergo resection to derive the benefit of combined-modality treatment.9 Preoperative (neoadjuvant) chemoradiation offers several specific advantages compared with postoperative chemoradiation for localized, resectable pancreatic cancer.4,9 Theoretical and practical advantages of preoperative chemoradiation for pancreatic cancer include: (1) radiation therapy is more effective on well-oxygenated cells that have not been devascularized by surgery; (2) peritoneal tumor-cell implantation caused by tumor manipulation at surgery may be minimized or prevented; (3) preoperative treatment provides a temporal window to observe the biology of an individual patient’s tumor, and therefore, patients with disseminated disease evident at restaging after chemoradiation are not subjected to the risks of morbidity and mortality associated with surgery; and (4) because preoperative chemoradiation is given first, delayed postoperative recovery will have no effect on the delivery of multimodality therapy. The Eastern Cooperative Oncology Group (ECOG) recently reported the outcome of a prospective multi-institutional trial performed to examine the tolerance to and efficacy of a program of preoperative chemoradiation and surgery for patients with localized pancreatic adenocarcinoma.10 In this phase II study, 62 patients were treated with preoperative external-beam radiation therapy (50.4 Gy in 28 fractions); 57 of them also received concomitant chemotherapy (5-FU, 1,000 mg/m2/d by continuous infusion on days 2 to 5 and 29 to 32; mitomycin, 10 mg/m2 on day 2). Thirty-one (50%) of the 62 patients underwent placement of either an endobiliary stent (18 patients) or percutaneous transhepatic biliary catheter (13 patients) for pretreatment relief of biliary obstruction. Fifty-six of the 62 patients completed radiation therapy, although five (9%) of the 56 required a treatment break. Ten (18%) of the 57 patients who received chemotherapy required a treatment delay or dose reduction despite the fact that 52 of the 57 patients received their chemotherapy as inpatients. During chemoradiation and the postchemoradiation preoperative period, 29 (51%) of 57 patients experienced toxic events that required hospital admission. Tumor- or stent-related biliary obstruction with cholangitis was believed to be responsible for 38% of hospital admissions for complications. Severe and lethal infections occurred only in patients with endoscopically placed biliary stents (six of 18 patients v none of the 13 patients with percutaneous transhepatic catheters, P = .011). Two patients died as a consequence of biliary stent–related toxicity and uncontrolled biliary sepsis. The ECOG investigators concluded that complications secondary to recurrent biliary obstruction represented a substantial disadvantage of preoperative chemoradiation for patients with localized, potentially resectable pancreatic cancer. The toxicity results of the ECOG trial have raised appropriate concerns regarding the safety and feasibility of preoperative chemoradiation for patients with potentially resectable adenocarcinoma of the pancreatic head. These patients usually require nonoperative biliary decompression before initiation of preoperative chemoradiation (which necessarily defers definitive surgery). Our experience with protocol-based treatment for pancreatic adenocarcinoma in small cohorts of patients has not suggested an increased risk for hepatic toxicity among patients treated with preoperative combined-modality therapy.9,11,12 However, to better address the issues raised by the ECOG trial, we reviewed our entire institutional experience with preoperative chemoradiation for localized, potentially resectable pancreatic and periampullary malignancies. This report represents the accrued experience over an 8-year period and includes all patients who received chemoradiation before planned pancreaticoduodenectomy for adenocarcinoma of the pancreas or periampullary region. The objectives of this analysis were to define the rates of hepatic toxicity and biliary stent–related complications and to evaluate the impact of this morbidity on the delivery of preoperative chemoradiation for pancreatic cancer at a tertiary care cancer center.
Patients A prospective pancreatic and periampullary cancer database was established at The University of Texas M.D. Anderson Cancer Center (MDACC) in 1990. Using this database, we identified the subset of 154 patients who were treated at MDACC with preoperative chemoradiation for presumed or histologically proven adenocarcinoma of the pancreas or periampullary region between September 1, 1990, and September 1, 1998. Preoperative chemoradiation was initiated as part of a combined-modality treatment strategy that was planned to include subsequent pancreaticoduodenectomy. The majority of the patients (n = 103) were treated on existing protocols evaluating preoperative combined-modality therapy.9,11 Written informed consent was obtained from all patients enrolled onto the protocols. Fifty-one patients were not eligible for protocols because of complications from laparotomies performed before referral to our institution, lack of tissue confirmation of malignancy, poor performance status, or other significant comorbidity. These patients received 5-FU–based chemoradiation outside the context of existing protocols. All patients underwent standard pretreatment evaluation that included thin-section, contrast-enhanced computed tomography of the abdomen; chest radiography; and physical examination. All patients were required to have potentially resectable disease based on physical examination and previously published objective radiographic criteria.13 Patients were also required to have a Karnofsky performance status of 70% or greater, an absolute granulocyte count above 3,000/mL, a platelet count of at least 100,000/mL, and a serum bilirubin level no higher than 10 mg/dL for patients treated with 5-FU or gemcitabine or 2.0 mg/dL for patients treated with paclitaxel. When necessary, obstructive jaundice was palliated with an endoscopically or transhepatically placed biliary stent. Most of the transhepatic catheters were placed early in our experience with neoadjuvant therapy for pancreatic cancer, before the recruitment of specialized interventional upper endoscopists (I.R., S.L.). We currently prefer endoscopic biliary decompression because it avoids the pain and discomfort associated with a transhepatic catheter and eliminates the potential for tumor-cell implantation along the catheter tract. Patients who presented, after laparotomy, with common bile duct exploration and placement of a common bile duct catheter (T-tube) underwent placement of an endobiliary stent with removal of the T-tube (n = 5). Evaluation during chemoradiation included daily toxicity assessment, weekly history and physical examinations, and weekly measurements of body weight, performance status, complete blood cell count, and liver function. Three to 4 weeks after completion of chemoradiation (before surgery), patients underwent a complete restaging evaluation, which included physical examination, laboratory studies, repeat chest radiography, and abdominal computed tomography. Patients without disease progression on restaging evaluation proceeded to laparotomy for planned pancreaticoduodenectomy. Patients with evidence of disease progression did not undergo surgery.
Preoperative Chemoradiation Patients underwent postchemoradiation (preoperative) radiographic restaging 3 to 4 weeks after the completion of chemoradiation. Therefore, the minimum period of time that patients were at risk for experiencing biliary stent–related morbidity was a function of the radiation treatment schedule; patients treated with 50.4 Gy in 28 fractions were at risk for 9 to 10 weeks (5.5 treatment weeks plus 4 posttreatment weeks), whereas patients treated with 30 Gy in 10 fractions were at risk for a minimum of 6 weeks (2 treatment weeks plus 4 posttreatment weeks).
Diagnostic and Therapeutic Biliary Manipulation
Freedom from biliary stent–related complications was plotted as a function of time by the Kaplan-Meier method.14 For patients who had no biliary stent–related complications during chemoradiation (period C) or the subsequent posttreatment follow-up period (period D), the date of radiologic restaging (Fig 1) was used as the date on which patients were censored from the actuarial analysis of freedom from stent-related complications.
Patients and Pretreatment Biliary Manipulation The clinicopathologic characteristics of the study group are outlined in Table 1. The median age was 63 years (range, 35 to 81 years). The histologic diagnosis was pancreatic adenocarcinoma in the majority of patients (92%).
The details of pretreatment diagnostic and therapeutic biliary manipulation among patients with biliary stents placed during periods A (prereferral) and B (MDACC evaluation) are outlined in Fig 2. During period A, prereferral cholangiography (with or without biliary stent placement) was performed in 71 patients (46%). Prereferral biliary drains were placed in 57 patients (37%); endobiliary stents in 48 patients and percutaneous transhepatic catheters in nine patients. Prereferral operative biliary drainage by cholecystojejunostomy or choledochojejunostomy was performed in 29 patients (19%). During period B, 72 patients underwent biliary decompression at MDACC. Endobiliary stents were placed in 29 patients, and percutaneous transhepatic catheters were placed in 15 patients; pretreatment exchange of biliary catheters was necessary in 28 patients. The most common reasons for pretreatment catheter exchange were the need to perform repeat cholangiography in the setting of marginal-quality prereferral cholangiography and presentation to MDACC with occlusion of a biliary stent placed before referral.
At the conclusion of all diagnostic and therapeutic biliary procedures performed during periods A and B, a biliary drain was present for pretreatment relief of jaundice in 101 patients (66%); biliary drainage was by endobiliary stents in 77 patients and percutaneous transhepatic catheters in 24 patients (Table 2).
Hepatic Toxicity and Biliary Stent–Related Complications Grade 4 hepatic toxicity was observed during chemoradiation (period C) in 10 patients. Each of the episodes was related to stent malfunction; no grade 3 or 4 hepatic toxicities were observed that were unrelated to biliary stents. Five additional patients experienced stent-related complications during the postchemoradiation preoperative period (period D). Details of the stent-related hepatic toxic effects and their management are given in Table 3. Hepatic toxicity was related to stent occlusion in 14 (93%) of the 15 patients; one patient experienced stent migration. Stent occlusion was manifested by hyperbilirubinemia alone in eight patients and hyperbilirubinemia in association with fever in seven patients. The treatment for each of these cases was stent exchange. This was performed on an outpatient basis in eight patients (53%), and seven patients (47%) were hospitalized for IV antibiotics and stent exchange. The median length of hospital stay was 3 days (range, 2 to 32 days; the patient with the 32-day hospital stay is discussed below). Among the 10 patients experiencing stent-related hepatic toxicity during chemoradiation, treatment interruption was required in four patients (2-day treatment break for one patient, 3-day treatment break for one patient, and two patients had chemoradiation treatment terminated with three of 10 planned radiation fractions remaining). No patient-related (eg, age, sex, or comorbidity), catheter-related (eg, biliary drain type or size), or treatment-related (eg, type of chemoradiation or duration of treatment) factors seemed to be associated with stent occlusion. The cumulative risk of biliary stent–related complications is plotted as a function of time from biliary stent placement in Fig 3. The actuarial risk of stent-related complications at 12 weeks (the maximum time between stent placement and the date of preoperative restaging) was 13%.
Two patients warrant specific comment. One patient died of a pulmonary embolism on day 4 of chemoradiation after having received three of 10 planned radiation fractions. This patient was at risk of experiencing stent-related complications for 25 days (from the date of stent placement to the date of death). A second patient died during the postchemoradiation preoperative period after a 32-day hospitalization. This patient was admitted with pulmonary sepsis 2 days after completion of chemoradiation. The patient developed disseminated intravascular coagulation associated with multisystem organ failure, which proved fatal. Nine days after hospital admission, while receiving treatment for multisystem organ failure, the patient developed endobiliary stent occlusion. This was treated by stent exchange without immediate complications. Given the temporal relationship of these events, stent occlusion seems to have been a comorbid event occurring during this complicated hospital admission but does not seem to have directly led to the patient’s death. We have previously described the clinical course of this patient.9 We have not seen a similar clinical event in our experience with preoperative 5-FU–based chemoradiation for pancreatic adenocarcinoma and do not believe that this death was directly related to chemoradiation or to biliary stent malfunction.
The substantial rates of biliary drain–related morbidity and mortality noted in the ECOG trial10 have raised concerns regarding the overall safety of preoperative treatment strategies for patients with resectable pancreatic cancer. To examine the potential relationship between pretreatment biliary drainage and the morbidity of chemoradiation, we reviewed our institutional experience with preoperative chemoradiation for patients with pancreatic and periampullary malignancies. We specifically included patients who were treated off-protocol to avoid the selection bias that may occur with protocol-based treatment; patients with suboptimal performance status or substantial comorbidities are often not offered protocol-based therapies. As the potential toxicity of protocol-based therapy increases, the selection bias introduced by treating physicians may also increase, thereby eliminating from analysis those expected to have the greatest treatment-related toxicity. Thus, if a significant relationship exists between pretreatment biliary drainage and chemoradiation morbidity, the likelihood of identifying such a relationship would be maximized by our larger sample size (v the ECOG trial) and the inclusion of patients treated off-protocol. Our experience with biliary stent–related hepatic toxicity occurring during chemoradiation and the postchemoradiation preoperative period contrasts with the recently reported experience of the ECOG phase II multicenter trial of preoperative chemotherapy (mitomycin and 5-FU) and concurrent standard-fractionation (50.4 Gy, 28 fractions) radiation therapy (Table 4).10 Although the number of patients at risk of experiencing biliary stent–related complications in the present study (101 of 154 patients; 66%) was more than three times greater than the group at risk in the ECOG trial (31 of 62 patients; 50%), the overall rate of stent-related complications and their severity were substantially lower than the 44% rate of grade 3 to 5 hepatic toxicity observed in the ECOG trial. In our experience, 15 (15%) of 101 patients experienced biliary stent–related complications between the time of definitive biliary decompression and the date of restaging, and there were no episodes of uncontrolled biliary sepsis. During chemoradiation (period C), grade 3 or 4 hepatic toxicity occurred in 10 (6%) of 154 patients. When present, grade 3 or 4 hepatic toxicity was always a consequence of a biliary stent–related complication (usually occlusion). Stent occlusion was managed with outpatient stent exchange in six of the 10 patients, and only four of the 10 patients required treatment interruption. Two of these four patients ultimately completed chemoradiation, and two discontinued chemoradiation after completion of seven of 10 planned radiation fractions. Thus, only two of the 101 patients with indwelling endobiliary stents were unable to complete chemoradiation because of stent-related hepatic toxicity. In contrast to the ECOG trial,10 we did not observe any episodes of biliary stent–related death.
The severity of stent-related complications occurring during period D (posttreatment preoperative period) also seems less than that observed in the ECOG trial. Stent-related complications occurred during period D in five of our patients; three of these patients required hospitalization for inpatient stent exchange and antibiotics. The ECOG investigators reported the frequency and reasons for hospital admissions that occurred during or within 4 weeks of the end of chemoradiation without stratifying for treatment versus posttreatment admission. Therefore, direct comparison of our posttreatment morbidity to that observed in the ECOG trial is not possible. In the ECOG trial, 29 (51%) of 57 patients were hospitalized for complications occurring during or within 4 weeks of the end of chemoradiation. Eleven of these admissions (38%) were for cholangitis, and one was for a liver abscess; all of these were believed to be related to stent malfunction.10 Thus, 11 (36%) of 31 patients at risk of developing stent-related complications required hospitalization for management of such complications. This is substantially different than the 7% rate of hospital admission for biliary stent complications observed in the 101 patients at risk in the current report (Table 4). There are several potential explanations for the differences in the incidences of hepatic toxicity and the severity of stent-related complications between the present report and the ECOG trial. First, the greater myelosuppressive potential of the chemotherapy regimen used in the ECOG trial may have increased the risk for and/or severity of biliary sepsis as compared with the single-agent preoperative chemotherapy used at our institution. Second, the single-institution nature of our experience may have resulted in a lower overall toxicity profile than can be achieved in a multicenter trial. Optimal care of these complex patients requires multidisciplinary interaction, which may be enhanced within the confines of a single-institution working group dedicated to the evaluation and treatment of pancreatic cancer. This is particularly important because early recognition of biliary obstruction or sepsis may substantially reduce the morbidity and mortality associated with biliary stents.15 Future preoperative chemoradiation trials should consider interval monitoring of liver function tests in at-risk patients to detect subclinical elevations in alkaline phosphatase and/or bilirubin. Third, it is possible that our policy to place large-diameter (usually 10.0 or 11.5 French) stents may have contributed to a lower occlusion rate during treatment. Comparative studies have demonstrated lower overall occlusion rates with larger biliary stents.16,17 Finally, all endobiliary stents in this study were placed by one of two interventional endoscopists with expertise in therapeutic upper gastrointestinal endoscopy. One would expect lower morbidity, mortality, and cost when such interventional procedures are performed frequently by the same endoscopists and support personnel. In our study, the incidence of stent-related complications as a function of time (Fig 3) is comparable with that observed when biliary stents are used for the relief of malignant biliary obstruction in patients with unresectable pancreatic cancer.18-20 However, we cannot exclude the possibility that chemoradiation-induced local tissue edema may contribute to earlier stent occlusion. This retrospective report is not the optimal means with which to investigate such a potential relationship. We have evaluated the patient-, biliary-, and treatment-related factors that may have contributed to morbidity in the 15 patients who experienced stent-related complications during periods C and D. No specific association could be demonstrated for demographic factors, comorbid conditions, biliary stent size, biliary stent type, chemotherapy regimen, or radiation treatment schedule. The small number of stent-related complications precludes further speculation on specific factors that may contribute to the risk for stent-related complications during or after chemoradiation. The delivery of chemoradiation to patients with localized pancreatic cancer may be complicated by the need for pretreatment biliary decompression when preoperative chemoradiation is used or by delayed postoperative recovery that prevents the delivery of planned postoperative chemoradiation. Indeed, the need to establish durable biliary-enteric drainage to relieve jaundice before the initiation of neoadjuvant treatment represents a frequently cited disadvantage to preoperative chemoradiation. On the basis of the significant biliary stent–related morbidity and mortality observed in the ECOG trial, one might conclude that the presence of obstructive jaundice requiring biliary decompression is a relative contraindication to preoperative chemoradiation. However, the current data clearly demonstrate that this is not the case; the incidence of biliary stent–related toxicity is low when patients are managed carefully with prompt recognition of stent occlusion and prompt stent exchange. In contrast, approximately 30% of patients who undergo pancreaticoduodenectomy before chemoradiation do not recover from surgery sufficiently to proceed with postoperative chemoradiation.4,5,7,8 Pretreatment endoscopic endobiliary drainage with subsequent preoperative chemoradiation represents one strategy to maximize the proportion of patients who receive all components of combined-modality therapy. In summary, our experience with preoperative chemoradiation for resectable pancreatic cancer demonstrates that stent occlusion or migration occurring between the onset of biliary stent placement and the time of planned pancreaticoduodenectomy is relatively uncommon; stent-related complications occurred in 15 (10%) of 154 patients overall, or 15 (15%) of 101 patients at risk of experiencing stent-related morbidity. The morbidity associated with these stent-related complications was relatively low, with more than half of such complications managed on an outpatient basis; no stent-related death was observed. Treatment interruption or inability to complete chemoradiation as a consequence of stent-related morbidity was rare. Given the present rate of biliary catheter-related complications and the acceptably low morbidity associated with stent-related occlusion, these findings suggest that the presence of malignant obstruction requiring pretreatment biliary decompression should not be viewed as a practical or theoretical disadvantage or as a contraindication to preoperative chemoradiation in patients with potentially resectable pancreatic adenocarcinoma.
Supported by University of Texas M.D. Anderson Various Donors Fund for Pancreatic Cancer Research. We thank Vivian Z. Garcia and Melissa Burkett for their assistance in the preparation of this manuscript.
1. Yeo CJ, Sohn TA, Cameron JL, et al: Periampullary adenocarcinoma: Analysis of 5-year survivors. Ann Surg 227:821-831, 1998[Medline] 2. Conlon KC, Klimstra DS, Brennan MF: Long-term survival after curative resection for pancreatic ductal adenocarcinoma: Clinicopathologic analysis of 5-year survivors. Ann Surg 223:273-279, 1996[Medline] 3. Gastrointestinal Tumor Study Group: Further evidence of effective adjuvant combined radiation and chemotherapy following curative resection of pancreatic cancer. Cancer 59:2006-2010, 1987[Medline]
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Spitz FR, Abbruzzese JL, Lee JE, et al: Preoperative and postoperative chemoradiation strategies in patients treated with pancreaticoduodenectomy for adenocarcinoma of the pancreas. J Clin Oncol 15:928-937, 1997 5. Yeo CJ, Abrams RA, Grochow LB, et al: Pancreaticoduodenectomy for pancreatic adenocarcinoma: Postoperative adjuvant chemoradiation improves survival—A prospective, single-institution experience. Ann Surg 225:621-633, 1997[Medline] 6. Demeure MJ, Doffek KM, Komorowski RA, et al: Molecular metastases in stage I pancreatic cancer: Improved survival with adjuvant chemoradiation. Surgery 124:663-669, 1998[Medline] 7. Klinkenbijl JHG, Jeckel J, Sahmoud T, et al: Radiotherapy and 5-FU after curative resection for cancer of the pancreas and peri-ampullary region: A phase III trial of the EORTC Gastrointestinal Tract Cancer Cooperative Group. Ann Surg 230:776-784, 1999[Medline] 8. Pendurthi TK, Hoffman JP, Ross E, et al: Preoperative versus postoperative chemoradiation for patients with resected pancreatic adenocarcinoma. Am Surg 64:686-692, 1998[Medline] 9. Pisters PWT, Abbruzzese JL, Janjan NA, et al: Rapid-fractionation preoperative chemoradiation, pancreaticoduodenectomy, and intraoperative radiation therapy for resectable pancreatic adenocarcinoma. Clin Oncol 16:3843-3850, 1998 10. Hoffman JP, Lipsitz S, Pisansky T, et al: Phase II trial of preoperative radiation therapy and chemotherapy for patients with localized, resectable adenocarcinoma of the pancreas: An Eastern Cooperative Oncology Group study. Oncol 16:317-323, 1998 11. Evans DB, Rich TA, Byrd DR, et al: Preoperative chemoradiation and pancreaticoduodenectomy for adenocarcinoma of the pancreas. Arch Surg 127:1335-1339, 1992[Abstract] 12. Staley CA, Lee JE, Cleary KR, et al: Preoperative chemoradiation, pancreaticoduodenectomy, and intraoperative radiation therapy for adenocarcinoma of the pancreatic head. Surg 171:118-124, 1996 13. Fuhrman GM, Charnsangavej C, Abbruzzese JL, et al: Thin-section contrast-enhanced computed tomography accurately predicts the resectability of malignant pancreatic neoplasms. Am J Surg 167:104-111, 1994[Medline] 14. Kaplan E, Meier P: Non-parametric estimation from incomplete observations. J Am Stat Assoc 53:457-481, 1958 15. Sung JJ, Chung SC: Endoscopic stenting for palliation of malignant biliary obstruction: A review of progress in the last 15 years. Dig Dis Sci 40:1167-1173, 1995[Medline] 16. Speer AG, Cotton PB, MacRae KD: Endoscopic management of malignant biliary obstruction: Stents of 10 French gauge are preferable to stents of 8 French gauge. Gastrointest Endosc 34:412-417, 1988[Medline] 17. Siegel JH, Pullano WE, Wright G: The ultimate large caliber endoprosthesis-12F: Poiseuille was right—Bigger is better. Endosc 31:158-159, 1985 (abstr 137) 18. Prat F, Chapat O, Ducot B, et al: A randomized trial of endoscopic drainage methods for inoperable malignant strictures of the common bile duct. Gastrointest Endosc 47:1-7, 1998[Medline] 19. Davids PH, Groen AK, Rauws EA, et al: Randomised trial of self-expanding metal stents versus polyethylene stents for distal malignant biliary obstruction. Lancet 340:1488-1492, 1992[Medline] 20. Knyrim K, Wagner HJ, Pausch J, et al: A prospective, randomized, controlled trial of metal stents for malignant obstruction of the common bile duct. Endoscopy 25:207-212, 1993[Medline] Submitted June 4, 1999; accepted September 29, 1999. This article has been cited by other articles:
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Copyright © 2000 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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ABSTRACT
INTRODUCTION
