|
1
|
Auer TA, Jonczyk M, Collettini F, Marth A, Wieners G, Hamm B, Gebauer B. Trans-arterial chemoembolization with degradable starch microspheres (DSM-TACE) versus selective internal radiation therapy (SIRT) in multifocal hepatocellular carcinoma. Acta Radiol 2021; 62:313-321. [PMID: 32498543 DOI: 10.1177/0284185120926474] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND To date there is no therapy consensus in patients with multifocal hepatocellular carcinoma (mHCC). PURPOSE To compare outcome of trans-arterial chemoembolization (TACE) with degradable starch microspheres (DSM-TACE) versus selective internal radiation therapy (SIRT) in mHCC. MATERIAL AND METHODS In this single-center study, 36 patients without portal vein invasion, treated between May 2014 and May 2018, were enrolled retrospectively. Eighteen consecutive patients received DSM-TACE and were matched by age, gender, BCLC stage, Child-Pugh status, and tumor volume and 18 patients underwent SIRT. Overall survival (OS), progression-free survival (PFS), and local tumor control (LTC) were evaluated. Toxicity profiles for both therapies were also evaluated and compared. RESULTS In the entire collective, median OS was 9.5, PFS 5.0, and LTC 5.5 months. Subgroup analysis revealed an OS of 9.5 months in both groups (P = 0.621). PFS was 6 months for the SIRT and 4 months for the DSM-TACE cohort (P = 0.065). Although not significantly, LTC was lower (4 months) in the SIRT compared to the DSM-TACE cohort (7 months; P = 0.391). When DSM-TACE was performed ≥3 times (n = 11), OS increased, however without statistical difference compared to SIRT, to 11 months, PFS to 7 months, and LTC to 7 months. When DSM-TACE was performed <3 times (n = 7), OS, PFS, and LTC decreased (5 months, P = 0.333; 2 months, P = 0.047; 2 months, P = 0.47). Toxicity profiles and adverse event analysis only revealed a significant difference for nausea and vomiting (more frequent in the SIRT cohort, P = 0.015), while no other parameter showed a significant difference (P > 0.05). CONCLUSION DSM-TACE might be an alternative to SIRT in multifocal HCC patients as OS, PFS, and LTC did not differ significantly and toxicity profiles seem to be comparable.
Collapse
Affiliation(s)
- Timo A Auer
- Department of Radiology, Charité - University Medicine Berlin, Berlin, Germany
| | - Martin Jonczyk
- Department of Radiology, Charité - University Medicine Berlin, Berlin, Germany
| | - Federico Collettini
- Department of Radiology, Charité - University Medicine Berlin, Berlin, Germany
| | - Adrian Marth
- Department of Radiology, Charité - University Medicine Berlin, Berlin, Germany
| | - Gero Wieners
- Department of Radiology, Charité - University Medicine Berlin, Berlin, Germany
| | - Bernd Hamm
- Department of Radiology, Charité - University Medicine Berlin, Berlin, Germany
| | - Bernhard Gebauer
- Department of Radiology, Charité - University Medicine Berlin, Berlin, Germany
| |
Collapse
|
|
2
|
Transarterial Chemoembolisation (TACE) with Degradable Starch Microspheres (DSM) and Anthracycline in Patients with Locally Extensive Hepatocellular Carcinoma (HCC): Safety and Efficacy. Cardiovasc Intervent Radiol 2019; 43:402-410. [PMID: 31705244 DOI: 10.1007/s00270-019-02364-w] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2019] [Accepted: 10/23/2019] [Indexed: 12/17/2022]
Abstract
PURPOSE To evalutate safety and efficacy of degradable starch microspheres (DSM) as embolic agent in transarterial chemoembolisation (TACE) of unresectable, locally extensive hepatocellular carcinoma (HCC). MATERIALS AND METHODS In this retrospective study, 37 patients with intermediate to advanced HCC treated with ≥ 3 chemoembolisations with doxorubicin/epirubicin and DSM were analysed. Patients were treated with three consecutive chemoembolisations in 4-weekly intervals. Clinical parameters and laboratory findings were obtained from patient records before and after each intervention. Tumour response was assessed after every 3 embolisations by CT/MRI according to modified response evaluation criteria in solid tumours. RESULTS Thirty-seven patients with HCC were treated with 177 DSM-TACEs (3-12/patient, mean 4.8). Disease stages according to the Barcelona Clinic Liver Cancer (BCLC) staging system were: 27 × B, 9 × C, 1 × D. Five patients had uninodular, 32 multinodular (23 bilobar) disease. Three patients had portal vein invasion. Apart from one possibly procedure-related grade 3 complication, only grade 1 adverse events occurred. These were pain reacting to analgesics (23%), transient nausea (11%), vomiting (3%) and post-embolisation syndrome (4%). Transient laboratory changes were bone marrow toxicity (29%) and increase in INR (14%), creatinine (8%) or bilirubin (38%). Tumour response was objective response rate 49%, disease control rate 83%. Median survival was 19 months: 22 months for BCLC stage B and 6.7 months for BCLC stages C + D. Responders had a significantly better prognosis than non-responders. CONCLUSION DSM-TACE of HCC is safe even in patients with advanced disease stages. Tumour response and survival rates were encouraging in our series of patients with locally extensive disease.
Collapse
|
|
3
|
Orlacchio A, Chegai F, Merolla S, Francioso S, Giudice CD, Angelico M, Tisone G, Simonetti G. Downstaging disease in patients with hepatocellular carcinoma outside up-to-seven criteria: Strategies using degradable starch microspheres transcatheter arterial chemo-embolization. World J Hepatol 2015; 7:1694-1700. [PMID: 26140089 PMCID: PMC4483551 DOI: 10.4254/wjh.v7.i12.1694] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2014] [Revised: 01/20/2015] [Accepted: 05/27/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the downstaging rates in hepatitis C virus-patients with hepatocellular carcinoma (HCC), treated with degradable starch microspheres transcatheter arterial chemoembolization (DSM-TACE), to reach new-Milan-criteria (nMC) for transplantation.
METHODS: This study was approved by the Ethics Committee of our institution. From September 2013 to March 2014 eight patients (5 men and 3 women) with liver cirrhosis and multinodular HCC, that did not meet nMC at baseline, were enrolled in this study. Patients who received any other type of treatment such as termal ablation or percutaneous ethanol injection were excluded. DSM-TACE was performed in all patients using EmboCept® S and doxorubicin. Baseline and follow-up computed tomography or magnetic resonance imaging was assessed measuring the longest enhancing axial dimension of each tumor according to the modified Response Evaluation Criteria In Solid Tumors measurements, and medical records were reviewed.
RESULTS: DSM-TACE was successfully performed in all patients without major complication. We treated 35 lesions (mean 4.3 per patient). Six of eight patients (75%) had their HCC downstaged to meet nMC. Every patient whose disease was downstaged eventually underwent transplantation. The six patients who received transplant were still living at the time of this writing, without recurrence of HCC. Baseline age (P = 0.25), Model for End-stage Liver Disease score (P = 0. 77), and α-fetoprotein level (P = 1.00) were similar between patients with and without downstaged HCC.
CONCLUSION: DSM-TACE represents a safely and effective treatment option with similar safety and efficacy of conventional chemoembolization and could be successfully performed also for downstaging disease in patients without nMC, allowing them to reach liver transplantation.
Collapse
|
|
4
|
Niessen C, Unterpaintner E, Goessmann H, Schlitt HJ, Mueller-Schilling M, Wohlgemuth WA, Stroszczynski C, Wiggermann P. Degradable starch microspheres versus ethiodol and doxorubicin in transarterial chemoembolization of hepatocellular carcinoma. J Vasc Interv Radiol 2013; 25:240-7. [PMID: 24291001 DOI: 10.1016/j.jvir.2013.10.007] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2013] [Revised: 09/27/2013] [Accepted: 10/03/2013] [Indexed: 12/28/2022] Open
Abstract
PURPOSE To compare outcomes of transarterial chemoembolization with degradable starch microspheres (DSMs) and conventional transarterial chemoembolization with doxorubicin and Ethiodol in patients with unresectable intermediate-stage hepatocellular carcinoma (HCC). MATERIALS AND METHODS A total of 69 patients underwent 169 chemoembolization procedures with Ethiodol (n = 35) or DSMs (n = 34) as the embolic agent. The same chemotherapeutic agent was used for all patients (50 mg doxorubicin). The primary endpoint was patient survival, and secondary endpoints were local tumor response and incidence of therapy-associated complications with conventional or DSM chemoembolization. Tumor response was evaluated by consensus reading by two radiologists in accordance with modified Response Evaluation Criteria In Solid Tumors. Mean survival was calculated according to Kaplan-Meier analysis, and differences in survival curves were assessed by univariate log-rank test. The statistical significance of quantitative variables was determined by parameter-free Wilcoxon-Mann-Whitney U test. RESULTS The study groups were similar with regard to demographic data and disease stage. For the DSM chemoembolization group, the objective response rate (ie, complete or partial response) was 44.1%, and the rate of stable disease was 38.2%. The respective rates for the conventional chemoembolization group were 48.6% and 31.4%. Mean survival (P = .337) and complications did not significantly differ between groups (P = .907; P = 1.000). CONCLUSIONS DSM chemoembolization represents an alternative method of HCC treatment with a safety profile similar to that of conventional transarterial chemoembolization. Regarding local tumor response and overall survival, results of DSM chemoembolization were similar to those of conventional chemoembolization.
Collapse
Affiliation(s)
- Christoph Niessen
- Department of Radiology, University Hospital Regensburg, Franz-Josef Strauss Allee 11, 93042 Regensburg, Germany.
| | - Eva Unterpaintner
- Department of Radiology, University Hospital Regensburg, Franz-Josef Strauss Allee 11, 93042 Regensburg, Germany
| | - Holger Goessmann
- Department of Radiology, University Hospital Regensburg, Franz-Josef Strauss Allee 11, 93042 Regensburg, Germany
| | - Hans J Schlitt
- Department of Surgery, University Hospital Regensburg, Franz-Josef Strauss Allee 11, 93042 Regensburg, Germany
| | - Martina Mueller-Schilling
- Department of Internal Medicine I, University Hospital Regensburg, Franz-Josef Strauss Allee 11, 93042 Regensburg, Germany
| | - Walter A Wohlgemuth
- Department of Radiology, University Hospital Regensburg, Franz-Josef Strauss Allee 11, 93042 Regensburg, Germany
| | - Christian Stroszczynski
- Department of Radiology, University Hospital Regensburg, Franz-Josef Strauss Allee 11, 93042 Regensburg, Germany
| | - Philipp Wiggermann
- Department of Radiology, University Hospital Regensburg, Franz-Josef Strauss Allee 11, 93042 Regensburg, Germany
| |
Collapse
|
|
5
|
Effect of transcatheter arterial infusion chemotherapy using iodized oil and degradable starch microspheres for hepatocellular carcinoma. J Gastroenterol 2012; 47:715-22. [PMID: 22322658 DOI: 10.1007/s00535-012-0537-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2011] [Accepted: 12/26/2011] [Indexed: 02/04/2023]
Abstract
BACKGROUND Transcatheter arterial infusion chemotherapy (TAI) using a combination of iodized oil (lipiodol) and degradable starch microspheres (DSMs) has been reported to be superior to TAI with either lipiodol or DSMs separately for the treatment of hepatocellular carcinoma (HCC), based on the results of a prospective randomized study. In the study reported here, we investigated the predictors influencing response and survival in HCC patients receiving TAI using lipiodol and DSMs. METHODS A total of 50 HCC patients [Child-Pugh A/B, 34/16 patients; maximum tumor size 2.9 cm (mean); tumor number <5/≥5 = 29/21 patients] were administered a mixture of cisplatin and lipiodol, followed by the injection of DSMs. RESULTS According to the criteria of the Liver Cancer Study Group of Japan, the response [complete response (CR) + partial response (PR)] rate and CR rate were 72 and 38%, respectively [CR, 19 patients; PR, 17; stable disease, 9; progressive disease, 5]. The 1-, 2-, 3-, and 4-year cumulative survival rates were 85, 67, 41, and 35%, respectively, and the median survival time was 32.6 months. Multivariate analysis identified tumor number <5 nodules [odds ratio 10.651, 95% confidence interval (CI) 2.168-52.317; P = 0.004] as an independent predictor of response and des-γ-carboxyprothrombin level <100 mAU/mL [hazard ratio (HR), 0.268, 95% CI 0.091-0.786, P = 0.017] and therapeutic effect CR or PR (HR 0.255, 95% CI 0.099-0.659; P = 0.005) as independent predictors of survival. CONCLUSION Transcatheter arterial infusion chemotherapy using lipiodol and DSMs might be considered as a potential intervention in HCC patients, especially those with tumors of <5 nodules.
Collapse
|
|
6
|
A novel transcatheter arterial infusion chemotherapy using iodized oil and degradable starch microspheres for hepatocellular carcinoma: a prospective randomized trial. J Gastroenterol 2011; 46:359-66. [PMID: 20737175 DOI: 10.1007/s00535-010-0306-5] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2010] [Accepted: 08/02/2010] [Indexed: 02/04/2023]
Abstract
BACKGROUND We designed a novel transcatheter arterial infusion chemotherapy (TAI) using iodized oil (lipiodol) and degradable starch microspheres (DSM) for hepatocellular carcinoma (HCC) patients. In this study, we investigated the efficacy of TAI using lipiodol and DSM in a prospective randomized trial. METHODS We randomly divided 45 patients with HCC into 3 groups: TAI using lipiodol (lipiodol group, n = 15), TAI using DSM (DSM group, n = 15), and TAI using lipiodol and DSM (lipiodol + DSM group, n = 15). In the lipiodol group, a mixture of cisplatin and lipiodol was administered. In the DSM group, a mixture of cisplatin and DSM was administered. In the lipiodol + DSM group, a mixture of cisplatin and lipiodol was administered, followed by DSM. RESULTS The response rates were 40% in the lipiodol group, 53.4% in the DSM group, and 80% in the lipiodol + DSM group, respectively. The response rate tended to improve in the lipiodol + DSM group (lipiodol group vs. lipiodol + DSM group, P = 0.07). The median progression-free survival time was 177 days in the lipiodol group, 287 days in the DSM group, and 377 days in the lipiodol + DSM group. The progression-free survival in the lipiodol + DSM group was significantly better than those in the DSM group (P = 0.020) and the lipiodol group (P = 0.035). There were no serious adverse effects among the 3 groups. CONCLUSIONS TAI using lipiodol and DSM was superior to TAI using lipiodol only and TAI using DSM only because of improvements in therapeutic effects and progression-free survival.
Collapse
|
|
7
|
Ishida K, Hirooka M, Hiraoka A, Kumagi T, Uehara T, Hiasa Y, Horiike N, Onji M. Treatment of hepatocellular carcinoma using arterial chemoembolization with degradable starch microspheres and continuous arterial infusion of 5-fluorouracil. Jpn J Clin Oncol 2008; 38:596-603. [PMID: 18772170 DOI: 10.1093/jjco/hyn076] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVE Transcatheter arterial embolization (TAE) with gelatin sponge particles and iodized oil often yields poor results when used to treat unresectable multifocal hepatocellular carcinoma (HCC). The present study retrospectively investigated the utility of a novel combination chemotherapy regimen for treating multifocal HCC resistant to TAE. METHODS Thirteen consecutive patients with unresectable multifocal HCC and resistance to TAE were treated with combination chemotherapy consisting of arterial chemoembolization with degradable starch microspheres (DSM) (150-4500 mg on Day 1), mitomycin-C (4-8 mg on Day 1), continuous arterial infusion of 5-fluorouracil (1250 mg/120 h), cisplatin (25-50 mg/120 h) and l-leucovorin (125 mg/120 h) for 10-19 weeks. RESULTS The response rate was 84.6%, with complete response in one patient and partial response (PR) in 10 patients. In four of 10 patients with PR, the tumor was not observable, although the tumor marker did not completely decline to the normal range. The 1-, 2- and 3-year survival rates were 100, 28.9 and 9.6% in all, and 100, 33.3 and 0% in six patients with portal vein tumor thrombosis (PVTT). The median survival was 22.1 months in all and 17.1 months in six patients with PVTT. Thrombocytopenia of Grade III or higher was observed in eight patients. Laparoscopic splenectomy was performed before therapy in four patients with platelet counts of <70,000/mm(3), and during therapy in five patients with severe thrombocytopenia. CONCLUSIONS This novel chemotherapy regimen achieved favorable results and may be useful in treating patients with unresectable multifocal HCC resistant to TAE.
Collapse
Affiliation(s)
- Kiyotaka Ishida
- Third Department of Internal Medicine, Ehime University School of Medicine, Touon, Ehime 791-0295, Japan
| | | | | | | | | | | | | | | |
Collapse
|
|
8
|
Li X, Wang YXJ, Zhou X, Guan Y, Tang C. Catheterization of the hepatic artery via the left common carotid artery in rats. Cardiovasc Intervent Radiol 2007; 29:1073-6. [PMID: 16670846 DOI: 10.1007/s00270-005-8268-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
The commonly used approach for rat hepatic artery catheterization is via the gastroduodenal artery, which is ligated after the procedure. A new method of rat hepatic artery catheterization via the left common carotid artery (LCCA) is described. The LCCA is repaired after catheterization. The catheterization procedures included the following: (1) opening the rat's abdominal cavity and exposing the portion of abdominal aorta at the level of the celiac trunk; (2) separating and exposing the LCCA; inserting a microguidewire and microcatheter set into the LCCA via an incision; after placement into the descending aorta, the microguidewire and microcatheter are maneuvered into the hepatic artery under direct vision; (3) after transcatheter therapy, the catheter is withdrawn and the incision at the LCCA is repaired. This technique was employed on 60 male Sprague-Dawley rats with diethylnitrosamine-induced liver cancer, using a 3F microguidewire and microcatheter set. Selective hepatic artery catheterization was successfully performed in 57 rats. One rat died during the operation and five rats died within 7 days after the procedure. It is envisaged that as experience increases, the catheterization success rate will increase and the death rate will decrease. A new approach for selective hepatic artery catheterization via the LCCA in rats is introduced, which makes repeat catheterization of this artery possible and allows large embolization particles to be delivered by using a 3F catheter.
Collapse
MESH Headings
- Alkylating Agents/adverse effects
- Angiography, Digital Subtraction
- Animals
- Aorta, Abdominal/diagnostic imaging
- Aorta, Abdominal/surgery
- Aorta, Thoracic/diagnostic imaging
- Aorta, Thoracic/surgery
- Carotid Artery, Common/diagnostic imaging
- Carotid Artery, Common/surgery
- Catheterization/instrumentation
- Catheterization/methods
- Celiac Artery/diagnostic imaging
- Celiac Artery/surgery
- Diethylnitrosamine/adverse effects
- Equipment Design
- Hepatic Artery/diagnostic imaging
- Hepatic Artery/surgery
- Liver Neoplasms, Experimental/chemically induced
- Liver Neoplasms, Experimental/diagnostic imaging
- Liver Neoplasms, Experimental/mortality
- Liver Neoplasms, Experimental/surgery
- Male
- Models, Animal
- Postoperative Complications/etiology
- Postoperative Complications/mortality
- Rats
- Rats, Sprague-Dawley
Collapse
Affiliation(s)
- Xiao Li
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, People's Republic of China
| | | | | | | | | |
Collapse
|
|
9
|
Marelli L, Stigliano R, Triantos C, Senzolo M, Cholongitas E, Davies N, Tibballs J, Meyer T, Patch DW, Burroughs AK. Transarterial therapy for hepatocellular carcinoma: which technique is more effective? A systematic review of cohort and randomized studies. Cardiovasc Intervent Radiol 2007; 30:6-25. [PMID: 17103105 DOI: 10.1007/s00270-006-0062-3] [Citation(s) in RCA: 615] [Impact Index Per Article: 34.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Chemoembolization (TACE) improves survival in cirrhotic patients with hepatocellular carcinoma (HCC). The optimal schedule, or whether embolization (TAE) alone gives the same survival advantage, is not known. PURPOSE To evaluate whether specific patient characteristics and/or radiological transarterial techniques result in better outcomes. METHOD A PubMed search was carried out for cohort and randomized trials (n = 175) testing transarterial therapies; meta-analysis was performed where appropriate. RESULTS Anticancer drugs were used as sole agent in 75% of cases (double 15% and triple 6%): doxorubicin (36%), cisplatin (31%), epirubicin (12%), mitoxantrone (8%), mitomycin (8%), and SMANCS (5%). Embolizing agents used were: gelatin sponge particles (71%), polyvinyl alcohol (PVA) particles (8%), degradable starch microspheres (DSM) (4%), and embospheres (4%). Sessions per patient were 2.5 +/- 1.5 (interval: 2 months). Objective response was 40 +/- 20%; survival rates at 1, 2, 3, and 5 years were: 62 +/- 20%, 42 +/- 17%, 30 +/- 15%, and 19 +/- 16%, respectively, and survival time was 18 +/- 9.5 months. The post-TACE complications were: acute liver failure, 7.5% (range 0-49%); acute renal failure, 1.8% (0-13%); encephalopathy, 1.8% (0-16%); ascites, 8.3% (0-52%); upper gastrointestinal bleeding; 3% (0-22%); and hepatic or splenic abscess, 1.3% (0-2.5%). Treatment-related mortality was 2.4% (0-9.5%), mainly due to acute liver failure. Our meta-analysis of nine randomized controlled trials (RCTs) confirmed that TACE improves survival; but a meta-analysis of TACE versus TAE alone (3 RCTs, 412 patients) demonstrated no survival difference. CONCLUSIONS No chemotherapeutic agent appears better than any other. There is no evidence for benefit with lipiodol. Gelatin sponge is the most used embolic agent, but PVA particles may be better. TAE appears as effective as TACE. New strategies to reduce the risk of post-TACE complications are required.
Collapse
Affiliation(s)
- Laura Marelli
- Liver Transplantation and Hepatobiliary Medicine Unit, Royal Free Hospital, Pond Street, NW3 2QG, London, UK
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
10
|
Deng SG, Wu ZF, Li WY, Yang ZG, Chang G, Meng FZ, Mo LL. Safety of Curcuma aromatica oil gelatin microspheres administered via hepatic artery. World J Gastroenterol 2004; 10:2637-42. [PMID: 15309710 PMCID: PMC4572184 DOI: 10.3748/wjg.v10.i18.2637] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM: To evaluate the safety of Curcuma aromatica oil gelatin microspheres (CAO-GMS) infused via hepatic artery against primary liver cancer.
METHODS: The safety of CAO-GMS was evaluated in view of its acute toxicity in rats, long-term toxicity in Beagle dogs and general pharmacology in rats and mongrel dogs.
RESULTS: The 50% lethal dose (LD50) of CAO-GMS infused via the hepatic artery was 17.19 mg/kg, and the serum biochemical indices of dying rats after the administration changed markedly while those of survived rats did not. Subsequent pathological examination of the tissues from the dead rats indicated improper embolism. Similar edema and small necrotic foci in the hepatic lobule were found in the hepatic tissue of rats receiving 10 and 5 mg/kg CAO-GMS and GMS 60 d after the last administration, while not in the rats of the blank control group, indicating that microspheres infused via the hepatic artery may induce irreversible liver damage dose-dependently. General pharmacological study showed that the activities (posture and gait), respiration frequency, blood pressure or heart rate of the dogs were not affected by CAO-GMS, nor were salivation, tremor or pupil changes of the rats observed or their balancing ability compromised, suggesting CAO-GMS infused via the hepatic artery did not significantly affect the nervous, respiratory and cardiovascular systems.
CONCLUSION: CAO-GMS embolization administered via the hepatic artery is safe but undesired embolization induced by vascular variation should be given due attention in its clinical application. Individualized embolization dosage and super-selective catheterization technique are recommended to avoid undesired embolism and reduce complications.
Collapse
Affiliation(s)
- Shi-Gui Deng
- Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou 510120, 111 Dade Road, Guangdong Province, China.
| | | | | | | | | | | | | |
Collapse
|
|
11
|
Furuse J, Ishii H, Satake M, Onaya H, Nose H, Mikami S, Sakai H, Mera K, Maru Y, Yoshino M. Pilot study of transcatheter arterial chemoembolization with degradable starch microspheres in patients with hepatocellular carcinoma. Am J Clin Oncol 2003; 26:159-64. [PMID: 12714888 DOI: 10.1097/00000421-200304000-00012] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
We prospectively evaluated the efficacy and safety of transcatheter arterial chemoembolization (TACE) with microembolization material, degradable starch microspheres (DSMs), and epirubicin, for treatment of multifocal hepatocellular carcinoma (HCC). Seventeen patients with multifocal HCC were treated. At the first treatment, DSMs were injected alone to determine the dose for embolization of the hepatic artery in each patient. After 4 weeks, TACE was performed every 4 to 6 weeks with a mixture of DSMs and epirubicin at a dose of 40 mg/m2. A necrotic area of more than 50% was produced in 6 patients by DSMs alone, and in 11 patients by TACE. The overall response rate was 52.9% (2 complete and 7 partial responses). The duration of the responses ranged from 4 to 21 months (median: 9 months). Common toxicities were transient abdominal pain, nausea/vomiting, fever, and leukopenia. In four patients, grade III or IV toxicity was observed as gamma-glutamyl transpeptidase elevation. TACE with DSMs had tumor necrosis efficacy with acceptable toxicity. The median survival time was 21.7 months, and the 2-year survival rate was 45.3%. Further investigation of the effects of DSM treatment on survival should be carried out.
Collapse
Affiliation(s)
- Junji Furuse
- National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
12
|
Abstract
Radiofrequency capacitive hyperthermia combined with intra-arterial chemotherapy or chemoembolization was performed in 45 patients with unresectable hepatic cancer. Intratumor temperature was measured in 26 (57.8%) of the 45 patients. The overall mean maximum core temperature (Tmax) was 41.3 +/- 0.3 degrees C (mean +/- SE), and the Tmax was > or = 42 degrees C in nine tumors (34.6%). The tumor temperature rise was related to the power applied, embolization with degradable starch microspheres, and obstruction of the portal vein. The overall response rate was 31.1% (14/45). The response rate was 55.6% when Tmax was > or = 42 degrees C; although this was higher than the response rate of 11.8% achieved with Tmax < 42 degrees C, the difference was not significant. There were no serious adverse effects of hyperthermia.
Collapse
Affiliation(s)
- K Yamamoto
- Department of Radiology, Kansai Medical University, Osaka, Japan
| | | |
Collapse
|
|
13
|
Cascinu S, Wadler S. Chemo-embolization in the treatment of liver metastases from colorectal cancer. Cancer Treat Rev 1996; 22:355-63. [PMID: 9118121 DOI: 10.1016/s0305-7372(96)90008-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Affiliation(s)
- S Cascinu
- Medical Oncology, Ancona University, Italy
| | | |
Collapse
|
|
14
|
Ball AB. Regional chemotherapy for colorectal hepatic metastases using degradable starch microspheres. A review. Acta Oncol 1991; 30:309-13. [PMID: 2036239 DOI: 10.3109/02841869109092376] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Biodegradable starch microspheres (DSM) given by intra-arterial injection provide a way of improving the delivery of cytotoxic drugs to hepatic metastases and simultaneously reducing systemic toxicity. Their effect depends on exploiting the different vascular properties of neoplastic and healthy tissue. Although clinical evaluation is at an early stage, the ability of DSM to produce a selective increase of drug concentration in hepatic metastases represents an improvement on conventional techniques of regional chemotherapy.
Collapse
Affiliation(s)
- A B Ball
- Academic Surgical Unit, Royal Marsden Hospital, London, England
| |
Collapse
|
|
15
|
Civalleri D, Scopinaro G, Balletto N, Claudiani F, De Cian F, DeCian F, Camerini G, DePaoli M, Bonalumi U. Changes in vascularity of liver tumours after hepatic arterial embolization with degradable starch microspheres. Br J Surg 1989; 76:699-703. [PMID: 2765804 DOI: 10.1002/bjs.1800760716] [Citation(s) in RCA: 28] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
The role of vascularity as a prognostic factor was investigated in 35 patients undergoing arterial chemotherapy for liver tumours. Compared with parenchyma, tumour vascularity was classified as hot (18 cases), cold (12 cases), and mixed (12 cases) using 99mTc-macroaggregated albumin (MAA) hepatic arterial scans. The proportion of patients showing complete and partial responses to treatment was higher in the hot group (56 per cent) than in the combined cold and mixed group (12 per cent). In 15 cases (six hot, six cold and three mixed lesions), additional MAA scans were performed immediately after arterial embolization with degradable starch microspheres (DSMs). Either complete or partial reversal of tumour vascularity was observed after DSM-embolization in five and seven cases respectively, two and two of them respectively showing native cold lesions. As tumour vascularity appears to be a prominent prognostic factor, DSM-embolization should improve the efficacy of treatment by improving liver extraction of drugs and causing flow redistribution towards hypovascular areas.
Collapse
Affiliation(s)
- D Civalleri
- Istituto di Patologia Chirurgica dell'Università, Genova, Italy
| | | | | | | | | | | | | | | | | |
Collapse
|
|
16
|
Persson BG, Jeppsson B, Andersson L, Strand SE, Ekelund L, Bengmark S. The prevention of arterial collaterals after repeated temporary blockade of the hepatic artery in pigs. World J Surg 1987; 11:672-7. [PMID: 3673101 DOI: 10.1007/bf01655846] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
|
|
17
|
Starkhammar H, Håkansson L, Morales O, Svedberg J. Intra-arterial mitomycin C treatment of unresectable liver tumours. Preliminary results on the effect of degradable starch microspheres. Acta Oncol 1987; 26:295-300. [PMID: 3120760 DOI: 10.3109/02841868709089978] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Regional chemotherapy might be more efficient if the cytostatic drug is injected together with degradable starch microspheres (DSM), which induce temporary blockage of arterioles and trap the co-injected drug in tumour. Eighteen patients with non-resectable liver cancer were included. Mitomycin C (15 mg/m2) was injected intra-arterially mixed with 900 mg of DSM every six weeks. For estimation of the effect of DSM in the liver a radiolabelled tracer was injected via the same route. Its passage through the liver to the systemic circulation was continuously measured by a detector situated over peripheral blood vessels. The effect of DSM on the tracer passage varied considerably between different patients. The study also indicated opening of new vascular pathways some minutes after the initial injection. The dose of DSM for total blockage of the arterial blood flow, indicated by angiography, also varied. In some patients 540 mg induced total occlusion. In others neither angiographic nor tracer passage were affected by the microspheres although 900 mg (or even more) were injected. Factors such as size of the vascular bed, portal and arterial blood flow and arterio-venous shunting seemed to be of great importance and should be controlled in order to optimize the use of DSM in conjunction with chemotherapy of liver tumours.
Collapse
Affiliation(s)
- H Starkhammar
- Department of Oncology, University Hospital, Linköping, Sweden
| | | | | | | |
Collapse
|
|
18
|
Starkhammar H, Håkansson L, Sjödahl R, Svedberg J, Ekberg S. Effect of portal blood flow and intra-arterially injected starch microspheres on the passage of a labelled tracer through the liver. An experimental study in pigs. Acta Oncol 1987; 26:217-21. [PMID: 3651267 DOI: 10.3109/02841868709091435] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Pig liver was used to study the influence of portal blood flow and degradable starch microspheres (DSM) on the passage of radiolabelled methylene-di-phosphonate from the hepatic artery to the systemic circulation. When the portal vein was clamped abut 70 per cent of the labelled marker injected into the hepatic artery passed to the systemic circulation and the remaining 30 per cent passed when the portal vein was opened. When the flow of the hepatic artery was stopped, the portal blood flow alone drained about 65 per cent of the marker, which was given as a small volume injection into the hepatic artery. When both the arterial perfusion and the portal blood flow were closed the marker only slowly passed to the systemic circulation. DSM injected into the hepatic artery reduced the passage of the marker through the liver to 75 per cent of the reference level when the portal vein was open. When it was clamped this figure was reduced to about 25 per cent. The effect of DSM on the passage of the labelled marker was found to be dose dependent. It is suggested that the reduced passage of a labelled tracer given mixed with DSM is a useful measure of degree of arterial occlusion in the liver. However, because of the drainage via the portal system the passage cannot be completely inhibited.
Collapse
Affiliation(s)
- H Starkhammar
- Department of Oncology, University Hospital, Linköping, Sweden
| | | | | | | | | |
Collapse
|
|
19
|
Civalleri D, Scopinaro G, Simoni G, Claudiani F, Repetto M, DeCian F, Bonalumi U. Starch microsphere-induced arterial flow redistribution after occlusion of replaced hepatic arteries in patients with liver metastases. Cancer 1986; 58:2151-5. [PMID: 3756831 DOI: 10.1002/1097-0142(19861101)58:9<2151::aid-cncr2820580932>3.0.co;2-f] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
In four patients with major anomalies of the hepatic artery undergoing intra-arterial chemotherapy, aberrant lobar vessels were ligated and catheters were inserted into the contralateral artery. Catheter perfusion scans performed early after ligation with 99mTc-macroaggregated albumin (MAA) showed a defective perfusion of the lobe supplied by the occluded artery (0.43, 0.23, 0.11, and 0.28, respectively, as compared to the contralateral lobe). Further MAA scans performed after catheter infusion of 90,000,000 parts of degradable starch microspheres (DSM) showed a near normal perfusion of the ischemic lobe (0.91, 0.96, 0.87, and 0.98). On the contrary, simple MAA scans performed in the first two patients 114 and 135 days after ligation showed a still defective arterial perfusion of the ischemic lobe (0.60, and 0.24). The DSM-induced redistribution of flow towards ischemic portions of the liver suggests a possible new role of DSM in regional treatment of liver tumors in cases with either occlusion of aberrant vessels or "hypovascular" tumors.
Collapse
|
|
20
|
Bechard S, McMullen JN. Pectin-gelatin microglobules: effect of a cross-linking agent (formaldehyde) on in vitro dissolution rate. Int J Pharm 1986. [DOI: 10.1016/0378-5173(86)90217-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
|
|
21
|
Teder H, Nilsson M, Aronsen KF. Gamma camera evaluation of the effects of degradable starch microspheres on arterial liver blood flow in the rat. RESEARCH IN EXPERIMENTAL MEDICINE. ZEITSCHRIFT FUR DIE GESAMTE EXPERIMENTELLE MEDIZIN EINSCHLIESSLICH EXPERIMENTELLER CHIRURGIE 1985; 185:391-7. [PMID: 2997892 DOI: 10.1007/bf01851919] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Degradable starch microspheres injected into an artery causes a temporary reduction of regional blood flow and improves the exposure of the organ to a drug injected simultaneously. The purpose of this study was to quantify this effect when microspheres are injected arterially into the liver of rats. As model substance radioactive pertechnetate ions (99TcmO4-) was used. The results were evaluated from external gamma camera measurements. The amounts of microspheres injected together with pertechnetate was 1.5-12 mg. When compared to injections of pertechnetate only, the integrated exposure of the liver to pertechnetate was increased by a factor of 1.4-2.4 when microspheres were added.
Collapse
|
|
22
|
Erichsen C, Bolmsjö M, Hugander A, Jönsson PE. Blockage of the hepatic-artery blood flow by biodegradable microspheres (Spherex) combined with local hyperthermia in the treatment of experimental liver tumors in rats. J Cancer Res Clin Oncol 1985; 109:38-41. [PMID: 3972883 DOI: 10.1007/bf01884252] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
The effect of local hyperthermia and a simultaneous blockage of the hepatic-artery blood flow by degradable starch microspheres (Spherex) was studied in a model of liver cancer in Wistar rats. Six days after each rat was inoculated with a cell suspension (NGW) in the central liver lobe, the rats were randomly allocated into four groups. The first group served as control, the second was treated with hyperthermia, the third by degradable starch microspheres (DSM) intraarterially, and the fourth with a combination of hyperthermia and DSM intraarterially. Tumor volumes were measured at laparotomy on days 0, 7, and 14. Temperature fluctuations in the tumor correlated well with those in the liver tissue, but were 2 degrees-4 degrees higher. The infusion of DSM did not change the pattern significantly. The tumor volumes were homogeneous between the groups at the start of treatment. The tumor growth was significantly reduced compared with the control group at day 7 in group III (P less than 0.05) and group IV (P less than 0.01) but only in group IV at day 14 (P less than 0.05). No differences in survival were found. Local hyperthermia concurrent with a blockage of the nutritional tumor blood flow seems to offer a more prominent and lasting tumor-growth inhibition.
Collapse
|