We developed a novel biliary BS and conducted an animal feasibility study to evaluate the preventive effect of the BS on biliary stricture after DD biliary anastomosis. This study revealed that the maintenance duration of the original shape of the PDO/Mg sheath-core BS could be adequately adjusted for the prevention of anastomosis-related stricture and fibrosis. The PDO/Mg sheath-core BS, in which the wire consisted of a double-structure of different materials with different degradation times, could remain intact for an adequate time before abruptly breaking and biodegrading. Because of the good wire-thinning process, the use of these BS could prevent biliary obstruction, and the BS can be safely and quickly degraded from the bile duct. Also, using the cross-and-hook knitting handmade method, a relatively narrow diameter self-expandable BS with an adequate radial force could be applied to DD biliary anastomosis. We think that a stent with a diameter of 4 mm or 6 mm can be applicable for LDLT.
Before starting this study, we thought about the optimal BS maintenance period for the prevention of anastomosis-related stricture. The optimal duration of stent placement in DD biliary anastomosis is not known. In general, it is expected that if the indwelling period is less than one month, it will be shorter than the period in which anastomosis-related fibrosis is initiated and terminated, and if it is too long, stent-related adverse events in the biliary tract will occur. Some authors mentioned that a stent should not be used in biliary anastomosis because it may promote fibrosis of the anastomosis due to long-term irritation of the ductal mucosa.23, 24 In addition, if a stent fracture occurs during the indwelling period and is not degraded quickly, fracture-related adverse events will occur.22
To solve these technical problems, we used a sheath-core technique in which different biodegradable materials were inserted into the center of biodegradable wires (Fig. 1 & Supplementary Fig. 1) and reported the results of a previous experimental study.22 Using this novel method, Mg with high elasticity and short degradation time was inserted into the center of an outer PDO polymer. Because the degradation times of the two materials differed, it was possible to control the phenomena caused by biodegradation. This could be maintained for a certain period of time, and then the outer polymer could degrade with a stent fracture, and at the same time, the exposed Mg core could degrade very quickly.
To use BS in DD biliary anastomosis, a thin BS with an adequate radial force is required. Initial animal studies were carried out in the form of a tube to make the thickness of the BS as thin as possible, and it was confirmed that it was completely degraded within six months.16–18 Then, a clinical trial using this tube-type BS in DDLT patients was conducted, and its potential was suggested.25 However, additional clinical trials using this tube-type BS are not in progress, and the effect and benefit cannot be objectively presented. In an animal study conducted by Laukkarinen J, et al,20 a braided, self-expandable BS with a diameter of 4 mm was used for hepaticojejunostomy. In general, a self-expandable BS could be considered to cause fewer adverse events than those of tube-type BS due to biodegradation or fracture-induced fragmentation. Six months after the operation, it was confirmed that the diameter of the anastomosis area was statistically significantly wider in the BS insertion group than in the control group. However, there was no specific mention of how the biodegradation process occurred. The same researchers conducted a clinical study with the same BS.26 However, after inserting the BS into the pancreato-jejunal anastomosis site, the BS disappearance time varied from less than one month to more than 12 months. Less than one month was probably due to migration, but the fact that it was not degraded for more than 12 months suggests that adverse events can occur due to this long-standing status.
Therefore, the ideal mechanical properties a BS used for DD biliary anastomosis should have are: 1) very thin but strong radial force; 2) the ability to stay in shape for as adequate as we want; and 3) when it begins to degrade, it must totally degrade as soon as possible. Our novel PDO/Mg sheath-core BS was maintained for an adequate time and degraded quickly after that for the prevention of anastomosis-related stricture and fibrosis. Using the cross-and-hook knitting handmade method, the BS had a relatively narrow diameter with an adequate radial force. As shown in Supplementary Fig. 1, the same degradation phenomenon was confirmed by conducting an animal study (Fig. 6). BS deformity (fracture) did not occur until four weeks, and then quickly disappeared. Histologic analysis was performed to determine whether this maintenance period could prevent anastomosis-related stricture. As seen in Table 3, the median circumference values and ranges in all the measured points were narrower in the control group than in the stent group. Although not statistically significant due to the limited number of specimens in each group, we think the results would have changed significantly, if the two animals in the control group did not die. As seen in Fig. 7, fibrosis of the DD anastomosis area was more marked in the control group than in the stent group. This thickening of fibrosis was statistically different (p < 0.05) (Table 4). Therefore, these results suggested that the BS, which were being accurately maintained for a certain period of time, had the effect of preventing anastomosis-related stricture because the BS inhibited the induction of fibrosis.
The limitations of this experimental study were as follows. 1) This study used an in vivo animal model, and the results from a human study may substantially differ from those of our experimental study. 2) A small number of BS was used in the in vivo animal model. This is because DD anastomosis can only be performed at one site per CBD. 3) Two animals died immediately after surgery in the control group, so statistics could not be obtained with the same sample number. The two deaths were not due to a CBD problem, but occurred in the control group and not the stent group. It is possible that this critical adverse event could have been prevented because stent insertion might improve the animal's postoperative condition. However, since we could not prove this, we cannot adequately comment on the possibility. 4) If more radiopaque markers were attached to the BS, it would have been possible to observe the BS shape more accurately. Previous reports showed that the overall shape of the BS could be observed by fluoroscopic examination by mixing barium sulfate with a biodegradable polymer. However, when barium sulfate is mixed with the biodegradable polymer, the properties of the polymer filament itself change significantly, so we could not obtain the desired properties. 5) Changes in the mechanical properties of the BS in the CBD during the follow-up period were not measured.
Nevertheless, although additional clinical studies are required to observe the biocompatibility and preventive effect of BS on biliary stricture after DD biliary anastomosis, our current findings provide basic proof of concept for its use to prevent stricture and fibrosis after surgery. Our present results have thus yielded important insight into the potential benefits of the novel BS placement.
In conclusion, our study showed that our novel PDO/Mg sheath-core BS maintained its original shape and radial force for an adequate time and then disappeared without adverse events. The BS could prevent postoperative complications and stricture after DD biliary anastomosis. After further investigations and clinical trials, the novel BS have the potential to be used for temporary stent placement.