Comparison of the preoperative transpapillary unilateral biliary drainage methods for the future remnant liver in patients with hilar cholangiocarcinoma

doi:10.21203/rs.3.rs-4931541/v1

Object:

Transpapillary preoperative biliary drainage (PBD) only for the future remnant liver (FRL) in hilar cholangiocarcinoma (HCCA) can be performed minimally invasively, with the expectation of swelling of the FRL. However, verification of the appropriate transpapillary unilateral PBD method for FRL is limited.

Methods:

Twelve unilateral across-the-papilla plastic stent placement cases (PS group), 14 unilateral intraductal plastic stent placement cases (IS group), and 11 unilateral endoscopic nasobiliary drainage cases (ENBD group) met the inclusion criteria. Each group was compared regarding thehospital stay duration, recurrent biliary obstruction (RBO), time to RBO (TRBO), and surgical outcomes.

Results:

No significant differences were observed in the patient characteristics between the groups. Hospital stay for the endoscopic procedure was significantly longer in the ENBD group (50[33-163]days) than in the PS group (14[2-36]days; P<0.01) or IS group (21[6-118]days; P<0.01). There were no significant differences in the RBO, TRBO, surgical time, amount of intraoperative blood loss, or post-surgical adverse events (AEs) between the groups.

Conclusions:

PS, IS, and ENBD groups showed similar clinical outcomes in liver resection cases for HCCA, excluding the hospital stay duration for the endoscopic procedure. Considering the hospital stay duration, unilateral PS and IS placement can be considered acceptable for transpapillary PBD.

Clinical Trial Registration: UMIN000052598

Biological sciences/Cancer/Gastrointestinal cancer/Biliary tract cancer/Bile duct cancer

Biological sciences/Cancer/Gastrointestinal cancer

hilar cholangiocarcinoma

preoperative endoscopic biliary drainage

plastic stent

intraductal plastic stent

endoscopic nasobiliary drainage

Hilar cholangiocarcinoma (HCCA) has significant prominence as a cancer type with an increasing incidence rate globally^1,2. Surgical resection is the only curative method for HCCA^3,4. The need for preoperative biliary drainage (PBD) remains controversial; however, PBD for cholangitis and/or jaundice is important for safe surgical resection and prevention of post-surgical adverse events (AEs)^5–7.

Although percutaneous transhepatic biliary drainage (PTBD) is an effective PBD method, it has disadvantages, including catheter tract implantation metastases and vessel injury. Transpapillary PBD can be performed as a minimally invasive and effective alternative. According to the Japanese guidelines, endoscopic nasobiliary drainage (ENBD) placement is considered to be better than across-the-papilla plastic stent (PS) placement because PS carries the risk of stent dysfunction⁸. However, evidence for the utility of ENBD is limited^9–11. Recently, intraductal PS (IS) placement was reported to have a longer stent patency than PS placement in unresectable malignant hilar biliary obstruction (MHBO) and validation of the usefulness of IS placement as a PBD is being^12–14.

Unilateral PBD for the future remnant liver (FRL) is generally recommended when swelling of the FRL is expected, especially in the Japanese guidelines^8,15,16. Although some articles have evaluated transpapillary PBD methods for HCCA, these articles included bilateral PBD with or without non-liver resection cases. Therefore, evidence for an appropriate transpapillary unilateral PBD method is insufficient. This study aimed to verify the appropriate transpapillary unilateral PBD methods for FRL limited to cases of liver resection and compared the unilateral PS, IS, and ENBD placement methods.

Study design and patients

Between November 2005 and November 2023, endoscopic retrograde cholangiography was performed for the preoperative diagnosis of HCCA in 63 patients with resectable MHBO at three tertiary medical centers in Japan (Gifu Municipal Hospital, Gifu University Hospital, and Gifu Prefectural General Medical Center). The inclusion criteria were as follows: (1) age > 20 years and (2) patients who underwent unilateral PBD for the FRL. The exclusion criteria were as follows: (1) patients who underwent bilateral PBD, (2) patients who did not require PBD for the FRL, (3) patients who did not undergo liver resection, (4) PTBD cases, and (5) inability to provide informed consent.

The data of these patients were retrospectively reviewed to evaluate the efficacy and safety of unilateral PBD, including PS, IS, and ENBD. This study was approved by the Institutional Review Boards at three medical centers (Gifu Municipal Hospital [No.20233029], Gifu University Hospital [No.2022 − 268], and Gifu Prefectural General Medical Center [No.844]) and was conducted in accordance with the Declaration of Helsinki. The study protocol was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000052598).

Procedure

Experienced endoscopists who were faculty members at the three medical centers performed all the endoscopic procedures. Superficial ductal spread of HCCA was diagnosed based on imaging findings (computed tomography [CT] and cholangiography) and/or histopathological findings of the mapping biopsy¹⁷. The stent placement side (FRL side) was decided based on imaging findings, and the PBD method was decided by the main endoscopic operator. Transpapillary PBD was performed using a standard duodenoscope (TJF-260V; Olympus Medical Systems, Tokyo, Japan). After cholangiography, a guidewire (0.025-inch VisiGlide2; Olympus Medical Systems, Tokyo, Japan) was inserted into the intrahepatic bile duct (IHBD). The patients underwent endoscopic sphincterotomy (ES) if necessary.

After biopsy specimens were obtained from patients with MHBO (Fig. 1), some patients underwent temporary biliary drainage using an ENBD tube while awaiting histopathological confirmation. Finally, a 7-F PS (Through & Pass; Gadelius Medical, Tokyo, Japan) was placed as the PBD in the PS group. A 7-F PS with a 3 − 0 nylon thread tied to the distal end of the stent (Through & Pass) was used in the IS group. The proximal portion of the 7-F PS was placed in the IHBD of the FRL. The distal end of the 7-F PS was placed in the duodenum via the main papilla in the PS group (Fig. 1A) and through the common bile duct (CBD) in the IS group (Fig. 1B). In the ENBD group, a 5-F or 6-F ENBD tube was placed in the IHBD of the FRL (Fig. 1C). After PS, IS, or ENBD placement, each drainage method was continued until undergoing the surgical resection, or the occurrence of recurrent biliary obstruction (RBO).

Study endpoints and definitions

The following outcomes of each drainage method were assessed for PBD: (1) procedure time, (2) technical and clinical success, (3) AEs, (4) hospital stay duration for endoscopic procedures, (5) RBO, and (6) time to RBO (TRBO). Technical success was defined as successful transpapillary drainage tube placement into the FRL. Clinical success was defined as a decrease in the bilirubin level to a normal level or by less than 50% within 7 days after the procedure. AEs after the endoscopic procedure were defined as the occurrence of AEs within 1 week after the endoscopic procedure and were classified according to established criteria¹⁸. RBO was defined as the presence of biliary dilation observed on CT and/or elevated liver enzyme and bilirubin levels compared to baseline values and endoscopic findings, based on the Tokyo Criteria 2014¹⁹.

The surgical outcomes of each drainage method were also evaluated to assess the impact of each drainage method on surgery, including (1) operation times, (2) amount of intraoperative blood loss, (3) hospital stay duration for surgical resection, and (4) post-surgical AEs. Post-surgical AEs, including surgical site infection (SSI), bile leakage, and bleeding, were also evaluated using the Clavien–Dindo classification criteria²⁰.

Statistical analyses

Values are expressed as the number of patients or median (range). Fisher’s exact test was used for categorical variable analysis, and the Mann-Whitney U test was used for continuous variables. The cumulative TRBO and overall survival (OS) were analyzed using log-rank tests. TRBO was calculated time from each drainage method to the occurrence of RBO¹². Patients who underwent surgical resection were censored for TRBO. When a patient discontinued follow-up, OS was censored.

The association between “the occurrence of RBO, and post-surgical AEs”, or “cumulative TRBO, and OS”, and other factors (external fistula [ENBD group], age, sex, ECOG performance status [0], Bismuth classification [III-IV], complete [R0] resection, MHBO length, percutaneous transhepatic portal embolization [PTPE], histopathological differentiation [well], and presence of cholangitis before the endoscopic procedure) were evaluated by “logistic regression analysis” or “Cox proportional hazards model analysis.” Continuous variables were divided by the median values.

Factors related to RBO, post-surgical AEs, TRBO, and OS (P < 0.20) in the univariate analysis were further assessed using multivariate analysis. Regression analysis results were expressed as odds ratios (ORs) for the occurrence of RBO and post-surgical AEs or hazard ratios (HRs) for TRBO and OS. A P-value < 0.05 was considered to be statistically significant. All analyses were conducted using R ver. 4.0.2 (The R Foundation for Statistical Computing, Vienna, Austria).

Patient selection and characteristics

A total of 63 patients with MHBO underwent endoscopic retrograde cholangiopancreatography (ERCP) before surgical resection at the three centers during the study period. Among these, 9 patients who underwent bilateral PBD, 8 patients who did not require PBD due to incomplete biliary stenosis, and 9 patients who underwent pancreaticoduodenectomy without liver resection were excluded based on the eligibility criteria. Finally, 37 patients with unilateral PBD were included: 12 underwent unilateral across-the-papilla PS placement (PS group), 14 underwent unilateral IS placement (IS group), and 11 underwent unilateral ENBD placement (ENBD group) (Fig. 2).

The baseline characteristics of each group are presented in Table 1. There were no significant differences in each group pair, including age, sex, performance states, Bismuth classification, MHBO length, the number of PTPE cases, the median T-Bil level, and chemotherapy after the endoscopic procedure. Because most patients underwent cholangiography during the endoscopic procedure, and after biliary drainage to evaluate the superficial ductal spread of HCCA, 83% of the PS (10/11) and 71% of the IS (10/14) group patients underwent temporary ENBD placement. The median CA19-9 level was significantly different between the PS (47.6 U/ml) and IS group (188.1 U/ml) (P = 0.019).

Table 1

The patient characteristics of the PS, IS, and ENBD groups
	PS	IS	ENBD	P-value
	n = 12	n = 14	n = 11	PS vs IS	ENBD vs PS	ENBD vs IS
Age (years), median (range)	69 (59–78)	71 (61–78)	72 (65–85)	0.90	0.21	0.28
Females, n (%)	6 (50)	5 (36)	4 (36)	0.42	1.0	0.43
Performance status 0, n (%)	5 (42)	6 (43)	3 (27)	1.0	0.67	0.68
Performance status 1, n (%)	7 (58)	8 (57)	8 (73)	1.0	0.67	0.68
Bismuth classification type, n (%)
II	5 (42)	7 (50)	5 (45)	0.71	1.0	1.0
IIIa or IIIb	5 (42)	6 (43)	2 (18)	1.0	0.37	0.23
IV	2 (16)	1 (7)	3 (27)	0.58	0.64	0.29
Cholangitis before endoscopic procedure, n (%)	1 (8)	3 (21)	0	0.60	1.0	0.23
Previous drainage before PS placement, n (%)	10 (83)	10 (71)	-	0.65	-	-
Malignant hilar biliary obstruction length (mm), median (range)	13 (7–39)	16 (7–35)	16 (8–27)	0.07	0.19	0.78
PTPE, n (%)	2 (16)	7 (50)	3 (27)	0.11	0.64	0.41
CA19-9 (U/mL), median (range)	47.6 (0.50-989.2)	188.1 (30.5-1052.8)	279.9 (10.8-13676.9)	0.019	0.06	0.51
Total bilirubin (mg/dL), median (range)	1.6 (0.40–8.9)	1.3 (0.4–16.4)	1.9 (0.9–16.3)	0.89	0.17	0.32
Chemotherapy after endoscopic procedure, n (%)	1 (8)	1 (7)	0	1.0	1.0	1.0
PS: plastic stent
IS: intraductal plastic stent
ENBD: endoscopic nasobiliary drainage
PTPE: percutaneous transhepatic portal embolization

Endoscopic procedures and AEs

The results of the endoscopic procedures are summarized in Table 2. All patients underwent ES. The median procedure time was 54 (5–78) minutes in the PS group, 29 (7–60) minutes in the IS group, and 68 (32–73) minutes in the ENBD group, without significant differences between each group pair. Technical and clinical success was achieved in all the patients. AEs after the endoscopic procedure occurred in one case (7%; mild post-ERCP pancreatitis) in the IS group. The median hospital stay duration of the ENBD group (50[33–163]days) was significantly longer than that of the PS group (14[2–36]days; P < 0.01) or the IS group (21[6-118]days; P < 0.01). There was no significant difference in the median hospital stay duration between the PS and IS groups (P = 0.08).

Table 2

Results of the initial and re-intervention endoscopic procedures
	PS	IS	ENBD	P-value
	n = 12	n = 14	n = 11	PS vs IS	ENBD vs PS	ENBD vs IS
Endoscopic sphincterotomy, n (%)	12 (100)	14 (100)	11 (100)	NA	NA	NA
Procedure time (min), median (range)	54 (5–78)	29 (7–60)	68 (32–73)	0.06	0.33	0.51
Technical success, n (%)	12 (100)	14 (100)	11 (100)	NA	NA	NA
Clinical success, n (%)	12 (100)	14 (100)	11 (100)	NA	NA	NA
Advanced events, n (%)	0	1 (7)	0	1.0	NA	1.0
PEP,n (%)	0	1 (7)	0	1.0	NA	1.0
Hospital stay duration for endoscopic procedure (day), median (range)	14 (2–36)	21 (6-118)	50 (33–163)	0.08	0.001	0.001
RBO, n (%)	5 (42)	4 (29)	1 (9)	0.68	0.16	0.34
Reason for RBO, n
Stent sludge occlusion	4	3	0	0.67	0.09	0.23
Cholangitis of the opposite side of the bile duct	1	1	1	1.0	1.0	1.0
Technical success of ERI, n (%)	5/5 (100)	4/4 (100)	1/1 (100)	NA	NA	NA
Clinical success of ERI, n (%)	5/5 (100)	4/4 (100)	1/1 (100)	NA	NA	NA
Endoscopic revision (unilateral ENBD/ bilateral ENBD/ bilateral IS)	4 / 0 / 1	3 / 0 / 1	0 / 1 / 0	-	-	-
Procedure time of ERI (min), median (range)	16 (10–50)	18 (14–28)	16	0.77	1.0	1.0
PS: plastic stent
IS: intraductal plastic stent
ENBD: endoscopic nasobiliary drainage
PEP: post-endoscopic retrograde cholangiopancreatography pancreatitis
RBO: recurrent biliary obstruction
ERI: endoscopic re-intervention
NA: not available

RBO and Endoscopic re-intervention

RBO occurred in 5 patients in the PS group (42%; 4 sludge occlusions and 1 case of cholangitis of the non-drained IHBD side), 4 patients in the IS group (29%; 3 sludge occlusions and 1 case of cholangitis of the non-drained IHBD side), and 1 patient in the ENBD group (9%; cholangitis of the non-drained IHBD side). No significant difference was observed in the RBO occurrence rate between the pairs of groups.

Endoscopic re-intervention (ERI) was attempted in all patients with RBO. Technical and clinical success was achieved in all ERI cases. The drainage methods used in the ERI cases were as follows: PS group (unilateral ENBD = 4, bilateral IS = 1), IS group (unilateral ENBD = 3, bilateral IS = 1), and ENBD group (bilateral ENBD = 1). The median procedure time for ERI was 16 (10–50) min in the PS group, 18 (14–28) min in the IS group, and 16 min in the ENBD group. There was no significant difference in the ERI procedure time between each group pair.

When evaluating the RBO-related factors, external fistula (ENBD group), performance status (0), and PTPE tended to be significant in the univariate analysis. However, the multivariate analysis showed that these factors were not related to RBO occurrence (Supplemental Table 1).

TRBO and OS

The median TRBO was 73 (8–86) days in the PS group. The median TRBO was not reached in the IS and ENBD groups. There were no significant differences among the TRBO groups (Fig. 3). When the drainage method was divided into internal (PS and IS groups) and external (ENBD group) fistulas, there was no significant difference in the median TRBO (P = 0.37, Supplemental Fig. 1). The median OS was 1393 (299–2460) days in the PS group and 1376 (200–2409) days in the PS and ENBD groups, respectively. In the IS group, the median OS was not reached. There were no significant differences between the pairs of groups (Fig. 4).

When evaluating TRBO-related factors, age (> 70 years), performance status (0), and PTPE tended to be significant in univariate analysis. However, the multivariate analysis showed that these factors were not related to TRBO (Supplemental Table 2).

When evaluating OS-related factors, PTPE was significantly related (P = 0.03), and MHBO length (> 15 mm) also tended to be significant. However, the multivariate analysis showed that these factors were not related to OS (Supplemental Table 2).

Surgical outcomes and histopathological findings

The surgical and histopathological outcomes are summarized in Table 3. Regarding surgical outcomes, there were no significant differences between each group pair, including the surgical procedure (hepatectomy or hepatopancreatoduodenectomy), median operation time, median amount of intraoperative blood loss, median hospital stay for surgical resection, or post-surgical AEs. The Clavien-Dindo classification grade of all post-surgical AEs was IIIa or IIIb. Cases of SSI and bile leakage were treated with percutaneous and/or endoscopic drainage, and bleeding was treated with arterial embolization via angiography.

Table 3

Surgical and histopathological outcomes
	PS	IS	ENBD	P-value
	n = 12	n = 14	n = 11	PS vs IS	ENBD vs PS	ENBD vs IS
Surgical procedure,n (%)
Hepatectomy	11 (92)	11 (79)	8 (73)	0.60	0.32	1.0
Hepatopancreatoduodenectomy	1 (8)	3 (21)	3 (27)	0.60	0.32	1.0
Operation time (min), median (range)	449 (399–638)	631 (288–1053)	493 (427–599)	0.15	0.67	0.19
Intraoperative blood loss (mL), median (range)	1067 (420–4300)	870 (142–7000)	1580 (1320–1860)	0.33	0.10	0.11
Post-surgical AEs, n (%)	3 (25)	4 (29)	2 (18)	1.0	1.0	0.66
Bile leakage	1	1	1	1.0	1.0	1.0
Surgical site infectiuon	2	3	0	1.0	0.48	0.23
Bleeding	1	0	1	0.46	1.0	0.44
Clavien-Dindo Classification
IIIa	3	3	2	1.0	1.0	1.0
IIIb	1	1	0	1.0	1.0	1.0
Hospital stay duration for surgical resection (day), median (range)	45 (12–117)	44 (8-137)	32 (19–79)	0.37	0.83	0.62
Resectability, n
R0	5	10	4	0.23	0.12	1.0
R0 / R1 / R2	5 / 6 / 1	10 / 3 / 1	4 / 7 / 0
UICC Stage, n				0.061	0.21	0.21
I / II / III / IV	2 / 7 / 3 / 0	2 / 2 / 9 / 1	0 / 4 / 5 / 2
Histopathological differentiation, n
well	11	5	4	< 0.01	< 0.01	1.0
mod	1	4	6	0.33	0.027	0.24
por	0	3	0	0.22	NA	0.23
other	0	2	1	0.48	0.48	1.0
PS: plastic stent
IS: intraductal plastic stent
ENBD: endoscopic nasobiliary drainage
AEs: adverse events
NA: not available

In the univariate analysis, age (> 70 years) and performance status (0) were significantly associated. However, multivariate analysis showed that these factors were not related to post-surgical AEs (Supplemental Table 3).

Regarding the histopathological findings, there were no significant differences in the complete (R0) resection rate or UICC for the International Cancer Control stage in each group pair. The number of histopathological differentiations (well) was significantly higher in the PS group than in the IS (P < 0.01) and ENBD (P < 0.01) groups.

Our study evaluated the utility of three unilateral PBD methods for liver resection based on the expected swelling of the FRL^8,15,16. Because the risk of cholangitis on the non-drained side of the IHBD has been reported for unilateral biliary drainage in unresectable MHBO cases^21,22, unilateral PBD also needs to be considered for cholangitis of the non-drained side of the IHBD. Our study had one case of cholangitis in non-drainage areas in each group, and these cases required bilateral drainage until surgical resection. However, the other patients underwent surgery with unilateral drainage, and there was no difference in the number of cases requiring bilateral drainage in each group pair. Therefore, none of the three different PBD methods increased infection on the non-drainage side, and it seemed acceptable to perform only unilateral PBD, regardless of PBD methods.

The presence of preoperative cholangitis affects post-surgical AEs and liver failure^5–7. ENBD drainage can be considered the most reliable method for managing drainage problems owing to the direct observation of bile flow. However, there were no significant differences between the two drainage methods in terms of surgical outcomes or post-surgical AEs. In addition, hospital stay for the endoscopic procedure was significantly longer in the ENBD group that required ENBD management. Long-term hospital stays and ENBD placement increase medical costs and decrease the quality of life (QOL)^23–25. The RBO occurrence rate and TRBO also showed no significant difference in each group pair, and the multivariate analysis for RBO occurrence and TRBO did not show any significance in the factors of external fistula (ENBD group) (Fig. 3, Table 2, and Supplemental Table 1–2). Therefore, the superiority of ENBD placement cannot be confirmed for unilateral PBD in liver resection cases.

The absence of an external fistula did not show significance related to stent patency and surgical waiting times. Usually, PS had 2–3 months of stent patency^26,27. In our study, surgery was performed approximately 1–2 months after the endoscopic procedure (Fig. 3) to avoid stent dysfunction by surgical procedure. Therefore, in cases where a surgical procedure is expected to be performed within a few months, unilateral internal fistulas (PS and IS placement) are acceptable, considering the costs associated with prolonged hospitalization and the reduction in patients’ QOL.

Regarding the selection of internal fistula type, our study did not observe a significant difference between the PS and IS groups in terms of RBO occurrence, TRBO, surgical outcomes, and OS. One comparative study of PS and IS for PBD included bilateral drainage and non-liver resection cases¹². In this study, it was reported that stent patency after IS placement was similar to that after PS placement. Because the surgery was performed approximately 1 month after stent placement, it was difficult to determine the superiority of IS placement owing to the short surgical waiting time.

In contrast, because RBO tended to increase 2 months after stent placement (Fig. 3), the difference between PS and IS placement may become clearer in cases with a long surgical waiting period. Neoadjuvant chemotherapy (NAC) was recently developed for HCCA²⁸. If NAC becomes the standard treatment in the future, the surgical waiting time will be extended, and the risk of stent dysfunction will increase. Therefore, it is important to select a stent type with a longer stent patency. IS placement was reported to have longer stent patency than PS placement because the risk of biofilm formation may be reduced owing to the avoidance of intestinal content reflux in unresectable MHBO cases^29,30. For PBD, one report that was observed for a long period after PS and IS placement, IS placement reported a longer patency period¹⁴. Prospective studies, including those on the use of NAC, are needed to evaluate the proper use of PS and IS placement for PBD.

Our study had several limitations. First, this was a small retrospective study. As no study has evaluated the three transpapillary PBD methods for liver resection and unilateral PBD for the FRL in HCCA, our study limited the inclusion criteria to select suitable cases for evaluation. Second, there were no criteria, including the selection of the PBD method, owing to the retrospective study design. However, since there were no significant differences in patient characteristics between each group pair, it was possible to evaluate the endoscopic and surgical outcomes. To resolve these limitations, a prospective randomized controlled trial should be conducted.

In conclusion, the preoperative unilateral PS, IS, and ENBD drainage methods showed similar clinical outcomes in liver resection cases of HCCA, excluding the duration of hospital stay for the endoscopic procedure. Considering the duration of hospital stay, unilateral PS and IS placement can be considered acceptable for PBD. To evaluate the proper use of PS and IS placement, prospective studies are needed, including a long-term observation period, such as NAC for HCCA.

AEs, adverse events; CBD, common bile duct; CI, confidence interval; CT, computed tomography; ENBD, endoscopic nasobiliary drainage; ERCP, endoscopic retrograde cholangiopancreatography; ERI, endoscopic re-intervention; ES, endoscopic sphincterotomy; FRL, future remnant liver; HCCA, hilar cholangiocarcinoma; HR, hazard ratio; IHBD, intrahepatic bile duct; IS, intraductal plastic stent; MHBO, malignant hilar biliary obstruction; NAC, neoadjuvant chemotherapy; OR, odds ratios; OS, overall survival; PBD, preoperative biliary drainage; PEP, post-ERCP pancreatitis; PS, plastic stent; PTBD, percutaneous transhepatic biliary drainage; PTPE, percutaneous transhepatic portal embolization; QOL, quality of life; RBO, recurrent biliary obstruction; SSI, surgical site infection; TRBO, time to recurrent biliary obstruction

Author's contribution

Conceptualization, methodology, formal analysis: Mitsuru Okuno, Keisuke Iwata, Tsuyoshi Mukai

Investigation: Mitsuru Okuno, Kota Shimojo, Yosuke Ohashi,Shota Iwata, Yuhei Iwasa, Akihiko Senju, Kensaku Yoshida, Akinori Maruta, Ryuichi Tezuka, Hironao Ichikawa, Naoki Mita, Shinya Uemura,

Writing original draft preparation: Mitsuru Okuno

Writing review and editing: Keisuke Iwata, Tsuyoshi Mukai

Supervision: Takuji Iwashita, Eiichi Tomita, Ichiro Yasuda, Masahito Shimizu

Conflicts of interest:

All authors have no Conflict of Interest for this article.

Acknowledgment:

This work was supported by JSPS KAKENHI Grant Number JP23K14646

Data availability

The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.

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No competing interests reported.

SupplementalFigure1.tiff
Supplemental Figure 1. Kaplan–Meier curve showing TRBO of internal (PS and IS) and external fistula (ENBD) group. There was no significant difference between both groups. TRBO: Time to recurrent biliary obstruction PS: plastic stent IS: intraductal plastic stent ENBD: endoscopic nasobiliary drainage
SupplementalTables.docx

Comparison of the preoperative transpapillary unilateral biliary drainage methods for the future remnant liver in patients with hilar cholangiocarcinoma

Status:

Version 1

Abstract

Figures

Introduction

Methods

Study design and patients

Procedure

Study endpoints and definitions

Statistical analyses

Results

Patient selection and characteristics

Endoscopic procedures and AEs

RBO and Endoscopic re-intervention

TRBO and OS

Surgical outcomes and histopathological findings

Discussion

Abbreviations

Declarations

References

Additional Declarations

Supplementary Files

Status:

Version 1