Living Donor Liver Transplantation for CRC Liver Metastases
Ontology highlight
ABSTRACT:
DISEASE(S): Neoplasm Metastasis,Liver Metastasis Colon Cancer,Liver Neoplasms
PROVIDER: 2399702 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
Similar Datasets
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.
| 2222218 | ecrin-mdr-crc
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.
| 2270149 | ecrin-mdr-crc
Project description:Ischemia-reperfusion injury during liver transplantation is responsible for early allograft dysfunction (EAD) and failure, both of which are associated with a high risk of morbidity and mortality in the recipient. The purpose of this study was to study major transcriptional alterations in livers procured from different types of human liver donors in order to identify genetic profiles predictive of post-implantation function. We have analyzed samples form living donors (LD), donors after cardiac death (DCD), donors after brain death, with subsequent post-implantation EAD in the recipient (DBD-EAD); and donors after brain death without EAD (DBD). Two samples were obtained from each donor: sample A was taken immediately before cold perfusion (baseline) and sample B 2h after portal reperfusion. We identified clear differences in gene expression patterns according to donor source. Both samples A and B from DBD-EAD and DCD demonstrated over-expression of pro-apoptotic and inflammatory transcripts. However, in DBD and LD, expression of these genes was low at baseline and rose only after reperfusion. DBD and LD demonstrated the greatest increase in overall genetic expression after reperfusion when sample B was contrasted with A, indicating less baseline graft injury in these two groups. Grafts from LD were characterized by activation of transcripts related to anti-ischemic and regenerative processes and fewer pro-inflammatory gene transcripts. This transcriptional events occurring in liver allografts could allow for the prediction of post-transplant function. Pro-inflammatory and ischemic transcriptional changes in the grafts are directly related to donor type and may be useful targets for the development of future therapeutic strategies. The complete database comprised the expression for samples taken from 33 liver grafts. Sample A was taken immediately before cold perfusion (baseline) and sample B 2 h after portal reperfusion. Donors were from one of four groups: living (LD); after cardiac death (DCD); after brain death, with subsequent post-implantation EAD in the recipient (DBD-EAD); and after brain death without EAD (DBD). RNA was extracted from the 66 samples and analyzed using Illumina Beadarray technology. A group of 3 samples from healthy volunteers and 3 samples form LD taken at the start of surgery are included as controls or reference samples. This dataset is part of the TransQST collection.
2013-07-01 | E-GEOD-23649 | biostudies-arrayexpress
Project description:Ischemia-reperfusion injury during liver transplantation is responsible for early allograft dysfunction (EAD) and failure, both of which are associated with a high risk of morbidity and mortality in the recipient. The purpose of this study was to study major transcriptional alterations in livers procured from different types of human liver donors in order to identify genetic profiles predictive of post-implantation function. We have analyzed samples form living donors (LD), donors after cardiac death (DCD), donors after brain death, with subsequent post-implantation EAD in the recipient (DBD-EAD); and donors after brain death without EAD (DBD). Two samples were obtained from each donor: sample A was taken immediately before cold perfusion (baseline) and sample B 2h after portal reperfusion. We identified clear differences in gene expression patterns according to donor source. Both samples A and B from DBD-EAD and DCD demonstrated over-expression of pro-apoptotic and inflammatory transcripts. However, in DBD and LD, expression of these genes was low at baseline and rose only after reperfusion. DBD and LD demonstrated the greatest increase in overall genetic expression after reperfusion when sample B was contrasted with A, indicating less baseline graft injury in these two groups. Grafts from LD were characterized by activation of transcripts related to anti-ischemic and regenerative processes and fewer pro-inflammatory gene transcripts. This transcriptional events occurring in liver allografts could allow for the prediction of post-transplant function. Pro-inflammatory and ischemic transcriptional changes in the grafts are directly related to donor type and may be useful targets for the development of future therapeutic strategies.
2013-07-01 | GSE23649 | GEO
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
| 2400483 | ecrin-mdr-crc
Project description:Because of inherent differences between deceased donor (DD) and living donor (LD) liver grafts, we hypothesize that the molecular signatures will be unique, correlating with specific biologic pathways and clinical patterns. Following reperfusion, 579 genes in DD grafts and 1324 genes in LDs were differentially expressed (p<0.005). Many up-regulated LD genes were related to regeneration, biosynthesis and cell cycle, and a large number of down-regulated genes were linked to hepatic metabolism and energy pathways correlating with post-transplant clinical laboratory findings. There was significant up-regulation of inflammatory/immune genes in both DD and LD, each with a distinct pattern. Gene expression patterns of select genes associated with inflammation and regeneration in LD and DD grafts correlated with protein expression. Unique patterns of early gene expression are seen in LD and DD liver grafts, correlating with protein expression and clinical results, demonstrating distinct inflammatory profiles and significant down-regulation of metabolic pathways in LD grafts. Keywords: liver transplantation, live donor transplantation, liver regeneration, microarrays, mRNA expression, reperfusion injury
2009-06-11 | GSE12720 | GEO
Project description:Graft-versus-host disease (GVHD) results from recognition of host antigens by donor T cells following allogeneic hematopoietic cell transplantion (AHCT). Notably, histoincompatibility between donor and recipient is necessary but not sufficient to elicit GVHD. Therefore, we tested the hypothesis that some donors may be “stronger alloresponders” than others, and consequently more likely to elicit GVHD. To this end, we analyzed the gene expression profile of CD4 and CD8 T cells from 50 AHCT donors. We found that pre-AHCT gene expression profiling segregates donors whose recipient suffered from GVHD or not. The “dangerous donor” trait (GVHD+ recipient) is under polygenic control and is shaped by the activity of genes that regulate diverse cell functions including TGF-β signaling and cell proliferation. We also performed gene expression profiling in T cells harvested from 40 AHCT recipients on day 365 post-AHCT. The donor gene profile defined on day 0 showed exceedingly strong correlation with that of recipient CD4 and CD8 T cells harvested one year post-AHCT. These data suggest that donor gene profiles linked with GVHD were largely imprinted at the hematopoietic stem cell level. The ability to discriminate strong and weak alloresponders using gene expression profiling could pave the way to personalized transplantation medicine. Keywords: comparative gene profile, cell type comparaison, GVHD+, GVHD-
2007-03-27 | GSE4624 | GEO
Project description:We analyzed the transcriptomes from 81139 cells from 5 kidney transplant biopsies. We sequenced the germline coding sequence from donor and recipient pairs corresponding to each biopsy as a reference to determine donor host chimerism in each kidney.
2020-07-22 | GSE145927 | GEO
Project description:The clear benefits of ischemic preconditioning (IPC) in reducing ischemia reperfusion injury (IRI) remain indistinct in human liver transplantation. To further understand the mechanistic aspects of IPC in human deceased donor liver transplantation (DDLT), we performed microarray analyses to determine global gene expression profiles associated with IPC administration. Donor and recipient characteristics in both groups were comparable. Clinical data from our study subset and larger trial were similar. IPC increased expression of 10 transcripts at either time point with roles in: antioxidant defenses, immunological response, lipid biosynthesis, and xenobiotic metabolism. IPC decreased the expression of 1 cell development related transcript. Conclusions: 1) IPC in DDLT increased the expression of antioxidant transcripts similar to studies in animal IPC, anesthetic, and remote IPC. 2) IPC increased expression of lipogenic transcripts, which may be relevant to the clinically observed increased IRI in our IPC group. 3) Our microarray findings support our clinical observations and are compatible with the varied outcomes of hepatic IPC studies in human liver transplantation. We conducted a nested sub-study in 12/101 subjects enrolled in a prospective randomized trial of 10 min IPC in DDLT during 2003-2006. Liver biopsies were performed at the end of cold storage and at 90 minutes after allograft reperfusion. Six biopsy pairs from both IPC and No IPC (STD) groups within a narrow donor risk index range were selected. Total RNA was extracted and hybridized with Affymetrix GeneChip Human Gene 1.0 ST Array. IPC effects were examined by comparing IPC vs. STD at both time points. Transcripts whose expression changed 2-fold with p<0.05 were considered significant.
2010-05-20 | E-GEOD-15480 | biostudies-arrayexpress
Project description:Primary graft dysfunction (PGD) continues to be a major cause of early death after lung transplantation. Moreover, there remains a lack of accurate pre-transplant molecular markers for predicting PGD. To identify distinctive gene expression signatures associated with PGD, we profiled human donor lungs using microarray technology prior to the graft implantation. The genomic profiles of 10 donor lung samples from patients who subsequently developed clinically defined severe PGD were compared with 16 case-matched donor lung samples from those who had a favorable outcome without PGD. Matched factors used were: recipient age (± 10 years), recipient gender, recipient lung disease, and type of transplantation (single or bilateral). Keywords: Observational case-control study
2008-09-15 | GSE9102 | GEO