Resectable Colorectal Cancer Liver Research Articles

Incidence and Risk Factors of Venous Thromboembolism Following Hepatectomy for Colorectal Metastases: A Population-Based Retrospective Cohort Study.

Incidence of venous thromboembolism (VTE) following hepatectomy for colorectal cancer (CRC) metastases is unclear. These patients may represent a vulnerable population due to increased tumour burden. We aim to identify the risk of VTE development in routine clinical practice among patients with resected CRC liver metastases, the associated risk factors, and its impact on survival. We conducted a population-based retrospective cohort study of Ontario patients undergoing hepatectomy for CRC metastases between 2002 and 2009 using linked universal healthcare databases. Multivariable logistic regression was used to estimate the association between patient characteristics and VTE risk at 30 and 90-days after surgery. Cox proportional-hazards regression was used to estimate the association between VTE and adjusted cancer specific (CSS) and overall survival (OS). 1310 patients were included with a mean age of 63 ± 11. 62% were male. 51% had one metastatic deposit. Major hepatectomy occurred in 64%. VTE occurred in 4% within 90days of liver resection. Only longer length of stay was associated with VTE development (OR 6.88 (2.57-18.43), p <0.001 for 15-21days versus 0-7days). 38% of VTEs were diagnosed after discharge, comprising 1.52% of the total cohort. VTE was not associated with inferior CSS or OS. Risk of VTE development in this population is similar to those undergoing hepatectomy for other indications, and to the risk following other cancer site resections where post-operative extended VTE prophylaxis is currently recommended. The number of VTEs occurring after discharge suggests there may be a role for extended VTE prophylaxis.

Comparison of short-term and long-term survival groups and prognostic factors in patients with liver metastasis of colorectal cancer

There was no report for comparing long-term survival group with short-term survival group in patients who underwent liver resection for colorectal cancer with liver metastasis. Here, we compared the difference between the short-term and long-term survivors and analyzed the factors that influence the prognosis. From January 2016 to December 2018, liver resections were performed for 478 patients of liver metastasis at the Yonsei University Severance Hospital. Except 111 patients due to lack of data, total 367 patients were analyzed retrospectively. Patients were divided into two groups: those who survived less than 24 months (short-term survival group, n = 87) and those who survived more than 24 months (long-term survival group, n = 280). In the short-term survival group, there were more patients with tumor size of 2 cm or more than the long-term survival group (p = 0.017). And the short-term survival group had more patients with margin positive than the long-term survival group (p < 0.05). The long-term survival group had more patients with single lesion than the short-term survival group (p = 0.028). In cox regression analysis, tumor size, tumor number, and resection margin were the prognostic factors effect survival. For long-term survival of patients with liver metastasis of colorectal cancer, when deciding whether to undergo liver resection, whether a tumor smaller than 2 cm or a single lesion or curative resection is possible should be considered.

Benefits of simultaneous laparoscopic colorectal surgery and liver resection for colorectal cancer with synchronous liver metastases: Retrospective case-matched study

IntroductionLaparoscopic surgery for colorectal cancer and liver tumors are accepted as alternative procedure to open surgery. However, few studies reported outcomes of simultaneous laparoscopic surgery of these two procedures. The aim of this study was to compare short-term outcomes between laparoscopic and open approach. Materials and methodsBetween June 2010 to December 2019, simultaneous laparoscopic cases were retrospectively matched (1:2) to open cases. Peri-operative and short-term outcomes were compared between both groups. ResultsTwelve patients in laparoscopic group were matched to 24 patients in open group according to age, gender, body mass index, american society of anesthesiologists physical status, preoperative laboratory data, number and size of liver metastases and extent of colorectal and liver resection, Most patients in each group had left-sided colon or rectal cancer and underwent wedge liver resection. The mean number of liver metastases was 1.3 vs 1.5 and size of liver metastases was 2.2 ± 1.4 vs 2.7 ± 1.1 cm in laparoscopic compared to open group. Estimated blood loss and length of hospital stay were significantly lower in laparoscopic group. However, operative time was significantly longer in laparoscopic group. Peri-operative complication was not significant difference between both groups and there was no mortality. ConclusionSimultaneous laparoscopic colorectal surgery and minor liver resection is feasible and safe. Laparoscopic approach has better peri-operative outcome in term of shorter length of hospital stay compared to open approach.

Simultaneous versus staged resection for synchronous colorectal cancer liver metastases: A population-based cohort study.

3612 Background: Simultaneous resection of colorectal cancer primary and liver metastases is not performed routinely due to concerns about safety. We hypothesized that simultaneous resection has steadily increased overtime and that the outcomes are similar. Methods: Population-based cohort study of patients undergoing resection for synchronous (resection of the primary colorectal cancer and liver metastases within six months) liver metastases from 2006-2015 by linking administrative datasets in Ontario, Canada. Outcomes: post-operative complications, length of hospital stay, and overall survival. Survival for the staged group was measured from the last surgical resection to death and estimated using Kaplan Meier and compared with the log-rank test. Cox proportional hazard models were used to calculate risks for death. We aimed to identify practice patterns, outcomes of simultaneous vs. staged resections for these patients. Results: Of 2,738 patients undergoing colorectal and liver resection for colorectal cancer, 1,168 were synchronous, of which, 442 underwent simultaneous resection. Rate of synchronous disease presentation increased on average by 3% per year (p = 0.02). Median length of stay was shorter (8 vs. 11 days, p &lt; 0.001); rate of major liver resections were lower (17% vs. 65%, p &lt; 0.001), and 90-day post-operative mortality was higher (6% vs. 1%) for simultaneous resections. Major postoperative complications were higher in the simultaneous group (28% vs. 23%, p = 0.067), mostly due to a higher reoperation rate (6% vs. 3%, p = 0.034). Median overall survival was worse with simultaneous resection (40 months, 95%CI 35-46 vs. 78 months, 95%CI 59-86). Risks factors for worse survival were comorbidities, rurality, right-sided primary and simultaneous resection. There is selection bias that favours survival in the staged group, as patients must have survived the first operation and have stable disease in order to undergo the second operation. Conclusions: Simultaneous resection is associated with worse postoperative outcomes. Considering selection bias, randomized studies would be necessary to determine the role of simultaneous.

Aspirin as adjuvant treatment for colorectal cancer: Rationale and progress of the Add-Aspirin trial.

TPS3624 Background: There is now a body of evidence indicating a potential role for aspirin in colorectal cancer (CRC) prevention. In cardiovascular trials, effects on incidence of cancer metastases and short-term mortality suggest further possible roles in the treatment setting, supported by observational studies of aspirin use after cancer diagnosis. In the prevention setting, aspirin use has been limited by toxicity concerns, particularly of serious bleeding. In the adjuvant setting, benefits associated with reducing recurrence and subsequent treatment may outweigh these risks. The Add-Aspirin trial will investigate this, and will also consider possible mechanisms of action for aspirin effects, including the impact of PIK3CA mutations, where there are currently several theories and conflicting data. Methods: Add-Aspirin (ISRCTN74358648) is an international, phase III, double-blind, randomised, placebo-controlled trial recruiting patients who have undergone surgery and relevant adjuvant treatment for stage II or III CRC, as well as those with completely resected CRC liver metastases. Parallel randomised cohorts will address the question in breast, gastro-oesophageal and prostate cancer. Participants take aspirin 100mg daily for an 8-week run-in, to assess adherence and toxicity, and those suitable to proceed are randomised (1:1:1) to aspirin 100mg, aspirin 300mg or placebo daily for at least 5 years. A number of measures – including blood pressure control and PPI use where relevant - are in place to reduce bleeding risk. The primary outcome is disease-free survival (target hazard ratio = 0.8, n = 2600 in 5 years) with a long term analysis of survival planned across the tumour groups. Translational work includes a sub-study monitoring urinary thromboxane B2 as a marker of platelet activation in a subgroup (n = 500) to investigate mechanisms of action. Add-Aspirin opened in 2015 and recruited 1505 CRC patients during the first 3 years from 137 UK centres. 1282 (85%) proceeded to randomisation. A pre-planned feasibility analysis of run-in data (n = 2253 across all 4 tumour groups) provided reassuring data on safety, tolerability and adherence, and recruitment continues with centres in India and Republic of Ireland recently joining. Clinical trial information: 74358648.

Simultaneous versus staged resection for synchronous colorectal cancer liver metastases: A population-based cohort study.

665 Background: While considered safe, simultaneous resection of colorectal cancer primary and liver metastases is not performed routinely. We aimed to identify practice patterns, short and long-term outcomes of simultaneous vs. staged resections for synchronous colorectal cancer liver metastases. Methods: We conducted a population-based cohort study of patients undergoing resection for synchronous colorectal cancer liver metastases from 2006-2015 by linking administrative healthcare datasets in Ontario, Canada. Resection of the primary colorectal cancer and liver metastases within six months was considered synchronous disease. Simultaneous (same hospital admission) and staged resections were compared. Outcomes were 90-day post-operative mortality, total length of hospital stay, overall survival and healthcare costs. Survival for the staged group was measured from the last surgical resection to death and estimated using Kaplan Meier. Cost analysis was undertaken from the perspective of a third-party payer and compared using t test. Results: Of 2,738 patients undergoing colorectal and liver resection for colorectal cancer, 1,168 were synchronous, of which, 442 underwent simultaneous resection. The rate of simultaneous resections increased on average by 3% per year (p = 0.02). Median total length of stay was shorter (8 vs. 11 days); 90-day post-operative mortality was higher for simultaneous resections (3.4% vs 1.2%). Median overall survival was worse with simultaneous resection (40 months, 95%CI 35-46 vs. 78 months, 95%CI 59-86), with a 5-year overall survival of 37% (simultaneous) and 55% (staged). Mean overall costs were lower for simultaneous resections ($12,722 CAD vs. $16,455 CAD. Conclusions: Simultaneous resection compared to staged resection for patients with synchronous colorectal cancer liver metastases is associated with higher 90-day postoperative mortality and worse survival. It was associated with shorter length of hospital stay and lower costs for the health cares system. Considering selection bias, randomized studies would be necessary to determine the role of simultaneous resection for synchronous disease colorectal cancer liver metastases.

The impact of advancing age on incidence of hepatectomy and post-operative outcomes in patients with colorectal cancer liver metastases: a population-based cohort study

BackgroundClinical outcomes for elderly patients undergoing liver resection for colorectal cancer (CRC) liver metastases are poorly characterised. This study aimed to investigate the impact of advancing age on the incidence of liver resection and post-operative outcomes. MethodsPatients in the National Bowel Cancer Audit undergoing major CRC resection from 2010 to 2016 in England were included. Liver resection was identified from linked Hospital Episode Statistics data. A Cox-proportional hazards model was used to compare 3-year mortality. ResultsOf 117,005 patients, 6081 underwent liver resection. For patients <65 years there was 1 liver resection per 12 cases, 65–74, 1 per 17, and ≥75, 1 per 40. 90-day mortality after liver resection increased with advancing age (<65 0.9% (26/2829), 65–74 2.8% (57/2070), ≥75 4.0% (47/1182); P < 0.001). Age was an independent risk factor for 3-year mortality. Patients 65–74 did not have adjusted mortality higher than those <65, yet age ≥75 was associated with increased overall mortality (Hazard ratio (HR) 1.47 (95% CI 1.30–1.68)) and cancer-specific mortality (HR 1.30 (95% CI 1.13–1.49)). ConclusionAlthough advancing age was associated with higher rates of 90-day mortality following liver resection, 3-year mortality for patients 65–74 years was comparable to younger patients. These results will aid clinicians and patients in pre-operative decision-making.

Molecular signatures reflecting microenvironmental metabolism and chemotherapy-induced immunogenic cell death in colorectal liver metastases.

BackgroundMetastatic colorectal cancer (CRC) is associated with highly variable clinical outcome and response to therapy. The recently identified consensus molecular subtypes (CMS1-4) have prognostic and therapeutic implications in primary CRC, but whether these subtypes are valid for metastatic disease is unclear. We performed multi-level analyses of resectable CRC liver metastases (CLM) to identify molecular characteristics of metastatic disease and evaluate the clinical relevance.MethodsIn this ancillary study to the Oslo-CoMet trial, CLM and tumor-adjacent liver tissue from 46 patients were analyzed by profiling mutations (targeted sequencing), genome-wide copy number alteration (CNAs), and gene expression.ResultsSomatic mutations and CNAs detected in CLM were similar to reported primary CRC profiles, while CNA profiles of eight metastatic pairs suggested intra-patient divergence. A CMS classifier tool applied to gene expression data, revealed the cohort to be highly enriched for CMS2. Hierarchical clustering of genes with highly variable expression identified two subgroups separated by high or low expression of 55 genes with immune-related and metabolic functions. Importantly, induction of genes and pathways associated with immunogenic cell death (ICD) was identified in metastases exposed to neoadjuvant chemotherapy (NACT).ConclusionsThe uniform classification of CLM by CMS subtyping may indicate that novel class discovery approaches need to be explored to uncover clinically useful stratification of CLM. Detected gene expression signatures support the role of metabolism and chemotherapy in shaping the immune microenvironment of CLM. Furthermore, the results point to rational exploration of immune modulating strategies in CLM, particularly by exploiting NACT-induced ICD.

Hepatic Resection After Prehepatectomy Chemotherapy for Metastatic Colorectal Cancer: A Propensity-Matched Analysis.

Liver metastases from colorectal cancer (CRC) are best managed using multiple modalities, but the role of chemotherapy prior to resection of marginally resectable liver metastases remains unsettled. Consecutive patients treated for marginally resectable CRC liver metastases were matched using a propensity-score analysis based on the probability of a patient having up-front surgery or prehepatectomy chemotherapy followed by surgery. The study group consisted of 70 propensity-matched patients undergoing up-front surgery or prehepatectomy chemotherapy followed by surgery. Groups were similar in terms of baseline characteristics. Median estimated blood loss (605 ml vs. 957 ml, p=0.006), number of patients requiring transfusion (5 vs. 14, p=0.016) and median postoperative hospital stay (13 vs. 17 days, p=0.005) were significantly less in the prehepatectomy chemotherapy group. Hepatic resection after prehepatectomy chemotherapy for patients with marginally resectable CRC liver metastases can lead to favorable short-term outcomes.

Prognostic factors after R0 resection of colorectal cancer liver metastases: A systematic review and pooled-analysis.

Prognostic variables associated with outcome after curative (R0) Resection of Colorectal Cancer (CRC) liver metastases are paramount in identifying high-risk patients after surgery. The aim of this study was to identify risk factors related to Overall Survival (OS) after R0 resection of CRC liver metastases. A literature search on prognostic factors after resection of liver metastases was performed. Studies were eligible if covariates associated with OS were reported in patients with R0 resected CRC liver metastases. Independent prognostic factors associated with OS were identified using multivariate analysis. Twenty-four publications with a total of 4855 patients were eligible. In multivariate analyses, a disease-free interval < 12 months (hazard ratio [HR] 1.47, P = 0.0002), the size of the largest metastasis (HR 1.56, P < 0.0001), the total number of metastases (HR 1.73, P < 0.00001), a primary tumor with node-positive status (HR 1.56, P = 0.002), a rectal primary tumor (HR 1.48, P < 0.00001), a high carcinoembryonic antigen level (HR 1.49, P = 0.02), a high tumor grade (HR 2.42, P < 0.00001), and extrahepatic disease (HR 2.03, P < 0.00001) were associated with an increased risk of death after R0 resection of CRC liver metastases in at least 3 studies. We identified 9 clinicopathological prognostic factors that could help identify high-risk patients and guide further treatment and follow up decisions. In particular burden of liver and extrahepatic metastases and grade are those associated with a higher risk of death.

Inflammation and uPAR-Expression in Colorectal Liver Metastases in Relation to Growth Pattern and Neo-adjuvant Therapy.

Proteolytic activity and inflammation in the tumour microenvironment affects cancer progression. In colorectal cancer (CRC) liver metastases it has been observed that three different immune profiles are present, as well as proteolytic activity, determined by the expression of urokinase-type plasminogen activator (uPAR).The main objectives of this study were to investigate uPAR expression and the density of macrophages (CD68) and T cells (CD3) as markers of inflammation in resected CRC liver metastases, where patients were neo-adjuvantly treated with chemotherapy with or without the angiogenesis inhibitor bevacizumab. Chemonaive patients served as a control group. The markers were correlated to growth patterns (GP) of liver metastases, i.e. desmoplastic, pushing and replacement GP. It was hypothesised that differences in proteolysis and inflammation could reflect tumour specific growth and therapy related changes in the tumour microenvironment. In chemonaive patients, a significantly higher level of uPAR was observed in desmoplastic liver metastases in comparison to pushing GP (p = 0.01) or replacement GP (p = 0.03). A significantly higher density of CD68 was observed in liver metastases with replacement GP in comparison to those with pushing GP (p = 0.01). In liver metastases from chemo treated patients, CD68 density was significantly higher in desmoplastic GP in comparison to pushing GP (p = 0.03). In chemo and bevacizumab treated patients only a significant lower CD3 expression was observed in liver metastases with a mixed GP than in those with desmoplastic (p = 0.01) or pushing GP (p = 0.05). Expression of uPAR and the density of macrophages at the tumour margin of liver metastasis differ between GP in the untreated patients. A higher density of T cells was observed in the bevacizumab treated patients, when desmoplastic and pushing metastases were compared to liver metastases with a mix of the GP respectively, however no specific correlations between the immune markers of macrophages and T cells or GP of liver metastases could be demonstrated.

Artificial neural networks – A method for prediction of survival following liver resection for colorectal cancer metastases

To construct an artificial neural network (ANN) model to predict survival after liver resection for colorectal cancer (CRC) metastases. CRC liver metastases are fatal if untreated and resection can possibly be curative. Predictive models stratify patients into riskcategories to predict prognosis and select those who can benefit from aggressive multidisciplinary treatment and intensive follow-up. Standard linear models assume proportional hazards, whereas more flexible non-linear survival models based on ANNs may better predict individual long-term survival. Clinicopathological and perioperative data on patients who underwent liver resection for CRC metastases between 1994 and 2009 were studied retrospectively. A five-fold cross-validated ANN model was constructed. Risk variables were ranked and minimised through calibrated ANNs. Time dependent hazard ratio (HR) was calculated using the ANN. Performance of the ANN model and Cox regression were analysed using Harrell's C-index. 241 patients with a median age of 66 years were included. There were no perioperative deaths and median survival was 56 months. Of 28 potential risk variables, the ANN selected six: age, preoperative chemotherapy, size of largest metastasis, haemorrhagic complications, preoperative CEA-level and number of metastases. The C-index was 0.72 for the ANN model and 0.66 for Cox regression. For the first time ANNs were used to successfully predict individual long-term survival for patients following liver resection for CRC metastases. In the future, more complex prognostic factors can be incorporated into the ANN model to increase its predictive ability.

Increased gene copy number and amplification of FGF2 and FGFR1 in metastatic colorectal cancer.

402 Background: Fibroblast growth factors (FGFs) and their receptors (FGFRs) play essential roles in tightly regulating cell proliferation, survival, migration, and angiogenesis in cancers. However, gene copy number and amplification of FGF2 and FGFR1 have not been extensively evaluated in patients with metastatic colorectal cancer (CRC). Methods: Two tissue microarrays (TMA) were constructed with resected CRC liver metastases from 120 patients. The TMAs included duplicated intratumoral regions and the invasive margin between tumor and normal hepatic parenchyma. Patients were either untreated, or previously treated with FOLFIRI or FOLFOX +/- bevacizumab. The TMA slides were subjected to a two-color FISH assay using a mixture of FGF2 and FGFR1 in-house developed probes. Results: Results were obtained from 118 patients. The analysis detected an average of 1.90 copies of FGF2 signal per cell (range, 1.10-3.46 copies) and an average of 2.27 copies of FGFR1 signal per cell (range, 1-12-7.14 copies). Three control specimens from each slide were also scored, with an average of 1.74 copies of FGF2 and 1.73 copies of FGFR1. High copy number per cell (mean &gt; 2.5 copies) was detected in 9.3% of specimens for FGF2 and 27.9% for FGFR1, including 2 patients (1.7%) for FGF2 and 5 (4.2%) for FGFR1 with focal amplification, defined by ≥ 10% cells with &gt; 4 copies. Additionally, duplications of gene signals in the same locus were detected in 10 samples (8.5%) for FGF2 and 19 (16.1%) for FGFR1. Intratumoral heterogeneity was rare (detected in 3 patients). There was no statistically significant correlation between FGF2 or FGFR1 gene copy number and prior treatment, pathologic response, relapse free survival, or overall survival, though there was a trend towards higher FGFR1 gene copy number in patients previously receiving bevacizumab (p=0.07). Conclusions: Both FGF2 and FGFR1 display variable copy number among resected CRC liver metastases, with larger variability detected for FGFR1. Gene amplification was rare but detected in several patients for both FGF2 and FGFR1. Follow up studies will investigate higher FGFR1 gene copy number in patients previously treated with bevacizumab, perhaps reflecting a potential escape or resistance mechanism.

Preoperative Chemotherapy and the Risk of Hepatotoxicity and Morbidity after Liver Resection for Metastatic Colorectal Cancer: A Single Institution Experience

Patients undergoing liver resection for colorectal cancer liver metastasis (CRCLM) are often treated with chemotherapy before surgery. However, the associations between chemotherapy, liver injury, perioperative outcomes, and other confounding factors remain unclear. This study investigates the effect of preoperative chemotherapy for CRCLM on nontumoral liver histology and perioperative outcomes in a contemporary cohort. Five hundred six patients underwent hepatic resection for CRCLM between April 2003 and March 2007. Histologic evaluation of nontumoral liver parenchyma for sinusoidal dilatation, steatosis, and steatohepatitis was performed in 384 cases for which tissue was available. Patient factors, tumor characteristics, chemotherapy regimens, histology of nontumoral liver, and perioperative morbidity were analyzed. Two hundred fifty patients (65%) received preoperative chemotherapy for a median duration of 24 weeks. Irinotecan, increased body mass index (BMI), and diabetes mellitus (DM) were associated with hepatic steatosis and steatohepatitis. Sinusoidal dilatation was not associated with chemotherapy or any clinicopathologic factors. Perioperative blood transfusion was independently associated with an increased risk of any complication. Major postoperative complications were independently associated with major (≥ 3 segments) resections (57%) and perioperative blood transfusion. The use of any preoperative chemotherapy decreased the odds of major complications. Liver-related complications were independently associated with major resection and blood transfusion, but not with chemotherapy. Three postoperative deaths (0.8%) occurred, all in patients who were not treated with chemotherapy and had no evidence of liver injury. With appropriate patient selection, liver resection for CRCLM can be safely performed in patients treated with preoperative chemotherapy.

Up-front Hepatic Resection for Metastatic Colorectal Cancer Results in Favorable Long-term Survival

Hepatic metastasis from colorectal cancer (CRC) is best managed with a multimodal approach; however, the optimal timing of liver resection in relation to administration of perioperative chemotherapy remains unclear. Our strategy has been to offer up-front liver resection for patients with resectable hepatic metastases, followed by post-liver resection chemotherapy. We report the outcomes of patients based on this surgical approach. A retrospective review of all patients undergoing liver resection for CRC metastases over a 5-year period (2002-2007) was performed. Associations between clinicopathologic factors and survival were evaluated by the Cox proportional hazard method. A total of 320 patients underwent 336 liver resections. Median follow-up was 40 (range 8-80) months. The majority (n=195, 60.9%) had metachronous disease, and most patients (n=286, 85%) had a major hepatectomy (>3 segments). Thirty-six patients (11%) received preoperative chemotherapy, predominantly for downstaging unresectable disease. Ninety-day mortality was 2.1%, and perioperative morbidity occurred in 68 patients (20.2%). Actual disease-free survival at 3 and 5 years was 46.2% and 42%, respectively. Actual overall survival (OS) at 3 and 5 years was 63.7% and 55%, respectively. Multivariate analysis identified four factors that were independently associated with differences in OS (hazard ratio; 95% confidence interval): size of metastasis>6 cm (2.2; 1.3-3.5), positive lymph node status of the primary CRC (N1 (2.0; 1.0-3.8), N2 (2.4; 1.2-4.9)), synchronous disease (2.1; 1.3-3.5), and treatment with chemotherapy after liver resection (0.42; 0.23-0.75). Up-front surgery for patients with resectable CRC liver metastases, followed by chemotherapy, can lead to favorable OS.

Combined portal vein embolization and preoperative chemotherapy prior to liver resection for colorectal cancer metastases

Objective. Compare perioperative course and long-term mortality after liver resection for colorectal cancer (CRC) metastases between patients who had preoperative treatment with portal vein embolization (PVE) and chemotherapy or chemotherapy alone. Methods.Among patients undergoing liver resection for CRC metastases following preoperative chemotherapy treatment, 17 patients who had received preoperative PVE (group A) were compared with 17 matched controls who had no PVE (group B). Perioperative course and long-term mortality were compared between groups A and B and between group A and the entire group of 75 cases with preoperative chemotherapy (group C). Results. Baseline characteristics for the matched groups A and B were similar. Group C included less major resections. Median intraoperative bleeding was 1600 ml in group A, 1200 ml in group B, and 1000 ml in group C (p < 0.05 vs. group A). Median postoperative stay was comparable in all groups (8–9 days). Operation time was 542 min in group A and 464 min in group B (p < 0.01). Mortality after 30 days and 1, 2, and 5 years was similar in all groups. Conclusion.Perioperative outcome and long-term survival did not differ when comparing liver resection for CRC liver metastases preceded by PVE and chemotherapy or chemotherapy alone, except for the operation time. The study supports the safety of this “aggressive” combination approach in patients in need of tumor “downstaging” by chemotherapy and PVE to increase the remnant liver volume.

The PROs and cons of liver resection in colorectal cancer

Approximately 40% of patients with colorectal cancer (CRC) develop liver metastases at some point during the course of the disease. A third of these patients can undergo hepatic resection, and half of these patients will achieve a 5-year overall survival but, what is the impact on quality of life of this kind of surgery? Jane Blazeby and colleagues have assessed the quality of life of 232 patients who underwent resection for CRC metastases by using generic and a disease specific patient-reported outcome measures (PROs); these data were obtained from the patients through questionnaires that assessed several aspects of health including physical, emotional and social functions. “The most significant findings were that liver resection for CRC has a relatively small and short-lived detrimental impact on most aspects of quality of life,” explains Blazeby. Because liver resection confers a chance of long-term survival, understanding the impact of surgery on PROs is critical as it provides information that can be used by surgeons when discussing the outcomes of this treatment with patients. However, the study also showed that despite the early recovery, some problems (abdominal pain and sexual disfunction) persisted 12 months after surgery. Blazeby explains how these problems highlight “the importance of using generic and disease-specific PROs as such issues may have passed undetected by standard clinical follow up or using generic PROs alone.”

Liver resection for metastatic colorectal cancer in the presence of extrahepatic disease

Early studies of liver resection for colorectal cancer metastases identified patients with concomitant extrahepatic disease as a group with poor outcomes. These studies concluded that the presence of extrahepatic disease should be a contraindication to resection. This contraindication has more recently been challenged. In this paper, we review the published work on metastatic colorectal cancer, pertaining to the role of surgery in patients with liver metastases and concomitant extrahepatic disease. 5-year survival after resection is worse in patients with extrahepatic disease than in patients with liver-only disease, but is similar to that seen in patients who underwent resection in the era before the use of modern chemotherapy. Recurrence occurs in most patients. There is a role for surgery in highly selected patients with single sites of extrahepatic disease, although expectations should be different than those of patients with liver-only metastases. Further studies are necessary to define the patient group best suited for resection of hepatic metastases with extrahepatic disease.

Safety of bevacizumab when given perioperatively for colorectal cancer with liver metastases: McGill University pilot study

e15083 Background: Bevacizumab (BV) increases responses and survival rates when used with chemotherapy in metastatic colorectal cancer (CRC). Current practice is to give peri-operative chemotherapy for resectable CRC liver metasases (LM). The safety and efficacy of chemo-BV in this setting is unknown. Post-operative complications have been reported in patients (pts) who underwent surgery while receiving BV. The goals were to determine safety of perioperative BV. Methods: In a prospective pilot study, patients with resectable LM from October 2005 to 2008 that received BV perioperatively along with chemotherapy. Of a total of 60 pts, 34 had oxaliplatin-based CTX, 22 CPT-11 (FOLFIRI) and 4 IROX. All but seven pts received BV pre and postoperatively. The average age was 55 years. All patients underwent liver surgery 6–8weeks post last dose of BV. Univariate Cox regression models were used to evaluate the association of patient and tumour characteristics, therapy and postoperative complications. Results: Postoperative complications developed in a total of 24 pts (40%). 12 pts (35%) who received Oxaliplatin CTX + BV, 9 pts (40%) with CPT 11 CTX + BV and 3 pts (75%) with Oxaliplatin + CPT-11 CTX +BV. The average time from BV discontinuation to surgery was 49 days. No significant associations were identified between BV and CTX regimen or timing and postoperative complications. Wound healing complication were most frequent with 8 pts (13%), DVT diagnosed in 6 pts (10%), protracted pancytopenia 4 pts (7%), sepsis 1pt, infections 2pts, MI 1pt, acute cardiomyopathy 1pt, and billiary leak 1pt. No bowel perforations or sudden deaths were reported. These side effects apart from thromboembolic events are comparable to previously reported post-operative complications. Conclusions: Neither the use of BV with CTX nor timing of BV administration were associated with a non acceptable increase in complication rates as compared to previously published by EORTC intergroup. Our data confirm that the combination of BV with neoadjuvant chemotherapy is feasible and safe in patients CRC LM. A higher incidence of thromboembolic events was seen. To determine the optimal timing and drug combination prospective randomized trials are urgently required. [Table: see text]

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

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. 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. 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%). 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.