Laparoscopic cholecystectomy is the first-line treatment for acute cholecystitis. However, patients with high age, severe heart disease, respiratory disease, or advanced cancer, gallbladder drainage is recommended as an alternative therapy.¹ Percutaneous transhepatic gallbladder drainage (PTGBD) is the most widely used technique, and its clinical improvement rate is about 90%.^2,3 However, the reported accidental complications, such as hemorrhage, pneumothorax, and bile peritonitis, occur in approximately 12%–15% patients.^4,5 Although endoscopic transpapillary gallbladder drainage (ETGBD) is an alternative to PTGBD, this therapeutic technique is frequently challenging due to the difficulty in selecting cystic duct and cannulating to the gallbladder.⁶ In recent years, endoscopic ultrasound-guided gallbladder drainage (EUSGBD) has been evolved to manage acute cholecystitis, in particular patients who are unsuitable for cholecystectomy, PTGBD, or ETGBD.⁷ Recent studies reported technical and clinical success rate of EUS-GBD was 90.0%–98.7% and 89.0%–98.4%, respectively.⁸ The adverse events, such as bile leakage, stent occlusion, and stent migration, after EUS-GBD using plastic stents and selfexpandable metallic stents (SEMS) occurred in 18.2% and 12.3%, respectively.⁹

Recently, a newly designed metal stent with a thin, tapered delivery catheter (Covered BileRush; Piolax Medical Devices Inc.) was introduced to skip dilation step during EUS-guided choledochoduodenostomy. However, there have been no reports regarding the feasibility, safety, and longterm outcomes of EUS-GBD with this newly designed metal stent. Therefore, we evaluated the clinical outcomes of EUS-GBD with the newly designed metal stent in this study.

Study design

The present study is a single-center retrospective cohort study. The primary outcome was the technical success rate of EUS-GBD. The secondary outcomes were the clinical success rate, cholecystitis recurrence rate, treatment-related adverse event rate, procedure time, and success rate of stent placement without using needle tract dilatation devices of EUS-GBD.

Patients

Patients with acute cholecystitis between April 2017 and March 2020 were included if they were ineligible for emergency cholecystectomy after surgical and anesthesiological evaluation. The diagnosis of acute cholecystitis was made if the patient met the Tokyo guideline criteria for cholecystitis, which included classic symptoms (right upper quadrant pain, fever, and leukocytosis) and findings of the thickened gallbladder wall on transabdominal ultrasonography or computed tomography (CT).¹⁰ We performed either of alternative non-surgical approaches, including percutaneous, transpapillary, or EUS-guided gallbladder drainage. Among them, we systematically collected data from patients who underwent EUS-GBD. Additionally, the patient was given informed consent before the endoscopic procedure. The protocol conforms to ethical guidelines in the Declaration of Helsinki (Fortaleza, October 2013, revised edition) and has been approved by the Ethics Committee of Wakayama Medical University.

Study device

The newly designed metal stent (Covered BileRush), with a diameter of 6 mm and a length of 6 cm is delivered through a 7.5 Fr delivery catheter with a sharp tip (Fig. 1). This new metal stent is equipped with antimigration structures and allows for easier penetration of the gallbladder because of its fine tapered tip and thin delivery catheter. To provide anchorage within the gallbladder and the gastrointestinal tract, the stent is made of laser-cut nitinol that is partially covered with a silicone membrane (5 mm of the distal portion is uncovered) with a flared structure at both end portions (sized 10 mm diameter).

Figure 1. Illustration of the newly designed metal stent used in the present cases (Covered BileRush; Piolax Medical Devices Inc.). (A) The newly designed metal stent mounted on a 7.5 Fr delivery system with a very sharp distal tip. (B) The stent, with a diameter of 6 mm and a length of 6 cm, being partially covered with a membrane except for 5 mm of the distal end. A flare structure 10 mm in diameter provides anchoring within the gallbladder and the gastrointestinal tract.

EUS-GBD procedure

EUS-GBD was performed under fluoroscopy using a conventional linear array echoendoscope (GF-UCT 260; Olympus Optical). All patients were sedated with intravenous administration of midazolam or propofol. We selected the duodenal bulb as a puncture site to access the body of the gallbladder or the neck, with no vessels in between. Using a 19-gauge needle (Sono Tip Pro Control 19 G; Medi-Globe GmbH), the gallbladder was punctured through the duodenal wall (Fig. 2A), then the bile was aspirated and cultured for microorganisms. Afterward, we injected the contrast media into the gallbladder under the X-ray fluoroscopy. A 0.025-inch guidewire (VisiGlide 2; Olympus Medical Systems) was passed through the needle and coiled into the gallbladder (Fig. 2B). In principle, the needle tract dilation devices were not used after removal of the needle, and the stent delivery system was immediately inserted into the gallbladder (Fig. 2C). After that, the distal flared structure of the stent was released under ultrasonographic guidance. The flared structure was then extended, and the delivery catheter was carefully retracted to hook the flare portion onto the inside of the gallbladder wall (Fig. 2D). The stent was then further released within the channel of the echoendoscope. Finally, we pushed out the delivery catheter, and slightly move the tip of the echoendoscope away from the duodenal wall until it was completely released (Fig. 2E, 2F). When it was difficult to insert the stent delivery system due to resistance in passing through the duodenal and gallbladder walls, we dilated the needle tract using a 4-mm balloon catheter (REN; Kaneka Medix) (Supplementary Materials).

Figure 2. Endoscopic ultrasound (EUS)-guided gallbladder drainage with the newly designed metal stent. (A) A 19-gauge needle was inserted into the gallbladder under EUS guidance. (B) A 0.025-inch guidewire was coiled inside the gallbladder using fluoroscopic image guidance. (C) A newly designed metal stent was inserted into the gallbladder. (D) The distal flare structure was hooked onto the gallbladder wall with careful retraction of the delivery system, and the stent was deployed under EUS guidance. (E) The metal stent was placed over the guidewire. (F) The deployed stent was observed in the duodenal bulb.

Follow-up after EUS-GBD

The patients were fasted 2 days after the procedure and underwent physical and laboratory examinations until symptoms and laboratory abnormalities were resolved. CT was performed in all patients immediately after EUS-GBD and the following morning to confirm the proper location of the metal stent. Patient followup was based on periodic outpatient examinations every 2–3 months. Blood tests and CT scans were performed at each visit. Regular stent replacement or removal was not performed.

Definition of outcomes

The technical success of EUS-GBD was defined as the completion of stent placement between the gallbladder and duodenum. Clinical success was defined as improvement in laboratory test values, the disappearance of signs and symptoms of typical acute cholecystitis, and improvement in radiological findings within 3 days after the procedure of EUS-GBD. Cholecystitis recurrence was defined as the development of acute cholecystitis during follow-up after successful EUS-GBD followed by clinical improvement. As for treatment-related adverse events, we defined early adverse events as those occurring within 2 weeks of EUS-GBD and late adverse events as those occurring after 2 weeks. Adverse events included biliary peritonitis due to bile leak, pneumoperitoneum, fever, abdominal pain, bleeding, infection, and perforation. The procedure time was defined as the time from endoscopic insertion to stent placement for EUS-GBD.

Statistical analysis

Statistical analysis was carried out using JMP Pro version 16 (SAS Institute). Descriptive statistics for quantitative variables were expressed as the mean (standard deviation) or median (interquartile range [IQR]), whereas categorical variables were expressed as percentages. The Kaplan–Meier method was used to estimate the survival and stent patency rate.

Fig. 3 shows the patient flow chart. Between April 2017 and March 2020, 57 patients with acute cholecystitis, who were considered unsuitable for cholecystectomy, were admitted to our hospital. Of these, 26 patients underwent PTGBD and/or percutaneous transhepatic gallbladder aspiration. ETGBD and conservative treatment were performed in 2 and 8 patients, respectively. The remaining 21 patients underwent EUS-GBD with this newly designed metal stent. The baseline characteristics are summarized in Table 1. The patients’ median age was 75 years (IQR 68.0–83.3), and 15 of the 21 patients were male. Acute cholecystitis was caused by calculous cholecystitis (8 cases), malignant biliary obstruction (12 cases), and xanthogranulomatous cholecystitis (1 case). All patients were considered unsuitable for cholecystectomy because of an advanced malignancy with a poor prognosis, an American Society of Anesthesiologist physical status classification score of III–IV, or because of their older age. Of these, placement of a transpapillary metal stent caused acute cholecystitis in 4 cases of pancreatic cancer. EUS-GBD was performed as emergency drainage in 19 patients. In the remaining 2 patients, a PTGBD tube was initially placed, after which internal drainage was established by EUS-GBD during the course.

Figure 3. The strategy of endoscopic ultrasound-guided gallbladder drainage procedure. PTGBA, percutaneous transhepatic gallbladder aspiration; PTGBD, percutaneous transhepatic gallbladder drainage; ETGBD, endoscopic transpapillary gallbladder drainage; EUS-GBD, endoscopic ultrasound-guided gallbladder drainage.

Table 1 . Characteristics of 21 Patients Who Underwent EUS-GBD (n = 21).

Characteristic	Value
Age (yr)	75 (68.0–83.3)
Sex
Male	15
Female	6
Causes of cholecystitis
Calculous cholecystitis	8
Malignant obstruction of cystic duct	12
Xanthogranulomatous cholecystisis	1
ASA classification
III	6
IV	2
Purpose of EUS-GBD
High risk of surgery	7
Advanced malignancy	12
Conversion after PTGBD	2

Values are presented as median (interquartile range) or number only.

ASA, American Society of Anesthesiologist; EUS-GBD, endoscopic ultrasoundguided gallbladder drainage; PTGBD, percutaneous transhepatic gallbladder drainage.

Technical and clinical outcomes

The procedural outcomes and adverse events are summarized in Table 2. The technical and the clinical success rate of EUS-GBD with a newly designed metal stent were 95.2% and 100%, respectively. One patient who failed the procedure had a very thick and hard gallbladder wall. Puncture of the gallbladder and placement of a guidewire into the lumen of the gallbladder were successful, a stent placement was not possible because the balloon dilator did not pass through the gallbladder wall. The mean procedure time was 34.5 ± 16.7 minutes. The median total hospital stay was 12 days (IQR 8–29 days). During a metal stent placement, only 5 patients required needle tract dilation using a balloon catheter because of the difficulty of passing the stent delivery catheter, while the remaining 15 patients did not need dilation of the needle tract using dilation devices. Patients who underwent stent placement without needle tract dilation had a significantly shorter procedure time (23.6 ± 9.8 minutes) than patients with needle tract dilation (38.4 ± 17.1 minutes; P = 0.036). The PTGBD tube could be removed in 2 patients who had undergone PTGBD as the initial treatment before conversion to EUS-GBD. There were no treatment-related early or late adverse events.

Table 2 . Procedural Outcomes of EUS-GBD with Newly Designed Metal Stent (n = 21).

EUS-GBD	Outcomes
Technical success rate	20/21 (95.2%)
Clinical success rate	20/20 (100%)
Approach route
Transgastric	0
Transduodenal	21
Metal stent placement without dilation	15/20 (75%)
Procedure time (min, mean ± standard deviation)
All patients	34.5 ± 16.7
Without needle tract dilation (15/20)	23.6 ± 9.8
With needle tract dilation (5/20)	38.4 ± 17.1
Procedural adverse event	0
Procedure-related mortality	0

EUS-GBD, endoscopic ultrasoundguided gallbladder drainage.

Follow-up

The follow-up outcomes are described in Table 3. All 21 patients treated with EUS-GBD (20 successful and 1 unsuccessful) were available for follow-up. The median follow-up period after EUS-GBD was 336 days (IQR 152–919 days). During the followup period, 16 patients died, with the median follow-up period of 271.5 days (IQR 110–425 days). The 5 patients who remained alive had a median follow-up period of 1,135 days (IQR 1,009– 1,675 days). There were no treatment-related deaths, recurrence of cholecystitis, or biliary obstruction during the follow-up period. None of the patients underwent cholecystectomy, reintervention, or intentional removal of the EUS-GBD stent. The Kaplan–Meier curves of overall cumulative survival and overall stent patency are shown in Fig. 4, respectively.

Figure 4. (A) Kaplan–Meier curve showing the cumulative survival of patients after endoscopic ultrasonography-guided gallbladder drainage, with newly designed metal stent. (B) Kaplan–Meier cumulative curves for overall stent patency.

Table 3 . Longterm Outcomes After Endoscopic Ultrasonography-Guided Gallbladder Drainage (n = 21).

After EUS-GBD	Outcomes
Median follow-up period (day)
All patients	336 (152–919)
Alive patients	1,135 (1,009–1,675)
Dead patients	272 (110–425)
Late adverse event (> 2 wk)	0
Status during follow-up
Recurrence of cholecystitis	0
Reintervention	0
Alive	5
Dead	16

Values are presented as median (interquartile range) or number only.

EUS-GBD, endoscopic ultrasoundguided gallbladder drainage.

This study shows that EUS-GBD with the newly designed metal stents has high technical and clinical success rates with no adverse events and could be considered as an alternative treatment for inoperable patients with acute cholecystitis. In addition, EUS-GBD with this novel metal stent demonstrated persistent stent patency showing no recurrence of cholecystitis during longterm follow-up.

In EUS-GBD, plastic stents were used initially.¹¹ However, because this procedure provides stenting via the abdominal cavity, bile leakage may occur through the needle tract. Thereafter, the study indicated that SEMS was less likely to cause adverse events than plastic stents.¹¹ Regarding safety and efficacy, firstly, SEMS has a self-expanding function and can seal the space between the stent and the needle tract, which reduces the risk of bile leakage from the needle tract.¹² However, there is a need to dilate the needle tract before insertion of a thick delivery system to allow stenting. During the period between the dilation of the needle tract and the deployment of the SEMS, there is a considerable possibility that infected bile may leak from the enlarged gallbladder lumen and cause biliary peritonitis. Therefore, a smaller fistulous tract is desirable to prevent that risk. The newly designed metal stent used in this study has a finely tapered tip, and the stent delivery catheter is made thin at 7.5 Fr. Compared to the conventional SEMS, this new stent can be inserted smoothly into the gallbladder with less resistance. Therefore, in 15 cases, the stent delivery catheter was inserted directly after guidewire placement without using the needle tract dilation devices. Notably, patients who underwent stenting without needle tract dilation had a significantly shorter procedure time. This result suggests that a thin, tapered delivery catheter may reduce the need for dilation step of the needle tract, thereby shortening the procedure time, and reducing the risk of adverse events such as infected bile leakage.

Secondly, it is important to maintain longterm stent patency in EUS-GBD. The major cause of stent dysfunction is obstruction or migration of the stent, which occurs frequently in plastic stents due to small luminal diameter. On the other hand, due to the large diameter of SEMS compared to the plastic stents, most of the previous studies have used stents with a diameter of 10 mm as EUSGBD stents, which provides by longterm patency.^7,8,13,14 Although this newly designed stent had a diameter of 6 mm, no stent occlusion occurred during longterm follow-up. In terms of preventing stent migration, the same stent had a 10 mm diameter-flared structure at both ends, which is necessary to anchor it in the gallbladder and gastrointestinal walls. The results showed no cases of stent migration and suggested that EUS-GBD using this new stent can provide sufficient longterm stent patency, prevent stent migration, and maintain sufficient anchoring function.

The most significant advantage of this newly designed metal stent is the excellent longterm stent patency (recurrence-free period of cholecystitis). During the follow-up period (median: 336 days, IQR: 152–919 days), all patients who underwent EUS-GBD did not have a cholecystitis recurrence or stent-related adverse events. In patients who were alive, the median stent patency, particularly, was achieved in > 1,000 days. These results suggest that longterm stent placement after EUS-GBD is feasible without planned stent replacement as long as no clinical symptoms or adverse events occur. Therefore, EUS-GBD with this stent is suitable for patients with poor general conditions and a high risk of complications.

Recently, many studies of EUS-GBD using lumen apposing metal stent (LAMS) have been conducted.^15–19 LAMS has large flanges for anchoring at both ends of the stent so that the lumen of the gastrointestinal tract and the gallbladder wall are brought close to each other to ensure fixation, and it is possible to promote mutual organ adhesion in the condition like the surgically formed anastomosis. Therefore, it is theoretically considered to have the ability to reduce potential bile leakage and prevent migration. Its wide lumen also reduces the stent obstruction risk. Additionally, LAMS has equipped with a cautery delivery system that can skip using the dilation device. However, cauterizing with the tip of a delivery catheter and then continuing to advance it through the gastrointestinal and gallbladder walls can be a risky procedure. The frequency of bleeding depends on the device used to expand the needle tract route. In a recent systematic review, the adverse event rates for needle tract dilation using a balloon catheter and cystotome were 20.4%, and 38.4%, respectively.²⁰ Although the electrocautery tip of the LAMS can be used almost coaxially with the guidewire, the heat may be spread over a larger area than expected and increase the risk of bleeding due to vascular damage caused. Compared to LAMS, using the present metal stent may be able to lower the risk of bleeding during the stent insertion.

There are two limitations to this report. First, it is based on retrospective outcomes, conducted in a single center with a relatively small number of patients. Second, since this study is a single-arm design, it may be difficult to make direct comparisons with other stents or other treatments, such as PTGBD. A large, multicenter, prospective comparative study with a control group undergoing PTGBD is needed to determine appropriate patient selection and treatment strategy.

In conclusion, EUS-GBD using the newly designed metal stent has excellent longterm outcomes and therapeutic safety and could be an alternative treatment option in patients with acute cholecystitis who are unsuitable for surgery.

Supplementary data is available at https://doi.org/10.18528/ijgii240051.

Video legends: First, the gallbladder was described from the duodenal bulb. Using a 19-gauge needle, the gallbladder was punctured through the duodenal wall. Afterward, we injected the contrast media into the gallbladder under the X-ray fluoroscopy. A 0.025-inch guidewire was passed through the needle and coiled into the gallbladder. The stent delivery system was immediately inserted into the gallbladder without dilation. After that, the stent was released under ultrasonographic guidance. The stent was then further released within the channel of the echoendoscope. Finally, it was completely released.

None.

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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