Hepatic Artery Infusion Chemotherapy for Primary and Secondary Malignancies of the Liver: State of the Art and Current High-Level Evidence.

BACKGROUND: Hepatic artery infusion chemotherapy (HAI) has been proposed as a valuable adjunct for multimodal therapy of primary and secondary liver malignancies. This review provides an overview of the currently available evidence of HAI, taking into account tumor response and long-term oncologic outcome. SUMMARY: In colorectal liver metastases (CRLM), HAI in combination with systemic therapy leads to high response rates (85-90%) and conversion to resectablity in primary unresectable disease in up to 50%. HAI in combination with systemic therapy in CRLM in the adjuvant setting shows promising long-term outcomes with up to 50% 10-year survival in a large, non-randomized single-center cohort. For hepatocellular carcinoma patients, response rates as high as 20-40% have been reported for HAI and long-term outcomes compare well to other therapies. Similarly, survival for patients with unresectable intrahepatic cholangiocarcinoma 3 years after treatment with HAI is reported as high as 34%, which compares well to trials of systemic therapy where 3-year survival is usually below 5%. However, evidence is mainly limited by highly selected, heterogenous patient groups, and outdated chemotherapy regimens. The largest body of evidence stems from small, often non-randomized cohorts, predominantly from highly specialized single centers. KEY MESSAGE: In well-selected patients with primary and secondary liver malignancies, HAI might improve response rates and, possibly, long-term survival. Results of ongoing randomized trials will show whether a wider adoption of HAI is justified, particularly to increase rates of resectability in advanced malignant diseases confined to the liver.

Efficacy of various adjuvant chemotherapy methods in preventing liver metastasis from potentially curative colorectal cancer: A systematic review network meta-analysis of randomized clinical trials.

PURPOSE: Various chemotherapy administration methods have been used to prevent liver metastasis (LM) in patients with colorectal cancer (CRC). This network meta-analysis evaluated the efficacy of these different methods in preventing LM in CRC patients who underwent curative surgery. METHOD: A systematic search of randomized controlled trials reporting the efficacy of various adjuvant chemotherapy methods in patients with colorectal cancer who underwent curative surgery was conducted. The primary outcome was the LM rate. RESULTS: This network meta-analysis included 19 studies reporting on 12,588 participants, comparing portal vein infusion chemotherapy (PVIC) versus hepatic arterial infusion chemotherapy (HAIC) versus systematic chemotherapy (SC) versus surgery alone. The HAIC group had the lowest LM rate when compared to the other three groups (odds ratio [OR] of PVIC vs. HAIC: 1.86; OR of SC vs. HAIC: 1.98; and HAIC vs. surgery alone: 0.43). The LM rate did not differ significantly between PVIC, SC, and surgery alone. The recurrence rates were lower for PVIC and HAIC than for surgery alone (the ORs for PVIC and HAIC were 0.73 [95% CI: 0.58-0.92] and 0.45 [95% CI: 0.26-0.77]). The mortality rates of patients undergoing PVIC and HAIC were lower than that of patients undergoing surgery alone (the ORs for PVIC and HAIC were 0.77 [95% CI: 0.64-0.93] and 0.49 [95% CI: 0.24-0.98]). Anastomotic leakage, cardiopulmonary leakage, diarrhea, nausea and vomiting, oral ulceration, wound infection, or ileus did not differ significantly between the four groups. PVIC showed the highest hepatic toxicity rate compared to those for SC, HAIC, and surgery alone. CONCLUSION: HAIC might be a satisfactory method for preventing LM in patients with CRC undergoing curative surgery.

Renal and hepatic artery embolization with Pickering gel emulsion of lipiodol in rabbit.

OBJECTIVE: This research aimed to evaluate the feasibility of a novel liquid embolic agent Pickering gel emulsion of lipiodol (PGEL) for renal and hepatic artery embolization in the rabbit experimental model. METHODS: Embolization was performed in the right renal artery of 24 adult New Zealand White rabbits and 24 VX2 tumors in the left liver lobe. The rabbits were randomly allocated to four treatment groups (n = 6 per group): (A) normal saline (NS), (B) lipiodol, (C) 180-300 µm polyvinyl alcohol (PVA), and (D) PGEL. RESULTS: Renal artery embolization in normal rabbits and transarterial embolization (TAE) in VX2 tumor-bearing rabbits indicated that PGEL achieved a better embolization effect for a longer time than lipiodol and PVA. The tumor growth ratio of the PGEL group was significantly lower than that of the NS, lipiodol, and PVA groups at 3 (P < 0.001) and 7 (P < 0.001) days after embolization. In addition, hematoxylin and eosin and immunohistochemical staining revealed that the tumor necrosis ratio was higher in the PGEL group than in the NS, lipiodol, and PVA groups (P < 0.01), and the expression levels of HIF-1α, VEGF, and CD31 decreased after PGEL embolization compared with the lipiodol and PVA treatments. CONCLUSION: PGEL is an effective embolic material that provides immediate and total occlusion of the renal artery and may be a potential therapeutic embolic agent for TAE of HCC.

Hepatic arterial infusion pump chemotherapy combined with systemic therapy for patients with advanced colorectal liver metastases: Outcomes in a newly established program.

BACKGROUND AND OBJECTIVES: Colorectal liver metastasis (CRLM) is a leading cause of morbidity and mortality in patients with colorectal cancer. Hepatic arterial infusion (HAI) chemotherapy has been demonstrated to improve survival in patients with resected CRLM and to facilitate conversion of technically unresectable disease. METHODS: Between 2016 and 2018, n = 22 HAI pumps were placed for CRLM. All patients received systemic chemotherapy concurrently with HAI floxuridine/dexamethasone. Overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan-Meier method. RESULTS: HAI pumps were placed in seven patients with completely resected CRLM and 15 patients with unresectable disease. Twenty-one patients received HAI floxuridine with a median of 5 total HAI cycles (interquartile range: 4-7). Biliary sclerosis was the most common HAI-related complication (n = 5, 24%). Of the 13 patients treated to convert unresectable CRLM, 3 (23%) underwent hepatic resection with curative intent after a median of 7 HAI cycles (range: 4-10). For all HAI patients, the mean OS was 26.7 months from CRLM diagnosis, while the median PFS and hepatic PFS from pump placement were 9 and 13 months, respectively. CONCLUSION: Concomitant HAI and systemic therapy can be utilized at multidisciplinary programs for patients with advanced CRLM, both in the adjuvant setting and to facilitate conversion of unresectable disease.

Efficacy of Lipid Nanoparticle-Loaded Sorafenib Combined with Hepatic Artery Chemoembolization in the Treatment of Primary Hepatocellular Carcinoma Complicated with Microvascular Invasion.

This work was to evaluate the therapeutic effect of lipid nanoparticle-loaded sorafenib combined with transcatheter artery chemoembolization (TACE) in patients with primary hepatocellular carcinoma (HC) complicated with microvascular invasion (MVI). In this work, 102 patients with primary HC combined with MVI after radical resection were divided into 4 groups according to different treatment methods. Experimental group 1 was treated with lipid nanoparticle-loaded sorafenib combined with TACE treatment group; experimental group 2 was treated with lipid nanoparticle-loaded sorafenib treatment group; experimental group 3 was TACE treatment group; control group was postoperative routine nursing group. Sorafenib lipid nanoparticles were prepared. The basic information, operation, MVI degree, tumor recurrence, and survival time of patients in each group were recorded and compared to evaluate the therapeutic effect of combined way. No great difference was found in MVI grade, average age, sex ratio, preoperative tumor markers, tumor size, number of patients with liver cirrhosis, operation time, and intraoperative bleeding among the four groups (P > 0.05). In addition, the tumor free survival time (TFST), overall survival time (OST), and postoperative 1-year and 2-year survival rates of patients in test group 1 were greatly higher than those in single mode treatment group and control group (P < 0.05). In summary, sorafenib nanoparticles combined with TACE can improve the survival status of patients after resection and delay the time of postoperative tumor recurrence.

[Prehepatectomy Chemotherapy Using Circadian Chrono-HAI for Liver Metastases from Colorectal Cancer].

We investigated the safety and efficacy of circadian chronotherapy via the hepatic artery(chrono-HAI)as a prehepatectomy chemotherapy for initially unresectable colorectal liver metastases. Five-day course of chrono-HAI using 5-FU, l-LV, and L-OHP plus systemic panitumumab with 9-day interval were administered to 24 patients with failure for previous chemotherapy. Response rate and Grade 3 adverse effect(AE) were 63% and 54%, respectively. Among 22 patients( excluding 2 CR patients), conversion surgery could be performed in 10(45%). Two-year overall survival of patients with surgery (58%)was longer in those without(20%, p=0.057). Although incidence of AE was a bit high, chrono-HAI plus systemic panitumumab is an effective prehepatectomy chemotherapy for patients with aggressive colorectal liver metastases.

Hepatic Artery Injection of 131I-Metuximab Combined with Transcatheter Arterial Chemoembolization for Unresectable Hepatocellular Carcinoma: A Prospective Nonrandomized, Multicenter Clinical Trial.

This prospective nonrandomized, multicenter clinical trial was performed to investigate the efficacy and safety of 131I-labeled metuximab in adjuvant treatment of unresectable hepatocellular carcinoma. Methods: Patients were assigned to treatment with transcatheter arterial chemoembolization (TACE) combined with 131I-metuximab or TACE alone. The primary outcome was overall tumor recurrence. The secondary outcomes were safety and overall survival. Results: The median time to tumor recurrence was 6 mo in the TACE + 131I-metuximab group (n = 160) and 3 mo in the TACE group (n = 160) (hazard ratio, 0.55; 95% CI, 0.43-0.70; P < 0.001). The median overall survival was 28 mo in the TACE + 131I-metuximab group and 19 mo in the TACE group (hazard ratio, 0.62; 95% CI, 0.47-0.82; P = 0.001). Conclusion: TACE + 131I-metuximab showed a greater antirecurrence benefit, significantly improved the 5-y survival of patients with advanced hepatocellular carcinoma, and was well tolerated by patients.

Clinical efficacy of targeted therapy, immunotherapy combined with hepatic artery infusion chemotherapy (FOLFOX), and lipiodol embolization in the treatment of unresectable hepatocarcinoma.

To evaluate the clinical efficacy of targeted therapy and immunotherapy combined with hepatic arterial infusion chemotherapy (HAIC) of FOLFOX and lipiodol embolization in the treatment of unresectable hepatocellular carcinoma. Patients included in the study were those who received targeted therapy and immunotherapy combined with HAIC of FOLFOX and lipiodol embolization in Zhongshan People's Hospital from December 2020 to June 2021 for unresectable hepatocellular carcinoma. Evaluation indicators included objective response rate (ORR), median progression-free survival (mPFS), median duration of response (mDOR), 1-year overall survival rate (OS), surgical conversion rate, and adverse events. Treatment response was assessed using Response Evaluation Criteria in Solid Tumors (mRECIST and RECIST v1.1). A total of 35 patients were included in this study, 30 of whom completed treatment evaluation. According to mRECIST evaluation criteria, the objective response rate (ORR) was 83.3% (25/30); the complete response (CR) was 60% (18/30); the partial response (PR) was 23.3% (7/30), and stable disease (SD) was 16.7% (5/30). The mDOR was 10.3 months (95% Cl: 8.27-NE), and the mPFS was 13.2 months (95% CI: 10.3-NE); the surgical conversion rate was 30.0% (9/30). The 1-year OS was 96.7%. There were no serious surgical complications and grade 4 or 5 adverse events of targeted therapy, immunotherapy and HAIC. Some patients had grade 3 adverse reactions in gastrointestinal toxicity or hepatotoxicity, and the adverse reactions were improved after corresponding symptomatic treatment. We concluded that HAIC of FOLFOX and lipiodol embolization combined with targeted therapy and immunotherapy had a significant curative effect in the treatment of unresectable hepatocellular carcinoma, with no serious adverse reactions and a high rate of surgical conversion rate.

Adjuvant intra-arterial chemotherapy for patients with resected colorectal liver metastases: a systematic review and meta-analysis.

BACKGROUND: The practice of adjuvant hepatic arterial infusion chemotherapy (HAIC) for colorectal liver metastasis (CRLM) varies widely. This meta-analysis investigates the effectiveness of adjuvant HAIC and the influence of variations in HAIC treatment in patients with resected CRLM. METHODS: PRISMA guidelines were followed for this study. The search was limited to comparative studies (HAIC vs non-HAIC) for overall survival. Subgroup meta-analyses using random-effects were performed for type of intra-arterial drug, method of catheter insertion, use of concomitant adjuvant systemic chemotherapy, and study design. RESULTS: Eighteen eligible studies were identified. After excluding overlapping cohorts, fifteen studies were included in the quantitative analysis, corresponding to 3584 patients. HAIC was associated with an improved overall survival (pooled hazard ratio (HR) 0.77; 95%CI 0.64-0.93). Survival benefit of HAIC was most pronounced in studies using floxuridine (HR 0.76; 95%CI: 0.62-0.94), surgical catheter insertion with subcutaneous pump (HR 0.71; 95%CI: 0.61-0.84), and concomitant adjuvant systemic chemotherapy (HR 0.75; 95%CI: 0.59-0.96). The pooled HR of RCTs was 0.91 (95%CI 0.72-1.14), of which only 3 used floxuridine. CONCLUSION: Adjuvant HAIC is a promising treatment for patients with resectable CRLM, in particular HAIC with floxuridine using a surgically placed catheter and a subcutaneous pump, and concomitant systemic chemotherapy.

In vivo evaluation of a monodisperse solid-in-oil-in-water miriplatin/ lipiodol emulsion in transcatheter arterial chemoembolization using a rabbit VX2 tumor model.

Transcatheter arterial chemoembolization (TACE) is a standard treatment for unresectable hepatocellular carcinoma; however, it does not always result in tumor control. Nevertheless, treatment outcome can be improved with monodisperse emulsions of anticancer agents. In this study, the distribution of a monodisperse miriplatin-Lipiodol emulsion in the tumor and its safety were evaluated in ten Japanese white rabbits. VX2 tumor was implanted into the left liver lobe. The animals were divided into control and experimental groups (of five animals each) and respectively administered a conventional miriplatin suspension or the emulsion via the left hepatic artery. Computed tomography (CT) was performed before, immediately after, and two days following TACE. All rabbits were sacrificed two days after the procedure. Each tumor was removed and cut in half for assessment of iodine concentration in one half by mass spectroscopy and evaluation of Lipiodol accumulation and adverse events in the other half. Mean Hounsfield unit (HU) values were measured using plain CT images taken before and after TACE. Iodine concentration was higher in the experimental group [1100 (750-1500) ppm, median (range)] than in the control group [840 (660-1800) ppm], although statistically not significant. Additionally, the HU value for the experimental group was higher than that for the control group immediately after [199.6 (134.0-301.7) vs. 165.3 (131.4-280.5)] and two days after [114.2 (56.1-229.8) vs. 58.3 (42.9-132.5)] TACE, although statistically not significant. Cholecystitis was observed in one rabbit in the control group. Ischemic bile duct injury was not observed in any group. The results show that Lipiodol accumulation and retention in VX2 tumor can possibly be improved with a monodisperse emulsion; however, it should be verified with a larger study. Moreover, no significant adverse events are associated with the use of the emulsion.

Pathological complete response by advanced hepatocellular carcinoma with massive macrovascular invasion to hepatic arterial infusion chemotherapy: a case report.

BACKGROUND: Advanced hepatocellular carcinoma (HCC) with macrovascular invasion has an extremely dismal prognosis. We report a rare case of multiple HCC with tumor thrombosis in the portal vein and inferior vena cava that was initially treated with hepatic arterial infusion chemotherapy (HAIC); later resection revealed pathological complete response. CASE PRESENTATION: A 75-year-old man presented with HCC in his right liver, with tumor thrombosis growing to the right portal vein and the inferior vena cava, and bilateral intrahepatic liver metastases. He underwent HAIC (5-fluorouracil [170 mg/m2] + cisplatin [7 mg/m2]) via an indwelling port. Although the tumor shrank and tumor marker levels decreased rapidly, we abandoned HAIC after one cycle because of cytopenia. We resumed HAIC 18 months later because of tumor progression, using biweekly 5-fluorouracil only [1000 mg] due to renal dysfunction. However, after 54 months, the HAIC indwelling port was occluded. The patient therefore underwent a right hepatectomy to resect the residual lesion. Histopathological findings showed complete necrosis with no viable tumor cells. The patient has been doing well without postoperative adjuvant therapy for more than 10 years after initially introducing HAIC and 6 years after the resection, without evidence of tumor recurrence. CONCLUSIONS: HAIC can be an effective alternative treatment for advanced HCC with macrovascular invasion.

Meropenem-Vaborbactam as Salvage Therapy for Ceftazidime-Avibactam-Resistant Klebsiella pneumoniae Bacteremia and Abscess in a Liver Transplant Recipient.

We report a case of a 24-year-old liver transplant recipient who developed hepatic artery thrombosis and graft failure, which was complicated by subphrenic abscess and persistent Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae bacteremia. Ceftazidime-avibactam treatment led to emergence of resistance, and alternative combination therapy failed due to persistent infection and toxicity. The infection resolved after initiation of meropenem-vaborbactam, which created a bridge to retransplantation. Treatment-emergent ceftazidime-avibactam resistance is increasingly recognized, suggesting a role for meropenem-vaborbactam.

First In Vivo Test of Thermoembolization: Turning Tissue Against Itself Using Transcatheter Chemistry in a Porcine Model.

PURPOSE: Embolotherapies are commonly used for management of primary liver cancer. Explant studies of treated livers, however, reveal an untreated tumor in a high fraction of cases. To improve on this, we propose a new concept referred to as thermoembolization. In this technique, the embolic material reacts in local tissues. Highly localized heat energy is released simultaneously with the generation of acid in the target vascular bed. Combined with ischemia, this should provide a multiplexed attack. We report herein our initial results testing the feasibility of this method in vivo. MATERIALS AND METHODS: Institutional approval was obtained, and three outbred swine were treated in a segmental hepatic artery branch (right or left medial lobe) with thermoembolic material (100, 400, or 500 µL). Solutions (2 or 4 mol/L) of an acid chloride were made using ethiodized oil as the vehicle. Animals were housed overnight, scanned by CT, and euthanized. Necropsy samples of treated tissue were obtained for histologic analysis. RESULTS: All animals survived the procedure. Vascular stasis occurred rapidly in all cases despite the small volumes used. The lower concentration (2 mol/L) penetrated more distally than the 4 mol/L solution. At CT the following day, vascular casts of ethiodized oil were observed, indicating recanalization had not occurred. Histology specimens demonstrated coagulative necrosis centered on the vessel lumen extending for several hundred microns with a peripheral inflammatory infiltrate. CONCLUSIONS: Thermoembolization is a new technique for embolization with initial promise. However, results indicate much work must be done to optimize the technique.

Resection of Locally Advanced Pancreatic Cancer without Regression of Arterial Encasement After Modern-Era Neoadjuvant Therapy.

INTRODUCTION: Modern-era systemic therapy for locally advanced pancreatic adenocarcinoma (LAPC) offers improved survival relative to historical regimens but not necessarily improved radiographic downstaging to allow more patients to undergo resection. The aim of this study was to evaluate the survival, progression, and pathologic outcomes after resection of LAPC that did not regress from > 180 degrees arterial encasement after neoadjuvant therapy. METHODS: Sixty-one LAPC patients were brought to the operating room after neoadjuvant therapy for NCCN-defined unresectable pancreatic cancer between 2012 and 2017. Pts were explored with intent of pancreatectomy and irreversible electroporation for margin extension; 5 (8%) had metastatic lesions on exploratory laparoscopy and were excluded from analyses. Imaging was re-examined to confirm LAPC prior to surgery. Data were analyzed from a prospective pancreatic cancer database. RESULTS: Patients had arterial involvement of the celiac axis (37.5%) and/or superior mesenteric artery (42.9%) and/or an extended length of the common hepatic (n = 44.6%) artery. Twenty-nine males and 27 females, median 65 years of age, received neoadjuvant gemcitabine-based (58.9%) or FOLFIRINOX (35.7%) chemotherapy and stereotactic body (42.9%) or intensity-modulated (51.8%) radiation therapy. Median months from initiation of neoadjuvant therapy to surgery was 7.5. Sixty-one percent underwent Whipple, 21% distal, and 18% modified Appleby procedures; 57% patients underwent venous reconstruction. Ninety-day mortality was 2%. An R0 margin was achieved in 80%, and 53% were N0. Median overall and progression-free survival was 18.5 (95%CI 12.27-32.33) and 8.5 months (95%CI 6.0-15.0), respectively. One- and 3-year survival from surgery was 68.5% (95%CI 53.0-79.7) and 39.0% (95%CI 23.7-53.8), respectively. CONCLUSION: With modern-era neoadjuvant therapy, R0 resections can be achieved in a majority of non-metastatic patients with locally advanced, unresectable disease based on cross-sectional imaging.

Basil polysaccharide attenuates hepatocellular carcinoma metastasis in rat by suppressing H3K9me2 histone methylation under hepatic artery ligation-induced hypoxia.

Hepatocellular carcinoma (HCC) is one of the most common and fatal cancers in the world. Tumor metastasis is an important factor of poor prognosis in patients with HCC. Tumor hypoxia can promote tumor cell metastasis in HCC. Epigenetic modification is closely related to tumor hypoxia and metastasis. In our previous research, we found that basil polysaccharide suppressed migration and invasion of HCC cell by inhibiting hypoxia induced histone methylation in vitro. In the present study, we investigated the effect of basil polysaccharide on the walker 256 carcinoma cell metastasis in rat. We established an intratumoral hypoxic model in rat by hepatic artery ligation (HAL). Then rats were treated with basil polysaccharide (75, 150 and 300mg/kg). The results showed that HAL could promote tumor metastasis by aggravating tumor hypoxia. However, basil polysaccharide could inhibit tumor metastasis in intratumoral hypoxia. Further, we demonstrated that basil polysaccharide could down-regulate the expression of HIF-1α, G9a, LSD1, JMJD1A, JMJD2B, JARID1B and H3K9me2. Synchronously, basil polysaccharide could increase E-cadherin and VMP1 expression, and decrease N-cadherin, vimentin and ß-catenin expression. The results indicated that histone modifying enzymes might be a new therapeutic target of basil polysaccharide on hepatocellular carcinoma metastasis.

Transarterial Embolization for Treatment of Symptomatic Polycystic Liver Disease: More than 2-year Follow-up.

BACKGROUND: Currently, treatment of symptomatic polycystic liver disease (PLD) is still a challenging problem, especially for these patients who are not feasible for surgery. Minimally invasive options such as laparoscopic fenestration and percutaneous cyst aspiration with sclerotherapy demonstrated disappointing results due to multiple lesions. Because the cysts in PLD are mostly supplied from hepatic arteries but not from portal veins, transcatheter arterial embolization (TAE) of the hepatic artery branches that supply the major hepatic cysts can lead to shrinkage of the cyst and liver size, relieve symptoms, and improve nutritional status. This study aimed to evaluate the effectiveness of TAE with a mixture of N-butyl-2-cyanoacrylate (NBCA) and iodized oil for patients with severe symptomatic PLD during a more than 2-year follow-up. METHODS: Institutional review board had approved this study. Written informed consent was obtained from all patients. From February 2007 to December 2014, twenty-three patients (20 women and 3 men; mean age, 49.0 ± 14.5 years) infeasible for surgical treatments underwent TAE. Changes in the abdominal circumferences, volumes of intrahepatic cysts, hepatic parenchyma volume, and whole liver, clinical symptoms, laboratory data, and complications were evaluated after TAE. RESULTS: Technical success was achieved in all cases. No procedure-related major complications occurred. The median follow-up period after TAE was 48.5 months (interquartile range, 30.0-72.0 months). PLD-related severe symptoms were improved remarkably in 86% of the treated patients; TAE failed to benefit in four patients (four patients did not benefit from TAE). The mean maximum abdominal circumference decreased significantly from 106.0 ± 8.0 cm to 87.0 ± 15.0 cm (P = 0.021). The mean intrahepatic cystic volume reduction rates compared with pre-TAE were 36% at 12 months, 37% at 24 months, and 38% at 36 months after TAE (P < 0.05). The mean liver volume reduction rates were 32% at 12 months, 31% at 24 months, and 33% at 36 months (P < 0.05). CONCLUSIONS: TAE with the mixture of NBCA and iodized oil appears to be a safe and effective treatment method for patients with symptomatic PLD, especially for those who are not good candidates for surgical treatments, to improve both hepatic volume and hepatic cysts volume.

Hepatic arterial damage after transarterial chemoembolization for the treatment of hepatocellular carcinoma: comparison of drug-eluting bead and conventional chemoembolization in a retrospective controlled study.

Background Transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) frequently causes feeding artery stenosis or occlusion that may interfere with repeated treatment. Purpose To investigate the incidence and predictors of hepatic arterial damage (HAD) after drug-eluting bead-TACE (DEB-TACE) in comparison with conventional TACE (Conv-TACE). Material and Methods We retrospectively analyzed 54 patients who underwent DEB-TACE for HCC as an initial treatment with follow-up angiography and 54 patients who underwent Conv-TACE using doxorubicin-lipiodol mixture and gelfoam particles for comparison. HAD was evaluated after a single session of TACE and graded as follows: grade I, no significant wall irregularity; grade II, overt stenosis; grade III, occlusion. Results The incidence of HAD was significantly higher in the DEB-TACE group than the Conv-TACE group when analyzed per branch (odds ratio [OR], 6.36; P < 0.001) and per patient (OR, 3.15; P = 0.005). For each HAD grade, the mean doxorubicin dose was greater in the DEB-TACE group than in the Conv-TACE group ( P < 0.001, P = 0.053, and P = 0.01 for grades I, II, and III, respectively). In multivariate analysis, risk factors of HAD included mean doxorubicin dose and selective embolization in the Conv-TACE group ( P = 0.03 and P < 0.001, respectively) and mean doxorubicin dose in the DEB-TACE group ( P = 0.004). Conclusion The incidence and grade of HAD were higher after DEB-TACE compared to Conv-TACE with doxorubicin dose as a possible risk factor. HAD was independent of overall survival in both groups.

Effects of Melatonin, Aluminum Oxide, and Polymethylsiloxane Complex on the Expression of LYVE-1 in the Liver of Mice with Obesity and Type 2 Diabetes Mellitus.

The effects of melatonin, aluminum oxide, and polymethylsiloxane complex on the expression of LYVE-1 (lymphatic vessel endothelial hyaluronan receptor) in the liver were studied in db/db mice with experimental obesity and type 2 diabetes mellitus. The complex or placebo was administered daily by gavage from week 8 to week 16 of life. The animals receiving the complex exhibited enhanced, in comparison with the placebo group, immunohistochemical LYVE-1+ staining of endothelial cells in sinusoids. Enhanced expression of LYVE-1 was associated with less pronounced dilatation of interlobular arteries, veins, and lymphatic vessels. Thee findings suggest a protective effect of the complex towards structural changes in the liver of mice with obesity and type 2 diabetes.