Long-Term Survival, Prognostic Factors, and Selection of Patients With Colorectal Cancer for Liver Transplant: A Nonrandomized Controlled Trial.

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.

Transplantation for metastatic liver disease.

The liver is a common site of metastases from many cancers, particularly those originating in the gastrointestinal tract. Liver transplantation is an uncommonly used but promising and at times controversial treatment option for neuroendocrine and colorectal liver metastases. Transplantation with meticulous patient selection has been associated with excellent long-term outcomes in individuals with neuroendocrine liver metastases, but questions remain regarding the role of transplantation in those who could also be eligible for hepatectomy, the role of neoadjuvant/adjuvant treatments in minimising recurrence, and the optimal timing of the procedure. A prospective pilot study of liver transplantation for unresectable colorectal liver metastases that reported a 5-year overall survival rate of 60% reinvigorated interest in this area following initially dismal outcomes. This has been followed by larger studies, and prospective trials are ongoing to quantify the potential benefits of liver transplantation over palliative chemotherapy. This review provides a critical summary of currently available knowledge on liver transplantation for neuroendocrine and colorectal liver metastases, and highlights avenues for further study to address gaps in the evidence base.

Transplantation for Nonresectable Colorectal Liver Metastases: Long-Term Follow-Up of the First Prospective Pilot Study.

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.

Liver transplantation for non-resectable colorectal liver metastases: the International Hepato-Pancreato-Biliary Association consensus guidelines.

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.

Liver transplantation versus liver resection for colorectal liver metastasis: a survival benefit analysis in patients stratified according to tumor burden score.

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.

Survival Outcomes After Portal Vein Embolization and Liver Resection Compared With Liver Transplant for Patients With Extensive Colorectal Cancer Liver Metastases.

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.

Selection criteria related to long-term survival following liver transplantation for colorectal liver metastasis.

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.

Survival Following Liver Transplantation for Patients With Nonresectable Liver-only Colorectal Metastases.

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.

Donor-derived strongyloidiasis after organ transplantation in Norway.

Strongyloides stercoralis is an intestinal helminth which in humans can cause asymptomatic chronic infection maintained for decades through its auto-infective cycle. During solid organ transplantation, recipients may unintentionally receive an organ infected with strongyloides. This is a very rare complication but may have deadly outcome if not detected. We hereby report two transplant recipients whom developed Strongyloides hyperinfection syndrome after organ transplantation from the same deceased donor. Recipient 1 was kidney transplanted and presented at day 65 post engraftment with diarrhea and subsequent septicemia and gastric retention. Larvae were detected in gastric aspirate. Recipient 2 was simultaneously kidney and pancreas transplanted and presented at day 90 post engraftment also with gastric retention and septicemia. Larvae were demonstrated on duodenal biopsy and stool sample. The clinical course was complicated with severe duodenal bleedings, gastric retention, meningitis, and prolonged hospitalization. Retrospective testing of pre-transplant donor serum was positive for Strongyloides stercoralis antibodies. As a result of disease severity and gastric retention albenazole was administered via a jejunal tube and ivermectin subcutaneously in both recipients. S stercoralis was successfully eradicated and the transplants ended up with unaffected graft function. Following these two cases, we started systematic screening of all deceased donors for serum Strongyloides IgG in October 2016. After having screened 150 utilized donors one tested positive for Strongyloides, which initiated prophylactic ivermectin treatment to organ recipients. No symptoms or disease developed. Our center will continue to screen all donors as prophylactic treatment may avert this potentially lethal complication in cases of donor-derived Strongyloides infection.

The Potential Role of Liver Transplantation as a Treatment Option in Colorectal Liver Metastases.

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.

CD8+ T Cells That Coexpress RORγt and T-bet Are Functionally Impaired and Expand in Patients with Distal Bile Duct Cancer.

CD8+ T cells that express retinoic acid-related orphan receptor (ROR)γt (TC17 cells) have been shown to promote procarcinogenic inflammation and contribute to a tolerogenic microenvironment in tumors. We investigated their phenotype and functional properties in relationship to the pathogenesis of human distal bile duct cancer (DBDC). DBDC patients had an elevated level of type 17 immune responses and the frequency of CD8+RORγt+ T cells (TC17 cells) was increased in peripheral blood. The CD8+RORγt+ T cells represented a highly activated subset and produced IL-17A in equal amount as CD4+RORγt+ T cells (TH17 cells). Most CD8+RORγt+ T cells coexpressed T-bet, a lineage transcription factor for TH1 and TC1 development, suggesting that CD8+RORγt+ T cells undergo plasticity toward a TC17/1-like phenotype with coproduction of IL-17A and INF-γ. In comparison with CD8+RORγt- T cells, the CD8+RORγt+ T cells had a higher level of TCR signaling and were terminally differentiated and exhausted. These cells also had impaired ability to re-express perforin after degranulation and reduced cytotoxic immune function. A subset of CD8+RORγt+ T cells expressing a low level of programmed cell death protein 1 and a high level of OX40 were associated with reduced patient survival. In conclusion, CD8+RORγt+ T cells are proinflammatory and functionally impaired and may contribute to the pathogenesis of DBDC.

Regulatory T cells that co-express RORγt and FOXP3 are pro-inflammatory and immunosuppressive and expand in human pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is highly infiltrated by CD4+T cells that express RORγt and IL-17 (TH17). Compelling evidence from the tumor microenvironment suggest that regulatory T cells (Treg) contribute to TH17 mediated inflammation. Concurrently, PDAC patients have elevated levels of pro-inflammatory cytokines that may lead to TH17 associated functional plasticity in Treg. In this study, we investigated the phenotype and functional properties of Treg in patients with PDAC. We report that PDAC patients have elevated frequency of FOXP3+Treg, which exclusively occurred within the FOXP3+RORγt+Treg compartment. The FOXP3+RORγt+Treg retained FOXP3+Treg markers and represented an activated subset. The expression of RORγt in Treg may indicate a phenotypic switch toward TH17 cells. However, the FOXP3+RORγt+Treg produced both TH17 and TH2 associated pro-inflammatory cytokines, which corresponded with elevated TH17 and TH2 immune responses in PDAC patients. Both the FOXP3+Treg and FOXP3+RORγt+Treg from PDAC patients strongly suppressed T cell immune responses, but they had impaired anti-inflammatory properties. We conclude that FOXP3+RORγt+Treg have a dual phenotype with combined pro-inflammatory and immunosuppressive activity, which may be involved in the pathogenesis of PDAC.

A Novel Concept for Partial Liver Transplantation in Nonresectable Colorectal Liver Metastases: The RAPID Concept.

OBJECTIVE: Selected patients with nonresectable colorectal liver metastases benefit from liver transplantation and have acceptable 5-year survival rates. However, allocating full-sized grafts to this group of patients is difficult due to the scarcity of grafts. This could be improved by utilizing small partial grafts, which mandates effective strategies to overcome the problems regarding insufficient functional liver mass. METHODS: We have developed a protocol incorporating previously reported experiences from living donor transplantation and recent developments in liver surgery, facilitating transplantation of very small liver grafts. At the time of transplantation, segments 1 to 3 are resected in the recipient and orthotopically replaced by a segment 2 to 3 allograft. Portal inflow is modulated by redirecting the portal flow to the graft with concomitant focus on keeping the portal vein pressure below 20 mm Hg. A second-stage hepatectomy is performed as soon as the graft has regenerated to a sufficient volume. RESULTS: A graft weighing 330 g was transplanted to a 50-year-old man weighing 92 kg, and the portal vein to the right remnant liver was closed. The volume of the liver graft was doubled 2 weeks after the first procedure, and it increased further after the second procedure, with extended right hepatectomy performed at day 23 after transplantation. There were no signs of liver failure or small-for-size syndrome. CONCLUSIONS: 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.

Is Liver Transplantation an Option in Colorectal Cancer Patients with Nonresectable Liver Metastases and Progression on All Lines of Standard Chemotherapy?

BACKGROUND: About 50 % of patients with metastatic colorectal cancer (CRC) will develop metastatic disease with liver as primary metastatic site. The majority of CRC patients has nonresectable disease and receives palliative chemotherapy. Overall survival (OS) from time of progression on last line of chemotherapy in metastatic CRC is about 5 months. CLM have been considered a contraindication for liver transplantation. However, we have previously reported 5-year OS of 60 % after liver transplantation for nonresectable CLM. There were six patients who had progressive disease (PD) on last line of standard chemotherapy at the time of liver transplantation; here we report the outcome for these six patients. METHODS: Patients with nonresectable liver-only CLM received liver transplantation in the SECA study, a subgroup of six patients whose disease had progressed on all standard lines of chemotherapy. RESULTS: These patients with nonresectable disease and PD on the last line of standard chemotherapy at time of liver transplantation had 8-35 metastatic lesions in the liver with the largest diameter at 2.8-13.0 cm. All patients had a relapse within 2.1-12.4 months after liver transplantation. Some patients received treatment with curative intent at the time of relapse, and median OS after transplantation was 41 months with a Kaplan-Meier calculated 5-year OS of 44 %. CONCLUSIONS: Liver transplantation in nonresectable CLM patients with extensive tumor load and PD on the last line of chemotherapy had extended OS compared with any other treatment option reported in the literature.

Chemotherapy or liver transplantation for nonresectable liver metastases from colorectal cancer?

OBJECTIVE: The primary objective was to compare overall survival (OS) in patients with colorectal cancer (CRC) with nonresectable liver-only metastases treated by liver transplantation or chemotherapy. BACKGROUND: CRC is the third most common cancer worldwide. About 50% of patients will develop metastatic disease primarily to the liver and the lung. The majority of patients with liver metastases receive palliative chemotherapy, with a median OS of trial patients of about 2 years, and less than 10% are alive at 5 years. METHODS: Patients with nonresectable liver-only CRC metastases underwent liver transplantation in the SECA study (n = 21). Disease-free survival (DFS) and OS of patients included in the SECA study were compared with progression-free survival (PFS) and OS in a similar cohort of CRC patients with liver-only disease included in a first-line chemotherapy study, the NORDIC VII study (n = 47). PFS/DFS and OS were estimated by the Kaplan-Meier method. RESULTS: DFS/PFS in both groups were 8 to 10 months. However, a dramatic difference in OS was observed. The 5-year OS rate was 56% in patients undergoing liver transplantation compared with 9% in patients starting first-line chemotherapy. The reason for the large difference in OS despite similar DFS/PFS is likely different metastatic patterns at relapse/progression. Relapse in the liver transplantation group was often detected as small, slowly growing lung metastases, whereas progression of nonresectable liver metastases was observed in the chemotherapy group. CONCLUSIONS: Compared with chemotherapy, liver transplantation resulted in a marked increased OS in CRC patients with nonresectable liver-only metastases.

Liver transplantation in treatment of colorectal liver metastases.

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.

Patterns of recurrence after liver transplantation for nonresectable liver metastases from colorectal cancer.

BACKGROUND: Surgical resection is the only curative modality for colorectal liver metastases (CLM), and the pattern of recurrences after resection affects survival. In a prospective study of liver transplantation (Lt) for nonresectable CLM we have shown a 5-year overall survival rate of 60 %, but 19 of 21 experienced recurrence. This study reports the pattern of recurrences after Lt for CLM and the effect on survival. METHODS: Characterization of metastatic lesions in a prospective study for Lt for nonresectable CLM was performed (n = 21). The study included reexamination of chest computed tomographic scans taken before Lt. RESULTS: At the time of first recurrence, 16 were a single site, and three were multiple sites. Thirteen of the single sites were pulmonary recurrences. The pulmonary recurrences appeared early and were slow growing, and several were accessible to surgical treatment. When chest computed tomographic scans were reexamined, seven patients had pulmonary nodules at the time of Lt without an effect on survival. There was no first single-site hepatic recurrence. Six of the seven patients who developed metastases to the transplanted liver died from metastatic disease. CONCLUSIONS: The pulmonary recurrences after Lt for CLM were of an indolent character, even those that were present at the time of Lt. This contrasts with the finding of metastases to the transplanted liver, which was prognostically adverse. The lack of single hepatic first-site recurrences and hepatic metastases only as part of disseminated disease is different from the pattern of recurrence after liver resection. This suggests two distinct mechanisms for hepatic recurrences after resection for CLM.

Liver transplantation for nonresectable liver metastases from colorectal cancer.

OBJECTIVE: The objective of this pilot study was to investigate the potential for long-term overall survival (OS) after liver transplantation for colorectal liver metastases (CLMs). BACKGROUND: Patients with nonresectable CLMs have poor prognosis, and few survive beyond 5 years. CLMs are currently considered an absolute contraindication for liver transplantation, although liver transplantation for primary and some secondary liver malignancies shows excellent outcome in selected patients. Before 1995, several liver transplantations for CLMs were performed, but outcome was poor (5-year survival rate: 18%) and liver transplantation for CLMs was abandoned. Since then, the survival rate after liver transplantation in general has improved by almost 30%. On the basis of this, a 5-year survival rate of about 50% after liver transplantation for CLMs could be anticipated. METHODS: In a prospective pilot study, liver transplantation for nonresectable CLMs was performed (n = 21). Main inclusion criteria were liver-only CLMs, excised primary tumors, and at least 6 weeks of chemotherapy. RESULTS: Kaplan-Meier estimates of the OS rate at 1, 3, and 5 years were 95%, 68%, and 60%, respectively. Metastatic recurrence of disease was common (mainly pulmonary). However, a significant proportion of the recurrences were accessible for surgery, and at follow-up (after median of 27 months; range, 8-60), 33% had no evidence of disease. Hepatic tumor load before liver transplantation, time from primary surgery to liver transplantation, and progressive disease on chemotherapy were identified as significant prognostic factors. CONCLUSIONS: OS exceeds by far reported outcome for chemotherapy, which is the only treatment option available for this patient group. Furthermore, OS is comparable with liver resection for resectable CLMs and survival after repeat liver transplantation for nonmalignant diseases. Selection strategies based on prognostic factors may further improve the outcome (ClinicalTrials.gov: NCT01311453).

Quality of life following liver transplantation in patients with liver metastases from colorectal carcinoma.

PURPOSE: To study quality of life (QoL) in patients with liver metastases from colorectal carcinoma (CRC) following liver transplantation (Ltx). METHODS: Ten patients participated in a prospective explorative pilot study. Inclusion criteria were nonresectable liver-only metastases determined by CT/MRI-, PET/CT- scans and colonoscopy, and ECOG 0-1. Primary outcome was QoL assessed by the EORTC-C30 questionnaires at baseline, and at 3, 6 and 12 months after Ltx. RESULTS: The patients' age ranged from 50 to 63 years. Nine of 10 patients were observed for 12 months. One patient did not return the form at 6 months and died shortly after because of recurrence of the malignant disease. Compared to baseline, Ltx resulted in sustained excellent global health status scale (score of 100) in one patient, improved scores in 4 and unchanged scores in 3 patients at 12 months. The majority of the patients also reported good functional scores at follow-ups. Although two patients had marked symptoms both before and after Ltx, the patients in general reported low levels of pain and fatigue before and after surgery. CONCLUSION: The present study indicates that CRC patients with liver-only metastases who receive Ltx have good QoL and have mostly minor symptoms the first year after Ltx.