Novel multiparametric MRI detects improved future liver remnant quality post-dual vein embolization.

BACKGROUND: Optimisation of the future liver remnant (FLR) is crucial to outcomes of extended liver resections. This study aimed to assess the quality of the FLR before and after dual vein embolization (DVE) by quantitative multiparametric MRI. METHODS: Of 100 patients with liver metastases recruited in a clinical trial (Precision1:NCT04597710), ten consecutive patients with insufficient FLR underwent quantitative multiparametric MRI pre- and post-DVE (right portal and hepatic vein). FLR volume, liver fibro-inflammation (corrected T1) scores and fat percentage (proton density fat fraction, PDFF) were determined. Patient metrics were compared by Wilcoxon signed-rank test and statistical analysis done using R software. RESULTS: All patients underwent uncomplicated DVE with improvement in liver remnant health, median 37 days after DVE: cT1 scores reduced from median (interquartile range) 790 ms (753-833 ms) to 741 ms (708-760 ms) p = 0.014 [healthy range <795 ms], as did PDFF from 11% (4-21%), to 3% (2-12%) p = 0.017 [healthy range <5.6%]. There was a significant increase in median (interquartile range) FLR volume from 33% (30-37%)% to 49% (44-52%), p = 0.002. CONCLUSION: This non-invasive and reproducible MRI technique showed improvement in volume and quality of the FLR after DVE. This is a significant advance in our understanding of how to prevent liver failure in patients undergoing major liver surgery.

Peri-operative thrombophilia in patients undergoing liver resection for colorectal metastases.

BACKGROUND: Routine chemical venous thromboembolism (VTE) prophylaxis for liver surgery remains controversial, and often delayed post-operatively due to perceived bleeding risk. This study asked whether patients undergoing hepatectomy for colorectal metastases (CRM) were at risk from VTE pre-operatively, and the impact of hepatectomy on that risk. METHODS: Single-centre prospective observational cohort study of patients undergoing open hepatectomy for CRM, comparing pre-, peri- and post-operative haemostatic variables. RESULTS: Of 336 hepatectomies performed October 2017-December 2019, 60 resections in 57 patients were recruited. There were 28 (46.7%) major resections, with median (interquartile range [IQR]) blood loss 150.0 (76.3-263.7) mls, no blood transfusions, post-operative VTE events or deaths. Patients were prothrombotic pre-operatively (high median factor VIIIC and increased thrombin generation velocity index), an effect exacerbated post-hepatectomy. Major hepatectomies had a significantly greater median drop in Protein C, rise in Factor VIIIC and von Willebrand Factor, versus minor resections (p = 0.001, 0.005, 0.001 respectively). Patients with parenchymal transection times greater than median (40 min), had significantly increased median (IQR) PMBC-TFmRNA expression [1.65(0.93-2.70)2ddCt], versus quicker transections [0.99(0.69-1.28)2ddCt, p = 0.020]. CONCLUSIONS: Patients with CRM are prothrombotic pre-operatively, an effect exacerbated by hepatectomy, particularly longer, complex resections, suggesting chemical thromboprophylaxis be considered early in the patient pathway.

Study protocol: HepaT1ca - an observational clinical cohort study to quantify liver health in surgical candidates for liver malignancies.

BACKGROUND: Accurate assessment of liver health prior to undertaking resectional liver surgery or chemoembolisation for primary and secondary cancers is essential for patient safety and optimal outcomes. LiverMultiScan™, an MRI-based technology, non-invasively quantifies hepatic fibroinflammatory disease, steatosis and iron content. We hypothesise that LiverMultiScan™can quantify liver health prior to surgery and inform the risk assessment for patients considering liver surgery or chemoembolization and seek to evaluate this technology in an operational environment. METHODS/DESIGN: HepaT1ca is an observational cohort study in two tertiary-referral liver surgery centres in the United Kingdom. The primary outcome is correlation between the pre-operative liver health assessment score (Hepatica score - calculated by weighting future remnant liver volume by liver inflammation and fibrosis (LIF) score) and the post-operative liver function composite integer-based risk (Hyder-Pawlik) score. With ethical approval and fully-informed consent, individuals considering liver surgery for primary or secondary cancer will undergo clinical assessment, blood sampling, and LiverMultiScan™multiparametric MRI before and after surgical liver resection or TACE. In nested cohorts of individuals undergoing chemotherapy prior to surgery, or those undergoing portal vein embolization (PVE) as an adjunct to surgery, an additional testing session prior to commencement of treatment will occur. Tissue will be examined histologically and by immunohistochemistry. Pre-operative liver health assessment scores and the post-operative risk scores will be correlated to define the ability of LiverMultiScan™to predict the risk of post-operative morbidity and mortality. Because technology performance in this setting is unknown, a pragmatic sample size will be used. For the primary outcome, n = 200 for the main cohort will allow detection of a minimum correlation coefficient of 0.2 with 5% significance and power of 80%. DISCUSSION: This study will refine the technology and clinical application of multiparametric MRI (including LiverMultiScan™), to quantify pre-existing liver health and predict post-intervention outcomes following liver resection. If successful, this study will advance the technology and support the use of multiparametric MRI as part of an enhanced pre-operative assessment to improve patient safety and to personalise operative risk assessment of liver surgery/non-surgical intervention. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov Identifier: NCT03213314 .

One-millimeter cancer-free margin is curative for colorectal liver metastases: a propensity score case-match approach.

OBJECTIVE: To investigate the influence of clear surgical resection margin width on disease recurrence rate after intentionally curative resection of colorectal liver metastases. BACKGROUND: There is consensus that a histological positive resection margin is a predictor of disease recurrence after resection of colorectal liver metastases. The dispute, however, over the width of cancer-free resection margin required is ongoing. METHODS: Analysis of observational prospectively collected data for 2715 patients who underwent primary resection of colorectal liver metastases from 2 major hepatobiliary units in the United Kingdom. Histological cancer-free resection margin was classified as positive (if cancer cells present at less than 1 mm from the resection margin) or negative (if the distance between the cancer and the margin is 1 mm or more). The negative margin was further classified according to the distance from the tumor in millimeters. Predictors of disease-free survival were analyzed in univariate and multivariate analyses. A case-match analysis by a propensity score method was undertaken to reduce bias. RESULTS: A 1-mm cancer-free resection margin was sufficient to achieve 33% 5-year overall disease-free survival. Extra margin width did not add disease-free survival advantage (P > 0.05). After the propensity case-match analysis, there is no statistical difference in disease-free survival between patients with negative narrow and wider margin clearance [hazard ratio (HR) 1.0; 95% (confidence interval) CI: 0.9-1.2; P = 0.579 at 5-mm cutoff and HR 1.1; 95% CI: 0.96-1.3; P = 0.149 at 10-mm cutoff]. Patients with extrahepatic disease and positive lymph node primary tumor did not have disease-free survival advantage despite surgical margin clearance (9 months for <1-mm vs 12 months for ≥1-mm margin clearance; P = 0.062). CONCLUSION: One-mm cancer-free resection margin achieved in patients with colorectal liver metastases should now be considered the standard of care.

Postoperative pain control using continuous i.m. bupivacaine infusion plus patient-controlled analgesia compared with epidural analgesia after major hepatectomy.

OBJECTIVES: There is debate concerning the best mode of delivery of analgesia following liver resection, with continuous i.m. infusion of bupivacaine (CIB) plus patient-controlled i.v. analgesia (PCA) suggested as an alternative to continuous epidural analgesia (CEA). This study compares these two modalities. METHODS: A total of 498 patients undergoing major hepatectomy between July 2004 and July 2011 were included. Group 1 received CIB + PCA (n = 429) and Group 2 received CEA (n = 69). Groups were analysed on baseline patient and surgical characteristics. Primary endpoints were pain severity scores and total opioid consumption. Secondary endpoints were pain management failures, need for rescue medication, postoperative (opioid-related) morbidity and hospital length of stay (LoS). RESULTS: In both groups pain was well controlled and >70% of patients had no or minimal pain on PoDs 1 and 2. The numbers of patients experiencing severe pain were similar in both groups: PoD 1 at rest: 0.3% in Group 1 and 0% in Group 2 (P = 1.000); PoD 1 on movement: 8% in Group 1 and 2% in Group 2 (P = 0.338); PoD 2 at rest: 0% in Group 1 and 2% in Group 2 (P = 0.126), and PoD 2 on movement: 5% in Group 1 and 5% in Group 2 (P = 1.000). Although the CIB + PCA group required more opioid rescue medication on PoD 0 (53% versus 22%; P < 0.001), they used less opioids on PoDs 0-3 (P ≤ 0.001), had lower morbidity (26% versus 39%; P = 0.018), and a shorter LoS (7 days versus 8 days; P = 0.005). CONCLUSIONS: The combination of CIB + PCA provides pain control similar to that provided by CEA, but facilitates lower opioid consumption after major hepatectomy. It has the potential to replace epidural analgesia, thereby avoiding the occurrence of rare but serious complications.

The Role of the Multiparametric MRI LiverMultiScanTM in the Quantitative Assessment of the Liver and Its Predicted Clinical Applications in Patients Undergoing Major Hepatic Resection for Colorectal Liver Metastasis.

Liver biopsy remains the gold standard for the histological assessment of the liver. With clear disadvantages and the rise in the incidences of liver disease, the role of neoadjuvant chemotherapy in colorectal liver metastasis (CRLM) and an explosion of surgical management options available, non-invasive serological and imaging markers of liver histopathology have never been more pertinent in order to assess liver health and stratify patients considered for surgical intervention. Liver MRI is a leading modality in the assessment of hepatic malignancy. Recent technological advancements in multiparametric MRI software such as the LiverMultiScanTM offers an attractive non-invasive assay of anatomy and histopathology in the pre-operative setting, especially in the context of CRLM. This narrative review examines the evidence for the LiverMultiScanTM in the assessment of hepatic fibrosis, steatosis/steatohepatitis, and potential applications for chemotherapy-associated hepatic changes. We postulate its future role and the hurdles it must surpass in order to be implemented in the pre-operative management of patients undergoing hepatic resection for colorectal liver metastasis. Such a role likely extends to other hepatic malignancies planned for resection.

Protocol for the CoNoR Study: A prospective multi-step study of the potential added benefit of two novel assessment tools in colorectal liver metastases technical resectability decision-making.

INTRODUCTION: Liver resection is the only curative treatment for colorectal liver metastases (CLM). Resectability decision-making is therefore a key determinant of outcomes. Wide variation has been demonstrated in resectability decision-making, despite the existence of criteria. This paper summarises a study protocol to evaluate the potential added value of two novel assessment tools in assessing CLM technical resectability: the Hepatica preoperative MR scan (MR-based volumetry, Couinaud segmentation, liver tissue characteristics and operative planning tool) and the LiMAx test (hepatic functional capacity). METHODS AND ANALYSIS: This study uses a systematic multistep approach, whereby three preparatory workstreams aid the design of the final international case-based scenario survey:Workstream 1: systematic literature review of published resectability criteria.Workstream 2: international hepatopancreatobiliary (HPB) interviews.Workstream 3: international HPB questionnaire.Workstream 4: international HPB case-based scenario survey.The primary outcome measures are change in resectability decision-making and change in planned operative strategy, resulting from the novel test results. Secondary outcome measures are variability in CLM resectability decision-making and opinions on the role for novel tools. ETHICS AND DISSEMINATION: The study protocol has been approved by a National Health Service Research Ethics Committee and registered with the Health Research Authority. Dissemination will be via international and national conferences. Manuscripts will be published. REGISTRATION DETAILS: The CoNoR Study is registered with ClinicalTrials.gov (registration number NCT04270851). The systematic review is registered on the PROSPERO database (registration number CRD42019136748).

Extrahepatic versus intrahepatic hilar control for right hepatectomy: an updated experience.

BACKGROUND: Inflow control prior to transection for right hepatectomy may be achieved either by dissection and ligation of the individual hilar structures outside of the liver (EHD) or by mass stapling of the inflow structures within the hepatic parenchyma. Our preference is for the anterior intrahepatic approach (AIA) with mass stapling, in order to minimise the risk of inadvertent injury of the left-sided inflow and to preserve as much parenchyma as possible. In this paper, we present our experience over the last 10 years and compare it with results from the EHD technique. METHODS: Data for a 10-year period from 2000 to 2010 were extracted retrospectively from a prospectively collected database. Results in each group were measured by a combination of technical and oncological outcomes. Groups were compared by way of descriptive statistics and differences tested for significance by appropriate statistical means. RESULTS: 411 right hepatectomies were performed for colorectal metastases. Of these, 242 were by AIA and 169 by EHD. Both groups were well matched in demographic terms and according to disease burden, although more extended resections were performed in the EHD group. Operative duration (433 vs. 350 min), blood loss (420 vs. 348 ml) and incidence of bile leaks (4 vs. 2) were all lower in the AIA group. All other technical and oncological outcomes were equivalent. CONCLUSION: The AIA approach provides equivalent morbidity, mortality and oncological outcome to the EHD dissection technique and may confer the benefits of being safer and providing greater scope to preserve hepatic parenchyma.

Detailed liver-specific imaging prior to pre-operative chemotherapy for colorectal liver metastases reduces intra-hepatic recurrence and the need for a repeat hepatectomy.

BACKGROUND: Neoadjuvant chemotherapy for colorectal liver metastases (CRLM) reduces the accuracy of liver imaging which may understage patients pre-operatively. Retrospective review of a prospective database to determine whether liver-specific magnetic resonance imaging (MRI) prior to pre-operative chemotherapy affects intra-hepatic recurrence and long-term outcome after hepatectomy. PATIENTS AND METHODS: Between 2003 and 2009, 242 patients with CRLM underwent a hepatectomy after ≥3 cycles of oxaliplatin or irinotecan-based chemotherapy. All had a liver-specific MRI immediately pre-operatively. The outcome of patients who had a liver-specific MRI prior to chemotherapy (PCI group, n= 92) was compared with those who did not (non-PCI group, n= 150). RESULTS: A liver-specific MRI pre-chemotherapy changed the staging in 56% of patients. At a median (range) follow-up of 55 (6-94) months, there was a higher incidence of intra-hepatic recurrence at a new site in the non-PCI group (65% vs. 48% in the PCI group, P= 0.041) and an increased rate of recurrence in patients with the same number of lesions pre- and post-chemotherapy [hazard ratio (HR) 2.02, 1:10-3.37, P= 0.024]. The non-PCI group underwent more repeat hepatectomies than the PCI group (24.7% vs. 13%, P= 0.034), achieving similar long-term survival. CONCLUSIONS: A liver-specific MRI prior to chemotherapy reduces intra-hepatic recurrence and avoids a repeat hepatectomy.

Precision medicine for liver tumours with quantitative MRI and whole genome sequencing (Precision1 trial): study protocol for observational cohort study.

INTRODUCTION: Radiogenomic analysis of patients being considered for liver resection is seldom performed in the clinic despite recent evidence indicating that quantitative MRI could improve posthepatectomy outcomes. Meanwhile, the increasingly accessible results from whole genome sequencing reporting on clinically actionable genetic biomarkers are yet to be fully integrated into the clinical care pathway. METHODS AND ANALYSIS: A prospective observational cohort study of up to 200 participants is planned, recruiting adults with primary or secondary liver cancer being considered for liver resection at Hampshire Hospitals NHS Foundation Trust. The data will be evaluated to address the primary endpoint to calculate the proportion of participants in which the results from whole genome sequencing would have resulted in a change in clinical management. Participants will be offered an additional non-invasive quantitative MRI scan prior to the operation and the impact of the imaging results on treatment decision-making will be evaluated. ETHICS AND DISSEMINATION: This study was reviewed by the NHS Health Research Authority and given favourable opinion by the Brighton and Sussex Research Ethics Committee (REC reference: 20/PR/0222). Research findings will be discussed with a patient and public involvement and engagement group, presented at relevant scientific conferences and published in open access journals. TRIAL REGISTRATION NUMBER: NCT04597710.

International multicentre prospective study on microwave ablation of liver tumours: preliminary results.

BACKGROUND: Microwave ablation (MWA) is increasingly utilized in the treatment of hepatic tumours. Promising single-centre reports have demonstrated its safety and efficacy, but this modality has not been studied in a prospective, multicentre study. METHODS: Eighteen international centres recorded operative and perioperative data for patients undergoing MWA for tumours of any origin in a voluntary Internet-based database. All patients underwent operative MWA using a 2.45-GHz generator with a 5-mm antenna. RESULTS: Of the 140 patients, 114 (81.4%) were treated with MWA alone and 26 (18.6%) were treated with MWA combined with resection. Multiple tumours were treated with MWA in 40.0% of patients. A total of 299 tumours were treated in these 140 patients. The median size of ablated lesions was 2.5 cm (range: 0.5-9.5 cm). Tumours were treated with a median of one application (range: 1-6 applications) for a median of 4 min (range: 0.5-30.0 min). A power setting of 100 W was used in 78.9% of cases. Major morbidity was 8.3% and in-hospital mortality was 1.9%. CONCLUSIONS: These multi-institution data demonstrate rapid ablation time and low morbidity and mortality rates in patients undergoing operative MWA with a high rate of multiple ablations and concomitant hepatic resection. Longterm follow-up will be required to determine the efficacy of MWA relative to other forms of ablative therapy.

Quantitative multiparametric MRI allows safe surgical planning in patients undergoing liver resection for colorectal liver metastases: report of two patients.

It is not uncommon for clinicians to encounter varying degrees of hepatic steatosis in patients undergoing resection for colorectal liver metastases (CRLM). Magnetic resonance imaging is currently the preferred investigation for identification and pre-operative planning of these patients. An objective assessment of liver quality and degree of steatosis is paramount for planning a safe resection, which is seldom provided by routine MRI sequences. We studied two patients who underwent an additional pre-operative multiparametric MRI scan (LiverMultiScanTM) as a part of an observational clinical trial (HepaT1ca, NCT03213314) to assess the quality of liver. Outcome was assessed in the form of post-hepatectomy liver failure. Both patients (Patient 1 and 2) had comparable pre-operative characteristics. Both patients were planned for an extended right hepatectomy with an estimated future liver remnant of approximately 30%. Conventional preoperative contrast MRI showed mild liver steatosis in both patients. Patient one developed post-hepatectomy liver failure leading to prolonged hospital stay compared to patient two who had uneventful post-operative course. Retrospective evaluation of multiparametric MRI scan revealed findings consistent with fibro-inflammatory disease and steatosis (cT1 829 ms, PDFF 14%) for patient 1 whereas patient two had normal parameters (cT1 735 ms, PDFF 2.4%). These findings corresponded with the resection specimen histology. Multiparametric MRI can objectively evaluate future liver health and volume which may help refine surgical decision-making and improve patient outcomes.

Open liver resection for colorectal metastases: better short- and long-term outcomes in patients potentially suitable for laparoscopic liver resection.

BACKGROUND: There is no prospective randomized data comparing laparoscopic to open hepatectomy. This study compared short- and long-term outcomes in patients undergoing hepatectomy for colorectal metastases (CRM), who were suitable for either laparoscopic or open surgery. METHODS: Data were prospectively collected from consecutive patients undergoing hepatic resection of CRM at a single centre (1987-2007). Patients who were suitable for laparoscopic resection (Group 1) were compared with patients whose tumour characteristics would best be considered for open resection (Group 2). RESULTS: Out of 1152 hepatectomies, 266 (23.1%) were deemed suitable for a laparoscopic approach. The median (IQR) number of metastases was greater in Group 2 [2(1-20) vs. 1(1-10), P < 0.001], as was the mean (SD) tumour size [5.3(3.6) cm vs. 3.3(1.2) cm, P < 0.001]. The median (IQR) operation time [210 (70) min vs. 240 (90) min, P < 0.001] and blood loss [270 (265) ml vs. 355 (320) ml, P < 0.001] were less in Group 1. There was no difference in length of stay, morbidity or mortality. Patients in Group 2 had a higher R1 resection rate (14.9%) compared with Group 1 (4.5%, P < 0.001) and lower 5-year survival (37.8% vs. 44.2%, P= 0.005). DISCUSSION: Current criteria for laparoscopic hepatectomy selects patients who have more straight-forward surgery, with less risk of an involved resection margin and better long-term survival, compared with patients unsuited to a laparoscopic approach. Clearly defined criteria for laparoscopic hepatectomy are essential to allow meaningful analysis of outcomes and the results of unrandomized series of laparoscopic hepatectomies must be interpreted with caution.

Quantitative magnetic resonance imaging predicts individual future liver performance after liver resection for cancer.

The risk of poor post-operative outcome and the benefits of surgical resection as a curative therapy require careful assessment by the clinical care team for patients with primary and secondary liver cancer. Advances in surgical techniques have improved patient outcomes but identifying which individual patients are at greatest risk of poor post-operative liver performance remains a challenge. Here we report results from a multicentre observational clinical trial (ClinicalTrials.gov NCT03213314) which aimed to inform personalised pre-operative risk assessment in liver cancer surgery by evaluating liver health using quantitative multiparametric magnetic resonance imaging (MRI). We combined estimation of future liver remnant (FLR) volume with corrected T1 (cT1) of the liver parenchyma as a representation of liver health in 143 patients prior to treatment. Patients with an elevated preoperative liver cT1, indicative of fibroinflammation, had a longer post-operative hospital stay compared to those with a cT1 within the normal range (6.5 vs 5 days; p = 0.0053). A composite score combining FLR and cT1 predicted poor liver performance in the 5 days immediately following surgery (AUROC = 0.78). Furthermore, this composite score correlated with the regenerative performance of the liver in the 3 months following resection. This study highlights the utility of quantitative MRI for identifying patients at increased risk of poor post-operative liver performance and a longer stay in hospital. This approach has the potential to inform the assessment of individualised patient risk as part of the clinical decision-making process for liver cancer surgery.

A diagnostic paradigm for resectable liver lesions: to biopsy or not to biopsy?

BACKGROUND: Despite a growing body of evidence reporting the deleterious mechanical and oncological complications of biopsy of hepatic malignancy, a small but significant number of patients undergo the procedure prior to specialist surgical referral. Biopsy has been shown to result in poorer longterm survival following resection and advances in modern imaging modalities provide equivalent, or better, diagnostic accuracy. METHODS: The literature relating to needle-tract seeding of primary and secondary liver cancers was reviewed. MEDLINE, EMBASE and the Cochrane Library were searched for case reports and series relating to the oncological complications of biopsy of liver malignancies. Current non-invasive diagnostic modalities are reviewed and their diagnostic accuracy presented. RESULTS: Biopsy of malignant liver lesions has been shown to result in poorer longterm survival following resection and does not confer any diagnostic advantage over a combination of non-invasive imaging techniques and serum tumour markers. CONCLUSIONS: Given that chemotherapeutic advances now often permit downstaging and subsequent resection of 'unresectable' disease, the time has come to abandon biopsy of solid lesions outside the setting of a specialist multi-disciplinary team meeting (MDT).

The impact of pre-operative serum creatinine on short-term outcomes after liver resection.

BACKGROUND: The aim of the present study was to determine whether raised pre-operative serum creatinine increased the risk of renal failure after liver resection. METHOD: Data were studied from 1535 consecutive liver resections. Outcomes in patients with pre-operative creatinine /=125 micromol/l (Group 2). RESULTS: The median age of the 1446 (94.3%) patients resected in Group 1 was 62 years compared with 67 years in the 88 (5.7%) patients in Group 2 (P < 0.0001). Similarly this latter group had double the number of patients who were American Society of Anesthesiologists (ASA) III or IV (34.1% vs. 15.2%, P= 0.00004). Overall, the incidence of post-operative renal failure requiring haemofiltration was low (0.9%) but significantly more in Group 2 patients (5.7% vs. 0.6, P= 0.0007). In addition, patients in Group 2 were more likely to suffer acute kidney injury post-operatively (18.2% vs. 4.3%, P < 0.0001). Patients with acute kidney injury had significantly higher blood loss. Although there was no difference in mortality, patients in Group 2 had higher post-operative morbidity (37.5%) than Group 1 (21.7%, P= 0.0006), with the incidence of cardiorespiratory complications being higher in Group 2 (25.9% vs. 8.9%, P= 0.0025). CONCLUSIONS: After liver resection, renal failure is rare but patients with an elevated creatinine pre-operatively are at an increased risk of both renal and non-renal complications.

Long-term results of liver resection for non-colorectal, non-neuroendocrine metastases.

INTRODUCTION: The safety and efficacy of liver resection for colorectal and neuroendocrine liver metastases is well established. However, there is lack of consensus regarding long-term effectiveness of hepatic resection for non-colorectal, non-neuroendocrine (NCNN) liver metastases. METHODS: A review of prospectively collected data of patients undergoing hepatic resection for NCNN liver metastases at two tertiary referral centres in the UK and Australia was undertaken. Survival analysis was used to evaluate the clinical, demographic and operative factors associated with long-term survival. RESULTS: A total of 114 hepatic resections in 102 patients were performed between 1986 and 2006. Postoperative mortality and morbidity was 0.8% and 21.1%, respectively. At 3 and 5 years overall survival was 56.1% and 38.5%, whereas disease-free survival was 37.2% and 26.5%, respectively. On multivariate analysis, factors associated with poor overall survival were diameter of liver metastasis [<5 cm versus >5 cm: hazard ratio (HR) = 2.83, p = 0.001] and the presence of extrahepatic nodal disease (HR = 3.58, p = 0.001). The type of tumor, the presence of distant extra-hepatic metastases, tumor-free interval, number and distribution of metastases did not effect long-term survival. CONCLUSION: These results of the present study suggest that liver resection is an effective management option in selected patients with NCNN metastases confined to the liver.

Quantification of risk of a positive (R1) resection margin following hepatic resection for metastatic colorectal cancer: an aid to clinical decision-making.

BACKGROUND AND AIMS: Margin involvement following liver resection for colorectal cancer is associated with early disease recurrence and shorter long-term survival. This study aimed to develop a predictive index for quantifying the likelihood of a positive resection margin (R1) for patients undergoing hepatic resection for metastatic colorectal cancer. METHODS: Clinical, pathological and complete follow-up data were prospectively collected from 1005 consecutive liver resections performed in 929 patients for colorectal liver metastases with curative intent at a single centre between 1987 and 2005. Ninety-four resections in 81 patients with extra-hepatic disease were excluded, leaving 911 resections (844 primary and 67 repeat) in 848 patients for analysis. Multivariate logistic regression was used to identify independent predictors of margin involvement and from the beta-coefficients generated, develop a predictive model that was validated using measures of discrimination and calibration. RESULTS: There were 80 (8.8%) R1 resections, with a 5-year cancer-specific survival for R0 and R1 hepatic resections of 39.7% and 17.8%, respectively; p<0.001. On multivariate analysis, five risk factors were found to be independent predictors of an R1 resection: non-anatomical resection vs. anatomical resection (odds ratio (OR)=4.3, p=0.001), >3 hepatic metastases involving >50% of the liver vs. <3 metastases (OR=4.0, p<0.001); bilobar vs. unilobar disease (OR=2.9, p<0.001); repeat vs. primary hepatic resection (OR=3.1, p=0.006); abnormal vs. normal pre-operative liver function tests (OR=1.6, p=0.044). These five factors were used to develop a predictive model, which when tested, fitted the data well, with an area under the receiver operating characteristic curve of 78.1% (S.E.=2.7%). CONCLUSIONS: This study describes an accurate model for quantifying the risk of a positive margin following hepatic resection for liver metastases. It may be used pre-operatively by multi-disciplinary teams to identify patients who may benefit from neoadjuvant therapy prior to liver surgery, thus minimizing the risk of a positive resection margin.

Predictive models in colorectal liver metastases--can we personalize treatment and outcome?

BACKGROUND/AIMS: Hepatic resection for colorectal liver metastases offers patients the best chance of long-term survival. Survival rates after resection range from 25 to 60%. Predictive models may risk-stratify patients and allow improved selection for surgery or other therapies. This review aims to achieve consensus regarding the predictors of survival after hepatic resection for colorectal metastases and evaluate current predictive models of outcome. METHODS: A comprehensive literature review of published studies with more than 500 patients describing models for predicting long-term survival in patients undergoing hepatic resection for colorectal metastases. RESULTS: Five large predictive models have been published to date. The three predictive models developed from the largest series agree over the key independent predictors of poor long-term outcome for patients undergoing liver resection for colorectal metastases. All five models have individual shortcomings, and whilst three have been internally validated, two have been externally validated with conflicting results. The Basingstoke Predictive Index appears to be accurate and internally validated. CONCLUSIONS: There is need within the international surgical oncology community for consensus regarding a predictive model to be universally adopted for risk-stratifying patients who may benefit from intensive surveillance and selection for adjuvant therapy and clinical trials.

Meta-analysis of clinical outcome after first and second liver resection for colorectal metastases.

BACKGROUND: The perioperative risk and long-term survival benefit of repeat hepatectomy for patients with liver metastases from colorectal cancer, compared with that of a first liver resection, has been reported with varying results in the literature. METHODS: The literature was searched using Medline, Embase, Ovid, and Cochrane databases for all studies published from 1992 to 2006. Two authors independently extracted data using the following outcomes: postoperative complications and mortality; disease recurrence; and long-term survival. Trials were assessed using the modified Newcastle-Ottawa Score. Random-effect meta-analytical techniques were used for analysis. RESULTS: Twenty-one studies met the inclusion criteria, comprising 3,741 patients. The use of adjuvant chemotherapy was similar in both groups (odds ratio [OR] = 0.97; 95% confidence interval [CI] = 0.54, 1.74; P = .92), as was the number of hepatic nodules present at the time of first or second resection (weighted mean difference [WMD] = 0.18; 95% CI = -0.22, 0.57; P = .380). Wedge resection was carried out less often at first hepatectomy (39% vs 46%; OR = 0.66; 95% CI = 0.44, 1.00; P = .05). There was significantly less blood loss in patients undergoing first versus second hepatectomy (WMD = 238 ml; 95% CI = 90, 385; P = .002). There was no difference in perioperative morbidity (OR = 1.01; 95% CI = 0.65, 1.55; P = .98), mortality (OR = 1.01; 95% CI = 0.18, 5.72; P = .99) or long-term survival (HR = 0.90; 95% CI = .66, 1.24; P = .530) between groups. CONCLUSIONS: Repeat hepatectomy for patients with colorectal cancer metastases is safe and provides survival benefit equal to that of a first liver resection.