Hepatectomy For Metastatic Colorectal Cancer Research Articles

Evaluation of the American College of Surgeons risk calculator in hepatectomy for metastatic colorectal cancer in a Southeast Asian population.

This study evaluated the accuracy of the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) calculator in predicting outcomes after hepatectomy for colorectal cancer (CRC) liver metastasis in a Southeast Asian population. Predicted and actual outcomes were compared for 166 patients undergoing hepatectomy for CRC liver metastasis identified between 2017 and 2022, using receiver operating characteristic curves with area under the curve (AUC) and Brier score. The ACS-NSQIP calculator accurately predicted most postoperative complications (AUC > 0.70), except for surgical site infection (AUC = 0.678, Brier score = 0.045). It also exhibited satisfactory performance for readmission (AUC = 0.818, Brier score = 0.011), reoperation (AUC = 0.945, Brier score = 0.002), and length of stay (LOS, AUC = 0.909). The predicted LOS was close to the actual LOS (5.9 vs. 5.0days, P = 0.985). The ACS-NSQIP calculator demonstrated generally accurate predictions for 30-day postoperative outcomes after hepatectomy for CRC liver metastasis in our patient population.

Preventing Futile Liver Resection: A Risk-Based Approach to Surgical Selection in Major Hepatectomy for Colorectal Cancer.

BackgroundEarly recurrence following liver resection for metastatic colorectal cancer generally portends poor survival. We sought to identify factors associated with early disease recurrence after major hepatectomy for metastatic colorectal cancer in order to improve patient selection and prevent futile hepatectomy.MethodsSequential major (four or more segments) liver resections performed for metastatic colorectal cancer between 1995 and 2019 were selected from our prospectively maintained database. Univariate analyses, multivariable regression modelling, and survival analyses were used to identify predictors of futile resection (recurrence within 6 months of hepatectomy).ResultsOf 259 patients included, the median age was 61.3 years (interquartile range [IQR] 15.3) and the median number of liver tumors was 3.0 (IQR 2.0); 78.0% of patients received prehepatectomy chemotherapy. Surgeries were right (56.4%), left (19.3%), and extended hepatectomy (24.3%). Futile resection occurred in 26 (12.6%) patients. Margin positivity was similar in the futile resection group compared with the non-futile resection group (11.5% vs. 11.4%). Extrahepatic disease that disappeared with chemotherapy was present in 23.1% of patients with a futile resection and 7.2% of those without (p = 0.019). After multivariable regression, the factors predictive of futile resection were extrahepatic disease (odds ratio [OR] 5.6; p = 0.004), more than three liver lesions (OR 4.9; p = 0.001), and extended hepatectomy (OR 2.6; p = 0.038). Notably, 70.8% of futile recurrences occurred within the liver remnant and 20.8% were pulmonary metastases. Overall survival was 11.7 months (95% confidence interval [CI] 7.1–16.2) for the futile resection cohort versus 45.6 (95% CI 39.1–52.1) for non-futile hepatectomies (p < 0.001).ConclusionsFutile hepatic resection can be predicted based on preoperative factors and carries a poor prognosis. Improved risk stratification for futility will aid in patient selection and treatment discussions.

Genomic and prognostic heterogeneity among RAS/BRAFV600E /TP53 co-mutated resectable colorectal liver metastases.

Hepatic resection is potentially curative for patients with colorectal liver metastases, but the treatment benefit varies. KRAS/NRAS (RAS)/TP53 co-mutations are associated with a poor prognosis after resection, but there is large variation in patient outcome within the mutation groups, and genetic testing is currently not used to evaluate benefit from surgery. We have investigated the potential for improved prognostic stratification by combined biomarker analysis with DNA copy number aberrations (CNAs), and taking tumor heterogeneity into account. We determined the mutation status of RAS, BRAFV600 , and TP53 in 441 liver lesions from 171 patients treated by partial hepatectomy for metastatic colorectal cancer. CNAs were profiled in 232 tumors from 67 of the patients. Mutations and high-level amplifications of cancer-critical genes, the latter including ERBB2 and EGFR, were predominantly homogeneous within patients. RAS/BRAFV600E and TP53 co-mutations were associated with a poor patient outcome (hazard ratio, HR, 3.9, 95% confidence interval, CI, 1.3-11.1, P=0.012) in multivariable analyses with clinicopathological variables. The genome-wide CNA burden and intrapatient intermetastatic CNA heterogeneity varied within the mutation groups, and the CNA burden had prognostic associations in univariable analysis. Combined prognostic analyses of RAS/BRAFV600E /TP53 mutations and CNAs, either as a high CNA burden or high intermetastatic CNA heterogeneity, identified patients with a particularly poor outcome (co-mutation/high CNA burden: HR 2.7, 95% CI 1.2-5.9, P=0.013; co-mutation/high CNA heterogeneity: HR 2.5, 95% CI 1.1-5.6, P=0.022). In conclusion, DNA copy number profiling identified genomic and prognostic heterogeneity among patients with resectable colorectal liver metastases with co-mutated RAS/BRAFV600E /TP53.

Video presentation: Robotic right hepatectomy for metastatic colorectal cancer

Video presentation: Robotic right hepatectomy for metastatic colorectal cancer

The Impact Of Frailty On Patients Undergoing Liver Resection For Colorectal Liver Metastasis: A Review Of The National Surgical Quality Improvement Program

Presenter: Jacqueline Dauch MD | University of Arizona Background: Frailty is highly prevalent in patients with malignancy and is associated with high risk of morbidity and mortality after operative interventions. However, the impact of frailty on patients undergoing liver resection for metastatic colorectal cancer has not been studied. The aim of this study was to assess the impact of frailty on short term outcomes after liver resection in patients with metastatic colorectal cancer to the liver. Methods: We performed a 4 year analysis of the National Surgical Quality Improvement Program (NSQIP) participant user files. All patients undergoing hepatectomy for metastatic colorectal cancer between 2014-2017 were reviewed. The 5-item Modified Frailty Index (mFI) was calculated using NSQIP variables. We included all patients with complete mFI information in the analysis. Patients were divided into three categories based on the mFI (0= no frailty indicators, 1=one frailty indicator, 2=two or more frailty indicator). Outcome measures in house included minor and major morbidity as defined by the Clavien-Dindo classification (I/II vs III/IV), 30 day mortality, need for readmission, unfavorable discharge (not to home), bile leak and liver failure. Results: A total of 5230 patients were included in the analysis. 2737 (52%) had a mFI score of 0, 1839 (35%) had a mFI score of 1, and 654 (13%) had a mFI score of 2 or more. On multivariate analysis and after adjusting for potential cofounders such as age, sex, race/ethnicity, BMI, ASA class, preoperative albumin, neoadjuvant chemotherapy and extent of surgery (minor vs major ); patients with a mFI score of 2 or over were more likely than those with mFI of 0 to experience minor morbidity (OR 1.47, 95% CI 1.14-1.91, p<0.01), major morbidity (OR 1.82, 95% CI 1.29-2.55, p<0.01), readmission (OR 1.56 95% CI 1.10-2.23, p<0.01), non-home discharge (OR 2.81, 95% CI 1.74-4.50, p<0.01), and bile leak (OR 1.64 95% CI.05-2.54, p=0.03). Those with a mFI score of 1 were more likely than those with mFI 0 to experience non-home discharge (OR 1.54 95% CI 1.03-2.31 p=0.04) and liver failure (OR 1.63, 95% CI 1.14-2.45, p<0.01). Conclusion: Frailty is associated with increased risk of morbidity, unfavorable discharge, readmission and bile leak in patients undergoing liver resection for metastatic colorectal cancer. We recommend the use of the 5-item Modified Frailty Index to guide risk stratification, optimization and counseling.

Laparoscopic &amp; robotic liver resection for colorectal cancer metastases

Distant metastasis of colorectal cancer to the liver will occur in approximately 50% of patients and surgical resection is associated with improved survival. Over the past decade minimally invasive techniques have been adopted with an increasing number of major hepatic resections performed for both benign and malignant disease, including colorectal cancer liver metastasis. This review aims to provide an overview and summary of the current data on the perioperative and oncologic outcomes of minimally invasive hepatectomy for metastatic colorectal cancer. Furthermore, the application of robotic assisted surgery and the use of minimally invasive techniques in locoregional treatment of colorectal liver metastasis (CRLM) are also examined.

Repeat hepatectomy with systemic chemotherapy might improve survival of recurrent liver metastasis from colorectal cancer\u2014a retrospective observational study

BackgroundAlthough hepatectomy for metastatic colorectal cancer (mCRC) prolongs survival in up to 40% of people, recurrence rates approach 70%. We used a multidisciplinary approach to treat recurrent liver metastases, including chemotherapy, surgery, and palliative care. On the other hand, development of chemotherapeutic agents is remarkable and improves long-term survival. However, whether chemotherapy and repeat hepatectomy combination therapy improve survival or not is still unclear. The aim of this study was to analyze the outcomes of repeat hepatectomy with systemic chemotherapy for mCRC.MethodsFollowing Institutional Review Board approval, we reviewed the records of all patients who underwent hepatectomy for mCRC between 1974 and 2015 at Fujita Health University Hospital. We used the Kaplan–Meier method to estimate overall survival from the first and last hepatectomy in multi hepatectomy cases after 2005 and compared outcomes between groups using the log-rank test.ResultsA total of 426 liver resections were performed for mCRC; of these, 236 cases were performed after 2005 (late group). In 118 (50%) cases, the site of recurrence was the liver, 59 (50%) underwent repeat hepatectomy, and 14 cases had ≥ 2 repeat hepatectomies.Overall survival (OS) before and after 2005 was 42.2 and 64.1 months, respectively, with the late group having better OS compared to the early (1974–2004) group. OS for single hepatectomy cases was 83.2 months, for two hepatectomies was 42.9 months, and for three hepatectomies was 35.3 months. In total, 59 patients did not undergo surgery after recurrence with an OS of 28.7 months. Mortality of the second and third repeat hepatectomy was 1.7% and 15.3%, respectively.ConclusionRepeat hepatectomy with systemic chemotherapy for mCRC is feasible and might achieve improved survival in carefully selected patients.

FBXW7 mutation is associated with decreased survival following hepatectomy for metastatic colorectal cancer

Introduction: Improved understanding of tumor genomics has transformed the treatment of colorectal liver metastases (CLM). F-box/WD repeat-containing protein 7 (FBXW7) is a tumor suppressor gene recognized in the degradation of mediators of cell cycle progression. We have previously reported the effect of frequently mutations in the setting of CLM, however the role of FBXW7 in the progression of this disease is underreported. We aimed to evaluate the impact of FBXW7 mutation on survival following hepatectomy for CLM. Method: Clinicopathologic data was abstracted for patients with documented mutational analysis who underwent hepatectomy from 2001-2016. Kaplan-Meier analysis was performed for overall survival (OS) and compared by log-rank test. Risk factors for overall survival were determined by Cox proportional hazards model. Result: In total, 462 patients were included with a median age of 55 years (IQR 46-62 years). Most had colon primary tumors (68.5%), were ≥T3 (87.5%), and had lymph node-positive primary disease (70.9%). Synchronous metastasis occurred in 76.5%, yet the minority had extrahepatic metastases (16.6%). Most (90.5%) underwent neoadjuvant chemotherapy, with 71% of these receiving concomitant targeted therapy. Few patients (20.4%) underwent R1 resection. The most common mutation associated with survival was TP53 (prevalence: 70.7%,HR:2.0, 95%CI 1.4-3.0, p<0.001), followed byRAS (50.4%, HR:2.4, 95%CI 1.7-3.5, p<001). Mutation in FBXW7 was found in 5.7% of patients, and it was a strong negative prognostic factor for OS (HR 1.99, p=0.015). BRAF was the least common mutation, found in 2.3%, but it was the strongest negative prognostic factor for OS (HR 2.47, p=0.023). Conclusion: Mutation of FBXW7 is a strong negative predictor of OS and is detected more frequently than other accepted mutations used for prognostication following hepatectomy for CLM. Further analyses of FBXW7 in combination with additional mutations and clinical factors may refine risk stratification and treatment decisions for patients with CLM.

Computed Tomography Image Texture: A Noninvasive Prognostic Marker of Hepatic Recurrence After Hepatectomy for Metastatic Colorectal Cancer.

Recurrence after resection of colorectal liver metastases (CRLMs) occurs in up to 75% of patients. Preoperative prediction of hepatic recurrence may inform therapeutic strategies at the time of initial resection. Texture analysis (TA) is an established technique that quantifies pixel intensity variations (heterogeneity) on cross-sectional imaging. We hypothesized that tumoral and parenchymal changes that are predictive of overall survival (OS) and recurrence in the future liver remnant (FLR) can be detected using TA on preoperative computed tomography (CT) images. Patients who underwent resection for CRLM between 2003 and 2007 with appropriate preoperative CT scans were included (n=198) in this retrospective study. Texture features extracted from the tumor and FLR, and clinicopathologic variables, were incorporated into a multivariable survival model. Quantitative imaging features of the FLR were an independent predictor of both OS and hepatic disease-free survival (HDFS). Tumor texture showed significant association with OS. TA of the FLR allowed patient stratification into two groups, with significantly different risks of hepatic recurrence (hazard ratio 2.09, 95% confidence interval 1.33-3.28; p=0.001). Patients with homogeneous parenchyma had approximately twice the risk of hepatic recurrence (41 vs. 20%). TA of the tumor and FLR are independently associated with OS, and TA of the FLR is independently associated with HDFS. Patients with homogeneous parenchyma had a significantly higher risk of hepatic recurrence. Preoperative TA of the liver represents a potential biomarker to identify patients at risk of liver recurrence after resection for CRLM.

Case-controlled study comparing peri-operative and cancer-related outcomes after major hepatectomy and parenchymal sparing hepatectomy for metastatic colorectal cancer

IntroductionLiver resection is potentially curative in selected patients with colorectal liver metastases (CLM). There has been a trend towards parenchyma sparing hepatectomy (PSH) rather than major hepatectomy (MH) due to lower perioperative morbidity. Although data from retrospective series suggest that long-term survival after PSM are similar to MH, these reports may be subject to selection bias. The aim of this study was to compare outcomes of PSH and MH in a case-controlled study. Patients and methods917 consecutive patients who underwent liver resection for CLM during 2000–2010 were identified from a prospective database. 238 patients who underwent PSH were case-matched with 238 patients who had MH, for age, gender, tumour number, maximum tumour diameter, primary Dukes' stage, synchronicity and chemotherapy status using a propensity scoring system. Peri-operative outcomes, recurrence and long-term survival were compared. ResultsFewer PSH patients received peri-operative blood transfusions (p < 0.0001). MH patients had greater incidence of complications (p = 0.04), grade III/IV complications (p = 0.01) and 90-day mortality (p = 0.03). Hospital stay was greater in the MH group (p = 0.04). There was no difference in overall/disease-free survival. ConclusionPatients with resectable CLM should be offered PSH if technically feasible. PSH is safer than MH without compromising long-term survival.

The relationship of blood transfusion with peri-operative and long-term outcomes after major hepatectomy for metastatic colorectal cancer: a multi-institutional study of 456 patients

BackgroundData on prognostic implications of peri-operative blood transfusion around resection of colorectal cancer liver metastases (CRLM) are conflicting. This retrospective study assesses the association of transfusion with complications and disease-specific survival (DSS). MethodsMajor hepatectomies for CRLM from 2000 to 2010 at three institutions were included. Transfusion was analyzed based on timing and volume. ResultsOf 456 patients, 140 (30.7%) received transfusions. Transfusion was associated with extended hepatectomy (28.6 vs 18.4%; p = 0.020), tumor size (5.7 vs 4.2 cm; p < 0.001), and operative blood loss (917 vs 390 mL; p < 0.001). Transfusion was independently associated with major complications (OR 2.61; 95% CI: 1.53–4.44; p < 0.001). Transfusion at any time was not associated with DSS; however, patients who specifically received blood post-operatively had reduced DSS (37.4 vs 42.7 months; p = 0.044). Increased volume of transfusion (≥3 units) was also associated with shortened DSS (Total: 37.4 vs 41.5 months, p = 0.018; Post-operative: 27.2 vs 40.3 months, p = 0.015). On multivariate analysis, however, transfusion was not independently associated with worsened DSS, regardless of timing and volume. ConclusionTransfusion with major hepatectomy for colorectal cancer metastases is independently associated with increased complications but not disease-specific survival. Judicious use of transfusion per a blood utilization protocol in the peri-operative period is warranted.

Recurrence After Partial Hepatectomy for Metastatic Colorectal Cancer: Potentially Curative Role of Salvage Repeat Resection.

Patients with recurrence after complete resection of colorectal liver metastases (CLM) are considered for repeat resection as a potential salvage therapy (PST). However, outcomes for this approach are not well defined. We sought to analyze the natural history of recurrence and PST in a large cohort of patients with long-term follow-up. Recurrence patterns, treatments, and outcomes in consecutive patients undergoing resection for colorectal liver metastases were analyzed retrospectively. PST was defined as repeat resection of all recurrent disease and effective salvage therapy (EST) as free of disease for 36months after last PST. Factors associated with PST, EST, and outcomes were analyzed. Of 952 patients who underwent resection, 594 (62%) experienced recurrence (median interval=13months). Initial recurrences involved liver (n=157,26%), lung (n=167,28%), multiple sites (n=171,29%), and other single sites (n=99,17%). PST was performed in 160 (27%) of 594, most commonly with a single site of recurrence (n=149). Young age (p=0.01), negative initial resection margin (p=0.003), initial tumor size <5cm (p=0.006), and recurrence pattern (p<0.001) were independently associated with PST. Thirty-six patients experienced EST (25% of PSTs). Overall median survival was 61 and 43months in those with recurrence. Median survival of patients undergoing PST was 87months compared to 34months for those who did not. Recurrence is common after CLM resection, but 27% of patients were able to undergo PST. Approximately one-quarter of these experienced EST and may be cured. PST is associated with long-term survival and possible cure, and therefore active surveillance after CLM resection is justified.

Src activity is modulated by oxaliplatin and correlates with outcomes after hepatectomy for metastatic colorectal cancer.

BackgroundThe nonreceptor tyrosine kinase Src regulates multiple pathways critical to tumor proliferation, chemoresistance, and epithelial-to-mesenchymal transition. It is robustly activated after acute oxaliplatin exposure and in acquired oxaliplatin resistance in vitro and in vivo, but not after 5-fluorouracil (5-FU) alone. However, activation of Src and its substrate focal adhesion kinase (FAK) in metastatic colorectal cancer treated with oxaliplatin has not been investigated. We retrospectively evaluated the activation of Src and FAK in hepatic metastases of colorectal cancer and correlated these findings with the clinical outcomes of patients treated with oxaliplatin.MethodsSamples from 170 hepatic resections from patients with metastatic colorectal cancer from two cohorts were examined by IHC for expression of Src, activated Src (pSrc), FAK, and activated FAK (pFAK). Patients in the first cohort (120 patients) were analyzed for immunohistochemical protein expression and for survival outcomes. In the second cohort, tissue was collected from 25 patients undergoing sequential hepatic metastasectomies (n = 50).ResultsIn the first cohort, Src activation was positively correlated with pFAK expression (P = 0.44, P < 0.001). Patients pretreated with oxaliplatin and 5-FU demonstrated increased expression of pFAK (P = 0.017) compared with patients treated with 5-FU alone or irinotecan/5-FU. Total Src expression was associated with the number of neoadjuvant cycles of oxaliplatin (P = 0.047). In the second cohort, pFAK expression was higher following exposure to oxaliplatin. When patients were stratified by expression of pFAK and pSrc, an inverse relationship was observed between relapse-free survival rates and levels of both pFAK (21.1 months, 16.5 months, and 7.4 months for low, medium, and high levels of pFAK, respectively; P = 0.026) and pSrc (19.6 months, 13.6 months, and 8.2 months, respectively; P = 0.013). No differences in overall survival were detected.ConclusionsPatients administered neoadjuvant oxaliplatin demonstrated higher levels of Src pathway signaling in hepatic metastases, a finding associated with poorer relapse-free survival. These results are consistent with prior in vitro studies and support the idea that combining Src inhibition with platinum chemotherapy warrants further investigation in metastatic colorectal cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-660) contains supplementary material, which is available to authorized users.

The association between preoperative chemotherapy and the prevalence of hepatic steatosis in hepatectomy for metastatic colorectal cancer.

BackgroundSome studies have suggested that preoperative chemotherapy for hepatic colorectal metastases may cause hepatic injury and increase perioperative morbidity and mortality.AimTo evaluate the prevalence of hepatic steatosis in patients undergoing preoperative chemotherapy for metastatic colorectal cancer.MethodsObservational retrospective cohort study in which 166 patients underwent 185 hepatectomies for metastatic colorectal cancer with or without associated preoperative chemotherapy from 2004 to 2011. The data were obtained from a review of the medical records and an analysis of the anatomopathological report on the non-tumor portion of the surgical specimen. The study sample was divided into two groups: those who were exposed and those who were unexposed to chemotherapy.ResultsFrom the hepatectomies, 136 cases (73.5%) underwent preoperative chemotherapy, with most (62.5%) using a regimen of 5-fluorouracil + leucovorin. A 40% greater risk of cell damage was detected in 62% of the exposed group. The predominant histological pattern of the cell damage was steatosis, which was detected in 51% of the exposed cases. Exposure to chemotherapy increased the risk of steatosis by 2.2 fold. However, when the risk factors were controlled, only the presence of risk of hepatopathy was associated with steatosis, with a relative risk of 4 (2.7-5.9).ConclusionPatients exposed to chemotherapy have 2.2 times the risk of developing hepatic steatosis, and its occurrence is associated with the presence of predisposing factors such as diabetes mellitus and hepatopathy.

Survival after hepatectomy for metastatic colorectal cancer in the presence of resectable extrahepatic disease

Background: The presence of extrahepatic disease, bilobar disease or greater than four hepatic lesions were once considered contraindications to hepatectomy for colorectal metastases but are being reconsidered. We reviewed our experience with resection of extrahepatic disease (EHD) at the time of hepatectomy for metastatic colorectal cancer to determine the impact on perioperative and long-term outcome. Methods: The medical records of 441 patients who underwent hepatectomy for colorectal cancer metastases from 1989 to 2010 were reviewed. Demographics, clinicopathologic characteristics, and outcomes were compared between those with and without extrahepatic disease. Overall survival curves were constructed using the Kaplan Meier method and compared with the log rank test. Multivariate analysis using logistic and Cox proportional hazards regression were used to determine predictors of perioperative mortality and longterm survival, respectively. Results: Fifty-nine (13%) patients presented with EHD at the time of hepatectomy. There were no significant differences between patients with and without EHD with regard to age, gender, disease free interval, or the number and distribution of hepatic metastases. Patients with EHD were as likely to undergo complete (i.e. R0) resection as those with isolated liver metastases (59% vs. 74%. p&gt;0.05). Perioperative mortality in the 441 patients was 2.3%. Only increasing number of liver segments resected and perioperative complications were predictive of perioperative mortality by multivariate analysis. Median overall survival was 20.5 months in patients with EHD compared to 35.2 months in patients without EHD (p&lt;0.001). Increasing age, the presence of EHD, bilobar disease, and length of stay in the ICU were significant predictors of decreased overall survival by multivariate analysis. Conclusion: Despite similar populations, extrahepatic disease remains a poor prognostic indicator for survival after hepatectomy for colorectal metastasis. Though a low perioperative mortality coupled with median survival of 20.5 months emphasizes the potential of a curative approach to patients with traditionally incurable disease, resection of EHD should be carefully weighed. The presence of resectable extrahepatic disease should not be a contraindication to hepatectomy for colorectal metastases but should be approached cautiously due to its poor prognostic factors.

Negative Effects of Transfused Blood Components after Hepatectomy for Metastatic Colorectal Cancer

There has been conflicting evidence regarding negative effects of blood transfusion in oncology patients. This study was undertaken to determine any negative effects of specific blood product transfusion after resection of hepatic colorectal metastases (CRM). Retrospective review of patients undergoing hepatectomy for CRM from 1995 to 2009 at a single institution was performed. Specific attention was paid to the effect of blood transfusion within 30 days of operation on overall survival, disease-free survival (DFS), and complications. To mitigate the bias introduced by complications that require blood transfusion to treat, only nonbleeding complications were considered. Complications were analyzed with univariate and multivariate logistic regression. Survival was analyzed according to Kaplan-Meier and Cox proportional hazards. There were 239 patients included in the study. There were 64 (26.8%) receiving a transfusion of any kind with 25.5 per cent getting red cells (PRBCs), 7.11 per cent getting fresh-frozen plasma, and 3.77 per cent getting platelets. Multivariate analysis revealed only PRBC transfusion to be independently associated with nonbleeding complications (odds ratio, 1.980; 95% confidence interval, 1.094 to 3.582; P = 0.0239). There was no significant adverse effect of transfusion with any product on overall or DFS. PRBC transfusion appears to increase the risk of postoperative complications; thus, strategies to minimize blood use may be warranted.

Impact of Simultaneous Diaphragm Resection During Hepatectomy for Treatment of Metastatic Colorectal Cancer

IntroductionFor colorectal cancer patients with liver metastases involving the hepatic dome or invading the diaphragm, a concomitant diaphragm resection is often required to achieve negative surgical margins. The purpose of this study is to determine whether diaphragm resection during partial hepatectomy for metastatic colorectal cancer influences short-term perioperative outcomes and overall survival. MethodsDemographics, treatments, and outcomes of 442 patients who underwent hepatic resection for metastatic colorectal cancer from 1996 to 2010 at a high-volume center were reviewed. Recurrence and survival were measured from the date of metastectomy. Actuarial curves were generated using the Kaplan–Meier method and compared using log–ranks testing. Multivariate predictors of worse survival were compared using a Cox-proportional hazards model. ResultsA total of 442 patients underwent hepatectomy for metastatic colorectal cancer. Of these, 34 required simultaneous diaphragm resection (DR) and 408 did not (LR). No significant differences existed in patient demographics or comorbidities. The DR group had longer median operative times (336 vs. 267 min, p = 0.0008) but had comparable rates of perioperative morbidity and mortality. Median overall survival was shorter in the DR group compared to the LR group (18.8 vs. 36 months, p = 0.0017). When controlling for potential cofounders, liver metastases size > 5 cm (HR 1.45 95 % CI (1.08–1.99), p = 0.015) and diaphragm resection (HR = 1.72 95 % CI (1.03–2.86), p = 0.038) predicted worse survival. ConclusionsSimultaneous diaphragm resection during partial hepatectomy does not significantly influence perioperative morbidity or mortality despite longer operative times. However, patients who require diaphragm resection have less favorable survival rates as compared to those who do not.

Relationship of Src activity and prior oxaliplatin on outcomes after hepatectomy for metastatic colorectal cancer.

3561 Background: The nonreceptor tyrosine kinase Src regulates pathways critical to tumor proliferation, chemoresistance, and epithelial-to-mesenchymal transition. In vitro, Src is activated after acute oxaliplatin exposure and in acquired oxaliplatin resistance, but not after 5-FU alone. Activation of Src and its substrate FAK in metastatic colorectal cancer treated with oxaliplatin has not been studied in human specimens. Methods: Samples from 170 hepatic resections from two cohorts of patients with metastatic colorectal cancer were examined by IHC for expression of activated Src (pSrc) and FAK (total and pFAK). In the first cohort (n=50), tissue was collected at consecutive hepatic resections before and after oxaliplatin. Patients in the second cohort (n=120) were compared based on whether or not oxaliplatin was administered after resection. IHC was graded semi-quantitatively, 0 to 4 based on intensity (first cohort), and by automated image analysis (second cohort). Results: In the first cohort, pFAK expression increased after oxaliplatin exposure (mean IHC score 2.04 vs. 1.18, p&lt;0.01). In the second cohort, Src activation was correlated with pFAK expression (p&lt;0.01). Patients pretreated with oxaliplatin demonstrated increased expression of activated FAK (p=0.02) compared to 5-FU alone or irinotecan regimens. There was a weak association between total Src expression and the number of oxaliplatin cycles (p=0.06). Among patients in the second cohort, five-year relapse-free survival was inversely related to levels of pFAK (21.1%, 16.5%, and 7.4% for low, medium, and high levels of pFAK, respectively; p=0.02) and of pSrc (19.6%, 13.6%, and 8.2% for low, medium, and high levels of pSrc, respectively; p= 0.01). Conclusions: Patients treated with neoadjuvant oxaliplatin demonstrated increased Src signaling in liver metastases, a finding associated with worse relapse-free survival. These results are consistent with prior in vitro studies correlating oxaliplatin exposure with Src pathway activation and support the idea that inhibition of Src, when used in combination with platinum chemotherapy, warrants further investigation in patients with metastatic colorectal cancer.

Repeat Hepatectomy for Metastatic Colorectal Cancer Is Safe but Marginally Effective

Although hepatectomy for metastatic colorectal cancer (mCRC) offers prolonged survival in up to 40% of people, recurrence rates are high, approaching 70%. Many patients experience recurrent disease in the liver after initial hepatectomy. We examined our experience with repeat hepatectomy for mCRC. After Institutional Review Board approval, we reviewed the records of all patients at a single institution who underwent hepatectomy for mCRC. Repeat hepatectomy was defined as partial liver resection any time after the initial hepatectomy for recurrent mCRC. We estimated time to recurrence and survival by using the Kaplan-Meier method and compared outcomes between groups by using the log-rank test. From 1998 to 2008, 405 patients underwent hepatectomy for mCRC, and 215 (53%) experienced disease recurrence at a median of 13 months. Of 150 patients with liver-only or liver-predominant recurrence, 52 (35%) underwent repeat hepatectomy. The median time to recurrence after repeat hepatectomy was 10 months, and median overall survival was 19 months. There was one (1.9%) perioperative death, and there were 14 (27%) major complications. The median overall survival in the repeat hepatectomy group from the time of recurrence after initial hepatectomy was 22 months, compared with 15 months in the 98 patients with liver recurrence who were not selected for repeat hepatectomy (P=0.02). Repeat hepatectomy for mCRC is feasible in highly selected patients, with acceptable perioperative morbidity and mortality. Although repeat hepatectomy should be considered, recurrence rates are high. Although the initial hepatectomy for mCRC is potentially curative, recurrence of metastatic disease in the liver is unlikely to be cured.

Recurrence Following Hepatectomy for Metastatic Colorectal Cancer: Development of a Model that Predicts Patterns of Recurrence and Survival

While several prognostic models have been developed to predict survival of patients who undergo hepatectomy for metastatic colorectal cancer (mCRC), few data exist to predict survival after recurrence. We sought to develop a model that predicts survival for patients who have developed recurrence following hepatectomy for mCRC. A retrospective analysis was performed on data from consecutive patients that underwent hepatectomy for mCRC. Clinicopathologic data, recurrence patterns, and outcomes were analyzed. Kaplan-Meier survival analysis and univariate and multivariate analyses were performed. An integer-based model was created to predict the patterns of recurrence and survival after recurrence. This analysis included 280 patients with a median follow-up of 50.1months. Of these, 53% underwent major hepatectomy and 87% had negative margins. Recurrent disease developed in 63% of patients. After hepatectomy, factors associated with short disease-free interval (DFI) and overall survival (OS) included CEA>200ng/ml (P<0.0005),>1 metastasis (P<0.0005), and a high Fong score (P<0.0005). After recurrence, the pattern of recurrence was a strong predictor of OS (P<0.0005). Independent predictors of the pattern of recurrence on multivariate analysis include CEA>200ng/ml, tumor size>5cm, and>1 liver metastasis. A simple predictive scoring system was developed from the beta coefficients of this analysis that correlated with recurrence pattern (P<0.0005). After hepatectomy, survival of patients with recurrent mCRC is strongly predicted by the patterns of recurrence, and the recurrence pattern can be predicted with a simple model. This can also be extended to create a scoring system that estimates expected survival.