The use of fully covered self-expandable metal stents in the endoscopic treatment of portal cavernoma cholangiopathy

In this single-center retrospective observational study, the efficacy of FCSEMS placement was investigated in patients with symptomatic PCC. Accordingly, FCSEMS was shown to be highly effective in patients with PCC. While the symptoms and strictures were eliminated in all patients with this treatment method, the most common complication observed was acute cholecystitis. The clinical presentation of acute cholecystitis was monitored in all the patients for the first 48 h; majority of the patients responded to conservative treatment. Therefore, according to the results of the present study, we recommend to closely monitor in patients with PCC with gallbladder who are planned to undergo FCSEMS placement, especially during the first 48 h.

Cholangiographic changes (narrowing, segmental upstream dilatation irregularity, undulation, nodular extrinsic defects, and gallstones) can be observed in almost all patients with PCC [12,13,14,15,16]. Abnormalities were seen in the common bile duct, left intra-hepatic ducts, and right intra-hepatic ducts [16]. In general, the main problem underlying the symptoms in patients with symptomatic PCC is thought to be the strictures caused by varices and fibrosis at the common hepatic duct level below the bifurcation, stones in the common bile and hepatic ducts, and in rare cases, stones in the IHBD [9, 14]. In this study, information regarding the cholangiography findings of all patients with PCC could not be provided since the study only included patients with symptomatic PCC. The most common cholangiography findings in our patients were strictures in the common bile duct, common hepatic duct, and/or left hepatic duct. In addition, half of the patients had stones in the common bile duct and/or IHBD.

In patients with symptomatic PCC, endoscopic sphincterotomy, balloon dilation, plastic stent placement, and nasobiliary drainage were the most employed endoscopic treatment methods [19,20,21, 25]. There are a few studies in the literature that included a limited number of patients receiving endoscopic treatment for PCC. The study with the largest number of patients with PCC who received endoscopic treatment was that of Saraswat et al. [26],; they published the data of 130 ERCP procedures performed for biliary strictures in 20 symptomatic patients. In this study, endoscopic sphincterotomy with stone extraction (SE) was performed in eight patients with common bile duct stones and nine patients were treated with plastic stent placement. Eleven patients with postoperative benign biliary strictures were treated (in a total of 101 procedures) with balloon dilation and plastic stent placement; exchange was performed every 3–4 months until liver function tests returned to normal; additionally, cholangiograms returned to normal in 8 of the 11 patients. Complications of ERCP included haemobilia in 9 of 130 and cholangitis in 40 of 130 procedures. As reported in this study, the most common complication (6–60%) observed in the endoscopic treatment of PCC was cholangitis [19, 23, 26]. Cholangitis is caused by an incomplete clearance of calculi and debris accumulated above the strictures. In addition, blockage of plastic stents occurring within a short period of time due to frequent haemobilia is considered another factor involved in the etiology of cholangitis. Consequently, these patients required repeated plastic stent replacements. Inadequate patient adherence to stent replacement time is also thought to cause cholangitis episodes [26]. According to previous studies, the need for repeated endoscopic interventions and the high complication rates associated with it led to a need for alternative treatments for PCC.

There is scarcity of data on the use of FCSEMS in patients with PCC [21, 23, 27,28,29,30]. Reports of previous studies are summarized in Table 3. The use of FCSEMSs including in the common hepatic duct and the common bile duct is thought to obliterate the varices on the surface of the bile duct by compressing the said varices and dilate the fibrotic strictures that can also be encountered in such patients much more effectively [27]. FCSEMS is not a common practice that has been a part of routine practice in the endoscopic treatment of patients with symptomatic PCC, and it is usually employed as a rescue treatment or in patients with a short life expectancy in the form of uncovered metallic stents [21, 23, 27,28,29,30]. A group of researchers used uncovered metallic stents in three patients, which we believe was already contraindicated for this treatment [27]. Another researcher published a case presentation and mentioned using a covered metallic stent, wherein the patient had a covered stent replacement due to bleeding that occurred while removing the previous stent and did not have to undergo stent replacement again [29]. Another researcher had to remove the stent because the patient who had a biliary stricture associated with PCC developed empyema of the gallbladder but reported that the stricture had improved [28]. This study is of considerable importance as it reported the highest number of symptomatic patients with biliary strictures associated with PCC undergoing FCSEMS placement in the literature. In this case series, cholangitis episodes were almost never encountered in patients treated with FCSEMS compared to those treated with other endoscopic methods. The relapse rate was very low (18.1%) and success was achieved with long-term FCSEMS application in all patients who had recurrence. Therefore, FCSEMS indwell time was increased to 12 weeks in the last seven patients.

Patients undergoing endoscopic treatment for PCC are at high risk of developing haemobilia [20, 29, 30]. Bleeding can be monitored during endoscopic sphincterotomy, balloon dilation, and stent replacement [20, 29, 31]. Distinguishing between stones and varices is highly challenging in cases wherein bile duct-related defects are observed on cholangiogram. Severe bleeding due to varices can be encountered during the elimination of these defects using a SE balloon or Dormia basket and may even lead to disrupted duodenoscopic view, which makes it more difficult to continue the procedure [31]. During the endoscopic treatment of our patients with PCC, the guide placed in the IHBD was kept in place until the end of the procedure when removing the stones in the bile duct with a balloon, and even if there was severe bleeding after removal, leading to disrupted endoscopic view, bleeding could be stopped, and effective bile duct drainage was achieved by placing a covered metallic stent under endoscopic guidance. As a matter of fact, one of our patients experienced severe bleeding during the repositioning of the guide that was dropped during sphincterotome-aided SE since the guide had entered the portal vein branches. The bleeding could be stopped after an FCSEMS was placed during the same session following the insertion of a guide into the IHBD under endoscopic guidance. In addition, venous collaterals in the region of the ampulla of Vater may lead to bleeding during papillotomy [27]. Covered metallic stents are also effective in stopping postpapillotomy bleeding [32]. Mutignani et al. [27], reported regarding perioperative bleeding that took place while removing stents in three patients who underwent plastic stent placement for PCC. In the said study, bleeding was stopped by using a covered metallic stent in the first patient (closure of the bilioportal fistula). In previous studies, a pigtail stent was most commonly used during endotherapy. It was stated that pigtails stent were preferred over straight stents as they carry increased bleeding risk as a result of their flank angles [27]. In our patients, no remarkable bleeding was observed after stent replacement.

Partially covered metallic stents are not recommended for patients with PCC. This is because “intimal hyperplastic tissue within metallic stents” are present on the uncovered areas located at the ends of partially covered stents, which can lead stent obstruction as well as bleeding and difficulties during stent removal [27, 29].

Although endoscopic treatment can temporarily relieve bile duct obstruction, it does not treat the underlying cause in patients with PCC. Therefore, it cannot be expected to be effective in the long term. On the other hand, performing direct surgery on the bile duct is not recommended as the first-line treatment due to high mortality and morbidity risks associated with it [33]. In this respect, shunt surgery is the recommended treatment option [33, 34]. It enables the decompression of varices that cause bile duct obstruction, thereby treating the stricture in the bile duct as well as leading to decreased risk of variceal bleeding due to the drop in portal pressure [32, 33]. It also facilitates performing surgery on the bile duct or endoscopic treatment that may be required after shunt surgery. Although shunt surgery was reported to have a low risk of morbidity and mortality, the most important disadvantage of the procedure is its invasive nature [34]. We believe that the use of FCSEMS may lead to a decreased need for proximal splenorenal shunt surgery since majority of our patients did not experience recurrence in the long term. To further validate this, prospective studies including many patients are necessary.

In this study, all patients were continuously administered ursodeoxycholic acid (UDCA) in order to prevent stricture recurrence and stone formation. However, UDCA administration has a limited role in PCC treatment. Several authors have reported the concomitant use of UDCA in patients with symptomatic PCC undergoing endoscopic treatment [3, 23, 24, 35]. Perlemuter et al. [35] used UDCA in 5 of 8 patients with liver fibrosis or secondary biliary cirrhosis confirmed via liver biopsy. Condat et al. [3] used UDCA in 3 of 4 patients with cholestasis who underwent endoscopic sphincterotomy and reported no recurrence of symptoms while the patients were receiving the treatment. Llop et al. [24] used UDCA in 10 of 14 patients with symptomatic PCC, including 5 patients with abdominal pain and cholestasis who were treated with UDCA alone, 2 patients with stricture but no calculi, and 3 of 6 patients with common bile duct stones that developed after sphincterotomy and ductal clearance. They reported “disappearance of symptoms and improvement of liver test results” during the follow-up of all treated patients. However, in the absence of appropriate controls, it is difficult to be sure that the achieved benefit is due to the use of UDCA.

The development of cholecystitis due to metallic stent use is a known complication. However, in our study, the cholecystitis rate was found to be higher after metallic stent compared to the literature rates. The most important reason for this is that since the stenosis reaches the main hepatic duct in all patients, long metallic stents must be used, thus increasing the possibility of closure of the cystic duct orifice. In addition, we speculate that in addition to the pressure of the metallic stent on the strictured bile ducts, there may also be stricture in the cystic duct secondary to PCC. However, in most patients, cholecystitis appears to regress with conservative treatment.

When the literature is examined, it is seen that metallic stents contribute to stricture resolution more effectively than plastic stents in the treatment of benign biliary stricture [36,37,38]. In a prospective study conducted by Tringali et al. [39] with 18 patients, it was observed that better results were obtained with stents applied for a longer period. We speculate that with the application of FCSEMS for a longer period of time, the chance of remodeling in the biliary tract increases and, accordingly, the success of the treatment increases.

This study had some limitations. First, the number of patients included was quite low. In addition, this study was an academic study wherein all the procedures were performed by an endoscopist who specializes in ERCP. Therefore, there is a need for multicenter studies involving endoscopists that are not ERCP experts to demonstrate the efficacy of FCSEMS placement. Moreover, prospective studies comparing plastic stents with FCSEMS can be more helpful in providing insight into treatment efficacy.