Hepatobiliary scintigraphy of bile excretion after endoscopic ultrasound-guided hepaticogastrostomy for malignant biliary obstruction: a retrospective study in Japan

Article information

Clin Endosc. 2024;.ce.2023.291

Publication date (electronic) : 2024 August 20

doi : https://doi.org/10.5946/ce.2023.291

Masanori Yamada, Kazuo Hara, Shin Haba, Takamichi Kuwahara, Nozomi Okuno, Yasuhiro Kuraishi, Takafumi Yanaidani, Sho Ishikawa, Tsukasa Yasuda, Toshitaka Fukui

Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan

Correspondence: Kazuo Hara Department of Gastroenterology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan E-mail: khara@aichi-cc.jp

Received 2023 November 16; Revised 2024 February 21; Accepted 2024 February 22.

Abstract

Graphical abstract

INTRODUCTION

Biliary drainage guided by endoscopic retrograde cholangiopancreatography (ERCP), is the gold standard for treating biliary obstruction.1 However, ERCP may not be feasible in complex cases of duodenal obstruction or surgically altered anatomy. As an alternative, percutaneous transhepatic cholangiography can be used; however, it has several disadvantages, such as external drainage and cosmetic concerns.2,3 Endoscopic ultrasound-guided biliary drainage (EUS-BD) has been developed as an alternative method for failed ERCP or percutaneous transhepatic biliary drainage.4,5 Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) can be performed in cases of duodenal bulb obstruction and surgically altered anatomy.6 Recent developments in medical devices have enabled the performance of HGS without the need for intrahepatic bile duct dilatation, broadening its range of indications.7-9

Hepatobiliary scintigraphy (HBS) is a physiological and non-invasive imaging method used to evaluate liver function, gallbladder function, duodenal papillary function, and bile excretion. ^99mTc-pyridoxal-5-methly-triptophan (^99mTc-PMT) stands out as an effective radiotracer among ^99mTc-pyridoxylaminates, and is used in HBS to diagnose diseases related to hepatobiliary function and system in Japan.10-12 In evaluating bile excretion with HBS using ^99mTc-PMT, the peak time, appearance time, decay time, and decay rate for each region are calculated from the time-activity curve (TAC) of the region of interest (ROI) set on the scintigram, facilitating a quantitative evaluation. Although bile excretion in HGS is expected to be non-physiological, it has not yet been studied. Therefore, this study aims to evaluate bile excretion in HGS using HBS.

METHODS

Study design

This single-center retrospective study was conducted at the Aichi Cancer Center Hospital. This study examined consecutive patients with malignant extrahepatic biliary obstruction who underwent HBS within one month of HGS between April 2015 and July 2022. However, patients with malignant extrahepatic biliary obstruction, in which the right and left hepatic ducts were separated, were excluded because transpapillary right biliary drainage was often performed in such patients in addition to HGS. Further, patients who received plastic stents for HGS stents and those who underwent HGS in conjunction with antegrade stenting were also excluded. Finally, a total of 78 consecutive patients with malignant extrahepatic biliary obstruction who underwent HBS after HGS were examined during the study period. A flowchart of the study is shown in Figure 1. This study was approved by Aichi Cancer Center Hospital (approval number: 2121-0-254). Informed consent was obtained from each patient for both the HGS and HBS procedures.

Fig. 1.

Study flowchart. Flowchart of 123 consecutive patients with malignant extrahepatic biliary obstruction who underwent hepatobiliary scintigraphy (HBS) within one month of undergoing hepaticogastrostomy (HGS) at Aichi Cancer Center Hospital between April 2015 and July 2022. Nine patients with separated left and right hepatic ducts due to malignant tumors, three patients who underwent HGS using plastic stents, and 33 patients who underwent HGS combined with antegrade stenting were excluded. Finally, a total of 78 consecutive patients with malignant extrahepatic biliary obstruction who underwent HBS after HGS were examined during the study period.

Hepatobiliary scintigraphy

HBS images are shown in Figure 2, and an example of an HBS video is shown in Supplemental Video 1. In all the studied patients, HBS was performed within one week to one month following HGS. The isotope preparation used for HBS was ^99mTc-PMT (185 MBq). Patients were required to fast in the morning before the isotopes were administered intravenously, while they lay in a supine position. The examination time was 60 minutes, during which sequential dynamic abdominal images were captured every 30 seconds. A video lasting a total of 6 seconds was compiled from these images (60× speeds). The ROI was set at the hilar bile duct, and a TAC was created. Peak time and decay rate were calculated from the TAC, using a scale to evaluate bile excretion. Peak time was defined as the time of maximum accumulation, and the decay rate was defined as the difference between the maximum and minimum accumulation divided by the maximum value. Peak time is the time required for the existing bile in the bile duct to be excreted and replaced by isotope-labeled bile. A shorter peak time indicated better bile excretion. The decay rate is the ratio of isotope-labeled bile excreted within the test time. A higher decay rate indicated better bile excretion.

Fig. 2.

Hepatobiliary scintigraphy. (A) The region of interest (ROI) set at the hilar bile duct. (B) Time-activity curve (TAC). The peak time and decay rate were calculated from the TAC and used as a scale to evaluate bile excretion. An example of a hepatobiliary scintigraphy is shown. The peak time and decay rate, in this case, are 10 minutes and 68.9%, respectively. (C) Key images at 5, 10, 20, and 60 minutes. At 5 minutes, the bile is excreted into the stomach via the hepaticogastrostomy (HGS) route. At 10 minutes, the accumulation in the hilar bile duct is maximal. At 20 minutes, the accumulation in the hilar bile duct is reduced, and at 60 minutes, the accumulation in the hilar bile ducts is further reduced, with most of the isotope-labeled bile excreted into the stomach. Supplemental Video 1 shows this case.

The scatter plots and scoring systems based on the peak time and decay rate for the 78 cases derived from biliary scintigraphy are shown in Figure 3. From this scatter plot, the peak time and decay rate were assigned scores of 0, 1, or 2 points based on thresholds of 20 and 35 minutes, and 10% and 50%, respectively. Bile excretion was then evaluated based on the sum of these scores. A total score of 4 or 3 indicates good bile excretion, whereas scores of 2, 1, or 0 indicate poor bile excretion. Examples of biliary scintigraphy findings in HGS cases classified according to the scoring system are shown in Figure 4.

Fig. 3.

Scatter plots and scoring system created based on peak time and decay rate for each case obtained from hepatobiliary scintigraphy. Scatter plots and scoring systems. From this scatter plot, the peak time and decay rate were scored as 0, 1, and 2 points based on 20 and 35 min, and 10% and 50%, respectively, and bile excretion was evaluated based on the sum of these scores. A total score of 4 or 3 was defined as good bile excretion, while scores of 2, 1, or 0 indicated poor bile excretion.

Fig. 4.

Examples of biliary scintigraphy in hepaticogastrostomy (HGS) cases classified according to the scoring system. In cases with a total score of 0, isotope-labeled bile stagnates in the bile ducts and excretion from the HGS route is poor. In cases with a total score of 4, the isotope-labeled bile was not stagnant and was excreted through the HGS route early on. In cases with a total score of 2, bile excretion was intermediate, ranging from 0 to 4. Supplemental Videos 2 and 3 show the cases with total scores of 4 and 0, respectively.

RESULTS

This study included 43 male (55.1%) and 35 female (44.9%) participants, with ages ranging from 24 to 85 years (median, 68 years). The primary diseases were all malignant, including pancreatic (41 patients, 52.6%), gastric (12 patients, 15.4%), bile duct (5 patients, 6.4%), duodenal (5 patients, 6.4%), gallbladder (5 patients, 6.4%), papillary (2 patients, 2.6%), and other malignancies (8 patients, 10.3%). The primary indications for undergoing endoscopic EUS-HGS were categorized as either primary and salvage drainages in 53 (67.9%) and 25 (32.1%) patients, respectively. Salvage drainage cases included those converted from attempted percutaneous transhepatic biliary drainage, cases difficult for ERCP and EUS-guided choledochoduodenostomy due to duodenal invasion, and cases of ERCP cannulation failure. Bile duct obstructions were classified based on their location as either upstream (upper biliary obstruction, n=19; 24.4%) or downstream (middle and lower biliary obstruction, n=59; 75.6%) areas, bordering the confluence of the cystic duct, using CT and MRI. Duodenal stents were placed in 16 patients (20.5%) due to duodenal obstruction. Sixteen patients (20.5%) had surgically altered anatomy, including Roux-en-Y (n=7), gastrojejunostomy (n=7), and Billroth II (n=2). Peritoneal dissemination was observed in 20 (25.6%) patients and ascites was observed in 15 patients (19.2%). Six (7.7%) patients had undergone cholecystectomy. The stenting routes were B2 and B3 in 50 (64.1%) and 28 (35.9%) patients, respectively. The clinical success rate was 100%. Early adverse events were observed in four cases, including peritonitis, cholangitis, and cholecystitis in one, two, and one case, respectively. Late adverse events were observed in one case, which was a case of biloma (Table 1).

Table 1.

Patient characteristics of hepaticogastrostomy (n=78)

The TRBO values of the good and poor bile excretion groups are shown in Figure 5. The TRBO in the good bile excretion group was significantly longer than that in the poor bile excretion group (p=0.026); the good excretion group did not reach the median TRBO value, while the median TRBO of the poor bile excretion group was 124 days.

Fig. 5.

Comparison between the good and poor bile excretion groups concerning the time to recurrent biliary obstruction (TRBO). The TRBO of the good bile excretion group was significantly longer than that of the poor bile excretion group; the good excretion groups did not reach the median TRBO value, while the median TRBO of the poor bile excretion group was 124 days. days (not reached vs. 124 days, p=0.026; log-rank test).

Univariate and multivariate analyses of the clinical factors affecting the rate of good bile excretion, which were evaluated using HBS, are presented in Table 2. The following variables with p<0.2 in the univariate analysis were included in the multivariate analysis: obstruction site, duodenal stent, peritoneal dissemination, and ascites. The multivariate analysis indicated that the site of obstruction was significantly associated with the rate of good bile excretion (odds ratio, 3.39; 95% confidence interval, 1.01–11.4, p=0.049), and upper biliary obstruction was associated with good bile excretion.

Table 2.

Univariable and multivariable analyses of clinical factors affecting rate of good bile excretion evaluated by hepatobiliary scintigraphy

DISCUSSION

In this study, HBS was used to assess bile excretion after HGS. Prior to this research, there had been no studies examining bile excretion post-endoscopic biliary drainage using HBS, highlighting the need to establish evaluation criteria. The evaluation of bile excretion employs both peak time and decay rate, yet each metric has its own limitations. Peak time measures the duration for the bile initially present in the bile duct to be expelled and replaced by isotope-labeled bile, indirectly assessing the excretion of isotope-labeled bile. In contrast, the decay rate is the ratio of isotope-labeled bile excreted within the test time, which directly evaluates the isotope-labeled bile itself. However, given that the examination duration was set to 60 min for all cases, and peak times varied from case to case; the time remaining post peak time was often not consistent. Therefore, cases with prolonged peak times often showed lower decay rates. However, there were also cases with late peak times but high decay rates, as well as cases with early peak times but low decay rates. Hence, a combined assessment of both metrics can enhance the efficacy of the evaluation criteria for HBS. A scoring system, derived from scatter plots based on the peak time and decay rate, was used to categorize patients into either good or poor bile excretion groups.

TRBO was significantly longer in the good bile excretion group, and the evaluation based on the scoring system showed a correlation with stent patency. Multivariate analysis of factors associated with bile excretion, as evaluated using HBS, identified the site of obstruction as the only significant factor. Patients with upper biliary obstruction experienced better bile excretion compared to those with middle or lower biliary obstruction. HBS footage of cases with upper biliary obstruction showed that, in cases with good bile excretion, the amount of isotope-labeled bile flowing into the extrahepatic bile duct was small and excreted from the HGS stent in many cases as shown in Supplemental Video 2. In contrast, HBS videos of cases with middle and lower biliary obstruction show good bile excretion, with little inflow of isotope-labeled bile into the extrahepatic bile duct. However, cases showing poor bile excretion, characterized by reduced bile excretion from the HGS stent, resulted from the inflow and stagnation of isotope-labeled bile into the extrahepatic bile duct, as shown in Supplemental Video 3. In cases of middle and lower biliary obstruction, the extrahepatic bile duct is wide, and in some cases, the bile tends to stagnate, possibly leading to biliary stasis.

This study has several limitations. Firstly, it was a single-center, retrospective study, and there was variability in patient characteristics and the types of biliary stents used. Secondly, our hospital adopts a strategy of periodically replacing plastic stents in patients undergoing chemotherapy. This approach aims to prevent segmental cholangitis, biloma, and secondary stenosis, which can arise from the prolonged use of metal stents and lead to hyperplasia. Therefore, several censored cases were included in this TRBO study. A scoring system was developed to assess bile excretion capability as evaluated by HBS and TRBO; however, this system may be inaccurate to some degree. To develop more accurate criteria for the evaluation of bile excretion by HBS, it is necessary to conduct a prospective study with a larger sample size, consistent patient characteristics, and fewer censored cases.

In conclusion, the site of the obstruction is significantly associated with the stent patency of HGS. Bile excretion from the HGS may be prone to greater bile stagnation and stasis with a wider extrahepatic bile duct. Therefore, in cases of middle and lower biliary obstruction, it may be better to consider HGS with antegrade stenting, or an alternative method to HGS, if feasible. However, further research is necessary to validate this recommendation.

Supplementary Material

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