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Importance: Tranexamic acid reduces bleeding and blood transfusion in many types of surgery, but its effect in patients undergoing liver resection for a cancer-related indication remains unclear., Objective: To determine whether tranexamic acid reduces red blood cell transfusion within 7 days of liver resection., Design, Setting, and Participants: Multicenter randomized clinical trial of tranexamic acid vs placebo conducted from December 1, 2014, to November 8, 2022, at 10 hepatopancreaticobiliary sites in Canada and 1 site in the United States, with 90-day follow-up. Participants, clinicians, and data collectors were blinded to allocation. A volunteer sample of 1384 patients undergoing liver resection for a cancer-related indication met eligibility criteria and consented to randomization., Interventions: Tranexamic acid (1-g bolus followed by 1-g infusion over 8 hours; n = 619) or matching placebo (n = 626) beginning at induction of anesthesia., Main Outcomes and Measures: The primary outcome was receipt of red blood cell transfusion within 7 days of surgery., Results: The primary analysis included 1245 participants (mean age, 63.2 years; 39.8% female; 56.1% with a diagnosis of colorectal liver metastases). Perioperative characteristics were similar between groups. Red blood cell transfusion occurred in 16.3% of participants (n = 101) in the tranexamic acid group and 14.5% (n = 91) in the placebo group (odds ratio, 1.15 [95% CI, 0.84-1.56]; P = .38; absolute difference, 2% [95% CI, -2% to 6%]). Measured intraoperative blood loss (tranexamic acid, 817.3 mL; placebo, 836.7 mL; P = .75) and total estimated blood loss over 7 days (tranexamic acid, 1504.0 mL; placebo, 1551.2 mL; P = .38) were similar between groups. Participants receiving tranexamic acid experienced significantly more complications compared with placebo (odds ratio, 1.28 [95% CI, 1.02-1.60]; P = .03), with no significant difference in venous thromboembolism (odds ratio, 1.68 [95% CI, 0.95-3.07]; P = .08)., Conclusions and Relevance: Among patients undergoing liver resection for a cancer-related indication, tranexamic acid did not reduce bleeding or blood transfusion but increased perioperative complications., Trial Registration: ClinicalTrials.gov Identifier: NCT02261415.

Hepatic resection remains the treatment of choice for colorectal liver metastases. The advancement of surgical technique and use of perioperative systemic therapy has expanded the number and complexity of patients eligible for surgical resection. In recent years, investigation into gene mutations, such as RAS/RAF pathway, have led to targeted therapies that have significantly improved outcomes. Next-generation sequencing allows analysis of large number of genes that may have potential prognostic relevance in the clinical setting. This review summarizes the current applications of next-generation sequencing technology in metastatic colorectal cancer, focusing on its prognostic implications on patient management., (© 2023. Crown.)

Background: Hepatocellular carcinoma (HCC) a leading cause of cancer mortality worldwide and approximately one-third of patients present with intermediate-stage disease. The treatment landscape of intermediate-stage HCC is rapidly evolving due to developments in local, locoregional and systemic therapies. Treatment recommendations focused on this heterogenous disease stage and that take into account the Canadian reality are lacking. To address this gap, a pan-Canadian group of experts in hepatology, transplant, surgery, radiation therapy, nuclear medicine, interventional radiology, and medical oncology came together to develop consensus recommendations on management of intermediate-stage HCC relevant to the Canadian context., Methods: A modified Delphi framework was used to develop consensus statements with strengths of recommendation and supporting levels of evidence graded using the AHA/ACC classification system. Tentative consensus statements were drafted based on a systematic search and expert input in a series of iterative feedback cycles and were then circulated via online survey to assess the level of agreement., Results & Conclusion: The pre-defined ratification threshold of 80 % agreement was reached for all statements in the areas of multidisciplinary treatment (n = 4), intra-arterial therapy (n = 14), biologics (n = 5), radiation therapy (n = 3), surgical resection and transplantation (n = 7), and percutaneous ablative therapy (n = 4). These generally reflected an expansion in treatment options due to developments in previously established or emergent techniques, introduction of new and more active therapies and increased therapeutic flexibility. These developments have allowed for greater treatment tailoring and personalization as well as a paradigm shift toward strategies with curative intent in a wider range of disease settings., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Robert J Abraham has served as Chief Medical Officer for and holds stock of ABK Biomedical Inc., has served as a consultant or advisor to Eisai Canada and holds patents WO2012101524A2 and WO2020082168A1. Kelly W Burak has received honoraria from CADTH, Health Canada. Prosanto Chaudhury has received honoraria from Astellas, Ipsen, AstraZeneca, Novartis, and Wyeth. Laura A Dawson has served as President and Chair of ASTRO (non-compensated) and received research funding (through institution; as a co-investigator) from Merck. Elijah Dixon declares no conflicts of interest. Howard J Lim has received Honoria from Ipsen, Merck, BMS, Taiho, Eisai, Roche and AstraZeneca and research funding from Roche, Eisai and AstraZeneca. David M Liu has served as consultant for Eisai Pharm, Sirtex Medical and Varian System, and received honoraria from Ipsen Pharma and AstraZeneca. Ilidio Martins declares no conflicts of interest. Brandon Meyers has served as a consultant or advisor to Roche, Eisai, Ipsen, Incyte, Bayer, Merck, and AstraZeneca, research funding from Roche and provided expert testimony for Roche and Eisai. Amol Mujoomdar has served as a consultant or advisor to and received honoraria from Boston Scientific, Terumo Medical, Esai, Teleflex, and Medtronic. Ravi Ramjeesingh has served as a consultant or on an advisory board for AstraZeneca, Incyte, Eisai and Ipsen, has received honoraria from AstraZeneca, Incyte, Eisai, Ipsen and Bayer and has received research funding from Eisai, Pfizer, AstraZeneca, Amgen and Ipsen. Setareh Samimi has served as an advisor for and received honoraria from Eisai and AstraZeneca. Gonzalo Sapisochin has served as consultant for AstraZeneca, Roche, Novartis, Integra, Evidera, Chiesi and has received grant support from Roche and Bayer. Maja Segedi received honoraria from Eisai. David Valenti has served as an advisor to Eisai Canada. Vincent C Tam has received honoraria from AstraZeneca, Eisai, Incyte, Ipsen, and Roche and research funding from AstraZeneca, Eisai, Ipsen, and Roche. Jason K Wong has served as a consultant or advisor to and received honoraria from AstraZeneca, BD, Boston Scientific, Cook Medical, Eisai, Medtronic, and Roche., (Copyright © 2023. Published by Elsevier Ltd.)

Introduction: In resected colonic liver metastasis (CLM), randomized studies of oxaliplatin-based chemotherapy have demonstrated improvements in disease-free survival (DFS), but not overall survival (OS). Additionally, oxaliplatin regimens have not been compared to non-oxaliplatin chemotherapy. Despite limited evidence, perioperative chemotherapy is often used in the management of CLM. The primary aim of this study was to assess the impact of oxaliplatin chemotherapy regimens on OS in patients who have undergone resection of CLM in a real-world setting., Patients and Methods: Patients who underwent resection of CLM in the provinces of Alberta and British Columbia, Canada, were identified from 1996 to 2016. Perioperative (pre- and/or post-) systemic therapy was categorized as oxaliplatin or non-oxaliplatin-based chemotherapy or no chemotherapy. The primary and secondary outcomes were OS and DFS, respectively., Results: We identified 511 patients who underwent R0 resection of CLM. A significant difference in median OS was identified among the oxaliplatin, non-oxaliplatin, and no-chemotherapy groups of 100, 60, and 59 months, respectively (P = .009). In multivariate analysis, patients who received oxaliplatin regimens had a lower risk of death (hazard ratio, 0.68; 95% confidence interval, 0.51-0.92; P = .012), whereas the non-oxaliplatin chemotherapy group did not (hazard ratio, 0.88; 95% confidence interval, 0.65-1.20; P = .422) compared with no chemotherapy., Conclusions: In this multicenter, retrospective, population-based study, perioperative oxaliplatin-based chemotherapy was associated with improved OS in conjunction with R0 resection of CLM. Further studies should evaluate the optimal duration and sequencing of perioperative chemotherapy in relation to curative-intent surgical resection of CLM., (Copyright © 2021. Published by Elsevier Inc.)

Background: Liver resection being the only potentially curative treatment for patients with liver metastasis, it is critical to select the appropriate preoperative imaging modality. The aim of this study was to assess the impact of preoperative gadoxetic acid-enhanced MRI compared to a conventional extracellular gadolinium-enhanced MRI on the surgical management of colorectal and neuroendocrine liver metastasis., Methods: We included 110 patients who underwent both a gadoxetic acid-enhanced MRI (hepatospecific contrast) and conventional extracellular gadolinium for the evaluation of colorectal or neuroendocrine liver metastases, from January 2012 to December 2015 at the CHU de Québec - Université Laval. When the number of lesions differed, a hepatobiliary surgeon evaluated if the gadoxetic acid-enhanced MRI modified the surgical management., Results: Gadoxetic acid-enhanced MRI found new lesions in 25 patients (22.7%), excluded lesions in 18 patients (16.4%) and identified the same number in 67 patients (60.9%). The addition of the gadoxetic acid-enhanced MRI directly altered the surgical management in 19 patients overall (17.3% (95% CI [10.73-25.65]))., Conclusion: Despite the additional cost associated with gadoxetic acid-enhanced MRI compared to conventional extracellular gadolinium-enhanced MRI, the use of this contrast agent has a significant impact on the surgical management of patients with liver metastases., (Copyright © 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Most prognostic scoring systems for colorectal liver metastases (CRLMs) account for factors related to tumour biology. Little is known about the effects of the host phenotype to the tumour. Our objective was to delineate the relationship of systemic inflammation and body composition features [i.e. low skeletal muscle mass (sarcopenia) and low visceral adipose tissue (VAT)], two well-described host phenotypes in cancer., Methods: Clinical data and pre-operative blood samples were collected from 99 patients who underwent resection of CRLM. Pre-operative computed tomography scans were available for 97 patients; body composition was analysed at the L3 level, stratified for sex and age. Clinicopathological variables, serum C-reactive protein (CRP), and various body composition variables were evaluated. Overall survival was evaluated as a function of these same variables in multivariate Cox regression analysis., Results: Skeletal muscle was significantly correlated with VAT (r = 0.46, P < 0.001). Of patients with sarcopenia, 35 (65%) also had low VAT. C-reactive protein was elevated (≥5 mg/mL) in 42 patients (43.3%). Elevated CRP was more common in patients with sarcopenia (73.8% vs. 51.1%, P = 0.029). The most significant prognostic factors were the coincidence of elevated CRP and adverse body composition features (sarcopenia and/or low VAT; hazard ratio 4.3, 95% confidence interval 1.5-13.0, P = 0.008), as well as Fong clinical prognostic score (hazard ratio 2.9, 95% confidence interval 1.5-5.5, P = 0.002)., Conclusions: Body composition in patients with CRLM is not directly linked to the presence of systemic inflammation. However, when systemic inflammation coincides with sarcopenia and/or low VAT, prognosis is adversely affected, independent of the Fong clinical prognostic score., (© 2018 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.)

Background: Acute kidney injury (AKI) is associated with increased morbidity and mortality after liver resection. Patients with hepatocellular carcinoma (HCC) have a higher risk of AKI owing to the underlying association between hepatic and renal dysfunction. Use of the Acute Kidney Injury Network (AKIN) diagnostic criteria is recommended for patients with cirrhosis, but remains poorly studied following liver resection. We compared the prognostic value of the AKIN creatinine and urine output criteria in terms of postoperative outcomes following liver resection for HCC., Methods: All patients who underwent a liver resection for HCC from January 2010 to June 2016 were included. We used AKIN urine output and creatinine criteria to assess for AKI within 48 hours of surgery., Results: Eighty liver resections were performed during the study period. Cirrhosis was confirmed in 80%. Median hospital stay was 9 (interquartile range 7–12) days, and 30-day mortality was 2.5%. The incidence of AKI was higher based on the urine output than on the creatinine criterion (53.8% v. 20%), and was associated with prolonged hospitalization and 30-day postoperative mortality when defined by serum creatinine (hospital stay: 11.2 v. 20.1 d, p = 0.01; mortality: 12.5% v. 0%, p < 0.01), but not urine output (hospital stay: 15.6 v. 10 d, p = 0.05; mortality: 2.3% v. 2.7%, p > 0.99)., Conclusion: The urine output criterion resulted in an overestimation of AKI and compromised the prognostic value of AKIN criteria. Revision may be required to account for the exacerbated physiologic postoperative reduction in urine output in patients with HCC., Competing Interests: None declared.

Background: Multimodal treatment of colorectal liver metastases (CRLMs) relies on precise upfront assessment of resectability. Variability in the definition of resectable disease and the importance of early consultation by a liver surgeon have been reported. In this pilot study we investigated the initial resectability assessment and patterns of referral of patients with CRLMs., Methods: Surgeons and medical oncologists involved in the management of colorectal cancer at 2 academic institutions and affiliated community hospitals were surveyed. Opinions were sought regarding resectability of CRLMs and the type of initial specialty referral (hepatobiliary surgery, medical oncology, palliative care or other) in 6 clinical cases derived from actual cases of successfully performed 1- or 2-stage resection/ablation of hepatic disease. Case scenarios were selected to illustrate critical aspects of assessment of resectability, best therapeutic approaches and specialty referral. Standard statistical analyses were performed., Results: Of the 75 surgeons contacted, 64 responded (response rate 85%; 372 resectability assessments completed). Hepatic metastases were more often considered resectable by hepatobiliary surgeons than all other respondents (92% v. 57%, p < 0.001). Upfront systemic therapy was most commonly prioritized by surgical oncologists ( p = 0.01). Hepatobiliary referral was still considered in 73% of "unresectable" assessments by colorectal surgeons, 59% of those by general surgeons, 57% of those by medical oncologists and 33% of those by surgical oncologists ( p = 0.1)., Conclusion: Assessment of resectability varied significantly between specialties, and resectability was often underestimated by nonhepatobiliary surgeons. Hepatobiliary referral was not considered in a substantial proportion of cases erroneously deemed unresectable. These disparities result largely from an imprecise understanding of modern surgical indications for resection of CRLMs.

Background: Recent advances in care for colorectal liver metastases (CRLM) have lengthened 5-year survival. In this new era, prognostic tools such as the clinical risk score (CRS) for colorectal liver metastases require reevaluation., Methods: Patients undergoing resection for CRLM between 2008 and 2012 at 4 specialty hepatobiliary centers in Canada (N = 740) were stratified by CRS and analyzed in Kaplan-Meier survival curves. Primary outcome of overall survival (OS) and secondary outcome of recurrence-free survival (RFS). Multivariate Cox regression compared CRS to patient factors., Results: Median OS not reached (>60 months), median RFS 16 months. Original CRS strata was a significant (p < 0.001) predictor of both OS (5-year OS: 0; 75%, 1; 71%, 2; 57%, 3; 57%, 4; 46%) and RFS (5-year RFS: 0; 39%, 1; 33%, 2; 21%, 3; 21%, 4; 8%). The presence of extrahepatic colorectal metastatic disease increased recurrence risk (RFS hazard ratio of 1.32 (1.06-1.65)), and the use of intraoperative portal pedicle clamping reduced recurrence risk (RFS hazard ratio of 0.78 (0.61-0.99))., Conclusions: The CRS remains a relevant tool for predicting long-term outcomes for patients undergoing resection of CRLM. Additional factors such as the presence of extrahepatic colorectal metastatic disease and the use of intraoperative portal pedicle clamping may improve the prognostic power of the CRS., (Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Perioperative red blood cell transfusions are required in up to 23 per cent of patients undergoing hepatectomy. Previous research has developed three transfusion risk scores to assess risk of perioperative red blood cell transfusion. Here, the performance of these transfusion risk scores was evaluated in a multicentre cohort of patients who underwent hepatectomy and compared with that of a simplified transfusion risk score., Methods: A database of patients undergoing hepatectomy at four specialized centres between 2008 and 2012 was developed. External validity was assessed by discrimination and calibration. Discrimination was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC). Calibration was evaluated by the degree of agreement between predicted and actual red blood cell transfusion probabilities. A simplified transfusion risk score using variables common to the three models was created, and discrimination and calibration were evaluated., Results: There were 1287 patients included in this study, with 341 (26·5 per cent) receiving a red blood cell transfusion. Discriminative ability was similar between the three transfusion risk scores, with AUCs of 0·66-0·68 and good calibration. A new three-point risk score was developed based on factors present in all models: haemoglobin 12·5 g/dl or less, primary liver malignancy and major resection (at least 4 segments). Discriminative ability and calibration of the three-point model were similar to those of the three existing models, with an AUC of 0·66., Conclusion: The three-point transfusion risk score simplifies assessment of perioperative transfusion risk in hepatectomy without sacrificing predictive ability., (© 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Background: The addition of cetuximab (CTX) to perioperative chemotherapy (CT) for operable colorectal liver metastases resulted in a shorter progression-free survival. Details of disease progression are described to further inform the primary study outcome., Methods: A total of 257 KRAS wild-type patients were randomised to CT alone or CT with CTX. Data regarding sites and treatment of progressive disease were obtained for the 109 (CT n=48, CT and CTX n=61) patients with progressive disease at the cut-off date for analysis of November 2012., Results: The liver was the most frequent site of progression (CT 67% (32/48); CT and CTX 66% (40/61)). A higher proportion of patients in the CT and group had multiple sites of progressive disease (CT 8%, 4/48; CT and CTX 23%, 14/61 P=0.04). Further treatment for progressive disease is known for 84 patients of whom 69 received further CT, most frequently irinotecan based. Twenty-two patients, 11 in each arm, received CTX as a further line agent., Conclusions: Both the distribution of progressive disease and further treatment are as expected for such a cohort. The pattern of disease progression seen is consistent with failure of systemic micrometastatic disease control rather than failure of local disease control following liver surgery.

In the last module of this consensus, controversial topics were discussed. Management of the disease after progression during first line chemotherapy was the first discussion. Next, the benefits of liver resection in the presence of extra-hepatic disease were debated, as soon as, the best sequence of treatment. Conversion chemotherapy in the presence of unresectable liver disease was also discussed in this module. Lastly, the approach to the unresectable disease was also discussed, focusing in the best chemotherapy regimens and hole of chemo-embolization., Competing Interests: none

Background: Resection of colorectal liver metastases (CRLM) is associated with improved survival; however, the impact of time to resection on survival is unknown. The current multi-institutional study sought to evaluate the influence of time from diagnosis (Dx) to resection (Rx) on survival outcomes among patients with resectable, metachronous CRLM and to compare practice patterns across hospitals., Study Design: Medical records of patients with ≤4 metachronous CRLM treated with surgery were reviewed and analyzed retrospectively. Time from Dx to Rx was analyzed as a continuous variable and also dichotomized into 2 groups (group 1: Dx to Rx <3 months and group 2: Dx to Rx ≥3 months) for additional analysis. Survival time distributions after resection were estimated using the Kaplan-Meier method. Between-group univariate comparisons were based on the log-rank test and multivariable analysis was done using Cox proportional hazards model., Results: From 2000 to 2010, six hundred and twenty-six patients were identified. Type of initial referral (p < 0.0001) and use of neoadjuvant (p = 0.04) and/or adjuvant (p < 0.0001) chemotherapy were significantly different among hospitals. Patients treated with neoadjuvant chemotherapy (n = 108) and those with unresectable disease at laparotomy (n = 5) were excluded from final evaluation. Median overall survival and recurrence-free survival were 74 months (range 63.8 to 84.2 months) and 29 months (range 23.9 to 34.1 months), respectively. For the entire cohort, longer time from Dx to Rx was independently associated with shorter overall survival (hazard ratio = 1.12; 95% CI, 1.06-1.18; p < 0.0001), but not recurrence-free survival. Median overall survival for group 1 was 76 months (range 62.0 to 89.2 months) vs 58 months (range 34.3 to 81.7 months) in group 2 (p = 0.10). Among patients with available data pertaining to adjuvant chemotherapy (N = 457; 318 treated and 139 untreated), overall survival (87 months [range 71.2 to 102.8 months] vs 48 months [range 25.3 to 70.7 months]; p <0.0001), and recurrence-free survival (33 months [range 25.3 to 40.7 months] vs 22 months [range 14.5 to 29.5 months]; p = 0.05) were improved significantly., Conclusions: In select patients undergoing initial resection for CRLM, longer time from Dx to Rx is independently associated with worse overall survival. In addition, despite uniform disease characteristics, practice patterns related to definitely resectable CRLM vary significantly across hospitals., (Copyright © 2016 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The modified Glasgow Prognostic Score (mGPS) has been reported to be an important prognostic indicator in a number of tumor types, including colorectal cancer (CRC). The features of the inflammatory state thought to accompany elevated C-reactive protein (CRP), a key feature of mGPS, were characterized in patients with colorectal liver metastases. Additional inflammatory mediators that contribute to prognosis were explored., Methods: In sera from 69 patients with colorectal liver metastases, a panel of 42 inflammatory mediators were quantified as a function of CRP levels, and as a function of disease-free survival. Multivariate statistical methods were used to determine association of each mediator with elevated CRP and truncated disease-free survival., Results: Elevated CRP was confirmed to be a strong predictor of survival (HR 4.00, p = 0.001) and recurrence (HR 3.30, p = 0.002). The inflammatory state associated with elevated CRP was comprised of raised IL-1β, IL-6, IL-12 and IL-15. In addition, elevated IL-8 and PDGF-AB/BB and decreased eotaxin and IP-10 were associated with worse disease-free and overall survival., Conclusions: Elevated CRP is associated with a proinflammatory state. The inflammatory state is an important prognostic indicator in CRC liver metastases. The individual contributions of tumor biology and the host to this inflammatory response will require further investigation.

Background: Surgery for colorectal liver metastases results in an overall survival of about 40% at 5 years. Progression-free survival is increased with the addition of oxaliplatin and fluorouracil chemotherapy. The addition of cetuximab to these chemotherapy regimens results in an overall survival advantage in patients with advanced disease who have the KRAS exon 2 wild-type tumour genotype. We aimed to assess the benefit of addition of cetuximab to standard chemotherapy in patients with resectable colorectal liver metastasis., Methods: Patients with KRAS exon 2 wild-type resectable or suboptimally resectable colorectal liver metastases were randomised in a 1:1 ratio to receive chemotherapy with or without cetuximab before and after liver resection. Randomisation was done using minimisation with factors of surgical centre, poor prognostic tumour (one or more of: ≥ 4 metastases, N2 disease, or poor differentiation of primary tumour), and previous adjuvant treatment with oxaliplatin. Chemotherapy consisted of oxaliplatin 85 mg/m(2) intravenously over 2 h and fluorouracil bolus 400 mg/m(2) intravenously over 5 min, followed by a 46 h infusion of fluorouracil 2400 mg/m(2) repeated every 2 weeks (regimen one) or oxaliplatin 130 mg/m(2) intravenously over 2 h and oral capecitabine 1000 mg/m(2) twice daily on days 1-14 repeated every 3 weeks (regimen two). Patients who had received adjuvant oxaliplatin could receive irinotecan 180 mg/m(2) intravenously over 30 min with fluorouracil instead of oxaliplatin (regimen three). Cetuximab was given as an intravenous dose of 500 mg/m(2) every 2 weeks with regimen one and three or a loading dose of 400 mg/m(2) followed by a weekly infusion of 250 mg/m(2) with regimen two. The primary endpoint was progression-free survival. This is an interim analysis, up to Nov 1, 2012, when the trial was closed, having met protocol-defined futility criteria. This trial is registered, ISRCTN22944367., Findings: 128 KRAS exon 2 wild-type patients were randomised to chemotherapy alone and 129 to chemotherapy with cetuximab between Feb 26, 2007, and Nov 1, 2012. 117 patients in the chemotherapy alone group and 119 in the chemotherapy plus cetuximab group were included in the primary analysis. The median follow-up was 21.1 months (95% CI 12.6-33.8) in the chemotherapy alone group and 19.8 months (12.2-28.7) in the chemotherapy plus cetuximab group. With an overall median follow-up of 20.7 months (95% CI 17.9-25.6) and 123 (58%) of 212 required events observed, progression-free survival was significantly shorter in the chemotherapy plus cetuximab group than in the chemotherapy alone group (14.1 months [95% CI 11.8-15.9] vs 20.5 months [95% CI 16.8-26.7], hazard ratio 1.48, 95% CI 1.04-2.12, p=0.030). The most common grade 3 or 4 adverse events were low neutrophil count (15 [11%] preoperatively in the chemotherapy alone group vs six [4%] in the chemotherapy plus cetuximab group; four [4%] vs eight [8%] postoperatively), embolic events (six [4%] vs eight [6%] preoperatively; two [2%] vs three [3%] postoperatively), peripheral neuropathy (six [4%] vs one [1%] preoperatively; two [2%] vs four [4%] postoperatively), nausea or vomiting (four [3%] vs six [4%] preoperatively; four [4%] vs two [2%] postoperatively), and skin rash (two [1%] vs 21 [15%] preoperatively; 0 vs eight [8%] postoperatively). There were three deaths in the chemotherapy plus cetuximab group (one interstitial lung disease and pulmonary embolism, one bronchopneumonia, and one pulmonary embolism) and one in the chemotherapy alone group (heart failure) that might have been treatment related., Interpretation: Addition of cetuximab to chemotherapy and surgery for operable colorectal liver metastases in KRAS exon 2 wild-type patients results in shorter progression-free survival. Translational investigations to explore the molecular basis for this unexpected interaction are needed but at present the use of cetuximab in this setting cannot be recommended., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: The role of portal vein embolization to increase future liver remnant (FLR) is well-established in the treatment of colorectal liver metastases. However, the role of hepatic vein embolization is unclear., Case Report: A patient with colorectal liver metastases received neoadjuvant chemotherapy prior to attempted resection. At the time of resection his tumor appeared to invade the left and middle hepatic vein, requiring an extended left hepatectomy including segments five and eight. Post-operatively, he underwent sequential left portal vein embolization followed by left hepatic vein embolization and finally, middle hepatic vein embolization. Hepatic vein embolization was performed to increase the FLR as well as to allow collateral drainage of the FLR to develop. A left trisectionectomy was then performed and no evidence of postoperative liver congestion or morbidity was found., Conclusion: Sequential portal vein embolization and hepatic vein embolization for extended left hepatectomy may be considered to increase FLR and may prevent right hepatic congestion after sacrificing the middle vein.

Background: Hepatectomy is an accepted standard of care for patients with resectable colorectal liver metastases (CLM). Given that it is unclear whether disparities exist between different patient populations, a population-based analysis was performed to analyze this issue with regards to resection rates and surgical mortality in patients with CLM., Methods: Using the Nationwide Inpatient Sample, characteristics and outcomes of adult patients with a diagnosis of colorectal cancer and colorectal metastases that subsequently underwent a liver resection during the years 1993-2007 were identified. Multivariate analysis was used to determine the effects of demographic and clinical covariables on resection rates and in-hospital mortality., Results: Incident colorectal and liver metastases were identified in 138,565 patients; 3,528 patients (2.6%) underwent subsequent resection. African American and Hispanic race were associated with lower resection rates compared to Caucasian patients (adjusted OR 0.61 (0.52 - 0.71) and 0.81 (0.68 - 0.96) respectively). Medicaid insurance was associated with decreased resection rates compared to private insurance (AOR 0.47 (0.40 - 0.56)). The overall inpatient mortality rate was 3.1%. Multivariate analysis determined that mortality rate was correlated to both insurance status and geographic region., Conclusions: The national resection rate is significantly lower than has been reported by most case series. Race and insurance status appear to be correlated to the likelihood of surgical resection. In-hospital mortality is equivalent to the rates reported elsewhere, but is correlated to insurance status and region.

Background: A major hepatic resection for malignancies requires an adequate post-operative liver reserve. Portal vein embolization (PVE) with intra-arterial therapy (IAT) may increase future liver remnant (FLR) hypertrophy. As such, the feasibility, safety and efficacy of IAT+PVE were investigated., Methods: Between 2000 to 2011, 86 patients with malignancy of the liver were identified from a multi-institutional database. Twenty-nine patients underwent sequential IAT+PVE, 25 had PVE alone and 32 had IAT alone. Clinicopathological data were evaluated., Results: Most patients had hepatocellular carcinoma (HCC) (65.1%) and 31.4% had secondary metastatic disease. A complete or partial response using European Association for the Study of the Liver (EASLD) criteria was seen in 48.3% of patients undergoing IAT+PVE vs. 56.6% among patients undergoing IAT (P = 0.601). The median increase in percentage FLR volume was comparable in IAT+PVE (7.4%) vs. PVE only (7.9%) (P = 0.203). There were no IAT+PVE-associated deaths and only one complication. Among patients treated with IAT+PVE (n = 29), 27 underwent a subsequent hepatic resection. Peri-operative morbidity and mortality was 29.6% and 7.4%, respectively. Among the patients with HCC who underwent curative intent surgery after IAT+PVE, the median survival was 59.0 months., Conclusions: Sequential IAT and PVE are feasible and safe. Utilization of IAT+PVE before a resection can lead to long-term survival and should be considered in the treatment of patients with advanced hepatic malignancies., (© 2012 International Hepato-Pancreato-Biliary Association.)

As the number of effective treatment options has increased, the management of patients with hepatocellular carcinoma has become complex. The most appropriate therapy depends largely on the functional status of the underlying liver. In patients with advanced cirrhosis and tumor extent within the Milan criteria, liver transplantation is clearly the best option, as this therapy treats the cancer along with the underlying hepatic parenchymal disease. As the results of transplantation has become established in patients with limited disease, investigation has increasingly focused on downstaging patients with disease outside of Milan criteria and defining the upper limits of transplantable tumors. In patients with well preserved hepatic function, liver resection is the most appropriate and effective treatment. Hepatic resection is not as constrained by tumor extent and location to the same degree as transplantation and ablative therapies. Some patients who recur after resection may still be eligible for transplantation. Ablative therapies, particularly percutaneous radiofrequency ablation and transarterial chemoembolization have been used primarily to treat patients with low volume irresectable tumors. Whether ablation of small tumors provides long term disease control that is comparable to resection remains unclear.

Staging of hepatocellular carcinoma (HCC) is complex and relies on multiple factors including tumor extent and hepatic function. No single staging system is applicable to all patients with HCC. The staging of the American Joint Committee on Cancer / International Union for Cancer Control should be used to predict outcome following resection or liver transplantation. The Barcelona Clinic Liver Cancer scheme is appropriate in patients with advanced HCC not candidate for surgery. Dual phase computed tomography or magnetic resonance imaging can be used for pretreatment assessment of tumor extent but the accuracy of these methods remains poor to characterize < 1 cm lesions. Assessment of tumor response should not rely only on tumor size and new imaging methods are available to evaluate response to therapy in HCC patients. Liver volumetry is part of the preoperative assessment of patients with HCC candidate for resection as it reflects liver function. Preoperative portal vein embolization is indicated in patients with small future liver remnant (≤ 20% in normal liver; ≤ 40% in fibrotic or cirrhotic liver). Tumor size is not a contraindication to liver resection. Liver resection can be proposed in selected patients with multifocal HCC. Besides tumor extent, surgical resection of HCC may be performed in selected patients with chronic liver disease.

Background: Liver resection (LR) is the only curative therapy for hepatic malignancy. Despite this, the rates of LR across Canada are unknown. We sought to determine the rate and regional variation of LR in Canada, its provinces and census divisions for the period 1995-2004., Methods: We obtained discharge data for 1995-2004 from all provinces but Quebec from the Canadian Institute for Health Information, and we searched for LR by residential site. Then we calculated rates and variations in rates., Results: The national age- and sex-adjusted rate of LR per 100,000 people aged 18 years and older increased from 3.22 in 1995 to 5.86 in 2004. There was a high degree of variation across provinces and census divisions., Conclusion: Liver resection volumes are increasing in Canada. Significant regional variation exists for LR in Canada, likely reflecting a variety of important supply-demand issues.

Background: Very few quality indicators of care exist for surgical procedures. These may be used to both score the quality of care received, and as a method of improving the quality of care delivered (quality improvement initiatives)., Materials and Methods: The goal of this study was to develop a set of evidence-based quality indicators by expert consensus for patients undergoing hepatic resection of colorectal metastases to the liver. A Delphi approach was used to develop a set of evidence-based quality indicators for patients undergoing hepatic resection of colorectal metastases to liver. A panel of experts was formed through nomination by members of the Canadian Hepatopancreaticobiliary Society (CHPBS). The Delphi process consisted of three iterations of questionnaires. During each round, the panel members were asked to score the potential indicators and suggest any new indicators., Results: A list of 70 potential indicators was generated from the literature, of which 27 achieved consensus for inclusion in the final list of quality indicators. After consolidating similar or redundant indicators, the final list had 18 quality indicators. All of the indicators in the final list were from our original literature search., Conclusions: This Delphi process has used the best available evidence, along with a consensus methodology employing the opinion of experts in the field, to identify 18 quality indicators for patients undergoing hepatic resection for metastatic colorectal cancer. These indicators will provide a means for benchmarking quality of care among surgeons, institutions, and health regions.

Background: Chemotherapy may improve survival in patients undergoing resection of colorectal liver metastases (CLM). Neoadjuvant chemotherapy may help identify patients with occult extrahepatic disease (averting unnecessary metastasectomy), and it provides in vivo chemosensitivity data., Methods: A phase II trial was initiated in which patients with resectable CLM received CPT-11, 5-FU and LV for 12 weeks. Metastasectomy was performed unless extrahepatic disease appeared. Postoperatively, patients with stable or responsive disease received the same regimen for 12 weeks. Patients with progressive disease received either second-line chemotherapy or best supportive care. The primary endpoint was disease-free survival (DFS); secondary endpoints included overall survival (OS) and safety., Results: 35 patients were accrued. During preoperative chemotherapy, 16 patients (46%) had grade 3/4 toxicities. Resection was not possible in 5 patients. One patient died of arrhythmia following surgery, and 1 patient had transient liver failure. During the postoperative treatment phase, 12 patients (55%) had grade 3/4 toxicities. Deep venous thrombosis (DVT) occurred in 11 patients (34%) at various times during treatment. Of those who underwent resection, median DFS was 23.0 mo. and median OS has not been reached. The overall survival from time of diagnosis of liver metastases was 51.6 mo for the entire cohort., Conclusion: A short course of chemotherapy prior to hepatic metastasectomy may serve to select candidates best suited for resection and it may also direct postoperative systemic treatment. Given the significant incidence of DVT, alternative systemic neoadjuvant regimens should be investigated, particularly those that avoid the use of a central venous line., Trial Registration: ClinicalTrials.gov NCT00168155.

Background: Metastatic neuroendocrine tumors (NETs) can present with complications of gastrointestinal tract obstruction or ischemia and carcinoid syndrome (CS). The purpose of this study was to assess whether aggressive surgical intervention of metastatic NETs provides effective palliation from these symptoms., Methods: Sixty-six patients with metastatic gastrointestinal tract NETs that presented with either CS and/or obstructive symptoms were retrospectively reviewed. All patients were managed according to a standardized protocol that involved initial surgical resection of regional and/or hepatic disease followed by appropriate medical therapy., Results: Symptoms of obstruction or ischemia were present in 24 patients (36%) and CS in 56 (85%). All patients with obstructive symptoms undergoing operative therapy had complete symptomatic relief. Hepatic cytoreduction was performed in 30 (45%). Overall symptoms of CS improved in 42 patients (75%); 86% of patients that underwent hepatic cytoreduction and 64% of those receiving medical therapy alone (P = .064). Postoperative morbidity was 22% with no mortality. Mean follow-up was 47 months (range, 6-156). Overall 5-year survival rate was 74%., Conclusions: Surgical resection is highly effective in relieving symptoms of intestinal obstruction and ischemia. Hepatic cytoreduction seems to enhance the ability to control the symptoms of carcinoid syndrome. A surgically aggressive approach in patients with metastatic NETs provides effective palliation in carefully selected patients.

Background: Higher hospital and surgeon volumes have been associated with improved outcomes after hepatic resection. Subspecialty training has not previously been associated with improved outcomes after hepatic resection. The objective of this study was to determine what effects, if any, surgeon's volume and training had on the outcomes after hepatic resection., Methods: Administrative procedure codes were used to identify all adult patients from the fiscal year 1991-1992 to 2003-2004 who underwent a hepatic resection in two large urban health regions in Canada (Calgary and Capital health regions). The primary outcomes were operative mortality and postoperative complications., Results: There were 1107 hepatic resections in the stated time period performed by a total of 72 surgeons. There were 66 deaths, resulting in an in-hospital mortality rate of 6.0%, and an overall complication rate of 46%. Statistically significant predictors of operative mortality were: urgency of admission, diagnosis of primary hepatic malignancy, extent of resection, and increasing burden of comorbid medical illness. Surgeon training along with patient's sex, the urgency of admission, diagnosis of primary hepatic malignancy, extent of resection, and increasing comorbidity were predictive of postoperative complications., Conclusions: This study found surgeon training to be highly predictive of postoperative complications after hepatic resection.

Background: Recently, there has been considerable interest in neoadjuvant chemotherapy for colorectal liver metastases. However, there is little information that defines how much liver should be removed after a favorable response., Methods: Liver metastases from 2 groups of patients were analyzed: 25 metastases were evaluated from a group that did not receive chemotherapy and 26 lesions were studied from patients who had received systemic chemotherapy before resection. All patients except for 1 had 5-fluorouracil (5-FU), leucovorin (LV), and irinotecan (CPT-11); 1 had 5-FU and LV alone. The average duration of chemotherapy was 2.9+/-0.7 months. Separate assessments of the histopathologic features of the central and peripheral portions of each tumor were made. The pathologist was blinded to all clinical information., Results: All of the untreated metastases had well-circumscribed borders. Irregular borders were seen in 6 of the postchemotherapy lesions (26%), which was particularly prominent in lesions that had significantly contracted. After chemotherapy, discrete islands of viable tumor cells outside of the main tumor mass were seen in 4 patients, but all were close to the peripheral margin of the tumor mass. Viable tumor cells were more frequent in the periphery of metastases, regardless of chemotherapy exposure. Central necrosis was prominent in untreated metastases, but disappeared after chemotherapy. In lesions treated with chemotherapy, central fibrosis was greater compared with untreated lesions., Conclusions: After a partial response to chemotherapy, liver metastases shrank in a generally concentric fashion. These findings support the practice of removing less liver after downsizing with chemotherapy.

Neurofibromas are generally well-circumscribed tumors of the nervous system, often found in association with neurofibromatosis 1 (NF1). They uncommonly present as a single sporadic form in the retroperitoneum and in the pancreas. We present a case of a 40-year-old man who presented with a 4- to 5-year history of right upper quadrant pain with associated nausea and vomiting. Medical imaging showed a 3.8 by 3.4-cm mass encasing the hepatic artery and the porta hepatis. Surgical resection was performed, with removal of the gallbladder. The mass was histologically diagnosed as a neurofibroma. At 1 year following his surgery, the patient is doing well.

Background: Systemic chemotherapy is being used increasingly in patients with colorectal cancer. The effects of prior systemic adjuvant or palliative chemotherapy on morbidity following hepatic resection for metastases are not well defined., Objectives: To assess the peri-operative impact of systemic chemotherapy on liver resection for colorectal cancer hepatic metastases., Methods: Ninety-six resections for colorectal cancer hepatic metastases performed from July 2001 to July 2003 (93% > or =2 segments) were reviewed. Pre-operative demographics, peri-operative features, and post-operative outcomes were collected prospectively. Type of chemotherapy and the temporal relationship of chemotherapy to the liver resection were analyzed., Results: Fifty-three of 96 patients (55%) received a mean of 5.7 cycles (6.1 months) of systemic chemotherapy prior to hepatic resection, with a median interval of 12 months from end of chemotherapy to liver resection (range 1-75 months). Thirty-five received 5-fluorouracil/leucovorin (5-FU/LV) alone, nine had irinotecan (CPT-11) in addition to 5-FU/LV, and nine were not specified. Pre-operative age, sex, co-morbidities, ASA score, biochemical and liver enzyme profiles, tumor number, and extent and technique of hepatic resection were the same in the chemotherapy and non-chemotherapy cohorts. Mean tumor size was smaller (4.5 cm vs. 5.8 cm) and synchronous metastases were half as common (25% vs. 49%) in the chemotherapy group. Liver resection operative time was equivalent (270 min) in the two groups. Higher estimated blood loss (EBL) (1,000 ml vs. 850 ml), but fewer transfusions (23% vs. 15%) were associated with the chemotherapy group. Although not statistically significant, post-operative liver enzyme peaks were higher in the chemotherapy group (AST = 402 U/L vs. 302 U/L, P = 0.09 and ALT = 433 U/L vs. 312 U/L, P = 0.1). Peak changes in INR and serum bilirubin did not differ. Complications and length of stay (LOS) did not differ between the groups. The only post-operative death was in the non-chemotherapy group. Interestingly, hepatic steatosis was present in 28% of the non-chemotherapy cases and 57% of the chemotherapy resection specimens (P = 0.005) and was marked (>30%) in 7% and 10%, respectively. Further analysis of the chemotherapy group based on the interval between completion of chemotherapy and the hepatic resection (<6 months, 7-12 months, 1-2 years, and >2 years) revealed a trend towards worse outcomes in most categories for those in the >2 years cohort. When comparing the 5-FU/LV alone, to the CPT-11 group there were no significant differences except higher intra-operative blood loss in the group receiving 5-FU/LV alone (1,295 ml vs. 756 ml, P = 0.01)., Conclusion: Despite variations in biochemical function and hepatic steatosis, short-term clinical outcomes are not affected by the administration of chemotherapy prior to hepatic resection. Furthermore, there is no detrimental effect of close timing of chemotherapy prior to resection, and there are no appreciable differences between irinotecan containing regimes and more traditional 5-FU-only based therapies, although the subset sample sizes were small in this study.

Aims: In Asian countries, transarterial chemoembolisation (TACE) has long been used for palliation of unresectable hepatocellular carcinoma (HCC) without strong evidence of improved survival or quality of life. In 2002, a survival benefi of TACE was shown in two randomised controlled trials in Europe and Hong Kong. The effectiveness of interventions fo HCC is influenced by geographical factors related to diverse patient characteristics and protocols. Therefore, the validation of TACE as palliative modality for unresectable HCC requires confirmation in diverse patient populations. The aim of the present study was to assess the effectiveness of TACE for HCC in a North American population., Materials and Methods: This was a single centre prospective cohort study. Child-Pugh A cirrhosis or better patients wit unresectable HCC and without radiological evidence of metastatic disease or segmental portal vein thrombosis wer assessed between November 2001 and May 2004. Of 54 patients who satisfied the inclusion criteria, 47 underwent 80 TACE sessions. Chemoembolisation was carried out using selective hepatic artery injection of 75 mg/m(2) doxorubicin and lipiodol followed by an injection of embolic particles when necessary. Repeat treatments were carried out at 2-3 month intervals for recurrent disease. The primary outcome was overall survival; secondary outcomes were morbidity and tumour response., Results: The survival probabilities at 1, 2 and 3 years were 76.6, 55.5 and 50%, respectively. At 6 months after the first intervention, 31% of patients had a partial response and 60% had stable disease by RECIST criteria. Minor adverse events occurred after 39% of TACEs and major adverse events after 20% of sessions, including two treatment-related deaths (4% of patients). One patient had complete cancer remission after undergoing three TACE treatments. Further progression of tumour growth was prevented in 91% of tumours at the 6 month point after the first TACE. At 3 months, serum levels of the tumour marker alpha-feto protein were significantly reduced in patients with elevated levels before TACE., Conclusions: The survival probabilities at 1 and 2 years after TACE were comparable with results in randomised studies from Europe and Asia. Most patients tolerated TACE well, but clinicians need to be aware that moderately severe sideeffects require close monitoring and prompt intervention.

Background and Method: This paper reviews the current status of radiofrequency ablation in the treatment of colorectal liver metastases. Relevant studies with at least ten patients that reported rates of complete tumour ablation, local recurrence, or survival from 1 to 5 years after treatment were included in the review., Results and Conclusion: Only six studies that reported at least 3-year survival were identified, with results ranging from 37 to 58 per cent. Some of these figures are promising, given that the patients were considered to have unresectable disease. However, available evidence is limited and hepatic resection remains the standard of care when feasible; radiofrequency ablation cannot be considered an equivalent. Radiofrequency ablation does, however, appear to have a role in treating unresectable disease, and may also be used in conjunction with resection to extend its limits.

Background: Resection represents the best treatment for potentially curable liver tumors; radiofrequency ablation (RFA) is an alternative. The curative potential of RFA may be hampered because the extent of burn is difficult to estimate by ultrasound. We postulated that intraoperative MRI (iMRI) would enable a more accurate assessment of ablation completeness., Methods: We performed open hepatic surgery in an operating room equipped with a unique, retractable 1.5-T magnet. Patients were selected because it was anticipated that RFA (with or instead of resection) was likelihood and that iMRI might be helpful in making intraoperative decisions. After baseline MRI, lesions were further assessed by ultrasound at the time of open surgery. Lesions were resected and/or ablated, and further imaging confirmed the margins of the procedure., Results: Nine patients underwent the procedure: 1 with metastatic carcinoid, 4 with hepatocellular carcinoma, and 4 with colorectal liver metastases. In 4 patients, iMRI had an effect on decision-making. In 5 individuals, there were nonlocal recurrences, and 1 patient who was never disease-free had a local recurrence., Comments: Intraoperative MRI could potentially impact operative decision-making when ablating extensive disease. Its ability to prevent local recurrences must be determined. Moreover, the role of this technology in the overall treatment armamentarium must be defined.

Background: Early recurrence (ER) (<1 year) after liver resection is one of the most important factors that impact the prognosis of patients with hepatocellular carcinoma (HCC). We sought to determine factors associated with ER of HCC and examine the outcomes thereafter., Study Design: From March 2001 to June 2003, 56 patients underwent hepatic resection for HCC at University of Toronto and were prospectively followed with median followup of 24 months. Patients with ER were compared with those who remained disease free for more than 1 year. Patient characteristics, tumor stage, and operative procedures were evaluated for their prognostic significance by univariate and multivariable analysis. Time to recurrence and time to death were analyzed using Kaplan-Meier survival curves and compared using log-rank analysis., Results: The initial procedure in all patients was surgical hepatectomy. ER occurred in 21 patients (38%), 31 (55%) remained disease free for more than 1 year, and 4 (7%) were omitted from evaluation because of early (<30 days) death. Median survival after initial hepatic resection for those with ER was 27 months, and 2-year survival was 54%. There were no deaths in the group that remained disease free for more than 1 year (100% 2-year survival, p < 0.05). By multivariate analysis, vascular invasion and positive microscopic margins were significant predictors when all 4 variables were considered in the model (p < 0.05). After ER, 11 of 21 patients (52%) underwent additional therapy with significant improvement in median survival (33 months) compared with those not eligible for conventional therapy (18 months, p = 0.05)., Conclusions: ER after liver resection for HCC is the leading cause of death during the first 2 years after potentially curative resection. ER will develop in approximately 75% of patients with either vascular invasion or positive margins. For patients with these predictive factors additional treatment might be advised.

Bleeding from hepatic veins remains a problem during liver surgery. Perceived difficulties in the dissection and isolation of these retrohepatic venous structures have limited the widespread use of hepatic vein control during liver resection. The purpose of this study was to delineate the anatomy of the hepatic veins and to apply this knowledge to a series of patients undergoing liver resection with intermittent hepatic vein-total vascular exclusion (IHV-TVE). A detailed description of the hepatic venous anatomy was formulated using 20 cadaveric dissections in conjunction with anatomic descriptions during 30 hepatectomies. With the benefit of improved anatomic knowledge, we evaluated a series of 45 consecutive major liver resections in which hepatic veins were isolated and the technique of IHV-TVE was applied. The hepatocaval ligament must be divided to isolate the right hepatic vein. It was closely associated with a caudate vein 69% of the time. The hepatic veins were isolated in 45 consecutive patients who underwent a major hepatic resection. The portal triad and the hepatic veins were occluded intermittently (20 minutes with 5 minutes of reperfusion) with Rommel tourniquets. Mean total warm ischemic time was 65 +/- 24.5 minutes. Mean estimated blood loss was 864 +/- 514 ml. Eighteen percent of patients required blood transfusions. Complications were identified in 16 patients (35.5%), and the average length of hospital stay was 10.5 +/- 3.4 days. There were no deaths. Detailed anatomic knowledge of the hepatocaval ligament and the hepatic veins allows for safe extrahepatic control of the hepatic veins during major hepatic surgery. The technique was well tolerated and may have limited intraoperative blood loss.

The use of hepatic arterial infusion (HAI) for the delivery of chemotherapeutic agents to treat residual microscopic disease after curative hepatic resection for colorectal cancer metastases remains controversial. In recent years, a number of studies examining adjuvant HAI have shown conflicting results. A meta-analysis of prospective clinical trials was performed to determine if adjuvant HAI confers a survival benefit in this setting. Two reviewers independently performed a literature search of MEDLINE, PubMed, EMBASE, the Cochrane library, and the Cochrane Clinical Trials Registry. Prospective clinical trials comparing hepatic arterial chemotherapy after curative hepatic resection for colorectal cancer metastases against a control arm were included. Non-English-language publications were excluded. The outcome measure was survival difference at 1 and 2 years after surgery. Seven studies met the inclusion criteria, and all except one were randomized trials. The survival difference in months (positive values favoring the treatment arm) was 1.8 at 1 year (95% confidence interval, -4.9, 8.5) and 9.6 at 2 years (95% confidence interval, -2.2, 21.4). Neither was statistically significant (at 2 years, P=0.11). Based on these findings, routine adjuvant HAI after curative resection for colorectal cancer of the liver cannot be recommended. However, given the trend toward a survival benefit at 2 years, further study is recommended.

Background: Following resection of liver metastases from colorectal cancer, 5-year survivals are reportedly 30 - 39%. It can be assumed that this clinical situation represents systemic disease. Therefore, it is postulated that systemic chemotherapy would improve outcomes, particularly in those whose disease is sensitive to the agents administered. One potential advantage of neoadjuvant chemotherapy is that it provides in vivo chemosensitivity data. Response to neoadjuvant chemotherapy could therefore guide adjuvant chemotherapy following resection of liver metastases from colorectal cancer., Methods and Design: This is a prospective Phase II evaluation of outcomes in patients with potentially resectable liver metastases. Patients will receive neoadjuvant chemotherapy and will undergo resection. Postoperative chemotherapy will be directed by the degree of response to preoperative chemotherapy. All patients with Stage IV colorectal adenocarcinoma isolated to the liver that have disease that is amenable to complete ablation by resection, radiofrequency ablation, and/or cryoablation will be candidates for the trial. Patients will receive CPT-11 180 mg/m2 IV (over 90 minutes) on day 1 with 5-FU 400 mg/m2 bolus and 600 mg/m2 by 22 hour infusion and calcium folinate 200 mg/m2 on days 1 and 2, every 2 weeks. Altogether, six cycles of chemotherapy will be administered. Patients will then undergo resection and/or radiofrequency ablation. Patients who had stable disease or a clinical response with preoperative chemotherapy will receive an additional 12 cycles of CPT-11 180 mg/m2 IV (over 90 minutes) on day 1 with 5-FU 400 mg/m2 bolus and 600 mg/m2 by 22 hour infusion and calcium folinate 200 mg/m2 on days 1 and 2 (given every 2 weeks). Patients with resectable disease who had progressive disease during neoadjuvant chemotherapy will receive best supportive care or an alternative agent, at the discretion of the treating physician. Those patients who are not rendered free of disease following the neoadjuvant chemotherapy and surgery will receive best supportive care or an alternative agent, at the discretion of the treating physician. The primary endpoint of the study is disease-free survival. Secondary endpoints include overall survival, safety and feasibility, response to chemotherapy, and quality of life.

Objectives: To describe the wide variation in presentation of cystadenomas of the liver and to delineate useful tests for diagnosis and effective surgical treatment., Design: A case series., Setting: A university-affiliated hospital., Patients: Four patients (3 women, 1 man) having cystadenoma of the liver, 2 of whom had associated mesenchymal stroma., Main Outcome Measures: Serum and cyst fluid carcinoembryonic antigen (CEA) and CA19-9 levels, type of surgery, morbidity and recurrence rates., Results: Cyst fluid CEA and CA19-9 levels were elevated. One patient had resection, 2 had complete enucleation and 1 had partial enucleation. There were no deaths. Morbidity included 1 wound infection; there were no biliary fistulas. The patient with partial enucleation had a radiologically confirmed recurrence., Conclusions: Analysis of cyst fluid CEA and CA19-9 is useful for diagnosis; besides hepatic resection, complete enucleation should be considered as a reasonable treatment for patients with this disease.