Survival and Quality of Life after Isolated Hepatic Perfusion with Melphalan as a Treatment for Uveal Melanoma Liver Metastases - Final Results from the Phase III Randomized Controlled Trial SCANDIUM.

OBJECTIVE: To investigate overall survival (OS) and health-related quality of life (HRQOL) of first-line isolated hepatic perfusion (IHP) compared to best alternative care (BAC) for patients with uveal melanoma liver metastases. SUMMARY BACKGROUND DATA: Approximately half of patients with uveal melanoma develop metastatic disease, most commonly in the liver and systemic treatment options are limited. Isolated hepatic perfusion (IHP) is a locoregional therapy with high response rates but with unclear effect on overall survival (OS). METHODS: In this phase III randomized controlled multicenter trial (the SCANDIUM trial) patients with previously untreated isolated uveal melanoma liver metastases were included between 2013-2021, with at least 24 months of follow-up. The planned accrual was 90 patients randomized 1:1 to receive a one-time treatment with IHP or BAC. Crossover to IHP was not allowed. The primary endpoint was the 24-month OS rate, with the hypothesis of a treatment effect leading to a 50% OS rate in the IHP group compared to 20% in the control group. HRQOL was measured by the EuroQol 5-domains 3-levels (EQ-5D-3L) questionnaire over 12 months. RESULTS: The intention-to-treat (ITT) population included 87 patients randomized to the IHP group (43 patients; 41 [89%] received IHP) or the control group (44 patients). The control group received chemotherapy (49%), immunotherapy (39%), or localized interventions (9%). In the ITT population, the median PFS was 7.4 months in the IHP group compared with 3.3 months in the control group, with a hazard ratio of 0.21 (95% CI, 0.12-0.36). The 24-month OS rate was 46.5% in the IHP group versus 29.5% in the control group (P=0.12). The median OS was 21.7 months versus 17.6 months, with a hazard ratio of 0.64 (95% CI, 0.37-1.10). EQ-5D-3L showed a sustained high health status for the IHP group over 12 months, compared to a deteriorating trend in the control group. CONCLUSIONS: For patients with liver metastases from uveal melanoma, IHP offers high response rates translating to a benefit in PFS including a trend of better HRQOL compared to the control group. However, the primary endpoint of OS at 24 months was not met.

Treatment and survival of patients with metachronous colorectal lung metastases.

INTRODUCTION: The lungs are the second most common site for metachronous metastases in colorectal cancer. No treatment algorithm is established, and the role of adjuvant chemotherapy is unclear. This study aimed to map pulmonary recurrences in a modern multimodal treated population, and to evaluate survival depending on management. METHODS: Retrospective study based on the COLOFOL-trial population of 2442 patients, radically resected for colorectal cancer stage II-III. All recurrences within 5 years were identified and medical records were scrutinized. RESULTS: Of 165 (6.8%) patients developing lung metastases as first recurrence, 89 (54%) were confined to the lungs. Potentially curative treatment was possible in 62 (37%) cases, of which 33 with surgery only and 29 with surgery and chemotherapy combined. The 5-year overall survival (5-year OS) for all lung recurrences was 28%. In patients treated with chemotherapy only the 5-year OS was 7.5%, compared with 55% in patients treated with surgery, and 72% when surgery was combined with chemotherapy. Hazard ratio for mortality was 2.9 (95% confidence interval 1.40-6.10) for chemotherapy only compared to surgery. CONCLUSION: A high proportion of metachronous lung metastases after colorectal surgery were possible to resect, yielding good survival. The combination of surgery and chemotherapy might be advantageous for survival.

Risk Factors for Postoperative Complications Following Resection of Colorectal Liver Metastases and the Impact on Long-Term Survival: A Population-Based National Cohort Study.

BACKGROUND: Postoperative complications (POCs) following resection of colorectal liver metastases (CRLM) are common. The objective of this study was to evaluate risk factors for developing complications and their impact on survival considering prognostic factors of the primary tumor, metastatic pattern and treatment in a well-defined national cohort. METHODS: Patients treated with resection for CRLM that was also radically resected for their primary colorectal cancer (diagnosed in 2009-2013) were identified in Swedish national registers. Liver resections were categorized according to extent of surgery (Category I-IV). Risk factors for developing POCs as well as prognostic impact of POCs were evaluated in multivariable analyses. A subgroup analysis of minor resections was performed to evaluate POCs after laparoscopic surgery. RESULTS: POCs were registered for 24% (276/1144) of all patients after CRLM resection. Major resection was a risk factor for POCs in multivariable analysis (IRR 1.76; P = 0.001). Comparing laparoscopic and open resections in the subgroup analysis of small resections, 6% (4/68) in the laparoscopic group developed POCs compared to 18% (51/289) after open resection (IRR 0.32; P = 0.024). POCs were associated with a 27% increased excess mortality rate (EMRR 1.27; P = 0.044). However, primary tumor characteristics, tumor burden in the liver, extrahepatic spread, extent of liver resection and radicality had higher impact on survival. CONCLUSION: Minimal invasive resections were associated with a decreased risk of POCs following resection of CRLM which should be considered in surgical strategy. Postoperative complications were associated with a moderate risk for inferior survival.

Evaluation of response in patients with hepatocellular carcinoma treated with intratumoral dendritic cell vaccination using intravoxel incoherent motion (IVIM) MRI and histogram analysis.

BACKGROUND: Immunotherapy of hepatocellular carcinoma (HCC) is an emerging method with promising results. Immunotherapy can have an antitumor effect without affecting tumor size, calling for functional imaging methods for response evaluation. PURPOSE: To evaluate the response to intratumoral injections with the immune primer ilixadencel in HCCs with diffusion-weighted magnetic resonance imaging (DW-MRI) using intravoxel incoherent motion (IVIM) and histogram analysis. MATERIAL AND METHODS: A total of 17 patients with advanced HCC were treated with intratumoral injections with ilixadencel on three occasions 2-5 weeks apart. The patients were examined with IVIM before each injection as well as approximately three months after the first injection. RESULTS: The 10th percentile of perfusion-related parameter D* decreased significantly after the first and second intratumoral injections of ilixadencel compared to baseline (P < 0.05). There was a non-significant trend of lower median region of interest f (perfusion fraction) before injection 2 compared to baseline (P = 0.07). There were significant correlations between the 10th percentile and median of D at baseline and change in tumor size after three months (r = 0.79, P < 0.01 and r = 0.72, P < 0.05, respectively). CONCLUSION: DW-MRI with IVIM and histogram analysis revealed significant reductions of D* early after treatment as well as an association between D at baseline and smaller tumor growth at three months. The lower percentiles (10th and 50th) were found more important. Further research is needed to confirm our preliminary findings of reduced perfusion after ilixadencel vaccinations, suggesting a treatment effect on HCC.

High resection rates of colorectal liver metastases after standardized follow-up and multimodal management: an outcome study within the COLOFOL trial.

BACKGROUND: Outcome after colorectal liver metastases (CRLM) resection has improved over time, despite increased resection rates. Hence, it's crucial to identify all patients possible to treat with curative intent. The objectives of this study were to map recurrence pattern, treatment strategy and survival depending on treatment and follow-up strategy. METHODS: In the COLOFOL-trial, patients with radically resected stage II-III colorectal cancer were randomized to high-frequency (6, 12, 18, 24 and 36 months; HF) or low-frequency (12 and 36 months; LF) follow-up. In this study, all CRLM within 5 years were identified and medical files scrutinized. Overall survival (OS) was analysed in uni- and multivariable analyses. Primary endpoint was 5-year OS. RESULTS: Of 2442 patients, 235 (9.6%) developed metachronous CRLM of which 123 (52.3%) underwent treatment with curative intent, resulting in 5-year OS of 58%. Five-year OS for patients with CRLM was 43% after HF versus 24% after LF. The survival benefit was confirmed for HF 8 years from resection of the primary tumour, HR 0.63 (CI 0.46-0.85). CONCLUSION: A high proportion of metachronous CRLM was possible to treat with curative intent, yielding high survival rates. More intense follow-up after colorectal cancer resection might be of value in high-risk patients.

Reduced calcineurin inhibitor exposure with antibody induction and recurrent hepatocellular carcinoma after liver transplantation.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common indication for liver transplantation (LT), but post-LT tumor recurrence remains a concern. Early post-LT immunosuppression is suggested to affect recurrence risk. We evaluated the impact on HCC recurrence of an immunosuppression protocol introduced in 2010 with interleukin-2 receptor antibody (IL-2RA) induction and delayed-introduction of reduced-dose tacrolimus with mycophenolate. METHODS: We included consecutive HCC patients transplanted 2000-2017 in Gothenburg. The impact on HCC recurrence of IL-2RA induction and mean tacrolimus trough concentration during the first 20 post-LT days was analyzed by multivariable Cox regression and propensity score-adjusted analyses. RESULTS: The study comprised 235 patients (mean age 57 yrs, men 80%, mean MELD 13, within Milan criteria 57%). The cumulative 5-yr HCC recurrence rate among patients transplanted before and after 2010 were 28.6% and 19.7%, respectively. IL-2RA induction had no independent effect on HCC recurrence. High tacrolimus exposure (mean 20-day tacrolimus concentration ≥8ng/mL) was associated with increased HCC recurrence risk on univariable analysis (HR 2.22, 95% CI 1.23-4.01, p = .008), but was non-significant on multivariable analysis (p = .17). Outside Milan criteria, high tacrolimus exposure was significant for HCC recurrence (HR 3.68, 95% CI 1.34-10.11, p = .012) independently of tumor characteristics and AFP level. This was confirmed on multivariable propensity score-adjusted analysis. CONCLUSIONS: Reduced early tacrolimus exposure, facilitated by IL-2RA induction, was associated with reduced risk for HCC recurrence among patients outside Milan criteria. Prospective studies are needed to confirm if early tacrolimus-minimization strategies can help reduce HCC recurrence rates and help extend transplant criteria.

ALPPS Improves Survival Compared With TSH in Patients Affected of CRLM: Survival Analysis From the Randomized Controlled Trial LIGRO.

OBJECTIVE: To evaluate the oncological outcome for patients with colorectal liver metastases (CRLM) randomized to associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) or 2-stage hepatectomy (TSH). BACKGROUND: TSH with portal vein occlusion is an established method for patients with CRLM and a low volume of the future liver remnant (FLR). ALPPS is a less established method. The oncological outcome of these methods has not been previously compared in a randomized controlled trial. METHODS: One hundred patients with CRLM and standardized FLR (sFLR) <30% were included and randomized to resection by ALPPS or TSH, with the option of rescue ALPPS in the TSH group, if the criteria for volume increase was not met. The first radiological follow-up was performed approximately 4 weeks postoperatively and then after 4, 8, 12, 18, and 24 months. At all the follow-ups, the remaining/recurrent tumor was noted. After the first follow-up, chemotherapy was administered, if indicated. RESULTS: The resection rate, according to the intention-to-treat principle, was 92% (44 patients) for patients randomized to ALPPS compared with 80% (39 patients) for patients randomized to TSH (P = 0.091), including rescue ALPPS. At the first postoperative follow-up, 37 patients randomized to ALPPS were assessed as tumor free in the liver, and also 28 patients randomized to TSH (P = 0.028). The estimated median survival for patients randomized to ALPPS was 46 months compared with 26 months for patients randomized to TSH (P = 0.028). CONCLUSIONS: ALPPS seems to improve survival in patients with CRLM and sFLR <30% compared with TSH.

The RETREAT score provides valid predictions regarding hepatocellular carcinoma recurrence after liver transplantation.

Prediction of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) with knowledge of explant data is important for guiding post-LT surveillance and treatment. The RETREAT score was recently introduced for this purpose, but has not been validated outside the USA. In a retrospective single-center study of 169 consecutive patients undergoing LT in Gothenburg, through 2000-2017 (mean age 57 years, 80% men), there were 34 HCC recurrences during a median 4.6-year follow-up. The 5-year cumulative incidence of HCC recurrence was 0% with RETREAT scores of 0-1 (18%), 11-22% with scores of 2-4 (58%), and 65% with scores of 5-8 (24%). The C-statistic, as a measure of discrimination for prediction of HCC recurrence was 0.762, 0.664, 0.616, and 0.717, for the RETREAT score, Milan criteria, UCSF criteria, and post-MORAL criteria. The RETREAT score had no significant impact on patient survival after HCC recurrence (HR 1.00, P = 0.97). In conclusion, the RETREAT score provided valid predictions of post-LT HCC recurrence in a European setting, with the ability to discriminate between high, intermediate, and low risk for HCC recurrence in a clinically important way. Prognosis after recurrence did not differ according to the RETREAT score in our study.

Myocardial, renal and intestinal injury in liver resection surgery-A prospective observational pilot study.

BACKGROUND: Post-operative organ complications in liver resection surgery are not uncommon. This prospective observational pilot study was performed to evaluate the incidence, degree and timing of myocardial, renal and intestinal injury in patients undergoing liver resection surgery using the low central venous pressure (LCVP) technique and the Pringle manoeuvre. METHODS: Blood samples were obtained before, during and after elective liver resection until post-operative day (POD) 5. High-sensitive troponin T (hs-TnT), serum creatinine, urea, intestinal fatty acid binding protein (I-FABP), D-lactate, arterial lactate, portal lactate, amylase, as well as urine N-acetyl-ß-D-glucosaminidase (NAG) were analysed. Systemic haemodynamics were measured intraoperatively. RESULTS: Eighteen patients fulfilled the protocol. The Pringle manoeuvre was used in all but 1 patient. hs-TnT increased significantly over time (P < .001) and 5 patients (28%) developed myocardial injury. Five patients had a pre-operative elevation of hs-TnT, four of those developed myocardial injury. Serum creatinine increased significantly over time (P = .015). Acute kidney injury (AKI) occurred in 5 patients (28%), while NAG, as a marker of tubular injury, was not affected. I-FABP increased over time (P < .001) with a maximal 75% increase at 3 hours after resection. D-lactate was below detection level at all measuring points. CONCLUSIONS: In patients undergoing liver resection surgery, using LCVP technique and Pringle manoeuvre, myocardial injury was seen in approximately 30% of the patients post-operatively and almost 30% developed transient AKI in the early post-operative period with no tubular injury. Furthermore, a transient increase of the enterocyte damage marker I-FABP was demonstrated with no signs of gut barrier dysfunction.

Survival and prognostic factors after transplantation, resection and ablation in a national cohort of early hepatocellular carcinoma.

BACKGROUND: In patients with early hepatocellular cancer (HCC) and preserved liver function, the choice between transplantation, resection and ablation and which factors to consider is not obvious and guidelines differ. In this national cohort study, we aimed to compare posttreatment survival in patients fulfilling predefined criteria, and to analyse preoperative risk factors that could influence decision. METHODS: We used data from HCC-patients registered with primary transplantation, resection or ablation 2008-2016 in the SweLiv-registry. In Child A-subgroups, 18-75 years, we compared survival after transplantation or resection, with different tumour criteria; either corresponding to our transplantation criteria (N = 257) or stricter with single tumours ≤50 mm (N = 159). A subgroup with single tumours ≤30 mm, compared all three treatments (N = 193). RESULTS: We included 1022 HCC-patients; transplantation n = 223, resection n = 438, ablation n = 361. In the transplant criteria subgroup, differences in five-year survival, adjusted for age and gender, were not significant, with 71.2% (CI 62.3-81.3) after transplantation (n = 109) and 63.5% (CI 54.9-73.5) after resection (n = 148). Good liver function (Child 5 vs. 6, Albumin ≥36), increased the risk after transplantation, but decreased the risk after resection and ablation. CONCLUSION: Even within Child A, detailed liver function assessment is important before treatment decision, and for stratifying survival comparisons.

mTOR Inhibition Is Most Beneficial After Liver Transplantation for Hepatocellular Carcinoma in Patients With Active Tumors.

OBJECTIVE: The aim of this study was to evaluate the survival benefit of sirolimus in patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC) (exploratory analysis of the SiLVER-trial). SUMMARY AND BACKGROUND DATA: Patients receiving LT) for HCC are at a high risk for tumor recurrence. Calcineurin inhibitors have shown evidence to promote cancer growth, whereas mammalian target of rapamycin (mTOR) inhibitors like sirolimus have anticancer effects. In the SiLVER-trial (Clinicaltrials.gov: NCT00355862), the effect of sirolimus on the recurrence of HCC after LT was investigated in a prospective randomized trial. Although the primary endpoint of improved disease-free survival (DFS) with sirolimus was not met, outcomes were improved for patients in the sirolimus-treatment arm in the first 3 to 5 years. To learn more about the key variables, a multivariate analysis was performed on the SiLVER-trial data. PATIENTS AND METHODS: Data from 508 patients of the intention-to-treat analysis were included in exploratory univariate and multivariate models for overall survival (OS), DFS and a competing risk analysis for HCC recurrence. RESULTS: Sirolimus use for ≥3 months after LT for HCC independently reduced the hazard for death in the multivariate analysis [hazard ratio (HR): 0.7 (95% confidence interval, CI: 0.52-0.96, P = 0.02). Most strikingly, patients with an alpha-fetoprotein (AFP) ≥10 ng/mL and having used sirolimus for ≥3 months, benefited most with regard to OS, DFS, and HCC-recurrence (HR: 0.49-0.59, P = 0.0079-0.0245). CONCLUSIONS: mTOR-inhibitor treatment with sirolimus for ≥3 months improves outcomes in LT for HCC, especially in patients with AFP-evidence of higher tumor activity, advocating particularly for mTOR inhibitor use in this subgroup of patients. CLINICAL TRIAL REGISTRATION: EudraCT: 2005-005362-36 CLINICALTRIALS.GOV:: NCT00355862.

Outcomes of Simultaneous Resections and Classical Strategy for Synchronous Colorectal Liver Metastases in Sweden: A Nationwide Study with Special Reference to Major Liver Resections.

BACKGROUND: About 20% of patients with colorectal cancer have liver metastases at the time of diagnosis, and surgical resection offers a chance for cure. The aim of the present study was to compare outcomes for patients that underwent simultaneous resection to those that underwent a staged procedure with the bowel-first (classical) strategy by using information from two national registries in Sweden. METHODS: In this prospectively registered cohort study, we analyzed clinical, pathological, and survival outcomes for patients operated in the period 2008-2015 and compared the two strategies. RESULTS: In total, 537 patients constituted the study cohort, where 160 were treated with the simultaneous strategy and 377 with the classical strategy. Patients managed with the simultaneous strategy had less often rectal primary tumors (22% vs. 31%, p = 0.046) and underwent to a lesser extent a major liver resection (16% vs. 41%, p < 0.001), but had a shorter total length of stay (11 vs. 15 days, p < 0.001) and more complications (52% vs. 36%, p < 0.001). No significant 5-year overall survival (p = 0.110) difference was detected. Twenty-five patients had a major liver resection in the simultaneous strategy group and 155 in the classical strategy group without difference in 5-year overall survival (p = 0.198). CONCLUSION: Simultaneous resection of the colorectal primary cancer and liver metastases can possibly have more complications, with no difference in overall survival compared to the classical strategy.

A prospective clinical trial on sorafenib treatment of hepatocellular carcinoma before liver transplantation.

BACKGROUND: Patients with hepatocellular carcinoma waiting for liver transplantation are commonly treated with locoregional treatments, such as TACE and ablation, to prevent tumor progression and dropout and to improve long-term outcome after transplantation. We wanted to prospectively assess feasibility of systemic antitumor treatment with sorafenib as neoadjuvant treatment for hepatocellular carcinoma while waiting for liver transplantation, evaluating tolerability, toxicity and posttransplant morbidity. We also wanted to evaluate perfusion CT parameters to assess tumor properties and response early after start of sorafenib treatment in patients with early hepatocellular carcinoma. METHODS: Twelve patients assigned for liver transplantation due to hepatocellular carcinoma, within the UCSF and who fulfilled other criteria, were included January 2012-August 2014. After baseline evaluation, sorafenib treatment was started. Treatment was evaluated by perfusion CT at 1, 4 and 12 weeks and thereafter every 8 weeks. Toxicity and quality of life was assessed at 1 and 4 weeks and every 4 weeks thereafter during treatment. Treatment was stopped when patients were prioritized on the transplantation waiting list or when intolerable side effects or tumor progress warranted other treatments. Posttransplant morbidity after 90 days was registered according to Clavien-Dindo. RESULTS: Baseline perfusion CT parameters in the tumors predicted the outcome according to RECIST/mRECIST at three months, but no change in CTp parameters was detected as a result of sorafenib. Sorafenib as neoadjuvant treatment was associated with intolerability and dose reductions. Therefore the prerequisites for evaluation of the sorafenib effect on both CT parameters and tumor response were impaired. CONCLUSIONS: This study failed to show changes in CTp parameters during sorafenib treatment. Despite the curative treatment intention, tolerability of neoadjuvant sorafenib treatment before liver transplantation was inadequate in this study. TRIAL REGISTRATION: EudraCT number: 2010-024306-36 (date 2011-04-07).

ALPPS Improves Resectability Compared With Conventional Two-stage Hepatectomy in Patients With Advanced Colorectal Liver Metastasis: Results From a Scandinavian Multicenter Randomized Controlled Trial (LIGRO Trial).

OBJECTIVE: The aim of the study was to evaluate if associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) could increase resection rates (RRs) compared with two-stage hepatectomy (TSH) in a randomized controlled trial (RCT). BACKGROUND: Radical liver metastasis resection offers the only chance of a cure for patients with metastatic colorectal cancer. Patients with colorectal liver metastasis (CRLM) and an insufficient future liver remnant (FLR) volume are traditionally treated with chemotherapy with portal vein embolization or ligation followed by hepatectomy (TSH). This treatment sometimes fails due to insufficient liver growth or tumor progression. METHODS: A prospective, multicenter RCT was conducted between June 2014 and August 2016. It included 97 patients with CRLM and a standardized FLR (sFLR) of less than 30%. Primary outcome-RRs were measured as the percentages of patients completing both stages of the treatment. Secondary outcomes were complications, radicality, and 90-day mortality measured from the final intervention. RESULTS: Baseline characteristics, besides body mass index, did not differ between the groups. The RR was 92% [95% confidence interval (CI) 84%-100%] (44/48) in the ALPPS arm compared with 57% (95% CI 43%-72%) (28/49) in the TSH arm [rate ratio 8.25 (95% CI 2.6-26.6); P < 0.0001]. No differences in complications (Clavien-Dindo ≥3a) [43% (19/44) vs 43% (12/28)] [1.01 (95% CI 0.4-2.6); P = 0.99], 90-day mortality [8.3% (4/48) vs 6.1% (3/49)] [1.39 [95% CI 0.3-6.6]; P = 0.68] or R0 RRs [77% (34/44) vs 57% (16/28)] [2.55 [95% CI 0.9-7.1]; P = 0.11)] were observed. Of the patients in the TSH arm that failed to reach an sFLR of 30%, 12 were successfully treated with ALPPS. CONCLUSION: ALPPS is superior to TSH in terms of RR, with comparable surgical margins, complications, and short-term mortality.

Quality of life as a prognostic factor for survival in hepatocellular carcinoma.

BACKGROUND & AIMS: Prognostication in hepatocellular carcinoma (HCC) is demanding. Not only tumour extent and performance status are to be considered, but also liver function, which is often limiting for both survival itself and for treatment possibilities. This study was conducted to assess whether patient-reported questionnaires containing general and liver-specific questions could improve prognostication of survival. METHODS: 185 patients with hepatocellular carcinoma in Norway and Sweden were prospectively included. Patients completed the quality-of-life questionnaires EORTC QLQ C30 and HCC18, and clinical, radiological and laboratory parameters were registered. Multivariate Cox regression and Harrell's C-statistics were used to identify the model that best predicted mortality. RESULTS: Quality-of-life data were prognostic for overall survival. Fatigue and nutrition scales were prognostic in the multivariable analyses alone and in combination with clinical parameters. The prognostic value of established scoring systems was increased by the addition of QoL data. The best prognostic power was achieved by combining HCC18 nutrition scale with selected background parameters. CONCLUSION: Quality-of-life questionnaires can prognosticate mortality in HCC patients. When combined with established scoring systems, both the general cancer questionnaire EORTC QLQ C30, and the additional liver cancer-specific HCC18 increased the prognostic accuracy slightly.

Addition of alfa fetoprotein to traditional criteria for hepatocellular carcinoma improves selection accuracy in liver transplantation.

OBJECTIVES: Liver transplantation in hepatocellular cancer (HCC) is curative only for a selection of patients. Commonly used criteria are mostly based on tumor size and number. However, patients within criteria do have tumor recurrences after transplantation and patients outside criteria are excluded even though some could benefit from transplantation. The tumor marker alpha fetoprotein (AFP) is associated with poor outcome and has already been reported to improve selection. We investigated the hypothesis that AFP level combined with traditional selection criteria could ameliorate the selection accuracy for liver transplantation in HCC. MATERIALS AND METHODS: A retrospective national cohort study in 336 patients who had liver transplantation for HCC in Sweden 1996-2014. RESULTS: AFP cut-off levels of 20, 100, 1000 and >1000 ng/mL stratified both survival and tumor recurrence, with estimated 5-year survival rates of 74, 61, 49 and 31%, respectively. A simple score, combining three risk levels according to Milan and UCSF fulfillment with three levels of AFP, increased predictive accuracy. A high score identified 35 at-risk patients with estimated post-transplant 5-year survival rate of only 29% compared to 50% for 76 patients excluded by UCSF. More patients were within the combined score cut-off compared to within UCSF, but 5-year survival was similar, 67% versus 66%. CONCLUSION: AFP combined with traditional selection criteria ameliorates the selection accuracy for liver transplantation in HCC.

The impact of post-hepatectomy liver failure on mortality: a population-based study.

BACKGROUND: Post-hepatectomy liver failure (PHLF) is considered a main reason for death after major hepatectomy. The reported PHLF-related mortality differs largely and the data mainly originate from single centers. AIM: A retrospective, population-based register study was designed to evaluate the impact of PHLF on 90-day mortality after hepatectomy. METHOD: All patients who underwent liver resection in Sweden between 2005 and 2009 were retrospectively identified using the Swedish Hospital Discharge Registry. 30- and 90-day mortality were identified by linkage to the Registry of Causes of Death. Additional clinical data were obtained from the medical charts in all seven university hospitals in Sweden. PHLF was defined according to Balzan criteria (Bilirubin >50 µg/L and international normalized ratio >1.5) on postoperative day 5. RESULTS: A total of 2461 liver resections were performed (2194 in university hospitals). 30- and 90-day mortality were 1.3% and 2.5%, respectively. 90-day mortality at university hospitals was 2.1% (n = 46). In 41% (n = 19) of these patients, PHLF alone or in combination with multi-organ failure was identified as cause of death. Between the PHLF and non-PHLF group, there was no significant difference regarding age, sex, American Society of Anesthesiologists-classification, or preoperative chemotherapy. Cholangiocarcinoma as indication for surgery, need for vascular reconstruction and an extended resection were significantly overrepresented in the PHLF-group. Between groups, the incidence of 50:50 criteria differed significantly already on postoperative day 3. CONCLUSION: Overall mortality is very low after hepatectomy in Sweden. PHLF represents the single most important cause of death even in a population-based setting.

Outcomes of liver-first strategy and classical strategy for synchronous colorectal liver metastases in Sweden.

BACKGROUND: Patients with synchronous colorectal liver metastases (sCRLM) are increasingly operated with liver resection before resection of the primary cancer. The aim of this study was to compare outcomes in patients following the liver-first strategy and the classical strategy (resection of the bowel first) using prospectively registered data from two nationwide registries. METHODS: Clinical, pathological and survival outcomes were compared between the liver-first strategy and the classical strategy (2008-2015). Overall survival was calculated. RESULTS: A total of 623 patients were identified, of which 246 were treated with the liver-first strategy and 377 with the classical strategy. The median follow-up was 40 months. Patients chosen for the classical strategy more often had T4 primary tumours (23% vs 14%, P = 0.012) and node-positive primaries (70 vs 61%, P = 0.015). The liver-first patients had a higher liver tumour burden score (4.1 (2.5-6.3) vs 3.6 (2.2-5.1), P = 0.003). No difference was seen in five-year overall survival between the groups (54% vs 49%, P = 0.344). A majority (59%) of patients with rectal cancer were treated with the liver-first strategy. CONCLUSION: The liver-first strategy is currently the dominant strategy for sCRLM in patients with rectal cancer in Sweden. No difference in overall survival was noted between strategies.