Hepatectomy For Colorectal Liver Metastases Research Articles

The long term impact of peri-operative red blood cell transfusions in patients undergoing hepatectomy for colorectal liver metastases (CRLM)

The long term impact of peri-operative red blood cell transfusions in patients undergoing hepatectomy for colorectal liver metastases (CRLM)

Sinusoidal obstruction syndrome (SOS): A light and electron microscopy study in human liver

AimsOxaliplatin is an important chemotherapeutic agent, used in the treatment of hepatic colorectal metastases, and known to induce the sinusoidal obstruction syndrome (SOS). Pathophysiological knowledge concerning SOS is based on a rat model. Therefore, the aim was to perform a comprehensive study of the features of human SOS, using both light microscopy (LM) and electron microscopy (EM). Methods and resultsIncluded were all patients of whom wedge liver biopsies were collected during a partial hepatectomy for colorectal liver metastases, in a 4-year period. The wedge biopsy were perfusion fixated and processed for LM and EM. The SOS lesions were selected by LM and details were studied using EM. Material was available of 30 patients, of whom 28 patients received neo-adjuvant oxaliplatin. Eighteen (64%) of the 28 patients showed SOS lesions, based on microscopy. The lesions consisted of sinusoidal endothelial cell detachment from the space of Disse on EM. In the enlarged space of Disse a variable amount of erythrocytes were located. ConclusionSinusoidal endothelial cell detachment was present in human SOS, accompanied by enlargement of the space of Disse and erythrocytes in this area. These findings, originally described in a rat model, were now for the first time confirmed in human livers under clinically relevant settings.

Neo-adjuvant chemotherapy followed by surgery versus surgery alone in high-risk patients with resectable colorectal liver metastases: The CHARISMA randomized multicenter clinical trial.

TPS790 Background: Colorectal carcinoma is a leading cause of cancer death worldwide, mostly as a consequence of metastatic disease. If metastases are confined to the liver, surgical resection is the only therapy providing potential for cure. Efforts to improve the outcome of hepatectomy for colorectal liver metastases (CRLM) by combining surgery with chemotherapy have failed to demonstrate overall survival (OS) benefit. This may partly be explained by the fact that previous trials on this subject involved strict inclusion criteria. Consequently, patients with a high oncological risk profile - who might benefit the most from chemotherapy – might have been underrepresented in previous trials. Several Clinical Risk Scores (CRS) have been developed predicting patients’ prognosis after resection of CRLM. The most widely used and validated CRS was described by Fong et al., which characterizes 2 risk groups (high versus low) based on 5 independent clinicopathologic prognostic variables. Each variable is assigned 1 point. Multiple retrospective observations showed that neo-/adjuvant chemotherapy induced significant OS benefit in patients with a high-risk profile (CRS of 3 to 5 points). The CHARISMA trial evaluates the impact of neo-adjuvant chemotherapy in patients with high-risk, primarily resectable liver-only colorectal metastases. We hypothesize that adding neo-adjuvant chemotherapy to surgery improves OS in this high-risk patient group. Methods: The CHARISMA trial is a randomized (1:1) phase III trial. Patients receive either surgery only for CRLM (arm A) or 6 cycles of neo-adjuvant Oxaliplatin + Capecitabine, followed by surgery (arm B). The primary endpoint is OS. On basis of retrospective data, the expected hazard ratio for arm B is 0.60. With an expected 5-year OS of 25% in arm A, a two-sided significance level α = 0.05 and power 1 - β = 0.8, 224 patients have to be recruited. Major eligibility criteria are: liver-only metastases, primarily resectable CRLM, high-risk patients (CRS 3-5). The trial is currently accruing in 10 Dutch liver centers and is registered in the “Dutch Trial Register”: NTR4893 ( www.trialregister.nl ). Clinical trial information: NTR4893.

Aggressive surgery for advanced colorectal liver metastases in the era of multidisciplinary approaches.

299 Background: The number of colorectal liver metastases (CLM) is accepted as a strong predictor of survival after surgery. However, recent advances in multidisciplinary approaches have dramatically changed surgical outcomes of CLM. Clinical implications of aggressive surgery for advanced CLM need to be reviewed in relation to the trend in treatment strategies. Methods: We reviewed 581 patients who underwent curative hepatectomy for CLM from 1999 to 2012. One hundred and eighty-nine patients underwent surgery for advanced CLM (n ≥ 4) and were classified according to year of surgery (first: 1999–2003 [n = 30]; second: 2004–2008 [n = 82]; and third: 2009–2012 [n= 77]). The frequency of perioperative chemotherapy for CLM, preoperative gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI), and contrast-enhanced intraoperative ultrasonography (CE-IOUS), and long-term outcomes were compared among the three periods. Results: The frequency of perioperative chemotherapy, EOB-MRI, and CE-IOUS increased with time (P <.001). The 3-/5-year overall survival in the third period (58.7/51.8%) was similar to that in the second period (59.8/43.9%, P =.828) and that of 72 patients who had 1–3 CLM in the first period (70.8/51.0%, P =.991). Advanced CLM was an independent factor in the first (P =.001, hazard ratio: 2.91) and second (P=.040, hazard ratio: 1.56) periods. However, multivariate analysis revealed that advanced CLM was not a predictive factor of overall survival in the third period. Conclusions: The prognostic impact of advanced CLM diminished owing to evolution in multidisciplinary treatment. Aggressive surgery for advanced CLM offers favorable prognosis similar to that of patients with few CLM in the early period.

THU-298 - The Influence of Chemotherapy-Associated Liver Injury on Outcome after Partial Hepatectomy for Colorectal Liver Metastases: A Systematic Review and Individual Patient Data Analysis

THU-298 - The Influence of Chemotherapy-Associated Liver Injury on Outcome after Partial Hepatectomy for Colorectal Liver Metastases: A Systematic Review and Individual Patient Data Analysis

155P Early recurrence after hepatectomy for colorectal liver metastases: the definition and predictive factors

155P Early recurrence after hepatectomy for colorectal liver metastases: the definition and predictive factors

Failure to Achieve a 2-Stage Hepatectomy for Colorectal Liver Metastases: How to Prevent It?

The aim of the study was to identify predictive factors of failure of 2-stage hepatectomy (TSH) for the selection of patients with extensive bilobar colorectal liver metastases (CRLM), who are candidates for TSH. The main weakness of TSH is the risk of failure to complete both the sequential procedures. Between 2000 and 2012, from a total cohort of 845 patients resected for CRLM, 125 patients (14.8%) with extensive CRLM were planned for TSH. All factors related to the failure of TSH were analyzed, and a predictive model was built utilizing the independent predictive factors of failure. Forty-four patients (35.2%) could not proceed to the second stage, and their overall survival (OS) was significantly worse than that of those who completed the TSH (5-year OS: 0% vs 44.2%; P < 0.0001). Multivariate analysis revealed that carcinoembryonic antigen >30 ng/mL [relative risk (RR) 2.73, P = 0.03], tumor size >40 mm (RR 2.89, P = 0.04), chemotherapy cycles >12 (RR 3.46, P = 0.01), and tumor progression during first-line chemotherapy (RR 6.56, P = 0.01) were independent predictive factors of failure. For patients not presenting any factors, the probability of failure was 10.5%, with a 5-year OS rate of 41.9%. The addition of each subsequent factor increased the risk to 43.5%, 72.7%, 88.5%, and 95.5%, and decreased the 5-year OS to 38.8%, 29.2%, 0%, and 0%, respectively, for 1, 2, 3, and 4 factors. TSH should not be recommended in patients with more than 2 risk factors. Avoidance of these factors significantly reduces the risk of failure and is crucial for long-term survival.

The impact of portal pedicle clamping on survival from colorectal liver metastases in the contemporary era of liver resection: a matched cohort study

IntroductionPortal pedicle clamping (PPC) may impact micro‐metastases’ growth. This study examined the association between PPC and survival after a hepatectomy for colorectal liver metastases (CRLM). MethodsA matched cohort study was conducted on hepatectomies for CRLM at a single institution (2003–2012). Cohorts were selected based on PPC use, with 1:1 matching for age, time period and the Clinical Risk Score. Outcomes were overall and recurrence‐free survival (OS and RFS). Cox regression was performed to assess the association between PPC and survival. ResultsOf 481 hepatectomies, 26.9% used PPC. One hundred and ten pairs of patients were matched in the cohorts. There was no significant difference in OS [hazard ratio (HR) 1.18; 95% confidence interval (CI): 0.76–1.83], with a 5‐year OS of 57.8% (95%CI: 52.4–63.2%) with PPC versus 62.3% (95%CI: 57.1–67.5%) without. Five‐year RFS did not differ (HR 0.98; 95%CI: 0.71–1.35) with 29.7% (95%CI: 24.9–34.5%) with PPC versus 28.0% (95%CI: 23.2–32.8%) without. When adjusting for extent of resection, transfusion, operative time and surgeon, there was no difference in OS (HR 0.91; 95%CI: 0.52–1.60) or RFS (HR: 0.86; 95%CI: 0.57–1.30). ConclusionsPPC was not associated with a significant difference in OS or RFS in a hepatectomy for CRLM. PPC remains a safe technique during hepatectomy.

Abstract 2277: Prognostic impact of enhancer of zeste homologue 2 (EZH2) in patients underwent hepatectomy for colorectal liver metastases who received preoperative oxaliplatin-based chemotherapy

Abstract Purpose: Colorectal cancer (CRC) is the second most commonly diagnosed cancer and the third leading cause of cancer mortality in Japan. Almost 15% and 10% of patients with CRC are diagnosed with synchronous and metachronous liver metastasis, respectively. In the last decade, the therapeutic strategies including chemotherapy and molecular targeted therapy have improved. However, the prognosis of patients with CRC remains poor because of their acquirement of chemoresistance. Previous studies have shown that enhancer of zeste homologue 2 (EZH2) is associated with proliferation of various cancers. EZH2 is the catalytic subunit of Polycomb repressive complex2 (PRC2) which catalyzes the methylation of lysine 27 on histone H3 (H3K27), leading to repress the transcription of tumor-suppressor genes. In addition, high EZH2 expression is associated with the resistance to cisplatin in non-small cell lung carcinoma. However, the association between the resistance to oxaliplatin and the expression of EZH2 is unrevealed. The aim of this study is to investigate the correlation between the expression of EZH2 and response to oxaliplatin-based chemotherapy as well as survival of patients with colorectal liver metastasis (CRLM). Experimental Design: Sixty-one patients who underwent first-line oxaliplatin-based chemotherapy before resection of CRLM were enrolled in this study. Immunohistochemistry of EZH2 was performed, and then the correlation between response to chemotherapy and survival was evaluated. Results: Immunohistochemistry revealed 38 patients (62.3%) with high EZH2 expression, and 23 patients (37.7%) with low EZH2 expression. Of the 38 patients with EZH2 high expression, 15 patients (39.5%) responded to oxaliplatin-based chemotherapy with either complete response or partial response. Of the 23 patients with low EZH2 expression, 14 patients (60.9%) exhibited a response to chemotherapy. There was significant difference in response to oxaliplatin-based chemotherapy between high and low EZH2 expression patients (p = 0.04). Univariate survival analysis indicated that patients with high EZH2 expression had a lower overall survival than those with low EZH2 expression. Moreover, multivariate Cox regression analysis revealed that high EZH2 expression was an independent prognostic factor for overall survival. Kaplan-Meier survival curves also confirmed that high EZH2 expression correlates with poor prognosis in patients who underwent hepatectomy for CRLM. Conclusions: Our results indicated that prognosis of patients with high EZH2 expression who received preoperative oxaliplatin-based chemotherapy and underwent hepatectomy for CRLM was worse than those with low EZH2 expression. EZH2 may be a predictive factor for oxaliplatin-based chemotherapy response and overall survival in patients with CRLM. Citation Format: Mayuko Ohuchi, Yasuo Sakamoto, Ryuma Tokunaga, Kenichi Nakamura, Yuki Kiyozumi, Daisuke Izumi, Keisuke Kosumi, Kazuto Harada, Junji Kurashige, Yukiharu Hiyoshi, Shiro Iwagami, Yoshifumi Baba, Yuji Miyamoto, Naoya Yoshida, Hideo Baba. Prognostic impact of enhancer of zeste homologue 2 (EZH2) in patients underwent hepatectomy for colorectal liver metastases who received preoperative oxaliplatin-based chemotherapy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2277. doi:10.1158/1538-7445.AM2015-2277

2015 Canadian Surgery Forum Abstracts.

The Canadian Surgery Forum Steering Committee acknowledges and thanks the following organizations for their support of the 2015 Forum: # 02 The usefulness and costs of routine contrast studies after laparoscopic sleeve gastrectomy for detecting staple line leaks {#article-title-2} Although

Intra-operative high intensity focused ultrasound in patients with colorectal liver metastases: results of a phase I-II study in 21 patients

Managing colorectal liver metastases (CLM) is a major clinical challenge, and surgery remains the only potentially curative treatment. Five-year survival rates of up to 51% have been recently reported. However, only 10-20% of patients are eligible for surgery, which is often precluded by the number, size and/or location of metastases, or because the necessary resection will leave insufficient volume of functional liver. A toroidal transducer for HIFU ablation has been developed and tested in vivo enabling destruction of large liver volumes. Preliminary in vitro and preclinical work demonstrated the potential, feasibility and safety of such HIFU ablations. These preclinical studies are now translated into clinical practice through controlled trials, and the aim of this study was to assess the feasibility and safety of HIFU ablation in patients undergoing hepatectomy for CLM, as well to collect preliminary efficacy and accuracy data.

PWE-154 The use of glasgow predictive scoring (gps) in determining patient survival following oesophageal and gastric resection for malignant disease

Introduction Oesophageal and gastric cancer resections carry a high risk of morbidity and mortality.1It is important that patients undergoing such surgery survive long enough to reap the benefits of resection. Pre-operative CRP and Albumin levels are simple markers that can be combined to form a Glasgow prognostic score (GPS), which has demonstrable prognostic value in colorectal cancers.2,3 The aim of this is study is to assess whether GPS can predict patient survival following oesophageal and gastric resections for malignant disease. Method NHS Highland holds a prospective database of all patients undergoing oesophageal and gastric resections for malignant disease. This database was reviewed for patients operated on between January 2005–June 2014. Data on pre-operative CRP and Albumin levels were collected retrospectively from the trust–s SCISTORE®results system, to calculate a GPS score: GPS-0: CRP GPS-1: CRP > 10 mg/L, Albumin > 35 g/L GPS-2: CRP > 10 mg/L; Albumin TNM staging of the pathology specimen was also recorded to derive a pathology score: TxNyMx: Pathology score = x + y + z Data on GPS, survival and pathology scores were analysed in SPSS®version 21 using one-way ANOVA tests. Results The database contained 179 patients. Of these 110 (61.5%) had both pre-operative CRP and Albumin levels documented to derive a GPS score. 61 patients had a GPS score of 0, 34 a score of 1 and 15 a score of 2. The median survival post-resection was 31, 24.5 and 6 months respectively. One-way ANOVA demonstrated a significant difference in survival between groups (p-value of 0.049). GPS scores were also compared to pathology scores. The mean pathology score was 2.88, 3.04 and 4.11 for the respective GPS groups of 0–2, with ANOVA tests again demonstrating a significant difference (p-value of 0.017). Conclusion GPS is a useful marker for patients about to embark of oesophageal and gastric resectional surgery for malignant disease. Patients with a GPS score of 2 appear to be poor surgical candidates, with more advanced tumours and survivals too short to derive benefit from surgical resection. The use of GPS scoring could be a helpful tool in MDT decision making. Disclosure of interest None Declared. References D. Amico T. Outcomes after surgery for oesophageal cancer. Gastrointest. Cancer Res. 2007 September-October;1(5):188-196 McMillan DC, Crozier JE, Canna K, et al. Evaluation of an inflammation-based prognostic score (GPS) in patients undergoing resection for colon and rectal cancer. Int J Colorectal Dis. 2007;22:881–6 Nakagawa K, Tanaka K, Kazunori N, et al. The modified glasgow prognostic score as a predictor of survival after hepatectomy for colorectal liver metastases. Ann Surg Oncol. 2014;21:1711–1718

PTH-117 What are the long- and short-term effects of polymorbidity following resection for colorectal liver metastases?

Introduction Increasingly older patients with co-existing co-morbidities are undergoing hepatectomies for colorectal liver metastases (CRLM). The primary objective was to ascertain the relationship between comorbidities and outcome (overall survival [OS] and disease free survival [DFS]) for patients undergoing hepatectomies. Secondary objectives included evaluating the effect of comorbidities on complications and length of stay (LOS). Method Data from a prospectively maintained database was collected for patients undergoing a liver resection for CRLM between 1 January 2005 and 31 December 2012. Patient and tumour demographics, comorbidity status, pathology and outcomes were collected. Charlson comorbidity index (CCI), ASA grade and index disease (ID) systems were used to quantify comorbidities, which were analysed against the primary and secondary outcome measures. Results The study included 866 patients, with a mean age of 66 years [range 23–91]. Of the sample population, 65.8% were male. There was a non-significant trend towards poorer survival with increased comorbidity, using the ASA grading system (ASA OS p = 0.07, ASA DFS p = 0.13). CCI showed a significant association with DFS (p = 0.039) but none with OS (p = 0.54). However ID did not show any association with either OS or DFS (ID OS p = 0.53 and ID DFS p = 0.93). Higher ASA grades and ID scores were more likely to be associated with major complications (Clavien-Dindo ≥3) using χ 2 (p = 0.02 for both ASA and ID). Patients with higher ID scores were more likely to have a prolonged LOS (p Conclusion Comorbidities appear to be associated with poorer survival outcomes. ASA grade and ID scores determine post-operative risk more optimally than CCI. There is an association between increased comorbidities, complication rates and LOS. Disclosure of interest None Declared.

The Impact of Perioperative Red Blood Cell Transfusions on Long-Term Outcomes after Hepatectomy for Colorectal Liver Metastases.

Red blood cell transfusions (RBCTs) are associated with cancer recurrence following resection of colorectal cancer. Their impact after colorectal liver metastases (CRLM) resection remains debated. We sought to explore the association between perioperative RBCT and oncologic outcomes following resection of CRLM. We reviewed patients undergoing partial hepatectomy for CRLM from 2003 to 2012 at a single institution. Date of death was abstracted from a validated population-based cancer registry. Primary outcome was overall survival (OS). Secondary outcome was recurrence-free survival (RFS). Survivals were estimated using Kaplan-Meier methods and compared with log-rank test based on transfusion status. Cox regression analysis examined the association of RBCT with OS and RFS, while adjusting for age, preoperative chemotherapy, Clinical Risk Score, and period of treatment (2003-2007 vs. 2008-2012). Among 483 patients, 27.5 % received RBCT. Ninety-day postoperative mortality was 4.8 %. At median follow-up of 33 (interquartile range 20.1-54.8) months, 5-year OS was inferior in transfused patients (45.9 vs. 61.0 %; p < 0.0001). Five-year RFS was decreased with RBCT (15.5 vs. 31.6 %; p < 0.0001). The difference persisted when considering only 90-day survivors for 5-year OS (53.1 vs. 61.9 %, p = 0.023) and RFS (15.6 vs. 31.6 %; p < 0.0001). After adjustment for prognostic factors, RBCT was independently associated with decreased OS (hazard ratio 2.24; 95 % confidence interval 1.60-3.15) and RFS (hazard ratio 1.71; 95 % confidence interval 1.28-2.28). Perioperative RBCT is independently associated with decreased OS and RFS following hepatectomy for CRLM. Interventions to minimize and rationalize the use of RBCT for hepatectomy are warranted to mitigate this detrimental effect on long-term outcomes.

Impact of overweight on postoperative complications and oncological outcome after radical hepatectomy for metastatic colorectal cancer

To evaluate the correlation between overweight and postoperative complications and prognosis after radical hepatectomy for colorectal liver metastasis (CRLM). A total of 192 patients who underwent hepatectomy for colorectal liver metastases between January 2000 and March 2012 were eligible for the study. We retrospectively summarized their clinicopathological data, BMI index and postoperative complications, and investigated the relation between these data and complications and prognosis. Of the 192 patients, 109 cases were classified as overweight with a BMI ≥24 and 83 patients were classified as non-overweight with a BMI <24. Seventy-five complications occurred in 68 of the 192 patients (35.4%) who underwent hepatectomy. Surgical complications (P=0.428), operation time (P=0.837), and blood loss (P=0.272) were not statistically significantly associated with BMI. 173 patients were included to analyze the influence of overweight on oncologic outcome. The median survival for the overweight patients was 59 months, while that of non-overweight patients was 31 months (P=0.016). The overweight patients had a longer OS assessed by both univariate analysis (P=0.016) and multivariate analysis (P=0.031). However, no statistical differences in disease-free survival (DFS) were detected between the overweight and non-overweight groups (P=0.058). Overweight is not independently associated with an increasing complication rate. BMI does not significantly affect the CRLM-DFS, and high BMI patients might have a better overall survival.

Prognostic value of poorly differentiated clusters in the primary tumor in patients undergoing hepatectomy for colorectal liver metastasis

This study aimed to determine the prognostic value of a novel grading system based on the histologic assessment of poorly differentiated clusters (PDCs) in the primary lesions in patients with hepatectomy for colorectal liver metastasis (CRLM). Preoperative survival predictors for CRLM are required to determine candidates for perioperative chemotherapy who would otherwise have a poor prognosis. In total, 411 consecutive patients undergoing curative resection of primary colorectal cancers and metastatic liver lesions at 2 institutions were enrolled. Cancer clusters comprising ≥ 5 cancer cells, lacking a gland-like structure, were defined as PDCs and quantifiably graded. According to PDCs, 65, 127, and 219 patients were classified as being grades (G)1, G2, and G3, respectively. PDCs were associated with T and N stages and tumor budding in primary tumor, extrahepatic disease, and serum CEA levels (P ≤ .0001-.045), but not with the number and size of liver metastasis. PDC grade significantly influenced recurrence rate in extrahepatic sites, including the lung and peritoneum (P < .0001). The 2-year disease-free survival after hepatectomy was 64.6%, 38.8%, and 22.4% in G1, G2, and G3, respectively. Based on multivariate analysis, PDC grade was selected as an independent prognostic factor together with other conventional factors such as extrahepatic disease and the number of liver metastasis. PDC grade in primary lesions is a novel potent prognostic indicator in CRLM independent of the anatomic extent of disease. Notably, PDC grade can bias survival rates in clinical studies targeting perioperative chemotherapy in CRLM.

In brief

Resection margin status has traditionally been associated with tumor recurrence and oncological outcome following liver resection for colorectal liver metastases. Previous studies, however, did not address the impact of resection margin on the site of tumor recurrence and did not differentiate between true local recurrence at the resection margin and recurrence elsewhere in the liver. This study aimed to determine whether positive resection margins determine local recurrence and whether recurrence at the surgical margin influences long-term survival.Clinicopathological data and oncological outcomes of patients who underwent curative resection for colorectal liver metastases between 2012 and 2017 at 2 major hepatobiliary centers (Bern, Switzerland, and Berlin, Germany) were assessed. Cross-sectional imaging following hepatectomy was reviewed by radiologists in both centers to distinguish between recurrence at the resection margin, defined as hepatic local recurrence, and intrahepatic recurrence elsewhere. The association between surgical margin status and location of tumor recurrence was evaluated, and the impact on overall survival was determined.During the study period, 345 consecutive patients underwent hepatectomy for colorectal liver metastases. Histologic surgical margins were positive for tumor cells (R1) in 63 patients (18%). After a median follow-up time of 34 months, tumor recurrence was identified in 154 patients (45%). Hepatic local recurrence was not detected more frequently after R1 than after R0 resection (P = .555). Hepatic local recurrence was not associated with worse overall survival (P = .436), while R1 status significantly impaired overall survival (P = .025). Additionally, overall survival was equivalent between patients with hepatic local recurrence and patients with any intrahepatic and/or extrahepatic recurrence. In patients with intrahepatic recurrence only, oncological outcomes improved if local hepatic therapy was possible (resection or ablation) in comparison to patients treated only with chemotherapy or best supportive care (3-year overall survival: 85% vs 39%; P < .0001).The incidence of hepatic local recurrence after hepatectomy for colorectal liver metastases is independent of R1 resection margin status. Additionally, hepatic local recurrence at the resection margin is not associated with worse overall survival compared with any other intra- or extrahepatic recurrence. Therefore, R1 status at hepatectomy seems to be a surrogate factor for advanced disease without influencing location of recurrence and thereby oncological outcome. This finding may support decision-making when extending the indication for surgery in borderline resectable colorectal liver metastases.

The impact of perioperative red blood cell transfusion on long-term survival after hepatectomy for colorectal liver metastases.

725 Background: Perioperative red blood cell transfusions (RBCT) are associated with postoperative morbidity and may increase cancer recurrence through immunologic mechanisms following resection of colorectal liver metastases (CRLM). We sought to explore the relationship between RBCTs and long-term survival following resection of CRLM in the contemporary surgical era. Methods: We conducted a retrospective review of a prospective database including all patients undergoing partial hepatectomy for CRLM from 2003-2012. Data regarding date of death was abstracted from a validated, population-based cancer registry. Primary outcome was overall survival (OS), compared based on RBCT (defined as time of surgery to 30 days following surgery) and on number of RBC units received using Kaplan-Meier curves. Cox regression analysis was performed to examine the association between RBCT and OS, while adjusting for prognostic factors including Fong score and period of treatment (2003-2007 vs. 2008-2012). Results: We included 483 patients operated for CRLM, of which 27.5% received RBCT. 90-day post-operative mortality was 4.8% and median follow-up was 33 (IQR: 20.1-54.8) months. Median survival in patients who received RBCT was 44.5 months compared with 93.5 months in patients who did not(p&lt;0.0001). The difference persisted in subgroup analysis excluding patients who died within 90 days of surgery (62.3 vs. 93.5 months, p=0.023). After adjustment for Fong score and period of treatment, RBCT was independently associated with decreased OS (HR 2.15; 95% CI: 1.52-3.04). Conclusions: Perioperative RBCT is independently associated with decreased OS following hepatectomy for CRLM. Interventions to minimize and rationalize the use of RBCT for hepatectomy are warranted in order to mitigate this detrimental effect on long-term outcomes.

Predicting early intrahepatic recurrence after curative resection of colorectal liver metastases with molecular markers.

The aim of this case-control study was to identify clinicopathological factors and test three relevant biomarkers for their ability to predict early intrahepatic recurrence after curative liver resection for colorectal liver metastases (CLM). Of the 184 patients with CLM undergoing hepatectomy between January 2007 and December 2009, thirty patients had intrahepatic disease recurrence within 6 months. The control group was randomly selected from a cohort of patients between April 1997 and December 2005 who have survived without disease recurrence after CLM resection for over 5 years. Both groups were matched for size of metastasis greater than 5.0 cm, the presence of multiple metastases, and synchronous versus metachronous CLM. The final study population consisted of 60 patients with CLM undergoing R0 hepatectomy, 30 of whom had early intrahepatic-only recurrences (study group) and 30 patients without recurrence for more than 5 years (control group). Both groups were analyzed and compared for the presence of clinical factors and expression levels of CD133, survivin, and Bcl-2 within tumor tissue. Characteristics of patients were similar between the two groups except primary tumor location and administration of postoperative chemotherapy. Expression level of CD133 and survivin were significantly increased in tumors of patients with recurrence compared to patients without recurrence. On multivariate analysis high tumor expression levels of CD133 (odds ratio [OR] 14.7, confidence interval [CI] 1.8-121.3, p = 0.012) and survivin (OR 9.5, CI 2.1-44.3, p = 0.004) and postoperative chemotherapy (OR 4.8, CI 1.01-22.9, p = 0.049) were independent factors associated with early intrahepatic recurrence. Tumor expression levels of CD133 and survivin may be a useful predictor of early intrahepatic recurrence after hepatectomy for CLM. Administration of postoperative chemotherapy may prevent early intrahepatic recurrence.

Role of associating liver partition and portal vein ligation for staged hepatectomy in colorectal liver metastases: a review.

Colorectal cancer is the third most common cancer in the Western world. Approximately half of patients will develop liver metastases, which is the most common cause of death. The only potentially curative treatment is surgical resection. However, many patients retain a to small future liver remnant (FLR) to allow for resection directly. There are therefore strategies to decrease the tumor with neoadjuvant chemotherapy and to increase the FLR. An accepted strategy to increase the FLR is portal vein occlusion (PVO). A concern with this strategy is that a large proportion of patients will never be operated because of progression during the interval between PVO and resection. ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) is a new procedure with a high resection rate. A concern with this approach is the rather high frequency of complications and high mortality, compared to PVO. In this review, it is shown that with ALPPS the resection rate was 97.1% for CRLM and the mortality rate for all diagnoses was 9.6%. The mortality rate was likely lower for patients with CRLM, but some data were lacking in the reports. Due to the novelty of ALPPS, the indications and technique are not yet established but there are arguments for ALPPS in the context of CRLM and a small FLR.