Project description:Surgical resection is the only curative modality for colorectal liver metastases (CLM) and 5-year overall survival after resection is about 40%. Nonresectable CLM is not curable and 5-year overall survival is currently about 10%. Before 1995, several liver transplantations for CLMs were performed, but outcome was poor (5-year survival rate: 18%). Liver transplantation for CLMs was abandoned and CLMs were even considered a contraindication to the procedure. Since then, the survival rate after liver transplantation in general has improved by almost 30%. In a prospective pilot study of liver transplantation for nonresectable CLM, a 5-year overall survival rate of 60% was demonstrated, however 19 of 21 patients experienced recurrence of disease. Here, current knowledge and ongoing research in this field is reviewed, and the potential role for liver transplantation as one of several treatment modalities for CLM discussed.
Project description:BackgroundColorectal cancer is the third most common malignancy worldwide. The occurrence of liver metastases worsens the prognosis of the patient significantly if the tumor burden is not resectable. Liver transplantation might be an option for otherwise irresectable colorectal liver metastases. In this study, we evaluate the role of two-stage hepatectomy in combination with a left-lateral living donor liver transplantation.MethodsPatients with irresectable liver metastases having a stable disease or tumor regression after at least 8 weeks of systemic chemotherapy without an extrahepatic tumor burden (except resectable lung metastases) are suitable for study inclusion. A randomization is not planned since the control arm (systemic chemotherapy) is well established and the superiority of the transplantation procedure has to be expected. The surgical treatment consists of two steps: in a first operation, a left hemihepatectomy in the recipient will be performed. At this place, the left lateral liver lobe (segments II and III) of a living donor will be transplanted. To induce a growth of the graft, a portal vein ligation will be performed. Approximately after 2 weeks, the removal of the right hemiliver will be conducted if the control imaging shows a sufficient growth of the graft.ResultsThe patient recruitment is ongoing. In total, three patients have been already transplanted with this protocol. Up to now, they are tumor-free and in good clinical health.DiscussionWith the design of the LIVER-T(W)O-HEAL study, it might be possible to offer patients with otherwise irresectable colorectal liver metastases a curative treatment option. The key point of this study will be, most probably, the patient's selection.Trial registrationRegistered at Clinical Trials; NCT03488953 ; registered on April 5, 2018.
Project description:Patients with nonresectable liver metastases from colorectal cancer have few therapeutic options and a dismal prognosis. Although liver transplantation for this indication has historically a poor reputation, recent advances in the field of chemotherapy and immunosuppression have paved the way to revisit the concept. New data have shown promising results that need to be validated in several ongoing clinical trials. Since liver grafts represent a scarce resource, several new tools are being explored to expand the donor pool for this indication. The purpose of this review is to present all current available data and perspectives about liver transplantation for nonresectable liver metastases from colorectal cancer.
Project description:We have performed gene expression profiling by exon-resolution microarrays of liver metastases from patients treated by liver transplantation for unresectable metastatic colorectal cancer.
Project description:Up to 50% of colorectal cancer (CRC) patients develop colorectal liver metastases (CRLM). The aim of this study was to gauge the awareness and perception of liver transplantation (LT) for non-resectable CRLM, and to describe the current referral patterns and management strategies for CRLM in Canada. Surgeons who provide care for patients with CRC were invited to an online survey through the Canadian Association of General Surgeons, the Canadian Society of Colon and Rectal Surgeons, and the Canadian Society of Surgical Oncology. Thirty-seven surveys were included. The most utilized management strategy for CRLM was to refer to a hepatobiliary surgeon for assessment of metastectomy (78%), and/or refer to medical oncologists for consideration of chemotherapy (73%). Among the respondents, 84% reported that their level of knowledge about LT for CRLM was low, yet the perception of exploring the option of LT for non-resectable CRLM seemed generally favorable (81%). The decision to refer for consideration of LT for CRLM treatment seemed to depend on patient-specific factors and the local hepatobiliary surgeon's recommendation. Providing CRC care providers with educational materials on up-to-date CRLM management may help raise the awareness of the use of LT for non-resectable CRLM.
Project description:The liver is the most common site of colorectal cancer metastasis. Complete resection of the metastatic tumor is currently the only treatment modality available with a potential for cure. However, only 20% of colorectal liver metastases (CRLM) are considered resectable at the time of presentation. Liver transplantation (LT) has been proposed as an alternative oncologic treatment for patients with unresectable CRLM. This review summarizes the published experiences of LT in the setting of unresectable CRLM from the previous decades and discusses the challenges and future horizons in the field. Contemporary experiences that come mostly from countries with broader access to liver grafts are also explored and their promising findings in terms of overall survival (OS) and disease-free survival (DFS) are outlined along with their study design and methods. The rationale of establishing specific patient selection criteria and the dilemmas around immunosuppressive regimens in patients undergoing LT for CRLM are also highlighted. Additionally, this review describes the findings of studies comparing LT vs chemotherapy alone and LT vs portal vein embolization plus resection for CRLM in terms of OS and DFS. Last but not least, we present current perspectives and ongoing prospective trials that try to elucidate the role of LT for CRLM.
Project description:Colorectal cancer (CRC) is the third most incident cancer worldwide. Most of CRC patients will develop distant metastases, mainly to the liver, and liver resection is the only potential chance for cure. On the other hand, only a small proportion of patients with hepatic CRC metastasis are candidates for upfront liver resection. Liver transplantation (LT) is an attractive option for patients with nonresectable CRC liver metastases (NRCLM) without extrahepatic involvement. Initial experiences with LT for NRCLM achieved very poor outcomes, with a 5-year overall survival (OS) lower than 20%. However, these initial studies did not have a standardized patient selection or neoadjuvant or adjuvant therapies. With recent advances in the surgical and medical oncology fields, the landscape has changed. Recent studies from Norway have shown an encouraging 5-year OS of 50% when transplanting patients with NRCLM. Nevertheless, the main concern when expanding the indications for LT is organ shortage. To manage this organ shortage, strategies utilizing live donor liver transplantation are gaining favor. A few ongoing trials are assessing the impact of LT in NRCLM patient survival. Therefore, the aim of this paper is to review the current status of LT for NRCLM.