Search

Background: Liver transplantation is an alternative treatment for patients with nonresectable colorectal cancer liver-only metastases (CRLM); however, the potential effects on wait-list time and life expectancy to other patients on the transplant waiting list have not been considered. We explored the potential effects of expanding liver transplantation eligibility to include patients with CRLM on wait-list time and life expectancy in Norway., Methods: We developed a discrete event simulation model to reflect the Norwegian liver transplantation waiting list process and included 2 groups: 1) patients currently eligible for liver transplantation and 2) CRLM patients. Under 2 alternative CRLM-patient transplant eligibility criteria, we simulated 2 strategies: 1) inclusion of only currently eligible patients (CRLM patients received standard-of-care palliative chemotherapy) and 2) expanding waiting list eligibility to include CRLM patients under 2 eligibility criteria. Model outcomes included median waiting list time, life expectancy, and total life-years., Results: For every additional CRLM patient listed per year, the overall median wait-list time, initially 52 d, increased by 8% to 11%. Adding 2 additional CRLM patients under the most restrictive eligibility criteria increased the CRLM patients' average life expectancy by 10.64 y and decreased the average life expectancy for currently eligible patients by 0.05 y. Under these assumptions, there was a net gain of 149.61 life-years over a 10-y programmatic period, which continued to increase under scenarios of adding 10 CRLM patients to the wait-list. Health gains were lower under less restrictive CRLM eligibility criteria. For example, adding 4 additional CRLM patients under the less restrictive eligibility criteria increased the CRLM patients' average life expectancy by 5.64 y and decreased the average life expectancy for currently eligible patients by 0.12 y. Under these assumptions, there was a net gain of 96.36 life-years over a 10-y programmatic period, which continued to increase up to 7 CRLM patients., Conclusions: Our model-based analysis enabled the consideration of the potential effects of enlisting Norwegian CRLM patients for liver transplantation on wait-list time and life expectancy. Enlisting CRLM patients is expected to increase the total health effects, which supports the implementation of liver transplantation for CRLM patients in Norway., Highlights: Given the Norwegian donor liver availability, adding patients with nonresectable colorectal cancer liver-only metastases (CRLM) to the liver transplantation waiting list had an overall modest, but varying, impact on total waiting list time.Survival gains for selected CRLM patients treated with liver transplantation would likely outweigh the losses incurred to patients listed currently.To improve the total life-years gained in the population, Norway should consider expanding the treatment options for CRLM patients to include liver transplantation.Other countries may also have an opportunity to gain total life-years by extending the waiting list eligibility criteria; however, country-specific analyses are required., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. The authors received no financial support for the research, authorship, and/or publication of this article.

Purpose of Review: Liver transplantation has emerged as a possible treatment for selected patients with nonresectable colorectal liver metastasis, but controversy still exists regarding optimal selection criteria and acceptable outcomes., Recent Findings: Univariate analysis in the largest cohorts confirms that metachronous disease, Oslo score = 0-1, metabolic tumor volume (MTV) less than 70 cm 3 , and tumor burden score less than 9 are positive predictive factors for good overall survival outcomes. Some recent trials might suggest that technical resectability is not a valid exclusion criterion for patients with high tumor load and favorable prognostic scores in the transplant evaluation. Recent developments in circulation DNA technology and liquid biopsy may play a future role in the selection and monitoring of patients., Summary: Evaluation for transplant needs multidisciplinary involvement and should not be delayed until the failure of conventional oncological therapy. Larger data sets are needed to refine the selection criteria for liver transplantation in colorectal liver metastasis (CRLM)., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Importance: Liver transplant for colorectal cancer with liver metastases was abandoned in the 1990s due to poor overall survival. From 2006, liver transplant for in nonresectable colorectal liver metastases has been reexamined through different prospective trials., Objective: To determine predictive factors for transplant long-term survival and cure after liver transplant., Design, Setting, and Participants: This was a prospective, nonrandomized controlled cohort study derived from different clinical trials on liver transplant for colorectal liver metastases from 2006 to 2020 at Oslo University Hospital. The trials differed in prognostic inclusion criteria, but the design was otherwise identical regarding follow-up scheme to determine disease recurrence, overall survival, and survival after relapse. Final data analysis was performed on December 31, 2021. All patients with colorectal liver metastases from comparable prospective liver transplant studies were included., Exposure: Liver transplant., Main Outcomes and Measures: Disease-free survival, overall survival, and survival time after recurrence were determined in all participants., Results: A total of 61 patients (median [range] age, 57.8 [28.7-71.1] years; 35 male [57.4%]) underwent liver transplant at Oslo University Hospital. Posttransplant observation time ranged from 16 to 165 months, and no patient was lost to follow-up. Median disease-free period, overall survival, and survival after relapse were 11.8 (95% CI, 9.3-14.2) months, 60.3 (95% CI, 44.3-76.4) months, and 37.1 (95% CI, 4.6-69.5) months, respectively. Negative predictive factors for overall survival included the following: largest tumor size greater than 5.5 cm (median OS, 25.3 months; 95% CI, 15.8-34.8 months; P <.001), progressive disease while receiving chemotherapy (median OS, 39.8 months; 95% CI, 28.8-50.7 months; P = .02), plasma carcinoembryonic antigen values greater than 80 μg/L (median OS, 26.6 months; 95% CI, 22.7-30.6 months; P <.001), liver metabolic tumor volume on positron emission tomography of greater than 70 cm3 (26.6 months; 95% CI, 11.8-41.5 months; P <.001), primary tumor in the ascending colon (17.9 months; 95% CI, 0-37.5 months; P <.001), tumor burden score of 9 or higher (23.3 months; 95% CI, 19.2-27.4 months; P = .02), and 9 or more liver lesions (42.5 months; 95% CI, 17.2-67.8 months; P = .02). An Oslo score of 0 or Fong Clinical Risk Score of 1 yielded 10-year survival of 88.9% and 80.0%, respectively., Conclusions and Relevance: Results of this nonrandomized controlled trial suggest that selected patients with liver-only metastases and favorable pretransplant prognostic scoring had long-term survival comparable with conventional indications for liver transplant, thus providing a potential curative treatment option in patients otherwise offered only palliative care.

Objective: To determine whether liver transplantation (LT) can provide long-term overall survival (OS) in selected patients with nonresectable liver-only colorectal liver metastases (nrCRLM)., Background: In 2005 the first prospective pilot study on LT for nrCRLM was initiated in Norway. We here report long-term data from this study., Methods: Main inclusion criteria were nrCRLM, excised primary tumors, and 6 weeks of chemotherapy. Carcinoembryonic antigen >80 µg/L, progressive disease on chemotherapy, size of largest lesion >5.5 cm, and <2 years from primary tumor resection to LT were previously found to be associated with survival. The sum of these factors constitutes the Oslo Score., Results: From 2006 to 2012, 23 patients underwent LT in the study. In February 2022, the actual 5-year and 10-year OS after LT were 43.5% and 26.1%, respectively. All patients alive were observed for more than 10 years (range: 133-168 months). Four patients were alive without signs of cancer and with no evidence for disease of median of 102 months (53-133 months). A fifth patient died of noncancer cause after 164 months with no evidence for disease for 31 months. For patients with Oslo Score of 0 or 1, the 5-year and 10-year actual OS was 75% and 50%, respectively (n=6). For patients with Oslo Score of 2, the 5-year and 10- year actual OS 50% was 33% (n=6). All patients with Oslo score 3 or 4 were deceased 86 months post-LT (n=9)., Conclusion: LT for nrCRLM can provide long term survival and perhaps cure for selected patients. The OS is excellent compared to oncological treatment options and in line with results from studies on resectable CRLM., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Liver transplantation (LT) for unresectable colorectal liver metastases (CRCLM) demonstrates good overall survival for selected patients in contemporary studies, with 5-year survival of 80%. A Fixed Term Working Group (FTWG), set up by NHS Blood and Transplant (NHSBT) Liver Advisory Group (LAG), advised whether CRCLM should be considered for LT in United Kingdom. Their recommendation was that LT may be undertaken for isolated and unresectable CRCLM using strict selection criteria as a national clinical service evaluation., Methods: Opinions were sought from colorectal cancer/LT patient representatives, experts in colorectal cancer surgery/oncology, LT surgery, hepatology, hepatobiliary radiology, pathology, and nuclear medicine, and appropriate patient selection criteria, referral and transplant listing pathways were identified., Results: This paper summarises selection criteria for LT in United Kingdom for isolated and unresectable CRCLM patients, and highlights referral framework and pre-transplant assessment criteria. Finally, oncology-specific outcome measures to be utilised for assessing applicability of LT are described., Conclusion: This service evaluation represents a significant development for colorectal cancer patients in United Kingdom and a meaningful step forward in the field of transplant oncology. This paper details the protocol for the pilot study, scheduled to begin in the fourth quarter of 2022 in United Kingdom., Competing Interests: Conflict of interest None to declare., (Copyright © 2023 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: In patients with neuroendocrine liver metastasis (NELM), liver transplantation (LT) is an alternative to liver resection (LR), although the choice of therapy remains controversial. In this multicenter study, we aim to provide novel insight in this dispute., Methods: Following a systematic literature search, 15 large international centers were contacted to provide comprehensive data on their patients after LR or LT for NELM. Survival analyses were performed with the Kaplan-Meier method, while multivariable Cox regression served to identify factors influencing survival after either transplantation or resection. Inverse probability weighting and propensity score matching was used for analyses with balanced and equalized baseline characteristics., Results: Overall, 455 patients were analyzed, including 230 after LR and 225 after LT, with a median follow-up of 97 months [95% confidence interval (CI): 85-110 months]. Multivariable analysis revealed G3 grading as a negative prognostic factor for LR [hazard ratio (HR)=2.22, 95% CI: 1.04-4.77, P =0.040], while G2 grading (HR=2.52, 95% CI: 1.15-5.52, P =0.021) and LT outside Milan criteria (HR=2.40, 95% CI: 1.16-4.92, P =0.018) were negative prognostic factors in transplanted patients. Inverse probability-weighted multivariate analyses revealed a distinct survival benefit after LT. Matched patients presented a median overall survival (OS) of 197 months (95% CI: 143-not reached) and a 73% 5-year OS after LT, and 119 months (95% CI: 74-133 months) and a 52.8% 5-year OS after LR (HR=0.59, 95% CI: 0.3-0.9, P =0.022). However, the survival benefit after LT was lost if patients were transplanted outside Milan criteria., Conclusions: This multicentric study in patients with NELM demonstrates a survival benefit of LT over LR. This benefit depends on adherence to selection criteria, in particular low-grade tumor biology and Milan criteria, and must be balanced against potential risks of LT., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To report 15 years of experience with metabolic tumor volume (MTV) of liver metastases from the preoperative 18 F-FDG PET/CT to predict long-term survival after liver transplantation (LT) for unresectable colorectal liver metastases (CRLM)., Methods: The preoperative 18 F-FDG PET/CT from all SECA 1 and 2 patients was evaluated. MTV was obtained from all liver metastases. The patients were divided into one group with low MTV (< 70 cm 3 ) and one group with high MTV (> 70 cm 3 ) based on a receiver operating characteristic analysis. Overall survival (OS), disease-free survival (DFS) and post recurrence survival (PRS) for patients with low versus high MTV were compared using the Kaplan-Meier method and log rank test. Clinopathological features between the two groups were compared by a nonparametric Mann-Whitney U test for continuous and Fishers exact test for categorical data., Results: At total of 40 patients were included. Patients with low MTV had significantly longer OS (p < 0.001), DFS (p < 0.001) and PRS (p = 0.006) compared to patients with high values. The patients with high MTV had higher CEA levels, number of liver metastases, size of the largest liver metastasis, N-stage, number of chemotherapy lines and more frequently progression of disease at LT compared to the patients with low MTV., Conclusion: MTV of liver metastases is highly predictive of long-term OS, DFS and PRS after LT for unresectable CRLM and should be implemented in risk stratification prior to LT., (© 2022. The Author(s).)

Purpose of Review: Liver transplantation for nonresectable colorectal liver metastases (CRLMs) is an emerging field within transplant oncology. This review summarizes recent developments within this field., Recent Findings: More stringent selection criteria can yield 5-year survival rates that are similar to conventional indications for liver transplantation. Response to chemotherapy, low carcinoembryonic antigen levels, limited tumor volume and stable disease with observation time exceeding 12 months are fundamental requirements in this context. Radiomic analysis of pre transplant PET/computed tomography scans to determine metabolic tumor volume (MTV) in the liver seems particularly promising with regards to prediction of a favorable tumor biology. MTV values below 70 cm3 are associated with excellent long-term survival after transplantation, whereas the MTV threshold for liver resection seem far smaller. Recent studies put into question whether technical nonresectability per se is a valid inclusion criterion for liver transplantation. In patients with high hepatic tumor burden, but otherwise favorable prognostic features as assessed by the Oslo score, liver transplantation could possibly give a clinically relevant survival benefit compared with liver resection., Summary: Liver transplantation is feasible treatment option in highly selected patients with nonresectable CRLMs. Robust and stringent selection criteria should be applied according to international consensus guidelines., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Many patients undergoing resection for colorectal liver metastases (CRLM) recur with poor survival. Overall survival (OS) following liver transplantation (LT) for CRLM is reported to be about 80% at 5 years. In this study, survival following resection versus transplantation for CRLM in patients with moderate (6-70 cm 3 ) metabolic tumor volume (MTV) from the preoperative positron emission tomography (PET) was compared., Methods: Disease-free survival (DFS), OS and post recurrence survival (PRS) following resection (n = 18) and LT (n = 12) was compared by using the Kaplan Meier method and log rank test for patients with moderate MTV., Results: Patients undergoing LT had unresectable metastases, significantly lower age, higher tumor burden score and number of liver metastases, longer time from diagnosis to surgery, and more patients received neoadjuvant chemotherapy. OS at 5 years was 39% in the resection group and 83% in the LT group (P = 0.012). PRS was significantly improved in patients treated with LT compared to resection with 71% alive at 5 years from recurrence compared to 17% in the resection group (P = 0.017)., Conclusion: LT for selected patients seems to be superior to resection as treatment for CRLM for patients with moderate MTV., (Copyright © 2021 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Liver transplantation (LTX) has been described as a rescue treatment option in severe, intractable post-hepatectomy liver failure (PHLF), but is not considered to be indicated for this condition by many hepatobiliary and transplant surgeons. In this article we describe the clinical experience of five northern European tertiary centers in using LTX to treat selected patients with severe PHLF., Methods: All patients subjected to LTX due to PHLF at the participating centers were identified from prospective clinical databases. Preoperative variables, surgical outcome (both resection surgery and LTX) and follow-up data were assessed., Results: A total of 10 patients treated with LTX due to severe PHLF from September 2008 to May 2020 were identified and included in the study. All patients but one were male and the median age was 70 years (range 49-72). In all patients the indication for liver resection was suspected malignancy, but in six patients post-resection pathology revealed benign or pre-malignant disease. There was no 90-day mortality after LTX. Patients were followed for a median of 49 months (13-153) and eight patients were alive without recurrence at last follow-up., Discussion: In selected patients with PHLF LTX can be a life-saving procedure with low short-term risk., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Liver transplantation (LT) for patients with non-resectable colorectal liver metastases (CRLM) offers improved survival and has gained increased interest internationally the last years. The aim of this study was to describe the health-related quality of life (HRQoL) in patients with non-resectable CRLM receiving LT and how baseline HRQoL factors affect overall survival (OS). HRQoL data in the SECA (SEcondary CAncer) LT cohort was compared to data obtained from colorectal cancer patients starting first-line chemotherapy for metastatic disease in a clinical trial and data from a Norwegian normal population. HRQoL data from the QLQ-C30 questionnaire used in the SECA LT study and the NORDIC- VII study were reported. The relationship between patient-reported symptom burden at baseline and OS was investigated. In the SECA study longitudinal HRQoL assessment was used to describe the time until definitive deterioration as well as mean values at different time points. Patients in the SECA and NORDIC-VII studies reported similar baseline HRQoL. The median time until definitive deterioration in the transplanted patients was estimated to 36 months. In the SECA study appetite loss and pain at baseline had negative impact on OS (25.3 versus 71.7 months, p = 0.002 and 39.7 versus 71.7 months, p = 0.038, respectively). Despite a relapse in most of the LT patients the Global Health Score (GHS) remained good. Pain, and especially appetite loss at time of transplantation is associated with poor outcome after LT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Smedman, Guren, Tveit, Thomsen, Andersen, Line and Dueland.)

Liver transplant in patients with prior nonhepatic cancer is a matter of concern, needing further research, development, and consensus guidelines. This International Liver Transplantation Society/Sociedad Española De Trasplante Hepático consensus conference document focuses on the role of liver transplantation in patients with a prior history of nonhepatic cancer. This document addresses (1) the evaluation of transplant candidates with prior cancers based on the assessment of prognosis, the natural history of individual cancers, and the emerging role for circulating DNA and minimal residual disease in these patients; (2) the impact of prior treatments, including immunotherapy for prior malignancies; and (3) the surveillance of posttransplant cancer recurrence. The consensus statement is based on previously published guidelines, as well as a review of the current, relevant, published literature., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Liver transplantation (LT) in selected colorectal cancer (CRC) patients with nonresectable liver-only metastases may result in 5-year overall survival of up to about 70-100%. However, the majority will have recurrent disease. All patients included in this report were included in prospective studies. Forty-four out of 56 patients had a relapse, and all 44 patients received treatment for recurrent disease. The organ of the first relapse was lung metastases in 23 of the 44 patients. The first treatment modality of the relapse was the treatment with curative intent in 55.8% of the patients, and chemotherapy was the first treatment administered to 25.6% of the patients. Patients receiving surgery of lung metastases had a 5-year overall survival of 66.5% from the time of metastasectomy. Patients receiving treatment with curative intent for metastases to other organs had a 5-year overall survival of 24.8%. Nine of the 44 patients had no evidence of disease (NED) at the end of the follow-up. Median time of NED in these patients was 54.3 months, and median overall survival from the time of LT was 8.4 years. Because of the high incidence of recurrent disease, these patients should have a systematic long-term follow-up since many of the relapses may be treated with curative intent., (© 2021 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)

Colorectal cancer is a prevalent disease worldwide, with more than 50% of patients developing metastases to the liver. Despite advances in improving resectability, most patients present with non-resectable colorectal liver metastases requiring palliative systemic therapy and locoregional disease control strategies. There is a growing interest in the use of liver transplantation to treat non-resectable colorectal liver metastases in well selected patients, leading to a surge in the number of studies and prospective trials worldwide, thereby fuelling the emerging field of transplant oncology. The interdisciplinary nature of this field requires domain-specific evidence and expertise to be drawn from multiple clinical specialities and the basic sciences. Importantly, the wider societal implication of liver transplantation for non-resectable colorectal liver metastases, such as the effect on the allocation of resources and national transplant waitlists, should be considered. To address the urgent need for a consensus approach, the International Hepato-Pancreato-Biliary Association commissioned the Liver Transplantation for Colorectal liver Metastases 2021 working group, consisting of international leaders in the areas of hepatobiliary surgery, colorectal oncology, liver transplantation, hepatology, and bioethics. The aim of this study was to standardise nomenclature and define management principles in five key domains: patient selection, evaluation of biological behaviour, graft selection, recipient considerations, and outcomes. An extensive literature review was done within the five domains identified. Between November, 2020, and January, 2021, a three-step modified Delphi consensus process was undertaken by the workgroup, who were further subgrouped into the Scientific Committee, Expert Panel, and Transplant Centre Representatives. A final consensus of 44 statements, standardised nomenclature, and a practical management algorithm is presented. Specific criteria for clinico-patho-radiological assessments with molecular profiling is crucial in this setting. After this, the careful evaluation of biological behaviour with bridging therapy to transplantation with an appropriate assessment of the response is required. The sequencing of treatment in synchronous metastatic disease requires special consideration and is highlighted here. Some ethical dilemmas within organ allocation for malignant indications are discussed and the role for extended criteria grafts, living donor transplantation, and machine perfusion technologies for non-resectable colorectal liver metastases are reviewed. Appropriate immunosuppressive regimens and strategies for the follow-up and treatment of recurrent disease are proposed. This consensus guideline provides a framework by which liver transplantation for non-resectable colorectal liver metastases might be safely instituted and is a meaningful step towards future evidenced-based practice for better patient selection and organ allocation to improve the survival for patients with this disease., Competing Interests: Declaration of interests PT receives honoraria from Astellas Pharma Europe, outside the current study. GS receives research grants from Bayer and Roche, and consulting fees from Astrazeneca, Novartis, and Roche, outside the current study. RA receives honoraria for symposia from Merck Serono and Sanofi, outside the current study. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Liver transplantation (LT) for colorectal liver metastasis (CRLM) may provide excellent survival rates in patients with unresectable disease. High tumor load is a risk factor for recurrence and low overall survival (OS) after liver resection (LR). We tested the hypothesis that LT could offer better survival than LR in patients with high tumor load. LR performed at Padua University Hospital for CRLM was compared with LT for unresectable CRLM performed both at Oslo and Padua. High tumor load was defined as tumor burden score (TBS) ≥ 9, and inclusion criteria were as in the SECA-I transplant study. 184 patients were eligible: 128 LRs and 56 LTs. 5-year OS after LR and LT was 40.5% and 54.7% (P = 0.102). In the high TBS cohort, 5-year OS after LR and LT was 22.7% and 52.2% (P = 0.055). In patients with Oslo score ≤ 2 and TBS ≥ 9 (13 LR; 24 LT) the 5-year OS after LR and LT was 14.6% and 69.1% (P = 0.002). The corresponding disease-free survival (DFS) was 0% and 22.9% (P = 0.005). Selected CRLM patients with low Oslo score and high TBS could benefit from LT with survival outcomes that are far better than what is achieved by LR., (© 2021 The Authors. Transplant International published by John Wiley & Sons Ltd on behalf of Steunstichting ESOT.)

Importance: Portal vein embolization (PVE) has been implemented in patients with extensive colorectal liver metastases to increase the number of patients able to undergo liver resection. Liver transplant could be an alternative in selected patients with extensive liver-only disease, and we have recently shown promising survival outcomes., Objective: To compare overall survival (OS) among patients with colorectal cancer and high liver metastasis tumor load who were treated with liver transplant or with PVE and liver resection., Design, Setting, and Participants: This comparative effectiveness research study assessed 50 patients with colorectal cancer liver metastases who were previously enrolled in liver transplant studies between November 2006 and August 2019 at Oslo University Hospital in Norway. Those patients were compared with a retrospective cohort of 53 patients in the Oslo University Hospital PVE database from March 2006 through November 2015 with similar selection criteria who underwent PVE and liver resection., Main Outcomes and Measures: The OS among patients with high tumor load after liver transplant was compared with that among patients with high tumor load who underwent PVE and liver resection. High tumor load was defined as 9 or more metastatic tumors or a diameter of 5.5 cm or longer for the largest liver lesion., Results: In the PVE cohort of 53 patients, the median age was 61.8 years (range, 34.3-71.3 years), and 36 patients (68%) were men. The 5-year OS rate among 38 patients who underwent liver resection after PVE was 44.6%. The 5-year OS rate for patients with high tumor load was 33.4% for those who underwent liver transplant and 6.7% for those who underwent PVE. Among patients with high tumor load and left-sided primary tumors, the 5-year OS rate was 45.3% for those receiving a liver allograft and 12.5% for those treated with PVE and liver resection., Conclusions and Relevance: Patients with nonresectable disease, an extensive liver tumor load, and left-sided primary tumors had long OS after liver transplant, exceeding the survival outcome for those patients treated with PVE and liver resection.

Assessing the balance between survival and recurrence after transplantation for secondary liver tumours should be based on the type of cancer in question. For neuroendocrine liver metastases, high recurrence rates are clearly related to reduced long-term survival. For colorectal liver metastases, experience to date indicates that pulmonary recurrence alone has a modest impact on survival outcomes. Further studies focusing on this group of patients will be important for the development of this field of transplant oncology. Liver transplantation for secondary liver tumours should be implemented in accordance with stringent transplant criteria and preferably in the context of prospective trials. Expansion of the donor pool by utilising extended criteria donors and partial liver transplantation could be considered for this indication., Competing Interests: Conflicts of interest Dr. Line and Dr. Dueland declare no conflicts of interest. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Objective: To test the degree of agreement in selecting therapeutic options for patients suffering from colorectal liver metastasis (CRLM) among surgical experts around the globe., Summary/background: Only few areas in medicine have seen so many novel therapeutic options over the past decades as for liver tumors. Significant variations may therefore exist regarding the choices of treatment, even among experts, which may confuse both the medical community and patients., Methods: Ten cases of CRLM with different levels of complexity were presented to 43 expert liver surgeons from 23 countries and 4 continents. Experts were defined as experienced surgeons with academic contributions to the field of liver tumors. Experts provided information on their medical education and current practice in liver surgery and transplantation. Using an online platform, they chose their strategy in treating each case from defined multiple choices with added comments. Inter-rater agreement among experts and cases was calculated using free-marginal multirater kappa methodology. A similar, but adjusted survey was presented to 60 general surgeons from Asia, Europe, and North America to test their attitude in treating or referring complex patients to expert centers., Results: Thirty-eight (88%) experts completed the evaluation. Most of them are in leading positions (92%) with a median clinical experience of 25 years. Agreement on therapeutic strategies among them was none to minimal in more than half of the cases with kappa varying from 0.00 to 0.39. Many general surgeons may not refer the complex cases to expert centers, including in Europe, where they also engage in complex liver surgeries., Conclusions: Considerable inconsistencies of decision-making exist among expert surgeons when choosing a therapeutic strategy for CRLM. This might confuse both patients and referring physicians and indicate that an international high-level consensus statements and widely accepted guidelines are needed.

Background: The resection and partial liver segment II/III transplantation with delayed total hepatectomy (RAPID) concept is a novel transplantation technique for removal of non-resectable liver tumours. The aim of this study was to establish a simulated RAPID model to explore the mechanism involved in the liver regeneration., Methods: A RAPID model was created in rats involving cold ischaemia and reperfusion of the selected future liver remnant (FLR), portal vein ligation, followed by resection of the deportalized lobes in a second step. Histology, liver regeneration and inflammatory markers in RAPID-treated rats were compared with those in controls that underwent 70 per cent hepatectomy with the same FLR size. The effects of interleukin (IL) 6 and macrophage polarization on hepatocyte viability were evaluated in an in vitro co-culture system of macrophages and BRL hepatocytes., Results: The survival rate in RAPID and control hepatectomy groups was 100 per cent. The regeneration rate was higher in the RAPID-treated rats, with higher levels of IL-6 and M1 macrophage polarization (P < 0·050). BRL hepatocytes co-cultured with M1 macrophages showed a higher proliferation rate through activation of the IL-6/signal transducer and activator of transcription 3/extracellular signal-regulated kinase pathway. This enhancement of proliferation was inhibited by tocilizumab or gadolinium trichloride (P < 0·050)., Conclusion: The surgical model provides a simulation of RAPID that can be used to study the liver regeneration profile. Surgical Relevance The mechanisms sustaining liver regeneration are a relevant field of research to reduce the 'small for size' liver syndrome when the future liver remnant is not adequate. Several surgical strategies have been introduced both for liver resection and transplant surgery, mostly related to this issue and to the scarcity of grafts, among these the RAPID concept involving the use of an auxiliary segment II/III donor liver that expands to a sufficient size until a safe second-stage hepatectomy can be performed. Understanding the mechanisms and pitfalls of the liver regeneration profile may help in tailoring surgical strategies and in selecting patients. In this experimental model the authors investigated liver histology, regeneration and inflammatory markers in RAPID-treated rats., (© 2020 The Authors. BJS Open published by John Wiley & Sons Ltd on behalf of British Journal of Surgery Society.)

Background: Patients with metastatic colorectal cancer receiving palliative chemotherapy have a 5-year survival rate of approximately 10 per cent. Liver transplantation using strict selection criteria in patients with colorectal cancer and unresectable liver-only disease will result in a 5-year survival rate of 56-83 per cent. The aim of this study was to evaluate survival of patients with colorectal liver metastases (CRLM) after liver transplantation using extended criteria for both patients and donors., Methods: This was a prospective single-arm study. Patients with synchronous unresectable CRLM who were not suitable for arms A, B or C of the SEcondary CAncer (SECA) II study who had undergone radical resection of the primary tumour and received chemotherapy were included; they underwent liver transplantation with extended criteria donor grafts. Patients who had resectable pulmonary metastases were eligible for inclusion. The main exclusion criteria were BMI above 30 kg/m 2 and liver metastases larger than 10 cm. Survival was estimated using Kaplan-Meier analysis., Results: Ten patients (median age 54 years; 3 women) were included. They had an extensive liver tumour load with a median of 20 (range 1-45) lesions; the median size of the largest lesion was 59 (range 15-94) mm. Eight patients had (y)pN2 disease, six had poorly differentiated or signet ring cell-differentiated primary tumours, and five had primary tumour in the ascending colon. The median Fong clinical risk score was 3 (range 2-5) and the median Oslo score was 1 (range 1-4). The median plasma carcinoembryonic antigen level was 4·3 (range 2-4346) μg/l. Median disease-free and overall survival was 4 and 18 months respectively., Conclusion: Patients with unresectable liver-only CRLM undergoing liver transplantation with extended patient and donor criteria have relatively short overall survival., (© 2020 The Authors. BJS Open published by John Wiley & Sons Ltd on behalf of British Journal of Surgery Society.)

Liver transplantation (LT) for unresectable colorectal liver metastases has long been abandoned because of dismal prognoses. After the dark ages, advances in chemotherapy and diagnostic imaging have enabled strict patient selection, and the pioneering study from the Oslo group has contributed to the substantial progress in this field. For unresectable neuroendocrine liver metastases, LT for patients who met the Milan criteria was able to achieve excellent long-term outcomes. The guidelines further adopted in the United States and Europe were based on these criteria. For hepatoblastoma, patients with unresectable and borderline-resectable disease are considered good candidates for LT; however, the indications are yet to be defined. In the budding era of transplant oncology, it is critically important to recognize the current status and unsolved questions for each disease entity. These guidelines were developed to serve as a beacon of light for optimal patient selection for LT and set the stage for future basic and clinical studies.

Objective: To determine overall survival and disease-free survival in selected patients with nonresectable liver-only colorectal cancer receiving liver transplantation., Background: Patients with nonresectable colorectal cancer receiving palliative chemotherapy has a 5-year overall survival of about 10%. Liver transplantation provided an overall survival of 60% in a previous study (SECA-I). Risk factors for death were carcinoembryonic antigen (CEA) >80 μg/L, progressive disease on chemotherapy, size of largest lesion>5.5 cm, and less than 2 years from resection of the primary tumor to transplantation., Methods: In this prospective (SECA-II) study, we included colorectal cancer patients with nonresectable liver-only metastases determined by computed tomography (CT)/magnetic resonance imaging/positron emission tomography scans and at least 10% response to chemotherapy. Time from diagnosis to liver transplant was required to be more than 1 year., Results: At a median follow-up of 36 months, Kaplan-Meier overall survival at 1, 3, and 5 years were 100%, 83%, and 83%, respectively. Disease-free survival at 1, 2, and 3 years were 53%, 44%, and 35%, respectively. Overall survival from time of relapse at 1, 2, and 4 years were 100%, 73%, and 73%, respectively. Recurrence was mainly slow growing pulmonary metastases amenable to curative resection. Fong Clinical Risk Score of 1 to 2 at the time of diagnosis resulted in longer disease-free survival than score 3 to 4 (P = 0.044). Patients included in the present study had significantly better prognostic factors than the previous SECA-I study., Conclusion: Liver transplantation provides the longest overall survival reported in colorectal cancer patient with nonresectable liver metastases. Improved selection criteria give patients with nonresectable colorectal liver metastases a 5-year overall survival comparable to other indications for liver transplantation.

Patients with nonresectable colorectal cancer receiving palliative chemotherapy have a 5-year overall survival rate of about 10%. Liver transplant provided a Kaplan-Meier-estimated 5-year overall survival of up to 83%. The objective of the study was to evaluate the ability of different scoring systems to predict long-term overall survival after liver transplant. Patients with colorectal cancer with nonresectable liver-only metastases determined by computed tomography (CT)/magnetic resonance imaging/positron emission tomography (PET)-CT scans from 2 prospective studies (SECA-I and -II) were included. All included patients had previously received chemotherapy. PET-CT was performed within 90 days of the liver transplant. Overall survival, disease-free survival, and survival after relapse based on the Fong Clinical Risk Score, total PET liver uptake (metabolic tumor volume), and Oslo Score were compared. At median follow-up of 85 months for live patients, Kaplan-Meier overall survival rates at 5 years were 100%, 78%, and 67% in patients with Fong Clinical Risk Score 0 to 2, metabolic tumor volume-low group, and Oslo Score 0 to 2, respectively. Median overall survival was 101, 68, and 65 months in patients with Fong Clinical Risk Score 0 to 2, metabolic tumor volume-low, and Oslo Score 0 to 2. These selection criteria may be used to obtain 5-year overall survival rates comparable to other indications for liver transplant., (© 2019 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)

Solid organ recipients have a 2-5 fold increased risk of malignancy compared to the general population. Because of the broader indications for transplantation, it is anticipated that an increasing number of organ graft recipients will present with malignancy. There are limited data about responses and tolerance to chemotherapy in solid organ transplanted patients. Twenty-three of 46 colorectal cancer (CRC) patients with nonresectable liver metastases who had undergone liver transplantation (LT) in three different studies were included. All patients had received chemotherapy both prior to LT and after LT, at recurrence of metastatic CRC (mCRC). Adverse reactions (grades 3-4) and clinical and radiological outcome were retrospectively registered. Overall survival was determined from start of palliative chemotherapy after LT. No graft rejection was observed. Chemotherapy for mCRC was overall well-tolerated and there was no increased bone marrow toxicity registered after LT; however, mucositis and diarrhea were more frequent in post-LT chemotherapy. Median overall survival from start of palliative chemotherapy after LT was 13 months. No graft loss was observed when chemotherapy for mCRC was given to LT recipients who had developed nonresectable metastases. Overall, the chemotherapy for mCRC was well-tolerated, induced responses, and long-term survival was obtained in some patients., (© 2019 The Authors. Transplant International published by John Wiley & Sons Ltd on behalf of Steunstichting ESOT.)

Background: Treatment outcome for hepatocellular carcinoma (HCC) is related to tumor burden and liver function. Grading systems assessing liver function need validation in different clinical settings., Purpose: To evaluate drug-eluting embolic transarterial chemoembolization (DEE-TACE) in Child-Pugh A HCC with respect to albumin-bilirubin (ALBI) and platelet-albumin-bilirubin (P-ALBI) grade., Material and Methods: Forty-nine patients with Child-Pugh class A, diagnosed with HCC and allocated to DEE-TACE treatment, were retrospectively analyzed regarding tumor and treatment characteristics, radiological response (mRECIST) one month post treatment, overall survival (OS), and adverse events (AEs; CTCAE, grades ≥3) with respect to ALBI and P-ALBI grade., Results: There were 21 ALBI 1 patients, 29 P-ALBI 1 patients, and 19 patients were both ALBI and P-ALBI 1. Objective response rate was 74% with no statistically significant difference for ALBI (1 vs. 2; P = 0.08), or P-ALBI (1 vs. 2; P = 0.49). OS was 14.8 months (range = 1.7-62.0; ALBI 1 vs. 2: P = 0.08; P-ALBI 1 vs. 2: P = 0.003). OS in responders with ALBI 1 and 2 was 28.9 vs.10.2 months ( P = 0.02), and P-ALBI 1 and 2 was 26.7 vs. 8.6 months ( P < 0.001). In multivariate analyses, both ALBI 2 (HR = 2.4, P = 0.02) and P-ALBI 2 (HR = 3.3, P < 0.01) were negative prognostic factors for survival. There were 15 AEs in 13 patients, with hepatic failure only occurring in ALBI 2 and P-ALBI 2 patients., Conclusion: P-ALBI grade 1 and 2 differentiated survival in Child-Pugh A patients treated with DEE-TACE. Both grading systems can differentiate survival in patients responding to treatment.

Background: The ERBB2 oncogene hypothesis is challenged in hepatocellular carcinoma (HCC) with the conflicting evidences of human epidermal growth factor receptor 2 (HER2) overexpression. HER2 could be a new target as a treatment option for HCC as well as tumor recurrence after surgery. HER2 in HCC biology needs further explorations., Methods: Clinical and mRNA data of HCC patients were obtained from TCGA HCC cohort, GSE89377 and GSE115018. Western Blotting and immunohistochemistry were employed to test expression of HER2, E-cadherin, and Vimentin. In HepG2, JM1, HER2-transfected McA cells, and TGF-β cocultured JM1 cells, HCC biology, including cell survival, proliferation, and epithelial-to-mesenchymal transition (EMT) phenotypes were evaluated., Results: ERBB2 mRNA amplification was found in HCC datasets, and its expression was downregulated in high grade HCC with a worse overall survival. HER2 overexpression was identified in H4IIE, HepG2, JM1 cells, and 82% (14/17) HCC samples, and tumor stage was correlated with expression of HER2, E-cadherin, and Vimentin (P < 0.05). Trastuzumab with the high concentrations suppressed proliferation of HER2-positive hepatoma cells (P < 0.05); in the coculture model to induce EMT of JM1 cells, HER2 expression increased with downregulated E-cadherin and upregulated Vimentin. Trastuzumab intravenous injection inhibited in vivo tumor size and metastases (P < 0.05). Signal analysis revealed that HER2 functioned through upregulation of β-catenin and inhibition of SMAD3., Conclusion: HER2 expression pattern is linked with tumor stage and overall survival; the transforming function of HER2 is found more relevant through β-catenin and SMAD3. HER2-targeted treatment is recommended to suppress the HER2-mediated tumor growth during postoperative liver regeneration., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Patients with non-resectable colorectal metastases are currently treated with chemotherapy. However, liver transplantation can increase the 5-year survival rate from 9 to 56 per cent if the cancer is confined to the liver. The aim of this study was to estimate the cost-effectiveness of liver transplantation for colorectal liver metastases., Methods: A Markov model with a lifetime perspective was developed to estimate the life-years, quality-adjusted life-years (QALYs), direct healthcare costs and cost-effectiveness for patients with non-resectable colorectal liver metastases who received liver transplantation or chemotherapy alone., Results: In non-selected cohorts, liver transplantation increased patients' life expectancy by 3·12 life-years (2·47 QALYs), at an additional cost of €209 143, giving an incremental cost-effectiveness ratio (ICER) of €67 140 per life-year (€84 667 per QALY) gained. In selected cohorts (selection based on tumour diameter, time since primary cancer, carcinoembryonic antigen levels and response to chemotherapy), the effect of liver transplantation increased to 4·23 life-years (3·41 QALYs), at a higher additional cost (€230 282), and the ICER decreased to €54 467 per life-year (€67 509 per QALY) gained. Given a willingness to pay of €70 500, the likelihood of transplantation being cost-effective was 0·66 and 0·94 (0·23 and 0·67 QALYs) for non-selected and selected cohorts respectively., Conclusion: Liver transplantation was cost-effective but only for highly selected patients. This might be possible in countries with good access to grafts and low waiting list mortality., (© 2018 BJS Society Ltd Published by John Wiley & Sons Ltd.)

The purpose of this registry study was to provide an overview of trends and results of liver transplantation (LT) in Europe from 1968 to 2016. These data on LT were collected prospectively from 169 centers from 32 countries, in the European Liver Transplant Registry (ELTR) beginning in 1968. This overview provides epidemiological data, as well as information on evolution of techniques, and outcomes in LT in Europe over more than five decades; something that cannot be obtained from only a single center experience., (© 2018 Steunstichting ESOT.)

Background: Liver transplantation for patients with non-resectable colorectal liver metastases offers increased survival, with median overall survival of more than 5 years. The aim of this study was to compare quality of life before and up to 3 years after liver transplantation for colorectal liver metastases., Methods: Quality of life was assessed using the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire version 3.0. The patients received the questionnaire before and up to 3 years after liver transplantation., Results: Some 23 patients were included in the analysis. Three months after liver transplantation they reported reduced quality of life (global health status scale), physical function and role function, and increased dyspnoea. At 6 months, global health status, physical function and role function had returned to pretransplant values. Three years after liver transplantation all symptom and function scores were comparable to baseline values. Patients with high scores for fatigue, pain and appetite loss at baseline had reduced 3-year overall survival., Conclusion: Patients with non-resectable colorectal liver-only metastases receiving liver transplantation had good long-term quality of life. Patients with high symptom scores before transplantation had reduced 3-year overall survival.

Objective: The aim of this study was to evaluate fluorine-18-fluorodeoxyglucose (F-FDG) PET/CT for the selection of patients with nonresectable colorectal liver metastases (NCLM) for liver transplantation (LT). In the secondary cancer study, we reported an improved 5-year overall survival in patients treated with LT for NCLM (56%) compared with chemotherapy (9%). However, many patients were rejected for LT owing to the detection of extrahepatic disease at preoperative imaging., Patients and Methods: F-FDG PET/CT and contrast-enhanced computed tomography (ceCT) examinations before tentative LT for NCLM were assessed, and findings contraindicating LT were registered. Maximum, mean and peak standardized uptake values; tumor-to-background ratio; metabolic tumor volume; and total lesion glycolysis were measured and calculated for all liver metastases. Overall survival was calculated by the Kaplan-Meier method., Results: Thirty-two patients excluded by F-FDG PET/CT and/or ceCT before tentative LT for NCLM were identified. F-FDG PET/CT from 20 of the 32 excluded patients revealed extrahepatic disease. Eight of the other 12 patients had a negative F-FDG PET/CT finding but were excluded by ceCT. Ten patients were excluded by F-FDG PET/CT only. Four patients were excluded owing to detected malignancy from frozen sections at the start of the intended transplant operation. Tumor-to-background ratio of the liver metastases was significantly higher in patients where F-FDG PET/CT detected extrahepatic disease (P=0.03). The median (range) survival after exclusion was 16 (0-52) months., Conclusion: The ability of F-FDG PET/CT to detect extrahepatic disease before LT for NCLM is vital to establish LT as a treatment option.

Background: Liver transplantation is considered the standard of care for patients with hepatocellular carcinoma (HCC) within the Milan criteria. Liver transplantation in patients with unresectable colorectal cancer with liver-only disease has been shown to be associated with a 5-year overall survival rate of 56 per cent, compared with 9 per cent in patients receiving standard palliative chemotherapy. The aim of the present study was to compare disease-free (DFS) and overall (OS) survival after liver transplantation in patients with HCC and those with colorectal metastases., Methods: Data were collected from the SEcondary CAncer (SECA) study database and an institutional (national) database of patients undergoing liver transplantation for HCC; all liver-transplanted patients were included. Patients with colorectal metastases treated by liver transplantation were divided into high- and low-risk groups for mortality based on carcinoembryonic antigen levels, response to chemotherapy, largest lesion at time of transplantation and time from primary surgery to transplantation., Results: Patients with colorectal metastases had a median of 8 lesions, compared with 1 in patients with HCC within the Milan criteria. DFS was shorter in both the high-risk and the low-risk colorectal cancer groups compared with that in patients with HCC. The 5-year OS rate in the low-risk colorectal cancer group was 75 per cent, compared with 76 per cent in patients with HCC within the Milan criteria. The 5-year OS rate in patients with HCC beyond the Milan criteria was 56 per cent., Conclusion: The low-risk group of patients with colorectal cancer and unresectable liver-only disease had a 5-year OS rate following liver transplantation similar to that of patients with HCC with lesions within the Milan criteria., (© 2018 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Cancer remains one of the most serious long-term complications after liver transplantation (LT). Data for all adult LT patients between 1982 and 2013 were extracted from the Nordic Liver Transplant Registry. Through linkage with respective national cancer-registry data, we calculated standardized incidence ratios (SIRs) based on country, sex, calendar time, and age-specific incidence rates. Altogether 461 cancers were observed in 424 individuals of the 4246 LT patients during a mean 6.6-year follow-up. The overall SIR was 2.22 (95% confidence interval [CI], 2.02-2.43). SIRs were especially increased for colorectal cancer in recipients with primary sclerosing cholangitis (4.04) and for lung cancer in recipients with alcoholic liver disease (4.96). A decrease in the SIR for cancers occurring within 10 years post-LT was observed from the 1980s: 4.53 (95%CI, 2.47-7.60), the 1990s: 3.17 (95%CI, 2.70-3.71), to the 2000s: 1.76 (95%CI, 1.51-2.05). This was observed across age- and indication-groups. The sequential decrease for the SIR of non-Hodgkin lymphoma was 25.0-12.9-7.53, and for nonmelanoma skin cancer 80.0-29.7-10.4. Cancer risk after LT was found to be decreasing over time, especially for those cancers that are strongly associated with immunosuppression. Whether immunosuppression minimization contributed to this decrease merits further study., (© 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Hepatocellular carcinoma (HCC) in childhood differs from adult HCC because it is often associated with inherited liver disease. It is, however, unclear whether liver transplantation (LT) for HCC in childhood with or without associated inherited disease has a comparable outcome to adult HCC. On the basis of data from the European Liver Transplant Registry (ELTR), we aimed to investigate if there are differences in patient and graft survival after LT for HCC between children and adults and between patients with underlying inherited versus noninherited liver disease, respectively. We included all 175 children who underwent LT for HCC and were enrolled in ELTR between 1985 and 2012. Of these, 38 had an associated inherited liver disease. Adult HCC patients with (n = 79) and without (n = 316, matched by age, sex, and LT date) inherited liver disease served as an adult comparison population. We used multivariable piecewise Cox regression models with shared frailty terms (for LT center) to compare patient and graft survival between the different HCC groups. Survival analyses demonstrated a superior longterm survival of children with inherited liver disease when compared with children with HCC without inherited liver disease (hazard ratio [HR], 0.29; 95% CI, 0.10-0.90; P = 0.03) and adults with HCC with inherited liver disease (HR, 0.27; 95% CI, 0.06-1.25; P = 0.09). There was no survival difference between adults with and without inherited disease (HR, 1.05; 95% CI, 0.66-1.66; P = 0.84). In conclusion, the potential survival advantage of children with an HCC based on inherited disease should be acknowledged when considering transplantation and prioritization for these patients. Further prospective studies accounting for tumor size and extension at LT are necessary to fully interpret our findings. Liver Transplantation 24 246-255 2018 AASLD., (© 2017 by the American Association for the Study of Liver Diseases.)

Background: The previously reported SECA study demonstrated a dramatic 5-year survival improvement in patients with unresectable colorectal liver metastases (CLM) treated with liver transplantation (LT) compared with chemotherapy. The objective of this study was to assess whether immunosuppressive therapy accelerates the growth of pulmonary metastases in patients transplanted for unresectable CLM., Methods: Chest CT scans from 11 patients in the SECA study resected for 18 pulmonary metastases were reviewed retrospectively. Tumour diameter, volume and CT characteristics were registered and tumour volume doubling time was calculated. Findings in the SECA group were compared with those of a control group consisting of 12 patients with non-transplanted rectal cancer resected for 26 pulmonary metastases. Disease-free survival (DFS) and overall survival (OS) after first pulmonary resection were determined., Results: Median doubling time based on tumour diameter and volume in the SECA and control groups were 125 and 130 days (P = 0·658) and 110 and 129 days (P = 0·632) respectively. The metastases in both groups were distributed to all lung lobes and were mostly peripheral. Median DFS after LT in the SECA group and after primary pelvic surgery in the control group was 17 (range 6-42) and 18 (2-57) months respectively (P = 0·532). In the SECA group, estimated 5-year DFS and OS rates after first pulmonary resection were 39 and 51 per cent respectively., Conclusion: Patients treated by LT for unresectable CLM have a good prognosis following resection of pulmonary metastases. Doubling time did not appear to be worse with the immunosuppression used after LT., (© 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Purpose: The main objective of this study was to evaluate the prognostic value of volumetric and metabolic information derivied from F-18 fluorodeoxyglucose positron emission tomography ( 18 F-FDG PET) in combination with computed tomography (CT) prior to liver transplantation (LT) in patients with nonresectable colorectal liver metastases (CLM). Due to scarcity of liver grafts, prognostic information enabling selection of candidates who will gain the highest survival after LT is of vital importance. 18 F-FDG PET/CT was a part of the preoperative study protocol. Patients without evidence of extrahepatic malignant disease on 18 F-FDG PET/CT who also fulfilled all the other inclusion criteria underwent LT., Methods: The preoperative 18 F-FDG PET/CT examinations of all patients included in the SECA (secondary cancer) study were retrospectively assessed. Maximum, mean and peak standardized uptake values (SUV max , SUV mean and SUV peak ), tumor to background (T/B) ratio, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured and calculated for all liver metastases. Total MTV and TLG were calculated for each patient. Cut-off values were determined for each of these parameters by using receiver operating characteristic (ROC) analysis dividing the patients into two groups. One, three and five-year overall survival (OS) and disease free survival (DFS) for patients over and under the cut-off value were compared by using the Kaplan-Meier method and log rank test., Results: Twenty-three patients underwent LT in the SECA study. Total MTV and TLG under the cut-off values were significantly correlated to improved OS at three and five years (p = 0.027 and 0.026) and DFS (p = 0.01). One, three and five-year OS and DFS were not significantly related to SUV max , SUV mean , SUV peak or T/B-ratio., Conclusion: Total MTV and TLG from 18 F FDG PET/CT prior to LT for nonresectable CLM were significantly correlated to improved three and five-year OS and DFS and can potentially improve the patient selection for LT.

Liver resection is the only potentially curative treatment option in patients with liver metastases from colorectal cancer, but only about 20% of the patients are resectable. Liver transplantation of patients with unresectable liver metastases was attempted in the early era but it was abandoned due to poor survival. During the last decade, several case reports, a controlled pilot study, and a retrospective cohort study indicated that prolonged disease-free survival and overall survival can be obtained in a proportion of these patients. Strict selection criteria have not yet been well defined, but tumor load, response to chemotherapy, pretransplant carcinoembryonic antigen level, and time interval from resection of the primary tumor to transplant are all factors related to outcome. Carefully selected patients may obtain 5-year overall survival that approaches conventional indications for liver transplant. The scarcity of liver grafts is a significant problem, but this can possibly to some extent be addressed by use of extended criteria grafts and novel surgical techniques. There is an increasing interest in liver transplantation in these patients in the transplant community, and currently 4 clinical trials are active and are recruiting.