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Background: Hepatocellular carcinoma (HCC) found in a non cirrhotic liver represents a minority of HCC cases and remains poorly studied. Due to its specific characteristics and evolution, this tumour requires a different management compared to HCC in a cirrhotic liver., Case Report: The authors describe the case of a 68-year-old man diagnosed with a large giant and only mildly symptomatic HCC in a non-cirrhotic liver. The 23 cm HCC was discovered when a thoracoabdominal computed tomography was performed following mild abdominal pain. After a multidisciplinary discussion the tumour was judged to be borderline, but potentially resectable after neoadjuvant therapy and preparation for surgery. The patient underwent selective internal radiation therapy radioembolization of the right hepatic artery lobe with 5,5 GBq of 90Y-labeled glass microspheres. It was followed by extended right hepatectomy after preparation by embolization of the right portal and the right hepatic veins. Thirty months after surgical resection the patient showed neither clinical, radiological nor biological signs of HCC recurrence., Discussion: HCC in non-cirrhotic liver is less common than in cirrhotic liver but has a better prognosis, thanks to a greater opportunity for surgical resection. The symptoms often emerge late and are unspecific, thus delaying the HCC diagnosis. Advances in surgical resection by laparotomy or laparoscopy, and neoadjuvant therapy in preparation for surgery, have proven to be effective. However, high mortality persists due to late diagnosis linked to the inability of identifying groups at risk of HCC in the non-cirrhotic population and inadequate screening.

Background: The purpose of this study was to compare 3-year overall survival after simultaneous portal (PVE) and hepatic vein (HVE) embolization versus PVE alone in patients undergoing liver resection for primary and secondary cancers of the liver., Methods: In this multicentre retrospective study, all DRAGON 0 centres provided 3-year follow-up data for all patients who had PVE/HVE or PVE, and were included in DRAGON 0 between 2016 and 2019. Kaplan-Meier analysis was undertaken to assess 3-year overall and recurrence/progression-free survival. Factors affecting survival were evaluated using univariable and multivariable Cox regression analyses., Results: In total, 199 patients were included from 7 centres, of whom 39 underwent PVE/HVE and 160 PVE alone. Groups differed in median age (P = 0.008). As reported previously, PVE/HVE resulted in a significantly higher resection rate than PVE alone (92 versus 68%; P = 0.007). Three-year overall survival was significantly higher in the PVE/HVE group (median survival not reached after 36 months versus 20 months after PVE; P = 0.004). Univariable and multivariable analyses identified PVE/HVE as an independent predictor of survival (univariable HR 0.46, 95% c.i. 0.27 to 0.76; P = 0.003)., Conclusion: Overall survival after PVE/HVE is substantially longer than that after PVE alone in patients with primary and secondary liver tumours., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.)

Background: Surgical resection (SR) is a potentially curative treatment of hepatocellular carcinoma (HCC) hampered by high rates of recurrence. New drugs are tested in the adjuvant setting, but standardised risk stratification tools of HCC recurrence are lacking., Objectives: To develop and validate a simple scoring system to predict 2-year recurrence after SR for HCC., Methods: 2359 treatment-naïve patients who underwent SR for HCC in 17 centres in Europe and Asia between 2004 and 2017 were divided into a development (DS; n = 1558) and validation set (VS; n = 801) by random sampling of participating centres. The Early Recurrence Score (ERS) was generated using variables associated with 2-year recurrence in the DS and validated in the VS., Results: Variables associated with 2-year recurrence in the DS were (with associated points) alpha-fetoprotein (<10 ng/mL:0; 10-100: 2; >100: 3), size of largest nodule (≥40 mm: 1), multifocality (yes: 2), satellite nodules (yes: 2), vascular invasion (yes: 1) and surgical margin (positive R1: 2). The sum of points provided a score ranging from 0 to 11, allowing stratification into four levels of 2-year recurrence risk (Wolbers' C-indices 66.8% DS and 68.4% VS), with excellent calibration according to risk categories. Wolber's and Harrell's C-indices apparent values were systematically higher for ERS when compared to Early Recurrence After Surgery for Liver tumour post-operative model to predict time to early recurrence or recurrence-free survival., Conclusions: ERS is a user-friendly staging system identifying four levels of early recurrence risk after SR and a robust tool to design personalised surveillance strategies and adjuvant therapy trials., (© 2023 The Authors. Liver International published by John Wiley & Sons Ltd.)

Study Purpose: The DRAGON 1 trial aims to assess training, implementation, safety and feasibility of combined portal- and hepatic-vein embolization (PVE/HVE) to accelerate future liver remnant (FLR) hypertrophy in patients with borderline resectable colorectal cancer liver metastases., Methods: The DRAGON 1 trial is a worldwide multicenter prospective single arm trial. The primary endpoint is a composite of the safety of PVE/HVE, 90-day mortality, and one year accrual monitoring of each participating center. Secondary endpoints include: feasibility of resection, the used PVE and HVE techniques, FLR-hypertrophy, liver function (subset of centers), overall survival, and disease-free survival. All complications after the PVE/HVE procedure are documented. Liver volumes will be measured at week 1 and if applicable at week 3 and 6 after PVE/HVE and follow-up visits will be held at 1, 3, 6, and 12 months after the resection., Results: Not applicable., Conclusion: DRAGON 1 is a prospective trial to assess the safety and feasibility of PVE/HVE. Participating study centers will be trained, and procedures standardized using Work Instructions (WI) to prepare for the DRAGON 2 randomized controlled trial. Outcomes should reveal the accrual potential of centers, safety profile of combined PVE/HVE and the effect of FLR-hypertrophy induction by PVE/HVE in patients with CRLM and a small FLR., Trial Registration: Clinicaltrials.gov: NCT04272931 (February 17, 2020). Toestingonline.nl: NL71535.068.19 (September 20, 2019)., (© 2022. The Author(s).)

Cancer-associated fibroblasts (CAF) are important constituents of the tumor microenvironment (TME) and are major drivers of tumorigenesis. Yet, therapies aiming at eliminating CAF have failed to cure patients. This setback has raised questions regarding whether CAF exclusively favour cancer progression, or if they may also assume tumor-suppressor functions. In the present study, we used proteomics and single cell RNA-sequencing analysis to examine the CAF landscape in hepatocellular carcinoma (HCC). We thereby unveil three major CAF populations in HCC, one of which specifically expressing the prolargin protein. This CAF subpopulation (further termed as CAF&#95;Port) shared a strong transcriptomic signature with portal liver fibroblasts. We further show that CAF&#95;Port deposit prolargin in the TME and that its levels are lower in tumors as compared to the peritumoral region. Mechanistically, aggressive cancer cells degraded prolargin using matrix metalloprotease activity. Survival analysis of 188 patients revealed that high prolargin protein levels correlate with good patient outcome (HR = 0.37; p = 0.01). In vivo, co-injection of cancer cells with fibroblasts silenced for prolargin, led to faster tumor development (5-fold; p = 0.01), mainly due to stronger angiogenesis. Using protein-protein interaction study and structural modelling, we further demonstrate that prolargin binds and inhibits the activity of several pro-agiogenic proteins, including hepatocyte and fibroblast growth factors. In conclusion, prolargin is angiogenesis modulator and CAF-derived tumor suppressor in HCC. Stabilizing prolargin levels in the CAF&#95;Port subpopulation may revert their tumor-antagonizing properties, warranting exploration in further pre-clinical studies., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The extent of liver resection for tumours is limited by the expected functional reserve of the future liver remnant (FRL), so hypertrophy may be induced by portal vein embolization (PVE), taking 6 weeks or longer for growth. This study assessed the hypothesis that simultaneous embolization of portal and hepatic veins (PVE/HVE) accelerates hypertrophy and improves resectability., Methods: All centres of the international DRAGON trials study collaborative were asked to provide data on patients who had PVE/HVE or PVE on 2016-2019 (more than 5 PVE/HVE procedures was a requirement). Liver volumetry was performed using OsiriX MD software. Multivariable analysis was performed for the endpoints of resectability rate, FLR hypertrophy and major complications using receiver operating characteristic (ROC) statistics, regression, and Kaplan-Meier analysis., Results: In total, 39 patients had undergone PVE/HVE and 160 had PVE alone. The PVE/HVE group had better hypertrophy than the PVE group (59 versus 48 per cent respectively; P = 0.020) and resectability (90 versus 68 per cent; P = 0.007). Major complications (26 versus 34 per cent; P = 0.550) and 90-day mortality (3 versus 16 per cent respectively, P = 0.065) were comparable. Multivariable analysis confirmed that these effects were independent of confounders., Conclusion: PVE/HVE achieved better FLR hypertrophy and resectability than PVE in this collaborative experience., (© The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Limited evidence exists to guide the management of patients with liver metastases from squamous cell carcinoma (SCC). The aim of this retrospective multicentre cohort study was to describe patterns of disease recurrence after liver resection/ablation for SCC liver metastases and factors associated with recurrence-free survival (RFS) and overall survival (OS)., Method: Members of the European-African Hepato-Pancreato-Biliary Association were invited to include all consecutive patients undergoing liver resection/ablation for SCC liver metastases between 2002 and 2019. Patient, tumour and perioperative characteristics were analysed with regard to RFS and OS., Results: Among the 102 patients included from 24 European centres, 56 patients had anal cancer, and 46 patients had SCC from other origin. RFS in patients with anal cancer and non-anal cancer was 16 and 9 months, respectively (P = 0.134). A positive resection margin significantly influenced RFS for both anal cancer and non-anal cancer liver metastases (hazard ratio 6.82, 95 per cent c.i. 2.40 to 19.35, for the entire cohort). Median survival duration and 5-year OS rate among patients with anal cancer and non-anal cancer were 50 months and 45 per cent and 21 months and 25 per cent, respectively. For the entire cohort, only non-radical resection was associated with worse overall survival (hazard ratio 3.21, 95 per cent c.i. 1.24 to 8.30)., Conclusion: Liver resection/ablation of liver metastases from SCC can result in long-term survival. Survival was superior in treated patients with liver metastases from anal versus non-anal cancer. A negative resection margin is paramount for acceptable outcome., (© The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd.)

In Belgium and around the world, the incidence of primary malignant liver tumours is increasing, both for hepatocarcinoma and cholangiocarcinoma. Their curative treatment is based on multidisciplinary and specialized care, of which surgery (including liver transplantation) remains the cornerstone, often associated with other logoregional treatments, as radioembolisation, radiofrequency ablation, and chemoembolisation. For advanced cases, the prognosis remains poor, in particular due to a certain chemoresistance of these tumours. New treatments include targeted therapies (including various tyrosine kinase inhibitors) and immunotherapy. A specialized multidisciplinary discussion is therefore necessary to define the best therapeutic management, individualized to each patient. In this article, the authors review the most recent data relating to the treatment of hepatocarcinoma and cholangiocarcinoma.

Liver transplantation (LT) remains the only curative option for patients suffering from end-stage liver disease, acute liver failure and selected hepatocellular carcinomas and access to the LT-waiting list is limited to certain strict indications. However, LT has shown survival advantages for patients in certain indications such as acute alcoholic hepatitis, hepatocellular carcinoma outside Milan criteria and colorectal cancer metastases. These newer indications increase the pressure in an already difficult context of organ shortage. Strategies to increase the transplantable organ pool are therefore needed. We will discuss here the use of HCV positive grafts as the use of normothermic isolated liver perfusion. Belgian Liver Intestine Advisory Committee (BeLIAC) from the Belgian Transplant Society (BTS) aims to guarantee the balance between the new indications and the available resources., Competing Interests: The authors declare that they have no conflict of interest, (© Acta Gastro-Enterologica Belgica.)

Colorectal cancer (CRC) cells are traditionally considered unresponsive to TGFβ due to mutations in the receptors and/or downstream signaling molecules. TGFβ influences CRC cells only indirectly via stromal cells, such as cancer-associated fibroblasts. However, CRC cell ability to directly respond to TGFβ currently remains unexplored. This represents a missed opportunity for diagnostic and therapeutic interventions. Methods: We examined whether cancer cells from primary CRC and liver metastases respond to TGFβ by inducing TGFβ-induced protein ig-h3 (TGFBI) expression, and the contribution of canonical and non-canonical TGFβ signaling pathways to this effect. We then investigated in vitro and in vivo TGFBI impact on metastasis formation and angiogenesis. Using patient serum samples and an orthotopic mouse model of CRC liver metastases we assessed the diagnostic/tumor targeting value of novel antibodies against TGFBI. Results: Metastatic CRC cells, such as circulating tumor cells, directly respond to TGFβ. These cells were characterized by the absence of TGFβ receptor mutations and the frequent presence of p53 mutations. The pro-tumorigenic program orchestrated by TGFβ in CRC cells was mediated through TGFBI, the expression of which was positively regulated by non-canonical TGFβ signaling cascades. TGFBI inhibition was sufficient to significantly reduce liver metastasis formation in vivo . Moreover, TGFBI pro-tumorigenic function was linked to its ability to stimulate angiogenesis. TGFBI levels were higher in serum samples from untreated patients with CRC than in patients who were receiving chemotherapy. A radiolabeled anti-TGFBI antibody selectively targeted metastatic lesions in vivo , underscoring its diagnostic and therapeutic potential. Conclusions: TGFβ signaling in CRC cells directly contributes to their metastatic potential and stromal cell-independence. Proteins downstream of activated TGFβ, such as TGFBI, represent novel diagnostic and therapeutic targets for more specific anti-metastatic therapies., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Recent studies indicate that a group of patients with cirrhosis receiving a liver transplantation for hepatocellular cancer (HCC) beyond the Milan Criteria (MC) can achieve a similar outcome compared to patients within these criteria. This study aims to investigate the value of the Asan critera (AC), up-to-7 criteria (UT7), French alpha-foetoprotein (AFP) model and Metroticket 2.0 (MT2.0) model compared to the MC., Methods: 526 patients transplanted for non-metastatic HCC were analyzed. Patient groups within and beyond MC and extended criteria were determined according to radiological assessment and AFP value at listing., Results: Overall survival (OS) and recurrence (RR) rates were similar between patients within MC and all extended criteria. Five-year OS within MC was 71.3% compared to 70.9% for AC, 71.4% for UT7, 69.7% for AFP-model and 71.0% for MT2.0 criteria. Five-year RR within MC was 12.3% compared to 13.5% for AC, 13.0% for UT7, 14.3% for AFP-model and 13.2% for MT2.0 criteria. Patients beyond MC but within the extended criteria had tendency towards higher recurrence., Conclusions: All validated extended criteria (AC, UT7, AFP-model and MT2.0) could be proposed as alternatives to the MC with similar outcome. Prospective data are awaited to assess recurrence beyond MC., Competing Interests: Declaration of competing interest No conflict of interest reported in relation to the presented work., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Ever since the initial description of the Milan criteria, used for selecting patients with hepatocellular carcinoma (HCC) for liver transplantation (LT), there has been a clear need to go further than solely morphological criteria. Tumours exceeding the Milan criteria, but presenting favourable biological behaviour, might still allow for comparable overall- and disease-free survivals after LT. As it is well established that the presence of microvascular invasion is a major factor that influences HCC recurrence after LT, several serum and tissue biomarkers in addition to imaging studies are attracting wider attention as more refined tools for selecting HCC patients for LT. A thorough review of the recent literature on the subject was conducted. In the future a combination of systemic inflammation markers, biomarkers and morphological criteria may be key to more accurate prediction of HCC recurrence after LT. This may allow LT in patients whose HCC tumours exceed the Milan criteria but have favourable biological behaviour. Further prospective studies are required in order to improve patient selection for transplantation in HCC and these could help a move towards more transparent and improved management., Competing Interests: The authors declare that they have no conflict of interest, (© Acta Gastro-Enterologica Belgica.)

Cancer research is increasingly dependent of patient-derived xenograft model (PDX). However, a major point of concern regarding the PDX model remains the replacement of the human stroma with murine counterpart. In the present work we aimed at clarifying the significance of the human-to-murine stromal replacement for the fidelity of colorectal cancer (CRC) and liver metastasis (CRC-LM) PDX model. We have conducted a comparative metabolic analysis between 6 patient tumors and corresponding PDX across 4 generations. Metabolic signatures of cancer cells and stroma were measured separately by MALDI-imaging, while metabolite changes in entire tumors were quantified using mass spectrometry approach. Measurement of glucose metabolism was also conducted in vivo using [ 18 F]-fluorodeoxyglucose (FDG) and positron emission tomography (PET). In CRC/CRC-LM PDX model, human stroma was entirely replaced at the second generation. Despite this change, MALDI-imaging demonstrated that the metabolic profiles of both stromal and cancer cells remained stable for at least four generations in comparison to the original patient material. On the tumor level, profiles of 86 water-soluble metabolites as well as 93 lipid mediators underlined the functional stability of the PDX model. In vivo PET measurement of glucose uptake (reflecting tumor glucose metabolism) supported the ex vivo observations. Our data show for the first time that CRC/CRC-LM PDX model maintains the functional stability at the metabolic level despite the early replacement of the human stroma by murine cells. The findings demonstrate that human cancer cells actively educate murine stromal cells during PDX development to adopt the human-like phenotype.

Aim: To evaluate the prognostic value of pretreatment FDG positron emission tomography computed tomography (PET-CT) in patients with hepatocarcinoma treated by liver transplantation (LT)., Methods: The authors retrospectively analyzed the data of 27 patients (mean age 58 ± 9 years) who underwent FDG PET-CT before LT for hepatocarcinoma. Mean follow-up was 26 ± 18 mo. The FDG PET/CT was performed according to a standard clinical protocol: 4 MBqFDG/kg body weight, uptake 60 min, low-dose non-enhanced CT. The authors measured the SUVmax and SUVmean of the tumor and the normal liver. The tumor/liver activity ratios (RSUVmax and RSUVmean) were tested as prognostic factors and compared to the following conventional prognostic factors: MILAN, CLIP, OKUDA, TNM stage, alphafoetoprotein level, portal thrombosis, size of the largest nodule, tumor differentiation, microvascular invasion, underlying cirrhosis and liver function., Results: Overall and recurrence free survivals were 80.7% and 67.4% at 3 years, and 70.6% and 67.4% at 5 years, respectively. According to a multivariate Cox model, only FDG PET/CT RSUVmax predicted recurrence free survival. Even though the MILAN criteria alone were not predictive, it is worth noting that none of the patients outside the MILAN criteria and with RSUVmax < 1.15 relapsed., Conclusion: FDG PET/CT with an RSUVmax cut-off value of 1.15 is a strong prognostic factor for recurrence and death in patients with HCC treated by LT in this retrospective series. Further prospective studies should test whether this metabolic index should be systematically included in the preoperative assessment.

Unlabelled: Tumor heterogeneity is a major obstacle for developing effective anticancer treatments. Recent studies have pointed to large stochastic genetic heterogeneity within cancer lesions, where no pattern seems to exist that would enable a more structured targeted therapy approach. Because to date no similar information is available at the protein (phenotype) level, we employed matrix assisted laser desorption ionization (MALDI) image-guided proteomics and explored the heterogeneity of extracellular and membrane subproteome in a unique collection of eight fresh human colorectal carcinoma (CRC) liver metastases. Monitoring the spatial distribution of over 1,000 proteins, we found unexpectedly that all liver metastasis lesions displayed a reproducible, zonally delineated pattern of functional and therapeutic biomarker heterogeneity. The peritumoral region featured elevated lipid metabolism and protein synthesis, the rim of the metastasis displayed increased cellular growth, movement, and drug metabolism, whereas the center of the lesion was characterized by elevated carbohydrate metabolism and DNA-repair activity. From the aspect of therapeutic targeting, zonal expression of known and novel biomarkers was evident, reinforcing the need to select several targets in order to achieve optimal coverage of the lesion. Finally, we highlight two novel antigens, LTBP2 and TGFBI, whose expression is a consistent feature of CRC liver metastasis. We demonstrate their in vivo antibody-based targeting and highlight their potential usefulness for clinical applications., Conclusion: The proteome heterogeneity of human CRC liver metastases has a distinct, organized pattern. This particular hallmark can now be used as part of the strategy for developing rational therapies based on multiple sets of targetable antigens., (© 2014 by the American Association for the Study of Liver Diseases.)

Background & Aims: The role of liver transplantation in the treatment of hepatocellular carcinoma in livers without fibrosis/cirrhosis (NC-HCC) is unclear. We aimed to determine selection criteria for liver transplantation in patients with NC-HCC., Methods: Using the European Liver Transplant Registry, we identified 105 patients who underwent liver transplantation for unresectable NC-HCC. Detailed information about patient, tumor characteristics, and survival was obtained from the transplant centers. Variables associated with survival were identified using univariate and multivariate statistical analyses., Results: Liver transplantation was primary treatment in 62 patients and rescue therapy for intrahepatic recurrences after liver resection in 43. Median number of tumors was 3 (range 1-7) and median tumor size 8 cm (range 0.5-30). One- and 5-year overall and tumor-free survival rates were 84% and 49% and 76% and 43%, respectively. Macrovascular invasion (HR 2.55, 95% CI 1.34 to 4.86), lymph node involvement (HR 2.60, 95% CI 1.28 to 5.28), and time interval between liver resection and transplantation < 12 months (HR 2.12, 95% CI 0.96 to 4.67) were independently associated with survival. Five-year survival in patients without macrovascular invasion or lymph node involvement was 59% (95% CI 47-70%). Tumor size was not associated with survival., Conclusions: This is the largest reported series of patients transplanted for NC-HCC. Selection of patients without macrovascular invasion or lymph node involvement, or patients ≥ 12months after previous liver resection, can result in 5-year survival rates of 59%. In contrast to HCC in cirrhosis, tumor size is not a predictor of post-transplant survival in NC-HCC., (Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Colorectal cancer is the most frequent digestive cancer. Prognosis is greatly depending on the TNM stage at the time of diagnosis. Fifty percent of all patients shall develop, synchronously or metachronously, liver metastases. Different means such as chemotherapy, targeted therapies, radiofrequency ablation, portal vein embolization and two-stage hepatectomy may be used to make these metastases eventually resectable and to increase overall survival. This is a short review of these different methods used to increase resectability but also on the integration of these parameters in a larger approach of colorectal liver metastasis surgery especially insisting on multidisciplinary discussion.

Hepatocellular carcinoma is the main primitive tumor of the liver. It occurs in the setting of liver cirrhosis in more than 90% of the cases in developing countries. The prognosis depends on the size, number and extension of the tumor as well as on the severity of the underlying liver disease. The Barcelona Clinic Classification takes into account these different parameters and helps the clinician in the therapeutic decision. Some patients (around 25%) are amenable to therapy with a curative intent (liver transplantation, resection, destruction by radiofrequency). In patients with hepatocellular carcinoma at an intermediate stage, lipiodolized chemoembolization gives a survival advantage in comparison with placebo. No conventional regimen of chemotherapy has a proven survival benefit. In patients with a hepatocellular carcinoma at an advanced stage, sorafenib, an oral multi-targeted kinase inhibitor, is the first compound to demonstrate a significant effect on survival free of disease progression in a selected group of patients. Its toxicity profile is particularly favourable. Combination of surgical and medical therapies should be properly evaluated in clinical trials in the near future.

Curative management of early-stage hepatocarcinoma may include partial hepatic resection, liver transplantation or tumoral necrosis using radiofrequency ablation or alcoholisation. Until recently, no efficient therapeutic mean was available for advanced hepatocarcinoma. Sorafenib (Nexavar, Bayer) is a multikinase inhibitor that decreases tumoral proliferation and angiogenesis, and increases apoptosis in many cancer models. The results of a phase 3 randomized, multicentric, study, entitled SHARP, have now demonstrated that sorafenib increases survival in patients with advanced hepatocarcinoma developed in Child A cirrhosis. Mean survival gain was a little less than 3 months, without any radiologic response or improvement in the delay before symptomatic progression of the disease. The monthly cost of sorafenib is a little more than 5,000 euros. It is now crucial to evaluate the potential role of sorafenib in adjuvant therapy after liver resection or radiofrequency ablation of hepatocarcinoma. The CHU of Liège is taking part to a randomized, multicentric study evaluating the use of sorafenib after liver resection or radiofrequency ablation for hepatocarcinoma. Another future evaluation could be the association of sorafenib with other antitumoral agents.

The epithelioid hemangioendothelioma is a rare malignant vascular lesion that may occur within the liver. In the hepatic multifocal and bilobar forms, liver transplantation is indicated as the curative management. In this case report, the authors describe the diagnosis and the management of a 52-year-old woman who was diagnosed with hepatic epithelioid hemangioendothelioma and who underwent successful liver transplantation.

6000 new cases of colorectal cancer are diagnosed each year in Belgium. 50% of these patients shall develop liver metastasis. Resection remains the only chance of long term survival and must be considered as an endpoint from the beginning of the treatment. It is the result of a multidisciplinary discussion and a global approach of the disease. It is rarely directly feasible, but there are many techniques which may make it achievable in the end. Today, resection criteria are exclusively technical and neither bad prognosis factors, nor the presence of extra-hepatic metastases should exclude liver resection. This resection must be assessed by a confirmed hepatobiliary surgeon and must be proposed to all patients whatever their age as long as their general state of health is good.

Although hepatocellular carcinoma (HCC) has become a recognized indication for liver transplantation, the rules governing priority and access to the waiting list are not well defined. Patient- and tumor-related variables were evaluated in 226 patients listed primarily for HCC in Belgium, a region where the allocation system is patient-driven, priority being given to sicker patients, based on the Child-Turcotte-Pugh (CTP) score. Intention-to-treat and posttransplantation survival rates at 4 years were 56.5 and 66%, respectively, and overall HCC recurrence rate was 10%. The most significant predictors of failure to receive a transplant in due time were baseline CTP score equal to or above 9 (relative risk [RR] 4.1; confidence interval [CI]: 1.7-9.9) and alpha fetoprotein above 100 ng/mL (RR 3.0; CI: 1.2-7.1). Independent predictors of posttransplantation mortality were age equal to or above 50 years (RR 2.5; CI: 1.0-3.7) and United Network for Organ Sharing pathological tumor nodule metastasis above the Milan criteria (RR 2.1; CI: 1.0-5.9). Predictors of recurrence (10%) were alpha fetoprotein above 100 ng/mL (RR 3.2; CI:1.1-10) and vascular involvement of the tumor on the explant (RR 3.6; CI: 1.1-11.3). Assessing the value of the pretransplantation staging by imaging compared to explant pathology revealed 34% accuracy, absence of carcinoma in 8.3%, overstaging in 36.2%, and understaging in 10.4%. Allocation rules for HCC should consider not only tumor characteristics but also the degree of liver impairment. Patients older than 50 years with a stage above the Milan criteria at transplantation have a poorer prognosis after transplantation., ((c) 2008 AASLD.)

Transmission of an undiagnosed cancer with solid organ transplantation is a rare but dreadful event. In this paper the authors report the transmission of an undiagnosed sarcoma to recipients of kidney and liver grafts procured in a Maastricht category 3 non-heart beating donor. To the authors' knowledge this case is the first report of such a transmission with a liver graft procured in a non-heart beating donor. The cancer transferal was diagnosed 1 year after transplantation in the recipients of the liver and of one kidney. The liver recipient died from multiple organ failure after a failed attempt of tumor resection. The kidney recipient underwent immunosuppression withdrawal and transplantectomy. Non-heart beating donors should not be particularly at risk for undiagnosed cancer transmission if the procurement is performed according to the same rules of careful inspection of the abdominal and thoracic organs. After diagnosis of donor cancer transmission, kidney recipients should have the graft removed, and immunosuppression should be interrupted. The management of liver graft recipients is very difficult in this setting, and long-term survival was very rarely reported.

In noncolorectal, nonendocrine liver metastases, the role of surgery is less define than in colorectal or neuroendocrine cancer. This role is marginal as liver is not the primary site of metastases of these cancers. Less than 2 to 5% of the patients with these malignancies might be one day considered as potential candidates for liver resection, as most patients suffer from extra hepatic tumour spread at the time they develop liver involvement. However, in these few cases with liver metastases only, as no other therapeutic option may provide mid- or long-term tumour-free survival, liver resection is indicated in resectable liver metastases. Some prognostic factors have been established in the literature from the few published series: unique versus multiple hepatic metastases, unilobar vs bilobar, metachronous vs synchronous, R0 vs R1 or R2 liver resections. The type of primary tumour is also of great importance, as cutaneous melanoma, pancreatic and gastric adenocarcinoma have a very bad prognosis for liver resection of metastases, even after R0 resection. In these cases, percutaneous or laparoscopic radiofrequency ablation may find its place. In sarcoma, breast carcinoma, uveal melanoma, and genitourinary cancers, liver resection may provide satisfactory long-term results in selected cases, and is the standard of care for isolated, resectable metastasis. However, due to the scarcity of indication of liver resection for noncolorectal, nonneuroendocrine metastases, the decision should be multidisciplinary, and the patients should be informed of the advantages and pitfalls of the surgical procedure.

Because of dismal mid-term and long-term results, secondary liver cancer is considered an absolute contra-indication to cadaveric liver transplantation, with the relative exception of metastases of symptomatic neuro-endocrine cancers. The authors present in this report the case of a patient who has been enjoying 10 years of cancer-free survival after liver transplantation as rescue therapy for acute liver failure after liver resection for isolated hepatic metastasis of colon adenocarcinoma. This case shows that in some highly selected cases, liver transplantation may be curative in patients with liver metastases of colon carcinoma.

Objective: The objective of this study was to assess the feasibility, safety, and outcome of laparoscopic liver resection for benign liver tumors in a multicenter setting., Background: Despite restrictive, tailored indications for resection in benign liver tumors, an increasing number of articles have been published concerning laparoscopic liver resection of these tumors., Methods: A retrospective study was performed in 18 surgical centres in Europe regarding their experience with laparoscopic resection of benign liver tumors. Detailed standardized questionnaires were used that focused on patient's characteristics, clinical data, type and characteristics of the tumor, technical details of the operation, and early and late clinical outcome., Results: From March 1992 to September 2000, 87 patients suffering from benign liver tumor were included in this study: 48 patients with focal nodular hyperplasia (55%), 17 patients with liver cell adenoma (21%), 13 patients with hemangioma (15%), 3 patients with hamartoma (3%), 3 patients with hydatid liver cysts (3%), 2 patients with adult polycystic liver disease (APLD) (2%), and 1 patient with liver cystadenoma (1%). The mean size of the tumor was 6 cm, and 95% of the tumors were located in the left liver lobe or in the anterior segments of the right liver. Liver procedures included 38 wedge resections, 25 segmentectomies, 21 bisegmentectomies (including 20 left lateral segmentectomies), and 3 major hepatectomies. There were 9 conversions to an open approach (10%) due to bleeding in 45% of the patients. Five patients (6%) received autologous blood transfusion. There was no postoperative mortality, and the postoperative complication rate was low (5%). The mean postoperative hospital stay was 5 days (range, 2-13 days). At a mean follow-up of 13 months (median, 10 months; range, 2-58 months), all patients are alive without disease recurrence, except for the 2 patients with APLD., Conclusions: Laparoscopic resection of benign liver tumors is feasible and safe for selected patients with small tumors located in the left lateral segments or in the anterior segments of the right liver. Despite the use of a laparoscopic approach, selective indications for resection of benign liver tumors should remain unchanged. When performed by expert liver and laparoscopic surgeons in selected patients and tumors, laparoscopic resection of benign liver tumor is a promising technique.

Important progress has been made in the treatment of liver metastases of advanced colorectal cancer. Surgery with curative intent, when possible, shows evidence of prolonged survival. Response rate and overall survival can be improved with modern polychemotherapy. Cytotoxic drug combinations and sequential treatments sometimes make surgery possible for initially non resectable lesions. Impact of loco-regional treatment such as hepatic arterial infusion chemotherapy must be defined in randomised trials. Radiofrequency ablation is also currently evaluated in clinical trials. In this review the benefit of each treatment is discussed.