Liver Resection For Colorectal Liver Metastases Research Articles

Postoperative surveillance after surgery for colorectal liver metastasis: a cross-sectional study.

Colorectal liver metastases (CRLM) are associated with a high recurrence rate after surgery. There is paucity of high-quality evidence regarding the nature and overall benefit of surveillance after hepatectomy for CRLM. As part of a broader programme of research, this study aimed to assess current strategies for surveillance after liver resection for CRLM and outline surgeons' opinions regarding the benefit of postoperative surveillance. An online survey was sent to clinicians performing surgery for CRLM at tertiary hepatobiliary centres in the UK. There were responses from a total of 23 centres (88% response rate); 15/23 centres used standardised surveillance protocols for all patients. Most centres followed patients up at six months, but there is variation in postoperative surveillance at 3, 9, 18 and beyond 60 months. Patient comorbidities, indeterminate findings on imaging, margin status and assessment of recurrence risk were identified as the major factors influencing personalised surveillance strategies. There was clear clinician equipoise regarding the costs and benefits of surveillance. There is heterogeneity in postoperative follow-up for CRLM in the UK. High-quality prospective studies and randomised trials are necessary to elucidate the value of postoperative surveillance and identify optimal follow-up strategies.

Preoperative Inflammatory Markers in Liver Resection for Colorectal Liver Metastases: A National Registry-Based Study

BackgroundPreoperative inflammatory markers were shown to be associated with prognosis following surgery for hepato-pancreato-biliary cancer. Yet little evidence exists about their role in patients with colorectal liver metastases (CRLM). This study aimed to examine the association between selected preoperative inflammatory markers and outcomes of liver resection for CRLM.MethodsData from the Norwegian National Registry for Gastrointestinal Surgery (NORGAST) was used to capture all liver resections performed in Norway within the study period (November 2015–April 2021). Preoperative inflammatory markers were Glasgow prognostic score (GPS), modified Glasgow prognostic score (mGPS) and C-reactive protein to albumin ratio (CAR). The impact of these on postoperative outcomes, as well as on survival were studied.ResultsLiver resections for CRLM were performed in 1442 patients. Preoperative GPS ≥ 1 and mGPS ≥ 1 were present in 170 (11.8%) and 147 (10.2%) patients, respectively. Both were associated with severe complications but became non-significant in the multivariable model. GPS, mGPS, CAR were significant predictors for overall survival in the univariable analysis, but only CAR remained such in the multivariable model. When stratified by the type of surgical approach, CAR was a significant predictor for survival after open but not laparoscopic liver resections.ConclusionsGPS, mGPS and CAR have no impact on severe complications after liver resection for CRLM. CAR outperforms GPS and mGPS in predicting overall survival in these patients, especially following open resections. The prognostic significance of CAR in CRLM should be tested against other clinical and pathology parameters relevant for prognosis.

Upfront Surgery versus Neoadjuvant Perioperative Chemotherapy for Resectable Colorectal Liver Metastases: A Machine-Learning Decision Tree to Identify the Best Potential Candidates under a Parenchyma-Sparing Policy.

Addressing patients to neoadjuvant systemic chemotherapy followed by surgery rather than surgical resection upfront is controversial in the case of resectable colorectal -liver metastases (CLM). The aim of this study was to develop a machine-learning model to identify the best potential candidates for upfront surgery (UPS) versus neoadjuvant perioperative chemotherapy followed by surgery (NEOS). Patients at first liver resection for CLM were consecutively enrolled and collected into two groups, regardless of whether they had UPS or NEOS. An inverse -probability weighting (IPW) was performed to weight baseline differences; survival analyses; and risk predictions were estimated. A mortality risk model was built by Random-Forest (RF) to assess the best -potential treatment (BPT) for each patient. The characteristics of BPT-upfront and BPT-neoadjuvant candidates were automatically identified after developing a classification -and -regression tree (CART). A total of 448 patients were enrolled between 2008 and 2020: 95 UPS and 353 NEOS. After IPW, two balanced pseudo-populations were obtained: UPS = 432 and NEOS = 440. Neoadjuvant therapy did not significantly affect the risk of mortality (HR 1.44, 95% CI: 0.95-2.17, p = 0.07). A mortality prediction model was fitted by RF. The BPT was NEOS for 364 patients and UPS for 84. At CART, planning R1vasc surgery was the main factor determining the best candidates for NEOS and UPS, followed by primitive tumor localization, number of metastases, sex, and pre-operative CEA. Based on these results, a decision three was developed. The proposed treatment algorithm allows for better allocation according to the patient's tailored risk of mortality.

Effect of chemotherapy and tumor clearance in hepatic resections for colorectal liver metastases. A single-centre cohort study.

BackgroundColorectal cancer (CRC) is the third most prevalent cancer and accounts for the second leading cause of cancer-related deaths. Up to 50% of CRC patients develop synchronous (10–20%) or metachronous liver deposits (20–30%). Hepatic resection is the gold standard and only curative treatment for colorectal liver metastases (CRLM). While excision significantly improves survival outcomes, more than 50% of patients experience recurrence after primary hepatic resection and usually, within the first 24 months after surgery. ObjectiveTo determine rates and patterns of recurrence following liver resections for CRLM at The Queen Elizabeth Hospital (Adelaide, Australia), and concurrently, characterise clinical, pathological, and treatment-related factors that could function as predictors of recurrence or survival, particularly neoadjuvant chemotherapy, and tumour clearance. MethodsRetrospective analysis of a prospectively collected database of 170 patients between 2004 and 2020, who underwent liver resections for CRLM at The Queen Elizabeth Hospital. ResultsThe prevalence of recurrence following liver resection for CRLM was 53.5% (84/157), with recurrence most likely to occur during the first 12 months post-surgery (median 209 days). Neoadjuvant chemotherapy was associated with a higher recurrence (X2 = 10.587, p-value = 0.001) rate in the univariate and multivariate analysis while resection margins greater than 1 mm showed to decrease the recurrence rate (X2 3.898, p = 0.047). Recurrence was significantly associated with a decreased overall survival (HR 2.58 [1.73; 3.85], p < 0.001), while neoadjuvant chemotherapy showed a negative non-significant marginal effect. ConclusionDespite the development of innovative diagnostic and therapeutic techniques for CRC and CRLM, the recurrence incidence remains high, and survival low. The role and impact of neoadjuvant chemotherapy and resection margins should continue to be reviewed to improve therapeutic outcomes for CRLM.

Parenchymal-sparing hepatectomy for colorectal liver metastases reduces postoperative morbidity while maintaining equivalent oncologic outcomes compared to non-parenchymal-sparing resection

Abstract Objective Modern chemotherapy and repeat hepatectomy allow to tailor the surgical strategies for the treatment of colorectal liver metastases (CRLM). This study addresses the hypothesis that parenchymal-sparing hepatectomy reduces postoperative complications while ensuring similar oncologic outcomes compared to the standardized non-parenchymal-sparing procedures. Methods Clinicopathological data of patients who underwent liver resection for CRLM between 2012 and 2019 at a major hepatobiliary center in Switzerland were assessed. Patients were stratified according to the tumor burden score [TBS2 = (maximum tumor diameter in cm)2 + (number of lesions)2)] and were dichotomized in a lower and a higher tumor burden cohort according to the median TBS. Postoperative outcomes, overall survival (OS) and disease-free survival (DFS) of patients following parenchymal-sparing resection (PSR) for CRLM were compared with those of patients undergoing non-PSR. Results During the study period, 153 patients underwent liver resection for CRLM with curative intent. PSR was performed in 79 patients with TBS &amp;lt; 4.5, and in 42 patients with TBS ≥ 4.5. In patients with lower tumor burden (TBS &amp;lt; 4.5), PSR was associated with lower complication rate (15.2% vs. 46.2%, p = 0.009), and shorter length of hospital stay (5 vs. 9 days, p = 0.006) in comparison to non-PSR. For TBS &amp;lt; 4.5, PSR resulted in equivalent 5-year OS (48% vs. 39%, p = 0.479) and equivalent 5-year DFS rates (DFS, 44% vs. 29%, p = 0.184) compared to non-PSR. For TBS ≥ 4.5, PSR resulted in lower postoperative complication rate (33.3% vs. 63.2%, p = 0.031), lower length of hospital stay (6 vs. 9 days, p = 0.005), equivalent 5-year OS (29% vs. 22%, p = 0.314), and equivalent 5-year DFS rates (29% vs. 22%, p = 0.896) compared to non-PSR. Among all patients treated with PSR, patients undergoing minimal-invasive hepatectomy had equivalent 5-year OS (42% vs. 37%, p = 0.261) and equivalent 5-year DFS (34% vs. 34%, p = 0.613) rates compared to patients undergoing open hepatectomy. Conclusion PSR for CRLM is associated with lower postoperative morbidity, shorter length of hospital stay, and equivalent oncologic outcomes compared to non-PSR independently from tumor burden. Our findings suggest that minimal-invasive PSR should be considered as the preferred method for the treatment of curatively resectable CRLM if allowed by tumor size and location.

Socioeconomic Deprivation Does Not Affect Short or Long Term Outcomes after Liver Resection for Colorectal Liver Metastases

Introduction: Socioeconomic deprivation (SED) is a well documented factor in poor outcomes following treatment for many primary cancers. We sought to examine if this is true for liver resections for colorectal liver metastases (CRLM). Methods: We did a retrospective study on a prospectively held database at Cardiff Liver unit on all patients having liver resections for CRLM between January 2013 and December 2018. Data was censored at 30 June 2019 or death. Demography, ASA status, length of stay, morbidity, mortality, margin status, vascular and bile duct invasion, tumour burden score and deprivation status (using Welsh Index of Multiple Deprivation (WIMD) recorded. WIMD 1 is most deprived and 5 least deprived. We combined the quintiles 1&2 and 3&4 to compare deprived vs non deprived patients. Results: 337 resections were perfomed in 275 patients. Males 66%. Median age 66(21-93), median hospital stay 7 days (2-216) and 90 day mortality of 2.4%. The overall survival(OS) was 90%, 70% and 52%. There was no difference in the baseline characterestics between the most (Q1&2) and least(Q3&4) deprived patients. The OS at 1,3,5 years for most and least deprived were 90%, 69%, 45% and 96%,72% and 60% respectively (P=0.26). There was no difference in the hospital stay, morbidity and mortality between the two groups. Only tumour burden and two stage procedure led to significantly poorer long term outcome. Conclusion: SED does not appear to affect OS after liver resection for CRLM. However, this needs to be confirmed in a larger cohort to avoid Type II error.

Prognostic Significance of CDH1, FN1 and VIM for Early Recurrence in Patients with Colorectal Liver Metastasis After Liver Resection.

PurposeThere are limited data on expression of epithelial–mesenchymal transition (EMT) markers in patients with colorectal liver metastases (CRLM). The study aim was to evaluate the expression and prognostic significance of E-cadherin (CDH1), fibronectin (FN1) and vimentin (VIM) in patients with CRLM after curative-intent liver resection.Patients and MethodsThirty patients with CRLM managed by curative-intent liver resection were included in this prospective pilot study. Blood samples, colorectal liver metastases and surrounding non-tumor liver tissue were collected. Expression of CDH1, FN1 and VIM was analyzed by quantitative real-time polymerase chain reaction. Expression in CRLM and non-tumor liver tissue was compared, while expression in serum was correlated with CRLM expression. One-year recurrence-free survival was compared between patients with low and high CDH1, FN1 and VIM expression.ResultsThe expression of CDH1 was similar in CRLM and non-tumor liver tissues, while FN1 and VIM expression was significantly lower in metastatic tissue (P=0.003 and pP<0.001, respectively). Serum expression of CDH1 and VIM was detected in 66.7% and 93.3% of patients, respectively, while FN1 was not detected in any of the patients. The correlation of CDH1 and VIM expression between CRLM and serum was not statistically significant. Decreased CDH1 expression in CRLM and decreased VIM expression in serum were associated with early recurrence after surgical treatment of CRLM.ConclusionLower expression of CDH1 in CRLM and lower serum expression of VIM were found to be associated with early recurrence after liver resection for CRLM.

Robotic and laparoscopic liver surgery for colorectal liver metastases: an experience from a German Academic Center

BackgroundMinimally invasive liver surgery (MILS) in the treatment of colorectal liver metastases (CRLM) is increasing in incidence. The aim of this work was to present our experience by reporting short-term and long-term outcomes after MILS for CRLM with comparative analysis of laparoscopic (LLS) and robotic liver surgery (RLS).MethodsTwenty-five patients with CRLM, who underwent MILS between May 2012 and March 2020, were selected from our retrospective registry of minimally invasive liver surgery (MD-MILS). Thirteen of these patients underwent LLS and 12 RLS. Short-term and long-term outcomes of both groups were analyzed.ResultsOperating time was significantly longer in the RLS vs. the LLS group (342.0 vs. 200.0 min; p = 0.004). There was no significant difference between the laparoscopic vs. the robotic group regarding length of postoperative stay (8.8 days), measured blood loss (430.4 ml), intraoperative blood transfusion, overall morbidity (20.0%), and liver surgery related morbidity (4%). The mean BMI was 27.3 (range from 19.2 to 44.8) kg/m2. The 30-day mortality was 0%. R0 resection was achieved in all patients (100.0%) in RLS vs. 10 patients (76.9%) in LLS. Major resections were carried out in 32.0% of the cases, and 84.0% of the patients showed intra-abdominal adhesions due to previous abdominal surgery. In 24.0% of cases, the tumor was bilobar, the maximum number of tumors removed was 9, and the largest tumor was 8.5 cm in diameter. The 1-, 3- and 5-year overall survival rates were 84, 56.9, and 48.7%, respectively. The 1- and 3-year overall recurrence-free survival rates were 49.6 and 36.2%, respectively, without significant differences between RLS vs. LLS.ConclusionMinimally invasive liver surgery for CRLM is safe and feasible. Minimally invasive resection of multiple lesions and large tumors is also possible. RLS may help to achieve higher rates of R0 resections. High BMI, previous abdominal surgery, and bilobar tumors are not a barrier for MILS. Laparoscopic and robotic liver resections for CRLM provide similar long-term results which are comparable to open techniques.

The prognostic impact of RAS on overall survival following liver resection in early versus late-onset colorectal cancer patients

BackgroundThe impact of molecular aberrations on survival after resection of colorectal liver metastases (CLM) in patients with early-age-onset (EOCRC) versus late-age-onset colorectal cancer (LOCRC) is unknown.MethodsPatients who underwent liver resection for CLM with known RAS, BRAF and MSI status were retrospectively studied. The prognostic impact of RAS mutations by age was analysed with age as a categorical variable and a continuous variable.ResultsThe study included 573 patients, 192 with EOCRC and 381 with LOCRC. The younger the age of onset of CRC, the greater the negative impact on overall survival of RAS mutations in the LOCRC, EOCRC, and ≤40 years (hazard ratio (HR), 1.64 (95% confidence interval (CI), 1.23–2.20), 2.03 (95% CI, 1.30–3.17), and 2.97 (95% CI, 1.44–6.14), respectively. Age-specific mortality risk and linear regression analysis also demonstrated that RAS mutations had a greater impact on survival in EOCRC than in LOCRC (slope: −4.07, 95% CI −8.10 to 0.04, P = 0.047, R2 = 0.08).ConclusionAmong patients undergoing CLM resection, RAS mutations have a greater negative influence on survival in patients with EOCRC, more so in patients ≤40 years, than in patients with LOCRC and should be considered as a prognostic factor in multidisciplinary treatment planning.

Aggressive recurrences determine oncologic outcomes after resection of liver metastases from primary right colon cancer: Results of a case-control study

BackgroundDespite recent studies suggest that, among patients operated on for colorectal liver metastases (CLM), the primary tumor location may impact on postoperative survivals, results are still contrasting. Objectiveevaluating survivals (overall (OS) and (DFS)) following liver resection of CLM from Right colon Cancer (RcC-CLM) versus Left colon Cancer (LcC-CLM), among patients undergoing preoperative chemotherapy (pCHT), identifying survival predictors, and investigating impact of recurrent disease pattern and management on survival. MethodsAmong 727 patients operated for CLM(1989–2016), after excluding patients with primary transverse colon/rectum tumor and patients not receving pCHT, 297 patients were identified. Among them, 81 with RcC-CLM were matched 1:1 with LcC-CLM, according to CLM number and diameter, disease-free interval between primary tumor and CLM diagnosis, primary tumor N-status, and the presence of extrahepatic disease. ResultsOverall, 66.7% of patients had multiple CLM, 21% had CLM>5 cm, 82.7% had DFI<12 months, 67.9% had N+ primary tumor, and 11.1% had extrahepatic disease at time of hepatectomy. RcC-CLM patients were similar to LcC-CLM in terms of demographic, clinical, perioperative, and pathologic characteristics. Patients operated for RcC-CLM, compared to LcC-CLM, had significantly shorter 5y-DFS(18% versus 39%) and 5y-OS(38% vs 65%). At multivariate analysis, being operated for RcC-CLM, compared to LcC-CLM, was the strongest predictor of recurrence (Hazard Ratio:2.265,p < .001) and death (HR:2.234,p = .001). Among 107 patients experiencing recurrent disease, curative recurrence resection was associated with higher 5y-OS(64% vs 17%; p < .001). However, recurrence resection was less frequently feasible among RcC-CLM(26%) patients, compared to LcC-CLM(44%,p = .05). Conclusionsresection of RcC-CLM, compared to LcC-CLM, is associated with worse survivals, probably related to a different pattern of recurrence precluding recurrence resection among RcC-CLM patients.

Impact of multidisciplinary tumour boards (MTB) on the clinicopathological characteristics and outcomes of resected colorectal liver metastases across time

BackgroundResection of colorectal liver metastases (CLM) has been established as the standard of care. This study aims to compare the change in clinicopathological characteristics of patients who underwent curative resection of CLM across two time periods—2000 to 2010 (P1) and 2011 to 2016 (P2) and evaluate the prognostic impact of these characteristics on survival outcomes.MethodsPatients who undergo liver resection for CLM at Singapore General Hospital from January 2000 to December 2016 were identified from a prospectively maintained database. The primary end point was overall survival.ResultsThere were 183/318 (57.5%) patients and 135/318 (42.5%) patients in P1 and P2, respectively. There was a lower proportion of patients who had nodal metastases from primary colorectal cancer and clinical risk score (CRS) less than 3 in P2 when compared to P1. There was no difference in survival between both time periods. Independent predictors of survival for the cohort were CEA levels ≥ 200 ng/ml, primary tumour grade and lymph nodal status. Independent predictors of poor survival in P1 were poorly differentiated colorectal cancer and nodal metastases while in P2, independent predictors of poor survival were multiple liver metastases and nodal metastases.ConclusionNodal metastases from primary colorectal cancer are an independent predictor of poor survival across time for resectable CLM. Although there is no difference in survival between the two time periods, patients with multiple liver metastases should be carefully considered prior to surgery as it is also an independent predictor of overall survival.

Short- and long-term outcomes of surgery for colorectal and non-colorectal liver metastasis: a report from a single center in the Baltic country

BackgroundThe liver is a major target organ for metastases of various types of cancers. Surgery is a well-established option for colorectal liver metastases (CRLM). Regarding the improved surgical and anesthetic techniques, the safety of liver resection has increased. Consequently, the interest in the surgical management of non-colorectal liver metastases (non-CRLM) has gained significant attention. Therefore, this study was designed to investigate the surgical treatment outcomes for non-CRLM and to compare it with an outcome of CRLM in a tertiary care center in the Baltic country—Lithuania.MethodsWe retrospectively analyzed data from all patients who underwent liver resection for CRLM or non-CRLM between 2010 and 2017 in a tertiary care center—Vilnius University hospital Santaros Clinics. Demographic and metastasis characteristics, as well as disease-free and overall survival, were compared between the study groups.ResultsIn total, 149 patients were included in the study. Patients in the CRLM group were older (63.2 ± 1.01 vs 54.1 ± 1.8 years, p < 0.001) and mainly predominant by males. Overall postoperative morbidity rate (16.3% vs 9.8%, p = 0.402) and major complications rate (10% vs 7.8%, p = 0.704) after liver resection for CRLM and non-CRLM was similar. Kaplan-Meier analysis showed higher disease-free survival in the CRLM group with 89.4% vs 76.5% and 64.9% vs 31.4% survival rates at 1 and 3 years, respectively (p = 0.042), although overall survival was not different between the CRLM and non-CRLM groups with 89.4% vs 78.4% and 72.0% vs 46.1% survival rates at 1 and 3 years, respectively (p = 0.300).ConclusionsIn this study, we confirmed comparable short- and long-term outcomes after liver resection for CRLM and non-CRLM. Surgical resection should be encouraged as an option in well-selected patients with non-CRLM.

Evolution of Surgical Management of Colorectal Liver Metastasis

AbstractThe treatment of colorectal liver metastasis (CRLM) has progressed markedly in the past decades. Main contributions stem from improvement in surgical approach and applications of chemotherapy. The availability of several perioperative and surgical techniques, including portal vein embolization, ablation techniques, and two-stage hepatectomies, has expanded surgical indications. In addition, preoperative imaging methods have contributed to these advances.In patients with high oncological risk of recurrence, or initially unresectable CRLM, highly individualized treatment regimens are becoming more widely utilized. These patients should be evaluated for surgical resection after several cycles of chemotherapy given the survival benefit afforded by liver resection for CRLM. Several biomarkers, including RAS mutation, BRAF mutation, and microsatellite stability, have become essential in guiding therapy. Immunotherapy has recently been highlighted, especially for cases of microsatellite instability. Looking forward, biomarkers will likely to continue to guide individualized treatment patterns.Liver transplantation as an option for patients with unresectable CRLM may boast comparable outcomes to patients with primary liver tumors, but it remains controversial considering the limited supply of donor livers.Management of CRLM requires the complex decision making process common to contemporary tumor board discussions, and a multidisciplinary approach likely figures into future directions of management for CRLM.

Retrospective cohort study of statin therapy effect on resected colorectal liver metastases.

BACKGROUNDAbove and beyond their role in cardiovascular risk reduction, statins appear to have a chemopreventive role in some gastro-intestinal cancers. In the quest for new chemopreventive agents, some existing established drugs such as statins have shown potential for re-purposing as chemoprevention. Probing existing drugs, whose pharmacodynamics are familiar, for novel beneficial effects offers a more cost-effective and less time-consuming strategy than establishing brand new drugs whose pharmacodynamic profile is unfamiliar. Observational studies show statins decrease the risk of developing colorectal cancer but there are no published studies exploring the potential impact of statins on carcinogenesis in colorectal liver metastases (CRLM).AIMTo evaluate impact of statins on outcomes of CRLM resection, and secondarily to assess if statins influence CRLM histo-pathology.METHODSWe conducted a retrospective cohort study of patients operated for CRLM over a 13-year period from 2005 to 2017. Patients were identified from a prospective database maintained in our Tertiary care hospital. All 586 patients included the study had undergone resection of CRLM following discussion at multidisclipinary team meeting, some patients requiring neoadjuvant chemotherapy to downstage CRLM prior to surgery. We analysed patient demographics, operative details, CRLM histopathology, Index of Deprivation, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and chemotherapy use in relation to clinical outcome. Statistics were performed using SPSS version 16.0; significance taken at 5%.RESULTSLiver resection for CRLM was undertaken in 586 patients at a median age of 68 (range 19 to 88) years. Statin therapy was used by 181 patients. Median follow-up time was 23 (range 12-96) mo and further colorectal cancer metastases developed in 267 patients. A total of 131 patients died. Multi-variate analysis identified 6 independent predictors of poorer disease-free survival: Synchronous presentation, multiple tumours, tumour size ≥ 5 cm, moderate–severe steatosis, peri-neural invasion, and R1-resection margin. Poorer overall survival was significantly associated with neo-adjuvant chemotherapy, major hepatectomy, peri-neural invasion and R1-resection margin. Neither histo-pathological nor radiological traits of CRLM were affected by statins, and, there was no demonstrable effect of statin therapy on patient outcomes.CONCLUSIONStatin therapy does not affect patient survival following liver resection for CRLM. We postulate the reason for this key finding is that statins do not modulate tumour biology of CRLM.

Impact of primary tumor location on survival following colorectal liver metastases resection

Background: Despite recent studies suggest that, among patients operated on for colorectal liver metastases (CLM), the primary tumor location (right versus left colon) may impact on postoperative survivals, Results are still contrasting. Objective: To evaluate survivals (overall(OS) and disease-free(DFS)) following liver resection of CLM from Right colon Cancer(RcC-CLM) versus Left colon Cancer(LcC-CLM), among patients undergoing preoperative chemotherapy. Methods: Among 727 patients operated on for CLM(1989-2016), following exclusion of patients with primary tumor located in the transverse colon or rectum and of patients not receving preoperative chemotherapy, 297 patients were identified. Among them, 81 operated for RcC-CLM were matched 1:1 with 81 operated for LcC-CLM, according to CLM number and diameter, disease-free interval(DFI) between primary tumor and CLM diagnosis, tumor N-status, and the presence of extrahepatic disease. Results: Overall, 66.7% of patients had multiple CLM, 21% had CLM>5 cm, 82.7% had DFI<12 months, 67.9% had N+ primary tumor, and 11.1% had extrahepatic disease at time of hepatectomy. RcC-CLM patients were similar to LcC-CLM in terms of demographic, clinical, perioperative, and pathologic characteristics. Patients operated for RcC-CLM, compared to LcC-CLM, had significantly shorter 5y-DFS(18% versus 39%) and 5y-OS(38% vs 65%). At multivariate analysis, being operated for RcC-CLM, compared to LcC-CLM, was the strongest predictor of recurrence(Hazard Ratio:2.265,p<.001) and death(HR:2.234,p=.001). In case of recurrence, recurrent disease resection was less frequent among RcC-CLM(26%), compared to LcC-CLM (44%,p=.05) and was associated with longer 5y-OS(64% vs 17%;p<.001). Conclusions: RcC-CLM, compared to LcC-CLM, are associated with worse survivals, probably related to a different pattern of recurrence precluding recurrence resection among RcC-CLM patients.

ACE Inhibitor Therapy Does Not Influence the Survival Outcomes of Patients with Colorectal Liver Metastases Following Liver Resection.

Angiotensin-converting enzyme (ACE) inhibitors have been shown to possibly influence the survival outcomes in certain cancers. The aim of this study was to evaluate the impact of ACE inhibitors on the outcomes of patients undergoing liver resection for colorectal liver metastases (CRLM). The secondary aim was to determine whether ACE inhibitors influenced histopathological changes in CRLM. Patients treated with liver resection for CRLM over a 13-year period were identified from a prospectively maintained database. Data including demographics, primary tumour treatment, surgical data, histopathology analysis and clinical outcome were collated and analysed. A total of 586 patients underwent primary hepatic resections for CRLM during this period including 100 patients on ACE inhibitors. The median follow-up period was 23 (range: 12-96) months, in which 267 patients developed recurrent disease and 131 patients died. Independent predictors of disease-free survival on multivariate analysis included synchronous presentation, neoadjuvant chemotherapy, major liver resection, tumour size and number, extent of hepatic steatosis, R0 resection and presence of perineural invasion. Poorer overall survival was associated with neoadjuvant treatment, major liver resection, presence of multiple metastases, perineural invasion and positive resection margins on multivariate analysis. ACE inhibitors did not influence the survival outcome or histological presentation in CRLM. The use of ACE inhibitors did not affect the survival outcome or tumour biology in patients with CRLM following liver resection.

Long-Term Results and Prognostic Significance of Non-ANATOMIC Liver Resection for Colorectal Liver Metastasis: Single Center Experience

Development of liver metastasis is a single poor prognostic indicator if left untreated, and therefore management of colorectal liver metastasis (CRLM) is a subject of active multidisciplinary approach. We aimed to evaluate the long-term results and poor prognostic indicators in patients undergoing liver resection for CRLM from a single center in Turkey. All patients who underwent hepatic resection due to colorectal metastasis between March 2007 and November 2011 in our institute were included. Demographic data, operative and postoperative parameters, and long-term follow-up data were analyzed. A total of 44 patients [29 (65.9%) male, median age: 61 (32–81) years] were included to the study. Most of the patients [28 (63.6%) had metachronous liver metastasis, and almost half of the patients [19 (45.2%)] was oligometastatic. Major resection was performed in 18 (40.9%) patients. Intraoperative US changed the operative strategy in 7 (19.4%) patients. Thirty-day mortality was observed in 4 (9.1%) patients. Reasons for mortality were uncontrolled sepsis [catheter infection (n = 1), anastomotic leak (n = 1), and intraabdominal abscess (n = 1)] and hepatic insufficiency (n = 1). Follow-up period excluding patients with early mortality was 30.4 (3–138) months. Kaplan-Meier survival analysis revealed that estimated median survival time after hepatic resection was 28 (95% CI: 20.6–35.4) months. Five-year and 10-year survival probabilities were 20.5% and 13.3%, respectively. Multivariate Cox regression analyses showed that surgical margin positivity was the only significant factor affecting survival. Our results suggest that tumor margin and number of metastasis are the two determinant prognostic indicators in patients with CRLM. Surgery seems to offer a chance for cure, and surgeons in the field should try to perform liver resections in order to obtain negative margins. Major hepatic resections are justified provided that patient selection and preparation is thorough and surgical procedure can be performed safely.

Adverse oncological outcome of surgical site infection after liver resection for colorectal liver metastases.

Postoperative complications are associated with poor overall and cancer-specific survival after resection of various types of cancer, including primary colorectal cancer. However, the oncological impact of surgical site infection (SSI) after liver resection for colorectal liver metastases (CLM) is unclear. The aim of this study was to investigate the oncological impact of SSI after liver resection for CLM. We reviewed data from 367 consecutive patients treated by curative liver resection for CLM between 1994 and 2015. Patients who underwent simultaneous resection of colorectal cancer and synchronous liver metastases (n = 86) were excluded from the analysis. Short- and long-term outcomes were analyzed. SSI developed in 18 (6.4%) of the 281 patients in the analytic cohort (SSI group). The remaining 93.6% (n = 263) did not suffer this complication (no-SSI group). The operative duration was significantly longer in the SSI group than in the No-SSI group (p = 0.002). The overall survival rates 5years after liver resection for CLM were 33.3% in the SSI group vs. 50.7% in the No-SSI group (p = 0.043). Multivariate analysis indicated that a liver tumor size ≥ 5cm, R1 resection, and SSI were independently associated with overall survival after liver resection. SSI after liver resection for CLM is associated with adverse oncological outcomes.

Prognostic impact of tumour biology compared to surgical margin clearance for colorectal liver metastases in the era of modern chemotherapy and surgery

Background: Historically, microscopically incomplete R1 resections have been associated with increased recurrence and lower survival rates for colorectal liver metastases (CLMs). With advances in chemotherapy, there is a shift towards a more aggressive surgical approach towards liver resection for CLMs. Recent studies have questioned the prognostic significance of obtaining complete surgical margin clearance. This study aims to compare R0 and R1 resections on oncologic outcomes. Methods: From January 2001 to December 2016, all patients who had liver resection for CLM at Singapore General Hospital were analysed retrospectively. Patients with extrahepatic metastases, macroscopic residual tumour and staged liver resections were excluded. Results: Of the 290 patients analysed, 228 (78.6%) and 62 (21.4%) patients underwent R0 and R1 resection respectively. R1 resections were associated with bilobar, multiple and synchronous liver metastases, major liver resections and adjuvant chemotherapy. Independent factors of poor overall and recurrence free-survival were primary colorectal tumour grade, presence of perineural invasion, nodal status, carcinoembryonic antigen (CEA) levels, number and size of liver metastases. R1 resection was likely associated with local intrahepatic recurrence. (HR: 0.74, 95% CI = 0.5 - 1.09, p = 0.122) However, on multivariate survival analysis, it was not an independent predictor for overall and recurrence free survival. Conclusion: Underlying tumour biology is a strong predictor of oncologic outcomes. The prognostic impact of R1 resection should be reviewed given that survival is similar to R0 resection in this current era of chemotherapy.

Preoperative Chemotherapy on Functional Liver Regeneration for Colorectal Liver Metastases Assessed With 99mTc-GSA SPECT/CT Imaging

Objective:To investigate the functional liver regeneration after chemotherapy and liver resection for colorectal liver metastases (CRLM).Background/Purpose:Preoperative chemotherapy followed by liver resection for CRLM has been increasing; however, its negative impact on liver regeneration remains unknown.Methods:From January 2009 to December 2013, we enrolled 40 selected patients who underwent major hepatectomy without viral hepatitis and severe liver fibrosis. CRLM patients with preoperative chemotherapy (CT-CRLM group, n = 12) and patients without preoperative chemotherapy (control group, n = 28) were evaluated. Liver volume (LV) and functional liver volume (FLV) was assessed using Tc-99m–labeled galactosyl human serum albumin (99mTc-GSA) scintigraphy, single-photon emission computed tomography (SPECT), CT-fused images. Preoperative, future remnant liver, and post 1-month values were compared.Results:Median course of preoperative chemotherapy was 8 (range: 6–16). Preoperative background factors were almost identical including resection rate and functional resection rate. In the CT-CRLM group and in the control group, the percentage increases in LV were 39.3% ± 29.0% and 23.2% ± 23.5% (P = 0.037), and FLV were 79.4% ± 43.1% and 57.0% ± 33.4% (P = 0.417), respectively; absolute differences in LV were 216.2 ± 155.7 cm3 and 148.7 ± 134.7 cm3 (P = 0.086) and FLV were 19.4% ± 8.5%/m2 and 17.4% ± 7.9%/m2 (P = 0.235), respectively. We found no obvious tendency for negative influence on liver functional regeneration by the preoperative regimens for CRLM.Conclusions:Several courses of preoperative chemotherapy may not affect functional liver regeneration for CRLM patients after major hepatectomy.