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Abstract

Background:

Intrahepatic cholangiocarcinoma (ICC) with obstructive jaundice presents a therapeutic challenge, as most patients are ineligible for surgery. While FOLFOX chemotherapy offers limited survival benefits, drug-eluting bead transarterial chemoembolization (DEB-TACE) combined with percutaneous transhepatic cholangial drainage (PTCD) may improve outcomes by addressing both tumor burden and biliary obstruction.

Objective:

To evaluate the efficacy and safety of DEB-TACE + PTCD versus DEB-TACE alone in unresectable ICC patients with obstructive jaundice.

Design:

Retrospective cohort study of 209 patients treated between January 2015 and November 2024.

Methods:

A total of 209 patients with ICC and obstructive jaundice were included, with 95 patients in the DEB-TACE + PTCD group (D + P group) and 114 patients in the DEB-TACE alone group (DEB group). Tumor responses were evaluated at 3 months to assess treatment efficacy, while statistical analyses of adverse events were conducted to evaluate treatment safety. Kaplan–Meier method was utilized to generate survival curves. Cox analysis was performed to identify factors influencing prognosis.

Results:

The median progression-free survival and OS were 6 and 14 months in D + P group and 5 and 11 months in the DEB group. The 3-month objective response rate (ORR) and disease control rate (DCR) were 36.2% and 76.6% in the D + P group. While in the DEB group, the ORR and DCR were 34.2% (p = 0.772) and 62.2% (p = 0.026). Multivariate Cox regression analysis revealed that lymph node metastasis (hazard ratio (HR) = 0.727, confidence interval (CI: 0.535–0.987), p = 0.041), level of cancer antigen (CA)-125 (HR = 0.670, CI (0.503–0.894), p = 0.006), and treatment (HR = 1.335, CI (1.002–1.780), p = 0.049) were predictors for prognosis.

Conclusion:

For patients with unresectable cholangiocarcinoma complicated by obstructive jaundice, DEB-TACE following PTCD may be a safer and more effective treatment.

Keywords

drug-eluting beads efficacy and safety intrahepatic cholangiocarcinoma percutaneous transhepatic cholangial drainage transcatheter arterial chemoembolization

Introduction

Intrahepatic cholangiocarcinoma (ICC), though rare, is the second most common primary liver malignancy after hepatocellular carcinoma,¹ accounting for 10%–15% of liver cancers according to statistics on global cancer patients in 2022.² Most ICC patients present with obstructive jaundice at diagnosis, precluding curative surgery and limiting treatment to palliative options.³ Only ~30% of patients are surgical candidates,⁴ and even after resection, recurrence rates reach 40%–80%, with 5-year survival at just 25%–35%.⁵ Untreated advanced ICC carries a dismal prognosis, with a median overall survival (OS) of 5–8 months.⁶

Currently, FOLFOX chemotherapy is the recommended treatment for patients with cholangiocarcinoma. While it serves as the first-line adjuvant therapy, the survival benefit remains modest, with a median survival of only 19.6 months based on a previous study.⁷ Transcatheter arterial chemoembolization (TACE) is a viable treatment option for most patients with unresectable cholangiocarcinoma. However, the limited blood supply characteristic of cholangiocarcinoma poses challenges for the sustained presence and drug release of iodinated oil within the tumor. Consequently, drug-eluting bead (DEB) embolization materials have become a preferred option in clinical practice, as they allow for precise embolization of blood vessels while enabling prolonged release of chemotherapy drugs directly within the tumor.^8,9 Specifically, the combination of drug-eluting bead transarterial chemoembolization (DEB-TACE) with hepatic arterial infusion chemotherapy has shown superior efficacy compared to conventional TACE in recent multicenter trials.¹⁰ It is disheartening that the median OS for patients undergoing TACE treatment remains only about 12 months, even when employing DEB-TACE with chemotherapy drug microspheres such as epirubicin and irinotecan.^11,12 Since bile duct obstruction commonly occurs in advanced cholangiocarcinoma, and drug-induced bile duct descent may worsen liver function, percutaneous transhepatic cholangial drainage (PTCD) is clinically prevalent. However, the safety and efficacy of PTCD prior to DEB-TACE remain unevaluated.

This study aimed to compare the efficacy and safety profiles of DEB-TACE following PTCD versus DEB-TACE in patients with unresectable cholangiocarcinoma complicated by obstructive jaundice, thereby providing critical evidence to guide treatment selection for unresectable ICC patients with biliary obstruction.

Methods

Patients

This retrospective cohort study analyzed all eligible patients (n = 209) undergoing DEB-TACE with or without PTCD at our institution between January 2015 and November 2024. The sample size estimation was based on detecting a target hazard ratio (HR) of 0.65 for OS, with a two-sided α = 0.05 and 80% power (β = 0.20). Initial calculations yielded 82 patients per group, which was adjusted to 95 per group (+15%) to account for potential incomplete data. Due to real-world clinical practice, the final cohort comprised 95 patients in the DEB-TACE + PTCD group and 114 in the DEB-TACE-alone group. Post hoc power analysis demonstrated 83.7% power to identify the observed HR of 0.71 for OS. The inclusion criteria for this study were as follows: (1) age greater than 18 years; (2) pathology-confirmed diagnosis of ICC; (3) availability of complete clinical data (such as a complete follow-up period, complete imaging data, and test results) and follow-up records; (4) Child-Pugh stage A or B; (5) presence of obstructive jaundice; and (6) patients not receiving combination therapy used medication would use medication to reduce bilirubin levels. The exclusion criteria included: (1) coexisting malignant tumors; (2) Child-Pugh stage C; (3) severe cardiopulmonary, hepatic, or renal dysfunction; and (4) prior surgical treatment. The study methodology was in accordance with the ethical guidelines of the 1975 Declaration of Helsinki. This study was approved by the Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology. The reporting of this study conforms to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement.¹³ The flow diagram was shown in Figure 1.

Figure 1.

The flowchart of patients’ selection.

Baseline clinical data

The baseline clinical data collected from the patients comprised age, sex, hepatitis history, Eastern Cooperative Oncology Group performance status score, Child-Pugh stage, treatment procedures, number of lesions, tumor locations, maximum tumor diameter, the presence of lymph node metastases, the level of alpha-fetoprotein (AFP), the level of CA-125, and CA-199. In addition, we collected results from liver function tests performed both before the procedure and 3 months after surgery. The change in the test indicators represents the difference between the postoperative and preoperative results (If the patient passes away within 3 months post-surgery, please gather the most recent hospitalization test results).

PTCD procedure

PTCD procedure is also performed by surgeons with more than 5 years of experience. The procedure was performed using a standardized protocol: (1) initial ultrasound localization of the target bile duct; (2) ultrasound-guided percutaneous transhepatic access using an 18G× 200 mm puncture needle; (3) contrast injection through the needle under digital subtraction angiography (DSA) to confirm biliary tree opacification; (4) ultrasound-guided placement of an 8-French pigtail drainage catheter; (5) final contrast administration through the drainage catheter to verify optimal positioning; and (6) secure fixation of the external drainage system.

DEB-TACE procedure

DEB-TACE procedure is performed by operators with over 5 years of experience in interventional surgery, and the diameter of CBs (Jiangsu Hengrui Medicine Co., Ltd., Lianyungang, Jiangsu, China) used in this study was 100–300 and 300–500 μm. Before the surgery, CBs were mixed with epirubicin or irinotecan in a 20 mL syringe for later use. First, we employed the Seldinger technique to puncture the right femoral artery. Subsequently, a 5-F RH catheter was utilized to identify the tumor-feeding artery in the abdominal trunk and the superior mesenteric artery. Upon visualization of tumor staining and the feeding artery through DSA, a 2.4F microcatheter was advanced for super-selective access to the tumor-feeding artery. Following this, DEBs and contrast agents, which had been prepared prior to the procedure, were aspirated into a syringe and injected through the microcatheter for embolization. The embolization procedure was halted when the flow rate of the contrast agent began to slow or stagnate. Finally, the microcatheter was removed, and angiography of the peritoneal trunk and superior mesenteric artery was performed again using the RH catheter to confirm whether the tumor staining had resolved.

Follow-up and assessment

Patients were followed up until November 30, 2024, with CT or MRI follow-up visits scheduled every 3 weeks after surgery at the outpatient department. Tumor response was evaluated using the modified Response Evaluation Criteria in Solid Tumors (mRECIST), which categorizes outcomes as complete response (CR), partial response (PR), stable disease (SD), or progressive disease.^14,15 The tumor responses at 3 months following TACE combined with PTCD treatment were evaluated by two experienced radiologists using the mRECIST criteria. The objective response rate (ORR) was defined as the proportion of patients achieving CR or PR among the total number of evaluable cases, while the DCR was defined as the proportion of patients achieving CR, PR, or SD among the total number of evaluable cases. The primary follow-up endpoints included OS and progression-free survival (PFS). OS was defined as the time from the start of treatment to the date of death or the end of follow-up, while PFS was defined as the time from the start of treatment to the date of imaging-documented progression or death. All deaths were treated as events in the OS analysis. And as for PFS, deaths before progression (n = 32) were counted as events.

Statistical analyses

All results were presented as either mean or median, along with the interquartile range. Missing data (e.g., 3-month tumor response due to early death) were excluded from response rate calculations but included in survival analyses via intention-to-treat. Prognostic factors for OS were assessed using univariate and multivariate Cox regression analyses. In univariate Cox regression analysis, p-values less than 0.1 will be included in multivariate Cox regression analysis. The Kaplan–Meier method was employed to generate survival curves, with the log-rank test applied for comparisons. All analyses were performed using SPSS software, version 29.0 (IBM, Armonk, NY, USA), while GraphPad Prism software, version 10.0 (San Diego, CA, USA) was utilized for additional statistical analyses. A p value of less than 0.05 was deemed statistically significant.

Results

Patient characteristics

After screening by inclusion and exclusion criteria, there were 95 patients in the D + P group and 114 patients in the DEB group. The baseline characteristics of all patients were presented in Table 1. Among the 209 patients in this study, 103 were under the age of 60, with the majority being men, accounting for 138 individuals. Tumor marker tests revealed elevated levels of AFP in 91 patients, CA-125 in 96 patients, and CA-199 in 100 patients. Imaging studies, including CT and MRI, identified lymph node metastasis in 71 patients. In addition, most tumors were solitary (131 patients) and had a diameter greater than 5 cm (117 patients). Except for the changes in aspartate aminotransferase and alanine aminotransferase, there was no difference in other clinical baseline information between the two groups (p > 0.05). Ten patients (10.5%) in the D + P group and 11 patients (9.6%) in the DEB group experienced an increase in bilirubin levels.

Table 1.

Baseline characteristics.

Characteristics	DEB-TACE + PTCD(n = 95)	DEB-TACE(n = 114)	p Value
Gender			0.505
Male	65(68.4%)	73(64.0%)
Female	30(31.6%)	41(36.0%)
Age (years)			0.743
<60	48(50.5%)	55(48.2%)
⩾60	47(49.5%)	59(51.8%)
Smoke history			0.919
Yes	41(43.2%)	50(43.9%)
No	54(56.8%)	64(56.1%)
Drink history			0.430
Yes	39(41.1%)	53(46.5%)
No	56(58.9%)	61(53.5%)
ECOG			0.446
0	40(42.1%)	54(47.4%)
1	55(57.9%)	60(52.6%)
HBV infection			0.698
Yes	44(46.3%)	51(44.7%)
No	51(53.7%)	63(55.3%)
AFP (ng/mL)			0.508
⩽25	56(58.9%)	62(54.4%)
>25	39(41.1%)	52(45.6%)
CA-125 (U/mL)			0.462
⩽35	54(56.8%)	59(51.8%)
>35	41(43.2%)	55(48.2%)
CA-199 (U/mL)
⩽35	53(55.8%)	56(49.1%)	0.337
>35	42(44.2%)	58(50.9%)
LN metastases			0.936
Yes	32(33.7%)	39(34.2%)
No	63(66.3%)	75(65.8%)
ALT (IU/L)	52.87 ± 31.15	48.04 ± 31.50	0.269
AST (IU/L)	51.31 ± 25.23	52.22 ± 29.27	0.811
TB (μmol/L)	74.99 ± 43.1	70.49 ± 55.91	0.522
Albumin (g/L)	36.99 ± 5.01	36.47 ± 4.75	0.447
PT(s)	14.04 ± 1.69	14.09 ± 1.08	0.818
ΔALT	−11.46 ± 87.68	11.32 ± 60.77	0.028
ΔAST	−9.32 ± 40.77	9.04 ± 55.57	0.240
ΔTB	−44.72 ± 65.40	−35.91 ± 41.79	0.240
ΔAlb	−1.07 ± 6.05	−0.33 ± 6.32	0.393
ΔPT	0.43 ± 1.41	0.16 ± 1.28	0.149
Tumor size (cm)			0.959
⩽5	42(44.2%)	50(43.9%)
>5	53(55.8%)	64(56.1%)
Tumor number			0.676
1	61(64.2%)	70(61.4%)
>1	34(35.8%)	44(38.6%)
Tumor location			0.421
Hilum	38(40.0%)	51(44.7%)
Periphery	57(60.0%)	63(55.3%)

AFP, alpha-fetoprotein; Alb, albumin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; DEB-TACE, drug-eluting bead transarterial chemoembolization; ECOG, Eastern Cooperative Oncology Group; HBV, Hepatitis B virus; LN metastases, lymph node metastasis; mRECIST, the modified Response Evaluation Criteria in Solid Tumors; PT, prothrombin time; PTCD, percutaneous transhepatic cholangial drainage; TB, total bilirubin.

The bold values denote p value less than 0.05 with statistical signifcance.

Tumor response

During the follow-up period of all patients, four patients did not receive mRECIST scores due to a survival period of less than 3 months. There was no significant difference in the ORR between the two groups, which stood at 36.2% and 34.2%, respectively (p = 0.772). Conversely, there was a statistically significant difference in DCR between the two groups, with rates of 76.6% and 62.2%, respectively (p = 0.026). The results were shown in Table 2.

Table 2.

The mRECIST scores for two groups.

mRECIST	DEB-TACE + PTCD (n = 95)	DEB-TACE (n = 114)	p value
CR	2	1
PR	32	37
SD	38	31
PD	22	42
ORR(CR + PR)	36.2%	34.2%	0.772
DCR(CR + PR + SD)	76.6%	62.2%	0.026

CR, complete response; DCR, disease control rate; DEB-TACE, drug-eluting bead transarterial chemoembolization; ORR, objective response rate; PD, progressive disease; PR, partial response; PTCD, percutaneous transhepatic cholangial drainage; SD, stable disease.

The bold values denote p value less than 0.05 with statistical signifcance.

Prognostic factors for OS

Univariate Cox regression analysis indicated that lymph node metastasis (HR = 0.690, confidence interval (CI; 0.508–0.935), p = 0.017), the cancer antigen (CA)-125 level (HR = 0.657, CI (0.492–0.877), p = 0.004), and type of treatment (HR = 1.442, CI (1.086–1.915), p = 0.012) were also linked to reduced survival durations in patients. These three factors were then included in a multivariate Cox regression analysis and results revealed that an increase in lymph node metastases (HR = 0.727, CI (0.535–0.987), p = 0.041), high level of CA-125 (HR = 0.670, CI (0.503–0.894), p = 0.006), and patients who received DEB-TACE alone (HR = 1.335, CI (1.002–1.780), p = 0.049) corresponded to a shorter survival period for patient. The results of univariate and multivariate Cox regression analysis are listed in Table 3.

Table 3.

Univariate and multivariate analysis of factors associated with overall survival.

Variable	Univariate analysis			Multivariate analysis
Variable	HR	95% CI	p	HR	95% CI	p
Gender Female/male	1.099	0.815–1.481	0.536
Age (years) ⩽60/>60	1.012	0.764–1.339	0.936
Smoking history Yes/no	1.106	0.833–1.469	0.485
Drinking history Yes/no	0.857	0.645–1.140	0.289
Treatment TACE + PTCD/TACE	1.442	1.086–1.915	0.012	1.335	1.002–1.780	0.049
ECOG 0/1	0.850	0.641–1.127	0.259
HBV infection Yes/No	1.108	0.837–1.467	0.474
AFP (ng/mL) ⩽25/>25	1.579	0.486–2.574	0.463
CA-125 (U/mL) >35/⩽35	0.657	0.492–0.877	0.004	0.670	0.503–0.894	0.006
CA-199 (U/mL) >35/⩽35	0.933	0.704–1.237	0.630
Tumor size (cm) ⩽5/>5	1.092	0.909–1.313	0.346
Tumor number Solitary/multiple	0.822	0.619–1.109	0.174
LN metastases Yes/no	0.690	0.508–0.935	0.017	0.727	0.535–0.987	0.041

AFP, alpha-fetoprotein; CA-125, cancer antigen 125; CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; HR, hazard ratio; LN, lymph node; PTCD, percutaneous transhepatic cholangial drainage; TACE, transarterial chemoembolization.

The bold values denote p value less than 0.05 with statistical signifcance.

Follow-up

In this study, the median OS and PFS of patients in the D + P group were 14 months (95% CI, 12.7–15.3) and 6 months (95% CI, 5.3–6.7), which in the DEB-TACE group, the median OS and PFS were 11 months (95% CI, 8.8–13.2) and 5 months (95% CI, 4.1–5.9). There is a difference in OS between the two groups (p = 0.007). In the D + P group, 10 patients (10.5%) and in the DEB group, 11 patients (9.6%) experienced an increase in bilirubin levels (p = 0.834). However, no significant difference was observed in PFS (p = 0.699). And the Kaplan–Meier curves of OS and PFS of the patients were shown in Figure 2. During the 3-month follow-up, seven patients exhibited an increase in bilirubin levels compared to their preoperative measurements, while the jaundice in the remaining patients was effectively managed. In addition, three patients demonstrated a notable decline in liver function during the follow-up assessment. Based on the findings from the multivariate Cox analysis, we categorized patients based on the presence of lymph node metastasis and whether their CA-125 levels were below 35. The results indicated that, in cases of lymph node metastasis and elevated CA-125 levels, the OS of the D + P group was significantly higher than that of the DEB group (16 vs 11 months, p < 0.0001, and 16 vs 10 months, p = 0.002). Conversely, there was no notable difference in OS between the two groups among patients without lymph node metastasis and with low CA-125 levels (p = 0.652 and p = 0.719). The results were shown in Figure 3.

Figure 2.

Kaplan–Meier curves show the OS and PFS. (a) The OS curve (95% CI, 12.7–15.3). (b) The PFS curve (95% CI, 5.3–6.7).

Figure 3.

The OS of different subgroups. (a) The OS curve of patients with LN metastases. (b) The OS curve of patients with non-LN metastases. (c) The OS curve of patients with a low level of CA-125. (d) The OS curve of patients with a high level of CA-125.

Adverse events

The adverse events experienced by patients during treatment are presented in Table 4. Notably, none of the patients in the entire research cohort reported grade 4 adverse reactions. Among all the patients, the most common adverse effects included nausea/vomiting (62.2%, 130/209), fever (56.9%, 119/209), abdominal pain (63.2%, 132/209), and aminotransferase elevation (51.2%, 107/209). There is a statistically significant difference in the number of patients exhibiting posterior abdominal pain and aminotransferase elevation between the two groups (p = 0.014 and 0.034).

Table 4.

Common toxic effects encountered after treatment.

Toxic effect	DEB-TACE + PTCD(n = 95)	DEB-TACE(n = 114)	p Value
Nausea/vomiting	61(64.2%)	69(60.5%)	0.070
Fever	56(58.9%)	63(55.3%)	0.592
Abdominal pain	69(72.6%)	63(54.4%)	0.014
Aminotransferase elevation	41(43.2%)	66(57.9%)	0.034
Fatigue	39(41.1%)	35(30.7%)	0.119
Infection	14(14.7%)	12(10.5%)	0.358

DEB-TACE, drug-eluting bead transarterial chemoembolization; PTCD, percutaneous transhepatic cholangiography.

The bold values denote p value less than 0.05 with statistical signifcance.

Discussion

ICC is a highly malignant tumor, and patients have almost no symptoms in the early stages of the tumor, so many patients have already lost the opportunity for surgery when diagnosed.¹⁶ Due to the characteristics of ICC itself, many patients often have symptoms of malignant obstructive jaundice. Severe obstructive jaundice can induce bilirubin to enter the bloodstream, causing multiple organ failure.¹⁷

In this study, we conducted a retrospective analysis to compare the efficacy and safety of DEB-TACE combined with PTCD and DEB-TACE alone in patients with unresectable cholangiocarcinoma complicated who complicated by obstructive jaundice. The 3-month ORR of the two groups was 36.2% and 34.2%, respectively. And the DCR of the two groups was 76.6% and 62.2%, respectively. There was no difference in the ORR between the two patient groups, although the combined treatment group exhibited a higher DCR. We speculate that this is mainly because PTCD improves liver function by relieving biliary obstruction, rather than directly anti-tumor, and therefore is more likely to affect disease stability (DCR) rather than tumor shrinkage (ORR). Compared to medication, PTCD has a lesser impact on liver function, enabling patients to undergo further treatment in a better overall condition. However, the ORRs in this study were lower than those reported in previous studies, while the DCRs were slightly higher than those findings.^11,18,19 This discrepancy can be attributed to the fact that patients with concurrent obstructive jaundice tend to have poorer baseline health and more advanced tumor staging compared to the general patient population. Consequently, achieving CR or PR 3 months post-treatment is often challenging, leading to a lower ORR. However, the treatment approach utilized in this study effectively managed tumor progression and alleviated biliary obstruction, which contributed to a more stable clinical condition. As a result, the DCR was slightly higher than that observed in earlier research.

Multivariate Cox regression analysis indicated that lymph node metastasis, CA-125 level type of treatment were associated with patient prognosis. Specifically, a greater extent of lymph node metastasis correlates with a shorter OS for patients. The same result appeared in the research of Asaoka T²⁰, and in a prospective study, CA-125 levels greater than 35 were also prognostic factors, which is similar to the results of this study.²¹ Based on the results above, we categorized patients according to the presence of lymph node metastasis and whether their CA-125 levels ⩾35 U/mL. The findings indicated that patients with lymph node metastasis and elevated CA-125 levels who received combination therapy experienced a higher OS compared to those who underwent DEB-TACE alone. However, there was no significant difference in OS between the two treatment methods in patients without lymph node metastasis or with low CA-125 levels. Therefore, we believe that when patients have poor baseline conditions, PTCD should be prioritized over medication to reduce bilirubin levels.

The OS of the two patient groups demonstrated a statistically significant difference, with durations of 14 and 11 months, respectively. However, there was no significant difference in PFS between the two groups, which were 6 and 5 months, respectively. These results indicated that patients treated with combination therapy have a better prognosis than those who received TACE after bilirubin levels were reduced through medication. While the absolute difference in median OS between combination therapy and DEB-TACE alone was 3 months, this statistically significant improvement carries substantial clinical importance for this challenging patient population. A recent meta-analysis demonstrated comparable median OS between DEB-TACE-treated ICC patients (13.8 months) and our PTCD plus DEB-TACE patients.²² We considered the inherently poor prognosis of advanced cholangiocarcinoma with obstructive jaundice (where even first-line regimens achieve limited survival). Therefore, the critical need for any meaningful survival extension is essential. Since PTCD is solely a treatment for biliary obstruction, it does not effectively control the progression of the lesion. As a result, there is no difference in PFS between the two groups. In comparison to previous studies, we found that the prognosis associated with combination therapy in this study was not superior. For instance, in a study comparing the treatment of unresectable cholangiocarcinoma using DEB-TACE and C-TACE, the median OS for patients receiving DEB-TACE was found to be 12 months.¹⁰ In addition, another study demonstrated that DEB-TACE combined with first-line chemotherapy achieved a median OS of 18 months and a median PFS of 12 months.²³ Furthermore, a study examining radiofrequency ablation, PTCD, and biliary stent placement for patients suffering from obstructive jaundice due to cholangiocarcinoma reported a median survival time of 11 months.²⁴ We believed that the relatively modest outcomes observed in our study can be attributed to the poorer baseline health status of patients with concomitant obstructive jaundice, and the patients included in the research before may include earlier-stage cases.

As for safety, no therapy-related deaths occurred in our study, and fortunately, none of the patients developed liver abscess after surgery. Previous studies have identified common complications following TACE and PTCD procedures, which primarily include fever, pain, and elevated transaminase levels.^22,25–27 In line with these findings, the present study observed that most patients experienced one to two of the aforementioned symptoms, all of which fully resolved within 1 month with appropriate postoperative medical treatment. It is noteworthy that the proportion of patients experiencing abdominal pain was higher in the combination therapy group, which may be attributed to the invasive nature of PTCD. Conversely, a greater proportion of patients in the DEB-TACE group alone exhibited elevated transaminase levels, primarily due to the use of medications aimed at reducing bile stasis, which significantly affected liver function in this patient group. Therefore, the findings of this study suggest that the short-term combination therapy of TACE and PTCD does not impose an additional burden on patients and does not result in serious side effects. And three severe biliary infections occurred exclusively in the DEB-TACE + PTCD cohort, all resolving with antibiotic therapy. This complication likely stems from PTCD-induced biliary tract manipulation and microstructural damage. The absence of liver failure cases in both treatment groups demonstrates favorable hepatic safety profiles for DEB-TACE with or without PTCD. This finding supports the overall tolerability of these interventions, even in patients with obstructive jaundice.

Our study has several limitations. First, while many patients with cholangiocarcinoma present complicated by obstructive jaundice, the number of cases included in this study remains relatively small after applying the inclusion and exclusion criteria. This may affect the statistical validity and require a larger sample size validation in the future. Second, as this is a single-center study, the total number of cases remains limited despite a relatively long observation period. Due to the long inclusion period of this study, the improvement of DEB-TACE technology during this period may become a confounding factor. Third, although experienced radiologists evaluated the imaging data, it was challenging to apply the mRECIST criteria to assess the safety and efficacy of DEB-TACE in ICC due to the presence of irregular necrosis. And while competing risks (e.g., liver failure) were rare in our cohort, future studies may consider dedicated competing risk models to dissect cancer-specific mortality. Therefore, future multicenter, prospective research should be conducted.

Conclusion

In conclusion, PTCD-mediated biliary decompression prior to DEB-TACE represented a safe and effective treatment strategy for patients with unresectable cholangiocarcinoma complicated by obstructive jaundice. Importantly, patients with lymph node metastasis and elevated CA-125 levels may opt for combination therapy. These findings may provide clinically actionable evidence for personalizing therapeutic decisions in this challenging patient population.

Supplemental Material

sj-docx-1-tag-10.1177_17562848251360114 – Supplemental material for Outcome of adding percutaneous transhepatic cholangial drainage to DEB-TACE in patients with unresectable cholangiocarcinoma with obstructive jaundice: comparison with sole DEB-TACE

Supplemental material, sj-docx-1-tag-10.1177_17562848251360114 for Outcome of adding percutaneous transhepatic cholangial drainage to DEB-TACE in patients with unresectable cholangiocarcinoma with obstructive jaundice: comparison with sole DEB-TACE by Jiajia Xu, Chao Chen, Yanhua Ye, Yanqiao Ren, Ke Chen, Guofeng Zhou, Chuan Cheng and Yuexiang Peng in Therapeutic Advances in Gastroenterology

Footnotes

Acknowledgements

We thank to all the medical workers in our department for their assistance with the study.

Declarations

ORCID iDs

Chao Chen

Yanqiao Ren

Supplemental material

Supplemental material for this article is available online.

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