Transjugular intrahepatic portosystemic shunt for the treatment of hepatic sinusoidal obstruction syndrome caused by pyrrolizidine alkaloids: A multicenter retrospective study.

Purpose: To assess the impact of transjugular intrahepatic portosystemic shunt (TIPS) on clinical outcomes and liver histology in patients with hepatic sinusoidal obstruction syndrome (HSOS) caused by pyrrolizidine alkaloids (PA), and compare these results with those of patients who received supportive treatment alone. Materials and methods: From June 2015 to August 2022, 164 patients diagnosed with PA-HSOS in six tertiary care centers were retrospectively included in this study and divided into TIPS group (n = 69) and supportive treatment (ST) group (n = 95). The main endpoint was to determine whether TIPS placement could improve survival in PA-HSOS patients. The clinical symptoms associated with portal hypertension were also evaluated in this study. Additionally, a small TIPS-subgroup of 7 patients received liver biopsies before and after TIPS for histological analysis. Results: The incidence of death was markedly lower in the TIPS group than in the ST group (log-rank p = 0.026). Multivariate Cox model revealed that group assignment (hazard ratio (HR) 5.146; 95 % confidence interval (CI) 1.587-16.687; p = 0.006), total bilirubin (HR 1.029; 95 % CI 1.020-1.038; p < 0.001), and INR (HR 13.291; 95 % CI 3.637-48.566; p < 0.001) were independent predictors for mortality. In addition, TIPS placement reduced the risk of complications associated with portal hypertension but did not increase the rate of overt hepatic encephalopathy (log-rank p = 0.731). Furthermore, six of 7 TIPS patients receiving liver biopsies improved after TIPS placement, and one patient developed fibrosis. Conclusions: TIPS placement decreased the mortality and risk of complications associated with portal hypertension. Histological evaluation in a few patients showed a potential improvement by TIPS.

Reversion of liver cirrhosis after endovascular treatment in Chinese patients with Budd-Chiari syndrome.

AIMS: To investigate the impact of endovascular (EV) treatment on liver cirrhosis in Chinese patients with Budd-Chiari syndrome (BCS). METHODS: From September 2011 to March 2022, 97 patients from four hospitals in China who were diagnosed with primary BCS complicated with liver cirrhosis and received EV treatment were retrospectively enrolled in this study for clinical analysis. In addition, liver tissues for basic research were acquired from 25 patients between June 2022 and March 2023, including six with benign liver tumors, 11 with BCS before EV treatment, and eight with EV-treated BCS. Liver cirrhosis was assessed by clinical outcomes, histological studies, and the expression of related genes at the mRNA and protein levels. RESULTS: The patients with BCS had better liver function after EV treatment, evidenced by an increased albumin level and reduced total bilirubin, ALT, and AST. The imaging findings suggested an amelioration of liver cirrhosis and portal hypertension, including increased portal vein velocity (13.52 ± 8.89 cm/s vs. 17.51 ± 6.67 cm/s, p < 0.001) and decreased liver stiffness (30.37 ± 6.39 kPa vs. 23.70 ± 7.99 kPa, p < 0.001), portal vein diameter (14.97 ± 3.42 mm vs. 13.36 ± 2.89 mm, p < 0.001), and spleen volume (870.00 ± 355.61 cm3 vs. 771.36 ± 277.45 cm3 , p < 0.001). Furthermore, histological studies revealed that EV treatment resulted in a restoration of liver architecture with reduced extracellular matrix deposition. Meanwhile, hepatic angiogenesis and inflammation, which have a close relationship with cirrhosis, were also inhibited. In addition, the state of hepatocytes switches from apoptosis to proliferation after EV treatment. CONCLUSIONS: BCS-induced liver cirrhosis could be reversed by EV treatment from macroscopic to microscopic dimensions. Our study may provide further insights into understanding BCS and treating cirrhosis.

Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular carcinoma (CHANCE001).

There is considerable potential for integrating transarterial chemoembolization (TACE), programmed death-(ligand)1 (PD-[L]1) inhibitors, and molecular targeted treatments (MTT) in hepatocellular carcinoma (HCC). It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations. In this nationwide, retrospective, cohort study, 826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT (combination group, n = 376) or TACE monotherapy (monotherapy group, n = 450) were included from January 2018 to May 2021. The primary endpoint was progression-free survival (PFS) according to modified RECIST. The secondary outcomes included overall survival (OS), objective response rate (ORR), and safety. We performed propensity score matching approaches to reduce bias between two groups. After matching, 228 pairs were included with a predominantly advanced disease population. Median PFS in combination group was 9.5 months (95% confidence interval [CI], 8.4-11.0) versus 8.0 months (95% CI, 6.6-9.5) (adjusted hazard ratio [HR], 0.70, P = 0.002). OS and ORR were also significantly higher in combination group (median OS, 19.2 [16.1-27.3] vs. 15.7 months [13.0-20.2]; adjusted HR, 0.63, P = 0.001; ORR, 60.1% vs. 32.0%; P < 0.001). Grade 3/4 adverse events were observed at a rate of 15.8% and 7.5% in combination and monotherapy groups, respectively. Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS, OS, and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice, with an acceptable safety profile.

Dynamic changes in liver function after transjugular intrahepatic portosystemic shunt in patients with cirrhosis.

Purpose: To evaluate the dynamic changes in liver function after transjugular intrahepatic portosystemic shunt (TIPS) creation in patients with cirrhosis and to explore its association with clinical outcomes. Methods: This retrospective study included patients who underwent TIPS between August 2016 and December 2020. Liver function was primarily evaluated using the model for end-stage liver disease (MELD) score, which was analyzed at baseline, 1 week, 1 month, 3 months, 6 months, and 12 months using one-way repeated measures ANOVA. The Kaplan-Meier method, log-rank test, and multivariate analysis were used as appropriate. Results: In total, 235 patients were included in this study. The MELD score was significantly higher at 1 week (11.8 â€‹± â€‹3.1 vs 13.5 â€‹± â€‹3.5, p â€‹< â€‹0.05) and 1 month (11.8 â€‹± â€‹3.1 vs 13.2 â€‹± â€‹4.6, p â€‹< â€‹0.05) than the baseline level and recovered at 3 months (11.8 â€‹± â€‹3.1 vs 11.9 â€‹± â€‹3.9, p â€‹> â€‹0.05). At 12 months, the MELD score was higher than the baseline level (11.8 â€‹± â€‹3.1 vs 12.4 â€‹± â€‹3.2, p â€‹< â€‹0.05). Patients with a recovery of the MELD score (n â€‹= â€‹151) at 3 months had a lower probability of overt and severe HE (log-rank p â€‹= â€‹0.015 and p â€‹= â€‹0.027, respectively) than those without recovery (n â€‹= â€‹84). Logistic regression analysis revealed that albumin (odds ratio [OR], 0.926; 95% confidence interval [CI], 0.863-0.992; p â€‹= â€‹0.029) and platelet count (OR, 0.993; 95% CI, 0.987-0.999; p â€‹= â€‹0.033) were independent predictive factors for non-recovery of the MELD score at 3 months. Conclusions: Liver function after TIPS creation showed a trend of deterioration at first, followed by recovery. Recovery of liver function at three months was associated with reduced overt and severe HE.

Covered vs. uncovered self-expandable metal stents for palliation of malignant afferent loop obstruction: a multicenter study.

BACKGROUND AND AIMS: Endoscopic stent placement is a palliative therapy for malignant digestive tract obstruction. However, its use for malignant afferent loop obstruction (mALO) has not been adequately investigated. METHODS: From March 2009 to December 2020, 137 patients with mALO who underwent endoscopic stent placement at three tertiary care centers were retrospectively enrolled. The primary aim of this study was to compare stent dysfunction (SD) between the covered self-expandable metal stent (CSEMS) and uncovered self-expandable metal stent (UCSEMS) groups, with subgroup analysis among patients with extrinsic and intrinsic tumors separately. RESULTS: Twenty-three patients developed SD in the CSEMS group and 29 patients in the UCSEMS group (log-rank p = .974). The primary contributors to SD included a higher risk of stent migration in the CSEMS group and stent ingrowth in the UCSEMS group (p = .003; p < .001). Among patients with extrinsic tumors, the CSEMS group showed a significantly higher probability of overall SD (p = .008) and stent migration (p = .001) with a shorter time to SD (log-rank p = .006) than the UCSEMS group. Among patients with intrinsic tumors, the CSEMS group showed a significantly lower incidence of overall SD (p < .001) and stent ingrowth (p < .001) with a longer time to SD (log-rank p = .011) than the UCSEMS group. CONCLUSIONS: Our results showed no significant difference in SD between the CSEMS and UCSEMS groups for palliation of mALO. Furthermore, subgroup analysis suggested using CSEMSs for patients with intrinsic tumors, and UCSEMSs for those with extrinsic tumors.

Preliminary clinical study: percutaneous lumbar discectomy combined with external drainage for treatment of intervertebral disc infections with epidural abscess.

INTRODUCTION: Percutaneous lumbar discectomy (PLD) combined with external drainage (ED) is a new technique for the treatment of intervertebral disc infection with epidural abscess. AIM: To discuss the feasibility, safety and efficacy of PLD and ED for the treatment of intervertebral disc infections with epidural abscess. MATERIAL AND METHODS: We enrolled 12 patients who underwent intervertebral disc infections with epidural abscess. The clinical efficacy was evaluated by visual analog scale (VAS) and standard Macnab's evaluation. Postoperative computed tomography and magnetic resonance imaging were also used to evaluate the clinical efficacy. RESULTS: The technical success rate is 100%. Preoperation mean VAS score was 8.18 ±0.98; 5.36 ±1.50 postoperation 1 month; 3.36 ±2.24 postoperation 6 months; 2.77 ±0.31 postoperation 12 months. The comparison of preoperation and postoperation VAS showed a significant difference (p < 0.05). According to standard Macnab's evaluation, of all 12 cases, postoperation 12 months - excellent 4 cases, good 7 cases, poor 1 case. The efficacy rate was 91.6%. No serious complications were recorded. CONCLUSIONS: Percutaneous lumbar discectomy combined with external drainage may be a safe and efficacy method for the treatment of intervertebral disc infections with epidural abscess.

Agitation thrombolysis combined with catheter-directed thrombolysis for the treatment of non-cirrhotic acute portal vein thrombosis.

AIM: To evaluate the safety and efficacy of agitation thrombolysis (AT) combined with catheter-directed thrombolysis (CDT) for the treatment of non-cirrhotic acute portal vein thrombosis (PVT). METHODS: Nine patients with non-cirrhotic acute PVT who underwent AT combined with CDT were analyzed retrospectively. Portography was carried out via the transjugular intrahepatic portosystemic (commonly known as TIP) or percutaneous transhepatic (commonly known as PT) route, followed by AT combined with CDT. Complications of the procedure, and the changes in clinical symptoms, hemodynamics of the portal vein and liver function were recorded. Follow-up was scheduled at 1, 3 and 6 mo after treatment, and every 6 mo thereafter, or when the patients developed clinical symptoms related to PVT. Color Doppler ultrasound and contrast-enhanced computed tomography/magnetic resonance imaging were performed during the follow-up period to determine the condition of the portal vein. RESULTS: AT combined with CDT was successfully performed. The portal vein was reached via the TIP route in 6 patients, and via the PT route in 3 patients. All clinical symptoms were relieved or disappeared, with the exception of 1 patient who died of intestinal necrosis 9 d after treatment. Significant differences in the changes in portal vein hemodynamics were observed, including the maximum lumen occupancy of PVT, portal vein pressure and flow velocity between pre- and post-treatment (P < 0.05). During the follow-up period, recurrence was observed in 1 patient at 19 mo after the procedure, and the portal vein was patent in the remaining patients. CONCLUSION: AT combined with CDT is a safe and effective method for the treatment of non-cirrhotic acute PVT.

Application of embolization microspheres in interventional therapy of malignant non-hypervascular tumor of liver.

OBJECTIVE: To investigate the efficacy and safety of transarterial embolization (TAE) using embolization microspheres in the treatment of non-hypervascular malignant liver tumors. METHODS: Patients with malignant non-hypervascular liver tumors, who were treated with TAE using embolization microspheres, were selected and analyzed retrospectively. The technical success rate, tumor response, and complications were assessed. RESULTS: Six patients were included in the study: 1 patient each with hepatocellular-cholangiocarcinoma, intrahepatic cholangiocarcinoma, hepatic metastasis after resection of common bile duct carcinoma, liver metastasis from colon cancer, liver metastasis from esophageal cancer, and liver metastasis from pancreatic cancer. The technical success rate was 100%. At 1 and 3 months after TAE, tumor local reactions were seen in 6/6 and 2/6 patients, respectively, and the tumor necrosis rates were 48%-73% and 22%-68%, respectively. The main complications were those related to the embolization syndrome, including 1 case of liver abscess and 1 case of severe pain on the first day after embolization. CONCLUSION: TAE with embolization microspheres is safe and effective in non-hypervascular liver tumors. It is a feasible option for palliative therapy of these tumors.

Clinical observation of fallopian tube obstruction recanalization by ozone.

OBJECTIVE: To investigate the clinical effect of fallopian tube obstruction recanalization by ozone. METHODS: Total 116 cases of patients undergoing the fallopian tube obstruction were randomly divided into the experimental group and control group, with 58 cases in each group. All patients underwent the interventional fallopian tube recanalization. The patients in the experimental group underwent the fallopian tube perfusion by the ozone water. Meanwhile, the patients in the control group were treated with the conventional anti-inflammatory and anti-adhesion drugs. After the follow-up visit for 6 months, the pregnancy rate and fallopian tube re-occlusion rate were counted and compared between the two groups. Meanwhile, the symptoms were evaluated and compared between the two groups after the operation for two weeks. RESULTS: The success rate of fallopian tube recanalization was 93.1% (54/58), the pregnancy rate was 79.3% (46/58) and the recurrence rate was 5.2% (3/58) in the experimental group. While the success rate of fallopian tube recanalization was 91.4% (53/58), the pregnancy rate was 60.3% (35/58) and the recurrence rate was 17.2% (10/58) in the control group. Analysis showed that there was no significant difference in the recanalization success rate between the two groups (P>0.05). However, the pregnancy rate and re-occlusion rate in the experimental group were significantly lower than those of the control group (P<0.05), and the difference was statistically significant. There was no significant difference in the discomfort symptoms between the experimental group and control group (P>0.05). CONCLUSION: Fallopian tube recanalization by ozone perfusion can effectively increase the postoperative pregnancy rate and reduce the fallopian tube re-occlusion.

Treatment of (131)I-labeled anti-CD147 monoclonal antibody in VX2 carcinoma-induced liver tumors.

Hepatocellular carcinoma (HCC) is a major health problem worldwide. CD147 has been reported to be overexpressed in HCC and blocking CD147 expression can decrease tumor growth. (131)I is often used in combination with other drugs to treat HCC and yields positive results. In this study, we combined the (131)I and CD147 monoclonal antibody to treat HCC in a rabbit VX2 animal model. In the (131)I-labeled CD147 antibody ((131)I-CD147-Ab) treatment group, the animals lived considerably longer than the animals in the other treatment groups. Metastasis and tumor growth in the (131)I-CD147-Ab treatment group were also inhibited. MMP2 and CD31 expression were significantly lower in the treatment group, whereas Tunel staining was overexpressed. These findings suggest that (131)I-CD147-Ab is a promising drug in the treatment of HCC, by inhibiting metastasis and growth and by decreasing the expression of MMP2 and CD31 or by inducing tumor necrosis. After testing the biochemical parameters, (131)I-CD147-Ab caused fewer side-effects in the animals.

Improvement of percutaneous transhepatic biliary internal-external drainage and its initial experience in patients with malignant obstruction of the upper biliary tree.

BACKGROUND/AIMS: To evaluate the feasibility and clinical results of modified percutaneous transhepatic biliary internal-external drainage (PTBIED) vs. conventional PTBIED in patients with malignant biliary obstruction. METHODOLOGY: Conventional PTBIED was modified by applying side-holes to an 8.5Fr external biliary drainage catheter. Eligible patients were randomly assigned 1:1 by the doctors to receive modified PTBIED (group A) or conventional PTBIED (group B). Technical success rate, complications, hepatic function and white cell count were recorded pre- and post-procedure. All patients were followed-up until death. RESULTS: Twenty-two patients were assigned in group A and 21 patients were involved in group B. Successful drainage was all achieved in both groups. Biliary tract infections were significantly reduced in group A (1/22) compared to group B (7/21, p<0.05). The leukocyte count fell slightly in group A post-procedure, while it rose in group B (group A: 8.45±3.22-109/L to 7.53±2.46-109/L; group B: 7.92±3.08-109/L to 10.52±5.09-109/L). Both procedures had similar effects in the recovery of hepatic function, median survival time and alleviating clinical symptoms (such as pruritis and abdominal pain). CONCLUSIONS: Modified PTBIED can reduce the complications resulting from retrograde reflux of duodenal contents. Improved PTBIED should be used for patients with inoperable high malignant biliary obstruction.

Arterial embolization hyperthermia using As2O3 nanoparticles in VX2 carcinoma-induced liver tumors.

BACKGROUND: Combination therapy for arterial embolization hyperthermia (AEH) with arsenic trioxide (As(2)O(3)) nanoparticles (ATONs) is a novel treatment for solid malignancies. This study was performed to evaluate the feasibility and therapeutic effect of AEH with As(2)O(3) nanoparticles in a rabbit liver cancer model. The protocol was approved by our institutional animal use committee. METHODOLOGY/PRINCIPAL FINDINGS: In total, 60 VX(2) liver-tumor-bearing rabbits were randomly assigned to five groups (n = 12/group) and received AEH with ATONs (Group 1), hepatic arterial embolization with ATONs (Group 2), lipiodol (Group 3), or saline (Group 4), on day 14 after tumor implantation. Twelve rabbits that received AEH with ATONs were prepared for temperature measurements, and were defined as Group 5. Computed tomography was used to measure the tumors' longest dimension, and evaluation was performed according to the Response Evaluation Criteria in Solid Tumors. Hepatic toxicity, tumor necrosis rate, vascular endothelial growth factor level, and microvessel density were determined. Survival rates were measured using the Kaplan-Meier method. The therapeutic temperature (42.5°C) was obtained in Group 5. Hepatotoxicity reactions occurred but were transient in all groups. Tumor growth was delayed and survival was prolonged in Group 1 (treated with AEH and ATONs). Plasma and tumor vascular endothelial growth factor and microvessel density were significantly inhibited in Group 1, while tumor necrosis rates were markedly enhanced compared with those in the control groups. CONCLUSIONS: ATON-based AEH is a safe and effective treatment that can be targeted at liver tumors using the dual effects of hyperthermia and chemotherapy. This therapy can delay tumor growth and noticeably inhibit tumor angiogenesis.

Enhancement of p53 gene transfer efficiency in hepatic tumor mediated by transferrin receptor through trans-arterial delivery.

Transferrin-DNA complex mediated by transferrin receptor in combination with interventional trans-arterial injection into a target organ may be a duel-target-oriented delivery means to achieve an efficient gene therapy. In this study, transferrin receptor expression in normal human hepatocyte and two hepatocellular-carcinoma cells (Huh7/SK-Hep1) was determined. p53-LipofectAMINE with different amounts of transferrin was transfected into the cells and the gene transfection efficiency was evaluated. After VX2 rabbit hepatocarcinoma model was established, the transferrin-p53-LipofectAMINE complex was delivered into the hepatic artery via interventional techniques to analyze the therapeutic p53 gene transfer efficiency in vivo by Western blot, immunohistochemical/immunofluorescence staining analysis and survival time. The results were transferrin receptor expression in Huh7 and SK-Hep1 cells was higher than in normal hepatocyte. Transfection efficiency of p53 was increased in vitro in both Huh7 and SK-Hep1 cells with increasing transferrin in a dose-dependent manner. As compared to intravenous administration, interventional injection of p53-gene complex into hepatic tumor mediated by transferrin-receptor, could enhance the gene transfer efficiency in vivo as evaluated by Western blot, immunohistochemical/immunofluorenscence staining analyses and improved animal survival (H = 12.567, p = 0.0019). These findings show the transferrin-transferrin receptor system combined with interventional techniques enhanced p53-gene transfer to hepatic tumor and the duel-target-oriented gene delivery may be an effective approach for gene therapy.