One of the most remarkable achievements in the history of therapeutic pancreatobiliary endoscopy is the introduction of biliary stent placement to prevent obstruction during endoscopic retrograde cholangiopancreatography (ERCP). This has become established as a treatment to resolve obstructive jaundice by a non-surgical approach. As this technique allows the relief of preoperative acute biliary obstruction, it is useful for stabilizing patients before surgery and enhancing their quality of life by enabling internal drainage in those who are not eligible for surgery [1,2].

The main disadvantage of plastic stents is their limited diameter. This is set by the working channel in the duodenoscope, which prevents use of plastic stents with an outer diameter of more than 12 Fr [3]. This is not a major problem for patients who only require temporary stent placement, but can be a major issue for patients who require long-term placement of a stent. Patients with early stent occlusion before scheduled replacement can experience sudden obstruction of bile flow and complain of symptoms of recurrent biliary obstruction. This can also lead to acute cholangitis and sepsis, which can be life-threatening. Frequent stent replacement also increases medical costs and reduces the quality of life of patients with general illness.

In this focused review, we will discuss mechanisms of plastic stent occlusion, along with a summary of previous efforts and related studies to improve stent patency, and potential new techniques to overcome existing limitations.

Biliary plastic stents were first introduced in 1979, and the mechanisms of biliary stent occlusion were thoroughly investigated 20 to 30 years ago [4]. Early stent occlusion within 30 days, although very rare, mostly occurred due to positioning error, blood clots, debris, or mucus from a mucin-producing tumor [5]. This review will focus on late stent occlusion (≥30 days post-placement).

The widely-accepted theory is that bacterial biofilm and biliary sludge both play major roles, along with the extent of bacterial infection and duodenobiliary reflux of dietary fiber [3,6-8]. Biliary sludge is different from cholesterol-rich sludge, which is generally related to gallstone formation. The biliary sludge that causes stent occlusion is mainly composed of crystals of calcium bilirubinate and calcium palmitate formed by bacterial enzymes [6-12]. It is also known that several types of proteins (such as fibronectin, vitronectin, laminin, fibrin, and collagen), which are derived from bacteria of unknown specific origin but are not naturally present in bile, form a conditioning film, making the bacteria more adhesive, and also work with the bacteria to produce biliary sludge [13-17]. The formation of a biofilm that occurs as a result of attachment of these proteins onto the inner surface of a stent is known to play a major role in the initiation of sludge accumulation, but its exact role in the process of stent occlusion is still unknown.

The most important factor in the process of stent occlusion is bacterial colonization. Micro-organisms isolated from occluded biliary stents include anaerobic bacterial species, fungi, and aerobic bacterial species. The gram-positive Enterococcus species, and gram-negative Escherichia coli and Klebsiella species are most commonly encountered among aerobic bacteria, with Clostridium species among anaerobic bacteria. The species identified vary greatly among reported series, possibly affected by sites where stents were implanted, time to test after removal, interval antibiotic use, and inadequate techniques to identify anaerobic species. In any case, the synergistic effect between bacterial adherence and biofilm formation caused by these bacteria is known to trigger stent obstruction. Studies have suggested that stent patency may vary depending on the types of bacteria or the types of byproducts and proteins released by different bacteria. Other studies on scanning electron microscopy (SEM) have suggested that biofilm thickness may vary depending on their combined action [18].

Biofilms generally do not become thick enough to cause complete stent occlusion. Removed biliary plastic stents evaluated by longitudinal sectioning show a less than 0.5-mm-thick inner layer of biofilm; the occlusion is mostly caused by debris, sludge, and food components (Fig. 1).

A SEM examination of stents revealed interesting facts in terms of the change in biofilm depending on the time they were retrieved. Fig. 2 shows the inner surface of a stent retrieved approximately 4 weeks after implantation. The biofilm starts to appear on the inner surface of the stent (Fig. 2A); the biofilm itself becomes gradually thicker relatively evenly, and the surface becomes more solid (Fig. 2B-D). Fig. 3 shows the inside of a stent retrieved approximately 8 weeks after implantation. Sludge covers the biofilm, rapidly narrowing the inner diameter of the stent (Fig. 3A-C). It also appears that debris, presumably derived from causes other than sludge, is attached to the inner layer of the stent without the sludge (Fig. 3D).

What this suggests is that the biofilm is associated with the initiation of stent occlusion but that overall thickening of the biofilm is not the cause of total occlusion. It may be possible that a biofilm on the inner surface of a stent can make the surface irregular, facilitating the accumulation of sludge or debris. Various biological factors mentioned above and a number of physical factors (such as stent shapes, side holes, duodenobiliary reflux of different food components, inner coating status, bile composition status due to underlying disease, and preexisting cholelithiasis) are also thought to work together to promote sludge attachment to the inner layer. To date, antibiotics to inhibit the formation of biofilm have not improved stent patency.

Endoscopic biliary stenting has been extensively investigated since the development of therapeutic endoscopy. For more than 30 years, however, no studies have produced any remarkable results to prolong stent patency, other than the implantation of larger-caliber stents or SEMS. As plastic biliary stents are easy to insert and remove, and financially less of a burden than SEMS, plastic stents with improved function to reduce occlusion are awaited. In the future, we also hope to see more studies on the following: (1) the development of self-expandable plastic stents or bioabsorbable plastic stents, ensuring larger calibers; (2) the development of new types of plastic stents with combined benefits of both straight and pigtail types, to eliminate the effect of food components on the flap without affecting flow velocity; (3) the development of new materials effective for preventing biofilm formation as a special coating agent on the inner surface; or (4) if it is not possible to inhibit biofilm effectively, methods of coating the inner surface with substances that can prevent surface irregularity caused by the biofilm itself, so that debris or sludge cannot be incorporated; (5) development of a larger-diameter channel ERCP scope; (6) testing of single versus multiple stents for routine malignant biliary obstruction (Table 1).