Results of endoscopic treatment of recurrent malignant biliary obstruction in patients with self-expanding metal stents

doi:10.21203/rs.3.rs-4951976/v1

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Research Article

Results of endoscopic treatment of recurrent malignant biliary obstruction in patients with self-expanding metal stents

https://doi.org/10.21203/rs.3.rs-4951976/v1

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Background and Aim:

Endoscopic biliary drainage with placement of a self-expanding metal stent (SEMS) is the preferred palliative treatment of malignant biliary obstruction. Recent advances in the treatment have prolonged survival, thus increasing the chance of recurrent biliary obstruction (RBO) after SEMS placement. The aim of this study was to compare different endoscopic approaches in patients with a SEMS and RBO, regarding clinical success and time to RBO.

Methods

This retrospective study included all patients with a SEMS placed because of malignant biliary strictures who underwent endoscopic retrograde cholangiopancreatography between January 2011 and December 2018. We evaluated the results of different endoscopic interventions to RBO, including insertion of a new SEMS, stent cleaning, and insertion of a plastic stent (PS).

Results

From January 2011 to December 2018, 70 (22.4%) patients developed RBO requiring endoscopic reintervention (n = 105 sessions). From the 105 ERCPs, technical success, clinical success and adverse events rates were 91,4%, 71,8%, 7,8%, respectively. Younger age (OR = 1.11 95%CI: 1.03–1.19) and the finding of a patent SEMS (OR = 0.17 95%CI: 0.04–0.08) were predictors of clinical failure (P = 0.006 and P = 0.024, respectively). The mean patency time (in days) after endoscopic reintervention was greater for SEMSs than for PSs (417.2 [95% CI: 250.0–584.4] vs 175.2 [95% CI: 124.0–226.5], P = 0.002).

Conclusions

Correct identification and treatment of the causal factor of RBO typically leads to technical and clinical success. Placement of a second SEMS provides longer patency compared to a plastic stent if ingrowth (overgrowth) occurs.

Biliary tract neoplasms

Cholestasis

Self expandable metallic stents

Cholangiopancreatography

endoscopic retrograde

Jaundice

obstructive

Endoscopic biliary drainage with self-expanding metal stent (SEMS) placement is the palliative strategy of choice in patients with malignant biliary obstruction due to unresectable neoplasia (1–6). Several randomized studies and meta-analyses showed that a SEMS is superior to a plastic stent (PS) in terms of patency and survival time, reducing the risk of cholangitis and endoscopic reintervention (7–12).

Recent advances in the treatment of unresectable malignant pancreatobiliary diseases have increased patient survival, thus increasing the prevalence of recurrent biliary obstruction (RBO) in patients with a SEMS (2, 13). Studies indicate that SEMS dysfunction occurs in 5–40% of such patients (2, 14–16).

The causes of RBO include tumor ingrowth (overgrowth), sludge formation, food impaction, primary gallstones and stent migration among others. In cases of RBO after SEMS, the best endoscopic strategy is unclear. The SEMS can be cleaned mechanically with a balloon catheter, a PS or a new SEMS can be inserted within the previous stent. Other less common approaches include replacing the SEMS and radiofrequency ablation (RFA) (17). Only a few studies have compared the various approaches of RBO (1, 3, 14, 18–24).

Although some strategies have been devised, there is no consensus regarding the best management of an occluded SEMS. The European Society of Gastrointestinal Endoscopy recommends that SEMS dysfunction should be managed by placing a new PS or SEMS, without making a distinction between the two (4). In a consensus statement, experts in interventional endoscopy in Asia proposed that the therapeutic approach to patients with RBO should be customized depending on the etiology and severity of the obstruction (5). In another consensus statement regarding RBO, from Japan, stent cleaning was described as ineffective and the insertion of a second SEMS would lead to greater patency in comparison with the insertion of a PS (6). Therefore, given the lack of a consensus in the literature regarding the approach to RBO, the management of SEMS dysfunction merits investigation.

The present study aimed to compare the results of different endoscopic approaches in patients with SEMS and RBO. The primary outcomes were clinical success and time to a new biliary obstruction.

This was an observational study including all patients with a SEMS for the treatment of malignant strictures, who underwent reintervention with endoscopic retrograde cholangiopancreatography (ERCP) to investigate RBO between January 2011 and December 2018 at the Cancer Institute of the University of São Paulo (ICESP), São Paulo, Brazil. This study was approved by our institution Research Ethics Committee (Reference no. 4.995.272).

Inclusion criteria were patients with a SEMS placed because of malignant biliary strictures who underwent ERCP to investigate and treat recurrent biliary obstruction. Exclusion criteria were patients lost to follow-up after the insertion of the first SEMS.

The sample selection process is shown in Fig. 1.

The indications for reintervention with ERCP were recorded and categorized as: recurrence of cholestasis; cholangitis; dilation of the biliary tree; or other. All procedures were performed in the Endoscopy Unit of our institution. During ERCP, the cause of the obstruction was identified and noted as follows: ingrowth; overgrowth; biliary sludge/gallstones or stent migration. The endoscopist intervened based on the cause of obstruction identified during ERCP. The expected procedures for treating RBO were the insertion of a PS or a second SEMS within the primary stent; mechanical cleaning of the SEMS with a balloon catheter and/or Dormia basket. In each reintervention, the choice between a PS and a SEMS was left at the discretion of the endoscopist.

Definitions

The definitions adopted in this study were based on the Tokyo criteria, updated in 2024 (26). Clinical success was defined as a reduction of at least 50% or normalization in the bilirubin level within the first 14 days after stent placement. Time to RBO was defined as the time between endoscopic reintervention and the new obstruction. Occlusion of a SEMS or PS was defined by biochemical evidence of cholestasis, accompanied by biliary dilation on imaging studies, together with endoscopic findings consistent with occlusion. Ingrowth was diagnosed when cholangiography demonstrated a persistent biliary stricture within a covered or uncovered SEMS (CSEMS or UCSEMS, respectively) after the bile duct had been cleaned. Similarly, overgrowth was diagnosed when there was persistent stenosis at the proximal or distal ends of the SEMS. Stent migration was defined as RBO caused by complete or partial (proximal or distal) stent migration. Technical success was defined as resolution of the cause of the obstruction with free flow of contrast under cholangiography.

Cholangitis were defined according to the 2018 Tokyo Guidelines (27), as signs of systemic inflammation, cholestasis, or imaging examinations showing bile duct obstruction. Adverse events were defined according to the 2024 Tokyo criteria (26), as RBO, pancreatitis, cholangitis, cholecystitis, bleeding, perforation or any other complication related to the placement of the stent in the bile duct.

Statistical analysis

Categorical variables were expressed as absolute and relative frequencies, whereas numerical variables were expressed as descriptive statistics (mean, standard deviation, range, median, and quartiles). For comparisons between categorical variables, we used the chi-square test (or Fisher’s exact test in the case of small samples). For comparisons of means, we used Student’s t-test for independent samples.

We used generalized estimating equations (GEEs) to evaluate the simultaneous effects that demographic and clinical characteristics had on clinical success. We used Kaplan–Meier curves to analyze survival to endoscopic reintervention or death. Survival functions were compared by the log-rank (Mantel–Cox) test. Because more than one approach could be taken in each patient, frailty models were used. For the time to RBO, the Cox competing-risks model (Fine–Gray model) was used (the survival function was expressed as the subhazard ratio - SHR).

Variables significant at 20% in the univariate analysis were selected for inclusion in the initial multivariate models. Variables that were not significant at 5% were then eliminated one by one in order of significance (backward elimination).

In our exploratory analyses, reinterventions were evaluated as independent events.

For all statistical tests, we adopted a significance level of 5%. Statistical analyses were performed with the IBM SPSS Statistics software package, version 20.0 (IBM Corp., Armonk, NY, USA) and Stata software, version 12.0 (Stata Corp LP, College Station, TX, USA).

Between January 2011 and December 2018, 312 patients underwent endoscopic SEMS insertion for the treatment of biliary obstruction at our institution. Of those, 71 (22.7%) developed RBO and required endoscopic reintervention. One patient was lost to follow up and was excluded of the analysis. The mean age was 61.3 ± 13.3 years, and 37 patients (52.9%) were men. The majority of patients had a good performance status (ECOG 0–2 in 70% of the patients), had previously undergone chemotherapy (89.7%) and had distal biliary obstruction (78.6%). Demographic and clinical characteristics are shown in Table 1.

Table 1

Demographic and clinical characteristics of the patients
Characteristic	(N = 70)
Sex, n (%)
Female	33 (47.1)
Male	37 (52.9)
Age* (years)
Mean ± SD	61.3 ± 13.3
Median (range)	61.0 (28.0–88.0)
ECOG performance status, n (%)
0	11 (15.7)
1	24 (34.3)
2	14 (20)
3	16 (22.9)
4	5 (7.1)
Treatment prior to ERCP, n (%)
None	7 (10.3)
Chemotherapy only	53 (77.9)
Chemotherapy and radiotherapy	8 (11.8)
No information available	2 (2.8)
Obstruction topography, n (%)
Hilar	15 (21.4)
Distal	55 (78.6)
SD, standard deviation; ECOG, Eastern Cooperative Oncology Group; ERCP, endoscopic retrograde cholangiopancreatography.
*At ERCP.

The main cause of RBO was ingrowth occurring in 65 procedures (63.7%), followed by sludge/gallstones in 14 procedures (13.7%). The reintervention involved PS insertion in 38.4%, SEMS insertion in 30 (28.8%) and stent cleaning in 23 (22%). In 9 cases, no obstructive factor was seen and thus no endoscopic reintervention was performed. In one case, the stent was only repositioned; in another, the existing SEMS was removed, and no further action was taken (Table 2).

Table 2

Characteristics of the endoscopic reinterventions
	Characteristic	(N = 105)
	Main ERCP finding (cause of RBO), n (%)*
	Ingrowth	65 (63.7)
	Gallstone(s)/debris	14 (13.7)
	Proximal migration of the SEMS	3 (2.9)
	Absence of obstructive factors	9 (8.8)
	SEMS not found^†	8 (7.8)
	Overgrowth	3 (2.9)
	Endoscopic reintervention, n (%)^‡
	PS insertion	40 (38.4)
	SEMS insertion	30 (28.8)
	Stent cleaning	23 (22.0)
	None	9 (8.7)
	Stent repositioning	1 (1.0)
	PS removal	1 (1.0)
Number of reintervention, n (%)
1st		50 (71,4)
2nd		11 (15,7)
3rd		6 (8,6)
> 4th		3 (3.2)
ERCP, endoscopic retrograde cholangiopancreatography; RBO, recurrent biliary obstruction; SEMS, self-expanding metal stent; PS, plastic stent.
*Data available for only 102 procedures.
^†Due to duodenal stenosis.
^‡Data available for only 104 procedures.

Fifty patients underwent only one reintervention and 20 required more than one resulting in a total of 105 ERCP sessions for maintaining stent patency

Technical success and Clinical success

Technical success was achieved in 91.4% of the 105 interventions. Causes of technical failure occurred in five patients with duodenal obstruction, which prevented endoscopic access to the bile duct.

Clinical success was achieved in 71.8% of the 105 interventions. As shown in Table S1, clinical success was not associated with the endoscopic approach, ECOG performance status or prior chemotherapy/radiotherapy. Of nine ERCPs in which no action was taken (because the stent was found to be well positioned and unobstructed), 67% had clinical failure and the risk of death was approximately 4 times higher in these patients (HR: 3.94; 95% CI: 1.57–9.92; P = 0.004).

In the multivariate analysis (Table 3), younger age (P = 0.006), no reintervention (P = 0.024), and shorter time to RBO (P = 0.008) were predictors of the clinical failure. The chance of clinical success was 83% (1-0.17) lower in patients who underwent no reintervention than in patients who underwent any reintervention (OR = 0.17; p = 0.024). When the time to RBO between reinterventions was longer, the odds of clinical success of that intervention was higher (OR: 1.007; 95% CI: 1.002–1.013; p = 0.008). However, the number of reinterventions did not impact on the odds of clinical success.

Table 3

Results of final logistic regression model for the predictors of clinical success
Variable	Initial model*		Final model^†
Variable	Adjusted OR (95% CI)	P	Adjusted OR (95% CI)	P
Age (years)	1.05 (1.01–1.09)	0.026	1.11 (1.03–1.19)	0.006
Obstruction topography
Hilar	0.32 (0.09–1.18)	0.086	-	-
Distal (reference)
Endoscopic reintervention
None	0.10 (0.02–0.51)	0.005	0.17 (0.04–0.80)	0.024
SEMS insertion	1.14 (0.32–3.99)	0.841	1.27 (0.41–3.92)	0.677
Stent cleaning	0.45 (0.10–2.07)	0.304	0.65 (0.19–2.24)	0.499
Other reinterventions^‡ (reference)
Number of reinterventions (1 - reference)
2	0.93 (0.30–2.92)	0.900	-	-
3	0.81 (0.15–4.37)	0.810	-	-
4	1.15 (0.36–3.73)	0.811	-	-
5	0.65 (0.23–1.84)	0.412	-	-
6	(1)^§	-	-	-
Adverse events	0.90 (0.14–5.84)	0.911	-	-
Time to RBO (days)	1.007 (1.001–1.013)	0.013	1.007 (1.002–1.013)	0.008
SEMS, self-expanding metal stent; RBO, recurrent biliary obstruction
*N = 96 reinterventions in 59 patients.
^†N = 102 reinterventions in 70 patients.
^‡PS insertion, PS removal, and stent repositioning.
^§Absence of clinical failure.

Recurrent biliary obstruction

The mean and median stent patency after endoscopic reintervention were 252.8 days (95% CI: 186.8–318.9) and 122.0 days (95% CI: 87.6–156.4), respectively. Time to RBO was longer in patients treated with SEMS compared with PS (p = 0.002, Table 4). UCSEMSs were comparable to CSEMSs (P = 0.546) and both were superior to PS (Table S2). Figure 2 shows the cumulative patency by stent type.

Table 4

Results of the post-reintervention patency analysis
Variable	Cumulative time to RBO (%)*					P^†
Variable	15 days	1 month	3 months	6 months	1 year	P^†
Total (n of interventions)	91.60 ± 2.15	88.29 ± 2.53	69.44 ± 3.90	40.73 ± 4.49	16.79 ± 3.74	-
Main ERCP finding						0.164
Ingrowth (65)	91.99 ± 2.72	89.79 ± 3.07	71.64 ± 4.86	40.76 ± 5.62	20.97 ± 5.05
Gallstone(s)/debris (14)	90.91 ± 6.13	90.91 ± 6.13	78.67 ± 9.67	65.56 ± 11.69	21.85 ± 11.01
Stent migration (3)	83.33 ± 15.21	83.33 ± 15.21	62.50 ± 21.35	62.50 ± 21.35	-
No obstructive factors (9)	88.24 ± 7.81	81.45 ± 9.72	43.44 ± 15.04	-	-
SEMS not found^‡ (8)	91.67 ± 7.98	83.33 ± 10.76	64.81 ± 14.26	16.20 ± 14.48	-
Overgrowth (3)	100.00 (-)	100.00 (-)	100.00 (-)	66.67 ± 27.22	-
Type of stent (general)						0.002
PS (40)	90.71 ± 3.34	87.88 ± 3.79	64.97 ± 5.98	33.14 ± 6.35	7.29 ± 3.96
SEMS (30)	97.44 ± 2.53	94.73 ± 3.63	80.28 ± 6.72	56.59 ± 8.91	39.69 ± 9.46
Type of stent (specific)						0.007
PS (40)	90.71 ± 3.34	87.88 ± 3.79	64.97 ± 5.98	33.14 ± 6.35	7.29 ± 3.96
UCSEMS (10)	100.00 (-)	100.00 (-)	81.25 ± 9.76	60.94 ± 12.52	45.70 ± 13.24
CSEMS (20)	95.45 ± 4.44	90.68 ± 6.28	80.61 ± 8.73	53.74 ± 12.42	33.59 ± 13.85
ERCP, endoscopic retrograde cholangiopancreatography; (-) absence of cases; SEMS, self-expanding metal stent; PS, plastic stent; UCSEMS, uncovered SEMS; CSEMS, covered SEMS.
*Estimated probability of survival ± standard error.
^†Log-rank (Mantel–Cox) test.
^‡Due to duodenal stenosis.

In the multivariate analysis, stent repositioning (P < 0.001) was predictive of RBO and overgrowth was a protective factor against RBO (p = 0.001) (Table 5). The risk of RBO did not differ among the various endoscopic reinterventions, including insertion of a PS, CSEMS, UCSEMS, stent cleaning, stent repositioning, and PS removal (P = 0.264^ǂ). The RBO risk was 35% lower in patients with overgrowth than in those with ingrowth (SHR: 0.65; 95% CI: 0.52–0.82; P < 0.001). The RBO risk was found to increase in parallel with an increase in the number of reinterventions, ranging from 1.66 times higher (for two reinterventions) to 3.04 times higher (for six reinterventions). In the final model, the proportional-hazards assumption, tested by using the Schoenfeld residuals, was not violated (P = 0.178).

Table 5

Results of the initial and final multivariate Cox models for competing risks of recurrent biliary obstruction
Variable	Competing-risks model
	Initial*		Final^†
	SHR (95% CI)	P	SRH (95% CI)	P
Age (years)	1.00 (1.00–1.01)	0.257	-	-
ECOG performance status (0 - reference)		0.337		-
1	0.62 (0.37–1.05)	0.073	-	-
2	0.61 (0.35–1.06)	0.079	-	-
3	0.55 (0.31–0.96)	0.037	-	-
4	0.60 (0.33–1.12)	0.110	-	-
Treatment prior to ERCP (ChT only - reference)		0.876	-	-
None	0.94 (0.73–1.20)	0.617	-	-
ChT and RT	0.99 (0.75–1.31)	0.935	-	-
Endoscopic reintervention (PS insertion - reference)		< 0.001		< 0.001
None	1.41 (0.76–2.60)	0.271	0.95 (0.68–1.32)	0.753
UCSEMS insertion	0.68 (0.38–1.22)	0.197	0.74 (0.53–1.05)	0.092
CSEMS insertion	1.20 (0.65–2.23)	0.566	1.15 (0.91–1.45)	0.255
Stent cleaning	1.19 (0.68–2.08)	0.548	1.18 (0.82–1.68)	0.377
Stent repositioning	7.56 (3.79–15.06)	< 0.001	6.51 (4.60–9.21)	< 0.001
PS removal	1.19 (0.57–2.50)	0.647	1.45 (0.78–2.73)	0.243
Main ERCP finding		0.005		0.001
Ingrowth (reference)
Gallstone(s)/debris	0.83 (0.53–1.30)	0.422	0.82 (0.50–1.33)	0.411
Stent migration	0.75 (0.47–1.19)	0.217	0.83 (0.67–1.03)	0.090
No obstructive factors	1.02 (0.55–1.89)	0.945	0.80 (0.49–1.32)	0.382
SEMS not found^‡	1.46 (0.74–2.86)	0.276	1.03 (0.56–1.87)	0.935
Overgrowth	0.41 (0.24–0.71)	0.002	0.65 (0.52–0.82)	< 0.001
Number of reinterventions (1 -reference)		< 0.001		< 0.001
2	1.50 (1.06–2.11)	0.021	1.66 (1.27–2.16)	< 0.001
3	2.02 (1.14–3.55)	0.015	1.90 (1.23–2.92)	0.004
4	2.34 (1.80–3.04)	0.000	1.97 (1.58–2.47)	< 0.001
5	1.82 (0.93–3.54)	0.079	2.82 (2.17–3.66)	< 0.001
6	3.71 (1.95–7.06)	0.000	3.04 (2.12–4.36)	< 0.001
SHR, subhazard ratio; ECOG, Eastern Cooperative Oncology Group; ERCP, endoscopic retrograde cholangiopancreatography; ChT, chemotherapy; RT, radiotherapy; SEMS, self-expanding metal stent; PS, plastic stent; UCSEMS, uncovered SEMS; CSEMS, covered SEMS.
*N = 67 patients (158 reinterventions)
^†N = 69 patients (165 reinterventions).
^‡Due to duodenal stenosis.

Adverse Events non-RBO

Adverse events occurred in 7.8% of the endoscopic reinterventions: pancreatitis in four patients, duodenal perforation in one, hepatogastric fistula in one, esophageal varix rupture in one and reintubation post-procedure in one patient.

The endoscopic management of patients with malignant biliary obstruction and an obstructed SEMS is not well stablished.

In our sample, the main cause of SEMS obstruction was ingrowth, as well as in most previous retrospective studies (18, 20–23, 25).

For most of our patients, SEMS dysfunction was treated by inserting a PS or by inserting a second SEMS, which are the two main reinterventions recommended in the literature (1, 14, 19–22). In our study we found a clinical success rate of 79.3% for SEMS, 74.4% for PS and stent cleaning resulted in clinical success of 69.6%, with no difference between them. In other studies evaluating insertion of a new stent or stent cleaning (1, 14, 19–22), the reported rates of clinical success ranged from 33–82%, although stent patency time was shorter and the number of reinterventions was higher with stent cleaning. In fact, three studies compared stent cleaning alone with the insertion of a PS or SEMS and showed that the former was less effective (19, 21, 22).

The fact that we found no difference in clinical success rates among SEMS insertion, PS insertion, and stent cleaning suggests that clinical success is associated with correct diagnosis of the cause of the obstruction. Most previous studies of this topic have evaluated the difference between PSs and SEMSs (CSEMSs or UCSEMSs). Tham et al. (20) reported 98% of clinical success on endoscopic management of stent occlusion, with no difference among SEMS insertion, PS insertion, and stent cleaning. The authors also found that a PS insertion was more cost-effective. Bueno et al. (21) reported that clinical success was achieved in 93% of patients undergoing insertion of a PS and in all 4 patients treated with a second SEMS but only in one of 6 patients treated with SEMS cleaning.

The lower clinical success observed in our study can partially be attributed by the fact that in 8.5% of our cases no obstruction was detected that would justify the clinical picture and therefore no endoscopic reintervention was implemented. Among those cases, cholestasis persisted in 66.7% and the chance of success was lower than in cases in which there was a reintervention due to the finding of an obstructed metal stent. It is possible that the cholestasis, jaundice, and dilation of the bile duct seen in those cases had non-obstructive causes, such as liver dysfunction resulting from chemotherapy or progression of the malignancy. These results suggest that the absence of an obstructive factor (and consequently no reintervention) is an independent predictor of clinical failure and increases the risk of death. Time to RBO was another predictor of clinical success which demonstrated that the longer the interval between reinterventions, the greater the probability of achieving a favorable clinical outcome. However, the number of reinterventions did not correlated with clinical success, which means that the chances of achieving clinical success did not decrease if it was the first, second or subsequent reintervention.

In the present study, patency time was longer after insertion of another SEMS than after insertion of a PS (p = 0.002). Various other studies have shown that SEMSs remain patent for longer.^{1,18,22,23,25} Ghazi et al. (28) showed that although re-occlusion rates are higher for PSs than for SEMSs (46.7% vs 19.7%), the clinical success, mortality, and survival rates were similar between them. However, other studies found no differences between the stent types (18–21). In one systematic review (29), no difference in patency time was found between PSs and SEMSs. Those differences of the results in the literature are probably related to the patient survival, e.g., in a cohort of patients with more advanced disease, the clinical advantage of the longer patency of SEMS may not be detected.

Togawa et al. (23). compared CSEMSs and UCSEMSs and found that the former presented better patency time. Cho et al. (18) evaluated the results obtained with different combinations of the first and second SEMS used. The authors found that the use of a CSEMS as the first or second stent provides longer patency than does the use of UCSEMSs as the first and second stents (18). However, one randomized study also compared the use of CSEMSs and UCSEMSs in patients with RBO and showed no difference in relation to patency time, time to occlusion, survival, and complications (3). In our study we found no difference between CSEMSs and UCSEMSs (P = 0.546) and both were superior to PS (p = 0.007).

We found that patient age, ECOG performance status, and previous chemotherapy or radiotherapy had no influence on time to RBO of the reintervention. Although statistical analysis indicated that stent repositioning was a predictor of recurrent biliary obstruction, the data was based on a single case, limiting the ability to confirm this hypothesis.

In our sample, although the number of previous reinterventions did not impact the chances of clinical success the risk of stent obstruction was found to increase with the number of reinterventions performed. That was probably due to longer survival of these patients.

The heterogeneity of our sample in terms of the primary neoplastic disease precluded any assessment of whether the underlying disease influenced the primary or secondary outcome measure. In the present study, 87% of the patients had previously undergone chemotherapy, radiotherapy, or both, none of which were found to have an impact on the clinical success, time to RBO or survival. A retrospective study involving 279 patients with a partially covered SEMS who developed RBO, showed that antineoplastic therapy was a risk factor for RBO in cases of distal malignant biliary obstruction (30). The hypothesis is that cancer treatment prolongs survival, thus increasing the chance of SEMS obstruction. However, in that study, the time to RBO did not differ between the patients treated with antineoplastic therapy and those receiving clinical support only.

Two studies compared the treatment of recurrent hilar versus distal bile duct obstruction (21, 25). Both showed that malignant strictures more proximal to the hepatic hilum result in shorter patency time for a second stent. In our study, we found an OR of 0.32 (0.09–1.18) for clinical success for hilar obstruction, not reaching statistical significance (p = 0.086). Maybe this is due to the fact that only 21.4% of our patients had hilar obstruction, resulting in a beta error.

Our study has some limitations, including the retrospective, unicentric design and the heterogeneity of the patient sample in relation to the underlying disease. Finally, the fact that the endoscopist decided which approach to take could have introduced a selection bias.

In conclusion, in patients with malignant biliary obstruction and an existing, dysfunctional SEMS, reintervention continues to be a challenge and the best approach is still much debated. Our findings indicate that a correct diagnosis is paramount in the management of such cases. Correct identification and treatment of the causal factor typically leads to technical and clinical success. If overgrowth or ingrowth are the cause of SEMS disfunction, the placement of a second SEMS provides longer patency compared to a plastic stent. Furthermore, it is possible that requiring a subsequent reintervention is increased when multiple reinterventions are performed. However, the probability of achieving clinical success in each reintervention remains unchanged. Future studies should also focus on quality of life since none of the endoscopic management options increase patient survival. Patients would probably benefit from procedures that result in a shorter hospital stays and fewer reinterventions.

Author Contribution

L.M.A.C.M.; B.C.M. and F..M.F wrote the main manuscript text and prepared figures 1-2. All authors revised the manuscript critically for important intellectual content.

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Results of endoscopic treatment of recurrent malignant biliary obstruction in patients with self-expanding metal stents

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Technical success and Clinical success

Recurrent biliary obstruction

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