Targeted redox-responsive peptide for arterial chemoembolization therapy of orthotropic hepatocellular carcinoma.

OBJECTIVE: Transcatheter Arterial Chemoembolization (TACE) is the first choice for the treatment of advanced-stage hepatocellular carcinoma (HCC). However, TACE suffers from a lack of specificity and rapid drug release. Herein, a targeted redox-responsive peptide (TRRP) was synthesized and used as a carrier of doxorubicin (DOX) to enhance the efficacy of TACE through tumor cells targeting and controlled drug release. METHODS: TRRP has a high loading capacity of DOX and a sensitive drug release behavior at high glutathione (GSH) concentration. Moreover, TRRP could bind to the transferrin receptor on the surface of tumor cells, which enhanced the efficacy of TACE and reduced side effects of TACE. TACE with TRRP@DOX dispersed in lipiodol shows an enhanced therapeutic outcome compared to the treatment with DOX + lipiodol emulsion in orthotopic rat HCC models. RESULTS: TRRP has a high loading capacity of DOX and a sensitive drug release behavior at GSH concentration. Moreover, TRRP could bind to the transferrin receptor on the surface of tumor cells, which enhanced the efficacy of TACE and reduced side effects of TACE. TACE with TRRP@DOX dispersed in lipiodol shows an enhanced therapeutic outcome compared to the treatment with DOX + lipiodol emulsion in orthotopic rat HCC models. CONCLUSIONS: This study demonstrated that TRRP was a promising therapeutic agent for enhancing TACE therapy for HCC treatment.

Hypoxic Conditioning: A Potential Perioperative Strategy to Reduce Abdominal Aortic Occlusion-Related Injury in Mouse Proximal and Distal Organs.

This study aimed to investigate the impact of abdominal aortic occlusion (AAO)- induced injury on the kidney, lower limb muscles, heart, and brain in mice, and the potential protective effects of hypoxic postconditioning (HyC). The experimental design employed an abdominal aortic occlusion (AAO) model, and involved three groups of mice: sham, AAO, and AAO+HyC. Ten minutes after the AAO model, mice were subjected to hypoxic treatment lowering oxygen concentration to 5% within 45 minutes, and then returned to a normal oxygen environment. Hematoxylin- eosin (HE) stain was used for Histopathological examinations, and Quantibody Mouse Array was used for detecting apoptosis and inflammation-related protein expression. Histopathological examinations showed that HyC mitigated pathological damage to proximal organs (kidneys and lower limb muscles), distal organs (heart and brain), and reduced inflammatory cell infiltration. Expression of apoptosis- and inflammation-related proteins in brain and heart tissues were also evaluated. HyC significantly increased cellular inhibitor of apoptosis 2 (cIAP2) in the brain and Bcl-2 and insulin-like growth factor 2 (IGF-2) in the heart. Additionally, HyC regulated the expression of several inflammation-related factors in both brain and heart tissues. Although further investigation is needed, particularly in human subjects, this study highlights the potential of HyC as a promising therapeutic strategy for reducing AAO-associated organ damage.

Hypoxic postconditioning drives protective microglial responses and ameliorates white matter injury after ischemic stroke.

BACKGROUND: Ischemic stroke (IS) is a cerebrovascular disease with high incidence and mortality. White matter repair plays an important role in the long-term recovery of neurological function after cerebral ischemia. Neuroprotective microglial responses can promote white matter repair and protect ischemic brain tissue. AIMS: The aim of this study was to investigate whether hypoxic postconditioning (HPC) can promote white matter repair after IS, and the role and mechanism of microglial polarization in white matter repair after HPC treatment. MATERIALS & METHODS: Adult male C57/BL6 mice were randomly divided into three groups: Sham group (Sham), MCAO group (MCAO), and hypoxic postconditioning group (HPC). HPC group were subjected to 45 min of transient middle cerebral artery occlusion (MCAO) immediately followed by 40 min of HPC. RESULTS: The results showed that HPC reduced the proinflammatory level of immune cells. Furthermore, HPC promoted the transformation of microglia to anti-inflammatory phenotype on the third day after the procedure. HPC promoted the proliferation of oligodendrocyte progenitors and increased the expression of myelination-related proteins on the 14th day. On the 28th day, HPC increased the expression of mature oligodendrocytes, which enhanced myelination. At the same time, the motor neurological function of mice was restored. DISCUSSION: During the acute phase of cerebral ischemia, the function of proinflammatory immune cells was enhanced, long-term white matter damage was aggravated, and motor sensory function was decreased. CONCLUSION: HPC promotes protective microglial responses and white matter repair after MCAO, which may be related to the proliferation and differentiation of oligodendrocytes.

Abdominal Aortic Occlusion and the Inflammatory Effects in Heart and Brain.

Background: Abdominal aortic occlusion (AAO) occurs frequently and causes ischemia/reperfusion (I/R) injury to distant organs. In this study, we aimed to investigate whether AAO induced I/R injury and subsequent damage in cardiac and neurologic tissue. We also aimed to investigate the how length of ischemic time in AAO influences reactive oxygen species (ROS) production and inflammatory marker levels in the heart, brain, and serum. Methods: Sixty male C57BL/6 mice were used in this study. The mice were randomly divided into either sham group or AAO group. The AAO group was further subdivided into 1-4 hr groups of aortic occlusion times. The infrarenal abdominal aorta was clamped for 1-4 hr depending on the AAO group and was then reperfused for 24 hr after clamp removal. Serum, hippocampus, and left ventricle tissue samples were then subjected to biochemical and histopathological analyses. Results: AAO-induced I/R injury had no effect on cell necrosis, cell apoptosis, or ROS production. However, serum and hippocampus levels of malondialdehyde (MDA) and lactate dehydrogenase (LDH) increased in AAO groups when compared to sham group. Superoxide dismutase and total antioxidant capacity decreased in the serum, hippocampus, and left ventricle. In the serum, AAO increased the level of inducible nitric oxide synthase (iNOS) and decreased the levels of anti-inflammatory factors (such as arginase-1), transforming growth factor- ß1 (TGF-ß1), interleukin 4 (IL-4), and interleukin 10 (IL-10). In the hippocampus, AAO increased the levels of tumor necrosis factor (TNF-α), interleukin 1ß (IL-1ß), interleukin 6 (IL-6), IL-4, and IL-6, and decreased the level of TGF-ß1. In the left ventricle, AAO increased the level of iNOS and decreased the levels of TGF-ß1, IL-4, and IL-10. Conclusions: AAO did not induce cell necrosis or apoptosis in cardiac or neurologic tissue, but it can cause inflammation in the serum, brain, and heart.

MRI/PAI Dual-modal Imaging-guided Precise Tracking of Bone Marrow-derived Mesenchymal Stem Cells Labeled with Nanoparticles for Treating Liver Cirrhosis.

Background and Aims: Stem cell transplantation is a potential treatment option for liver cirrhosis (LC). Accurately and noninvasively monitoring the distribution, migration, and prognosis of transplanted stem cells using imaging methods is important for in-depth study of the treatment mechanisms. Our study aimed to develop Au-Fe3O4 silica nanoparticles (NPs) as tracking nanoplatforms for dual-modal stem cell imaging. Methods: Au-Fe3O4 silica NPs were synthesized by seed-mediated growth method and co-precipitation. The efficiency and cytotoxicity of the NPs-labeled bone marrow-derived mesenchymal stem cells (BM-MSCs) were evaluated by Cell Counting Kit-8 assays, ICP-MS, phenotypic characterization, and histological staining. The biodistribution of labeled BM-MSCs injected through different routes (the hepatic artery or tail vein) into rats with LC was detected by magnetic resonance imaging (MRI), photoacoustic imaging (PAI), and Prussian blue staining. Results: Synthesized Au-Fe3O4 silica NPs consisted of a core (star-shaped Au NPs) and an outside silica layer doped with Fe3O4 NPs. After 24 h coincubation with 2.0 OD concentration of NPs, the viability of BM-MSCs was 77.91%±5.86% and the uptake of Au and Fe were (22.65±1.82) µg/mL and (234.03±11.47) µg/mL, respectively. The surface markers of labeled BM-MSCs unchanged significantly. Labeled BM-MSCs have osteogenic and adipogenic differentiation potential. Post injection in vivo, rat livers were hypointense on MRI and hyperintense on PAI. Prussian blue staining showed that more labeled BM-MSCs accumulated in the liver of the hepatic artery group. The severity of LC of the rats in the hepatic artery group was significantly alleviated. Conclusions: Au-Fe3O4 silica NPs were suitable MRI/PAI dual-modal imaging nanoplatforms for stem cell tracking in regenerative medicine. Transhepatic arterial infusion of BM-MSCs was the optimal route for the treatment of LC.

Transarterial chemoembolization failure in patients with hepatocellular carcinoma: Incidence, manifestation and risk factors.

BACKGROUND: To identify the incidence, manifestation and risk factors of transarterial chemoembolization (TACE) failure defined as untreatable progression (UP) in patients with hepatocellular carcinoma (HCC) on short-term observation. METHODS: Patients from two hospitals with HCC treated with TACE were considered. According to the definition of UP, TACE failure was considered to be present in at least one of the following situations: situation I, failure to achieve objective response in the targeted tumor after at least two initial TACE treatments; situation II, failure to achieve objective response in local tumor progression or new intrahepatic tumor after another TACE session; situation III, presence of major progression; and situation IV, presence of impaired liver function or performance status that contraindicates TACE treatment. Patients were assessed for TACE failure on follow-up visits after two or three TACE sessions. Risk factors for TACE failure were evaluated with logistic regression analysis. RESULTS: A total of 206 patients were included. TACE failure occurred in 42 (42/206, 20.4%) patients, of whom 21, 1, 4, 0 and 16 patients manifested as situation I, II, III, IV alone, and combination of situation I with the others, respectively. Multivariate analysis showed that tumor without complete capsule (P < .001) and non-smooth margin (P = .004) were independent predictors of the presence of TACE failure. CONCLUSIONS: TACE failure was uncommon in patients with HCC, which manifested predominantly as failure of treatment response of the initial intrahepatic tumor. Non-smooth tumor margin and tumors without complete capsule were associated with the presence of TACE failure.

Liver infiltration of multiple immune cells during the process of acute liver injury and repair.

BACKGROUND: Immune cells, including neutrophils, natural killer (NK) cells, T cells, NKT cells and macrophages, participate in the progression of acute liver injury and hepatic recovery. To date, there has been no systematic study on the quantitative changes in these different immune cells from initial injury to subsequent recovery. AIM: To investigate the infiltration changes of various immune cells in acute liver injury models over time, and to study the relationship between the changes in leukocyte cell-derived chemotaxin 2 (LECT2) and the infiltration of several immune cells. METHODS: Carbon tetrachloride- and concanavalin A-induced acute liver injury models were employed to mimic toxin-induced and autoimmune-mediated liver injury respectively. The quantitative changes in various immune cells were monitored at different time points. Serum samples were collected, and liver tissues were harvested. Ly6G, CD161, CD4, CD8 and F4/80 staining were used to indicate neutrophils, NK/NKT cells, CD4+ T cells, CD8+ T cells and macrophages, respectively. Lect2-KO mice were used to detect the function of LECT2. RESULTS: During the injury and repair process, different types of immune cells began to increase, reached their peaks and fell into decline at different time points. Furthermore, when the serum alanine transaminase (ALT) and aspartate transaminase (AST) indices reverted to normal levels 7 d after the injury, the infiltration of immune cells still existed even 14 d after the injury, showing an obvious lag effect. We found that the expression of LECT2 was upregulated in acute liver injury mouse models, and the liver injuries of Lect2-KO mice were less severe than those of wild-type mice. Compared with wild-type mice, Lect2-KO mice had different immune cell infiltration. CONCLUSION: The recovery time of immune cells was far behind that of serum ALT and AST during the process of liver repair. LECT2 could regulate monocyte/macrophage chemotaxis and might be used as a therapeutic target for acute liver injury.

Safety and efficacy of lenvatinib combined with camrelizumab plus transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma: A two-center retrospective study.

Objectives: To compare the safety and efficacy of lenvatinib (LEN) combined with camrelizumab plus transcatheter arterial chemoembolization (TACE-LEN-C) and TACE combined with LEN (TACE-LEN) in patients with unresectable hepatocellular carcinoma (uHCC). Methods: Eighty-three patients with uHCC treated with TACE-LEN-C or TACE-LEN from September 2018 to May 2021 were enrolled in this retrospective study. Overall survival (OS), progression-free survival (PFS), local tumor response, and adverse events (AEs) were evaluated. Univariate and multivariate analyses were used to determine the factors affecting survival. Results: There were 31 patients in the TACE-LEN-C group and 52 patients in the TACE-LEN group. The median follow-up period was 14.2 months (range 7.2-25.2 months) in the whole study. The combination of triple therapy was found to significantly prolong the PFS (12.5 months vs. 6.6 months, P<0.001) and OS (18.9 months vs. 13.9 months, P<0.001. In terms of tumor response, the combination demonstrated a higher objective response rate (71% vs. 42.3% by the modified Response Evaluation Criteria in Solid Tumors, P=0.023) without a statistically significant difference in the disease control rate (93.5% in TACE-LEN-C, 80.8% in TACE-LEN, P=0.195). In the multivariate analysis, two independent factors affecting PFS were identified: number of tumors and treatment. Three independent factors affected OS: number of tumors, Barcelona Clinic Liver Cancer (BCLC) stage, and treatment. All the AEs were tolerable. Conclusion: TACE-LEN-C is a safe and effective treatment for patients with uHCC, and could be a potential treatment option.

Effect of partial splenic embolization on transarterial chemoembolization for hepatocellular carcinoma with hypersplenism.

ABSTRACT: This study retrospectively studied transarterial chemoembolization (TACE) combined with partial splenic embolization (PSE) in the treatment of hepatocellular carcinoma (HCC) with severe hypersplenism.Seventy patients with HCC in Barcelona Clinic Liver Cancer (BCLC) stage B or C with hypersplenism were divided into non-partial splenic embolization group (N-PSE, n = 51) and partial splenic embolization group (PSE, n = 19). The N-PSE group was further divided into N-PSE with mild to moderate hypersplenism (N-PSE-M, 47 cases) and N-PSE with severe hypersplenism (N-PSE-S, 4 cases).In the PSE group, leukocytes, neutrophils, lymphocytes, and platelets were significantly increased (P < .05) and were significantly different from that in the N-PSE group (P < .05). In the N-PSE group, except for a slight increase in neutrophils, other blood cells were decreased, including lymphocytes that were significantly decreased (P < .05). There was no significant difference in the changes of liver function between the 2 groups before and after surgery (P > .05). The analysis showed a significant increase in ascites after 6 months of TACE in the N-PSE group (P < .05). According to the follow-up results, the median overall survival (OS) in the PSE group was 24.47 ±â€Š3.68 (months) and progression-free survival (PFS) was 12.63 ±â€Š4.98 (months). Regardless of OS or PFS, the PSE group was superior to the N-PSE group and its subgroups, with a statistically significant difference in PFS between the N-PSE group and PSE group (P < .05). Moreover, the time of extrahepatic progression was significantly earlier in the N-PSE group than in the PSE group (P < .05). N-PSE-S group had the worst prognosis, and PFS and OS were worse than the other 2 groups, suggesting that PSE in severe hypersplenism may improve PFS and OS.In patients with HCC and severe hypersplenism, TACE should be actively combined with PSE treatment.

Artificial pneumothorax improves radiofrequency ablation of pulmonary metastases of hepatocellular carcinoma close to mediastinum.

BACKGROUND: To investigate the feasibility, safety and efficacy of percutaneous radiofrequency ablation (RFA) of pulmonary metastases from hepatocellular carcinoma (HCC) contiguous with the mediastinum using the artificial pneumothorax technique. METHOD: A total of 40 lesions in 32 patients with pulmonary metastases from HCC contiguous with the mediastinum accepted RFA treatment from August 2014 to May 2018 via the artificial pneumothorax technique. After ablation, clinical outcomes were followed up by contrast enhanced CT. Technical success, local tumor progression (LTP), intrapulmonary distant recurrence (IDR), and adverse events were evaluated. Overall survival (OS) and local tumor progression free survival (LTPFS) were recorded for each patient. RESULTS: The tumor size was 1.4 ± 0.6 cm in diameter. RFA procedures were all successfully performed without intra-ablative complications. Technical success was noted in 100% of the patients. Five cases of LTP and 8 cases of IDR occurred following the secondary RFA for treatment. Slight pain was reported in all patients. No major complications were observed. The 1, 2, and 3-year LTPFS rates were 90.6, 81.2, and 71.8%, and the 1, 2, and 3-year OS rates were 100, 100 and 87.5%, respectively. CONCLUSION: Artificial pneumothorax adjuvant RFA is a feasible, safe, and efficient method for treatment of pulmonary metastases from HCC contiguous with the mediastinum.

Pretreatment Apparent Diffusion Coefficient as a Predictor of Response to Transcatheter Arterial Chemoembolization Immediately Combined with Radiofrequency Ablation for Treatment of Solitary Large Hepatocellular Carcinoma.

PURPOSE: To evaluate whether the pretreatment apparent diffusion coefficient (ADC) measured with diffusion weighted imaging (DWI) of tumor can be used as an imaging biomarker for predicting prognosis in solitary large hepatocellular carcinomas (HCCs) treated with transcatheter arterial chemoembolization (TACE) immediately combined with radiofrequency ablation (RFA). PATIENTS AND METHODS: In this single institution retrospective study, 40 solitary large HCCs that underwent treatment with TACE immediately combined with RFA were analyzed. All patients underwent abdominal dynamic contrast-enhanced magnetic resonance imaging within one month before treatment with DWI, and ADC values in the lesions were measured by two independent radiologists. Associations among patients' preoperative ADC values and objective response (OR), progression-free survival (PFS) and overall survival (OS) were examined. Survival curves were drawn with the Kaplan-Meier method, and differences were determined with the Log rank test. The Cox proportional-hazards model was used for univariate and multivariate analyses of PFS and OS. RESULTS: Forty solitary large HCCs (mean 9.54 cm, range 5.04-16.06 cm) were successfully treated with TACE in immediate combination with RFA (OR 75%). The ADC values were significantly higher in the response group than the non-response group (1.51±0.32×10-3 mm2/s vs 1.09±0.17×10-3 mm2/s; P<0.001). As predicted on the basis of the ADC values, the optimal cutoff value for the efficacy of TACE combined with RFA was 1.32×10-3 mm2/s, with a predictive sensitivity of 0.63 and a specificity of 1.00. Patients with high ADC had longer PFS than those with low ADC (14.9 months vs 5.3 months; P<0.001) and had significantly longer survival rates (22.6 months vs 12.1 months; P=0.004). CONCLUSION: Preoperative ADC values <1.32×10-3 mm2/s are an independent predictor of poorer prognosis in patients with solitary large HCCs who have undergone TACE immediately combined with RFA.

MOF-Derived Double-Layer Hollow Nanoparticles with Oxygen Generation Ability for Multimodal Imaging-Guided Sonodynamic Therapy.

The high reactive oxygen species (ROS) generation ability and simple construction of sonosensitizer systems remain challenging in sonodynamic therapy against the hypoxic tumor. In this work, we rationally prepared MOF-derived double-layer hollow manganese silicate nanoparticle (DHMS) with highly effective ROS yield under ultrasound irradiation for multimodal imaging-guided sonodynamic therapy (SDT). The presence of Mn in DHMS increased ROS generation efficiency because it could be oxidized by holes to improve the electron-hole separation. Moreover, DHMS could produce oxygen in the tumor microenvironment, which helps overcome the hypoxia of the solid tumor and thus enhance the treatment efficiency. In vivo experiments demonstrated efficient tumor inhibition in DHMS-mediated SDT guided by ultrasound and magnetic resonance imaging. This work presents a MOF-derived nanoparticle with sonosensitive and oxygen generating ability, which provides a promising strategy for tumor hypoxia in SDT.

A three-dimensional, anatomy-based nephrometry score to guide nephron-sparing surgery for renal sinus tumors.

BACKGROUND: A quantitative nephrometry scoring system specifically for renal sinus tumors will assist in classifying surgical complexity and treatment planning. METHODS: By using preoperative computed tomography, magnetic resonance imaging, and 3-dimensional image reconstruction, 5 critical components were assessed: the ratio of the sinus area occupied by the tumor in relation to the whole sinus area (R), the compression of the renal segmental vessels or collection system by the tumor (O), the anteroposterior relation of the tumor relative to the segmental vessels or collection system (A), the tumor diameter (D), and whether the tumor affects a solitary kidney (S) ("ROADS"). The ROADS score, indicating low, moderate, or high surgical complexity, was then used to guide surgical strategy planning, including cooling techniques, surgical approaches, and parenchyma incision techniques. A cohort of 134 patients with renal sinus tumors was treated based on their ROADS score and was retrospectively analyzed. RESULTS: The authors successfully performed 113 nephron-sparing surgeries and 21 radical nephrectomies with a complication rate of 7.9%. During follow-up, 3 cases were classified according to surgical margin status because they lacked an intact tumor capsule. There was only 1 case of local recurrence, and there were no cases of metastasis. A high ROADS score was correlated with greater operative complexity, such as longer operation and ischemia times and higher estimated blood loss and complication rates. However, renal function and short-term oncologic outcomes were not related to the score. CONCLUSIONS: The ROADS scoring system provides a standardized, quantitative, 3-dimensional anatomic classification to guide surgical strategy in renal sinus tumors.

Robot-assisted Cavectomy Versus Thrombectomy for Level II Inferior Vena Cava Thrombus: Decision-making Scheme and Multi-institutional Analysis.

BACKGROUND: Robot-assisted thrombectomy (RAT) for inferior vena cava (IVC) thrombus (RAT-IVCT) is being increasingly reported. However, the techniques and indications for robot-assisted cavectomy (RAC) for IVC thrombus are not well described. OBJECTIVE: To develop a decision-making program and analyze multi-institutional outcomes of RAC-IVCT versus RAT-IVCT. DESIGN, SETTING, AND PARTICIPANTS: Ninety patients with renal cell carcinoma (RCC) with level II IVCT were included from eight Chinese urological centers, and underwent RAC-IVCT (30 patients) or RAT-IVCT (60 patients) from June 2013 to January 2019. SURGICAL PROCEDURE: The surgical strategy was based on IVCT imaging characteristics. RAT-IVCT was performed with standardized cavotomy, thrombectomy, and IVC reconstruction. RAC-IVCT was mainly performed in patients with extensive IVC wall invasion when the collateral blood vessels were well-established. For right-sided RCC, the IVC from the infrarenal vein to the infrahepatic veins was stapled. For left-sided RCC, the IVC from the suprarenal vein to the infrahepatic veins was removed and caudal IVC reconstruction was performed to ensure the right renal vein returned through the IVC collaterals. MEASUREMENTS: Clinicopathological, operative, and survival outcomes were collected and analyzed. RESULTS AND LIMITATIONS: All procedures were successfully performed without open conversion. The median operation time (268 vs 190 min) and estimated blood loss (1500 vs 400 ml) were significantly greater for RAC-IVCT versus RAT-IVCT (both p < 0.001). IVC invasion was a risk factor for progression-free and overall survival at midterm follow-up. Large-volume and long-term follow-up studies are needed. CONCLUSIONS: RAC-IVCT or RAT-IVCT represents an alternative minimally invasive approach for selected RCC patients with level II IVCT. Selection of RAC-IVCT or RAT-IVCT is mainly based on preoperative IVCT imaging characteristics, including the presence of IVC wall invasion, the affected kidney, and establishment of the collateral circulation. PATIENT SUMMARY: In this study we found that robotic surgeries for level II inferior vena cava thrombus were feasible and safe. Preoperative imaging played an important role in establishing an appropriate surgical plan.

Initial Series of Robotic Segmental Inferior Vena Cava Resection in Left Renal Cell Carcinoma With Caval Tumor Thrombus.

OBJECTIVE: To present our preliminary experience of robotic left radical nephrectomy (LRN) and segmental inferior vena cava (IVC) resection without caval replacement for left renal cell carcinoma (RCC) with inferior vena cava tumor thrombus. MATERIALS AND METHODS: Between 2017 and 2018, 7 patients underwent segmental IVC resection and LRN robotically. All patients underwent preoperative cavography, demonstrating complete IVC occlusion. Computed tomography-based 3-dimensional reconstruction revealed sufficient collateralization of the IVC and right renal vein (RRV). The cephalic IVC was circumferentially resected and ligated just below the second porta hepatis. The caudal IVC was circumferentially resected above the RRV with preservation of the major collaterals. The RRV was not dissected during the procedure to avoid compromising its neocollaterals. The IVC portion between the RRV and the second porta hepatis was removed en bloc with the tumor thrombus, and the LRN was performed. RESULTS: All cases were successfully performed by robotic surgery without conversion. Median operative time was 420 minutes. Median intensive care unit stay was 3 days. Four grade Ⅱ complications occurred in 2 patients. One patient had mild LEE postoperatively and recovered without special medication. Median preoperative and 3-6 months follow-up serum creatinine was 118.7 µmol/L and 135.2 µmol/L, respectively. No patient needed dialysis postoperatively. One case occurred disease progression. No patient died during the follow-up period. CONCLUSION: Robotic segmental IVC resection for left RCC with inferior vena cava tumor thrombus is feasible in well-selected cases. Three-dimensional reconstruction and cavography are helpful in the preoperative evaluation of neocollaterals in patients with suprarenal IVC occlusion.

Comparison of Angio-CT and cone-beam CT-guided immediate radiofrequency ablation after transcatheter arterial chemoembolization for large hepatocellular carcinoma.

PURPOSE: To evaluate the rapeutic effectiveness of Angio-CT or cone-beam CT (CBCT)-guided immediate radiofrequency ablation (RFA) after transcatheter arterial chemoembolization (TACE) for large hepatocellular carcinoma (HCC). METHODS: 117 large HCC patients (mean maximum diameter: 9.3 cm; range 5.3-17.7 cm) were retrospective studied and divided into Angio-CT group (n = 66 cases), CBCT group (n = 21 cases), and single TACE group (n = 30 cases) according to treatment (Angio-CT/CBCT-guided immediate RFA after TACE, single TACE, respectively). The operative time, effective radiation dose, local-regional tumor responses, overall survival (OS), and progression­free survival (PFS) time and complications were recorded. RESULTS: The operative time and effective radiation dose of Angio-CT group and CBCT group were higher than those of TACE group (P < 0.01). The local-regional tumor responses on 1-month follow-up MRI (complete response + partial response) of Angio-CT group and CBCT group were 100%, which were significantly higher than that of single TACE group (76.7%, P < 0.05). There was no significant difference in local-regional tumor responses of 1-month follow-up between Angio-CT group and CBCT group (P = 0.831). The median PFS and OS time of Angio-CT group were 14.7 ± 1.43 months and 18.21 ± 0.88 months, CBCT group were 13.9 ± 1.53 months and 17.87 ± 1.78 months, TACE group were 10.4 ± 1.21 months and 12.87 ± 0.91 months, respectively. No procedure-related major complications occurred. CONCLUSIONS: MIYABI Angio-CT or CBCT-guided immediate RFA after TACE for large HCC both have more effective than single TACE. The former is worth popularizing, due to its advantages of convenience, shorter operative time, and less radiation dose for doctors.

Robot-assisted Level III-IV Inferior Vena Cava Thrombectomy: Initial Series with Step-by-step Procedures and 1-yr Outcomes.

BACKGROUND: Level III-IV robot-assisted inferior vena cava (IVC) thrombectomy (RA-IVCT) has been reported in limited series. OBJECTIVE: To report our initial series of level III-IV RA-IVCT with step-by-step procedures and 1-yr outcomes. DESIGN, SETTING, AND PARTICIPANTS: From November 2014 to January 2018, 13 patients with level III-IV IVC tumor thrombi underwent RA-IVCT with a minimum of 1-yr follow-up. SURGICAL PROCEDURE: Level III RA-IVCT requires liver mobilization and clamping of first porta hepatis (FPH), and suprahepatic and infradiaphragmatic IVC. Level IV RA-IVCT requires establishment of cardiopulmonary bypass (CPB). Thoracoscopy-assisted thrombectomy was performed for the intra-atrium part of the thrombus under CPB. Infradiaphragmatic RA-IVCT was completed in a manner similar to that of level III RA-IVCT. MEASUREMENTS: Detailed techniques were described for various scenarios. Baseline and perioperative outcomes were reported, and descriptive statistical analysis was performed. RESULTS AND LIMITATIONS: Median operative time was 465 (interquartile range [IQR]: 338-567) min. Median estimated intraoperative blood loss was 2000 (IQR: 1000-3000) ml. The rates of intraoperative blood transfusion and postoperative transformation to the intensive care unit ward were 92.3% and 100%, respectively. Median FPH blocking time was 40 (IQR: 25-60) min and the CPB time was 72 (IQR: 51-87) min. Three cases had grade IV complications, including two vascular injuries that were treated with intraoperative endoscopic sutures and one perioperative death. The perioperative mortality rate was 7.7%. During an 18-mo follow-up, two patients died and one patient progressed. CONCLUSIONS: Although the risks involved are high, level III-IV RA-IVCT is feasible and serves as an alternative minimally invasive method for selected patients. It also requires more complex techniques and multidisciplinary cooperation. PATIENT SUMMARY: We studied the treatment of patients with level III-IV inferior vena cava (IVC) tumor thrombi using a robotic approach. This technique was feasible for well-selected patients. However, level III-IV robot-assisted IVC thrombectomy requires more complex techniques and multidisciplinary cooperation.

Local application of doxorubicin- loaded Iron oxid nanoparticles and the vascular disrupting agent via the hepatic artery: chemoembolization-photothermal ablation treatment of hepatocellular carcinoma in rats.

OBJECTIVES: This study investigates the effectiveness of local application of doxorubicin(Dox)-loaded, polydopamine (PDA)- coated single crystal hematite (α- Fe2O3) nanocubes (Fe2O3-PDA-Dox) and combretastatin A-4 phosphate disodium(CA4P)in treating hepatocellular carcinoma (HCC) in rats. METHODS: The magnetic characteristics and photothermal effects of the nanoparticles were determined in vitro. Tumor-bearing Sprague-Dawley rats were divided into 3 groups of 8 according to treatment: controls, transarterial chemoembolization-photothermal ablation (pTACE) (Lipidol+Fe2O3-PDA-Dox + NIR), and CA4P + pTACE (CA4P+ Lipidol+Fe2O3-PDA-Dox + NIR). Drugs were administered through the hepatic artery, and the tumors exposed to 808-nm near-infrared radiation. The Fe content of tumors was assessed using neutron activation analysis. Treatment effectiveness was assessed using heating curves, magnetic resonance imaging, pathology results, and immunohistochemical analysis. RESULTS: The mean tumor Fe content was greater in rats treated with CA4P + pTACE (1 h, 23.72 ± 12.45 µg/g; 24 h, 14.61 ± 8.23 µg/g) than in those treated with pTACE alone (1 h, 5.66 ± 4.29 µg/g; 24 h, 2.76 ± 1.33 µg/g). The tumor T2 imaging signal was lower in rats treated with CA4P + pTACE. Following laser irradiation, the tumor temperature increased, with higher temperatures reached in the CA4P + pTACE group (62 °C vs 55 °C). Tumor cells exhibited necrosis, apoptosis, and proliferation inhibition, with greater effects in the CA4P + pTACE group. Transient liver and kidney toxicity were observed on day 3, with more severe effects after CA4P + pTACE. CONCLUSIONS: Fe2O3-PDA-Dox nanoparticles are effective for TACE-PTA. Pretreatment with CA4P increases nanoparticle uptake by tumors, increasing the treatment effectiveness without increasing hepatorenal toxicity.