08634476

August 30, 2025, 08:41

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Dear Editor, We read with great interest the article “Outcomes of iodine-125 seed strips combined with double self-expandable metallic stent for Bismuth type III and IV malignant biliary obstruction” by Zhou et al. This study pioneers the evaluation of a novel combination therapy for advanced hilar malignant biliary obstruction (MBO), a clinical challenge with limited treatment options, and reports promising technical success and safety profiles. However, three aspects could be further clarified or expanded to enhance the study’s validity and clinical translational value. First, the study lacks subgroup analysis of outcomes based on stent configuration types and primary disease etiology. The authors employed four stent configurations (Type X, T, Y, and Tandem) tailored to different biliary obstruction patterns, yet they did not compare key endpoints—such as median overall survival (OS), stent patency, or complication rates—across these configurations. For example, Type Y stents (used in 41.2% of patients) may have distinct drainage efficiency or patency durability compared to Tandem stents, which could guide clinicians in selecting the optimal configuration for specific Bismuth subtypes. Additionally, the cohort includes patients with diverse primary diseases (13 with hilar cholangiocarcinoma, 2 with gallbladder cancer liver metastasis, etc.), but no analysis was conducted to determine if the therapy’s efficacy varies by tumor type. Given that different malignancies have distinct biological behaviors (e.g., gallbladder cancer tends to be more aggressive than hilar cholangiocarcinoma), stratifying outcomes by etiology would help identify patient subgroups most likely to benefit from this treatment. Second, the impact of concurrent systemic anticancer therapy on survival outcomes was not adequately addressed. The study mentions that 6 of 17 patients received sequential systemic treatments (e.g., lenvatinib, hepatic artery infusion chemotherapy). These therapies are known to improve survival in advanced biliary tract cancers, yet the current analysis does not adjust for their potential confounding effect—for instance, whether patients receiving systemic therapy had longer OS independent of the combination stent-seed treatment. Without subgroup comparisons (e.g., OS between patients with vs. without concurrent systemic therapy) or multivariate analysis incorporating these treatments as covariates, it is difficult to isolate the true efficacy of the 125I seed strip-double stent regimen. This gap limits the ability to conclude whether the observed survival benefit (median OS 189 days) is primarily driven by the local intervention or concurrent systemic therapy. Third, the study provides insufficient details on long-term radiation-related safety and late complications. While the authors report no severe early complications and only one case of seed strip migration, they do not mention long-term monitoring for radiation-induced adverse events—such as bile duct stricture progression, liver parenchyma damage, or secondary malignancies—despite 125I’s half-life of 60.1 days and cumulative absorbed dose of 82.3–83.6 Gy. Additionally, the definition of “late complications” is unclear, and the follow-up period (final follow-up July 31, 2023) is not specified in terms of median duration for surviving patients. For a therapy involving radioactive seeds, documenting long-term radiation safety (e.g., imaging evidence of liver injury, changes in liver function over time) is critical to assessing its overall risk-benefit profile, especially for patients with prolonged survival (e.g., the 3 surviving patients with patent stents). In summary, Zhou et al.’s study makes a valuable contribution to the management of advanced hilar MBO by introducing a novel combination therapy. Addressing the above issues—through subgroup analyses of stent configurations and etiology, adjustment for concurrent systemic therapy, and detailed long-term safety monitoring—would further strengthen the study’s evidence base and provide more actionable guidance for clinical practice. We look forward to seeing supplementary data or follow-up studies to address these points. Sincerely, Xiong Yuezhihong Yichang Central People's Hospital

First, thank you very much for your professional comments on the article published in World Journal of Gastrointestinal Surgery. Second, we read your comments with great interest. You are welcome to format your valuable comments into a Letter to the Editor and submit it online to World Journal of Gastrointestinal Surgery at https://www.f6publishing.com. There are no restrictions on the number of words, figures (color, B/W) or authors for a Letter to the Editor. In addition, the article processing charge will be exempted for this Letter to the Editor. As with all articles published by the Baishideng Publishing Group, the Letter to the Editor will be published online after completing peer review. The guidelines for a Letter to the Editor can be found at: https://www.wjgnet.com/bpg/GerInfo/219. Finally, we look forward to receiving your high-quality Letter to the Editor, which will promote academic communication and lead the development of this discipline.

Replied on September 02, 2025, 09:02

Thank you very much for your professional comments. Reply as follows： Comments 1 and 2: The number of patients who satisfied the inclusion criteria is limited, but as of now, about 29 patients have satisfied the criteria. We hope that future research can be conducted subgroup analyses of stent configurations and etiology, adjusts for concurrent systemic therapy. Comments 3: Patients with implantation of 125I strips and double SEMS have excellent safety and tolerability, and no severe complications such as stent rupture, liver necrosis, or biliary bleeding have occurred. Sincerely Yours, Dr. Zhou