Hypoxia-activated cascade nanovaccine for synergistic chemoembolization-immune therapy of hepatocellular carcinoma.

In this work, a promising treatment strategy for triggering robust antitumor immune responses in transarterial chemoembolization of hepatocellular carcinoma (HCC) is presented. The zeolitic imidazolate framework nanoparticles loaded with hypoxia-activated prodrug tirapazamine and immune adjuvant resiquimod facilitated in situ generation of nanovaccine via a facile approach. The nanovaccine can strengthen the ability of killing the liver cancer cells under hypoxic environment, while was capable of improving immunogenic tumor microenvironment and triggering strong antitumor immune responses by increasing the primary and distant intratumoral infiltration of immune cells such as cytotoxic T cells. Moreover, a porous microcarrier, approved by FDA as pharmaceutical excipient, was designed to achieve safe and effective delivery of the nanovaccine via transarterial therapy in rabbit orthotopic VX2 liver cancer model. The microcarrier exhibited the characteristics of excellent drug loading and occlusion of peripheral artery. The collaborative delivery of the microcarrier and nanovaccine demonstrated an exciting inhibitory effect on solid tumors and tumor metastases, which provided a great potential as novel combination therapy for HCC interventional therapy.

Mild Prolongation of Prothrombin Time Does Not Affect the Safety and Prognosis of Transjugular Intrahepatic Portal Shunt: Based on Real-World Data.

BACKGROUND/AIMS: The aim was to investigate the safety and prognosis of transjugular intrahepatic portal shunt in patients with mildly prolonged prothrombin time. MATERIALS AND METHODS: Two hundred fifty-three patients with portal hypertension who received transjugular intrahepatic portal shunt from November 2015 to May 2021 in Wuhan Union Hospital were retrospectively selected. According to the preoperative prothrombin time, they were divided into 2 groups: 126 patients in the non-clinical significance group (prothrombin time prolongation <3 seconds) and 127 patients in the clinical significance group (3 seconds ≤ prothrombin time prolongation <6 seconds). A line chart of postoperative liver and kidney function was drawn, and Kaplan-Meier curve was used to analyze and compare the prognosis of the 2 groups. RESULTS: Transjugular intrahepatic portal shunt was successfully performed in all patients; the technical success rate was 100%, and no puncture-related complications occurred during perioperative period. The mean preoperative prothrombin time was 14.9 ± 0.7 seconds in the non-clinical significance group and 17.2 ± 0.8 seconds in the clinical significance group. During follow-up, 1-year stent dysfunction rates in the non-clinical significance group and clinical significance group were 3.5% and 6.9%, respectively, with no statistically significant difference (hazard ratio = 0.77, 95% CI = 0.30-1.93, log-rank P = .575). In addition, there were no significant differences in the cumulative survival rate (log rank P = .255), rebleeding rate (log-rank P = .392), and incidence of hepatic encephalopathy (log-rank P = .404) between the 2 groups. Subgroup analysis of the clinical significance group showed no significant difference in safety and prognosis between the 2 subgroups. CONCLUSION: Transjugular intrahepatic portal shunt is safe for portal hypertension patients with prothrombin time prolongation <6 seconds. There was no significant difference in prognosis between the non-clinical significance group and the clinical significance group.

Management of traumatic peripheral artery pseudoaneurysm: A 10-year experience at a single center.

Purpose: This study aimed to report our 10-year experience with the management of iatrogenic (penetrating trauma) and traumatic (blunt or penetrating trauma) peripheral artery pseudoaneurysms, based on data from a tertiary referral center. Methods: From January 2012 to December 2021, the medical records of consecutive patients with iatrogenic and traumatic peripheral artery pseudoaneurysms were retrospectively reviewed. Patient demographics, clinical features, imaging data, treatment details, and follow-up results were analyzed. Results: Sixty-one consecutive patients were included in this study; 48 (79%) were men and 13 (21%) women, with a mean age of 49.4 â€‹± â€‹13.4 years (range 24-73 years). There were 42 patients (69%) who underwent open surgery, 18 (29%) undergoing endovascular embolization or stent implantation, and one (2%) undergoing ultrasound-guided thrombin injection. All patients successfully underwent open or interventional treatment. The median follow-up was 46.8 months (2.5-117.9 months), and the overall reintervention rate was 10%. Of these, one (5%) patient in the interventional treatment group and five (12%) patients in the open surgery group underwent reintervention. The overall complication rate was 8%, with complications occurring only in the open surgery group. No deaths occurred in the peri-operative period. No late complications, such as thrombosis or pseudoaneurysm recurrence, were observed. Conclusion: Peripheral artery pseudoaneurysms arising from iatrogenic or traumatic causes can be effectively treated by both open surgery and interventional procedures in selected patients with acceptable mid- and long-term outcomes.

Changes and influencing factors of liver volume after transjugular intrahepatic portosystemic shunt: a retrospective cohort study.

Background: Liver volume is an important measure of liver reserve and helps to determine the course of liver disease. This study aimed to observe the dynamic changes of liver volume after transjugular intrahepatic portosystemic shunt (TIPS) and analyze the related factors. Methods: Clinical data of 168 patients who underwent TIPS procedures between February 2016 and December 2021 were collected and analyzed retrospectively. The changes in liver volume after TIPS in the patients were observed, and the independent predictors affecting increases in liver volume were analyzed using a multivariable logistic regression model. Results: The mean liver volume was decreased by 12.9% at 2±1 months post TIPS and rebounded at 9±3 months post TIPS, but did not recover to its pre-TIPS level completely. Most patients (78.6%) had decreased liver volume at 2±1 months post TIPS, and in multivariable logistic regression, a lower albumin (ALB) level, a lower subcutaneous fat area at L3 (L3-SFA), and a higher degree of ascites were identified as independent factors predicting increased liver volume. The risk score model for predicting increased liver volume was Logit(P)=1.683-0.078 (ALB) -0.01 (pre TIPS L3-SFA) +0.996 (grade 3 ascites =1; non-grade 3 ascites =0). The area under the curve of the receiver operating characteristic curve was 0.729, and the cut-off value was 0.375. The rate of liver volume change at 2±1 months post TIPS was significantly correlated with that of spleen volume change (R2=0.378, P<0.001). The rate of subcutaneous fat change at 9±3 months post TIPS was significantly correlated with that of liver volume change (R2=0.782, P<0.001). In patients with a liver volume increase, the mean computed tomography value (Hounsfield units) decreased significantly after TIPS placement (65.9±17.7 vs. 57.8±18.2, P=0.009). Conclusions: Liver volume was decreased at 2±1 months post TIPS and slightly increased at 9±3 months post TIPS; however, it did not recover to its pre-TIPS level completely. A lower ALB level, a lower L3-SFA, and a higher degree of ascites were all predictors for increased liver volume post TIPS.

The Added Value of Sarcopenia on Existing Risk Scores to Predict Mortality after TIPS Placement: A Multicenter Study.

RATIONALE AND OBJECTIVES: Multiple prognostic scores have been applied for predicting survival after TIPS placement. The aim was to evaluate the added value of sarcopenia on existing risk scores and develop a sarcopenia-based scoring system for survival prediction and risk stratification. MATERIALS AND METHODS: In the derivation cohort of 386 cirrhotic patients undergoing TIPS, five risk scores (Child-Pugh, MELD, MELD-Na, MELD 3.0, and FIPS) were compared for prediction of short- and long-term mortality after TIPS. Sarcopenia was diagnosed based on the L3 skeletal muscle index and was incorporated into existing scores to assess its added value. A novel sarcopenia-based score was developed and externally validated in an independent cohort of 198 patients undergoing TIPS. RESULTS: Among existing scores, the FIPS score showed the highest discrimination (c-index: 0.756-0.783) and calibration (Brier score: 0.059-0.127). Besides, the FIPS score was significantly associated with the severity of baseline sarcopenia and reversal of sarcopenia after TIPS. The inclusion of sarcopenia improved discrimination of existing scores in different degrees and sarcopenia could stratify the low-risk categories deemed by these scores. A FIPS-sarcopenia score was developed, showing superior discrimination over existing scores (c-index: 0.777-0.804 in the derivation cohort, 0.738-0.788 in the validation cohort). With a determined cutoff of 0.8, this score allowed for the identification of two prognostic subgroups with distinct prognoses. CONCLUSION: FIPS score was highly correlated with the severity of sarcopenia and sarcopenia reversal after TIPS, and sarcopenia could improve the prognostic ability of existing scores. A FIPS-sarcopenia score was developed and validated, showing improved survival prediction and risk stratification.

Improvement of sarcopenia is beneficial for prognosis in cirrhotic patients after TIPS placement.

BACKGROUND: The relationship between the improvement of sarcopenia and post-TIPS prognosis has not been fully investigated. AIMS: To assess what level of sarcopenia improvement is required for potential benefits to post-TIPS prognosis. METHODS: In this retrospective study, 109 cirrhotic patients with sarcopenia who underwent TIPS between February 2016 and January 2021 were included. The change in skeletal muscle index (SMI) at 6 months post-TIPS was assessed and the correlations of SMI improvement with clinical outcomes were analyzed. RESULTS: During follow up, 59 (65.6%) patients reversed from sarcopenic to non-sarcopenic, and the cumulative mortality (8.5 % vs. 26.0%, log rank P = 0.013) and incidence of overt hepatic encephalopathy (OHE) (18.6% vs. 44.0%, log rank P = 0.004) in patients who reversed were significantly lower than who did not. SMI improvement rate was identified as an independent risk factor for mortality and OHE. In addition, the cumulative survival rate of patients with sarcopenia reversal or SMI improvement rate > 10.4% was significantly higher than that of patients with an SMI improvement rate ≤ 10.4% (92.5% vs. 58.6%, log rank P < 0.001). CONCLUSION: Reversal of sarcopenia or significant SMI improvement by TIPS could reduce the risk of death and OHE.

The impact of thrombocytopenia on variceal bleeding in cirrhotic patients with transjugular intrahepatic portosystemic shunt.

Thrombocytopenia is the most frequent haematologic disorder in patients with cirrhosis, and it is perceived as a contributory factor for bleeding events. Cirrhosis patients with portal hypertension (PHT) is often accompanied with mild to moderate thrombocytopenia when they treated with transjugular intrahepatic portosystemic shunt (TIPS). To address whether the risk of variceal hemorrhage after TIPS varies with different platelet count in patients with normal platelet count and thrombocytopenia, we conducted the retrospective controlled study to evaluate the association of platelet count with the risk of variceal bleeding after TIPS. 304 patients were selected to the study. Propensity score matching was performed to adjust for potential selection bias. 63 patients from each group could be paired. Cox proportional hazards models were used to evaluate the association between platelet and variceal bleeding after TIPS. Platelet counts of two groups are 185.0 ± 98.7 × 109/L (normal platelet count) and 70.6 ± 39.3 × 109/L (thrombocytopenia) respectively. The bleeding rates of two groups in overall cohort are 10.9% (normal platelet count) and 12.9% (thrombocytopenia). After matched, the bleeding rates of two groups are 11.1% (normal platelet count) and 14.3% (thrombocytopenia) There was no statistically significant difference in bleeding rates between the two groups, either in the whole cohort (P = 0.671) or in the matched cohort (P = 0.593). Platelet count was not associated with bleeding events after TIPS (hazard ratio (HR) 95% confidence interval: 0.986-1.005, P = 0.397 in normal platelet count and 95% confidence interval: 0.968-1.020, P = 0.648 in thrombocytopenia). Thrombocytopenia in patients with cirrhosis was not associated with the risk of variceal bleeding episodes post-TIPS. Thrombocytopenia should not be viewed as an absolute contraindication for TIPS.

Predictors of Improvement of Sarcopenia after Transjugular Intrahepatic Portosystemic Shunt Creation in Cirrhotic Patients.

To investigate the risk factors affecting the improvement of sarcopenia after transjugular intrahepatic portosystemic shunt (TIPS) in cirrhotic patients, this study retrospectively analyzed the data of 111 cirrhotic patients with sarcopenia who underwent TIPS creation. Computed tomography-based measurement of skeletal muscle area was used to calculate skeletal muscle index (SMI) in all patients at baseline and 6 months after TIPS creation. Multivariate logistic regression analysis was used to identify independent risk factors, which showed a significant increase in 6-month post-TIPS SMI compared with that at baseline in both men and women (for both, P < .001). Pre-TIPS SMI (odds ratio [OR], 0.93; 95% CI, 0.87-0.99; P = .031) and change in portal pressure gradient (OR, 1.13; 95% CI, 1.03-1.24; P = .009) were found to be independent risk factors for experiencing substantial improvement in post-TIPS SMI.

Sarcopenia Defined by Psoas Muscle Thickness Predicts Mortality After Transjugular Intrahepatic Portosystemic Shunt.

PURPOSE: To assess and compare the value of psoas muscle thickness at the level of the third lumbar (L3) vertebra (TPML) or umbilicus (TPMU) and skeletal muscle index (SMI) for diagnosing sarcopenia and predicting mortality in patients undergoing transjugular intrahepatic portosystemic shunt (TIPS). MATERIALS AND METHODS: Two hundred forty-nine patients undergoing TIPS were included in this retrospective study. The cut-offs of L3-SMI for sarcopenia were 42.0 cm2/m2 in men and 38.0 cm2/m2 in women. The cut-offs for TPML/height and TPMU/height to predict mortality was established using a receiver-operating characteristic analysis. The Kaplan-Meier and Cox regression were used for survival analyses. RESULTS: Compared with TPMU/height, TPML/height was more consistent with L3-SM for the diagnosis of sarcopenia (Kappa coefficient: 0.63 vs. 0.36 in men; 0.61 vs. 0.45 in women). The Cox analysis showed that both TPML/height and TPMU/height were independent risk factors for mortality. The optimal cut-off values of TPML/height and TPMU/height for mortality in men and women were 11.2 mm/m, 9.4 mm/m, 18.4 mm/m, 15.1 mm/m, respectively. There were 119 (47.8%), 87 (34.9%), and 82 (32.9%) patients diagnosed with sarcopenia in the TPMU/height, TPML/height, and L3-SMI models, respectively. Kaplan-Meier analysis showed that the overall survival was significantly lower in the sarcopenia group in all three models. CONCLUSION: TPMU/height and TPML/height have a similar survival prognostic value as L3-SMI. TPML/height has better consistency with L3-SMI in diagnosing sarcopenia and is a more stable alternative to L3-SMI for diagnosing sarcopenia in patients undergoing TIPS.

TIPS placement as the first-line therapy to prevent variceal rebleeding in patients with cirrhosis and sarcopenia.

PURPOSE: Sarcopenia increases the risk of mortality and hepatic encephalopathy (HE) in cirrhosis, and is a potential indication for transjugular intrahepatic portosystemic shunt (TIPS). The aim was to investigate the prognostic effect of sarcopenia in patients with cirrhosis who received TIPS for prevention of variceal rebleeding. METHOD: We retrospectively included 262 patients with cirrhosis receiving TIPS as the first-line treatment for prevention of rebleeding. L3 skeletal muscle index (SMI) was measured and sarcopenia was defined using sex-specific cutoffs. Incidence of post-TIPS mortality and overt HE, and changes of L3-SMI before and after TIPS were compared between the non-sarcopenia and sarcopenia group. Moreover, 21 patients with sarcopenia who received TIPS as the second-line treatment were included for additional comparison. RESULTS: At admission, 99 (37.8 %) and 163 (62.2 %) patients were diagnosed as sarcopenia and non-sarcopenia, respectively. Compared with the non-sarcopenia group, the sarcopenia group had a similar risk of mortality (adjusted hazard ratio [HR] 1.04, 95 % confidence interval [CI]: 0.55-1.96, p = 0.900) and overt HE (adjusted HR 1.20, 95 %CI 0.72-2.00, p = 0.479). The sarcopenia group achieved higher extent of L3-SMI improvement after TIPS than the non-sarcopenia group (7.0 vs 2.4 cm2/m2 in males; 4.2 vs 3.3 cm2/m2 in females). For patients with sarcopenia, TIPS as the second-line treatment significantly increased mortality risk compared with TIPS as the first-line treatment (adjusted HR 2.68, 95 %CI 1.05-6.87, p = 0.04). CONCLUSIONS: For patients treated with TIPS as the first-line treatment for prevention of rebleeding, baseline sarcopenia did not increase the risk of post-TIPS mortality and overt HE.

A VEGFR targeting peptide-drug conjugate (PDC) suppresses tumor angiogenesis in a TACE model for hepatocellular carcinoma therapy.

Transcatheter arterial chemoembolization (TACE) has become the preferred therapy for unresectable advanced hepatocellular carcinoma (HCC). However, the embolization of tumor-feeding arteries by TACE always leads to hypoxia-related tumor angiogenesis, which limited the therapeutic effect for HCC. In this paper, we used a VEGFR targeting peptide VEGF125 - 136 (QKRKRKKSRYKS) to conjugate with a lytic peptide (KLUKLUKKLUKLUK) to form a peptide-drug conjugate (PDC). We used cell affinity assay to detect the peptide binding ability to VEGFR highly expressed cell lines, and CCK8, cell apoptosis to confirm the cellular toxicity for different cell lines. Meanwhile, we created a VX2 tumor-bearing rabbit model to assess the in vivo anti-tumor effect of the peptide conjugate in combination with TAE. HE staining was used to verify the in vivo safety of the peptide conjugate. IHC was used to assess the anti-angiogenesis and cell toxicity of the peptide conjugate in tumor tissues. The peptide conjugate could not only target VEGFR in cell surface and inhibit VEGFR function, but also have potent anti-cancer effect. We luckily found the peptide conjugate showed potent cytotoxicity for liver cancer cell Huh7 (IC50 7.3 ± 0.74 µM) and endothelial cell HUVEC (IC50 10.7 ± 0.292 µM) and induced cell apoptosis of these two cell lines. We also found the peptide conjugate inhibited cell migration of HUVEC through wound healing assay. Besides, these peptides also showed better in vivo anti-tumor effect than traditional drug DOX through TACE in VX2 rabbit tumor model, and efficiently inhibit angiogenesis in tumor tissues with good safety. In conclusion, our work may provide an alternative option for clinical HCC therapy via TACE combination.

Efficacy and safety of transjugular intrahepatic portosystemic shunt for the treatment of schistosomiasis-induced portal hypertension: a retrospective case series.

BACKGROUND AND AIM: The aim of this study was to evaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) in the treatment of portal hypertension caused by schistosomiasis. METHODS: This study included 43 patients with schistosomiasis-induced portal hypertension treated with TIPS in our institution from December 2015 to May 2021. The demographic, imaging, clinical and follow-up data of patients were recorded retrospectively to evaluate the efficacy and safety of the procedure. RESULTS: All patients were successfully implanted with stents to establish shunt, and 90.7% of the patients were in good postoperative condition with no complications. After TIPS, the Yerdel grade of portal vein thrombosis decreased, and the portal pressure gradient decreased from 27.0 ± 4.9 mmHg to 11.3 ± 3.8 mmHg (P < 0.001). Bleeding was effectively controlled, with a postoperative rebleeding rate of 9.3%, which was an 87.9% reduction from the preoperative rate. The cumulative incidence of postoperative refractory ascites, shunt dysfunction, overt hepatic encephalopathy (OHE) and death were all similar to those of TIPS for nonschistosomiasis portal hypertension. There were no differences in liver and kidney function and blood coagulation indexes before and 3 months after TIPS. Albumin was identified as an independent risk factor for mortality after TIPS for schistosomal liver fibrosis. CONCLUSION: TIPS can be used as a well-tolerated and effective treatment for schistosomiasis-induced portal hypertension, effectively reduce portal pressure gradient and improve portal vein thrombosis.

Portal flow diversion based on portography is superior than puncture site in the prediction of overt hepatic encephalopathy after TIPS creation.

BACKGROUND: Targeted puncture of an appropriate portal venous branch during transjugular intrahepatic portosystemic shunt (TIPS) procedure may reduce the risk of postprocedural overt hepatic encephalopathy (HE). This study aimed to describe blood distribution under portography and combined it with puncture site to determine portal flow diversion, and to evaluate its prognostic value in predicting post-TIPS overt HE. METHODS: In this retrospective analysis of patients with cirrhosis undergoing TIPS, we included 252 patients to describe blood distribution under portography and 243 patients to assess the association between portal flow diversion and post-TIPS overt HE. RESULTS: At the first stage, 51 (20.2%) patients were identified as type A (unilateral type with the right portal branch receives blood from splenic vein [SV]), 16 (6.4%) as type B (unilateral type with the right branch receives blood from superior mesenteric vein [SMV]) and 185 (73.4%) as type C (fully mixed type). At the second stage, 40 patients were divided into the SV group, 25 into the SMV group and 178 into the mixed group. Compared with the mixed group, the risk of post-TIPS overt HE was significantly higher in the SMV group (adjusted HR 3.70 [95% CI 2.01-6.80]; p < 0.001), whereas the SV group showed a non-significantly decreased risk (adjusted HR 0.57 [95% CI 0.22-1.48]; p = 0.25). Additionally, the SMV group showed a substantial increase in ammonia level at 3 days and 1 month after procedure. CONCLUSIONS: Our results support the clinical use of portal flow diversion for risk stratification and decision-making in the management of post-TIPS overt HE.

Effect of underdilated transjugular intrahepatic portosystemic shunt on prognosis in patients with prior splenectomy: a propensity score-matched case-control study.

PURPOSE: This study aimed to investigate whether underdilated transjugular intrahepatic portosystemic shunt (TIPS) could reduce the risk of hepatic encephalopathy (HE) and ameliorate impaired hepatic function in patients with a history of splenectomy. METHODS: A retrospective case-control study was conducted with 96 patients who had prior splenectomy and TIPS placement from August 2016 to May 2022. All patients were divided into two groups based on the diameter of expansion balloon catheters, the underdilated group (6-mm balloon catheter, n = 60) and a control group (8-mm balloon catheter, n = 36). Following the 1:1 propensity score matching (PSM), 33 patients in the underdilated group and 33 patients in the control group were included. RESULTS: During a median follow-up of 36 months, a quicker recovery in liver function after TIPS placement was showed in the underdilated group. The mean TBIL content (16.562 ± 6.549 µmol/L vs 23.871 ± 11.609 µmol/L, P = 0.019) and the mean CLIF-C AD score (41.108 ± 5.223 vs 45.100 ± 4.429, P = 0.033) in the underdilated group were significantly lower than those in the control group during 6 to 12 months after the procedure. In line with the control group, the ability to reduce portal pressure gradient (PPG) and achieve a significantly clinical remission of PVT and ascites severity was showed in the underdilated group 3 months after TIPS creation (P < 0.001). The Kaplan-Meier analysis demonstrated that no statistically significant differences were found in the cumulative incidence of no overt HE (OHE) (log-rank P = 0.383), cumulative incidence without shunt dysfunction (log-rank P = 0.283), cumulative incidence of no variceal rebleeding (log-rank P = 0.696), and survival (log-rank P = 0.341) (log-rank P = 0.341) between the two groups during the follow-up period. CONCLUSION: For patients with prior splenectomy, it is safe to employ underdilated TIPS, as the stents will eventually self-expand to 8 mm. The present study has shown some degree of liver function preservation in the underdilated group, which may be related to slower progressive changes in the portal hemodynamics.

Dynamic Changes in the Aorta During the Cardiac Cycle Analyzed by ECG-Gated Computed Tomography.

Background: To characterize the difference in aortic dimensions during the cardiac cycle with electrocardiogram (ECG)-gated computed tomography angiography (CTA) and to determine whether other parameters in comparison to diameter could potentially provide a more accurate size reference for stent selection at the aortic arch and the proximal thoracic descending aorta. Methods: The CTA imaging of 90 patients during the cardiac cycle was reviewed. Three anatomic locations were selected for analysis (level A: 1 cm proximal to the innominate artery; level B: 1 cm distal to the left common carotid artery; and level C: 1 cm distal to the left subclavian artery). We measured the maximum diameter, the minimum diameter, the lumen area, the lumen perimeter, and the diameter derived from the lumen area, and the changes of each parameter at each level during the cardiac cycle were compared. Results: The mean age was 60.9 ± 12.4 years (range, 16-78 years). There was a significant difference in the aortic dimensions during the cardiac cycle (p < 0.001). The diameter derived from the lumen area at all three levels was changed least over time when compared to the area, perimeter, and the maximum aortic diameter (all p < 0.01). Conclusion: The aortic dimensional differences during the cardiac cycle are significant. The aortic diameter derived from the lumen area over other parameters may provide a better evaluation for selecting the size of the stent at the aortic arch and the proximal thoracic descending aorta. A prospective study comparing these different measurement parameters regarding the outcomes is still needed to evaluate the clinical implications.

Inclusion of sarcopenia improves the prognostic value of MELD score in patients after transjugular intrahepatic portosystemic shunt.

OBJECTIVE: To explore the predictive value of model for end-stage liver disease (MELD)-Sarcopenia score for survival of cirrhotic patients after transjugular intrahepatic portosystemic shunt (TIPS) placement. METHODS: 289 patients who underwent TIPS between February 2016 and December 2020 were included, they were divided into the sarcopenia group ( n = 138) and non-sarcopenia group ( n = 151) according to whether they were complicated with sarcopenia. Kaplan-Meier curve was used to analyze and compare the prognosis of the above two groups and multivariate Cox regression analysis was used to identify the independent prognostic factors. The performance of different predictive models was compared using C-index. RESULTS: During the follow-up, Kaplan-Meier analyses indicated that cumulative survival was significantly lower in sarcopenia group than that in non-sarcopenia group [74.6% vs. 92.7%, HR, 0.24 (95% confidence interval (CI), 0.12-0.46), Log-rank P < 0.001]. After multivariate Cox analysis, age [HR, 1.040 (95% CI, 1.015-1.065), P = 0.002], sarcopenia [HR, 3.948 (95% CI, 1.989-7.838), P < 0.001], albumin [HR, 0.945 (95% CI, 0.897-0.997), P = 0.037], and MELD score [HR, 1.156 (95% CI, 1.097-1.217), P < 0.001] were identified as the independent risk factors for mortality after TIPS. The C-indexes of MELD-Sarcopenia, Child-Pugh, MELD, MELD-Na, and the Freiburg index of post-TIPS survival (FIPS) scores were 0.782, 0.688, 0.719, 0.734, and 0.770, respectively. CONCLUSION: Sarcopenia is independently correlated with post-TIPS mortality, and MELD-Sarcopenia score showed the best performance in predicting post-TIPS mortality than the traditional predictive models.

Comparison of DEB-TACE and cTACE for the initial treatment of unresectable hepatocellular carcinoma beyond up-to-seven criteria: A single-center propensity score matching analysis.

PURPOSE: To evaluate clinical outcomes of drug-eluting beads transarterial chemoembolization (DEB-TACE) with CalliSpheres microspheres and conventional TACE (cTACE) as the initial treatment in patients with unresectable hepatocellular carcinoma (HCC) beyond up-to-seven criteria. METHODS: The study retrospectively assessed the medical records of HCC patients beyond up-to-seven criteria who received the initial treatment of DEB-TACE or cTACE from June 2016 to December 2019 in our institution. To reduce the patient selection bias, propensity score matching (PSM) analysis was used. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and adverse events (AEs) were compared between the two groups. In addition, prognostic factors affecting PFS and OS were analyzed by univariate and multivariate methods. RESULTS: A total of 312 eligible HCC patients were included in the study, including 140 patients in the DEB-TACE group and 172 patients in the cTACE group. 110 patients were chosen in each group after PSM analysis and there were no significant differences in baseline characteristics (P > 0.05). Before PSM analysis, DEB-TACE had better ORR and DCR compared to cTACE group (P < 0.05). After PSM analysis, the ORR for DEB-TACE group was still higher than that for cTACE group, while no significant difference in the DCR between the two groups. In addition, DEB-TACE group had better survival benefits than cTACE group before PSM analysis (mPFS: 11.5 months vs 9.0 months, P < 0.001; mOS: 24.0 months vs 19.2 months, P = 0.045). Similarly, after PSM analysis, the median PFS and OS in the DEB-TACE group were still higher than that in the cTACE group (mPFS: 11.1 months vs 9.0 months, P = 0.015; mOS: 25.0 months vs 19.0 months, P = 0.030). Further, the univariate and multivariate analysis indicated that DEB-TACE treatment was a positive prognostic factor for PFS and OS. CONCLUSION: DEB-TACE with CalliSpheres microspheres might be an effective and safe treatment for patients with unresectable HCC beyond up-to-seven criteria.

Transjugular intrahepatic portosystemic shunt in patients with autoimmune hepatitis-induced cirrhosis and variceal bleeding.

BACKGROUND AND AIM: An increasing number of patients with autoimmune hepatitis (AIH)-induced cirrhosis and variceal bleeding are currently referred for transjugular intrahepatic portosystemic shunt (TIPS). The aim of this study was to evaluate the safety and efficacy of TIPS in such patients, and to compare these results with data from patients with hepatitis B virus (HBV)-induced cirrhosis. MATERIALS AND METHODS: This retrospective study consisted of 211 patients between August 2016 and May 2021, and patients were allocated to AIH (n = 35) and HBV (n = 176) groups according to the etiology of the cirrhosis. The primary endpoint was mortality after TIPS use; the secondary endpoints were recurrent bleeding, overt hepatic encephalopathy (OHE), shunt dysfunction, and dynamic changes in liver function over time. RESULTS: During a median follow-up period of 27 months, 23 (10.9%) patients died, 22 (10.4%) experienced recurrent bleeding, 50 (23.7%) experienced OHE, and 25 (11.8%) developed shunt dysfunction. Compared with the HBV group, the AIH group exhibited a similar mortality risk (adjusted hazard ratio, HR 1.199; 95% confidence interval, CI 0.367-3.917; p = 0.764), OHE (adjusted HR 1.023, 95% CI 0.483-2.167, p = 0.954), and shunt dysfunction (adjusted HR 0.862, 95% CI 0.285-2.610, p = 0.792); but a higher risk of recurrent bleeding (adjusted HR 2.731, 95% CI 1.112-6.708, p = 0.028). The dynamic changes in liver function manifested an initial trend toward deterioration, and then subsequent recovery in both the AIH and HBV groups. CONCLUSIONS: TIPS is a safe and effective treatment, and should be considered for those patients with AIH-induced cirrhosis and variceal bleeding.

Natural History and Influence on Long-term Outcomes of Isolated Type II Endoleak after Endovascular Aneurysm Repair: A 10-year Experience at a Single Center.

BACKGROUND: The management of type II endoleaks (T2ELs) remains controversial in current literature. Hence, this study aimed to explore the natural history of isolated type II endoleak after endovascular aneurysm repair (EVAR) and its influence on long-term outcomes based on a 10-year follow-up at a tertiary medical center. METHODS: From January 2011 to April 2021, consecutive patients who underwent elective EVAR were reviewed. The demographics, clinical characteristics, treatment details, imaging information, in the event of T2ELs, and outcomes were extracted. RESULTS: A total of 287 patients were included for analysis. Isolated T2EL was identified in 79 patients (27.5%), while no endoleak was found in 208 patients (72.5%). The mean age at EVAR was 68.1 ± 8.9 years (range, 41-92 years) and the majority of patients were male (81.5%). The mean follow-up duration was 42.7 months (range, 2-119.7 months). Among the 79 patients with isolated T2ELs, 33 (41.8%, 33/79) were early and 46 (58.2%, 46/79) were late. Spontaneous resolution of T2ELs was identified in 29 patients (36.7%, 29/79). Persistent T2ELs were observed in 50 patients (63.3%, 50/79). No sac growth was seen in 33 patients (66%, 33/50) and these patients were managed conservatively. The remaining 17 patients (34%, 17/50) showed significant sac growth. Six of them declined intervention due to various reasons and the remaining 11 patients underwent interventional embolization for T2ELs. Following the embolization, 2 patients had complete resolution of T2ELs and 9 patients had persistent T2ELs. Among the patients with persistent T2ELs, 2 patients (2/9) still showed progressive sac growth, and one of them died from aneurysm rupture; the remaining 7 patients (7/9) showed no sac growth. Patients with isolated T2ELs had a higher incidence of sac growth than patients without any endoleak (21.5% vs 4.3%, p < 0.001), while no difference was found in overall survival between the two groups. In Cox regression analysis, only higher age was independently associated with worse survival. CONCLUSIONS: Type II Endoleak was significantly associated with aneurysm sac growth and no association with survival was observed.

Late combination of transarterial chemoembolization with apatinib and camrelizumab for unresectable hepatocellular carcinoma is superior to early combination.

OBJECTIVE: The purpose of this study was to explore the efficacy and safety of transarterial chemoembolization (TACE) combined with apatinib and camrelizumab (TACE + AC) for unresectable hepatocellular carcinoma (HCC), and the impact of the timing of the combination on it. METHODS: In this single-arm retrospective study, consecutive data of patients with unresectable HCC treated to our hospital from March 2017 to September 2021 were collected. These patients were treated with TACE and started on camrelizumab and apatinib within one week of TACE. Camrelizumab 200 mg intravenously once every three weeks and apatinib 250 mg orally once daily. Repeat TACE treatment was available on an on-demand basis. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), and safety. The univariate and multivariate Cox regression analyses were used to assess the effect of early and late combination on OS and PFS. RESULTS: A total of 80 patients were enrolled in this study. The median OS was 22.1 months (95% confidence interval [CI]: 13.8-30.5 months) and the median PFS was 15.7 months (95% CI: 14.7-16.6 months). The ORR was 58.8% (95% CI: 47.2-69.6) and DCR reached 81.2% (95% CI: 71.0-89.1). Multivariable Cox proportional hazard regression analyses showed that TACE late combined with apatinib and camrelizumab provided better OS than early combination (HR = 0.175, 95% CI:0.060-0.509, P = 0.001), as did PFS (HR = 0.422, 95% CI:0.184-0.967, P = 0.041). All treatment-related adverse events were tolerable, and no serious adverse events were observed. CONCLUSION: TACE combined with apatinib plus camrelizumab for patients with unresectable HCC has promising antitumor activity and a manageable safety profile. For unresectable HCC with large tumor burden, late combination provides better OS and PFS compared to early combination.