Ischemic Reperfusion Injuryannie-liverNCT04257240
Recurrence of Liver Malignancy After Ischemia/Reperfusion Injury
An observational study of Ischemic Reperfusion Injury and Liver Injury, run by Aretaieion University Hospital.
Trial summary
Severe ischemic changes of the liver remnant after hepatectomy could expedite tumor recurrence on the residual liver. Our study aimed at assessing the effect of warm ischemic/reperfusion (I/R) injuries on surgery-to-local recurrence interval and patient overall survival, during major hepatectomies under inflow and… Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Ischemic Reperfusion Injury, Liver Injury, Cancer Recurrence
- What is being tested?
- selective hepatic vascular exclusion and semielective hepatic vascular exclusion
- Type of treatment
- Surgery or procedure
- How many people
- 230 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2000to 31 Dec 2012
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: retrospective analysis of an internal hepatectomy database
Who may be able to join
- Adult patients
- American Society of Anesthesiologists (ASA) distribution I to III
- Patients scheduled for major liver resection (≥3 segments)
Who cannot join
- patients with extrahepatic disease
- patients with metastatic liver tumors
About this study
Official title: Does Vascular Occlusion in Liver Resections Predispose to Recurrence of Malignancy in the Liver Remnant Due to Ischemia/Reperfusion Injury?
Severe ischemic changes of the liver remnant after hepatectomy could expedite tumor recurrence on the residual liver. Our study aimed at assessing the effect of warm ischemic/reperfusion (I/R) injuries on surgery-to-local recurrence interval and patient overall survival, during major hepatectomies under inflow and outflow vascular control.
Read the detailed description
One hundred and eighteen patients were subjected to liver resection under total inflow and outflow vascular clamping and were assigned as study group. These individuals were retrospectively matched to 112 counterparts, who underwent liver surgery applying inflow and outflow vascular clamping only of the segment harboring the tumor, sparing the liver remnant from any I/R injury (control group). The two cohorts were compared regarding recurrence-free survival and overall survival.
- Being tested
- selective hepatic vascular exclusion, semielective hepatic vascular exclusion
- Keywords
- ischemia reperfusion injury, liver surgery, cancer recurrence, malignancy, hepatectomy
- Medical subject headings
- Neoplasms, Liver Neoplasms, Reperfusion Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
selective hepatic vascular exclusionProcedure or surgery
major hepatectomy with vascular control of blood inflow and outflow of the whole liver
semielective hepatic vascular exclusionProcedure or surgery
major liver resection by selectively clamping the portal and hepatic vessels only of the lobe harboring the tumor
| Study group | Role | What they receive |
|---|---|---|
| study group | patients subjected to major hepatectomy with vascular control of blood inflow and outflow of the whole liver Receives: Procedure: selective hepatic vascular exclusion | |
| control group | patients subjected to major hepatectomy by selectively clamping the portal and hepatic vessels only of the lobe harboring the tumor Receives: Procedure: semielective hepatic vascular exclusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
time to malignant recurrence
recurrence-free survival
Measured: from time of operation until time of malignant recurrence, assessed up to 15 years
time to death
overall survival
Measured: from time of operation until time of death, assessed up to 20 years
Secondary outcomes (1)
aspartate aminotrasferase (AST) levels
aspartate aminotransferase levels
Measured: second postoperative day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2020
- Study start1 Jan 2000
- Primary completion31 Dec 2012
- Study completion31 Dec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Ischemic Reperfusion InjuryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 230 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aretaieion University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr Kassiani Theodoraki, Aretaieion University Hospital
- Investigators
- Kassiani Theodoraki, PhD, Principal investigator, Aretaieion University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04257240
- Sponsor's protocol ID
- liver IR
- Acronym
- annie-liver
- Status last verified
- Feb 2020
- First submitted
- 2 Feb 2020
- Last updated
- 5 Feb 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Smyrniotis V, Farantos C, Kostopanagiotou G, Arkadopoulos N. Vascular control during hepatectomy: review of methods and results. World J Surg. 2005 Nov;29(11):1384-96. doi: 10.1007/s00268-005-0025-x.
PubMed 16222453Smyrniotis VE, Kostopanagiotou GG, Contis JC, Farantos CI, Voros DC, Kannas DC, Koskinas JS. Selective hepatic vascular exclusion versus Pringle maneuver in major liver resections: prospective study. World J Surg. 2003 Jul;27(7):765-9. doi: 10.1007/s00268-003-6978-8.
PubMed 14509502Huang J, Tang W, Hernandez-Alejandro R, Bertens KA, Wu H, Liao M, Li J, Zeng Y. Intermittent hepatic inflow occlusion during partial hepatectomy for hepatocellular carcinoma does not shorten overall survival or increase the likelihood of tumor recurrence. Medicine (Baltimore). 2014 Dec;93(28):e288. doi: 10.1097/MD.0000000000000288.
PubMed 25526466Liu L, Ren ZG, Shen Y, Zhu XD, Zhang W, Xiong W, Qin Y, Tang ZY. Influence of hepatic artery occlusion on tumor growth and metastatic potential in a human orthotopic hepatoma nude mouse model: relevance of epithelial-mesenchymal transition. Cancer Sci. 2010 Jan;101(1):120-8. doi: 10.1111/j.1349-7006.2009.01363.x. Epub 2009 Sep 14.
PubMed 19832842Serracino-Inglott F, Habib NA, Mathie RT. Hepatic ischemia-reperfusion injury. Am J Surg. 2001 Feb;181(2):160-6. doi: 10.1016/s0002-9610(00)00573-0.
PubMed 11425059Man K, Ng KT, Lo CM, Ho JW, Sun BS, Sun CK, Lee TK, Poon RT, Fan ST. Ischemia-reperfusion of small liver remnant promotes liver tumor growth and metastases--activation of cell invasion and migration pathways. Liver Transpl. 2007 Dec;13(12):1669-77. doi: 10.1002/lt.21193.
PubMed 18044786Ozaki M, Todo S. Surgical stress and tumor behavior: impact of ischemia-reperfusion and hepatic resection on tumor progression. Liver Transpl. 2007 Dec;13(12):1623-6. doi: 10.1002/lt.21230. No abstract available.
PubMed 18044752Cho JY, Han HS, Choi Y, Yoon YS, Kim S, Choi JK, Jang JS, Kwon SU, Kim H. Association of Remnant Liver Ischemia With Early Recurrence and Poor Survival After Liver Resection in Patients With Hepatocellular Carcinoma. JAMA Surg. 2017 Apr 1;152(4):386-392. doi: 10.1001/jamasurg.2016.5040.
PubMed 28052154Portolani N, Coniglio A, Ghidoni S, Giovanelli M, Benetti A, Tiberio GA, Giulini SM. Early and late recurrence after liver resection for hepatocellular carcinoma: prognostic and therapeutic implications. Ann Surg. 2006 Feb;243(2):229-35. doi: 10.1097/01.sla.0000197706.21803.a1.
PubMed 16432356Theodoraki K, Papadoliopoulou M, Petropoulou Z, Theodosopoulos T, Vassiliu P, Polydorou A, Xanthakos P, Fragulidis G, Smyrniotis V, Arkadopoulos N. Does vascular occlusion in liver resections predispose to recurrence of malignancy in the liver remnant due to ischemia/reperfusion injury? A comparative retrospective cohort study. Int J Surg. 2020 Aug;80:68-73. doi: 10.1016/j.ijsu.2020.06.019. Epub 2020 Jun 30.
PubMed 32619621
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Does Vascular Occlusion in Liver Resections Predispose to Recurrence of Malignancy in the Liver Remnant Due to Ischemia/Reperfusion Injury?
- ClinicalTrials.gov ID
- NCT04257240
- Acronym / sponsor ID
- annie-liver / liver IR
- Keywords
- ischemia reperfusion injury, liver surgery, cancer recurrence, malignancy, hepatectomy
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 230 participants (actual)
- Lead sponsor
- Aretaieion University HospitalUniversity, hospital or other
- Study start
- 1 Jan 2000 (actual)
- Primary completion
- 31 Dec 2012 (actual)
- Study completion
- 31 Dec 2012 (actual)
- First posted
- 5 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Severe ischemic changes of the liver remnant after hepatectomy could expedite tumor recurrence on the residual liver. Our study aimed at assessing the effect of warm ischemic/reperfusion (I/R) injuries on surgery-to-local recurrence interval and patient overall survival, during major hepatectomies under inflow and outflow vascular control.
Detailed description
One hundred and eighteen patients were subjected to liver resection under total inflow and outflow vascular clamping and were assigned as study group. These individuals were retrospectively matched to 112 counterparts, who underwent liver surgery applying inflow and outflow vascular clamping only of the segment harboring the tumor, sparing the liver remnant from any I/R injury (control group). The two cohorts were compared regarding recurrence-free survival and overall survival.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| study group | – | Procedure: selective hepatic vascular exclusionpatients subjected to major hepatectomy with vascular control of blood inflow and outflow of the whole liver |
| control group | – | Procedure: semielective hepatic vascular exclusionpatients subjected to major hepatectomy by selectively clamping the portal and hepatic vessels only of the lobe harboring the tumor |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- retrospective analysis of an internal hepatectomy database
Key inclusion criteria (3 listed)
- Adult patients
- American Society of Anesthesiologists (ASA) distribution I to III
- Patients scheduled for major liver resection (≥3 segments)
Key exclusion criteria (2 listed)
- patients with extrahepatic disease
- patients with metastatic liver tumors
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| selective hepatic vascular exclusionmajor hepatectomy with vascular control of blood inflow and outflow of the whole liver | Procedure or surgery | study group |
| semielective hepatic vascular exclusionmajor liver resection by selectively clamping the portal and hepatic vessels only of the lobe harboring the tumor | Procedure or surgery | control group |
Primary outcome
time to malignant recurrence
Time frame: from time of operation until time of malignant recurrence, assessed up to 15 years
recurrence-free survival
time to death
Time frame: from time of operation until time of death, assessed up to 20 years
overall survival
1 secondary outcome
aspartate aminotrasferase (AST) levels
Time frame: second postoperative day
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2020.
- Background: PubMed 16222453Smyrniotis V, Farantos C, Kostopanagiotou G, Arkadopoulos N. Vascular control during hepatectomy: review of methods and results. World J Surg. 2005 Nov;29(11):1384-96. doi: 10.1007/s00268-005-0025-x.
- Background: PubMed 14509502Smyrniotis VE, Kostopanagiotou GG, Contis JC, Farantos CI, Voros DC, Kannas DC, Koskinas JS. Selective hepatic vascular exclusion versus Pringle maneuver in major liver resections: prospective study. World J Surg. 2003 Jul;27(7):765-9. doi: 10.1007/s00268-003-6978-8.
- Background: PubMed 25526466Huang J, Tang W, Hernandez-Alejandro R, Bertens KA, Wu H, Liao M, Li J, Zeng Y. Intermittent hepatic inflow occlusion during partial hepatectomy for hepatocellular carcinoma does not shorten overall survival or increase the likelihood of tumor recurrence. Medicine (Baltimore). 2014 Dec;93(28):e288. doi: 10.1097/MD.0000000000000288.
- Background: PubMed 19832842Liu L, Ren ZG, Shen Y, Zhu XD, Zhang W, Xiong W, Qin Y, Tang ZY. Influence of hepatic artery occlusion on tumor growth and metastatic potential in a human orthotopic hepatoma nude mouse model: relevance of epithelial-mesenchymal transition. Cancer Sci. 2010 Jan;101(1):120-8. doi: 10.1111/j.1349-7006.2009.01363.x. Epub 2009 Sep 14.
- Background: PubMed 11425059Serracino-Inglott F, Habib NA, Mathie RT. Hepatic ischemia-reperfusion injury. Am J Surg. 2001 Feb;181(2):160-6. doi: 10.1016/s0002-9610(00)00573-0.
- Background: PubMed 18044786Man K, Ng KT, Lo CM, Ho JW, Sun BS, Sun CK, Lee TK, Poon RT, Fan ST. Ischemia-reperfusion of small liver remnant promotes liver tumor growth and metastases--activation of cell invasion and migration pathways. Liver Transpl. 2007 Dec;13(12):1669-77. doi: 10.1002/lt.21193.
- Background: PubMed 18044752Ozaki M, Todo S. Surgical stress and tumor behavior: impact of ischemia-reperfusion and hepatic resection on tumor progression. Liver Transpl. 2007 Dec;13(12):1623-6. doi: 10.1002/lt.21230. No abstract available.
- Background: PubMed 28052154Cho JY, Han HS, Choi Y, Yoon YS, Kim S, Choi JK, Jang JS, Kwon SU, Kim H. Association of Remnant Liver Ischemia With Early Recurrence and Poor Survival After Liver Resection in Patients With Hepatocellular Carcinoma. JAMA Surg. 2017 Apr 1;152(4):386-392. doi: 10.1001/jamasurg.2016.5040.
- Background: PubMed 16432356Portolani N, Coniglio A, Ghidoni S, Giovanelli M, Benetti A, Tiberio GA, Giulini SM. Early and late recurrence after liver resection for hepatocellular carcinoma: prognostic and therapeutic implications. Ann Surg. 2006 Feb;243(2):229-35. doi: 10.1097/01.sla.0000197706.21803.a1.
- Derived from this study: PubMed 32619621Theodoraki K, Papadoliopoulou M, Petropoulou Z, Theodosopoulos T, Vassiliu P, Polydorou A, Xanthakos P, Fragulidis G, Smyrniotis V, Arkadopoulos N. Does vascular occlusion in liver resections predispose to recurrence of malignancy in the liver remnant due to ischemia/reperfusion injury? A comparative retrospective cohort study. Int J Surg. 2020 Aug;80:68-73. doi: 10.1016/j.ijsu.2020.06.019. Epub 2020 Jun 30.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kassiani Theodoraki, PhD principal investigator
Aretaieion University Hospital
Questions about this trial
What is this clinical trial studying?
An observational study of Ischemic Reperfusion Injury and Liver Injury, run by Aretaieion University Hospital.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
time to malignant recurrence (time frame: from time of operation until time of malignant recurrence, assessed up to 15 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04257240, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2020.