Article Search
검색
검색 팝업 닫기

Metrics

Help

  • 1. Aims and Scope

    Gut and Liver is an international journal of gastroenterology, focusing on the gastrointestinal tract, liver, biliary tree, pancreas, motility, and neurogastroenterology. Gut atnd Liver delivers up-to-date, authoritative papers on both clinical and research-based topics in gastroenterology. The Journal publishes original articles, case reports, brief communications, letters to the editor and invited review articles in the field of gastroenterology. The Journal is operated by internationally renowned editorial boards and designed to provide a global opportunity to promote academic developments in the field of gastroenterology and hepatology. +MORE

  • 2. Editorial Board

    Editor-in-Chief + MORE

    Editor-in-Chief
    Yong Chan Lee Professor of Medicine
    Director, Gastrointestinal Research Laboratory
    Veterans Affairs Medical Center, Univ. California San Francisco
    San Francisco, USA

    Deputy Editor

    Deputy Editor
    Jong Pil Im Seoul National University College of Medicine, Seoul, Korea
    Robert S. Bresalier University of Texas M. D. Anderson Cancer Center, Houston, USA
    Steven H. Itzkowitz Mount Sinai Medical Center, NY, USA
  • 3. Editorial Office
  • 4. Articles
  • 5. Instructions for Authors
  • 6. File Download (PDF version)
  • 7. Ethical Standards
  • 8. Peer Review

    All papers submitted to Gut and Liver are reviewed by the editorial team before being sent out for an external peer review to rule out papers that have low priority, insufficient originality, scientific flaws, or the absence of a message of importance to the readers of the Journal. A decision about these papers will usually be made within two or three weeks.
    The remaining articles are usually sent to two reviewers. It would be very helpful if you could suggest a selection of reviewers and include their contact details. We may not always use the reviewers you recommend, but suggesting reviewers will make our reviewer database much richer; in the end, everyone will benefit. We reserve the right to return manuscripts in which no reviewers are suggested.

    The final responsibility for the decision to accept or reject lies with the editors. In many cases, papers may be rejected despite favorable reviews because of editorial policy or a lack of space. The editor retains the right to determine publication priorities, the style of the paper, and to request, if necessary, that the material submitted be shortened for publication.

Search

Search

Year

to

Article Type

Original Article

Split Viewer

Efficacy Analysis of Suprapapillary versus Transpapillary Self-Expandable Metal Stents According to the Level of Obstruction in Malignant Extrahepatic Biliary Obstruction

Sung Yong Han1 , Tae Hoon Lee2 , Sung Ill Jang3 , Dong Uk Kim1 , Jae Kook Yang2 , Jae Hee Cho3 , Min Je Sung4 , Chang-Il Kwon4 , Jin-Seok Park5 , Seok Jeong5 , Don Haeng Lee5 , Sang-Heum Park2 , Dong Ki Lee3

1Department of Internal Medicine, Pusan National University School of Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, 2Department of Internal Medicine, Soonchunhyang University Hospital Cheonan, Cheonan, 3Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, 4Digestive Disease Center, CHA Bundang Medical Center, CHA University, Seongnam, and 5Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea

Correspondence to: Tae Hoon Lee
ORCID https://orcid.org/0000-0002-3545-9183
E-mail taewoolee9@gmail.com

Received: October 9, 2022; Revised: November 27, 2022; Accepted: December 6, 2022

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Gut Liver 2023;17(5):806-813. https://doi.org/10.5009/gnl220437

Published online April 4, 2023, Published date September 15, 2023

Copyright © Gut and Liver.

Background/Aims: The use of a self-expandable metal stent (SEMS) is recommended for unresectable malignant biliary obstruction (MBO). Stent-related adverse events might differ according to the position of the stent through the ampulla of Vater (AOV). We retrospectively evaluated SEMS patency and adverse events according to the position of the SEMS.
Methods: In total, 280 patients who underwent endoscopic SEMS placement due to malignant distal biliary obstruction were analyzed retrospectively. Suprapapillary and transpapillary SEMS insertions were performed on 51 patients and 229 patients, respectively.
Results: Between the suprapapillary group (SPG) and transpapillary group (TPG), the stent patency period was not significantly different (median [95% confidence interval]: 107 days [82.3 to 131.7] vs 120 days [99.3 to 140.7], p=0.559). There was also no significant difference in the rate of adverse events. In subgroup analysis, the stent patency for an MBO located within 2 cm from the AOV was found to be significantly shorter than that for an MBO located more than 2 cm from the AOV in the SPG (64 days [0 to 160.4] vs 127 days [82.0 to 171.9], p<0.001) and TPG (87 days [52.5 to 121.5] vs 130 [97.0 to 162.9], p<0.001). Patients with an MBO located within 2 cm from the AOV in both groups had a higher percentage of duodenal invasion (SPG: 40.0% vs 4.9%, p=0.002; TPG: 28.6% vs 2.9%, p<0.001) than patients with an MBO located more than 2 cm from the AOV.
Conclusions: The SPG and TPG showed similar results in terms of stent patency and rate of adverse events. However, patients with an MBO located within 2 cm from the AOV had a higher percentage of duodenal invasion with shorter stent patency than those with an MBO located more than 2 cm from the AOV, regardless of stent position.

Keywords: Self expandable metallic stents, Adverse events, Bile duct neoplasms, Ampulla of Vater, Endoscopic retrograde cholangiopancreatography

Malignant biliary obstruction (MBO) can occur due to cholangiocarcinoma, pancreatic adenocarcinoma, and other etiologies, such as hepatocellular carcinoma and metastasis from carcinoma of other organs.1 Cases of unresectable status require biliary drainage. Drainage is typically performed with endoscopic retrograde cholangiopancreatography (ERCP). The use of a self-expandable metal stent (SEMS) can prolong stent patency compared to the use of a plastic stent due to its large diameter.2 Therefore, SEMS is recommended for unresectable MBO due to its cost-effectiveness and ability to increase the quality of life of patients with expected survival of more than 3 months.3

However, technically, there are a few questions that should be considered before the insertion of a covered or uncovered SEMS. The position of the stent through the ampulla of Vater (AOV) can affect the occurrence of stent-related adverse events such as pancreatitis, cholangitis, and stent malfunction. There is no definite consensus regarding the effects of these factors due to a lack of studies. Stent placement across the level of AOV (transpapillary) is weak for the reflux of duodenal contents (Fig. 1). It may also increase the risk of pancreatitis. However, when stent malfunction develops, stent revision is technically easy. On the other hand, stent placement above the level of AOV (suprapapillary) may prevent reflux of duodenal contents, which may prolong stent patency or decrease adverse events such as cholangitis and sludge formation (Fig. 1). A previous study has shown that placement of the stent above the intact sphincter of Oddi is associated with longer stent patency and lower occlusion rate.4 In hilar MBO, stent patency is affected by various factors such as insertion method (side-by-side, stent-in-stent) and how much intrahepatic bile duct drainage has been performed. Thus, there is a limit to the interpretation of the role of stent position with AOV.

Figure 1.Fluoroscopy (A, B) and endoscopic (C) images of transpapillary stent placement and suprapapillary stent placement (D, E, F).

Except for in the case of a far distal biliary obstruction or AOV cancer, which it is agreed upon should be drained using the transpapillary method, there is still controversy regarding the position of stent placement in the case of extrahepatic MBO (>2 cm distal to the hilum). Therefore, the objective of this study was to evaluate SEMS patency and adverse events according to the position of SEMS.

1. Patients

In total, 280 patients who underwent SEMS placement by ERCP in five medical institutions between January 2016 and December 2020 were retrospectively reviewed. The inclusion criteria were as follows: (1) technically successful SEMS placement; (2) advanced or inoperable extrahepatic MBO defined as the presence of an unresectable malignant distal biliary obstruction (>2 cm distal to the hilum) with pathologicor radiologic diagnosis prior to endoscopic intervention;5 and (3) procedure performed by an experienced endoscopist without the involvement of a trainee. Meanwhile, the exclusion criteria were as follows: (1) AOV cancer; (2) uncontrolled coagulopathy; or (3) need for insertion of bilateral drainage (such as bismuth type II, III, IV). This study was conducted in accordance with the ethical guidelines of the Declaration of Helsinki (revised in 2013). The study protocol was approved by the Institutional Review Board of Soonchunhyang University Hospital (IRB number: 2020-03-022-005) and informed consent was waived.

2. Clinical measurement

We evaluated laboratory findings, radiologic information, and clinical characteristics such as age, sex, pathologic result of tumor (biliary tract cancer [BTC], pancreatic cancer, others), information of ERCP procedure, and follow-up data. The radiologic information that we considered included obstruction level (proximal, mid, distal common bile duct) and the presence of cystic duct invasion. Information on the ERCP procedure included stent type (fully covered, partially covered, uncovered), length of stent, and distance from AOV to distal malignant stricture, which were measured prior to performing ERCP by magnetic resonance imaging or from the coronal view of the computed tomography scan from duodenal wall to tumor distal obstruction level. Clinical success was defined as decline in total bilirubin over 50% or below 3 mg/dL within 1 week.5,6 Laboratory findings included total bilirubin, amylase, and lipase at pre-ERCP and 1 week after ERCP. Post-ERCP complications were defined by Cotton’s criteria.7 Early complication was defined as a complication that occurred within 1 month from ERCP. Late complication was defined as a complication that occurred at least 1 month after ERCP. Follow-up data included stent obstruction cause, revision method, success of revision, duodenal invasion that occurred at the time of ERCP or follow-up period, stent patency (defined as the time elapsed between successful stent placement and cholangitis or jaundice due to obstruction of stent), and overall survival duration.

3. Subgroup analysis

Subgroup analysis was performed for MBO within 2 cm from AOV versus MBO over 2 cm from AOV. In stent deployment, it is recommended that the stent cover more than 1 to 2 cm from MBO with SEMS to prevent tumor overgrowth.8 There is no consensus for stent deployment through ERCP. However, 1 to 2 cm from the MBO is typically covered with SEMS to prevent overgrowth. In the case of MBO within 2 cm from the AOV, it was judged that transpapillary was performed for most cases. Thus, subgroup analysis was performed to compare the transpapillary group (TPG) and the suprapapillary group (SPG), except for this part.

4. Statistical analysis

Statistical analysis was performed using SPSS software version 21.0 (IBM Corp., Armonk, NY, USA). Categorical data are expressed as frequency and percentage, with between-group differences having been evaluated using the chi-square test. Continuous data are expressed as mean±standard deviation, with between-group differences having been evaluated using the independent Student t-test. Statistical significance was determined at p<0.05. Stent patency and overall survival are expressed as median value and 95% confidence interval (CI), respectively. They were plotted using the Kaplan-Meier survival plot and tested using log-rank tests. Cox regression analysis was used to evaluate the factors affecting stent patency.

1. Baseline characteristics

In total, 280 patients with SEMS insertion in extrahepatic MBO were enrolled in this study. This included 51 patients with suprapapillary SEMS insertion and 229 patients with transpapillary SEMS insertion. Regarding baseline characteristics, sex ratio, age, stent type, clinical success rate, and laboratory findings pre-procedure and 1 week after ERCP were not significantly different between the two groups (Table 1). SPG had a higher ratio of cystic duct invasion (21.6% vs 4.8%, p<0.001) and BTC (78.5% vs 31.9%, p<0.001) than TPG. TPG had a higher ratio of pancreatic cancer (58.1% vs 17.6%, p<0.001), higher ratio of location in distal common bile duct (62.4% vs 25.5%, p<0.001), and longer stent length (6.41±0.99 cm vs 6.04±0.72 cm, p=0.012) than SPG.

Table 1 Baseline Characteristics of Patients Who Underwent Suprapapillary or Transpapillary Self-Expandable Metal Stent Insertion

CharacteristicSuprapapillary (n=51)Transpapillary (n=229)p-value
Male sex28 (54.9)122 (53.3)0.834
Age, yr73.2±9.572.0±11.50.486
Diagnosis<0.001
Biliary tract cancer40 (78.5)73 (31.9)
Pancreas cancer9 (17.6)133 (58.1)
Others2 (3.9)23 (10.0)
Obstruction level of common bile duct<0.001
Proximal12 (23.5)22 (9.6)
Middle26 (51.0)64 (27.9)
Distal13 (25.5)143 (62.4)
Cystic duct invasion11 (21.6)11 (4.8)<0.001
Stent length, cm6.04±0.726.41±0.990.012
Stent type0.103
Uncovered41 (80.4)160 (69.9)
Covered8 (15.7)62 (27.1)
Partially2 (3.9)7 (3.1)
Clinical success49 (96.1)216 (95.6)0.874
Pre-laboratory findings
Total bilirubin, mg/dL5.98±5.086.92±7.070.370
Amylase, U/L183.5±742.4103.3±211.20.175
Lipase, U/L57.5±61.1150.2±354.50.070
1 wk after laboratory findings
Total bilirubin, mg/dL3.18±3.092.60±2.980.246
Amylase, U/L72.1±54.287.9±78.20.259
Lipase, U/L69.8±118.9112.5±175.60.166

Data are presented as number (%) or mean±SD.



2. Clinical outcomes

There was no significant difference in early or late complications between the two groups. Post-ERCP pancreatitis was slightly higher in TPG (9.2% vs 2.0%, p=0.131). SPG had a higher ratio of stone in obstruction cause (47.8% vs 23.5%, p=0.025), higher ratio of cleansing only in the method of endorevision via ERCP (35.7% vs 16.1%, p=0.035), and lower ratio of ERCP in the revision method (82.4% vs 96.9%, p=0.027) than TPG. There was no significant difference in stent patency period (median [95% CI]: 107 days [82.3 to 131.7] vs 120 days [99.3 to 140.7], p=0.559) or overall survival days (142 days [35.6 to 248.3] vs 180 days [146.0 to 213.9], p=0.386) between the two groups (Table 2).

Table 2 Clinical Outcome According to the Route of Self-Expandable Metal Stent Insertion

VariableSuprapapillary (n=51)Transpapillary (n=229)p-value
Early adverse events
Cholangitis2 (3.9)9 (3.9)0.998
Pancreatitis1 (2.0)21 (9.2)0.131
Cholecystitis01 (0.4)0.638
Bleeding02 (0.9)0.505
Malfunction1 (2.0)4 (1.7)0.917
Late adverse events
Cholangitis9 (17.6)38 (16.7)0.876
Cholecystitis3 (5.9)7 (3.1)0.334
Malfunction18 (35.3)57 (25.1)0.140
Obstruction cause0.025
Ingrowth6 (31.6)39 (57.4)
Overgrowth2 (10.5)8 (11.8)
Both2 (10.5)5 (7.4)
Stone9 (47.8)16 (23.5)
Revision method17640.027
ERCP14 (82.4)62 (96.9)
Percutaneous3 (17.6)2 (3.1)
Revision success17 (100)63 (98.4)0.609
Endorevision method0.035
Restenting8 (57.1)51 (82.3)
Cleansing5 (35.7)10 (16.1)
Stent exchanging1 (7.1)1 (1.6)
Chemotherapy17 (33.3)98 (42.7)0.196
Stent patency, day107 (82.3–131.7)120 (99.3–140.7)0.559
Overall survival, day142 (35.6–248.3)180 (146.0–213.9)0.386

Data are presented as number (%) or median (95% confidence interval).

ERCP, endoscopic retrograde cholangiopancreatography.



3. Subgroup analysis

Clinically meaningful factors such as obstruction level, pathologic diagnosis, SEMS length, SEMS type, stent level (suprapapillary vs transpapillary), duodenal invasion, and MBO within or over 2 cm from AOV were included in the Cox regression analysis about stent patency (Table 3). In univariable analysis, MBO within 2 cm from AOV (hazard ratio [HR], 1.529; 95% CI, 1.186 to 1.197; p=0.001) and SEMS type (HR, 0.657; 95% CI, 0.501 to 0.862; p=0.002) were both found to be significant. In the multivariable analysis, MBO within 2 cm from AOV (HR, 1.447; 95% CI, 1.101 to 1.901; p=0.008) and SEMS type (HR, 0.667; 95% CI, 0.502 to 0.885; p=0.005) remained significant.

Table 3 Analysis of Factors Affecting Stent Patency According to Cox Regression Analysis

FactorUnivariable analysisMultivariable analysis
HR (95% CI)p-valueHR (95% CI)p-value
Obstruction level
Proximal CBD vs mid CBD1.194 (0.796–1.791)0.3911.241 (0.820–1.880)0.308
Proximal CBD vs distal CBD1.411 (0.961–2.073)0.0791.161 (0.735–1.834)0.522
Diagnosis (BTC vs non-BTC)1.153 (0.092–1.473)0.2571.273 (0.962–1.684)0.091
SEMS type (uncovered vs covered)0.657 (0.501–0.862)0.0020.667 (0.502–0.885)0.005
SEMS length1.007 (0.891–1.137)0.9141.047 (0.918–1.194)0.492
Stent level (suprapapillary vs transpapillary)0.911 (0.665–1.247)0.5600.729 (0.512–1.038)0.079
Duodenal obstruction1.352 (0.946–1.933)0.0981.286 (0.855–1.936)0.227
MBO within 2 cm from AOV1.529 (1.186–1.197)0.0011.447 (1.101–1.901)0.008

HR, hazard ratio; CI, confidence interval; CBD, common bile duct; BTC, biliary tract cancer; SEMS, self-expandable metal stent; MBO, malignant biliary obstruction; AOV, ampulla of Vater.



Table 4 lists the results of subgroup analysis according to MBO within or over 2 cm from AOV. In TPG, MBO over 2 cm from AOV had higher covered stent than others (36.2% vs 13.2%, p<0.001). Duodenal invasion was higher in MBO within 2 cm from AOV than it was in MBO over 2 cm from AOV (SPG: 40.0% vs 4.9%, p=0.002; TPG: 28.6% vs 2.9%, p<0.001). Stent patency in MBO within 2 cm from the AOV was significantly shorter than that in MBO over 2 cm from the AOV (SPG: 64 days [0 to 160.4] vs 127 days [82.0 to 171.9], p<0.001; TPG: 87 days [52.5 to 121.5] vs 130 days [97.0 to 162.9], p<0.001). Fig. 2 shows stent patency according to SPG or TPG and MBO within or over 2 cm from AOV. Overall survival duration was also shorter in MBO within 2 cm from AOV in SPG (71 days [40.5 to 101.5] vs 196 days [121.0 to 270.9], p<0.001) and TPG (140 days [95.1 to 184.9] vs 227 days [182.1 to 271.9], p=0.008). In MBO within 2 cm from AOV, TPG had a longer overall survival duration than SPG (227 days [182.1 to 271.9] vs 196 days [121.0 to 270.9], p=0.037).

Table 4 Subgroup Analysis for MBO within 2 cm and MBO over 2 cm from the AOV for Patients Undergoing Suprapapillary or Transpapillary Self-Expandable Metal Stent Insertion

VariableSuprapapillary (n=51)Transpapillary (n=229)
MBO within 2 cm
from AOV (n=10)
MBO over 2 cm
from AOV (n=41)
p-valueMBO within 2 cm
from AOV (n=91)
MBO over 2 cm
from AOV (n=138)
p-value
Diagnosis0.014
Biliary tract cancer4 (40.0)36 (87.8)22 (24.2)51 (36.9)
Pancreas cancer6 (60.0)3 (7.3)61 (67.0)72 (52.2)
Others02 (4.9)8 (8.8)15 (10.8)
Stent obstruction cause0.979
Ingrowth06 (40.0)15 (48.4)24 (64.9)
Overgrowth02 (13.3)2 (6.5)6 (16.2)
Both02 (13.3)2 (6.5)3 (8.1)
Stone4 (100)5 (33.3)12 (38.7)4 (10.8)
Stent type0.004
Uncovered8 (80.0)33 (80.5)0.82678 (85.7)82 (59.4)<0.001
Covered2 (20.0)6 (14.6)12 (13.2)50 (36.2)
Partially02 (4.9)1 (1.1)6 (4.3)
Duodenal invasion4 (40.0)2 (4.9)0.00226 (28.6)4 (2.9)<0.001
Chemotherapy17 (33.3)98 (42.7)0.196
3 (30.0)14 (34.1)0.56936 (39.5)62 (44.9)0.412
Stent patency, day107 (82.3–131.7)120 (99.3–140.7)0.559
64 (0–160.4)127 (82.0–171.9)<0.00187 (52.5–121.5)130 (97.0–162.9)<0.001
127 (82.0–171.9)130 (97.0–162.9)0.595
Overall survival, day142 (35.6–248.3)180 (146.0–213.9)0.386
71 (40.5–101.5)196 (121.0–270.9)<0.001140 (95.1–184.9)227 (182.1–271.9)0.008
196 (121.0–270.9)227 (182.1–271.9)0.037

Data are presented as number (%) or median (95% confidence interval).

MBO, malignant biliary obstruction; AOV, ampulla of Vater.



Figure 2.Kaplan-Meier stent patency in patients with suprapapillary and transpapillary MBO within and over 2 cm from AOV (A), MBO over 2 cm from AOV (B).
MBO, malignant biliary obstructions; AOV, ampulla of Vater.

When comparing the SPG and TPG groups, the stent patency period was found to be similar regardless of whether MBO was within 2 cm from AOV. The rates of adverse events in SPG and TPG were also similar. For MBO within 2 cm from AOV, SPG had a shorter stent patency than TPG (64 days [0 to 160.4] vs 87 days [52.5 to 121.5], p=0.006). The stent patency of MBO within 2 cm from the AOV was significantly lower than that of MBO over 2 cm from the AOV (SPG: 64 days [0 to 160.4] vs 127 days [82.0 to 171.9], p<0.001; TPG: 87 days [52.5 to 121.5] vs 130 days [97.0 to 162.9], p<0.001). Duodenal invasion was higher in MBO within 2 cm from the AOV than it was in MBO over 2 cm from the AOV (SPG: 40.0% vs 4.9%, p=0.002; TPG: 28.6% vs 2.9%, p<0.001).

There have been few studies examining suprapapillary or transpapillary stenting.9 In particular, to our knowledge, there has been no study investigating SEMS to extrahepatic MBO. Shin et al.10 has shown that the effectiveness and safety of suprapapillary and transpapillary stent insertions of hilar cholangiocarcinoma are similar, although the success rate of endobiliary revision is significantly higher in TPG. One meta-analysis has shown that SPG has longer stent patency than TPG.11 However, the enrolled studies used plastic stents. Thus, our result showing that both methods have similar stent patency is meaningful for comparing SPG and TPG in extrahepatic MBO using SEMS.

Stent placement suprapapillary may prevent reflux of duodenal contents, which may prolong stent patency or decrease the incidence of adverse events such as cholangitis and sludge formation. The sphincter of Oddi is a barrier to protective reflux of duodenal contents. Thus, the usefulness of endoscopic sphincterotomy is one of the issues involved in suprapapillary stenting.12,13 However, the role of this barrier was thought to be limited in our study, as small endoscopic sphincterotomy was performed in all enrolled patients before stenting or biopsy via ERCP. To maximize the advantages of a suprapapillary deployment, there is a need for further studies comparing stent patency in patients without in the future.

MBO within 2 cm from the AOV had a shorter stent patency than MBO over 2 cm from the AOV in both groups (SPG and TPG). This result might be due to a higher ratio of duodenal invasion. Food passage was faster in the duodenum than it was in the stomach. If there was a duodenal invasion, the passage of food in the duodenum might be slowed. This food retention will increase the chance of reflux of duodenal contents and obstruction. It is known that 38% to 45%14-16 of patients with pancreatic cancer or distal bile duct cancer patients will experience duodenal invasion during follow-up periods. In our results, MBO within 2 cm from the AOV was shown to have a higher rate of duodenal obstruction (SPG: 40.0% vs 4.9%, p=0.002; TPG: 28.6% vs 2.9%, p<0.001). The rate of duodenal invasion was similar to those obtained in other studies.14-16 Duodenal invasion mainly occurred in MBO within 2 cm from the AOV. MBO within 2 cm from the AOV had a higher frequency of stone as a cause of obstruction than MBO over 2 cm from the AOV (16/35 [45.7%] vs 9/52 [17.3%], p<0.001). This was believed to be highly correlated with the high rate of duodenum invasion in MBO within 2 cm from the AOV. In patients with MBO within 2 cm from the AOV, SPG had a shorter stent patency than TPG (64 days [0 to 160.4] vs 87 days [52.4 to 121.5], p=0.006). Thus, transpapillary stenting is preferable for patients with MBO within 2 cm of the AOV. Even with transpapillary stenting, the patency seems to be short. Thus, it might be better to perform biliary drainage using other methods.

In the results of the Cox regression about stent patency, the type of SEMS was found to influence stent patency (uncovered vs covered: 103 days [83.1 to 122.9] vs 160 days [110.7 to 209.2], p=0.002). However, meta-analysis revealed similar or slightly longer stent patency in covered SEMS than in uncovered SEMS, showing no statistically significant difference.17,18 Overall survival days were significantly longer in MBO over 2 cm from the AOV in both groups (SPG: 196 days [121.0 to 270.9] vs 71 days [40.5 to 101.5], p<0.001; TPG: 227 days [182.1 to 271.9] vs 140 days [95.1 to 184.9], p=0.008). In addition, overall survival days in MBO over 2 cm from the AOV were longer in TPG than in SPG (227 days [182.1 to 271.9] vs 196 days [121.0 to 270.9], p=0.037). Duodenal invasion is one of the important prognostic factors in pancreatic cancer and distal common bile duct cancer.15,16 As mentioned above, MBO within 2 cm from AOV had a high rate of duodenal invasion, which could explain the shorter overall survival compared to the other group. The composition ratios of pancreatic cancer and BTC in TPG and SPG are different. This could lead to differences in overall survival. However, in keynote trials of each of the malignancies, overall survival days were found to be similar between BTC and pancreatic cancer.19-21 In stent patency, one meta-analysis reported that clinical studies examining biliary stent in MBO did not show significant differences in clinical outcomes according to underlying diseases.22 The results of our Cox regression showed that the pathologic result did not influence stent patency.

Our study had some limitations: first, our study had heterogeneity for many factors, such as cancer pathology (BTC, pancreatic cancer, and others). There were no differences in stent patency or overall survival by pathologic result, although we did not present these results in this article. Second, our study was a retrospective multicenter study; there might have been inconsistencies in patient management. Third, some patients were lost to follow-up. For this reason, we could not accurately check the stent patency for some patients. In addition, the last follow-up periods of patients were defined as stent patency days. Fourth, we did not investigate the number of chemotherapy sessions. The ratio of received chemotherapy was not different in inter-groups. The tumor characteristics (pancreatic cancer or BTC) and number of chemotherapy sessions might be important prognostic factor about survival.23 Our study was focused on stent patency rather than survival. Therefore, more large-sized prospective studies are warranted.

In conclusion, when SEMS insertion was performed in extrahepatic MBO via ERCP, SPG and TPG showed similar stent patency and adverse events rates. However, in subgroup analysis according to the level of tumors, patients with MBO within 2 cm from the AOV revealed a higher ratio of duodenal invasion, shorter stent patency, and shorter survival than those with MBO over 2 cm from the AOV regardless of stent position. There is a need for further large-scaled prospective comparative studies to confirm our results.

This work was supported by Soonchunhyang University Research Fund and clinical research grant from Pusan National University Hospital in 2021.

Study concept and design: T.H.L., S.Y.H. Data acquisition: S.Y.H., S.I.J., J.K.Y., M.J.S., J.S.P. Data analysis and interpretation: S.Y.H., T.H.L. Drafting of the manuscript: S.Y.H., T.H.L. Critical revision of the manuscript for important intellectual content: D.U.K., J.H.C., C.I.K., S.J., D.H.L., S.H.P., D.K.L. Statistical analysis: S.Y.H. study supervision: T.H.L. Approval of final manuscript: all authors.

  1. Leng JJ, Zhang N, Dong JH. Percutaneous transhepatic and endoscopic biliary drainage for malignant biliary tract obstruction: a meta-analysis. World J Surg Oncol 2014;12:272.
    Pubmed KoreaMed CrossRef
  2. Takenaka M, Kudo M. Endoscopic reintervention for recurrence of malignant biliary obstruction: developing the best strategy. Gut Liver 2022;16:525-534.
    Pubmed KoreaMed CrossRef
  3. Barkun AN, Adam V, Martel M, AlNaamani K, Moses PL. Partially covered self-expandable metal stents versus polyethylene stents for malignant biliary obstruction: a cost-effectiveness analysis. Can J Gastroenterol Hepatol 2015;29:377-383.
    Pubmed KoreaMed CrossRef
  4. Kuwatani M, Kawakubo K, Sakamoto N. Possible reasons for the regrettable results of patency of an inside stent in endoscopic transpapillary biliary stenting. Dig Endosc 2022;34:334-344.
    Pubmed CrossRef
  5. Paik WH, Lee TH, Park DH, et al. EUS-guided biliary drainage versus ERCP for the primary palliation of malignant biliary obstruction: a multicenter randomized clinical trial. Am J Gastroenterol 2018;113:987-997.
    Pubmed CrossRef
  6. Woo HY, Han SY, Heo J, et al. Role of endoscopic biliary drainage in advanced hepatocellular carcinoma with jaundice. PLoS One 2017;12:e0187469.
    Pubmed KoreaMed CrossRef
  7. Cotton PB, Lehman G, Vennes J, et al. Endoscopic sphincterotomy complications and their management: an attempt at consensus. Gastrointest Endosc 1991;37:383-393.
    Pubmed CrossRef
  8. Kobayashi N, Watanabe S, Hosono K, et al. Endoscopic inside stent placement is suitable as a bridging treatment for preoperative biliary tract cancer. BMC Gastroenterol 2015;15:8.
    Pubmed KoreaMed CrossRef
  9. Pécsi D, Vincze Á. Are suprapapillary biliary stents superior to transpapillary biliary stents? Dig Dis Sci 2020;65:925-927.
    Pubmed CrossRef
  10. Shin J, Park JS, Jeong S, Lee DH. Comparison of the clinical outcomes of suprapapillary and transpapillary stent insertion in unresectable cholangiocarcinoma with biliary obstruction. Dig Dis Sci 2020;65:1231-1238.
    Pubmed CrossRef
  11. Pécsi D, Farkas N, Hegyi P, Szakács Z, Vincze A. Suprapapillary biliary stent placement might have longer patency time compared to transpapillary stent placement: a systematic review and meta-analysis. Endoscopy 2018;50:S43.
    CrossRef
  12. Walters JR, Tasleem AM, Omer OS, Brydon WG, Dew T, le Roux CW. A new mechanism for bile acid diarrhea: defective feedback inhibition of bile acid biosynthesis. Clin Gastroenterol Hepatol 2009;7:1189-1194.
    Pubmed CrossRef
  13. Nam HS, Kang DH, Kim HW, et al. Efficacy and safety of limited endoscopic sphincterotomy before self-expandable metal stent insertion for malignant biliary obstruction. World J Gastroenterol 2017;23:1627-1636.
    Pubmed KoreaMed CrossRef
  14. Shah A, Fehmi A, Savides TJ. Increased rates of duodenal obstruction in pancreatic cancer patients receiving modern medical management. Dig Dis Sci 2014;59:2294-2298.
    Pubmed CrossRef
  15. Patel BN, Olcott EW, Jeffrey RB. Duodenal invasion by pancreatic adenocarcinoma: MDCT diagnosis of an aggressive imaging phenotype and its clinical implications. Abdom Radiol (NY) 2018;43:332-339.
    Pubmed CrossRef
  16. Ebata T, Nagino M, Nishio H, Igami T, Yokoyama Y, Nimura Y. Pancreatic and duodenal invasion in distal bile duct cancer: paradox in the tumor classification of the American Joint Committee on Cancer. World J Surg 2007;31:2008-2015.
    Pubmed CrossRef
  17. Chen MY, Lin JW, Zhu HP, et al. Covered stents versus uncovered stents for unresectable malignant biliary strictures: a meta-analysis. Biomed Res Int 2016;2016:6408067.
    Pubmed KoreaMed CrossRef
  18. Qin WY, Li JZ, Peng WP, et al. Covered and uncovered self-expandable metallic stents in the treatment of malignant biliary obstruction. Iran Red Crescent Med J 2020;22:e99928.
    CrossRef
  19. Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011;364:1817-1825.
    Pubmed CrossRef
  20. Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 2013;369:1691-1703.
    Pubmed KoreaMed CrossRef
  21. Valle J, Wasan H, Palmer DH, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med 2010;362:1273-1281.
    Pubmed CrossRef
  22. Park CH, Park SW, Jung JH, Jung ES, Kim JH, Park DH. Comparative efficacy of various stents for palliation in patients with malignant extrahepatic biliary obstruction: a systematic review and network meta-analysis. J Pers Med 2021;11:86.
    Pubmed KoreaMed CrossRef
  23. Saito K, Nakai Y, Isayama H, et al. A prospective multicenter study of partially covered metal stents in patients receiving neoadjuvant chemotherapy for resectable and borderline resectable pancreatic cancer: BTS-NAC study. Gut Liver 2021;15:135-141.
    Pubmed KoreaMed CrossRef

Article

Original Article

Gut and Liver 2023; 17(5): 806-813

Published online September 15, 2023 https://doi.org/10.5009/gnl220437

Copyright © Gut and Liver.

Efficacy Analysis of Suprapapillary versus Transpapillary Self-Expandable Metal Stents According to the Level of Obstruction in Malignant Extrahepatic Biliary Obstruction

Sung Yong Han1 , Tae Hoon Lee2 , Sung Ill Jang3 , Dong Uk Kim1 , Jae Kook Yang2 , Jae Hee Cho3 , Min Je Sung4 , Chang-Il Kwon4 , Jin-Seok Park5 , Seok Jeong5 , Don Haeng Lee5 , Sang-Heum Park2 , Dong Ki Lee3

1Department of Internal Medicine, Pusan National University School of Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, 2Department of Internal Medicine, Soonchunhyang University Hospital Cheonan, Cheonan, 3Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, 4Digestive Disease Center, CHA Bundang Medical Center, CHA University, Seongnam, and 5Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea

Correspondence to:Tae Hoon Lee
ORCID https://orcid.org/0000-0002-3545-9183
E-mail taewoolee9@gmail.com

Received: October 9, 2022; Revised: November 27, 2022; Accepted: December 6, 2022

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background/Aims: The use of a self-expandable metal stent (SEMS) is recommended for unresectable malignant biliary obstruction (MBO). Stent-related adverse events might differ according to the position of the stent through the ampulla of Vater (AOV). We retrospectively evaluated SEMS patency and adverse events according to the position of the SEMS.
Methods: In total, 280 patients who underwent endoscopic SEMS placement due to malignant distal biliary obstruction were analyzed retrospectively. Suprapapillary and transpapillary SEMS insertions were performed on 51 patients and 229 patients, respectively.
Results: Between the suprapapillary group (SPG) and transpapillary group (TPG), the stent patency period was not significantly different (median [95% confidence interval]: 107 days [82.3 to 131.7] vs 120 days [99.3 to 140.7], p=0.559). There was also no significant difference in the rate of adverse events. In subgroup analysis, the stent patency for an MBO located within 2 cm from the AOV was found to be significantly shorter than that for an MBO located more than 2 cm from the AOV in the SPG (64 days [0 to 160.4] vs 127 days [82.0 to 171.9], p<0.001) and TPG (87 days [52.5 to 121.5] vs 130 [97.0 to 162.9], p<0.001). Patients with an MBO located within 2 cm from the AOV in both groups had a higher percentage of duodenal invasion (SPG: 40.0% vs 4.9%, p=0.002; TPG: 28.6% vs 2.9%, p<0.001) than patients with an MBO located more than 2 cm from the AOV.
Conclusions: The SPG and TPG showed similar results in terms of stent patency and rate of adverse events. However, patients with an MBO located within 2 cm from the AOV had a higher percentage of duodenal invasion with shorter stent patency than those with an MBO located more than 2 cm from the AOV, regardless of stent position.

Keywords: Self expandable metallic stents, Adverse events, Bile duct neoplasms, Ampulla of Vater, Endoscopic retrograde cholangiopancreatography

INTRODUCTION

Malignant biliary obstruction (MBO) can occur due to cholangiocarcinoma, pancreatic adenocarcinoma, and other etiologies, such as hepatocellular carcinoma and metastasis from carcinoma of other organs.1 Cases of unresectable status require biliary drainage. Drainage is typically performed with endoscopic retrograde cholangiopancreatography (ERCP). The use of a self-expandable metal stent (SEMS) can prolong stent patency compared to the use of a plastic stent due to its large diameter.2 Therefore, SEMS is recommended for unresectable MBO due to its cost-effectiveness and ability to increase the quality of life of patients with expected survival of more than 3 months.3

However, technically, there are a few questions that should be considered before the insertion of a covered or uncovered SEMS. The position of the stent through the ampulla of Vater (AOV) can affect the occurrence of stent-related adverse events such as pancreatitis, cholangitis, and stent malfunction. There is no definite consensus regarding the effects of these factors due to a lack of studies. Stent placement across the level of AOV (transpapillary) is weak for the reflux of duodenal contents (Fig. 1). It may also increase the risk of pancreatitis. However, when stent malfunction develops, stent revision is technically easy. On the other hand, stent placement above the level of AOV (suprapapillary) may prevent reflux of duodenal contents, which may prolong stent patency or decrease adverse events such as cholangitis and sludge formation (Fig. 1). A previous study has shown that placement of the stent above the intact sphincter of Oddi is associated with longer stent patency and lower occlusion rate.4 In hilar MBO, stent patency is affected by various factors such as insertion method (side-by-side, stent-in-stent) and how much intrahepatic bile duct drainage has been performed. Thus, there is a limit to the interpretation of the role of stent position with AOV.

Figure 1. Fluoroscopy (A, B) and endoscopic (C) images of transpapillary stent placement and suprapapillary stent placement (D, E, F).

Except for in the case of a far distal biliary obstruction or AOV cancer, which it is agreed upon should be drained using the transpapillary method, there is still controversy regarding the position of stent placement in the case of extrahepatic MBO (>2 cm distal to the hilum). Therefore, the objective of this study was to evaluate SEMS patency and adverse events according to the position of SEMS.

MATERIALS AND METHODS

1. Patients

In total, 280 patients who underwent SEMS placement by ERCP in five medical institutions between January 2016 and December 2020 were retrospectively reviewed. The inclusion criteria were as follows: (1) technically successful SEMS placement; (2) advanced or inoperable extrahepatic MBO defined as the presence of an unresectable malignant distal biliary obstruction (>2 cm distal to the hilum) with pathologicor radiologic diagnosis prior to endoscopic intervention;5 and (3) procedure performed by an experienced endoscopist without the involvement of a trainee. Meanwhile, the exclusion criteria were as follows: (1) AOV cancer; (2) uncontrolled coagulopathy; or (3) need for insertion of bilateral drainage (such as bismuth type II, III, IV). This study was conducted in accordance with the ethical guidelines of the Declaration of Helsinki (revised in 2013). The study protocol was approved by the Institutional Review Board of Soonchunhyang University Hospital (IRB number: 2020-03-022-005) and informed consent was waived.

2. Clinical measurement

We evaluated laboratory findings, radiologic information, and clinical characteristics such as age, sex, pathologic result of tumor (biliary tract cancer [BTC], pancreatic cancer, others), information of ERCP procedure, and follow-up data. The radiologic information that we considered included obstruction level (proximal, mid, distal common bile duct) and the presence of cystic duct invasion. Information on the ERCP procedure included stent type (fully covered, partially covered, uncovered), length of stent, and distance from AOV to distal malignant stricture, which were measured prior to performing ERCP by magnetic resonance imaging or from the coronal view of the computed tomography scan from duodenal wall to tumor distal obstruction level. Clinical success was defined as decline in total bilirubin over 50% or below 3 mg/dL within 1 week.5,6 Laboratory findings included total bilirubin, amylase, and lipase at pre-ERCP and 1 week after ERCP. Post-ERCP complications were defined by Cotton’s criteria.7 Early complication was defined as a complication that occurred within 1 month from ERCP. Late complication was defined as a complication that occurred at least 1 month after ERCP. Follow-up data included stent obstruction cause, revision method, success of revision, duodenal invasion that occurred at the time of ERCP or follow-up period, stent patency (defined as the time elapsed between successful stent placement and cholangitis or jaundice due to obstruction of stent), and overall survival duration.

3. Subgroup analysis

Subgroup analysis was performed for MBO within 2 cm from AOV versus MBO over 2 cm from AOV. In stent deployment, it is recommended that the stent cover more than 1 to 2 cm from MBO with SEMS to prevent tumor overgrowth.8 There is no consensus for stent deployment through ERCP. However, 1 to 2 cm from the MBO is typically covered with SEMS to prevent overgrowth. In the case of MBO within 2 cm from the AOV, it was judged that transpapillary was performed for most cases. Thus, subgroup analysis was performed to compare the transpapillary group (TPG) and the suprapapillary group (SPG), except for this part.

4. Statistical analysis

Statistical analysis was performed using SPSS software version 21.0 (IBM Corp., Armonk, NY, USA). Categorical data are expressed as frequency and percentage, with between-group differences having been evaluated using the chi-square test. Continuous data are expressed as mean±standard deviation, with between-group differences having been evaluated using the independent Student t-test. Statistical significance was determined at p<0.05. Stent patency and overall survival are expressed as median value and 95% confidence interval (CI), respectively. They were plotted using the Kaplan-Meier survival plot and tested using log-rank tests. Cox regression analysis was used to evaluate the factors affecting stent patency.

RESULTS

1. Baseline characteristics

In total, 280 patients with SEMS insertion in extrahepatic MBO were enrolled in this study. This included 51 patients with suprapapillary SEMS insertion and 229 patients with transpapillary SEMS insertion. Regarding baseline characteristics, sex ratio, age, stent type, clinical success rate, and laboratory findings pre-procedure and 1 week after ERCP were not significantly different between the two groups (Table 1). SPG had a higher ratio of cystic duct invasion (21.6% vs 4.8%, p<0.001) and BTC (78.5% vs 31.9%, p<0.001) than TPG. TPG had a higher ratio of pancreatic cancer (58.1% vs 17.6%, p<0.001), higher ratio of location in distal common bile duct (62.4% vs 25.5%, p<0.001), and longer stent length (6.41±0.99 cm vs 6.04±0.72 cm, p=0.012) than SPG.

Table 1 . Baseline Characteristics of Patients Who Underwent Suprapapillary or Transpapillary Self-Expandable Metal Stent Insertion.

CharacteristicSuprapapillary (n=51)Transpapillary (n=229)p-value
Male sex28 (54.9)122 (53.3)0.834
Age, yr73.2±9.572.0±11.50.486
Diagnosis<0.001
Biliary tract cancer40 (78.5)73 (31.9)
Pancreas cancer9 (17.6)133 (58.1)
Others2 (3.9)23 (10.0)
Obstruction level of common bile duct<0.001
Proximal12 (23.5)22 (9.6)
Middle26 (51.0)64 (27.9)
Distal13 (25.5)143 (62.4)
Cystic duct invasion11 (21.6)11 (4.8)<0.001
Stent length, cm6.04±0.726.41±0.990.012
Stent type0.103
Uncovered41 (80.4)160 (69.9)
Covered8 (15.7)62 (27.1)
Partially2 (3.9)7 (3.1)
Clinical success49 (96.1)216 (95.6)0.874
Pre-laboratory findings
Total bilirubin, mg/dL5.98±5.086.92±7.070.370
Amylase, U/L183.5±742.4103.3±211.20.175
Lipase, U/L57.5±61.1150.2±354.50.070
1 wk after laboratory findings
Total bilirubin, mg/dL3.18±3.092.60±2.980.246
Amylase, U/L72.1±54.287.9±78.20.259
Lipase, U/L69.8±118.9112.5±175.60.166

Data are presented as number (%) or mean±SD..



2. Clinical outcomes

There was no significant difference in early or late complications between the two groups. Post-ERCP pancreatitis was slightly higher in TPG (9.2% vs 2.0%, p=0.131). SPG had a higher ratio of stone in obstruction cause (47.8% vs 23.5%, p=0.025), higher ratio of cleansing only in the method of endorevision via ERCP (35.7% vs 16.1%, p=0.035), and lower ratio of ERCP in the revision method (82.4% vs 96.9%, p=0.027) than TPG. There was no significant difference in stent patency period (median [95% CI]: 107 days [82.3 to 131.7] vs 120 days [99.3 to 140.7], p=0.559) or overall survival days (142 days [35.6 to 248.3] vs 180 days [146.0 to 213.9], p=0.386) between the two groups (Table 2).

Table 2 . Clinical Outcome According to the Route of Self-Expandable Metal Stent Insertion.

VariableSuprapapillary (n=51)Transpapillary (n=229)p-value
Early adverse events
Cholangitis2 (3.9)9 (3.9)0.998
Pancreatitis1 (2.0)21 (9.2)0.131
Cholecystitis01 (0.4)0.638
Bleeding02 (0.9)0.505
Malfunction1 (2.0)4 (1.7)0.917
Late adverse events
Cholangitis9 (17.6)38 (16.7)0.876
Cholecystitis3 (5.9)7 (3.1)0.334
Malfunction18 (35.3)57 (25.1)0.140
Obstruction cause0.025
Ingrowth6 (31.6)39 (57.4)
Overgrowth2 (10.5)8 (11.8)
Both2 (10.5)5 (7.4)
Stone9 (47.8)16 (23.5)
Revision method17640.027
ERCP14 (82.4)62 (96.9)
Percutaneous3 (17.6)2 (3.1)
Revision success17 (100)63 (98.4)0.609
Endorevision method0.035
Restenting8 (57.1)51 (82.3)
Cleansing5 (35.7)10 (16.1)
Stent exchanging1 (7.1)1 (1.6)
Chemotherapy17 (33.3)98 (42.7)0.196
Stent patency, day107 (82.3–131.7)120 (99.3–140.7)0.559
Overall survival, day142 (35.6–248.3)180 (146.0–213.9)0.386

Data are presented as number (%) or median (95% confidence interval)..

ERCP, endoscopic retrograde cholangiopancreatography..



3. Subgroup analysis

Clinically meaningful factors such as obstruction level, pathologic diagnosis, SEMS length, SEMS type, stent level (suprapapillary vs transpapillary), duodenal invasion, and MBO within or over 2 cm from AOV were included in the Cox regression analysis about stent patency (Table 3). In univariable analysis, MBO within 2 cm from AOV (hazard ratio [HR], 1.529; 95% CI, 1.186 to 1.197; p=0.001) and SEMS type (HR, 0.657; 95% CI, 0.501 to 0.862; p=0.002) were both found to be significant. In the multivariable analysis, MBO within 2 cm from AOV (HR, 1.447; 95% CI, 1.101 to 1.901; p=0.008) and SEMS type (HR, 0.667; 95% CI, 0.502 to 0.885; p=0.005) remained significant.

Table 3 . Analysis of Factors Affecting Stent Patency According to Cox Regression Analysis.

FactorUnivariable analysisMultivariable analysis
HR (95% CI)p-valueHR (95% CI)p-value
Obstruction level
Proximal CBD vs mid CBD1.194 (0.796–1.791)0.3911.241 (0.820–1.880)0.308
Proximal CBD vs distal CBD1.411 (0.961–2.073)0.0791.161 (0.735–1.834)0.522
Diagnosis (BTC vs non-BTC)1.153 (0.092–1.473)0.2571.273 (0.962–1.684)0.091
SEMS type (uncovered vs covered)0.657 (0.501–0.862)0.0020.667 (0.502–0.885)0.005
SEMS length1.007 (0.891–1.137)0.9141.047 (0.918–1.194)0.492
Stent level (suprapapillary vs transpapillary)0.911 (0.665–1.247)0.5600.729 (0.512–1.038)0.079
Duodenal obstruction1.352 (0.946–1.933)0.0981.286 (0.855–1.936)0.227
MBO within 2 cm from AOV1.529 (1.186–1.197)0.0011.447 (1.101–1.901)0.008

HR, hazard ratio; CI, confidence interval; CBD, common bile duct; BTC, biliary tract cancer; SEMS, self-expandable metal stent; MBO, malignant biliary obstruction; AOV, ampulla of Vater..



Table 4 lists the results of subgroup analysis according to MBO within or over 2 cm from AOV. In TPG, MBO over 2 cm from AOV had higher covered stent than others (36.2% vs 13.2%, p<0.001). Duodenal invasion was higher in MBO within 2 cm from AOV than it was in MBO over 2 cm from AOV (SPG: 40.0% vs 4.9%, p=0.002; TPG: 28.6% vs 2.9%, p<0.001). Stent patency in MBO within 2 cm from the AOV was significantly shorter than that in MBO over 2 cm from the AOV (SPG: 64 days [0 to 160.4] vs 127 days [82.0 to 171.9], p<0.001; TPG: 87 days [52.5 to 121.5] vs 130 days [97.0 to 162.9], p<0.001). Fig. 2 shows stent patency according to SPG or TPG and MBO within or over 2 cm from AOV. Overall survival duration was also shorter in MBO within 2 cm from AOV in SPG (71 days [40.5 to 101.5] vs 196 days [121.0 to 270.9], p<0.001) and TPG (140 days [95.1 to 184.9] vs 227 days [182.1 to 271.9], p=0.008). In MBO within 2 cm from AOV, TPG had a longer overall survival duration than SPG (227 days [182.1 to 271.9] vs 196 days [121.0 to 270.9], p=0.037).

Table 4 . Subgroup Analysis for MBO within 2 cm and MBO over 2 cm from the AOV for Patients Undergoing Suprapapillary or Transpapillary Self-Expandable Metal Stent Insertion.

VariableSuprapapillary (n=51)Transpapillary (n=229)
MBO within 2 cm
from AOV (n=10)
MBO over 2 cm
from AOV (n=41)
p-valueMBO within 2 cm
from AOV (n=91)
MBO over 2 cm
from AOV (n=138)
p-value
Diagnosis0.014
Biliary tract cancer4 (40.0)36 (87.8)22 (24.2)51 (36.9)
Pancreas cancer6 (60.0)3 (7.3)61 (67.0)72 (52.2)
Others02 (4.9)8 (8.8)15 (10.8)
Stent obstruction cause0.979
Ingrowth06 (40.0)15 (48.4)24 (64.9)
Overgrowth02 (13.3)2 (6.5)6 (16.2)
Both02 (13.3)2 (6.5)3 (8.1)
Stone4 (100)5 (33.3)12 (38.7)4 (10.8)
Stent type0.004
Uncovered8 (80.0)33 (80.5)0.82678 (85.7)82 (59.4)<0.001
Covered2 (20.0)6 (14.6)12 (13.2)50 (36.2)
Partially02 (4.9)1 (1.1)6 (4.3)
Duodenal invasion4 (40.0)2 (4.9)0.00226 (28.6)4 (2.9)<0.001
Chemotherapy17 (33.3)98 (42.7)0.196
3 (30.0)14 (34.1)0.56936 (39.5)62 (44.9)0.412
Stent patency, day107 (82.3–131.7)120 (99.3–140.7)0.559
64 (0–160.4)127 (82.0–171.9)<0.00187 (52.5–121.5)130 (97.0–162.9)<0.001
127 (82.0–171.9)130 (97.0–162.9)0.595
Overall survival, day142 (35.6–248.3)180 (146.0–213.9)0.386
71 (40.5–101.5)196 (121.0–270.9)<0.001140 (95.1–184.9)227 (182.1–271.9)0.008
196 (121.0–270.9)227 (182.1–271.9)0.037

Data are presented as number (%) or median (95% confidence interval)..

MBO, malignant biliary obstruction; AOV, ampulla of Vater..



Figure 2. Kaplan-Meier stent patency in patients with suprapapillary and transpapillary MBO within and over 2 cm from AOV (A), MBO over 2 cm from AOV (B).
MBO, malignant biliary obstructions; AOV, ampulla of Vater.

DISCUSSION

When comparing the SPG and TPG groups, the stent patency period was found to be similar regardless of whether MBO was within 2 cm from AOV. The rates of adverse events in SPG and TPG were also similar. For MBO within 2 cm from AOV, SPG had a shorter stent patency than TPG (64 days [0 to 160.4] vs 87 days [52.5 to 121.5], p=0.006). The stent patency of MBO within 2 cm from the AOV was significantly lower than that of MBO over 2 cm from the AOV (SPG: 64 days [0 to 160.4] vs 127 days [82.0 to 171.9], p<0.001; TPG: 87 days [52.5 to 121.5] vs 130 days [97.0 to 162.9], p<0.001). Duodenal invasion was higher in MBO within 2 cm from the AOV than it was in MBO over 2 cm from the AOV (SPG: 40.0% vs 4.9%, p=0.002; TPG: 28.6% vs 2.9%, p<0.001).

There have been few studies examining suprapapillary or transpapillary stenting.9 In particular, to our knowledge, there has been no study investigating SEMS to extrahepatic MBO. Shin et al.10 has shown that the effectiveness and safety of suprapapillary and transpapillary stent insertions of hilar cholangiocarcinoma are similar, although the success rate of endobiliary revision is significantly higher in TPG. One meta-analysis has shown that SPG has longer stent patency than TPG.11 However, the enrolled studies used plastic stents. Thus, our result showing that both methods have similar stent patency is meaningful for comparing SPG and TPG in extrahepatic MBO using SEMS.

Stent placement suprapapillary may prevent reflux of duodenal contents, which may prolong stent patency or decrease the incidence of adverse events such as cholangitis and sludge formation. The sphincter of Oddi is a barrier to protective reflux of duodenal contents. Thus, the usefulness of endoscopic sphincterotomy is one of the issues involved in suprapapillary stenting.12,13 However, the role of this barrier was thought to be limited in our study, as small endoscopic sphincterotomy was performed in all enrolled patients before stenting or biopsy via ERCP. To maximize the advantages of a suprapapillary deployment, there is a need for further studies comparing stent patency in patients without in the future.

MBO within 2 cm from the AOV had a shorter stent patency than MBO over 2 cm from the AOV in both groups (SPG and TPG). This result might be due to a higher ratio of duodenal invasion. Food passage was faster in the duodenum than it was in the stomach. If there was a duodenal invasion, the passage of food in the duodenum might be slowed. This food retention will increase the chance of reflux of duodenal contents and obstruction. It is known that 38% to 45%14-16 of patients with pancreatic cancer or distal bile duct cancer patients will experience duodenal invasion during follow-up periods. In our results, MBO within 2 cm from the AOV was shown to have a higher rate of duodenal obstruction (SPG: 40.0% vs 4.9%, p=0.002; TPG: 28.6% vs 2.9%, p<0.001). The rate of duodenal invasion was similar to those obtained in other studies.14-16 Duodenal invasion mainly occurred in MBO within 2 cm from the AOV. MBO within 2 cm from the AOV had a higher frequency of stone as a cause of obstruction than MBO over 2 cm from the AOV (16/35 [45.7%] vs 9/52 [17.3%], p<0.001). This was believed to be highly correlated with the high rate of duodenum invasion in MBO within 2 cm from the AOV. In patients with MBO within 2 cm from the AOV, SPG had a shorter stent patency than TPG (64 days [0 to 160.4] vs 87 days [52.4 to 121.5], p=0.006). Thus, transpapillary stenting is preferable for patients with MBO within 2 cm of the AOV. Even with transpapillary stenting, the patency seems to be short. Thus, it might be better to perform biliary drainage using other methods.

In the results of the Cox regression about stent patency, the type of SEMS was found to influence stent patency (uncovered vs covered: 103 days [83.1 to 122.9] vs 160 days [110.7 to 209.2], p=0.002). However, meta-analysis revealed similar or slightly longer stent patency in covered SEMS than in uncovered SEMS, showing no statistically significant difference.17,18 Overall survival days were significantly longer in MBO over 2 cm from the AOV in both groups (SPG: 196 days [121.0 to 270.9] vs 71 days [40.5 to 101.5], p<0.001; TPG: 227 days [182.1 to 271.9] vs 140 days [95.1 to 184.9], p=0.008). In addition, overall survival days in MBO over 2 cm from the AOV were longer in TPG than in SPG (227 days [182.1 to 271.9] vs 196 days [121.0 to 270.9], p=0.037). Duodenal invasion is one of the important prognostic factors in pancreatic cancer and distal common bile duct cancer.15,16 As mentioned above, MBO within 2 cm from AOV had a high rate of duodenal invasion, which could explain the shorter overall survival compared to the other group. The composition ratios of pancreatic cancer and BTC in TPG and SPG are different. This could lead to differences in overall survival. However, in keynote trials of each of the malignancies, overall survival days were found to be similar between BTC and pancreatic cancer.19-21 In stent patency, one meta-analysis reported that clinical studies examining biliary stent in MBO did not show significant differences in clinical outcomes according to underlying diseases.22 The results of our Cox regression showed that the pathologic result did not influence stent patency.

Our study had some limitations: first, our study had heterogeneity for many factors, such as cancer pathology (BTC, pancreatic cancer, and others). There were no differences in stent patency or overall survival by pathologic result, although we did not present these results in this article. Second, our study was a retrospective multicenter study; there might have been inconsistencies in patient management. Third, some patients were lost to follow-up. For this reason, we could not accurately check the stent patency for some patients. In addition, the last follow-up periods of patients were defined as stent patency days. Fourth, we did not investigate the number of chemotherapy sessions. The ratio of received chemotherapy was not different in inter-groups. The tumor characteristics (pancreatic cancer or BTC) and number of chemotherapy sessions might be important prognostic factor about survival.23 Our study was focused on stent patency rather than survival. Therefore, more large-sized prospective studies are warranted.

In conclusion, when SEMS insertion was performed in extrahepatic MBO via ERCP, SPG and TPG showed similar stent patency and adverse events rates. However, in subgroup analysis according to the level of tumors, patients with MBO within 2 cm from the AOV revealed a higher ratio of duodenal invasion, shorter stent patency, and shorter survival than those with MBO over 2 cm from the AOV regardless of stent position. There is a need for further large-scaled prospective comparative studies to confirm our results.

ACKNOWLEDGEMENTS

This work was supported by Soonchunhyang University Research Fund and clinical research grant from Pusan National University Hospital in 2021.

CONFLICTS OF INTEREST

No potential conflict of interest relevant to this article was reported.

AUTHOR CONTRIBUTIONS

Study concept and design: T.H.L., S.Y.H. Data acquisition: S.Y.H., S.I.J., J.K.Y., M.J.S., J.S.P. Data analysis and interpretation: S.Y.H., T.H.L. Drafting of the manuscript: S.Y.H., T.H.L. Critical revision of the manuscript for important intellectual content: D.U.K., J.H.C., C.I.K., S.J., D.H.L., S.H.P., D.K.L. Statistical analysis: S.Y.H. study supervision: T.H.L. Approval of final manuscript: all authors.

Fig 1.

Figure 1.Fluoroscopy (A, B) and endoscopic (C) images of transpapillary stent placement and suprapapillary stent placement (D, E, F).
Gut and Liver 2023; 17: 806-813https://doi.org/10.5009/gnl220437

Fig 2.

Figure 2.Kaplan-Meier stent patency in patients with suprapapillary and transpapillary MBO within and over 2 cm from AOV (A), MBO over 2 cm from AOV (B).
MBO, malignant biliary obstructions; AOV, ampulla of Vater.
Gut and Liver 2023; 17: 806-813https://doi.org/10.5009/gnl220437

Table 1 Baseline Characteristics of Patients Who Underwent Suprapapillary or Transpapillary Self-Expandable Metal Stent Insertion

CharacteristicSuprapapillary (n=51)Transpapillary (n=229)p-value
Male sex28 (54.9)122 (53.3)0.834
Age, yr73.2±9.572.0±11.50.486
Diagnosis<0.001
Biliary tract cancer40 (78.5)73 (31.9)
Pancreas cancer9 (17.6)133 (58.1)
Others2 (3.9)23 (10.0)
Obstruction level of common bile duct<0.001
Proximal12 (23.5)22 (9.6)
Middle26 (51.0)64 (27.9)
Distal13 (25.5)143 (62.4)
Cystic duct invasion11 (21.6)11 (4.8)<0.001
Stent length, cm6.04±0.726.41±0.990.012
Stent type0.103
Uncovered41 (80.4)160 (69.9)
Covered8 (15.7)62 (27.1)
Partially2 (3.9)7 (3.1)
Clinical success49 (96.1)216 (95.6)0.874
Pre-laboratory findings
Total bilirubin, mg/dL5.98±5.086.92±7.070.370
Amylase, U/L183.5±742.4103.3±211.20.175
Lipase, U/L57.5±61.1150.2±354.50.070
1 wk after laboratory findings
Total bilirubin, mg/dL3.18±3.092.60±2.980.246
Amylase, U/L72.1±54.287.9±78.20.259
Lipase, U/L69.8±118.9112.5±175.60.166

Data are presented as number (%) or mean±SD.


Table 2 Clinical Outcome According to the Route of Self-Expandable Metal Stent Insertion

VariableSuprapapillary (n=51)Transpapillary (n=229)p-value
Early adverse events
Cholangitis2 (3.9)9 (3.9)0.998
Pancreatitis1 (2.0)21 (9.2)0.131
Cholecystitis01 (0.4)0.638
Bleeding02 (0.9)0.505
Malfunction1 (2.0)4 (1.7)0.917
Late adverse events
Cholangitis9 (17.6)38 (16.7)0.876
Cholecystitis3 (5.9)7 (3.1)0.334
Malfunction18 (35.3)57 (25.1)0.140
Obstruction cause0.025
Ingrowth6 (31.6)39 (57.4)
Overgrowth2 (10.5)8 (11.8)
Both2 (10.5)5 (7.4)
Stone9 (47.8)16 (23.5)
Revision method17640.027
ERCP14 (82.4)62 (96.9)
Percutaneous3 (17.6)2 (3.1)
Revision success17 (100)63 (98.4)0.609
Endorevision method0.035
Restenting8 (57.1)51 (82.3)
Cleansing5 (35.7)10 (16.1)
Stent exchanging1 (7.1)1 (1.6)
Chemotherapy17 (33.3)98 (42.7)0.196
Stent patency, day107 (82.3–131.7)120 (99.3–140.7)0.559
Overall survival, day142 (35.6–248.3)180 (146.0–213.9)0.386

Data are presented as number (%) or median (95% confidence interval).

ERCP, endoscopic retrograde cholangiopancreatography.


Table 3 Analysis of Factors Affecting Stent Patency According to Cox Regression Analysis

FactorUnivariable analysisMultivariable analysis
HR (95% CI)p-valueHR (95% CI)p-value
Obstruction level
Proximal CBD vs mid CBD1.194 (0.796–1.791)0.3911.241 (0.820–1.880)0.308
Proximal CBD vs distal CBD1.411 (0.961–2.073)0.0791.161 (0.735–1.834)0.522
Diagnosis (BTC vs non-BTC)1.153 (0.092–1.473)0.2571.273 (0.962–1.684)0.091
SEMS type (uncovered vs covered)0.657 (0.501–0.862)0.0020.667 (0.502–0.885)0.005
SEMS length1.007 (0.891–1.137)0.9141.047 (0.918–1.194)0.492
Stent level (suprapapillary vs transpapillary)0.911 (0.665–1.247)0.5600.729 (0.512–1.038)0.079
Duodenal obstruction1.352 (0.946–1.933)0.0981.286 (0.855–1.936)0.227
MBO within 2 cm from AOV1.529 (1.186–1.197)0.0011.447 (1.101–1.901)0.008

HR, hazard ratio; CI, confidence interval; CBD, common bile duct; BTC, biliary tract cancer; SEMS, self-expandable metal stent; MBO, malignant biliary obstruction; AOV, ampulla of Vater.


Table 4 Subgroup Analysis for MBO within 2 cm and MBO over 2 cm from the AOV for Patients Undergoing Suprapapillary or Transpapillary Self-Expandable Metal Stent Insertion

VariableSuprapapillary (n=51)Transpapillary (n=229)
MBO within 2 cm
from AOV (n=10)
MBO over 2 cm
from AOV (n=41)
p-valueMBO within 2 cm
from AOV (n=91)
MBO over 2 cm
from AOV (n=138)
p-value
Diagnosis0.014
Biliary tract cancer4 (40.0)36 (87.8)22 (24.2)51 (36.9)
Pancreas cancer6 (60.0)3 (7.3)61 (67.0)72 (52.2)
Others02 (4.9)8 (8.8)15 (10.8)
Stent obstruction cause0.979
Ingrowth06 (40.0)15 (48.4)24 (64.9)
Overgrowth02 (13.3)2 (6.5)6 (16.2)
Both02 (13.3)2 (6.5)3 (8.1)
Stone4 (100)5 (33.3)12 (38.7)4 (10.8)
Stent type0.004
Uncovered8 (80.0)33 (80.5)0.82678 (85.7)82 (59.4)<0.001
Covered2 (20.0)6 (14.6)12 (13.2)50 (36.2)
Partially02 (4.9)1 (1.1)6 (4.3)
Duodenal invasion4 (40.0)2 (4.9)0.00226 (28.6)4 (2.9)<0.001
Chemotherapy17 (33.3)98 (42.7)0.196
3 (30.0)14 (34.1)0.56936 (39.5)62 (44.9)0.412
Stent patency, day107 (82.3–131.7)120 (99.3–140.7)0.559
64 (0–160.4)127 (82.0–171.9)<0.00187 (52.5–121.5)130 (97.0–162.9)<0.001
127 (82.0–171.9)130 (97.0–162.9)0.595
Overall survival, day142 (35.6–248.3)180 (146.0–213.9)0.386
71 (40.5–101.5)196 (121.0–270.9)<0.001140 (95.1–184.9)227 (182.1–271.9)0.008
196 (121.0–270.9)227 (182.1–271.9)0.037

Data are presented as number (%) or median (95% confidence interval).

MBO, malignant biliary obstruction; AOV, ampulla of Vater.


References

  1. Leng JJ, Zhang N, Dong JH. Percutaneous transhepatic and endoscopic biliary drainage for malignant biliary tract obstruction: a meta-analysis. World J Surg Oncol 2014;12:272.
    Pubmed KoreaMed CrossRef
  2. Takenaka M, Kudo M. Endoscopic reintervention for recurrence of malignant biliary obstruction: developing the best strategy. Gut Liver 2022;16:525-534.
    Pubmed KoreaMed CrossRef
  3. Barkun AN, Adam V, Martel M, AlNaamani K, Moses PL. Partially covered self-expandable metal stents versus polyethylene stents for malignant biliary obstruction: a cost-effectiveness analysis. Can J Gastroenterol Hepatol 2015;29:377-383.
    Pubmed KoreaMed CrossRef
  4. Kuwatani M, Kawakubo K, Sakamoto N. Possible reasons for the regrettable results of patency of an inside stent in endoscopic transpapillary biliary stenting. Dig Endosc 2022;34:334-344.
    Pubmed CrossRef
  5. Paik WH, Lee TH, Park DH, et al. EUS-guided biliary drainage versus ERCP for the primary palliation of malignant biliary obstruction: a multicenter randomized clinical trial. Am J Gastroenterol 2018;113:987-997.
    Pubmed CrossRef
  6. Woo HY, Han SY, Heo J, et al. Role of endoscopic biliary drainage in advanced hepatocellular carcinoma with jaundice. PLoS One 2017;12:e0187469.
    Pubmed KoreaMed CrossRef
  7. Cotton PB, Lehman G, Vennes J, et al. Endoscopic sphincterotomy complications and their management: an attempt at consensus. Gastrointest Endosc 1991;37:383-393.
    Pubmed CrossRef
  8. Kobayashi N, Watanabe S, Hosono K, et al. Endoscopic inside stent placement is suitable as a bridging treatment for preoperative biliary tract cancer. BMC Gastroenterol 2015;15:8.
    Pubmed KoreaMed CrossRef
  9. Pécsi D, Vincze Á. Are suprapapillary biliary stents superior to transpapillary biliary stents? Dig Dis Sci 2020;65:925-927.
    Pubmed CrossRef
  10. Shin J, Park JS, Jeong S, Lee DH. Comparison of the clinical outcomes of suprapapillary and transpapillary stent insertion in unresectable cholangiocarcinoma with biliary obstruction. Dig Dis Sci 2020;65:1231-1238.
    Pubmed CrossRef
  11. Pécsi D, Farkas N, Hegyi P, Szakács Z, Vincze A. Suprapapillary biliary stent placement might have longer patency time compared to transpapillary stent placement: a systematic review and meta-analysis. Endoscopy 2018;50:S43.
    CrossRef
  12. Walters JR, Tasleem AM, Omer OS, Brydon WG, Dew T, le Roux CW. A new mechanism for bile acid diarrhea: defective feedback inhibition of bile acid biosynthesis. Clin Gastroenterol Hepatol 2009;7:1189-1194.
    Pubmed CrossRef
  13. Nam HS, Kang DH, Kim HW, et al. Efficacy and safety of limited endoscopic sphincterotomy before self-expandable metal stent insertion for malignant biliary obstruction. World J Gastroenterol 2017;23:1627-1636.
    Pubmed KoreaMed CrossRef
  14. Shah A, Fehmi A, Savides TJ. Increased rates of duodenal obstruction in pancreatic cancer patients receiving modern medical management. Dig Dis Sci 2014;59:2294-2298.
    Pubmed CrossRef
  15. Patel BN, Olcott EW, Jeffrey RB. Duodenal invasion by pancreatic adenocarcinoma: MDCT diagnosis of an aggressive imaging phenotype and its clinical implications. Abdom Radiol (NY) 2018;43:332-339.
    Pubmed CrossRef
  16. Ebata T, Nagino M, Nishio H, Igami T, Yokoyama Y, Nimura Y. Pancreatic and duodenal invasion in distal bile duct cancer: paradox in the tumor classification of the American Joint Committee on Cancer. World J Surg 2007;31:2008-2015.
    Pubmed CrossRef
  17. Chen MY, Lin JW, Zhu HP, et al. Covered stents versus uncovered stents for unresectable malignant biliary strictures: a meta-analysis. Biomed Res Int 2016;2016:6408067.
    Pubmed KoreaMed CrossRef
  18. Qin WY, Li JZ, Peng WP, et al. Covered and uncovered self-expandable metallic stents in the treatment of malignant biliary obstruction. Iran Red Crescent Med J 2020;22:e99928.
    CrossRef
  19. Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011;364:1817-1825.
    Pubmed CrossRef
  20. Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 2013;369:1691-1703.
    Pubmed KoreaMed CrossRef
  21. Valle J, Wasan H, Palmer DH, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med 2010;362:1273-1281.
    Pubmed CrossRef
  22. Park CH, Park SW, Jung JH, Jung ES, Kim JH, Park DH. Comparative efficacy of various stents for palliation in patients with malignant extrahepatic biliary obstruction: a systematic review and network meta-analysis. J Pers Med 2021;11:86.
    Pubmed KoreaMed CrossRef
  23. Saito K, Nakai Y, Isayama H, et al. A prospective multicenter study of partially covered metal stents in patients receiving neoadjuvant chemotherapy for resectable and borderline resectable pancreatic cancer: BTS-NAC study. Gut Liver 2021;15:135-141.
    Pubmed KoreaMed CrossRef
Gut and Liver

Vol.18 No.2
March, 2024

pISSN 1976-2283
eISSN 2005-1212

qrcode
qrcode

Share this article on :

  • line

Popular Keywords

Gut and LiverQR code Download
qr-code

Editorial Office