Background and aims

Patients with distal malignant biliary obstruction (MBO) and cystic duct orifice tumoral involvement have an increased risk for the development of acute cholecystitis after self-expandable metallic stent (SEMS) placement. We aimed to determine whether primary EUS-guided gallbladder drainage prevents acute cholecystitis in these patients.

Methods

This was a single-center, randomized control trial in patients with distal MBO enrolled from July 2018 to July 2020. Patients were randomized into 2 groups: an interventional group treated with conventional ERCP biliary drainage with SEMS placement and subsequent primary EUS-guided gallbladder drainage (EUS-GBD) and a control group treated with conventional biliary drainage alone. The primary outcome of the study was the occurrence of post-treatment acute cholecystitis, assessed for ≤12 months or until death. The secondary outcomes were hospitalization length and median survival time.

Results

Forty-four patients were included in the study: 22 in each group. Five patients in the control group (22.7%) and none in the intervention group experienced acute cholecystitis. The median hospitalization time was significantly lower in the interventional group than in the control group (2 days vs 1 day, P = .017). There was no difference in the observed median survival rates in the primary EUS-GBD group (2.9 months) and the control group (2.8 months) (P = .580).

Conclusion

In this single-center study of patients with unresectable MBO and occlusion of the cystic duct orifice, prophylactic EUS-GBD demonstrated a reduced incidence of acute cholecystitis.

Discussion

In this randomized trial, we evaluated the role of prophylactic EUS-GBD in preventing acute cholecystitis in patients with distal MBO and tumor involvement of the OCD. We found that this approach prevents the development of acute cholecystitis after SEMS placement for palliative biliary therapy, inasmuch as none of the patients in the intervention group experienced acute cholecystitis during the follow-up period (median survival, 2.9 months). Interestingly, patients undergoing conventional palliative therapy with SEMS placement without EUS-GBD, namely, the control group, had an acute cholecystitis rate of 22.7%, a higher frequency of requiring reintervention, and a higher median number of hospitalization days.

Among the multiple risk factors proposed for the development of acute cholecystitis in patients with distal MBO, tumor involvement of the OCD (odds ratio 5.85),

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and obstruction of the OCD by the stent itself are the main predictors.

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In the present study, all patients had tumor involvement of the OCD and were at high risk for the development acute cholecystitis after palliative therapy with SEMS placement.

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Therefore, evaluating a safe and effective technique that prevents acute cholecystitis in this subset of patients is crucial, because unplanned admission or reintervention increases morbidity and mortality while decreasing the quality of life of these patients receiving palliative care.

Even though the overall acute cholecystitis rate after SEMS placement has been reported to be approximately 6% to 12%,

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it can increase in ≤16.8% in patients with tumor involvement of the OCD and ≤25% in those with OCD tumor involvement in whom a metallic stent with a high axial force is deployed.

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In our study, the acute cholecystitis rate in the control group, which did not receive EUS-GBD, was 22.7%. This is consistent with rates in previous studies, and this high rate may be explained by the increased risk of our specific included subset, all of whom had tumor involvement of the OCD.

In our study, patients prophylactically treated with EUS-GBD had no long-term adverse events during the follow-up period (median survival, 2.9 months). In a previous report describing EUS-GBD using SEMS long-term outcomes, the late adverse event rate was 7%; these events were related mainly to stent migration and recurrent acute cholecystitis due to stent occlusion. However, the 3-year cumulative stent patency rate was 86%,

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supporting the safety of prophylactic EUS-GBD in patients with a high acute cholecystitis risk after palliative biliary drainage with SEMS deployment.

One previous study evaluated transpapillary gallbladder stenting after covered SEMS placement for the prevention of acute cholecystitis. Even though none of the patients experienced acute cholecystitis in the treatment group, this therapy was feasible in only 58% of the patients; causes of failure were cystic duct accessing problems or cystic duct wire perforation.

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EUS-GBD was previously proposed to treat acute cholecystitis in high-risk surgical patients, showing high technical and clinical success rates and a 10.7% adverse event rate.

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In a previous matched cohort study of patients unfit for cholecystectomy, EUS-GBD was associated with significantly lower overall adverse event rates (32.2% vs 74.6%) and serious adverse events (23.7% vs 74.6%), and a lower readmission rate (6.8% vs 71.2%) than percutaneous cholecystostomy, although the rates of acute cholecystitis recurrence (0% vs 6.8%) were not significantly different.

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In our study, we did not observe any postprocedural adverse event in patients treated with primary EUS-GBD, reporting a 100% rate of technical and clinical success. For the technical aspect, performing this procedure in patients who are not acutely ill may be more convenient because fewer adverse events should be expected.

In a recent randomized controlled trial, EUS-GBD was compared with percutaneous cholecystostomy in very high-risk surgical patients. The EUS-guided procedure was associated with significantly lower numbers of adverse events, reinterventions, unplanned readmissions, and episodes of recurrent cholecystitis. Nevertheless, there was no difference in technical or clinical success in terms of 30-day mortality.

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Furthermore, in a recent propensity score analysis comparing EUS-GBD with laparoscopic cholecystectomy, the technical and clinical success rates, lengths of hospital stay, and 30-day adverse events and mortality rates were similar between groups; additionally, the 1-year recurrent biliary event, reintervention, and unplanned readmission rates were not significantly different.

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These 2 latter studies support the role of EUS-GBD as an alternative to percutaneous or laparoscopic cholecystectomy, and the procedure should be considered for patients who may not be surgically fit for definitive cholecystectomy and who could benefit from prophylactic gallbladder drainage because of an increased risk of experiencing acute cholecystitis after biliary SEMS placement.

Defining which patients are at an increased risk of experiencing acute cholecystitis and should benefit from prophylactic therapy after SEMS placement is essential. In the univariate analysis of our study, we found that the type of SEMS did not significantly predict the development of acute cholecystitis in patients with distal MBO and tumor involvement of the OCD, in comparison with other studies in which covered stents were associated with an increased risk of stent migration and cholecystitis.

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^,

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Interestingly, a history of cholelithiasis detected during the index procedure indeed predicted acute cholecystitis after SEMS placement and should thus be noted when one decides which patients would benefit from prophylactic EUS-GBD. Moreover, 45.5% of patients in the intervention group already had bile retention that was evident after EUS-GBD; this retained bile may precipitate and play a role in the pathogenesis of cholelithiasis. This bile retention is likely related to the distal MBO; yet, this factor was not associated with the development of acute cholecystitis in our univariate analysis.

Regarding the hospitalization length, of the conventionally treated patients in our study with palliative biliary drainage by SEMSs who experienced acute cholecystitis, 22.7% required reintervention and nonplanned readmission, significantly increasing the hospitalization length of the control group. Even so, we noted no significant difference in the median survival rates of the groups.

The present study has the advantage of being one of the first to evaluate the role of prophylactic EUS-GBD during SEMS placement in patients with distal, unresectable MBO and OCD tumoral involvement. Regardless, this study is limited by its single-center design with 1 expert endoscopist enrolled as the operator, limiting the generalizability of these findings. Additionally, we compared prophylactic EUS-GBD against conventional therapy instead of transpapillary gallbladder stent placement. Therefore, more extensive prospective trials comparing prophylactic EUS-GBD with ERCP-guided gallbladder stent placement should be conducted, with particular interest in feasibility, efficacy, and health-related cost implications. Another limitation is the lack of objective evaluation of the impact of these procedures on quality of life in the 2 study groups. We consider quality of life to be a relevant outcome for future large-scale studies.

Nowadays, in addition to EUS-GBD, EUS-guided biliary drainage may also be performed in specialized centers if required (together with EUS-GBD or even alone as a first-line therapy), especially in patients with altered anatomy and/or inaccessible transpapillary approach. Patients treated with palliative biliary therapy share high-risk surgical patient features, such as older age and cardiovascular and metabolic comorbidities. Therefore, the development of a preventable episode of acute cholecystitis in high-risk surgical patients presents a management dilemma and affects a patient’s overall well-being, which is one of the main objectives of palliative therapy. These episodes also increase readmission rates, hospitalization lengths, and overall health-related costs and diminish patients’ quality of life.

In conclusion, in this single-center study of patients with unresectable MBO and occlusion of the OCD, prophylactic EUS-GBD demonstrated a reduced incidence of acute cholecystitis. It seems that those with cholelithiasis mainly benefit from this approach. Nonetheless, larger multicenter trials are necessary to validate the observed findings of this study.

Abbreviations:

EUS-GBD (EUS-guided gallbladder drainage), MBO (malignant biliary obstruction), OCD (orifice of cystic duct), SEMS (self-expandable metal stent)

Source: http://www.giejournal.org