TY - JOUR
T1 - Percutaneous ethanol injection for liver metastases
AU - Swierz, Mateusz J.
AU - Storman, Dawid
AU - Riemsma, Robert P.
AU - Wolff, Robert
AU - Mitus, Jerzy W.
AU - Pedziwiatr, Michal
AU - Kleijnen, Jos
AU - Bala, Malgorzata M.
N1 - Funding Information:
We would like to thank Dimitrinka Nikolova for help and Christian Gluud for advice on preparing this systematic review.? ? Peer Reviewers of the protocol of the review: Thomas Karlas, Germany, and Hans Christian Spangenberg, Germany.? Peer Reviewer of the previous review and the current review: Janus Christian Jakobsen, Denmark.? Contact Editor: Emil Eik Nielsen, Denmark.? Sign-off Editor: Christian Gluud, Denmark.? Cochrane Abdomen and Endocine Network Associate Editor: Liz Bickerdike, UK. Cochrane Review Group funding acknowledgement: the Danish State is the largest single funder of the Cochrane Hepato-Biliary Group through its investment in the Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Denmark. Disclaimer: the views and opinions expressed in this review are those of the authors and do not necessarily reflect those of the Danish State or the Copenhagen Trial Unit.
Publisher Copyright:
Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
PY - 2020/2/4
Y1 - 2020/2/4
N2 - BackgroundThe liver is affected by two of the most common groups of malignant tumours: primary liver tumours and liver metastases from colorectal carcinoma or other extrahepatic primary cancers. Liver metastases are significantly more common than primary liver cancer, and the reported long-term survival rate after radical surgical treatment is approximately 50%. However, R0 resection (resection for cure) is not feasible in the majority of patients; therefore, other treatments have to be considered. One of these is percutaneous ethanol injection (PEI), which causes dehydration and necrosis of tumour cells, accompanied by small-vessel thrombosis, leading to tumour ischaemia and destruction of the tumour.ObjectivesTo assess the beneficial and harmful effects of percutaneous ethanol injection (PEI) compared with no intervention, other ablation methods, or systemic treatments in people with liver metastases.Search methodsWe searched the following databases up to 10 September 2019: the Cochrane Hepato-Biliary Group Controlled Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; MEDLINE Ovid; Embase Ovid; Science Citation Index Expanded; Conference Proceedings Citation Index - Science; Latin American Caribbean Health Sciences Literature (LILACS); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL). We also searched clinical trials registers such as ClinicalTrials.gov, the International Clinical Trials Registry Platform (ICTRP), and the US Food and Drug Administration (FDA) (17 September 2019).Selection criteriaRandomised clinical trials assessing beneficial and harmful effects of percutaneous ethanol injection and its comparators (no intervention, other ablation methods, systemic treatments) for liver metastases.Data collection and analysisWe followed standard methodological procedures as outlined by Cochrane. We extracted information on participant characteristics, interventions, study outcomes, study design, and trial methods. Two review authors performed data extraction and assessed risk of bias independently. We assessed the certainty of evidence by using GRADE. We resolved disagreements by discussion.Main resultsWe identified only one randomised clinical trial comparing percutaneous intratumour ethanol injection (PEI) in addition to transcatheter arterial chemoembolisation (TACE) versus TACE alone. The trial was conducted in China and included 48 trial participants with liver metastases: 25 received PEI plus TACE, and 23 received TACE alone. The trial included 37 male and 11 female participants. Mean participant age was 49.3 years. Sites of primary tumours included colon (27 cases), stomach (12 cases), pancreas (3 cases), lung (3 cases), breast (2 cases), and ovary (1 case). Seven participants had a single tumour, 15 had two tumours, and 26 had three or more tumours in the liver. The bulk diameter of the tumour on average was 3.9 cm, ranging from 1.2 cm to 7.6 cm.Participants were followed for 10 months to 43 months. The trial reported survival data after one, two, and three years. In the PEI + TACE group, 92%, 80%, and 64% of participants survived after one year, two years, and three years; in the TACE alone group, these percentages were 78.3%, 65.2%, and 47.8%, respectively. Upon conversion of these data to mortality rates, the calculated risk ratio (RR) for mortality at last follow-up when PEI plus TACE was compared with TACE alone was 0.69 (95% confidence interval (CI) 0.36 to 1.33; very low-certainty evidence) after three years of follow-up. Local recurrence was 16% in the PEI plus TACE group and 39.1% in the TACE group, resulting in an RR of 0.41 (95% CI 0.15 to 1.15; very low-certainty evidence). Forty-five out of a total of 68 tumours (66.2%) shrunk by at least 25% in the PEI plus TACE group versus 31 out of a total of 64 tumours (48.4%) in the TACE group. Trial authors reported some adverse events but provided very few details. We did not find data on time to mortality, failure to clear liver metastases, recurrence of liver metastases, health-related quality of life, or time to progression of liver metastases.The single included trial did not provide information on funding nor on conflict of interest.Authors' conclusionsEvidence for the effectiveness of PEI plus TACE versus TACE in people with liver metastases is of very low certainty and is based on one small randomised clinical trial at high risk of bias. Currently, it cannot be determined whether adding PEI to TACE makes a difference in comparison to using TACE alone. Evidence for benefits or harms of PEI compared with no intervention, other ablation methods, or systemic treatments is lacking.
AB - BackgroundThe liver is affected by two of the most common groups of malignant tumours: primary liver tumours and liver metastases from colorectal carcinoma or other extrahepatic primary cancers. Liver metastases are significantly more common than primary liver cancer, and the reported long-term survival rate after radical surgical treatment is approximately 50%. However, R0 resection (resection for cure) is not feasible in the majority of patients; therefore, other treatments have to be considered. One of these is percutaneous ethanol injection (PEI), which causes dehydration and necrosis of tumour cells, accompanied by small-vessel thrombosis, leading to tumour ischaemia and destruction of the tumour.ObjectivesTo assess the beneficial and harmful effects of percutaneous ethanol injection (PEI) compared with no intervention, other ablation methods, or systemic treatments in people with liver metastases.Search methodsWe searched the following databases up to 10 September 2019: the Cochrane Hepato-Biliary Group Controlled Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; MEDLINE Ovid; Embase Ovid; Science Citation Index Expanded; Conference Proceedings Citation Index - Science; Latin American Caribbean Health Sciences Literature (LILACS); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL). We also searched clinical trials registers such as ClinicalTrials.gov, the International Clinical Trials Registry Platform (ICTRP), and the US Food and Drug Administration (FDA) (17 September 2019).Selection criteriaRandomised clinical trials assessing beneficial and harmful effects of percutaneous ethanol injection and its comparators (no intervention, other ablation methods, systemic treatments) for liver metastases.Data collection and analysisWe followed standard methodological procedures as outlined by Cochrane. We extracted information on participant characteristics, interventions, study outcomes, study design, and trial methods. Two review authors performed data extraction and assessed risk of bias independently. We assessed the certainty of evidence by using GRADE. We resolved disagreements by discussion.Main resultsWe identified only one randomised clinical trial comparing percutaneous intratumour ethanol injection (PEI) in addition to transcatheter arterial chemoembolisation (TACE) versus TACE alone. The trial was conducted in China and included 48 trial participants with liver metastases: 25 received PEI plus TACE, and 23 received TACE alone. The trial included 37 male and 11 female participants. Mean participant age was 49.3 years. Sites of primary tumours included colon (27 cases), stomach (12 cases), pancreas (3 cases), lung (3 cases), breast (2 cases), and ovary (1 case). Seven participants had a single tumour, 15 had two tumours, and 26 had three or more tumours in the liver. The bulk diameter of the tumour on average was 3.9 cm, ranging from 1.2 cm to 7.6 cm.Participants were followed for 10 months to 43 months. The trial reported survival data after one, two, and three years. In the PEI + TACE group, 92%, 80%, and 64% of participants survived after one year, two years, and three years; in the TACE alone group, these percentages were 78.3%, 65.2%, and 47.8%, respectively. Upon conversion of these data to mortality rates, the calculated risk ratio (RR) for mortality at last follow-up when PEI plus TACE was compared with TACE alone was 0.69 (95% confidence interval (CI) 0.36 to 1.33; very low-certainty evidence) after three years of follow-up. Local recurrence was 16% in the PEI plus TACE group and 39.1% in the TACE group, resulting in an RR of 0.41 (95% CI 0.15 to 1.15; very low-certainty evidence). Forty-five out of a total of 68 tumours (66.2%) shrunk by at least 25% in the PEI plus TACE group versus 31 out of a total of 64 tumours (48.4%) in the TACE group. Trial authors reported some adverse events but provided very few details. We did not find data on time to mortality, failure to clear liver metastases, recurrence of liver metastases, health-related quality of life, or time to progression of liver metastases.The single included trial did not provide information on funding nor on conflict of interest.Authors' conclusionsEvidence for the effectiveness of PEI plus TACE versus TACE in people with liver metastases is of very low certainty and is based on one small randomised clinical trial at high risk of bias. Currently, it cannot be determined whether adding PEI to TACE makes a difference in comparison to using TACE alone. Evidence for benefits or harms of PEI compared with no intervention, other ablation methods, or systemic treatments is lacking.
KW - Administration
KW - Cutaneous
KW - Colorectal Neoplasms
KW - Chemoembolization
KW - Therapeutic [methods] [mortality]
KW - Ethanol [administration & dosage];
KW - Liver Neoplasms [mortality] [secondary] [therapy]
KW - Randomized Controlled Trials as Topic
KW - Humans
KW - TRIAL SEQUENTIAL-ANALYSIS
KW - ACETIC-ACID INJECTION
KW - RANDOMIZED-TRIALS
KW - RADIOFREQUENCY ABLATION
KW - HEPATOCELLULAR-CARCINOMA
KW - EMPIRICAL-EVIDENCE
KW - CANCER STATISTICS
KW - DESIGN CHARACTERISTICS
KW - COLORECTAL-CANCER
KW - COCHRANE REVIEWS
U2 - 10.1002/14651858.CD008717.pub3
DO - 10.1002/14651858.CD008717.pub3
M3 - (Systematic) Review article
C2 - 32017845
SN - 1469-493X
VL - 2020
JO - Cochrane Database of Systematic Reviews
JF - Cochrane Database of Systematic Reviews
IS - 2
M1 - CD008717
ER -