Intraductal Papillary Neoplasm of the Bile Duct Treated with Argon Plasma Coagulation via Endoscopic Ultrasound-guided Choledochoduodenostomy

Abstract

A 93-year-old man presented to our hospital with a fever, abdominal pain, and jaundice. Computed tomography revealed bilateral bile duct dilation, cystic lesions with bile duct communication, and intraluminal solid nodules arising from the bile duct wall. The patient was diagnosed with intraductal papillary neoplasm of the bile duct. Surgery was not performed, considering the patient's age. It was impossible to control cholangitis using conventional endoscopic therapy. We therefore created an access route to the bile duct using endoscopic ultrasound-guided choledochoduodenostomy and inserted a lumen-apposed metal stent. Thereafter, we performed argon plasma coagulation of the tumor in the bile duct, which successfully prevented cholangitis recurrence.

Introduction

Intraductal papillary neoplasm of the bile duct (IPNB) is an epithelial tumor that produces mucus and can cause obstructive jaundice and recurrent cholangitis. IPNB is thought to represent the biliary counterpart of pancreatic intraductal papillary mucinous neoplasm (IPMN) and is thus considered premalignant. All patients with IPNB are recommended for treatment, as mucus produced by tumors often causes recurrent cholangitis and obstructive jaundice, even if the tumor is not malignant. The prognosis of patients undergoing IPNB is relatively good when curative surgery is performed.

A previous systematic review and meta-analysis reported that the absolute survival after IPNB resection was 96% [95% confidence interval (CI): 93-99%] at 1 year, 79% (95% CI: 69-88%) at 3 years, and 65% (95% CI: 46-76%) at 5 years (1). Therefore, the first choice of treatment is surgery because it is the only curative treatment. However, surgery may be difficult because of advanced tumor growth, the patient's general condition, and severe comorbidities. Several studies (2-5,7) have reported that argon plasma coagulation (APC), performed with cholangioscopy either orally or via the percutaneous route, is an effective palliative treatment for inoperable patients.

We herein report a rare case of a patient with IPNB in whom recurrence of cholangitis was successfully prevented by performing APC via an access route created by endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS).

Case Report

A 93-year-old man visited a local clinic with a fever and left upper abdominal pain. Transabdominal ultrasonography revealed dilation of the intrahepatic bile duct. As cholangitis was suspected, the patient was referred to our hospital.

He had a history of diabetes, hypertension, asthma, and cholecystitis (for which cholecystectomy was performed). His medications included ursodeoxycholic acid, vildagliptin, amlodipine, montelukast, and tulobuterol. A physical examination revealed jaundice in the conjunctiva and no abdominal pain.

Laboratory data revealed the following findings: white blood cells: 16,700/μL, total bilirubin: 8.23 mg/dL, direct bilirubin: 6.11 mg/dL, aspartate aminotransferase: 129 IU/L, alanine aminotransferase: 128 IU/L, alkaline phosphatase: 1,388 IU/L, γ-glutamyl transpeptidase: 476 IU/L, and C-reactive protein: 7.33 mg/dL. Other data showed no abnormalities. Abdominal contrast-enhanced computed tomography (CT) revealed severe dilation of the common bile duct and intrahepatic bile duct (Fig. 1a), but no mass lesions or stones were detected in the bile duct near the major papilla. Magnetic resonance cholangiopancreatography (MRCP) also did not reveal any stone but uncovered a papillary tumor showing a high intensity on diffusion-weighted images of the left intrahepatic bile duct (Fig. 1b-d). Transabdominal ultrasound, contrast-enhanced CT and MRCP revealed the absence of tumor progression into the hepatic parenchyma.

Figure 1.

Images of an intraductal papillary neoplasm of the bile duct. a: Contrast-enhanced computed tomography image showing dilation of the bilateral intrahepatic bile ducts and a papillary lesion in the left intrahepatic bile duct (arrow). b-d: Magnetic resonance imaging (MRI) and cholangiopancreatography (MRCP). b: MRI revealing a papillary lesion more definitely on a T2-weighted image (arrow). c: The papillary lesion shows a high-intensity area on diffusion-weighted imaging (arrow). d: MRCP showed marked dilation of the intrahepatic and common bile ducts. e-g: Images of the first endoscopic retrograde cholangiopancreatography (ERCP). e: Major papillae before cannulation show no abnormalities. f: After endoscopic sphincterotomy, the major papilla showed the characteristic ‘fish-eye sign’ of an intraductal papillary mucinous neoplasm (arrows). g: Fluoroscopic cholangiography shows speckled defects in the common bile duct, indicating mucus (arrows).

Initial endoscopic retrograde cholangiopancreatography (ERCP) showed no abnormality of the major papilla (Fig. 1e) but did reveal severe dilatation of the common bile duct and intrahepatic bile duct with no obvious obstructive mechanism. The common bile duct showed speckled defects that appeared as mucus (Fig. 1g). At that time, bile cytology was classified as Class II.

We placed a plastic stent (7 Fr, 7 cm, double pigtail) to treat cholangitis. However, while the cholangitis improved, obstructive jaundice occurred four days later. Therefore, we performed endoscopic sphincterotomy, endoscopic papillary large-balloon dilation, and mucus drainage using retrieval balloon catheters. Major papilla exhibited the so-called “fish-eye sign” of an IPMN (Fig. 1f). The cholangitis improved, and the patient was discharged.

Surgery was not performed because of the patient's age. A self-expandable metal stent (SEMS) was not inserted because of the high risk of stent migration due to bile dilation. Thereafter, cholangitis recurred every month. After eight sessions of ERCP, we learned that this technique was ineffective and performed EUS. Although it was difficult to discriminate mucus from mural nodules using ERCP, EUS revealed that the tumor was located only in the left intrahepatic bile duct, and there was no apparent horizontal progression of the tumor to the extrahepatic bile duct.

Finally, as palliative treatment, we performed argon plasma coagulation (APC) therapy to reduce mucus production, as described in previous reports. First, we performed EUS-CDS and inserted the SEMS (HANAROSTENT^Ⓡ Biliary Full Cover Benefit™ 8 mm×80 mm, 8 mm×60 mm) into the common bile duct (Fig. 2a-d). Two weeks later, the SEMS was removed, and the fistula was dilated gradually from 14 mm to 18 mm using a balloon catheter (Giga II™ Biliary Dilatation Balloon; Century Medical, Tokyo, Japan) (Fig. 2e-g). Esophagogastroduodenoscopy (GIF-HQ290) of the bile duct confirmed rich mucus production and spread of the papillary tumor (Fig. 3a-c). A biopsy revealed a pathological diagnosis of IPNB with low-grade intraepithelial neoplasia.

Figure 2.

Procedure for the creation of an access route using endoscopic ultrasonography-guided choledochoduodenostomy (EUS-CDS). a: EUS revealed dilation of the common bile duct (arrows). b-d: EUS-CDS. b: The common bile duct was punctured under endosonographic guidance, and contrast medium was injected. A guidewire was advanced into the bile duct. c, d: A self-expandable metal stent (SEMS) was inserted. e: Esophagogastroduodenoscopy (EGD) revealed the fistula after removing the SEMS. The access route for EGD insertion was formed. f: Endoscopic dilation from 14 mm up to 18 mm with a balloon catheter. g: No intraperitoneal leakage of contrast medium after balloon dilation.

Figure 3.

APC treatment for the tumor. a: Endoscopic image of the intrahepatic bile duct revealed abundant mucus. b, c: Spreading of papillary tumors to the intrahepatic and extrahepatic bile ducts (arrows). d, e: Tumors were coagulated by APC with a power of 25 watts and a flow rate of 0.6 L/min (arrows). f: Mucus production from the bile duct was markedly reduced by APC treatment.

The first APC procedure was performed with a power of 25 watts and a flow rate of 0.2 L/min, after which a lumen-apposing metal stent (Hot Axios™ System; diameter, 20 mm; length, 10 mm; Boston Scientific Japan, Tokyo, Japan) was inserted (Fig. 4). Additional APC procedures were performed with a power of 25 watts and a flow rate of 0.6 L/min 3 times within 2 weeks (Fig. 3d, e). Finally, we performed APC procedures four times, which markedly reduced mucus production (Fig. 3f) and removed the lumen apposing metal stent (LAMS) at that time. A 7-Fr plastic stent was placed to maintain the fistula. The tumor in the bile duct had spread widely by the time the intervention had almost been completed. After APC therapy, jaundice and liver disorders gradually improved, with no recurrence of cholangitis. Approximately eight months have now passed since the last APC treatment was performed.

Figure 4.

Insertion of the lumen-apposing metal stent (LAMS). a, b: The LAMS was inserted into the access route created using EUS-CDS (arrows). c: Radiographic imaging showed insertion of the EGD into the intrahepatic bile duct through the LAMS.

Discussion

The gold-standard treatment for IPNB is surgery, which is the only radical treatment. Representative surgical methods include hepatectomy, pancreatectomy, bile duct resection, and combinations thereof. However, surgery is invasive, and the recurrence rate after surgery is relatively high (6). Rocha et al. reported that IPNB recurrence after surgery was approximately 51% (20/39) (6). Surgery is generally not performed because it is considered inappropriate for elderly patients with comorbidities. Palliative treatment was used for such patients. APC was performed in some cases, and radio-frequency ablation (RFA) was performed in other cases. Between 2008 and 2022, we searched the numbers of IPNB or biliary papillomatosis that had been treated by APC or RFA in PubMed using keywords such as ‘intraductal papillary neoplasm of the bile duct,' ‘biliary papillomatosis,' ‘argon plasma coagulation,' and ‘radio-frequency ablation.' This revealed that 11 patients (including our patient) during this period had been diagnosed with IPNB or biliary papillomatosis and treated with APC or RFA (Table) (2-5,7-12). Among these 11 patients, APC was performed in 6 cases using the same procedure as in our report. Arai et al. reported that APC treatment for IPNB resolves obstructive jaundice and stabilizes the clinical condition of patients for more than two years (7). Other studies have reported the long-term survival of APC-treated patients, resulting in APC therapy being considered an alternative to surgery.

Table.

Case Reports of IPNB or Biliary Papillomatosis Treated with APC, RFA and Photo-dynamic Therapy.

Reference	Gender	Age (years)	Follow-up	Diagnosis	Scope	Procedure (number of sessions)	Access route	Year	Complication
(2)	Man	86	1 month (died from another disease)	IPNB	EGD GIF-H180	APC (1)	Trans-papillary	2008	None
(3)	Woman	65	17 months (died from another disease)	Biliary papillomatosis	Cholangioscopy	APC (2)	Percutaneous	2009	None
(4)	Man	37	4 months	Biliary papillomatosis	Cholangioscopy	APC (1)	Anastomotic site (post-hepaticojejunostomy)	2009	None
(5)	Man	81	8 months	IPNB	EGD GIF-Q260J	APC (3)	Trans-papillary	2019	None
(7)	Woman	74	2 years	IPNB	EGD GIF-XP260N	APC (3)	Percutaneous	2021	None
(8)	Man	76	10 months	IPNB	Duodenoscopy	RFA Habib (2)	Trans-papillary	2017	None
(9)	Man	71	1 year	IPNB	Cholangioscopy	RFA Habib (1)	Percutaneous	2019	None
(10)	Woman	87	1 year	IPNB	Duodenoscopy	RFA Habib (3)	Trans-papillary	2021	None
(11)	Woman	85	8 months	IPNB	Duodenoscopy	RFA (1)	Trans-papillary	2021	None
(12)	Man	54	4 months	IPNB	Cholangioscopy	Photo-dynamic therapy (1)	Trans-papillary	2022	None
Our report	Man	93	At least 8 months	IPNB	EGD GIF-HQ290	APC (4)	EUS-CDS route	2022	None

IPNB: intraductal papillary neoplasm of the bile duct, EGD: esophagogastroduodenoscopy, APC: argon plasma coagulation, RFA: radio-frequency ablation, GIF: gastrointestinal fiberscope, EUS-CDS: endoscopic ultrasonography-guided choledochoduodenostomy

Natov et al. reported RFA treatment of IPNB via the transpapillary route (8). Furthermore, Hollenbach et al. reported the RFA treatment of IPNB via the percutaneous route (9). Both studies used the Habib™ Endo HPB Catheter (Boston Scientific Corporation, Massachusetts, USA). The outer diameter is 8 Fr (2.7 mm); therefore, it is too thick to insert into the working channel of a cholangioscope. In other words, it is impossible to confirm sufficient ablation because it is difficult to observe the shape and spread of the tumor directly.

In contrast, the APC probe was very slim, with a diameter of 4-5 Fr (1.5 mm). If we insert the ultraslim endoscope into the bile duct, we can perform the procedure directly. This is preferable for RFA. However, the insertion of an ultraslim endoscope into the bile duct via the transpapillary route is often unsuccessful. In addition, when the tumor is located in the peripheral intrahepatic bile duct, an ultraslim endoscope may not be able to reach the tumor. These are the limitations of APC treatment. We attempted to insert the endoscope directly from the major papilla into the bile duct, although this was difficult in the present case. Subsequently, we inserted the cholangioscope under the guidance of the duodenoscope; however, we did not perform this procedure, as the APC device could not be inserted into the channel of the cholangioscope (SpyGlass™ DS, Boston Scientific Japan, Tokyo, Japan). Finally, we performed EUS-CDS followed by APC using an esophagogastroduodenoscope.

In previous reports, all treatments were performed via the percutaneous or transpapillary route. These access routes have the aforementioned advantages and disadvantages. In the present case, we created a new access route using ‘EUS-CDS' for APC therapy. We also performed ‘EUS-CDS' using the Hot Axios™ system (LAMS). Because the LAMS had a diameter of 20 mm, we were able to pass the standard esophagogastroduodenoscope (Olympus GIF-HQ 290, Olympus, Tokyo, Japan) through the LAMS. To our knowledge, this is the first report of EUS-CDS in which LAMS was used as the access route for APC treatment.

Compared with ultraslim endoscopy, standard esophagogastroduodenoscopy results in a better image quality and visibility of tumor spreading and can remove mucus with a water jet. As shown in Fig. 3a, mucus produced by the IPNB obscured the field of view. We used the water-jet function to wash the mucus and the suction function to remove it, although the mucus easily became stuck inside the endoscope. Mucus had to be expelled into the stomach several times before performing APC. In addition, APC made the lesion more visible by inhibiting mucus production. By repeating these processes, we were eventually able to obtain a good field of view, as shown in Fig. 3b. Because of this feature, it is possible to perform APC on a tumor directly and accurately. In addition, this access route allows APC to be performed over a wide region of intrahepatic bile ducts. Scope movement in the bile duct is expected to be difficult because inverted movement is needed. However, in this case, because the bile ducts were significantly dilated, we inserted the endoscope into the wide lumen of the bile duct through the LAMS and reached the tumor located in the left intrahepatic bile duct without using a guidewire. Fluoroscopic imaging was helpful in determining the direction in which the endoscope should be advanced. We performed four APC procedures approximately two weeks before and after inserting the LAMS insertion. This treatment was very effective, as we were able to treat the patient within a short period. One reason for using LAMS was that we expected that multiple sessions would be necessary due to the large amount of mucus and extensive spread of the tumor. In addition, we expected that it would be useful to drain the mucus. Another reason for using LAMS is the risk of bleeding or perforation when balloon dilation is performed every time.

Arai et al. used an ultraslim video upper endoscope (Olympus GIF-XP260N, Olympus, Tokyo, Japan) inserted through a percutaneous dilated fistula (7). They stated that the drawback of APC therapy with percutaneous transhepatic cholangioscopy is the lengthy period needed for preparation, as gradual fistula dilation is necessary before insertion of the scope used to accommodate the APC probe. In addition, when cholangitis recurs, the puncture procedure causes patient discomfort and pain because it involves an external fistula. Similarly, the EUS-CDS access route involves several steps. However, once an internal fistula is formed, repeated APC procedures are possible. Although the number of sessions (APC, RFA, etc.) in previous reports ranged from one to three, we performed four sessions of APC in the present case (Table).

Tsuchida et al. reported a patient with IPNB who was treated only with endoscopic procedures for 10 years (13), suggesting that some patients with benign IPNB can be followed up conservatively without radical resection. Considering this report, the use of topical treatments may increase, although surgery remains the gold-standard treatment.

In conclusion, we performed APC treatment via an access route created using EUS-CDS for the first time. The patient reported no discomfort or pain due to the internal fistula. Furthermore, the use of standard esophagogastroduodenoscopy made it possible to perform APC treatment of the tumor directly and accurately, with a better image quality, visibility, and water jet function than an ultraslim video upper endoscope. Thus, this treatment may be a viable option for inoperable patients, particularly elderly ones. However, the long-term prognosis of endoscopic treatment for IPNB remains unclear; thus, it is necessary to include more cases.

The authors state that they have no Conflict of Interest (COI).