Hepatic Transcatheter Arterial Chemoembolization Research Articles

Clinical application of gelatin sponge microparticles combined with pirarubicin for hepatic transcatheter arterial chemoembolization in breast cancer liver metastasis treatment: results of a single-center long-term study

ObjectiveTo retrospectively analyze the safety and long-term clinical efficacy of gelatin sponge microparticles combined with the chemotherapy drug pirarubicin for hepatic transcatheter arterial chemoembolization (GSMs-TACE) in order to treat breast cancer liver metastasis (BCLM).MethodsTwenty-seven BCLM patients who underwent GSMs-TACE from July 2010 to July 2016 were enrolled. Tumor target blood vessels were slowly and regionally embolized with absorbable gelatin sponge particles and pirarubicin injections. Plain computed tomography (CT) scans and biochemical indexes were re-examined at 4 days after treatment, and enhanced CT scans or magnetic resonance images and biochemical indexes, 1 month later. For patients with stable tumors, the follow-up period was 2 to 3 months, and the tumor response was evaluated using Modified Response Evaluation Criteria in Solid Tumors. Adverse reactions, survival time, and prognostic factors were assessed.ResultsBy October 2019, 27 patients with BCLM had undergone GSMs-TACE, with an average of 2.44 ± 1.58 treatments. The 1-, 3-, and 5-year survival rates were 62.96%, 22.22%, and 14.81%, respectively, and the mOS was 22.0 months. No serious complications, such as acute liver failure and liver abscess, had occurred. There were two cases of acute cholecystitis that recovered after symptomatic treatment. Multivariate analysis of the prognosis showed that the primary tumor size, number of metastatic lymph nodes, estrogen receptor/progesterone receptor (ER/PR) status, and time to postoperative liver metastasis and combination therapy were statistically significant.ConclusionsThe overall prognosis of BCLM was poor. GSMs-TACE was safe and effective for BCLM treatment and could prolong the median survival time of patients. Therefore, it is worthy of widespread clinical application.

Arterial Infusion of Rapamycin in the Treatment of Rabbit Hepatocellular Carcinoma to Improve the Effect of TACE.

BackgroundHepatocellular carcinoma is one of the leading causes of cancer-related death. Hepatic transcatheter arterial chemo-embolization (TACE) is commonly used clinically for advanced hepatocellular carcinoma treatment.AIMThe aim of this study was to evaluate whether arterial infusion of rapamycin can improve the effect of TACE in treatment of rabbit hepatocellular carcinoma.Material and MethodsEighteen healthy New Zealand white rabbits weighing 2.6 ± 0.3 kg were used in a standardised hepatocellular carcinoma model and randomly divided into three groups of 6 rabbits. Group A: the rabbits were treated with rapamycin and TACE by administering arterial perfusion of 2 mg/kg rapamycin + 1 mg/kg epirubicin, 0.2 mg/kg mitomycin, and lipiodol emulsion embolization. Group B: rapamycin was reduced to 1 mg/kg. And for Group C, the rabbits received only TACE treatment. 14 days post operation, CT scan and digital subtraction angiography (DSA) was performed to examine TACE efficacy. The rabbits were killed by air embolism and the expression of HIF-1a, VEGF, iNOS, and CD34 were measured in an immunohistochemical assay of thetumor tissue.ResultsHIF-1a, VEGF and iNOS protein expression in Group A was significantly lower than that of Group B and Group C (P<0.05). The tumor MVD in group C was significantly higher than that of group A and group B (P<0.05); and the tumor MVD of group B was significantly higher than group A (P<0.05).ConclusionArterial infusion of rapamycin combined with TACE can improve treatment efficacy by decreasing HIF-1a, VEGF, iNOS and CD34 expression.

Zoledronic acid inhibits infiltration of tumor-associated macrophages and angiogenesis following transcatheter arterial chemoembolization in rat hepatocellular carcinoma models.

Hepatic transcatheter arterial chemoembolization (TACE), a minimally invasive procedure to block the blood supply of tumors and release of cytotoxic agents, is preferentially applied to patients with hepatocellular carcinoma (HCC) who are not able to receive radical treatments. However, the long-term effects of TACE are unsatisfactory, as the microenvironment following procedure stimulates tumor angiogenesis, which promotes recurrence and metastasis of residual tumors. Tumor associated macrophages (TAMs) have been revealed to stimulate tumor growth and angiogenesis associated with poor prognosis in HCC. The present study focused on the changes in TAMs following TACE, and explored the effects of TACE in combination with the TAM inhibitor zoledronic acid (ZA) in rat HCC models. Orthotropic HCC rats were divided into three groups: Sham TACE, TACE alone and TACE combined with ZA treatment. At 7 or 14 days following TACE, tumor growth was evaluated by magnetic resonance imaging (MRI). Infiltration of TAMs was assessed by histological analysis and flow cytometry. Tumor angiogenesis was measured as the mean vessel density, and initial slope was calculated from dynamic contrast enhancement MRI. Local and systemic levels of vascular endothelial growth factor (VEGF) were determined by western blotting or an ELISA, respectively. The results revealed that TACE inhibited tumor growth at 7 days following the procedure, but this inhibition was attenuated at 14 days following the procedure compared with the sham TACE control. If combined with ZA treatment, TACE exhibited a stable inhibition effect on tumor growth until the end of observation. Investigation of the underlying mechanisms demonstrated that TACE combined with ZA treatment inhibited infiltration of F4/80 positive TAMs and tumor angiogenesis compared with the TACE alone group at 14 days following the procedure. Additionally, the combination treatment significantly inhibited secretion of VEGF in the present models. In conclusion, ZA treatment enhanced the effects of TACE through inhibiting TAM infiltration and tumor angiogenesis in rat HCC models.

Association of hepatic vein Lipiodol tram-track sign during transcatheter arterial chemoembolization with perioperative death.

ObjectiveTo assess the relationship between the hepatic vein Lipiodol tram-track sign during transcatheter arterial chemoembolization (TACE) and perioperative death.MethodsPatients treated for hepatic carcinoma at the Beijing Shijitan Hospital, Capital Medical University from January 2010 to December 2015 were retrospectively evaluated. The patients underwent hepatic TACE with Lipiodol. The incidence of the hepatic vein Lipiodol tram-track sign, prognosis, and possible risk factors were analyzed.ResultsA total of 5372 patients underwent hepatic TACE and had complete available intraoperative imaging data. Among them, nine patients showed the hepatic vein Lipiodol tram-track sign, including five who died intraoperatively. The patients who died had liver metastasis from hepatocellular carcinoma, cholangiocarcinoma, or breast cancer and had previously received doxorubicin. The survivors had metastasis from gastric or colorectal cancer and had not received doxorubicin.ConclusionOccurrence of the hepatic vein Lipiodol tram-track sign during hepatic TACE is likely to result in perioperative death.

Hepatic Transcatheter Arterial Chemoembolization Complicated by Postembolization Syndrome

Postembolization syndrome (PES) is a common complication after embolic procedures, and it is a frequent cause of extended inpatient hospital admissions. PES is a self-limited constellation of symptoms consisting of fevers, unremitting nausea, general malaise, loss of appetite, and variable abdominal pain following the procedure. Although a definite cause is unknown, this syndrome is thought to be a result of therapeutic cytotoxicity, tumor ischemia, and resulting intrahepatic and extrahepatic inflammation. The authors report a case of PES precipitated by transcatheter intrarterial chemoembolization of hepatic metastases.

Lipiodol brain embolism during hepatic transcatheter arterial chemoembolization

Sir, Transcatheter arterial chemoembolization (TACE) for advanced hepatocellular carcinoma, i.e., the injection of a mixture of iodized oil (lipiodol) and a chemotherapeutic via the tumor feeding artery, hitherto has been complicated by lipiodol brain embolism (LBE) in a few cases [1–5]. Only two of these patients had repeat MRI that documented extensive reversion of the initial DWI abnormalities [5]. We present a case of TACE-associated LBE that demonstrated near-complete resolution of DWI lesions suggesting cytotoxic edema. During his fourth course of TACE, a 71-year-old man with advanced hepatocellular carcinoma presented a modest monoparesis of the right arm along with transient dysarthria and dizziness. CT scan immediately after the procedure showed multiple infraand supratentorial brain lesions consistent with the deposition of iodized oil. Three hours later, MRI disclosed multiple nonenhancing cortical and subcortical hyperintense lesions, which represented areas of decreased diffusion on DWI. In particular, the magnitude of ADC decrease in the lesioned areas ranged roughly between 15 and 25% compared to contralateral normal-appearing brain tissue. The patient recovered completely over the following 48 h. A repeat MRI after 1 month documented near-complete resolution of the lesions (Fig. 1). Hyperintense DWI lesions that exhibit low ADC values are typically suggestive of cytotoxic edema in a setting of acute brain ischemia. Although ischemia-associated DWI hyperintensities can be reversible to a certain extent, it is remarkable that in a setting of both cerebral fat [6, 7] and LBE post-TACE [5], widespread areas of presumed cytotoxic edema have been reported not to evolve to complete infarction (established T2 or FLAIR lesions). To the best of our knowledge, such an extensive reversal of DWI abnormalities has not been reported in acute ischemic stroke. A possible explanation would be that what looks like cytotoxic edema in DWI is actually an overestimation of the true extent of the lesion or a cytotoxic edema ‘‘mimic.’’ A MRI spectroscopy study [6] has suggested that soon after fat embolism, areas of restricted diffusion may simply reflect the presence of large quantities of ‘‘sluggish’’ lipids compared to water. However, secondary ischemia [6] or a neurotoxic effect of free fatty acids [7] may occur later if the embolic material is not rapidly cleared from the brain circulation. This would also explain the ‘‘preference’’ of the lipid emboli and of the associated permanent lesions for the watershed areas of the brain where a slow blood flow cannot be compensated quickly and adequately by collaterals. In our patient, fast clearance of the lipid burden may account for the rapid clinical recovery and the reversion of DWI abnormalities. Concerning the etiology of brain embolism in patients undergoing TACE, right-to-left shunt (either via a patent foramen ovale or intrapulmonary arteriovenous shunts), shunt from the inferior phrenic artery to the pulmonary vasculature, and an increased dose of infused lipiodol are commonly advocated [1–4]. However, the passage of oil T. Karapanayiotides (&) G. Georgiadis Department of Neurology, Hippokrateion Hospital, 50, Aigaiou Str., 551 33 Thessaloniki, Greece e-mail: theonen@ath.forthnet.gr; tkarapanayiotides@yahoo.gr

Pulmonary embolism after transcatheter arterial chemoembolization

Metastatic hepatic tumours can be treated with hepatic transcatheter arterial chemoembolization (TACE). Common complications associated with TACE include hepatic insufficiency, fever, and pain. However, pulmonary embolism is rarely documented as a fatal adverse effect. We report a case of pulmonary embolism following TACE in a renal cell carcinoma patient with liver metastases. Total recovery is noted after the effective treatment.

A New Chemoembolization Protocol in Refractory Liver Metastasis of Colorectal Cancer – a Feasibility Study

Introduction: In patients with advanced colorectal cancer (CRC) refractory to systemic chemotherapy including 5-fluorouracil (5-FU) / folinic acid (FA), oxaliplatin and irinotecan we assessed the feasibility, toxicity and response to hepatic transcatheter arterial chemoembolization (TACE). At the time of treatment, patients had exclusively or dominantly liver metastasis of CRC. Patients and Methods: The following protocol was applied via a selective transfemoral hepatic arterial approach: mitomycin C 5 mg/m², interferon-α2b 4.5 Mio IU, dexamethasone 20 mg mixed with Amilomer DSM 45/25 (Spherex^®) days 1 and 2 i.a. (bolus), oxaliplatin 50 mg/m² (2 h) day 1 i.a., FA 500 mg/m² (2 h) day 1 i.v., and 5-FU 1.500 mg/m² (24 h) day 1 i.a. Cycles have been repeated at days 15–22. The dose was adjusted according to the pretreatment performance status and elevation of alkaline phosphatase, bilirubin and serum albumin. Treatment was continued until progression or emergence of intolerable toxicity. Results: 11 patients received a total number of 43 TACE, with a range of 2–6 per patient. There was no TACE-related mortality. 4 patients died 5, 8, 10 and 11 months after initiation of treatment due to progression of disease. 7 patients are alive at 4+ (n = 2), 5+ (n = 1), 6+ (n = 1), 7+ (n = 1) and 11+ (n = 2) months after start of treatment. Toxicity (CTC) was mild with grade I–II asthenia (n = 10), grade I–II neurotoxicity (n = 5), grade II nausea and/or vomiting (n = 2) and grade II diarrhea (n = 1). Treatment had to be postponed due to grade I thrombocytopenia in 2 patients. No bleeding episodes or obvious infectious complications occurred during treatment intervals. 1 patient experienced an allergic reaction to oxaliplatin which led to exclusion from further therapy. Arterial catheter dislocation occurred in 3 patients. In 10 patients evaluable for response we observed 3 partial responses, 2 minor responses, and 4 times stable disease. Only 1 patient had further progression of disease under treatment. Conclusion: TACE, using a combination of mitomycin C, dexamethasone and interferon-α2b mixed with Spherex^®, followed by oxaliplatin, FA and 5-FU, appears to be an effective and feasible treatment option in the case of liver metastasis of CRC refractory to standard systemic chemotherapy. This treatment is associated with tolerable toxicity, which becomes apparent mainly as asthenia, neurotoxicity or thrombocytopenia. These preliminary data warrant further evaluation for patients with refractory disease and would probably also be of interest for first-line treatment in this patient population.