J Hepatobiliary Pancreat Sci (2015) 22:79–85 DOI: 10.1002/jhbp.170
ORIGINAL ARTICLE
Risk factors for technical failure of endoscopic double self-expandable metallic stent placement by partial stent-in-stent method Kazumichi Kawakubo · Hiroshi Kawakami · Yoshihide Toyokawa · Koichi Otani · Masaki Kuwatani · Yoko Abe · Shuhei Kawahata · Kimitoshi Kubo · Yoshimasa Kubota · Naoya Sakamoto Published online: 12 October 2014 © 2014 Japanese Society of Hepato-Biliary-Pancreatic Surgery
Abstract Background Endoscopic double self-expandable metallic stent (SEMS) placement by the partial stent-in-stent (PSIS) method has been reported to be useful for the management of unresectable hilar malignant biliary obstruction. However, it is technically challenging, and the optimal SEMS for the procedure remains unknown. The aim of this study was to identify the risk factors for technical failure of endoscopic double SEMS placement for unresectable malignant hilar biliary obstruction (MHBO). Methods Between December 2009 and May 2013, 50 consecutive patients with MHBO underwent endoscopic double SEMS placement by the PSIS method. We retrospectively evaluated the rate of successful double SEMS placement and identified the risk factors for technical failure. Results The technical success rate for double SEMS placement was 82.0% (95% confidence interval [CI]: 69.2–90.2). On univariate analysis, the rate of technical failure was high
in patients with metastatic disease and unilateral placement. Multivariate analysis revealed that metastatic disease was a significant risk factor for technical failure (odds ratio: 9.63, 95% CI: 1.11–105.5). The subgroup analysis after double guidewire insertion showed that the rate of technical success was higher in the laser-cut type SEMS with a large mesh and thick delivery system than in the braided type SEMS with a small mesh and thick delivery system. Conclusions Metastatic disease was a significant risk factor for technical failure of double SEMS placement for unresectable MHBO. The laser-cut type SEMS with a large mesh and thin delivery system might be preferable for the PSIS procedure. Keywords Endoscopic biliary drainage · Malignant hilar biliary obstruction · Self-expandable metallic stent · Stentin-stent method Introduction
K. Kawakubo · N. Sakamoto Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan H. Kawakami (*) · Y. Abe · S. Kawahata · K. Kubo · Y. Kubota Department of Gastroenterology and Hepatology, Hokkaido University Hospital, Kita 14, Nishi 5, Kita-Ku, Sapporo, Hokkaido 0608648, Japan e-mail: [email protected] M. Kuwatani Division of Endoscopy, Hokkaido University Hospital, Sapporo, Hokkaido, Japan Y. Toyokawa · K. Otani Research and Development Center, Piolax Medical Devices, Inc., Yokohama, Kanagawa, Japan K. Kawakubo and H. Kawakami contributed equally to this work.
In the era of the development of endoscopic intervention, endoscopic self-expandable metallic stent (SEMS) placement was considered optimal for the management of unresectable malignant hilar biliary obstruction (MHBO) [1–3]. However, there was controversy regarding bilateral versus unilateral placement [4, 5]. Bilateral SEMS placement might be physiologically advantageous for prolongation of stent patency, but the question of clinical efficacy of the various methods, such as partial stent-in-stent (PSIS) and side-by-side, remained unresolved [6, 7]. Recently, the efficacy of endoscopic bilateral SEMS placement by the SIS method has been reported [8–10]. The SIS method has the advantage of reducing excessive expansion of the bile duct in the region of SEMS overlap as compared with the side-byside method [11]. However, the procedure is technically challenging.
80
J Hepatobiliary Pancreat Sci (2015) 22:79–85
Table 1 Characteristics of self-expandable metallic stent (SEMS)
Niti-S large cell D-type [14] Modified Niti-S large cell D-type [8] ZEO stent [12] Bilerush [28]
Type
Mesh size (mm2)
Diameter of delivery system (Fr)
Braided Braided Laser-cut Laser-cut
6.84 12.97 23.16 29.21
8.5 8.0 7.2 7.0
There are many kinds of SEMS, and it has been unclear which SEMS is the most suitable for the PSIS procedure. Also, the relationship between the mechanical properties of each SEMS and its clinical efficacy has not been well known [12, 13]. Previous studies have shown that the overall technical success rate of PSIS methods ranges from 76.9% to 100% [8–10, 14–16], but no prior study has evaluated the factors associated with technical failure of SEMS placement for unresectable MHBO by the SIS method. The aim of this retrospective study was to identify the risk factors for technical failure of endoscopic double SEMS placement for unresectable MHBO.
A standard ERCP catheter was used, corresponding to the 0.025 and 0.035-inch guidewire (endoscopy catheter article no. 0120211, 1.6 mm diameter; MTW Endoskopie, Wesel, Germany). A CleverCut 3V TM with a tip length of 7 mm and a cutting wire length of 20 mm was used as a sphincterotome (KD-V411M-0720, Olympus Medical Systems). A 0.035inch hydrophilic hard-type guidewire (Jagwire, Boston Scientific Japan, Tokyo, Japan), 0.035-inch hydrophilic soft-type guidewire (Radifocus, Termo, Tokyo, Japan), and a 0.025-inch hydrophilic hard-type guidewire (VisiGlide, Olympus Medical Systems) with the same stiffness as a regular 0.035-inch guidewire were used for ease of manipulation.
Patients and methods Patients Between December 2009 and May 2013, 50 patients with unresectable MHBO underwent endoscopic double metallic stent placement by the PSIS method at Hokkaido University Hospital. Inclusion criterion was unresectable MHBO of Bismuth II or higher. Patients who previously underwent percutaneous biliary drainage or SEMS placement were excluded. The Bismuth classification was used to classify tumor locations in relation to the confluence of the hepatic duct [17]. We retrospectively reviewed the prospectively collected database regarding these patients. The institutional review board of our hospital approved this study. The study was performed in accordance with the Declaration of Helsinki and is registered with the University Hospital Medical Information Network-Clinical Trial Registry (UMIN-CTR; No. UMIN000011879). Endoscopic protocol and equipment All patients provided written informed consent. Endoscopic procedures were performed on an inpatient basis, under conscious sedation with fentanyl citrate and midazolam. After selective bile duct cannulation, the stricture was evaluated by endoscopic retrograde cholangiopancreatography (ERCP). ERCP was performed using a duodenoscope with a 15° backward-oblique angle with an elevator function (TJF260V; Olympus Medical Systems, Tokyo, Japan).
Endoscopic double SEMS placement by the PSIS method Before endoscopic double SEMS placement, all patients underwent multidetector computed tomography (MDCT) and/or magnetic resonance cholangiopancreatography (MRCP) and were evaluated for surgery by a hepatobiliary surgeon. Pathological diagnosis was confirmed by endoscopic transpapillary biopsy or endoscopic ultrasoundguided fine-needle aspiration biopsy. The criteria for surgical unresectability were determined according to our previous study [18–21], with the addition of advanced age or comorbid disease precluding surgery in some cases. The bile duct for drainage was determined by MDCT or MRCP [22]. In patients with biliary obstruction involving three or more branches with ipsilateral lobar atrophy, unilateral SEMS placement in the contralateral hepatic duct was performed. In the remaining patients, bilateral SEMS placement was attempted. The characteristics and photographs of the SEMSs used during the study period are shown in Table 1 and Figure 1, respectively. We used a laser-cut type SEMS (ZEO stent [Zeon Medical, Tokyo, Japan] and Bilerush [Piolax Medical Devices, Kanagawa, Japan]) or braided type SEMS (Niti-S large cell d-type and modified Niti-S large cell d-type, Taewoong-Medical, Gyeonggi-do, Korea). We classified the patients into either group A (Niti-S large-cell d-type and modified Niti-S large-cell d-type: a laser-cut type with a large mesh and thin delivery system) or group B (ZEO stent and Bilerush: a braided type with a small mesh and thick delivery system).
J Hepatobiliary Pancreat Sci (2015) 22:79–85 Fig. 1 (a) Niti-S large cell d-type [14], (b) modified Niti-S large cell d-type [8], (c) ZEO stent [12], and (d) Bilerush [28]
81
(a)
(b)
1.0 mm (c)
(d)
1.0 mm
Endoscopic double SEMS placement consisted of four steps. In step 1, after successful selective bile duct cannulation, a cholangiogram was obtained and a 0.025inch guidewire (Visiglide, Olympus Medical Systems) was advanced into the target intrahepatic biliary system. Endoscopic sphincterotomy was performed at the discretion of the endoscopist. In step 2, the first SEMS was usually inserted into the intrahepatic duct. In step 3, the guidewire inside the first placed SEMS was gradually withdrawn up to the central portion of the SEMS and then advanced into the contralateral intrahepatic bile duct through the first SEMS. If the guidewire could not be passed through the mesh of the first SEMS, the first SEMS was dilated using a balloon catheter (Hurricane RX biliary balloon dilatation catheter, Boston Scientific Japan). In step 4, the second SEMS was deployed through the mesh of the first SEMS along the guidewire. All endoscopic procedures were performed by highly experienced endoscopists (H.K., M.K., and K.K.) or under their supervision. Outcome measures The primary outcome of this study was the technical success rate of endoscopic double SEMS placement by the PSIS method. Technical success was defined as the single-session passage of the SEMS across a patient’s stricture by the PSIS method. Secondary outcomes of this study were the rate of complications and stent patency calculated using the Kaplan–Meier method. Stent occlusion was defined as the recurrence of biliary obstruction and jaundice and/or evi-
1.0 mm
1.0 mm
dence of cholestasis, confirmed by ultrasound (US) or computed tomography (CT), requiring biliary reintervention. Stent patency was defined as the period between insertion and stent occlusion. Any death before stent occlusion was treated as censored data in calculating stent patency. Early and late complications were defined as those occurring within 30 and after 30 days of stent placement, respectively. ERCP-related complications were included and assessed according to the consensus criteria [23]. Cholangitis in an undrained hepatic duct was diagnosed if a new onset of fever lasting more than 24 h was associated with dilatation of an undrained hepatic duct in the absence of stent occlusion or sources of infection outside the biliary tract. Statistical analysis Continuous variables were presented using the median and range, and categorical variables were presented using proportions. Categorical variables were compared between the technical success and failure groups using the χ2 test or logistic regression analysis. Factors with P < 0.1 by logistic regression analysis were considered potential risk factors for technical failure and were incorporated into a multivariate logistic regression analysis. In order to evaluate the differences in technical success between metallic stents, we performed subgroup analyses excluding patients with step 1 failure. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each factor. Stent patency and patient survival were calculated using the Kaplan–Meier method. All statistical analyses were performed using JMP
82
J Hepatobiliary Pancreat Sci (2015) 22:79–85
Table 2 Patient characteristics Number of patients Age (years), median range Sex (male/female) Diagnosis, n (%) Cholangiocarcinoma Gallbladder carcinoma Metastatic disease Previous biliary drainage, n (%) ENBD/EBS Bismuth classification, n II IIIa IIIb IV Type of metallic stent SEMS group A/B Site of the first metallic stent Left/Right posterior/Right anterior Bilateral/Unilateral
50 73 (48–87) 28/22 25 (50) 20 (40) 5 (10) 37 (74) 35/2 18 10 5 17
Fig. 2 Flow chart of this study.
19/31 28/5/17 45/5
EBS endoscopic biliary stenting, ENBD endoscopic nasobiliary drainage, SEMS self-expandable metallic stent SEMS group A: Niti-S large-cell d-type and modified Niti-S large-cell d-type, and SEMS group B: ZEO stent and Bilerush
version 9.0.2 (SAS Institute). P < 0.05 was considered statistically significant in all analyses. Results Fifty patients were included in this study, and their characteristics are shown in Table 2. The cause of MHBO was cholangiocarcinoma in 25, gallbladder carcinoma in 20, and metastatic disease in five (primary origin: pancreatic cancer, renal cell carcinoma, gastric cancer, orbital cancer, and cancer of unknown primary origin). Thirty-seven patients (74%) had previously received a biliary stent or nasobiliary drainage tube, while the remaining patients underwent endoscopic double SEMS placement by the PSIS method as an initial drainage. Five patients underwent unilateral double SEMS placement in the right hepatic lobe, and 45 patients underwent bilateral double SEMS placement. Primary outcomes A flow chart of this study is shown in Figure 2. Overall, 41 patients had successful endoscopic double SEMS placement by the PSIS method. The technical success rate was 82.0% (95% CI: 69.2–90.2). In nine patients, endoscopic double SEMS placement by the PSIS method was unsuccessful. In three of these patients, all designated to receive unilateral
double SEMS placement, double guidewires could not pass through the MHBO (step 1). In another three patients, guidewire insertion through the mesh of the first SEMS failed (step 3). In the remaining three patients, the second SEMS could not pass through the mesh of the first SEMS (step 4). Risk factors for technical failure of double SEMS placement by the PSIS method are shown in Table 3. Metastatic disease, unilateral placement, and Bismuth classification IIII or IV were risk factors for technical failure on univariate analysis. Multivariate analysis using these three factors revealed that metastatic disease was the only significant risk factor for technical failure in double SEMS placement by the PSIS method (Table 3). Subgroup analysis after step 1 revealed that metastatic disease was a significant risk factor, and group B SEMS was associated with technical success. Multivariate analysis showed that group B SEMS was significantly associated with technical success (Table 4). Secondary outcomes Secondary outcomes are summarized in Table 5. Twentytwo complications occurred in this study. Early complications within 30 days of stent placement were observed in 10 (20%) patients (four segmental cholangitis, two cholecystitis, one liver abscess, one post-ERCP pancreatitis, and two stent occlusions). Late complications after 30 days occurred in 12 (24%) patients (one cholecystitis and 12 stent occlusions). There were no significant differences in the complication rates between the patients with successful and those with failed stent placement (39% and 22%; P = 0.327). The median stent patency was 171 days (95% CI: 117–285). There was no significant difference in stent patency between both groups (P = 0.299). Endoscopic reintervention was successful in eight (62%) patients, while the remaining five required percutaneous drainage.
J Hepatobiliary Pancreat Sci (2015) 22:79–85
83
Table 3 Risk factors for technical failure Univariate analysis
Age < Median ≥ Median Sex Male Female Non-metastatic disease Metastatic disease Previous biliary drainage Yes No Bismuth classification II III or IV SEMS group A SEMS group B Bilateral placement Unilateral placement
Multivariate analysis
OR
95% CI
P-value
OR
95% CI
P-value
1 2.32
0.53–12.2
0.432
–
–
–
–
–
1.11–105.5
0.041
1 1.02 1 9.75
0.23–4.46
0.976
1.36–87.1
0.024
– 1 9.63
1 2.84
0.60–13.3
0.182
–
–
–
0.91–110.1
0.064
1 3.56
0.45–76.3
0.244
0.09–1.80
0.237
–
–
1.36–87.2
0.024
0.81–75.1
0.076
1 5.67 1 0.41 1 9.75
– 1 7.07
CI confidence interval, OR odds ratio, SEMS self-expandable metallic stent SEMS group A: Niti-S large-cell d-type and modified Niti-S large-cell d-type, and SEMS group B: ZEO stent and Bilerush Table 4 Risk factors for technical failure after step 1 Univariate analysis
Age < median ≥ median Sex Male Female Non-metastatic disease Metastatic disease Previous biliary drainage Yes No Bismuth classification II III or IV SEMS group A SEMS group B
Multivariate analysis
OR
95% CI
P-value
OR
95% CI
P-value
1 2.32
0.40–18.1
0.349
–
–
–
–
–
0.55–81.2
0.133
1 1.28 1 9.75
0.21–7.64
0.780
0.97–103.1
0.053
– 1 6.36
1 3.56
0.57–22.3
0.165
–
–
–
0.51–71.1
0.219
–
–
0.01–0.72
0.021
– 1 0.19
0.01–0.99
0.049
1 3.54 1 0.10
CI confidence interval, OR odds ratio, SEMS self-expandable metallic stent SEMS group A: Niti-S large-cell d-type and modified Niti-S large-cell d-type, and SEMS group B: ZEO stent and Bilerush
Discussion Our study showed that the technical success rate for double SEMS placement was significantly lower in patients with
metastatic disease than for those with bile duct and gallbladder carcinoma. The biliary stricture in metastatic disease is extrinsic rather than intrinsic in nature and requires multiple procedures, including both percutaneous and endoscopic
84
J Hepatobiliary Pancreat Sci (2015) 22:79–85
Table 5 Secondary outcomes Complications, n (%) Early (
ORIGINAL ARTICLE
Risk factors for technical failure of endoscopic double self-expandable metallic stent placement by partial stent-in-stent method Kazumichi Kawakubo · Hiroshi Kawakami · Yoshihide Toyokawa · Koichi Otani · Masaki Kuwatani · Yoko Abe · Shuhei Kawahata · Kimitoshi Kubo · Yoshimasa Kubota · Naoya Sakamoto Published online: 12 October 2014 © 2014 Japanese Society of Hepato-Biliary-Pancreatic Surgery
Abstract Background Endoscopic double self-expandable metallic stent (SEMS) placement by the partial stent-in-stent (PSIS) method has been reported to be useful for the management of unresectable hilar malignant biliary obstruction. However, it is technically challenging, and the optimal SEMS for the procedure remains unknown. The aim of this study was to identify the risk factors for technical failure of endoscopic double SEMS placement for unresectable malignant hilar biliary obstruction (MHBO). Methods Between December 2009 and May 2013, 50 consecutive patients with MHBO underwent endoscopic double SEMS placement by the PSIS method. We retrospectively evaluated the rate of successful double SEMS placement and identified the risk factors for technical failure. Results The technical success rate for double SEMS placement was 82.0% (95% confidence interval [CI]: 69.2–90.2). On univariate analysis, the rate of technical failure was high
in patients with metastatic disease and unilateral placement. Multivariate analysis revealed that metastatic disease was a significant risk factor for technical failure (odds ratio: 9.63, 95% CI: 1.11–105.5). The subgroup analysis after double guidewire insertion showed that the rate of technical success was higher in the laser-cut type SEMS with a large mesh and thick delivery system than in the braided type SEMS with a small mesh and thick delivery system. Conclusions Metastatic disease was a significant risk factor for technical failure of double SEMS placement for unresectable MHBO. The laser-cut type SEMS with a large mesh and thin delivery system might be preferable for the PSIS procedure. Keywords Endoscopic biliary drainage · Malignant hilar biliary obstruction · Self-expandable metallic stent · Stentin-stent method Introduction
K. Kawakubo · N. Sakamoto Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan H. Kawakami (*) · Y. Abe · S. Kawahata · K. Kubo · Y. Kubota Department of Gastroenterology and Hepatology, Hokkaido University Hospital, Kita 14, Nishi 5, Kita-Ku, Sapporo, Hokkaido 0608648, Japan e-mail: [email protected] M. Kuwatani Division of Endoscopy, Hokkaido University Hospital, Sapporo, Hokkaido, Japan Y. Toyokawa · K. Otani Research and Development Center, Piolax Medical Devices, Inc., Yokohama, Kanagawa, Japan K. Kawakubo and H. Kawakami contributed equally to this work.
In the era of the development of endoscopic intervention, endoscopic self-expandable metallic stent (SEMS) placement was considered optimal for the management of unresectable malignant hilar biliary obstruction (MHBO) [1–3]. However, there was controversy regarding bilateral versus unilateral placement [4, 5]. Bilateral SEMS placement might be physiologically advantageous for prolongation of stent patency, but the question of clinical efficacy of the various methods, such as partial stent-in-stent (PSIS) and side-by-side, remained unresolved [6, 7]. Recently, the efficacy of endoscopic bilateral SEMS placement by the SIS method has been reported [8–10]. The SIS method has the advantage of reducing excessive expansion of the bile duct in the region of SEMS overlap as compared with the side-byside method [11]. However, the procedure is technically challenging.
80
J Hepatobiliary Pancreat Sci (2015) 22:79–85
Table 1 Characteristics of self-expandable metallic stent (SEMS)
Niti-S large cell D-type [14] Modified Niti-S large cell D-type [8] ZEO stent [12] Bilerush [28]
Type
Mesh size (mm2)
Diameter of delivery system (Fr)
Braided Braided Laser-cut Laser-cut
6.84 12.97 23.16 29.21
8.5 8.0 7.2 7.0
There are many kinds of SEMS, and it has been unclear which SEMS is the most suitable for the PSIS procedure. Also, the relationship between the mechanical properties of each SEMS and its clinical efficacy has not been well known [12, 13]. Previous studies have shown that the overall technical success rate of PSIS methods ranges from 76.9% to 100% [8–10, 14–16], but no prior study has evaluated the factors associated with technical failure of SEMS placement for unresectable MHBO by the SIS method. The aim of this retrospective study was to identify the risk factors for technical failure of endoscopic double SEMS placement for unresectable MHBO.
A standard ERCP catheter was used, corresponding to the 0.025 and 0.035-inch guidewire (endoscopy catheter article no. 0120211, 1.6 mm diameter; MTW Endoskopie, Wesel, Germany). A CleverCut 3V TM with a tip length of 7 mm and a cutting wire length of 20 mm was used as a sphincterotome (KD-V411M-0720, Olympus Medical Systems). A 0.035inch hydrophilic hard-type guidewire (Jagwire, Boston Scientific Japan, Tokyo, Japan), 0.035-inch hydrophilic soft-type guidewire (Radifocus, Termo, Tokyo, Japan), and a 0.025-inch hydrophilic hard-type guidewire (VisiGlide, Olympus Medical Systems) with the same stiffness as a regular 0.035-inch guidewire were used for ease of manipulation.
Patients and methods Patients Between December 2009 and May 2013, 50 patients with unresectable MHBO underwent endoscopic double metallic stent placement by the PSIS method at Hokkaido University Hospital. Inclusion criterion was unresectable MHBO of Bismuth II or higher. Patients who previously underwent percutaneous biliary drainage or SEMS placement were excluded. The Bismuth classification was used to classify tumor locations in relation to the confluence of the hepatic duct [17]. We retrospectively reviewed the prospectively collected database regarding these patients. The institutional review board of our hospital approved this study. The study was performed in accordance with the Declaration of Helsinki and is registered with the University Hospital Medical Information Network-Clinical Trial Registry (UMIN-CTR; No. UMIN000011879). Endoscopic protocol and equipment All patients provided written informed consent. Endoscopic procedures were performed on an inpatient basis, under conscious sedation with fentanyl citrate and midazolam. After selective bile duct cannulation, the stricture was evaluated by endoscopic retrograde cholangiopancreatography (ERCP). ERCP was performed using a duodenoscope with a 15° backward-oblique angle with an elevator function (TJF260V; Olympus Medical Systems, Tokyo, Japan).
Endoscopic double SEMS placement by the PSIS method Before endoscopic double SEMS placement, all patients underwent multidetector computed tomography (MDCT) and/or magnetic resonance cholangiopancreatography (MRCP) and were evaluated for surgery by a hepatobiliary surgeon. Pathological diagnosis was confirmed by endoscopic transpapillary biopsy or endoscopic ultrasoundguided fine-needle aspiration biopsy. The criteria for surgical unresectability were determined according to our previous study [18–21], with the addition of advanced age or comorbid disease precluding surgery in some cases. The bile duct for drainage was determined by MDCT or MRCP [22]. In patients with biliary obstruction involving three or more branches with ipsilateral lobar atrophy, unilateral SEMS placement in the contralateral hepatic duct was performed. In the remaining patients, bilateral SEMS placement was attempted. The characteristics and photographs of the SEMSs used during the study period are shown in Table 1 and Figure 1, respectively. We used a laser-cut type SEMS (ZEO stent [Zeon Medical, Tokyo, Japan] and Bilerush [Piolax Medical Devices, Kanagawa, Japan]) or braided type SEMS (Niti-S large cell d-type and modified Niti-S large cell d-type, Taewoong-Medical, Gyeonggi-do, Korea). We classified the patients into either group A (Niti-S large-cell d-type and modified Niti-S large-cell d-type: a laser-cut type with a large mesh and thin delivery system) or group B (ZEO stent and Bilerush: a braided type with a small mesh and thick delivery system).
J Hepatobiliary Pancreat Sci (2015) 22:79–85 Fig. 1 (a) Niti-S large cell d-type [14], (b) modified Niti-S large cell d-type [8], (c) ZEO stent [12], and (d) Bilerush [28]
81
(a)
(b)
1.0 mm (c)
(d)
1.0 mm
Endoscopic double SEMS placement consisted of four steps. In step 1, after successful selective bile duct cannulation, a cholangiogram was obtained and a 0.025inch guidewire (Visiglide, Olympus Medical Systems) was advanced into the target intrahepatic biliary system. Endoscopic sphincterotomy was performed at the discretion of the endoscopist. In step 2, the first SEMS was usually inserted into the intrahepatic duct. In step 3, the guidewire inside the first placed SEMS was gradually withdrawn up to the central portion of the SEMS and then advanced into the contralateral intrahepatic bile duct through the first SEMS. If the guidewire could not be passed through the mesh of the first SEMS, the first SEMS was dilated using a balloon catheter (Hurricane RX biliary balloon dilatation catheter, Boston Scientific Japan). In step 4, the second SEMS was deployed through the mesh of the first SEMS along the guidewire. All endoscopic procedures were performed by highly experienced endoscopists (H.K., M.K., and K.K.) or under their supervision. Outcome measures The primary outcome of this study was the technical success rate of endoscopic double SEMS placement by the PSIS method. Technical success was defined as the single-session passage of the SEMS across a patient’s stricture by the PSIS method. Secondary outcomes of this study were the rate of complications and stent patency calculated using the Kaplan–Meier method. Stent occlusion was defined as the recurrence of biliary obstruction and jaundice and/or evi-
1.0 mm
1.0 mm
dence of cholestasis, confirmed by ultrasound (US) or computed tomography (CT), requiring biliary reintervention. Stent patency was defined as the period between insertion and stent occlusion. Any death before stent occlusion was treated as censored data in calculating stent patency. Early and late complications were defined as those occurring within 30 and after 30 days of stent placement, respectively. ERCP-related complications were included and assessed according to the consensus criteria [23]. Cholangitis in an undrained hepatic duct was diagnosed if a new onset of fever lasting more than 24 h was associated with dilatation of an undrained hepatic duct in the absence of stent occlusion or sources of infection outside the biliary tract. Statistical analysis Continuous variables were presented using the median and range, and categorical variables were presented using proportions. Categorical variables were compared between the technical success and failure groups using the χ2 test or logistic regression analysis. Factors with P < 0.1 by logistic regression analysis were considered potential risk factors for technical failure and were incorporated into a multivariate logistic regression analysis. In order to evaluate the differences in technical success between metallic stents, we performed subgroup analyses excluding patients with step 1 failure. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each factor. Stent patency and patient survival were calculated using the Kaplan–Meier method. All statistical analyses were performed using JMP
82
J Hepatobiliary Pancreat Sci (2015) 22:79–85
Table 2 Patient characteristics Number of patients Age (years), median range Sex (male/female) Diagnosis, n (%) Cholangiocarcinoma Gallbladder carcinoma Metastatic disease Previous biliary drainage, n (%) ENBD/EBS Bismuth classification, n II IIIa IIIb IV Type of metallic stent SEMS group A/B Site of the first metallic stent Left/Right posterior/Right anterior Bilateral/Unilateral
50 73 (48–87) 28/22 25 (50) 20 (40) 5 (10) 37 (74) 35/2 18 10 5 17
Fig. 2 Flow chart of this study.
19/31 28/5/17 45/5
EBS endoscopic biliary stenting, ENBD endoscopic nasobiliary drainage, SEMS self-expandable metallic stent SEMS group A: Niti-S large-cell d-type and modified Niti-S large-cell d-type, and SEMS group B: ZEO stent and Bilerush
version 9.0.2 (SAS Institute). P < 0.05 was considered statistically significant in all analyses. Results Fifty patients were included in this study, and their characteristics are shown in Table 2. The cause of MHBO was cholangiocarcinoma in 25, gallbladder carcinoma in 20, and metastatic disease in five (primary origin: pancreatic cancer, renal cell carcinoma, gastric cancer, orbital cancer, and cancer of unknown primary origin). Thirty-seven patients (74%) had previously received a biliary stent or nasobiliary drainage tube, while the remaining patients underwent endoscopic double SEMS placement by the PSIS method as an initial drainage. Five patients underwent unilateral double SEMS placement in the right hepatic lobe, and 45 patients underwent bilateral double SEMS placement. Primary outcomes A flow chart of this study is shown in Figure 2. Overall, 41 patients had successful endoscopic double SEMS placement by the PSIS method. The technical success rate was 82.0% (95% CI: 69.2–90.2). In nine patients, endoscopic double SEMS placement by the PSIS method was unsuccessful. In three of these patients, all designated to receive unilateral
double SEMS placement, double guidewires could not pass through the MHBO (step 1). In another three patients, guidewire insertion through the mesh of the first SEMS failed (step 3). In the remaining three patients, the second SEMS could not pass through the mesh of the first SEMS (step 4). Risk factors for technical failure of double SEMS placement by the PSIS method are shown in Table 3. Metastatic disease, unilateral placement, and Bismuth classification IIII or IV were risk factors for technical failure on univariate analysis. Multivariate analysis using these three factors revealed that metastatic disease was the only significant risk factor for technical failure in double SEMS placement by the PSIS method (Table 3). Subgroup analysis after step 1 revealed that metastatic disease was a significant risk factor, and group B SEMS was associated with technical success. Multivariate analysis showed that group B SEMS was significantly associated with technical success (Table 4). Secondary outcomes Secondary outcomes are summarized in Table 5. Twentytwo complications occurred in this study. Early complications within 30 days of stent placement were observed in 10 (20%) patients (four segmental cholangitis, two cholecystitis, one liver abscess, one post-ERCP pancreatitis, and two stent occlusions). Late complications after 30 days occurred in 12 (24%) patients (one cholecystitis and 12 stent occlusions). There were no significant differences in the complication rates between the patients with successful and those with failed stent placement (39% and 22%; P = 0.327). The median stent patency was 171 days (95% CI: 117–285). There was no significant difference in stent patency between both groups (P = 0.299). Endoscopic reintervention was successful in eight (62%) patients, while the remaining five required percutaneous drainage.
J Hepatobiliary Pancreat Sci (2015) 22:79–85
83
Table 3 Risk factors for technical failure Univariate analysis
Age < Median ≥ Median Sex Male Female Non-metastatic disease Metastatic disease Previous biliary drainage Yes No Bismuth classification II III or IV SEMS group A SEMS group B Bilateral placement Unilateral placement
Multivariate analysis
OR
95% CI
P-value
OR
95% CI
P-value
1 2.32
0.53–12.2
0.432
–
–
–
–
–
1.11–105.5
0.041
1 1.02 1 9.75
0.23–4.46
0.976
1.36–87.1
0.024
– 1 9.63
1 2.84
0.60–13.3
0.182
–
–
–
0.91–110.1
0.064
1 3.56
0.45–76.3
0.244
0.09–1.80
0.237
–
–
1.36–87.2
0.024
0.81–75.1
0.076
1 5.67 1 0.41 1 9.75
– 1 7.07
CI confidence interval, OR odds ratio, SEMS self-expandable metallic stent SEMS group A: Niti-S large-cell d-type and modified Niti-S large-cell d-type, and SEMS group B: ZEO stent and Bilerush Table 4 Risk factors for technical failure after step 1 Univariate analysis
Age < median ≥ median Sex Male Female Non-metastatic disease Metastatic disease Previous biliary drainage Yes No Bismuth classification II III or IV SEMS group A SEMS group B
Multivariate analysis
OR
95% CI
P-value
OR
95% CI
P-value
1 2.32
0.40–18.1
0.349
–
–
–
–
–
0.55–81.2
0.133
1 1.28 1 9.75
0.21–7.64
0.780
0.97–103.1
0.053
– 1 6.36
1 3.56
0.57–22.3
0.165
–
–
–
0.51–71.1
0.219
–
–
0.01–0.72
0.021
– 1 0.19
0.01–0.99
0.049
1 3.54 1 0.10
CI confidence interval, OR odds ratio, SEMS self-expandable metallic stent SEMS group A: Niti-S large-cell d-type and modified Niti-S large-cell d-type, and SEMS group B: ZEO stent and Bilerush
Discussion Our study showed that the technical success rate for double SEMS placement was significantly lower in patients with
metastatic disease than for those with bile duct and gallbladder carcinoma. The biliary stricture in metastatic disease is extrinsic rather than intrinsic in nature and requires multiple procedures, including both percutaneous and endoscopic
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J Hepatobiliary Pancreat Sci (2015) 22:79–85
Table 5 Secondary outcomes Complications, n (%) Early (
