Introduction

Malignant biliary obstruction (MBO) encompasses a variety of malignancies arising from the pancreaticobiliary system. The relatively common occurrence of duodenobiliary reflux (DBR) in patients with transpapillary stent placement for palliative management raises the importance of the development of alternative methods to prevent adverse outcomes.

Aims & Methods

We aimed to compare supra-papillary to trans-papillary stenting in patients with MBO for stent dysfunction and adverse events. PubMed, Embase, and Cochrane were systematically searched for randomized controlled trials (RCTs). The primary outcome was stent occlusion. Secondary outcomes included stent migration, occurrence of cholangitis or pancreatitis, cumulative duration of stent patency in days, and patient survival in days. Statistical analyses were conducted using R (version 4.3.1) and a random-effects model was employed.

Results

We found 3 RCTs with 161 patients (80 in the supra-papilla stent group vs. 81 in the trans-papilla group). Supra-papillary stent placement was associated with significantly lower rates of stent occlusion (OR 0.42; 95% CI 0.20 to 0.87; p = 0.019), and longer cumulative duration of stent patency (MD 77.59; 95% CI 23.84 to 131.34; p < 0.01). The Trial Sequential Analysis for this outcome showed that this study has surpassed the required information size (n = 158) to ascertain the statistical difference for this outcome. The analyses of stent migration (p = 0.471) occurrence of cholangitis (p = 0.525), and patient survival (p = 0.05) revealed no significant difference between both groups.

Conclusion

We found a significant improvement in stent occlusion rates and cumulative duration of stent patency favoring the supra-papilla group, with no difference for stent migration, occurrence of cholangitis, and patient survival for this comparison.

Introduction

There are two types of covered self-expandable metallic stents (CSEMS): laser-cut (L) and braided (B). The B-type has a strong axial force and can cause problems such as recurrent obstructive jaundice and cholangitis. The L-type is less stressful for the bile duct.

Aims & Methods

This study aims to compare CSEMS B-type versus L-type in patients with unresectable distal malignant biliary obstruction. We performed a systematic review in PubMed, Embase and Cochrane databases, searching for studies comparing both types of CSEMS in this population. The primary outcome was stent occlusion. The secondary outcomes were tumor ingrowth, tumor overgrowth, stent migration, pancreatitis and cholecystitis. The odds ratio (OR) was used for binary outcomes with their respective 95% confidence interval (CI). Heterogeneity was assessed using the Cochran Q test and I² statistics.

Results

The meta-analyses included 4 studies and 430 patients. There was no significant difference for any outcome: stent occlusion (OR 1.28; 95% CI 0.73 to 2.23; p=0.388; I²=0%), tumor ingrowth (OR 1.12; 95% CI 0.46 to 2.76; p=0.800; I²=0%), tumor overgrowth (OR 1.23; 95% CI 0.36 to 4.25; p=0.740; I²=0%), stent migration (OR 1.60; 95% CI 0.28 to 9.20; p=0.600; I²=73%), pancreatitis (OR 1.28; 95% CI 0.53 to 2.90; p=0.559; I²=0%) and cholecystitis (OR 0.73; 95% CI 0.26 to 2.06; p=0.553; I²=0%).

Conclusion

In patients with distal malignant biliary obstruction, no significant difference was observed between CSEMS B-type and L-type.

References

1. HASEGAWA, S. et al. Braided-type stent versus laser-cut-type stent for patients with unresectable distal malignant biliary obstruction: a randomized controlled trial. Gastrointestinal Endoscopy, v. 99, n. 5, p. 739-746.e1, 1 maio 2024.
2. OKUNO, M. et al. The evaluation of bilateral stenting using braided or laser-cut self-expandable metallic stent for malignant hilar biliary obstruction. Surgical Endoscopy, v. 37, n. 11, p. 8489–8497, 1 nov. 2023.
‌3. KITAGAWA, K. et al. Laser-cut-type versus braided-type covered self-expandable metallic stents for distal biliary obstruction caused by pancreatic carcinoma: a retrospective comparative cohort study. Clinical Endoscopy, v. 55, n. 3, p. 434–442, 1 maio 2022.
​4. TANISAKA, Y. et al. Can the laser-cut covered self-expandable metallic stent be the first choice for patients with unresectable distal malignant biliary obstruction? (with video). Journal of Hepato-Biliary-Pancreatic Sciences, v. 29, n. 5, p. 585–593, 1 maio 2022.
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Introduction

Endoscopic drainage of malignant biliary obstruction using metal stents is widely used to treat obstructive jaundice. However, the occurrence of stent occlusion or migration raises the hypothesis using stents with larger diameters may be associated with better outcomes.

Aims & Methods

PubMed, Embase, and Cochrane were systematically searched for randomized controlled trials (RCTs) and observational studies comparing 10-mm vs. 12-mm metallic stents for recurrent unresectable biliary obstruction. The primary outcome was stent obstruction. Secondary outcomes included overall adverse events and stent migration. Statistical analyses were performed using R software version 4.3.1. The odds ratio (OR) was used for binary outcomes, and the mean difference (MD) for continuous outcomes with their respective 95% confidence interval (CI). Heterogeneity was assessed using the Cochran Q test and I² statistics.

Results

We included six studies comprising 592 patients who underwent stent placement. Of those, 328 patients received a 10mm and 264 patients a 12mm stent. 12mm stent is associated with a lower incidence of stent obstruction (OR 0.48; 95% CI 0.27 to 0.88; p=0.02; I²=53%). However, no statistically significant differences between groups were found for stent migration (OR 0.68; 95% CI 0.39 to 1.19; p=0.18; I²=0%) and incidence of adverse events (OR 0.84; 95% CI 0.39 to 1.82;p= 0.66; I²=46%).

Conclusion

12-mm metallic stents significantly reduce the incidence of stent obstruction compared to 10-mm stents in managing recurrent unresectable biliary obstruction. However, our analysis did not demonstrate statistically significant differences between the two stent sizes regarding stent migration and overall adverse events.

References

1. CHIKUGO, K. et al. Re-intervention with 10-mm vs 12-mm covered self-expandable metallic stent for recurrent unresectable distal biliary obstruction in patients with previous stent implantation. Journal of Hepato-Biliary-Pancreatic Sciences.
‌2. NAKAOKA, K. et al. Evaluation of a 12-mm diameter covered self-expandable end bare metal stent for malignant biliary obstruction. Endoscopy International Open.
‌3. LEE, H. W. et al. Usefulness of newly modified fully covered metallic stent of 12 mm in diameter and anti-migration feature for periampullary malignant biliary strictures: Comparison with conventional standard metal stent. Journal of Gastroenterology and Hepatology.
‌4. MUKAI, T. et al. Comparison of covered self-expandable metallic stents with 12-mm and 10-mm diameters for unresectable malignant distal biliary obstructions: a prospective randomized trial. Gastrointestinal Endoscopy.
‌5. DO, M. Y. et al. Safety and Efficacy of a Large-Bore Biliary Metallic Stent for Malignant Biliary Obstruction. Journal of Clinical Medicine.
6. CAILLOL, F. et al. Evaluation of a new metal biliary stent of 12-mm diameter: A case control study. Jounal of Gastrointestinal and Digestive System​.
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Introduction

The management of malignant hilar biliary obstruction can be done by endoscopic biliary stenting, which is a well-established palliative treatment, improving the quality of life by relieving symptoms.

Aims & Methods

This systematic review and meta-analysis aimed to compare the use of stents placed above and across the sphincter of Oddi in patients with malignant hilar biliary obstruction. We performed a systematic search of the PubMed, Embase, and Cochrane Library databases in April 2025. Article screening was conducted independently by two authors using Rayyan software. Inclusion criteria were randomized controlled trials (RCTs) comparing stent placement above and across the sphincter of Oddi for malignant hilar biliary obstruction, evaluating at least one of the outcomes of interest. The outcomes were stent migration, stent patency, cholangitis, stent occlusion, and successful placement of the stent. RStudio software was used for statistical analysis, applying a random-effects model to calculate the risk ratio (RR) in binary outcomes and mean differences (MD) in continuous outcomes.

Results

We included three RCTs comprising 161 patients. There was no significant difference between the transpapillary and suprapapillary stents regarding the rates of stent migration (RR 2.03; 95% CI 0.41–10.16; p=0.39; I²=55%), cholangitis (RR 0.65; 95% CI 0.08–5.07; p=0.68; I²=0%), technical success (RR 0.99; 95% CI 0.95–1.04; p=0.80; I²=0%), and stent occlusion (MD 89.20; 95% CI 16.30–162.10; p=0.02; I²=78%). However, the mean number of patent stents was significantly lower in the suprapapillary stent group.

Conclusion

The two types of stent seem similar in terms of technique, efficacy, and safety, although the suprapapillary stent seems superior in terms of stent patency.

References

Ko SW, Joo HD, Song TJ, Kim S, Choi SJ, Oh CH, Oh D, Park JS, Yoon SB, Yoon JH, Seo DW, Lee SK. Impact of the suprapapillary method on patency in distal malignant biliary obstruction: a multicenter randomized controlled trial. Gastrointest Endosc. 2024 Oct;100(4):679-687.e1. doi: 10.1016/j.gie.2024.03.024. Epub 2024 Mar 21. PMID: 38521477.
Kurita A, Uza N, Asada M, Yoshimura K, Takemura T, Yazumi S, Kodama Y, Seno H. Stent placement above the sphincter of Oddi is a useful option for patients with inoperable malignant hilar biliary obstruction. Surg Endosc. 2022 May;36(5):2869-2878. doi: 10.1007/s00464-021-08576-x. Epub 2021 Jun 2. PMID: 34076770.
Finn Møller Pedersen, MD, Annmarie Touborg Lassen, Ove B. Schaffalitzky de Muckadell. Finn Møller Pedersen, MD, Annmarie Touborg Lassen, Ove B. Schaffalitzky de Muckadell. Gastroint Endosc. 1998;48(6):574-579.

Introduction

Distal malignant biliary obstruction (dMBO) presents a significant clinical challenge, necessitating effective drainage strategies to improve patient outcomes. Various drainage procedures have been utilized, encompassing percutaneous transhepatic biliary drainage (PTBD), endoscopic retrograde cholangiopancreatography (ERCP), or Endoscopic ultrasound-guided biliary drainage (EUS-BD) including EUS choledochoduodenostomy (EUS-CDS). However, the first-line optimal drainage approach remains debated. This network meta-analysis aims to compare the efficacy and safety of different drainage techniques for distal malignant biliary obstruction.

Aims & Methods

We conducted a systematic literature search of randomized control trials (RCTs) comparing different drainage methods as first-line treatment for distal malignant biliary obstruction. MEDLINE database was searched for relevant studies. Studies reporting outcomes such as technical success, clinical success, adverse events, and stent patency were included. Data were extracted, and a network meta-analysis was performed to compare the efficacy and safety of PTBD, ERCP and EUS-BD.

Results

Review of 649 studies yielded 7 RCTs meeting inclusion criteria for quantitative synthesis. These studies were published between 1987 and 2023, with 3 conducted in single centers and 4 at multiple centers, spanning all continents worldwide. They collectively involved 653 patients with distal malignant biliary obstruction. In terms of technical success, EUS-CDS demonstrates a significant superiority over ERCP (risk ratio [RR] 1.17, 95% CI 1.01–1.35), while no significant differences were observed in other comparisons. Furthermore, for clinical success, EUS-CDS outperforms alternative interventions (RR 1.12, 95% 1.02-1.24). Both in terms of technical and clinical success, EUS-CDS ranked the highest (surface under the cumulative ranking [SUCRA] score, respectively 0.90 and 0.86). Consequently, EUS-CDS emerges as the premier treatment modality. Regarding adverse events, PTBD exhibits a pronounced inferiority compared to all other interventions (RR 2.74, 95% CI 1.25–6.02), whereas no statistically significant distinctions were noted among the remaining treatments.

Conclusion

In conclusion, our network meta-analysis suggests that EUS-CDS emerges as the most effective first-line intervention for distal malignant biliary obstruction, demonstrating superior technical and clinical success rates compared to ERCP. Furthermore, PTBD appears to carry a higher risk of adverse events compared to alternative treatments. These results underscore the importance of considering EUS-CDS as the preferred initial drainage approach in clinical practice, with potential implications for improving patient outcomes in this challenging condition.

Introduction

Bacterial translocation exacerbates circulatory dysfunction present in patients with liver cirrhosis. Probiotics can reduce bacterial translocation and consequently improve the outcomes in this population.

Aims & Methods

This study aims to evaluate the efficacy of probiotics in the cirrhotic patients. We performed a systematic review in PubMed, Embase and Cochrane Central database, searching for studies analyzing the effects of probiotics use in overt hepatic encephalopathy incidence in cirrhotic patients. A Bayesian network meta-analysis was conducted to estimate the relative effects between treatments using risk ratios (RR) and to rank each one according to the Surface Under the Cumulative Ranking Curve (SUCRA).

Results

We included eight studies, comprising 975 patients. The assessment of SUCRA values indicated that lactulose plus probiotics (0.95) emerged as the most effective prevention for overt hepatic encephalopathy. Moreover, lactulose plus probiotics demonstrated superior efficacy compared to lactulose (0.54), probiotics only (0.51), LOLA (0.48), placebo (0.24), and no therapy (0.21). The risk of overt hepatic encephalopathy was low for lactulose plus probiotics (0.000025; credible interval [CrI] 1.3x1016, 1.5), lactulose only (RR 0.64; CrI 0.09, 4.0), probiotics (RR 0.69; CrI 0.17, 2.9), LOLA (RR 0.64; CrI 0.04, 8.9) and no therapy (RR 1.1; CrI 0.22, 7.0).

Conclusion

In our network meta-analysis, the best results in the treatment of the patients with cirrhosis and hepatic encephalopathy was seen with the association of lactulose plus probiotics. Both drugs have good tolerability and are widely disponible, so we suggest considering this association.

Introduction

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths. Unresectable HCC can be treated with transarterial chemoembolization (TACE), which causes hypoxia and induces the expression of vascular endothelial growth factor (VEGF). Antiangiogenic drugs can be useful in this setting.

Aims & Methods

This study aims to compare TACE plus Apatinib (antiangiogenic drug, TACE+A) versus TACE plus Apatinib plus Camrelizumab (immune checkpoint inhibitor, TACE+AC). We performed a systematic review in PubMed, Embase, Cochrane and Web of Science databases, searching for studies comparing TACE+A versus TACE+AC in patients with unresectable HCC. The primary outcomes were overall survival and disease-free progression survival. The secondary outcomes were treatment response and adverse events grade III or IV. The odds ratio (OR) was used for binary outcomes with their respective 95% confidence interval (CI). Heterogeneity was assessed using the Cochran Q test and I² statistics. ​

Results

The meta-analyses included 3 studies and 1,134 patients. There was a significant difference favoring TACE+AC in overall survival (HR 0.41; 95% CI 0.28 to 0.60; p<0.01; I²=87%) and in disease-free progression survival (HR 0.29; 95% CI 0.15 to 0.55; p<0.01; I0²=0%) compared to TACE+A. There is no difference in adverse events grade III or IV between groups (OR 1.08; 95% CI 0.83 to 1.40; p=0.586; I²=0%).

Conclusion

In patients with unresectable HCC, TACE+AC demonstrated superior efficacy compared to TACE+A. The two combinations showed similar safety profiles.

References

1. Duan X, Li H, Kuang D, Chen P, Zhang K, Li Y, et al. Transcatheter arterial chemoembolization plus apatinib with or without camrelizumab for unresectable hepatocellular carcinoma: a multicenter retrospective cohort study. Hepatol Int. 2023 Aug;17(4):915–26.
2. Liu H, Yu Q, Gu T, Qu P, Ma X, Zhou S, et al. Transarterial Chemoembolization plus Apatinib with or without Camrelizumab for the Treatment of Advanced HBV-related Hepatocellular Carcinoma. J Gastrointest Liver Dis JGLD. 2023 Jun 22;32(2):182–9.
3. Zhu D, Ma K, Yang W, Zhou HF, Shi Q, Ren JW, et al. Transarterial chemoembolization plus apatinib with or without camrelizumab for unresected hepatocellular carcinoma: A two-center propensity score matching study. Front Oncol. 2022;12:1057560.