|Year : 2021 | Volume
| Issue : 3 | Page : 784-789
Trans-jugular intrahepatic portosystemic shunt in patients with hepatic cellular carcinoma: A preliminary study
Hong Dong1, Cunjing Zhang2, Zheng Li3, Haiyan Yang3, Yongzheng Wang3, Jibing Liu4, Bin Liu3, Shuzhi Mao5
1 Nursing Department, The Second Hospital of Shandong University; Interventional Oncology Institute, Shandong University, Jinan, Shandong Province, China
2 Dean' s Office, Jinan Vocational College of Nursing, Jinan, Shandong Province, China
3 Interventional Oncology Institute, Shandong University; Department of Interventional Medicine, The Second Hospital of Shandong University, Jinan, Shandong Province, China
4 Interventional Oncology Institute, Shandong University; Department of Interventional Medicine, Shandong Cancer Hospital, Jinan, Shandong Province, China
5 Interventional Oncology Institute, Shandong University; Department of Sterilization and Supply, The Second Hospital of Shandong University, Jinan, Shandong Province, China
|Date of Submission||21-Mar-2021|
|Date of Decision||22-Mar-2021|
|Date of Acceptance||23-Mar-2021|
|Date of Web Publication||9-Jul-2021|
Department of Sterilization and Supply, Second Hospital of Shandong University, Jinan, Shandong Province, CN-250 033
Source of Support: None, Conflict of Interest: None
Purpose: To analyze the effects of trans-jugular intrahepatic portosystemic shunt (TIPS) on portal hypertension and liver function in patients with hepatocellular carcinoma (HCC).
Materials and Methods: Thirteen patients with hemorrhage caused by portal hypertension and HCC who received TIPS and antitumor treatment were retrospectively analyzed. Trans-arterial chemoembolization, microwave ablation, target therapy, and immunetherapy or combined therapy were performed to treat HCC. Child-Pugh score was applied to estimate liver functions before and after TIPS. Shunting patency, overall survival (OS), and progression-free survival were analyzed.
Results: The median age was 58 (interquartile range: 52.5–62.5) years. The ratio with ascites before and after TIPS was 84.6% (11/13) and 7.7% (1/13), with P < 0.001. The ratio with Child-Pugh A before and after TIPS were 61.5% (8/13) and 84.6% (11/13) respectively, with P = 0.179. Mean portal vein pressure before and after TIPS was 27.85 ± 7.02 mmHg and 16.23 ± 6.61 mmHg, respectively, with P = 0.001. Two-year shunting patency rate was 61.5%. Median OS was 29.8 ± 11.5 months (95% confidence interval [CI] 22.8–36.7), and median progression-free survival was 20.2 ± 13.2 months (95% CI 12.2–28.1).
Conclusion: TIPS could reduce ascites, down-regulate the Child-Pugh score, and give a chance for further anti-tumor therapy.
Keywords: Ascites, hepatocellular carcinoma, survival, trans-jugular intrahepatic portosystemic shunt
|How to cite this article:|
Dong H, Zhang C, Li Z, Yang H, Wang Y, Liu J, Liu B, Mao S. Trans-jugular intrahepatic portosystemic shunt in patients with hepatic cellular carcinoma: A preliminary study. J Can Res Ther 2021;17:784-9
|How to cite this URL:|
Dong H, Zhang C, Li Z, Yang H, Wang Y, Liu J, Liu B, Mao S. Trans-jugular intrahepatic portosystemic shunt in patients with hepatic cellular carcinoma: A preliminary study. J Can Res Ther [serial online] 2021 [cited 2021 Jul 26];17:784-9. Available from: https://www.cancerjournal.net/text.asp?2021/17/3/784/321032
| > Introduction|| |
Hepatocellular carcinoma (HCC) remains one of the most common cancers worldwide. The majority of patients with HCC have associated liver cirrhosis, which will cause severe clinical complications due to progressively increased portal hypertension., Patients may develop gastroesophageal varices and/or other portosystemic collaterals, but even more importantly, hepatic decompensation. Ascites, as one clinical manifestation of hepatic decompensation, will down regulate Child-Pugh score, which makes patients are deprived of further anti-tumor treatments, and eventually reduces the overall survival (OS).,
Transjugular intrahepatic portosystemic shunt (TIPS) is an established procedure that has proven benefits in the treatment of patients who have the complications of portal hypertension, including ascites., Theoretically, the reduction or elimination of ascites reflects improved liver function and down-regulates the Child-Pugh score, which gives a chance for further anti-tumor therapy., However, the comparisons of portal vein pressure (PVP) and liver function staging before and after TIPS have not yet been analyzed. We hereby report a consecutive cohort of patients with HCC treated with TIPS and retrospectively analyze the effect of TIPS on portal hypertension and liver function.
| > Materials and Methods|| |
From Jun 2015 to Jul 2018, patients with hemorrhage caused by portal hypertension [Figure 1]a and HCC [Figure 1]b who received TIPS and antitumor treatment were selected, and 13 of them were eventually analyzed [Figure 2]. The study protocol was approved by the ethics committees by participating hospitals. Written informed consent was obtained from all participants. The study was performed in compliance with Good Clinical Practices and human investigations committee guidelines.
|Figure 1: (a) Hypertension demonstrated by esophagogastric varices (blue arrow). (b) A tumor located in segment V (blue arrow). (c) Right hepatic vein was punctured through the transjugular approach. (d) Esophagogastric vein varices demonstrated by angiography (blue arrow). (e) Coils (blue arrow) and glues (red arrow) located in esophagogastric vein after embolization. (f) Stents (blue arrow) was placed and angiography revealed shunting patency. (g) Microwave antennas (blue arrows) were inserted into the tumor. A puncture needle (red arrow) was used to for bile extraction to protect the gallbladder. (h) Computed tomography after the procedure demonstrated complete ablation (blue arrow). A drainage catheter (red arrow) was placed in the gallbladder|
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Longest diameter of the tumor was measured according to the modified Response Evaluation Criteria in Solid Tumors criteria. Barcelona Clinic Liver Cancer (BCLC) staging system and Child-Pugh score were applied to estimate the tumor stages and liver functions, respectively.
The definition of refractory ascites was according to the International Ascites Club: (a) intensive diuretics (spironolactone 400 mg/day combined with furosemide 160 mg/day) and sodium-restricted diet (<90 mmoVd) for at least 1 week have no response; (b) Lack of response to diuretic therapy; (c) Early recurrence of ascites within 4 weeks; and (d) Diuretic-induced complications. The grading of ascites was divided into mild ascites, moderate ascites, and large or gross ascites.
Inclusion and exclusion criteria
(1) Clinical or pathological diagnosis of HCC; (2) portal hypertension that is verified by ultrasonography, computed tomography (CT), or magnetic resonance imaging (MRI); (3) previous hemorrhage due to gastroesophageal varices; (4) 18–70 years.
(1) Tumor volume >70% of the liver; (2) East Coast Oncology Group score >2; (3) extrahepatic metastasis; (4) portal vein invasion; (5) obstructive jaundice; (6) severe cardiac insufficiency (New York Heart Association Class III-IV) or advanced lung disease as determined by consultation with respiratory disease specialists; (7) uncorrectable coagulopathy (prothrombin time was prolonged by more than 3 s and/or platelet count ≤60 × 109/L with baseline value of 125–350 × 109/L).
Transjugular intrahepatic portosystemic shunt procedure
Patients underwent moderate sedation receiving 0.1 mg fentanyl bolus and dexmedetomidine infusion at a rate of 1.5 μg/kg/h. Right hepatic vein was punctured through the transjugular approach [Figure 1]c, and the parenchymal tract was dilated by a balloon catheter (Cook Medical, Bloomington, Indiana, U. S. A.). Esophagogastric vein was embolized with a mixture of α-Butyl-2-Cyanoacrylate (Compont, Beijing, China) and Ethiodized Poppyseed Oil (Hengrui Pharmaceutical, Lianyungang, China), as well as coils if necessary (Interlock, Boston Scientific, Natrik, Massachusetts) [Figure 1]d, [Figure 1]e. Bare stent (Zilver vascular stent, Cook Medical, Bloomington, Indiana, U. S. A.) and covered stent (Viabahn endoprosthesis, W. L. Gore and Associates, Flagstaff, Arizona, U. S. A.) were put in the parenchymal tract successively [Figure 1]f. Usually, the diameter of bare and covered stent was 8 mm. The length of bare stent was 60 mm or 80 mm, and the length of covered stent was 50 mm. The PVP was measured before and after shunt creation. After the procedure, all participants with normal prothrombin time received anticoagulant therapy by oral administration of Rivaroxaban.
One month after TIPS, BCLC stage and Child-Pugh score were estimated. For participants with Child-Pugh A-B and BCLC Stage A-B, trans-arterial chemoembolization (TACE), microwave ablation (MWA), target therapy, immune therapy, or combined therapy were performed to treat HCC.
TACE was conducted for to decrease the vascularity and localize the tumors. MWA was performed to eliminate or reduce tumors [Figure 1]g and [Figure 1]h. Target therapy (Sorafenib, Bayer, Leverkusen, Germany; or Apatinib, Hengrui Pharmaceutical, Lianyungang, China) and immune therapy (Camrelizumab, Hengrui Pharmaceutical, Lianyungang, China) were recommended after TACE and MWA.
Follow-up was conducted at the 3rd and 6th months and every 3 months thereafter, including standard blood count, liver functional tests, alpha fetoprotein, blood clotting function, enhanced abdominal CT, and enhanced MRI.
The responses to TIPS are defined as follows: Complete response (CR): No clinically obvious ascites or no requirement for diuretics and sodium limitation. Partial response (PR): Clinically obvious ascites and no need for further paracentesis. Absent response (AR): Development of large amounts of ascites after TIPS.
Shunt dysfunction was defined as follows: A maximum flow velocity within the shunt of ≤60 cm/s or >180 cm/s or within the portal vein of ≤30 cm/s, recurrent ascites, or variceal bleeding. Suspected dysfunction was diagnosed using portography and an evaluation of the portosystemic pressure gradient of ≥15 mmHg.
Primary outcome was OS, defined as the interval from TIPS to death or lost to follow-up. Secondary outcomes included progress free survival (PFS), change in Child–Pugh stage, change in Child–Pugh scores, and the response of TIPS and complications.
Categorical variables were presented as number and percentage, and analyzed using the Chi-square or Fisher's exact test. Continuous variables with normal distribution are expressed as mean ± standard deviation, and analyzed with Student's t-test. Continuous variables not following normal distribution are expressed as median and interquartile range (IQR), and analyzed using Wilcoxon rank-sum test. Quantitative data before and after TIPS were evaluated using the paired t-tests.
All statistical analyses were conducted using the SPSS software version 24.0 (SPSS Inc., Chicago, IL, USA). Statistical significance was defined as P < 0.05.
| > Results|| |
A total of 24 patients with HCC and portal vein hypertension were selected. Nine patients were excluded due to tumor volume >70% of the liver (n = 2), extrahepatic metastasis (n = 2), portal vein invasion (n = 2), obstructive jaundice (n = 1), severe cardiac insufficiency (n = 1), and advanced lung disease (n = 1). Two patients lost to follow-up. Thirteen participants (8 males) were eventually analyzed.
The participants' characteristics were listed in [Table 1]. The median age was 58 (IQR: 52.5–62.5) years. The etiologies of cirrhosis included hepatitis B (92.3%, 12/13) and alcohol (7.6%, 1/13). Tumors were located in segment V (23.1%, 3/13), VI (23.1%, 3/13), VII (23.1%, 3/13), VIII (23.1%, 3/13) and V/VI/VIII (7.6%, 1/123). Eight participants (61.5%) were estimated in BCLC stage A and 5 (38.5%) in Stage B. Mild ascites were found in 7 participants (53.8%) and moderate ascites in four participants (30.8%). Eight participants (61.5%) were estimated in Child-Pugh Stage A and 5 (38.5%) in Stage B.
TIPS were performed successfully in 13 participants. One month after TIPS, Child-Pugh staging in three participants estimated as Stage B before TIPS was changed to Stage A after TIPS [Table 2]. The ratio with Child-Pugh A before and after TIPS were 61.5% (8/13) and 84.6% (11/13) respectively, with P = 0.179. Ascites in 10 participants before TIPS disappeared after TIPS. The ratio with ascites before and after TIPS was 84.6% (11/13) and 7.7% (1/13), respectively, with P < 0.001. Mean PVP before and after TIPS were 27.85 ± 7.02 mmHg and 16.23 ± 6.61 mmHg, respectively, with P = 0.001. Twelve participants achieved CR (92.3%) and 7 participants achieved PR (7.7%). Mean patency of shunting was 23.9 ± 12.7 months (95% confidence interval [CI] 16.2–31.6), and median patency was 24 months. The 1-year and 2-year patency rate were 76.9% (8/13) and 61.5% (10/13), respectively.
|Table 2: Comparison between indexes before and after transjugular intrahepatic portosystemic shunt|
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All 13 participants underwent anti-tumor treatments after TIPS, including immune therapy with Camrelizumab. A total of 23 TACE and 14 MWA were performed, respectively [Table 3]. Five participants underwent oral administration of Sorafenib (38.5%) and 8 participants with Apatinib (61.5%). Mean OS and median OS were 32 months and 29.8 ± 11.5 months (95% CI 22.8–36.7), respectively [Figure 3]. Mean PFS and median PFS were 22 months and 20.2 ± 13.2 months (95% CI 12.2–28.1), respectively [Figure 4].
| > Discussion|| |
Patients with HCC and cirrhosis may suffer from the complication of portal hypertension, especially ascites. Down-regulated liver function endangers the possibility of anti-tumor treatments and decreases patients' OS. Our study revealed that the ratio with ascites before and after TIPS were 84.6% (11/13) and 7.7% (1/13), with P < 0.001. Subsequently, the ratio with Child-Pugh A before and after TIPS were 61.5% (8/13) and 84.6% (11/13), respectively, with P = 0.179.
PVP decreased dramatically after TIPS. Bettinger et al. found that PVP decreased from median 26.5 (15–38) mmHg to 21 (10–27) mmHg. In our study, mean PVP before and after TIPS were 27.85 ± 7.02 mmHg and 16.23 ± 6.61 mmHg respectively, with P = 0.001. Yan et al. reported that the percentages of CR, PR, and absent AR of RA were 55.9%, 30.9%, and 13.2%, respectively. The control rate (proportion of CR and PR) for refractory ascites was 86.8%. Our study revealed CR in 12 participants (92.3%) and PR in one participant (7.7%), which was better than Yan's research. This result may be attributed to the fact that most of the participants have mild ascites, and no refractory ascites occurred before TIPS.
Technical advancements in skills and stents have reduced complications and improved patency of TIPS. The patency ensures durable improved liver function, decreases the risk of hemorrhage, and creates the chance for anti-tumor treatments. One randomized controlled trial in 2007 reported that PTFE covered stent revealed a patency rate of 76% in 2 years, compared with a patency rate of 36% with bare metal stent. Our study revealed a patency rate of 61.5% in 2 years after TIPS. As we have stated in Materials and Method section, the combination of covered stent and bare stent was applied to keep the shunting tract, since Viatorr stent is not available in both participating hospitals. This may have led to relatively poor patency rate.
Following anti-tumor treatments eliminated or reduced tumor load, which was beneficial for participants' survivals. Strong evidence has been obtained for the combination of Atezolizumab and Bevacizumab for unresectable HCC. Local treatments (TACE and/or MWA) combined with Camrelizumab and Sorafenib or Apatinib in our study demonstrated a median OS of 29.8 ± 11.5 months (95% CI 22.8–36.7) and a median PFS of 20.2 ± 13.2 months (95% CI 12.2–28.1). Luo et al. analyzed 217 patients with HCC and portal hypertension who underwent the TIPS procedure, and reported median survival of 50 months after TIPS for patients with HCC and portal hypertension. Luo et al. reported a median follow-up time of 33.1 months after TIPS in 34 patients with HCC meeting the Milan criteria. In our study, most patients chose incomplete anti-tumor treatments due to negative expectations of liver tumor and cirrhosis, which yields shorter survival.
| > Conclusion|| |
In conclusion, our results indicate that TIPS could reduce ascites, down-regulate the Child-Pugh score, and give a chance for further anti-tumor therapy. Nevertheless, this study has two limitations. First, the number of patients was small. Second, the retrospective character of the study may cause a selection bias of cases. Prospective study should be performed to confirm these findings.
Financial support and sponsorship
This research was supported by Fund from Shandong Provincial Department of Finance (S190009280000), Key Research & Development Plan of Shandong Province (2019GSF108105), National Natural Science Foundation of China (11971269), National Science and Technology Major Project of the Ministry of Science and Technology of China (2018ZX10303502-001), National Science Fund for Distinguished Young Scholars of China (61625102) and and Science and technology project of Jinan Health Committee (2020-3-65).
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3]