Cholecystitis can occur after the placement of covered self-expandable metallic stents for distal malignant biliary obstructions. We aimed to identify risk factors for cholecystitis following covered self-expandable metallic stent placement.
We investigated risk factors related to cholecystitis following covered self-expandable metallic stent placement in 118 patients with distal malignant biliary obstructions between January 1, 2015 and April 30, 2019. Endoscopic assessments and tumor invasion to the arteries feeding the gallbladder were determined by a pancreaticobiliary endoscopist and a radiologist, respectively.
The median patient age was 72 years (men, 61.0%). The flow of the contrast agent into the gallbladder and tumor involvement in the orifice of the cystic duct were observed in 35 (29.7%) and 35 (29.7%) patients, respectively. During the observation period (median, 179 days), cholecystitis occurred in 18 (15.3%) patients. Multivariate analysis revealed the flow of the contrast agent into the gallbladder (
The flow of the contrast agent into the gallbladder and tumor involvement in the orifice of the cystic duct are potential independent risk factors for cholecystitis following the placement of covered self-expandable metallic stents. A follow-up prospective study is warranted to validate their influence.
Since its introduction in the 1980s, endoscopic stent placement has been used to treat patients with jaundice associated with distal malignant biliary obstructions that occur in cases of pancreatic and biliary tract cancer and to help maintain an effective quality of life [
Some of the previously reported risk factors for cholecystitis following CSEMS placement are tumor involvement in the orifice of cystic duct (OCD) [
We performed a retrospective study using endoscopic retrograde cholangiopancreatography (ERCP) registry data of Kitasato University Hospital. The study adhered to the principles of the Declaration of Helsinki. Our study was reviewed and approved by our institutional ethics committee (approval number: B18–113). The study is registered with the University Hospital Medical Information Network (UMIN) Center of Japan (Clinical trial registration number: UMIN000040028).
Our analysis included 160 consecutive patients who underwent SEMS placement for distal malignant biliary obstructions at the Kitasato University Hospital between January 1, 2015, and April 30, 2019. Informed consent was obtained from all individual participants included in the study. Patients who had a history of cholecystectomy, could not be followed-up after SEMS placement due to transfer to other hospitals, underwent USEMS and preparatory or concurrent gallbladder drainage placement, and were not assessed by multidetector computed tomography (MDCT) before SEMS placement were excluded from the analysis.
The following parameters were investigated in the present study: age, sex, primary disease, previous biliary duct drainage using PS before SEMS placement, pre-SEMS papillary treatment, flow of contrast agent into the gallbladder (including the cystic duct) during the SEMS placement, type of SEMS used (SEMS length and braided or laser-cut type), location of the placed SEMS (above or across the papilla), tumor involvement to the OCD, tumor invasion to the arteries feeding the gallbladder, gallstones presence, TRBO and survival time during the observation period, and incidence of cholecystitis. Medical data for the period from SEMS placement to the last day of observation (August 31, 2019) were collected from electronic charts.
The flow of the contrast agent to the gallbladder was determined as positive when it was visible on fluoroscopic images (
The operating physician determined whether a papillary treatment was performed before SEMS placement. SEMS length and type were selected by the operating physician to achieve adequate coverage of the stricture as imaged on ERC. The CSEMSs used in this study were the BONA STENT® (Sewoon Medical Co., Ltd., Seoul, Korea), Evolution® (COOK Medical, Bloomington, IN, USA), M-intraductal stent® (SciTech Inc., Seoul, Korea), HANARO STENT® (MI-Tech, Seoul, Korea), X-suit NIR® (Olympus Medical Systems, Tokyo, Japan), and WallFlex® (Boston Scientific Co., Natick, MA, USA).
TRBO was estimated using the Kaplan-Meier method and was compared between the groups using the log-rank test. A logistic regression model was used for univariate and multivariate analyses of independent factors for cholecystitis. All factors with
Of the 160 consecutive patients, 17, 9, 8, 4, and 4 patients who had cholecystectomy history, could not be followed-up, underwent USEMS placement, had previous or concurrent gallbladder drainage for SEMS placement, and were not assessed by MDCT before SEMS placement, respectively, were excluded. Thus, 118 patients (median age, 72 years [range, 22–92 years]; sex, 72 men [61.0%] and 46 women [39.0%]) were finally enrolled.
During the observation period (median, 179 days [range, 17–1,231 days]), cholecystitis occurred in 18 (15.3%) patients after a median of 13 days (range, 1–269 days) following CSEMS placement. Thirteen patients developed early cholecystitis (72.2%) within 30 days of CSEMS placement.
The cholecystitis was mild, moderate, and severe in 1 (5.6%), 16 (88.9%), and 1 (5.6%) patients, respectively. The first treatment performed for cholecystitis was percutaneous transhepatic gallbladder aspiration (PTGBA) only in seven patients, PTGBA plus CSEMS removal in four, percutaneous transhepatic gallbladder drainage (PTGBD) only in four, watchful waiting with antibiotic therapy in two, and CSEMS removal plus endoscopic nasogallbladder drainage in one patient (
The TRBO was 291 days (range, 0–1,159 days), and there was no significant difference between patients who developed cholecystitis (median, 285 days [range, 7–530 days]) and those who did not (median, 291 days [range, 0–1,159 days]) (
The univariate and multivariate analyses revealed that the contrast agent flow into the gallbladder (univariate: odds ratio [OR], 3.750; 95% confidence interval [CI], 1.333–10.546;
Nakai et al. conducted a multicenter retrospective investigation to identify the risk factors for post-SEMS cholecystitis and reported that OCD tumor involvement (OR, 5.4;
Isayama et al. reported that endoscopic ultrasound-guided BD (EUS-BD) should be considered for patients in high risk, including those with OCD tumor involvement to prevent cholecystitis after SEMS placement [
In this study, flow of the contrast agent into the gallbladder was also identified as a significant risk factor for cholecystitis. In a recent study evaluating endoscopic biliary stenting, including the use of PSs in patients with malignant extrahepatic bile duct obstruction, Kim et al. previously evaluated contrast agent injection into the gallbladder as an important predictive factor for cholecystitis and suggested that it may potentially be associated with the location of cancer because if the cancer is in the vicinity of the OCD, there may be retention of the contrast agent [
Tumor invasion to the arteries feeding the gallbladder, which was raised as a significant risk factor of cholecystitis onset by Sogabe et al. [
There were several limitations to the present study. First, it was a single-center retrospective study and there might have been some bias in patient selection. Second, it was difficult to measure the AF. Thus, an AF unknown for the majority of SEMS was used in the present investigation, and consequently, we could not investigate the risk factors associated with different AFs. Nakai et al. [
In conclusion, the present study suggested that the contrast agent flow into the gallbladder and the tumor involvement to the OCD were risk factors for cholecystitis development following CSEMS placement. A prospective investigation is warranted to validate the effectiveness of EUS-BD for the prevention of cholecystitis in patients with OCD tumor involvement.
None.
Conceptualization: Masafumi Watanabe, Kosuke Okuwaki
Data curation: MW, KO, Jun Woo, Mitsuhiro Kida, Hiroshi Imaizumi, Tomohisa Iwai
Formal analysis: MW, KO
Investigation: MW, KO
Methodology: MW, KO
Project administration: MW, KO
Resources: MW, KO
Software: MW, KO
Supervision: MW, KO
Validation: MW, KO
Visualization: MW, KO
Writing-original draft: MW, KO
Writing-review&editing: KO, JW, MK, HI, TI, Hiroshi Yamauchi, Toru Kaneko, Rikiya Hasegawa, Takahiro Kurosu, Naoki Minato, Hiroki Haradome, Wasaburo Koizumi
Flow of contrast agent into the gallbladder. Flow of the contrast agent into the gallbladder was deemed positive when the contrast agent was observed flowing into the gallbladder or cystic duct on fluoroscopic imaging in endoscopic retrograde cholangiopancreatography.
Tumor invasion to the cystic artery. Tumor invasion to the cystic artery (arrow) was visible on multidetector computed tomography.
Tumor involvement to the orifice of cystic duct. Multidetector computed tomography (A) shows cholangiocarcinoma of the common bile duct (*) and contrast enhancement at the cystic duct (arrow). Infiltration of the tumor from the bile to the cystic duct was visible on intraductal ultrasonography (arrowheads) (B).
Patient Characteristics (
Median age, yr [range] | 72 [22–92] |
Sex, male/female | 72 (61.0)/46 (39.0) |
Etiology of malignant biliary obstruction | |
Pancreatic cancer | 98 (83.1) |
Biliary tract cancer | 15 (12.7) |
Other malignancies | 5 (4.2) |
Previous biliary duct drainage using plastic stent | 78 (66.1) |
Papillary treatment | |
EST | 104 (88.1) |
EPBD | 2 (1.7) |
None | 12 (10.2) |
Flow of contrast agent into gallbladder | 35 (29.7) |
Median stent length | |
>60 mm/≤60 mm | 65 (55.1)/53 (44.9) |
Location of the SEMS placement | |
Across/above the papilla | 107 (90.7)/11 (9.3) |
Tumor involvement to OCD | 35 (29.7) |
Artery feeding the gallbladder | |
Cystic artery | 114 (96.6) |
Unidentifiable | 4 (3.4) |
Origin of the cystic artery | |
RHA | 95 (80.5) |
Replaced RHA | 10 (8.5) |
GDA | 4 (3.4) |
PHA | 2 (1.7) |
LHA | 1 (0.8) |
SMA | 1 (0.8) |
Unidentifiable | 5 (4.2) |
Tumor invasion to the cystic artery | 3 (2.5) |
Tumor invasion to the origin of the cystic artery | 10 (8.5) |
Gallbladder stones | 17 (14.4) |
EPBD, endoscopic papillary balloon dilation; EST, endoscopic sphincterotomy; GDA, gastroduodenal artery; LHA, left hepatic artery; OCD, orifice of cystic duct; PHA, proper hepatic artery; RHA, right hepatic artery; SEMS, self-expandable metallic stent; SMA, superior mesenteric artery.
Incidence of Cholecystitis (
Severity grading of cholecystitis after stent placement | |
Mild | 1 (5.6) |
Moderate | 16 (88.9) |
Severe | 1 (5.6) |
Initial therapy for cholecystitis | |
PTGBA only | 7 (38.9) |
PTGBA plus CSEMS removal | 4 (22.2) |
PTGBD only | 4 (22.2) |
Watchful waiting with antibiotics | 2 (11.1) |
CSEMS removal plus ENGBD | 1 (5.6) |
CSEMS, covered self-expandable metallic stent; ENGBD, endoscopic nasogallbladder drainage; PTGBA, percutaneous transhepatic gallbladder aspiration; PTGBD, percutaneous transhepatic gallbladder drainage.
Analysis of Risk Factors Related to Cholecystitis
Univariate analysis |
Multivariate analysis |
|||
---|---|---|---|---|
Patients | OR (95% CI) | |||
Sex | 0.594 | |||
Male | 12/72 | |||
Female | 6/46 | |||
Causative disease | n.c. | |||
Pancreatic and biliary cancer | 18/113 | |||
Others | 0/5 | |||
Previous biliary duct drainage using plastic stent | 0.553 | |||
Yes | 13/78 | |||
No | 5/40 | |||
Flow of contrast agent into gallbladder | 0.012 | 3.496 (1.184–10.322) | 0.023 | |
Yes | 10/35 | |||
No | 8/83 | |||
Median stent length | 0.287 | |||
>60 mm | 12/65 | |||
≤60 mm | 6/53 | |||
Location of SEMS placement | 0.255 | |||
Across the papilla | 15/107 | |||
Above the papilla | 3/11 | |||
Tumor involvement at the OCD | 0.003 | 4.702 (1.591–13.895) | 0.005 | |
Yes | 11/35 | |||
No | 7/83 | |||
Tumor invasion to cystic artery |
n.c. | |||
Yes | 0/3 | |||
No | 18/111 | |||
Tumor invasion to the origin of cystic artery |
0.596 | |||
Yes | 1/10 | |||
No | 17/103 | |||
Gallbladder stones | 0.767 | |||
Yes | 3/17 | |||
No | 14/101 | |||
Structure of SEMS | 0.398 | |||
Braded | 17/115 | |||
Laser-cut | 1/3 |
CI, confidence interval; n.c., not calculated; OCD, orifice of cystic duct; OR, odds ratio; SEMS, self-expandable metallic stent.
Four patients were excluded because of non-evaluability.
Five patients were excluded because of non-evaluability.