Adjuvant Transarterial Chemoembolization With Sorafenib for Portal Vein Tumor Thrombus: A Randomized Clinical Trial.

Importance: Certain patients with hepatocellular carcinoma with portal vein tumor thrombus could benefit from surgical resection, and postoperative adjuvant therapy may lower the incidence of tumor recurrence. Objective: To compare the efficacy and safety of sorafenib plus transarterial chemoembolization vs sorafenib alone as postoperative adjuvant therapy for patients with hepatocellular carcinoma with portal vein tumor thrombus. Design, Setting, and Participants: This was a phase 3, multicenter, randomized clinical trial conducted in 5 hospitals in China. A total of 158 patients were enrolled and randomized from October 2019 to March 2022, with a median follow-up of 28.4 months. Portal vein tumor thrombus was graded by the Cheng classification. Eligible patients with hepatocellular carcinoma with Cheng grade I to III portal vein tumor thrombus (ie, involving segmental or sectoral branches, right- or left-side branch, or main trunk of portal vein) were included. Interventions: Patients were randomly assigned 1:1 to receive transarterial chemoembolization with sorafenib or sorafenib alone as postoperative adjuvant therapy. Sorafenib treatment was started within 3 days after randomization, with an initial dose of 400 mg orally twice a day. In the transarterial chemoembolization with sorafenib group, transarterial chemoembolization was performed 1 day after the first administration of sorafenib. Main Outcomes and Measures: The primary end point was recurrence-free survival. Efficacy was assessed in the intention-to-treat population and safety was assessed in patients who received at least 1 dose of study treatment. Results: Of 158 patients included, the median (IQR) age was 54 (43-61) years, and 140 (88.6%) patients were male. The median (IQR) recurrence-free survival was significantly longer in the transarterial chemoembolization with sorafenib group (16.8 [12.0-NA] vs 12.6 [7.8-18.1] months; hazard ratio [HR], 0.57; 95% CI, 0.39-0.83; P = .002). The median (IQR) overall survival was also significantly longer with transarterial chemoembolization with sorafenib than with sorafenib alone (30.4 [20.6-NA] vs 22.5 [15.4-NA] months; HR, 0.57; 95% CI, 0.36-0.91; P = .02). The most common grade 3/4 adverse event was hand-foot syndrome (23 of 79 patients in the transarterial chemoembolization with sorafenib group [29.1%] vs 24 of 79 patients in the sorafenib alone group [30.4%]). There were no treatment-related deaths in either group. The transarterial chemoembolization with sorafenib group did not show additional toxicity compared with the sorafenib monotherapy group. Conclusion and Relevance: In this study, the combination of sorafenib and transarterial chemoembolization as postoperative adjuvant therapy in patients with hepatocellular carcinoma with portal vein tumor thrombus resulted in longer recurrence-free survival and overall survival than sorafenib alone and was well tolerated. Trial Registration: ClinicalTrials.gov Identifier: NCT04143191.

Anlotinib combined with transarterial chemoembolization for unresectable hepatocellular carcinoma associated with hepatitis B virus: a retrospective controlled study.

Purpose: To investigate the efficacy and safety of combined treatment of anlotinib and transarterial chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma (uHCC) associated with hepatitis B virus (HBV) infection. Methods: We retrospectively collected the data of 96 uHCC patients associated with HBV infection who received either TACE only (TO group; n = 64) or anlotinib combined with TACE (TA group; n = 32) from January 2017 to January 2021. The primary endpoint was overall survival (OS). The secondary outcomes included progression-free survival (PFS), tumor response according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) and RECIST 1.1, and adverse events (AEs). Results: The median OS and median PFS were significantly longer in the TA group compared to the TO group (17.6 months vs. 9.4 months, p = 0.018; 6.7 months vs. 3.8 months, p = 0.003, respectively). In addition, the overall objective response rate (ORR) and disease control rate (DCR) numerically increased in the TA group (mRECIST, ORR 65.6% vs. 46.9%, p = 0.064, DCR 90.6% vs. 85.9%, p = 0.382; RECIST 1.1, ORR 46.9% vs. 15.6%, p = 0.001, DCR 90.6% vs. 85.9%, p = 0.382, respectively). It was worth noting that no treatment-related mortality occurred during the study. The most common AEs included elevated transaminases (56.3%), decreased appetite (46.9%), and abdominal pain (37.5%) in the TA group. Although the incidence rate of grade 3/4 AEs was higher in the TA group, all of them were controllable. Conclusions: The combination of anlotinib and TACE has shown promising results in improving outcomes for patients with HBV-related uHCC, as compared to TACE monotherapy. In addition, this combination therapy has demonstrated a controllable safety profile. However, further validation is urgently needed through randomized controlled trials with large sample sizes.

Hepatic Arterial Infusion Chemotherapy Plus Lenvatinib and Tislelizumab with or Without Transhepatic Arterial Embolization for Unresectable Hepatocellular Carcinoma with Portal Vein Tumor Thrombus and High Tumor Burden: A Multicenter Retrospective Study.

Purpose: The current therapeutic strategies for high-risk, unresectable hepatocellular carcinoma (HCC) patients demonstrate suboptimal outcomes. This study aimed to assess the clinical efficacy of the combined approach of hepatic arterial infusion chemotherapy (HAIC), lenvatinib, and tislelizumab, either with or without transhepatic arterial embolization (TAE), in managing HCC patients with portal vein tumor thrombus (PVTT) and significant tumor load. Patients and Methods: In this multicenter retrospective study, we analyzed patients diagnosed with primary, unresectable HCC presenting with PVTT and substantial tumor load who had undergone treatment with HAIC, lenvatinib, and tislelizumab, with or without TAE (referred to as the THLP or HLP group), between January 2019 and February 2022 across four medical centers in China. The outcomes included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and progression-free survival (PFS). Results: The study cohort comprised 100 patients, 50 each in the THLP and HLP groups. The THLP group demonstrated a significantly superior ORR (72% vs 52%, P=0.039). However, both groups exhibited comparable DCR (88% vs 76%, P=0.118), as assessed by the modified response evaluation criteria in solid tumors. The median OS and PFS for the entire cohort were 12.5 months (95% CI, 10.9-14.8) and 5.0 months (95% CI, 4.2-5.4), respectively. The THLP group exhibited a significantly extended OS (median, 14.1 vs 11.3 months, P=0.041) and PFS (median, 5.6 vs 4.4 months, P=0.037) in comparison to the HLP group. The most frequently reported treatment-related adverse events included abdominal pain and nausea, both reported by 59% of patients. Conclusion: The combination of HAIC, lenvatinib, tislelizumab, and TAE was feasible in HCC patients with PVTT and high tumor burden, with tolerable safety.

Lenvatinib Combined With Transarterial Chemoembolization as First-Line Treatment for Advanced Hepatocellular Carcinoma: A Phase III, Randomized Clinical Trial (LAUNCH).

PURPOSE: Lenvatinib (LEN) is a first-line therapy for patients with advanced hepatocellular carcinoma (HCC); however, it has shown modest survival benefits. Therefore, we aimed to compare clinical outcomes of LEN combined with transarterial chemoembolization (LEN-TACE) versus LEN monotherapy in patients with advanced HCC. MATERIALS AND METHODS: This was a multicenter, randomized, open-label, parallel group, phase III trial. Patients with primary treatment-naive or initial recurrent advanced HCC after surgery were randomly assigned (1:1) to receive LEN plus on-demand TACE (LEN-TACE) or LEN monotherapy. LEN was initiated within 3 days after random assignment (initial dose: 12 mg once daily for patients ≥ 60 kg; 8 mg once daily for patients < 60 kg). TACE was initiated one day after LEN initiation. The primary end point was overall survival (OS). RESULTS: Between June 2019 and July 2021, a total of 338 patients underwent random assignment at 12 centers in China: 170 to LEN-TACE and 168 to LEN. At a prespecified event-driven interim analysis after a median follow-up of 17.0 months, the median OS was significantly longer in the LEN-TACE group (17.8 v 11.5 months; hazard ratio, 0.45; P < .001). The median progression-free survival was 10.6 months in the LEN-TACE group and 6.4 months in the LEN group (hazard ratio, 0.43; P < .001). Patients in the LEN-TACE group had a higher objective response rate according to the modified RECIST (54.1% v 25.0%, P < .001). Multivariable analysis revealed that portal vein tumor thrombus and treatment allocation were independent risk factors for OS. CONCLUSION: The addition of TACE to LEN improves clinical outcomes and is a potential first-line treatment for patients with advanced HCC.

Efficacy of radiation plus transarterial chemoembolization and lenvatinib in hepatocellular carcinoma with portal vein tumor thrombus.

Background: We aimed to investigate the efficacy of a novel regimen, external beam radiation (RT) combined with trans arterial chemoembolization (TACE) and lenvatinib (LEN), in the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombus. Methods: We prospectively observed 102 participants from three tertiary medical centers in China between October 2018 and October 2020, who chose either RT plus TACE and LEN (RT-TACE-LEN) or TACE and LEN (TACE-LEN). LEN (12 mg or 8 mg daily) was administrated orally and continued until progression or intolerable side effects were noted. TACE was given one day after administration of LEN, and RT began within 4 weeks after the first TACE. The median dose/fraction of RT was 50 Gy/25 fractions (range: 45-60 Gy/25 fractions). Overall survival and progression free survival were compared between two groups, and complications were assessed. Results: Both 51 patients received RT-TACE-LEN and TACE-LEN, respectively. Most patients had tumor size> 5 cm (73.8%) and tumor number≥ 2 (69.9%). The overall incidence of toxicities was significantly higher in RT-TACE-LEN group than TACE-LEN group (100% vs. 64.7%, p< 0.001), but incidences of grade 3-4 toxicities were comparable (54.9% vs. 49.0%, p= 0.552). Both median overall survival (22.8 vs. 17.1 months, p= 0.031) and median progression-free survival (12.8 vs. 10.5 months, p= 0.035) were significantly longer after RT-TACE-LEN treatment than TACE-LEN. Conclusions: The addition of RT to TACE and LEN was safe, and might improve clinical outcomes of patients with advanced HCC, which needs conformation from further studies.

Efficacy and safety of transcatheter arterial chemoembolization plus hepatic arterial infusion chemotherapy in the treatment of advanced hepatocellular carcinoma with portal vein tumor thrombosis in the main trunk.

Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the sixth most prevalent malignancy worldwide. The incidence of portal vein tumor thrombosis (PVTT) is recorded as high as 10%-60% in HCC patients. The purpose of this study was to assess the efficacy and safety of transcatheter arterial chemoembolization (TACE) plus hepatic arterial infusion chemotherapy (HAIC) in advanced HCC patients complicated with PVTT in the main trunk. Patients and Methods: A total of 33 HCC patients were treated with TACE + HAIC or TACE, respectively. The primary endpoint was overall survival (OS), while the secondary endpoints included progression-free survival, objective response rate (ORR), and disease control rate (DCR) of HCC lesions and PVTT in the trunk. Adverse events and main complications were also investigated. A COX model was used to identify the risk factors associated with OS. Results: There were 16 patients receiving TACE + HAIC and 17 receiving TACE. The median OS was longer in the TACE + HAIC group than the TACE group (P < 0.05). There were no significant differences in the ORR and DCR of HCC lesions and PVTT response between the two groups (P > 0.05). Alpha-fetoprotein was <400 ng/ml. Multivariate analysis showed that cavernous transformation of portal vein was associated with longer OS. In terms of complications, the addition of HAIC showed more myelosuppression than the TACE alone group (P < 0.05). Conclusion: Compared with TACE alone, HAIC + TACE may be more safe and provide more benefits for HCC patients complicated with PVTT in the trunk.

Lenvatinib plus TACE with or without pembrolizumab for the treatment of initially unresectable hepatocellular carcinoma harbouring PD-L1 expression: a retrospective study.

PURPOSE: The aim of this retrospective study was to compare the clinical outcomes of pembrolizumab-lenvatinib-transarterial chemoembolization (TACE) versus lenvatinib-TACE sequential therapy in selected populations of Chinese patients with initially unresectable hepatocellular carcinoma (uHCC) harbouring programmed cell death ligand-1 (PD-L1) expression. METHODS: Consecutive patients with initial PD-L1-positive uHCC who received pembrolizumab-lenvatinib-TACE or lenvatinib-TACE sequential therapy were retrospectively identified from three medical institutions during 2016-2020. The primary endpoints included the rate of conversion therapy, defined as converting initially uHCC to hepatectomy, overall survival (OS), and progression-free survival (PFS); secondary endpoint was the frequency of key adverse events (AEs). RESULTS: In total, 220 consecutively recruited patients were retrospectively reviewed, 78 of whom were ineligible according to the current criteria, leaving 142 patients [pembrolizumab-lenvatinib-TACE: n = 70, median age 58 years (range 36-69) and lenvatinib-TACE: n = 72, 57 years (35-68)] who were eligible for the study. The median duration of follow-up was 27 months [95% confidence interval (CI), 26.3-28.7 months]. At the last follow-up, the rate of conversion therapy was 25.7% in the pembrolizumab-lenvatinib-TACE group and 11.1% in the lenvatinib-TACE group (p = 0.025). The median OS was 18.1 months (95% CI 16.5-20.7) in the pembrolizumab-lenvatinib-TACE group versus 14.1 months (95% CI 12.2-16.9) in the lenvatinib-TACE group [hazard ratio (HR) 0.56, 95% CI 0.38-0.83; p = 0.004]. A distinct difference in the median PFS interval between the groups was detected [9.2 months (95% CI 7.1-10.4) in the pembrolizumab-lenvatinib-TACE group vs. 5.5 months (95% CI 3.9-6.6) in the lenvatinib-TACE group (HR 0.60; 95% CI 0.39-0.91; p = 0.006)]. The rates of the key AEs assessed, which were hypertension, nausea, and rash, were higher in the pembrolizumab-lenvatinib-TACE group than in the lenvatinib-TACE group (all p < 0.05). CONCLUSION: Among the selected populations of patients with initial PD-L1-positive uHCC, pembrolizumab-lenvatinib-TACE sequential therapy may have promising antitumour activity, with an acceptable conversion rate and a well-characterized safety profile.

Establishing an in vitro model of MR-T1ρ imaging technology to quantify nucleus pulposus tissue proteoglycans: a preliminary study.

BACKGROUND: The aim of the present study was to construct an in vitro model of degenerated nucleus pulposus with different combinations of biochemical components, and to find an in vitro model for the early degeneration of nucleus pulposus suitable for the detection of magnetic resonance T1rho (MR-T1ρ) sequence for the early diagnosis of degeneration of lumbar intervertebral disc. METHODS: The proteoglycan concentration gradient in the first experimental group was 5%, with a concentration range of 7 samples in vitro models from 5% to 35%. The second experimental group had 15 samples with a 1% concentration gradient of proteoglycan (range, 10-24%), with a higher water content compared with the first group. The third experimental group contained 20 samples with a concentration gradient of 1% proteoglycan (range, 10-29%), with 75% water content. All of the in vitro models were scanned using a 3.0T GE MR. To analyze the correlation between the proteoglycan content of the in vitro model and the T1ρ value, we investigated the feasibility and stability of modeling. RESULTS: There was no correlation between the in vitro model proteoglycan concentration and T1ρ value in the first experimental group; however, there was a significant negative correlation between the proteoglycan concentration and T1ρ value in the second experimental group (Y=-3.02X+131.8, R2=0.852, P<0.05). In the third experimental group, the proteoglycan concentration was significantly positively correlated with T1ρ value (Y=3.05X+11.99, R2=0.834, P<0.05). The comparison of the T1ρ values in the third experimental group before and 3 months after yielded an intraclass correlation coefficient value of 0.980, indicating that the biochemical components in the third experimental group were still stable after 3 months of storage. The slope of the regression equation between the Pfirrmann grading and T1ρ value in the third experimental group was not statistically different from the volunteer group (F=0.54, P=0.814), suggesting that the lumbar disc nucleus pulposus tissue of in vitro model samples fitted well with the volunteer group. CONCLUSIONS: In this experiment, we successfully constructed an in vitro model of nucleus pulposus tissue proteoglycan that can be used for the quantitative evaluation of the MR-T1ρ imaging.

The prognostic role of ovarian endometriosis in symptomatic adenomyosis patients underwent uterine artery embolization.

BACKGROUND: To explore the prognostic role of ovarian endometriosis in symptomatic adenomyosis patients underwent uterine artery embolization (UAE). METHODS: This was a retrospective, single-center study. A total of 76 patients with adenomyosis who underwent UAE in The First Affiliated Hospital of Sun Yat-sen University between May 2009 and July 2016 were enrolled in this study. These patients were divided into two groups based on whether complicated with ovarian endometriosis. After UAE, the patients were followed up for 12 months. The improvements of dysmenorrhea and menorrhagia were evaluated according to the symptom relief criteria. The improvement rates in both groups were analyzed and compared. RESULTS: Among the 76 patients with adenomyosis, 17 (22.3%) were diagnosed with OE and 59 (77.6%) were non-OE. In the OE group, all patients (17/17, 100%) had dysmenorrhea and 11 (11/17, 64.7%) had menorrhagia. In non-OE group, 57 patients (57/59, 96.6%) had dysmenorrhea and 50 (50/59, 84.7%) had menorrhagia. The improvement rates of dysmenorrhea in the two groups were 47.1% (OE group) and 86.0% (non-OE group), respectively (P<0.05). The improvement rates of menorrhagia in the two groups were 63.6% (OE group) and 84.0% (non-OE group), respectively (P=0.263). CONCLUSIONS: Patients without OE showed a lower incidence of dysmenorrhea and may have an advantage in the improvement of dysmenorrhea compared with those with OE when they underwent UAE. However, no significant difference was observed in the improvement of menorrhagia.

Determinants of pain in advanced HCC patients recieving hepatic artery infusion chemotherapy.

Purpose Hepatic arterial infusion chemotherapy (HAIC) is one of the options to treat unresectable hepatocellular carcinoma (HCC). The majority of HCC patients suffer great pain in the course of HAIC treatment. To improve the quality of life and the efficacy of HAIC treatment, the causes of pain, the choice of an analgesic regimen, and the relationship between pain and prognosis of HCC were analyzed. Methods A total of 376 HCC patients under HAIC in our hospital were recriuted between March 2017 and September 2019. Multivariate linear regression analysis (stepwise) was used to calculate the potential factors related to the severe pain in HCC patients under HAIC. Analgesics treatments were carried out based on the results of the visual analogue scale (VAS) score which was used to evaluate the pain. Results The mean value of the VAS score is 3.604, which indicates that the pain in most patients is mild and endurable. Intra-arterial lidocaine injection is an effective method in most patients (96%, 361 of 376), and the total score of VAS is reduced from 1355 to 195 following lidocaine injection. Multivariate analysis suggestes that oxaliplatin (OXA) preparation time, hepatic artery diameter and OXA manufacturers (R2 = 0.859) are influential factors for pain scores. Conclusion This study demonstrates an effective way to systematically assess and ease pain in HCC patients with HAIC treatment. OXA preparation time, hepatic artery diameter, and OXA manufacturers are the potential influencing factors for pain. This work presented here will provide a detailed understanding of the clinical application of HAIC in advanced HCC patients.

Efficacy and Safety of Transarterial Chemoembolization Combined With Anlotinib for Unresectable Hepatocellular Carcinoma: A Retrospective Study.

OBJECTIVE: This study aimed to explore the efficacy and safety of using transarterial chemoembolization (TACE) combined with anlotinib in patients with unresectable hepatocellular carcinoma, compared with TACE alone. METHODS: This was a single-center study, retrospectively recruited 82 unresectable HCC patients who received either TACE alone (TA group; n = 46) or TACE combined with anlotinib (TC group; n = 36) between Jan 2018 and Jan 2019. The primary outcomes were progression-free survival (PFS) and overall survival (OS). While the secondary outcomes were the objective response rate (ORR), the disease control rate (DCR), and main complications. Log-rank test and Kaplan-Meier method was used to calculate the survival difference. All statistical tests were 2-sided and P value <0.05 were taken as statistically significant. RESULTS: Patients in TC group had a significant higher PFS than those in TA group (7.35 months vs. 5.54 months, p = 0.035). Although 3-month survival rate in the 2 groups was not statistically different (97.2% vs. 93.5%, p = 0.627), the survival rate at 6 months and 1 year were strongly higher in TC group (83.3% vs. 56.5%, p = 0.016; 66.7% vs. 19.6%, respectively, p < 0.05). Furthermore, there was a significantly higher ORR in TC group, while no statistical difference existed in DCR. Neither treatment-related mortality nor grade 4 adverse events (AEs) occurred. However, 2 patients in TC group had grade 3 AEs (one suffered with erythra, and the other with hand-foot-skin reaction), which disappeared after prompt treatment. CONCLUSION: TACE combined with anlotinib is safe and may improve outcomes for unresectable HCC patients comparing with TACE alone. Randomized controlled trials are warranted to further evaluate treatment effects of anlotinib in HCC.

Efficacy and safety of hepatic arterial infusion chemotherapy combined with transarterial embolization for unresectable hepatocellular carcinoma: A propensity score-matching cohort study.

PURPOSE: The aim of this study was to assess the effectiveness and safety of hepatic arterial infusion chemotherapy (HAIC) using the FOLFOX regimen combined with transarterial embolization (TAE + HAIC) in patients with unresectable hepatocellular carcinoma (HCC). METHODS: Unresectable HCC patients treated with TAE + HAIC and conventional transcatheter arterial chemoembolization (TACE), respectively, between January 2015 and October 2016 in China were retrospectively assessed. The primary outcome was progression-free survival (PFS), while secondary outcomes included the objective response rate (ORR), the disease control rate (DCR), and main complications. Propensity score matching (PSM) was estimated by multiple logistic regression using caliper matching (caliper 0.2). A Cox proportional hazards model was used to identify those factors shown to be associated with PFS. RESULTS: A total of 113 patients were analyzed, with 41 and 72 receiving TAE + HAIC and TACE, respectively. After PSM, 35 pairs of patients were assessed. The median PFS was 7.93 months (95% confidence interval [CI], 4.44-11.42) for the TAE + HAIC group, which was higher compared with 2.60 months (95% CI, 0.93-4.27, P = 0.003) for TACE. The subgroup with Barcelona clinic liver cancer (BCLC) stage C obtained more PFS benefit from TAE + HAIC (P = 0.002). ORRs in the TAE + HAIC and TACE groups were 37.14% (13/35) and 20.00% (7/35, P = 0.112), respectively; DCRs were 88.57% (31/35) and 60.00% (21/35, P = 0.006), respectively. Abundant blood supply (hazard ratio [HR] =0.327, 95% CI 0.173-0.615, P < 0.001) and TAE + HAIC (HR = 0.332, 95% CI 0.177-0.621, P < 0.001) were associated with longer PFS in multivariate analysis. CONCLUSIONS: Compared with conventional TACE, TAE + HAIC provides more PFS benefits to patients with unresectable HCC, especially in those with BCLC stage C.

Crustal movement and strain distribution in East Asia revealed by GPS observations.

East Asia is bounded by the Indian plate to the southwest and the Pacific and Philippine plates to the east, and has undergone complex tectonic evolution since ~55 Ma. In this study, we collect and process three sources of GPS datasets, including GPS observations, GPS positioning time series, and published GPS velocities, to derive unified velocity and strain rate fields for East Asia. We observed southward movement and arc-parallel extension along the Ryukyu Arc and propose that the maximum principal stress axis (striking NEE) in North China could be mainly induced by westward subduction of the Pacific plate and the southward movement of the Ryukyu Arc. The large EW-trending sinistral shear zone that bounds North China has been created by eastward movement of South China to the south and westward subduction of the Pacific plate to the north. GPS velocity profiles and strain rates also demonstrate that crustal deformation in mainland China is controlled by northeastward collision of the Indian plate into Eurasia and westward subduction of the Pacific and Philippine Sea plates beneath Eurasia. In particular, the India-Eurasia continental collision has the most extensive impact, which can reach as far as the southern Lake Baikal. The viscous behavior of the subducting Pacific slab also drives interseismic deformation of North China. The crustal deformation caused by Philippine oceanic subduction is small and is limited to the region between the southeast coast of mainland China and Taiwan island. However, the principal compressional strain around eastern Taiwan is the largest in the region.

Computed tomography-guided sub-end plate injection of pingyangmycin for a novel rabbit model of slowly progressive disc degeneration.

BACKGROUND CONTEXT: Different animal models are used in disc degenerative disease research by now. To our knowledge, a functional animal model that mimics ischemic and slowly progressive disc degeneration of humans does not exist. STUDY DESIGN: This is an experimental animal study of disc degeneration. PURPOSE: The purpose of this study was to establish an ischemic and slowly progressive intervertebral disc (IVD) degeneration model with an injection of pingyangmycin (PYM) into subchondral bone adjacent to the disc, using bone marrow needle guided by computed tomography (CT) scan. METHODS: The subchondral bone adjacent to the lumbar IVDs (from L3-L4 to L5-L6) of 18 rabbits was randomly injected with 3 mL PYM solution (1.5 mg/mL PYM), 3 mL phosphate-buffered saline (vehicle control), or exteriorized but not injected with anything (sham), with using bone marrow needle guided by CT scan. The degenerative process was investigated by using radiography and magnetic resonance imaging at 1, 3, and 6 months postoperatively, combined with histological scoring, immunohistochemistry, and real-time polymerase chain reaction analysis. RESULTS: Significant disc space narrowing was observed at 6 months in the discs adjacent to the subchondral bone injected with PYM, compared with the control groups (p<.05). The magnetic resonance imaging assessment also demonstrated a progressive loss of T2-weighted signal intensity postoperatively. The histological score increased significantly compared with that of the control groups from 3 months to the end point (p<.05). The bone tissue area of the end plate increased significantly at the end point, compared with that of the control groups (p<.05). The results of molecular analysis showed significant increase of matrix metalloproteinase-3, a disintegrin and metalloproteinase with thrombospondin motif-5, and marked reduction of aggrecan and Type II collagen after 3 months at the messenger RNA levels in the discs of PYM group (p<.05). The von Willebrand factor expression of PYM group also showed a significant reduction after 1 month (p<.05). CONCLUSIONS: Percutaneous injection of PYM into the subchondral bone adjacent to the lumbar IVDs of rabbits, using bone marrow needle guided by CT scan, can result in ischemic and slowly progressive disc degeneration model, which mimics the onset of human disc degeneration.

Pharmacokinetics of continuous transarterial infusion of 5-fluorouracil in patients with advanced hepatocellular carcinoma.

Numerous studies concerning hepatic arterial infusion chemotherapy (HAIC) have been conducted by adopting regimens containing 5-fluorouracil (FU), with a favourable efficacy compared with conventional transcatheter arterial chemoembolisation (TACE) treatment; however, the detailed mechanism of HAIC remains unclear. The present study aimed to evaluate peripheral concentration time curves of 5-FU administered through the hepatic artery, which may additionally explain the mechanism of action of HAIC. A total of 10 eligible patients underwent transcatheter arterial embolization and a 2-day HAIC treatment regimen using a folinic acid, fluorouracil and oxaliplatin regimen. Peripheral venous blood sampling was performed in each patient prior to infusion, and at 0, 0.5, 1, 1.5, 2, 5, 10, 15, 22 and 23 h following the start of infusion. The blood sample at 0 h was analysed for dihydropyrimidine dehydrogenase (DPD) levels by high performance liquid chromatography, and the rest of the samples were analysed for 5-FU by optimised liquid chromatography-mass spectrometry (LC-MS). The lower limit of quantification of optimised LC-MS for 5-FU was 5 ng/ml. The steady-state plasma concentration of 5-FU administered through the hepatic artery was achieved after 15 h. This concentration largely varied, ranging from 8.64-152.00 ng/ml. Optimised LC-MS may detect low concentrations of 5-FU. The steady-state concentration of 5-FU administered through the hepatic artery was achieved after 15 h. DPD levels were analysed through determining the ratio of plasma uracil (U) and dihydrouracil (UH2) by HPLC, and the results indicated a mild DPD deficiency in the patients with HCC. These results may provide a basis for the explanation of the clinical efficacy of HAIC, and to additionally optimise its efficacy.

Establishment of a new animal model for ischemic lumbar vertebrae.

Degeneration and ischemia of lumbar intervertebral disc has become a more and more important issue for elder people. However the mechanism for this is still known, largely due to a lack of a suitable animal model. In this study, we constructed a new animal model for the study of ischemic lumbar vertebrae. 42 New Zealand white rabbits were chosen for the study. For each rabbit, two vertebrae were used. L5 was set as the experimental group and L4 was set as the control group. Percutaneous lumbar puncture needles were applied in vertebrae adjacent to endplate for L5 and L4. For L4 1 ml saline was injected and for L5 1 ml pingyangmycin (2 mg/mL) was used. 1, 2, 3, 4, 5 weeks; 2 and 3 months after surgery, 6 rabbits at each time point were randomly chosen and underwent MRI, pathological test. The results in L5 and L4 were compared. Another 6 rabbits were used for DSA (Digital Subtraction Angiography) and vascular cast to study the length and diameters of the branches of lumbar artery. It was identified that since the third week, slightly hyperintense signal on T2-weighted image (T2WI) and fat-suppression T2-weighted image (FS T2WI) were detected. Lumbar vertebrae damage could be identified since the fourth week. Results of MRI and the size of pathological area were positively related (r=0.965, P<0.05). DSA and vascular cast could both clearly show the third level branches of lumbar artery. Our study suggested that injection of pingyangmycin via percutaneous lumbar needle could successfully induce ischemia in lumbar endplate. This method had little trauma, required a simple operation process and is highly repetitive. Besides, by vascular cast, the most important source of blood supply is the media branch of the lumbar artery. This branch could be a new therapy pathway for the degeneration of lumbar vertebrae.

Comparison of contrast-enhanced ultrasound and contrast-enhanced computed tomography in evaluating the treatment response to transcatheter arterial chemoembolization of hepatocellular carcinoma using modified RECIST.

PURPOSE: We aimed to compare contrast-enhanced ultrasound (CEUS) with contrast-enhanced computed tomography (CECT) for evaluating the treatment response to transcatheter arterial chemoembolization (TACE) of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Treatment responses of 130 patients who underwent TACE were evaluated by CEUS and CECT. We initially compared the abilities of CEUS and CECT to detect residual tumour, which were confirmed by histology or angiography. Then, we compared the tumour response to TACE assessed by CEUS and CECT, according to Modified Response Evaluation Criteria in Solid Tumours (mRECIST). RESULTS: The sensitivity and accuracy of detecting residual tumour by CEUS vs. CECT were 95.9 % vs. 76.2 % (p < 0.001) and 96.2 % vs. 77.7 % (p < 0.001), respectively. For target lesions, 13 patients were observed as complete response (CR) by CEUS, compared to 36 by CECT (p < 0.001). For nontarget lesions, 12 patients were observed as CR by CEUS, compared to 22 by CECT (p = 0.006). For overall response, eight patients were observed as CR by CEUS, compared to 31 by CECT (p < 0.001). CONCLUSION: The diagnostic performance of CEUS was superior to CECT for detecting residual tumour after TACE. In clinical, CEUS should be recommended as an optional procedure for assessing the tumour response to TACE. KEY POINTS: • The mRECIST are widely applied for evaluating the response of HCC. • Imaging method has been applied to assess the therapeutic response to TACE. • The diagnostic performance of CEUS was superior to CECT for residual tumours. • CEUS can be a valuable method for assessing tumour response to TACE.

Transarterial embolization for serious renal hemorrhage following renal biopsy.

The goal of this study is to evaluate the feasibility and efficacy of percutaneous transarterial embolization for the treatment of serious renal hemorrhage after renal biopsy. Nine patients with renal hemorrhage had frank pain and gross hematuria as main symptoms after renal biopsy. Intrarenal arterial injuries and perinephric hematoma were confirmed by angiography in all cases. The arterial injuries led to two types of renal hemorrhage, Type I: severe renal injure or intrarenal renal artery rupture (n=5), with contrast medium spilling out of the artery and spreading into renal pelvis or kidney capsule in angiography; Type II, pseudo aneurysm or potential risk of intrarenal artery injure (n=4), where contrast medium that spilled out of intraartery was retained in the parenchyma as little spots less than 5 mm in diameter in angiography. Transcatheter superselective intrarenal artery embolization was performed with coils or microcoils (Type I intrarenal artery injure) and polyvinyl alcohol particles (Type II injure). The intrarenal arterial injuries were occluded successfully in all patients. Light or mild back or abdominal pain in the side of the embolized kidney was found in three patients following embolization procedures and disappeared 3 days later. Serum creatinine and perinephric hematoma were stable, and gross hematuresis stopped immediately (n=4) or 3-5 days (n=3) after embolization. In conclusions, transcatheter superselective intrarenal artery embolization as a minimally invasive therapy is safe and effective for treatment of serious renal hemorrhage following percutaneous renal biopsy.

A pilot study of uterine artery embolization with tris-acryl gelatin microspheres in guinea pigs.

OBJECTIVE: This study was designed to establish guinea pigs as an animal model for uterine artery embolization (UAE) with tris-acryl gelatin microspheres (TAGM). METHODS: Twenty-five female adult guinea pigs were randomly divided into two groups, including a uterine artery casting mould group (n=10) and a UAE group (n=15). Pelvic angiography and vascular casting mould were performed in the first group. The anatomical characters of the pelvic cavity in guinea pigs were described. In the second group, the technical feasibility of performing UAE with TAGM in guinea pigs was investigated. The histopathological slides of the uterus of guinea pigs after UAE were examined to inspect the outcomes of UAE. RESULTS: The uterine artery springs from the internal iliac artery, ascends tortuously along the cervix, and gives off vertically 8-10 branches to the cervix uteri and uterine horns. The diameters of the trunk of the uterine artery and its first branch were 0.32±0.027 mm and 0.14±0.01 mm, respectively. For UAE animals, the dosages of 40-120 and 100-300 µm TAGM were 0.033±0.003 ml and 0.015±0.002 ml, respectively. On histopathological slides, embosphere particles were found in the first branches of the uterine artery, the subserous arteries, and the intramural arteries. Inflammatory reactions in the uterus were common in guinea pigs after UAE. Local or dispersed areas of necrosis in uterus also were observed in a few guinea pigs. CONCLUSIONS: Guinea pigs are an appropriate and feasible model for UAE with TAGM.

Preoperative angiography and transarterial embolization in the management of carotid body tumor: a single-center, 10-year experience.

BACKGROUND: Sixty percent of paragangliomas are located unilaterally at the carotid bifurcation. These are referred to as carotid body tumors (CBTs). OBJECTIVE: To present our 10-year experience in the management of patients with CBTs, and to evaluate the efficacy of angiography and preoperative embolization technique in this retrospective study. METHODS: Sixty-two patients with surgically removed CBTs (Shamblin class II and III), were divided into two groups. Group I, the preoperative embolization group, included 33 patients with 11 class II lesions and 25 class III lesions. Group II, the group that had surgery only, without preoperative embolization, included 29 patients with 9 class II lesions and 21 class III lesions. Comparisons were made between the groups in terms of mean intraoperative blood loss, mean operation time, mean postoperative hospital stay, and clinical complications. RESULTS: In group I, post-embolization angiography demonstrated complete tumor devascularization in 25 (76%) lesions and partial devascularization in 11 (24%) lesions. All but 1 (2%) lesion were completely excised. Mean intraoperative blood loss, mean operation time, and mean hospital stay were 354.8 ± 334.4 mL, 170.3 ± 75.4 min, 8.0 ± 2.1 days in group I and 656.4 ± 497.4 mL, 224.6 ± 114.0 min, 9.5 ± 3.5 days in group II, respectively. In group II, 27 lesions (91%) were completely removed. The transient ischemic attack (TIA) and cranial nerve injury incidence rates were 10.3% and 13.8% in group II and only 3% for TIA in group I. CONCLUSION: These results suggest angiography is highly valuable for the diagnosis of CBT. Preoperative selective embolization of CBT is an effective and safe adjunct for surgical resection, especially for Shamblin class II and III tumors.