A Novel Concept for Partial Liver Transplantation in Nonresectable Colorectal Liver Metastases

Line, Pål–Dag; Hagness, Morten; Berstad, A; Foss, Aksel; Dueland, Svein

doi:10.1097/sla.0000000000001165

Cited by 156 publications

(129 citation statements)

References 15 publications

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“…Interestingly, in a principle of partial liver transplantation, necessary regeneration has been demonstrated despite a standard immunosuppressive regimen (Fig. ) . The complete mechanisms behind liver regeneration in humans are unknown, but experimental models reveal that complement seems to have an important role in these complex cellular processes.…”

Section: Complement and Liver Regenerationmentioning

confidence: 99%

The Role of Complement in Liver Injury, Regeneration, and Transplantation

et al. 2019

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The liver is both an immunologically complex and a privileged organ. The innate immune system is a central player, in which the complement system emerges as a pivotal part of liver homeostasis, immune responses, and crosstalk with other effector systems in both innate and adaptive immunity. The liver produces the majority of the complement proteins and is the home of important immune cells such as Kupffer cells. Liver immune responses are delicately tuned between tolerance to many antigens flowing in from the alimentary tract, a tolerance that likely makes the liver less prone to rejection than other solid organ transplants, and reaction to local injury, systemic inflammation, and regeneration. Notably, complement is a double‐edged sword as activation is detrimental by inducing inflammatory tissue damage in, for example, ischemia–reperfusion injury and transplant rejection yet is beneficial for liver tissue regeneration. Therapeutic complement inhibition is rapidly developing for routine clinical treatment of several diseases. In the liver, targeted inhibition of damaged tissue may be a rational and promising approach to avoid further tissue destruction and simultaneously preserve beneficial effects of complement in areas of proliferation. Here, we argue that complement is a key system to manipulate in the liver in several clinical settings, including liver injury and regeneration after major surgery and preservation of the organ during transplantation.

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Section: Complement and Liver Regenerationmentioning

confidence: 99%

The Role of Complement in Liver Injury, Regeneration, and Transplantation

et al. 2019

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“…An attractive option to expand access to transplant is the Resection And Partial Liver Segment 2/3 Transplantation With Delayed Total Hepatectomy (RAPID) protocol . With segments II and III from either a deceased or a living donor, recipients with oncologic conditions and lack of liver cirrhosis can be treated successfully.…”

Section: Critical Appraisalmentioning

confidence: 99%

Con: Liver transplantation for expanded criteria malignant diseases

Schaefer¹,

Zoller²,

Schneeberger

2017

Liver Transpl

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Organ shortage requires policies and guidelines to aid organ allocation along the principles of urgency or utility. Identifying patients with significant benefit and withholding liver transplantation (LT) from patients too sick for transplantation are ongoing challenges, in particular in patients with malignancies. An arbitrary threshold of >50% 5-year overall survival (OS) is broadly considered a minimum standard for LT. In patients transplanted for intrahepatic cholangiocarcinoma (iCC), this was only achieved in select cases and when the tumor had a diameter of <2 cm. In patients with extrahepatic and hilar cholangiocarcinoma (CCC), strict selection criteria and combined preoperative radiotherapy/chemotherapy according to the Mayo protocol showed that acceptable longterm results can be achieved in a single high-volume center but are difficult to repeat elsewhere. Furthermore, only rigorously selected patients with neuroendocrine tumors (NETs) meeting the NET Milan criteria adopted by United Network for Organ Sharing can also have >50% 5-year OS. A prospective study in patients with unresectable colorectal cancer metastases in the liver has shown promising OS rates, but further prospective trials are warranted. Current evidence shows that none of the proposed expanded malignant criteria justify deviation of scarce donor organs to patients with hilar CCC, iCC > 2 cm, metastatic NET beyond NET Milan criteria, or metastatic colorectal cancer (CRC) outside clinical trials.Liver Transplantation 24 104-111 2018 AASLD.Received September 1, 2017; accepted October 4, 2017. Utility of Liver Transplantation for Malignant DiseasesListing, delisting, and allocation policies aim at selecting patients with a projected 5-year survival rate of over 50% and is referred to as rationing. (1) As a result, allocation and distribution policies are not restricted to the best interest of an individual patient. To avoid ethical conflicts and litigations for physicians, treatment guidelines and allocation policies have been introduced by national transplant programs. (2) These recommendations and policies are based on empirical data with the aim to allocate donor livers to patients with the greatest need and best utility to society. (1) Recent reports suggest that selected patients with hepatobiliary malignancies despite advanced tumor stage but favorable tumor biology can have outcomes that are at least equivalent or even better than patients meeting conventional listing criteria. Expanded CriteriaIndividual candidates with tumors exceeding these criteria or with neuroendocrine tumors (NETs) or

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“…Outcomes still need to be improved and validated before potentially justifying a systematic use of liver grafts for this indication on a common waiting list with patients with end-stage liver failure and hepatocellular carcinoma. In the meantime, domino, and living-donor liver grafts should be favored, and the RAPID concept further explored (5). In addition, current transplantation for non-resectable colo-rectal metastasis should be conducted within prospective trials with strict inclusion and exclusion criteria.…”

Section: Liver Transplantationmentioning

confidence: 99%

Liver transplantation for colorectal liver metastasis: Survival without recurrence can be achieved

et al. 2017

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The management of patients with colo-rectal liver metastases has improved significantly over the recent years. However, most patients still cannot undergo complete resection, generally because the location of the metastases within the liver prevents any radical management, and explaining the interest for transplantation. The first attempts were performed in the eighties with poor outcomes, in part due to a high proportion of death not related to the neoplastic disease (1). More recently, the group of Oslo has shown a 60% five-year survival, in 21 patients with colo-rectal metastases (2). Such a survival was better than the one expected on chemotherapy alone (2-4). However, 95% (20/21) of patients had cancer recurrence, most within the first 18 months after transplantation. At present, liver transplantation for colo-rectal metastases remains highly controversial. The potential for long-term disease-free survival needs to be explored, which is the aim of this multi-centric collaborative retrospective study.A total of 12 patients (6 females/6 males) underwent liver transplantation for colo-rectal liver metastasis, at centers affiliated to the "Compagnons Hépato-Bilaires", an association of hepato-pancreato-biliary and transplant surgeons, most trained at the Paul Brousse Hospital, Paris, France under the guidance of Professor H. Bismuth. Median age at transplant was 56 years (Table 1). Patients were managed in Lisbon (n=8), Coimbra (n=2), Paris (n=1), and Geneva (n=1) between October 1995 and October 2015 (date of transplant), and no other patient underwent transplantation for this indication at these respective transplant centers. Data collection was conducted according the relevant ethical standards at each institution. The location of the primary adenocarcinoma was the colon in 11 patients, and the rectum in one. Most primary cancers were T3 on pathology, and many presented between 1 and 3 involved -N1-lymph nodes (two patients were N2 with more than 3 nodes involved, Table 1).For most patients, liver metastases (9/12) were diagnosed within 12 months after the diagnosis of the primary cancer, and were considered as synchronous. When not diagnosed at the same time as the primary, liver metastases were discovered 4, 7, 19, 24 and 29 months after the primary. At the time of transplantation, patients presented a median of 9 liver metastases. Two had lesions >5 cm, of 5.5 and 8 cm. Median CEA level was 16.9 µg/l, and one patients had CEA >200 µg/l, of 314 µg/l.Most (11/12) patients received chemotherapy prior to transplantation. Chemotherapy included irinotecan and oxaliplatin in 9 (82%) patients, and a biological agent in 6 (cetuximab in 2, bevacizumab in 3, and both agents in 1). Another patient was treated by intra-hepatic chemotherapy prior to transplantation. All patients responded to chemotherapy, and none was in progression at the time of the transplantation. The decision to conduct a post-transplant adjuvant chemotherapy was based, at least in the recent years, on the aim to obtain a minimum of four month...

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A Novel Concept for Partial Liver Transplantation in Nonresectable Colorectal Liver Metastases

Abstract: The current protocol and ongoing study could represent a possible strategy to increase the availability of liver transplantation to patients with nonresectable liver tumors such as hepatocellular carcinoma and colorectal liver metastases.

Cited by 156 publications

References 15 publications

The Role of Complement in Liver Injury, Regeneration, and Transplantation

The Role of Complement in Liver Injury, Regeneration, and Transplantation

Con: Liver transplantation for expanded criteria malignant diseases

Liver transplantation for colorectal liver metastasis: Survival without recurrence can be achieved

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