Liver Transplantation From Living Donors For Treatment Of Non-Resectable Colorectal Carcinoma Liver Metastases: A Registry Study
Ontology highlight
ABSTRACT:
DISEASE(S): Neoplasm Metastasis,Colorectal Neoplasms,Colorectal Cancer Metastatic,Carcinoma, Hepatocellular
PROVIDER: 2405353 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Patients with unresectable liver metastases (LM) from colorectal cancer (CRC)have a poor prognosis. In patients with resectable disease, surgery offers a distinct survival benefit. This study will offer live donor liver transplantation (LDLT) to select patients with unresectable metastases that are 1) limited to the liver and 2) stable (non-progressing) on standard chemotherapy. Potential participants will be evaluated for liver transplant suitability and must also have a willing, healthy living donor come forward for evaluation. Those participants who undergo LDLT will be followed for survival, disease-free survival and quality of life for 5 years and compared to a "control group" of participants who drop out of study prior to transplantation due to reasons other than cancer progression.
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2020-04-10 | GSE119748 | GEO
Project description:Nearly one third of patients with colorectal cancer develop liver metastases. It is well known that the achievement of a R0-situation is one of the most important factors for a positive long-term outcome. Despite further advantages in multimodal treatment concepts, only 20 - 30 % of the patients with metastases can be resected in curative intention.
Recent studies, especially from Norway, have shown that liver transplantation might be a feasible option in well selected patients since the complete hepatectomy with subsequent liver transplantation can be an option for the achievement of a R0 situation.
In this study, we pursue the strategy of two-stage hepatectomy combined with a left-lateral living donor liver transplantation.
Inclusion criteria are as follows: non-resectable liver metastases of a primary colorectal carcinoma with an assumed portal-venous drainage of the tumor and at least a "stable disease" after a period of eight weeks systemic chemotherapy. Patients are excluded from the study if there is an extrahepatic tumor burden (with the exception of resectable lung metastases) or if the patient is not suitable for liver transplantation due to co-morbidities.
The transplantation itself will be undertaken as a living donor liver transplantation where the left lateral liver lobe (liver segments 2 & 3) from a healthy volunteer donor will serve as graft. Prior transplantation, a left hemihepatectomy in the recipient is performed and the left lateral graft will be transplanted in this position. At the end of the transplantation procedure, the right portal vein will be closed to induce a rapid growth of the graft. The second step, and therefore the completion of the operation is performed after a growth period of the transplanted left-lateral lobe: in this procedure, the right hemi-liver of the recipient will be removed and the patient is supposed to be free of tumor at this point in time.
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Project description:We have studied the genes activated in human liver transplantation to identify potential target genes for the prevention or treatment of related injuries. In a first protocol, in order to evaluate the effect of Ischemia-Reperfusion Injury (IRI) on gene expression profile, we compared gene expression levels in transplanted-reperfused livers versus basal values in donor livers, identifying 795 genes significantly modified in human liver after transplantation. Some genes are likely to be completely activated by IRI, as they are not expressed at all in basal livers. In a second protocol, in order to identify gene dysregulations already present in donor livers, which might affect gene expression profile after transplantation, gene expression evaluated in the first study was compared to control livers (espression data retrieved from ArrayExpress database). About 900 genes in donor livers are dysregulated if compared to the control condition. At least 400 of them remain dysregulated or become more and more dysregulated after transplantation. For the first protocol, two biopsies were collected from each liver: 1 biopsy before explantation from the donor, immediately after opening, before ice was applied, and 1 biopsy about 2-3 hours after liver reperfusion in the recipient organism. Gene expression of 5 transplanted livers was compared to that of 5 donor livers. In the second protocol gene expression both of transplanted and donor livers was compared to gene expression data from 5 control livers retrieved from ArrayExpress repository SAMPLE ID: E-AFMX-11. This dataset is part of the TransQST collection.
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Project description:This study will test the safety and efficacy of living donor liver transplant after standard-of-care chemotherapy for participants with non-resectable liver metastases (LM) from colorectal cancer. 25 donor-recipient pairs will be enrolled (50 participants). Donors will be on study for 2 years and recipients will be on study for up to 5 years.
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Project description:We have studied the genes activated in human liver transplantation to identify potential target genes for the prevention or treatment of related injuries. In a first protocol, in order to evaluate the effect of Ischemia-Reperfusion Injury (IRI) on gene expression profile, we compared gene expression levels in transplanted-reperfused livers versus basal values in donor livers, identifying 795 genes significantly modified in human liver after transplantation. Some genes are likely to be completely activated by IRI, as they are not expressed at all in basal livers. In a second protocol, in order to identify gene dysregulations already present in donor livers, which might affect gene expression profile after transplantation, gene expression evaluated in the first study was compared to control livers (espression data retrieved from ArrayExpress database). About 900 genes in donor livers are dysregulated if compared to the control condition. At least 400 of them remain dysregulated or become more and more dysregulated after transplantation.
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Project description:Liver tissues of 12h after brain death donor liver transplantation and matched non-brain death donor liver transplantation.
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Project description:Brain death donor liver is an important organ source for liver transplantation.The liver injury after brain death donor liver transplantation is serious and the mechanism is unknown.In order to explore the role of lncRNAs and circRNAs expression profile and their biological functions in liver injury after brain death and liver transplantation, lncRNA and mRNA microarray expression profile were tested in the liver after brain death and normal liver transplantation.And this study lays a foundation for future studies on the potential role of lncRNAs in liver injury after brain death donor liver transplantation. To determine the LncRNA expression profile in hepar tissues of 12h after brain death donor liver transplantation and matched non-brain death donor liver transplantation, we uesed LncRNA microArray analysis form Arraystar to examine the expression of LncRNAs and circRNAs in hepar tissues of 12h after brain death donor liver transplantation and matched non-brain death donor liver transplantation.
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Project description:The study aims to evaluate the efficacy of liver transplantation in the context of non-resectable colorectal liver metastasis. The primary endpoint is the overall survival in this group of patients while the secondary endpoint is the disease-free survival.
Patients included in this protocol will be evaluated either for whole or partial liver transplantation from deceased or living donors.
Type of different transplantations proposed are as follows:
1. Whole liver graft or partial liver (split) from a deceased donor
2. Partial liver graft retrieved from a deceased donor and orthotopically implanted after having performed a left hepatectomy in the recipient.
3. Partial liver graft retrieved from a deceased donor and heterotopically implanted if total hepatectomy can not be performed.
4. Partial liver graft retrieved from a living donor and orthotopically implanted after having performed total hepatectomy.
5. Partial liver graft retrieved from a living donor and orthotopically implanted after having after having performed a left hepatectomy in the recipient.
6. Partial liver graft retrieved from a living donor and heterotopically implanted if total hepatectomy can not be performed.
In cases 2-3-5-6 total hepatectomy of native liver can be secondarily performed after having achieved a proper graft hypertrophy in order to avoid a small for size syndrome
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