Number Of Colorectal Liver Metastases Research Articles

Prediction of remnant liver volume using 3D simulation software in patients undergoing R1vasc parenchyma-sparing hepatectomy for multiple bilobar colorectal liver metastases: reliability, clinical impact, and learning curve

BackgroundAssessment of the future liver remnant (FLR) is routinely performed before major hepatectomy. In R1-vascular one-stage hepatectomy (R1vasc-OSH), given the multiplanar dissection paths, the FLR is not easily predictable. Preoperative 3D-virtual casts may help. We evaluated the predictability of the FLR using the 3D-virtual cast in the R1vasc-OSH for multiple bilobar colorectal liver metastases (CLM). MethodsThirty consecutive patients with multiple bilobar CLMs scheduled for R1vasc-OSH were included. Predicted and real-FLRs were compared. Propensity score-matched analysis was used to determine the impact of 3D-virtual cast on postoperative complications. ResultsMedian number of CLM and resection areas were 12 (4–33) and 3 (1–8). Median predicted-FLR was 899 ml (558–1157) and 60% (42–85), while for the real-FLR 915 ml (566–1777) and 63% (43–87). Median discrepancy between predicted and real-FLR was −0.6% (p = 0.504), indicating a slight tendency to underestimate the FLR. The difference was more evident in more than 12 CLMs (p = 0.013). A discrepancy was not evident according to the number of resection areas (p = 0.316). No mortality occurred. Patients in virtual-group had lower major complications compared to nonvirtual-group (0% vs 18%, p-value 0.014). ConclusionFLR estimation based on 3D-analysis is feasible, provides a safe surgery and represents a promising method in planning R1vasc-OSH for patients with multiple bilobar CLMs.

Risk Factors for Overall and Disease Free Survival in Those Patients with Multiple Colorectal Liver Metastases in the Era of Target Therapy

Purpose: Although,the number of colorectal liver metastases (CRLM) is decreasingly considered as contraindication to surgery, most of the scores still include the number of lesions (GAME score, Tumor Burden Score) as one of main predictors of worst overall survival.This study aimed to evaluate the outcome after liver surgery of those patients with 5 or more lesions and to identify prognostic factors for survival in such group of patients. Methods: The study population consisted of an european unicentre cohort of patients with CRLM operated from January 2010 to December 2019 and whose data were prospectively collected in the LivermetSurvey registry after Ethics Committee aproval. An univariate and multivariate analyses was performed to identify the risk factors associated with overall and disease free survival in those patients with ≥5 lesions at diagnoses. Results: We included 250 patients of whom 54 patients had ≥5 lesions.The main characteristics of this group: right side primary tumor in 22%, stage N positive of primary tumor in 65%, CEA level at diagnoses in 16.8ng/mL (0.5-2,933), synchronous disease in 78%, KRAS and BRAF mutation 43% and 4%, GAME Score≥4 in 22% and preoperative chemotherapy 91% of whom targeted therapy was administered in 50% of the patients. The median overall survival (OS) and disease free survival (DFS) in this group was 25 months (4-108) and 10 months (0-103) respectively. Multivariate analyses showed that the primary tumor stage N positive (HR=3.41) and right side primary tumor (HR= 1.93) emerged as the strongest risk factor for OS. Regarding DFS, R1 resection (HR=3.09), right side primary tumor (HR=1.88) and KRAS mutation (HR= 1.56) were the main risk factors. The model demonstrated that a median of 30 months of OS could be achieved in selected cases and more than 16 months of DSF was possible providing R0 resection associated with at least an more additional favorable factor. Conclusions: Multiple CRLM is an important factor with impact in long-term survival however longer OS and DFS could be achieved in selected cases.

Hospital variation in combined liver resection and thermal ablation for colorectal liver metastases and impact on short-term postoperative outcomes: a nationwide population-based study

BackgroundCombining resection and thermal ablation can improve short-term postoperative outcomes in patients with colorectal liver metastases (CRLM). This study assessed nationwide hospital variation and short-term postoperative outcomes after combined resection and ablation. MethodsIn this population-based study, all CRLM patients who underwent resection in the Netherlands between 2014 and 2018 were included. After propensity score matching for age, ASA-score, Charlson-score, diameter of largest CRLM, number of CRLM and earlier resection, postoperative outcomes were compared. Postoperative complicated course (PCC) was defined as discharge after 14 days or a major complication or death within 30 days of surgery. ResultsOf 4639 included patients, 3697 (80%) underwent resection and 942 (20%) resection and ablation. Unadjusted percentage of patients who underwent resection and ablation per hospital ranged between 4 and 44%. Hospital variation persisted after case-mix correction. After matching, 734 patients remained in each group. Hospital stay (median 6 vs. 7 days, p = 0.011), PCC (11% vs. 14.7%, p = 0.043) and 30-day mortality (0.7% vs. 2.3%, p = 0.018) were lower in the resection and ablation group. Differences faded in multivariable logistic regression due to inclusion of major hepatectomy. ConclusionSignificant hospital variation was observed in the Netherlands. Short-term postoperative outcomes were better after combined resection and ablation, attributed to avoiding complications associated with major hepatectomy.

Alteration of FBXW7 is Associated with Worse Survival in Patients Undergoing Resection of Colorectal Liver Metastases

BackgroundFor patients undergoing resection of colorectal liver metastases (CLMs), the prognostic role of somatic gene alterations is increasingly recognized. F-box/WD repeat–containing protein 7 (FBXW7) is a tumor suppressor gene found in approximately 10% of patients with colorectal cancer. The aim of this study is to assess the association of FBXW7 with overall survival after CLM resection. MethodsPatients who underwent initial CLM resection during 2001–2016 and had genetic sequencing data were studied. Risk factors for overall survival (OS) were evaluated with Cox proportional hazards models using backward elimination. ResultsOf 2045 patients who underwent CLM resection during the study period, 476 were included. The majority (90.5%) underwent prehepatectomy chemotherapy. A total of 27 patients (5.7%) had FBXW7 alteration, along with 240 (50.4%) RAS, 337 (70.8%) TP53, 51 (10.7%) SMAD4, and 27 (5.7%) BRAF. Cox proportional hazards model analyses including 5 somatic gene alteration status and 12 clinicopathologic factors revealed FBXW7(hazard ratio [HR] 1.99, P = 0.015), BRAF (HR 2.47, P = 0.023), RAS (HR 2.42, P < 0.001), TP53 (HR 2.00, P < 0.001), and SMAD4 alterations (HR 1.90, P = 0.004) as significantly associated with OS, together with three clinicopathologic factors, prehepatectomy chemotherapy > 6 cycles (HR 1.51, P = 0.021), number of CLM (HR 1.05, P = 0.007), and largest liver metastasis diameter (HR 1.07, P = 0.023). The covariate-adjusted 5-year OS was significantly lower in patients with FBXW7 alteration than in patients with FBXW7 wild-type (40.4% vs.59.4%, P = 0.015). ConclusionsFBXW7 alterations are associated with worse survival after CLM resection. The information on multiple somatic gene alterations is imperative for risk stratification and patient selection for CLM resection.

Factors Associated With Local Tumor Control and Complications After Thermal Ablation of Colorectal Cancer Liver Metastases: A 15-year Retrospective Cohort Study

IntroductionThe purpose of this study was to identify risk factors associated with local tumor progression-free survival (LTPFS) and complications after colorectal liver metastases (CLM) thermal ablation (TA). Patients and MethodsThis retrospective analysis included 286 patients with 415 CLM undergoing TA (radiofrequency and microwave ablation) in 378 procedures from January 2003 to July 2017. Prior hepatic artery infusion (HAI), bevacizumab, pre-existing biliary dilatation, ablation modality, minimal ablation margin (MM), prior hepatectomy, CLM number, and size were analyzed as factors influencing complications and LTPFS. Statistical analysis included the Kaplan-Meier method, Cox proportional hazards model, competing risk analysis, univariate/multivariate logistic/exact logistic regressions, and the Fisher exact test. Complications were reported according to modified Society of Interventional Radiology guidelines. ResultsThe median follow-up was 31 months. There was no LTP for MM > 10 mm. Smaller tumor size, increased MM, and prior hepatectomy correlated with longer LTPFS. The major complications occurred following 28 (7%) of 378 procedures. There were no biliary complications in HAI-naive patients, versus 11% in HAI patients (P < .001), of which 7% were major. Biliary complications predictors in HAI patients included biliary dilatation, bevacizumab, and MM > 10 mm. In HAI patients, ablation with 6 to 10 mm and > 10 mm MM resulted in major biliary complication rates of 4% and 21% (P = .0011), with corresponding LTP rates of 24% and 0% (P = .0033). In HAI-naive patients, the LTP rates for 6 to 10 mm and > 10 mm MM were 27% and 0%, respectively. ConclusionsNo LTP was seen for MM > 10 mm. Biliary complications occurred only in HAI patients, especially in those with biliary dilatation, bevacizumab, and MM > 10 mm. In HAI patients, MM of 6 to 10 mm resulted in 76% local tumor control and 4% major biliary complications incidence.

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.

Implementation of a Hepatic Artery Infusion Program: Initial Patient Selection and Perioperative Outcomes of Concurrent Hepatic Artery Infusion and Systemic Chemotherapy for Colorectal Liver Metastases.

Hepatic artery infusion (HAI) combined with systemic chemotherapy is a treatment strategy for patients with unresectable liver-only or liver-dominant colorectal liver metastases (CRLM). Although HAI has previously been performed in only a few centers, this study aimed to describe patient selection and initial perioperative outcomes during implementation of a new HAI program. The study enrolled patients with CRLM selected for HAI after multi-disciplinary review November 2018-January 2020. Demographics, prior treatment, and perioperative outcomes were assessed. Objective hepatic response was calculated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. During a 14-month period, 21 patients with CRLM underwent HAI pump placement. Of these 21 patients, 20 (95%) had unresectable disease. Most of the patients had synchronous disease (n = 18, 86%) and had received prior chemotherapy (n = 20, 95%) with extended treatment cycles (median 16; interquartile range, 8-22; range, 0-66). The median number of CRLMs was 7 (range, 2-40). Operations often were performed with combined hepatectomy (n = 4, 19%) and/or colectomy/proctectomy (n = 11, 52%). The study had no 90-day mortality. The overall surgical morbidity was 19%. The HAI-specific complications included pump pocket seroma (n = 2), hematoma (n = 1), surgical-site infection (n = 1), and extrahepatic perfusion (n = 1). HAI was initiated in 20 patients (95%). The hepatic response rates at 3months included partial response (n = 4, 24%), stable disease (n = 9, 53%), and progression of disease (n = 4, 24%), yielding a 3-month hepatic disease control rate (DCR) of 76%. Implementation of a new HAI program is feasible, and HAI can be delivered safely to selected patients with CRLM. The initial response and DCR are promising, even for patients heavily pretreated with chemotherapy.

Pros and Cons of Portal Vein Embolization With Hematopoietic Stem Cells Application in Colorectal Liver Metastases Surgery.

Portal vein embolization (PVE) with autologous stem cells application (aHSC) is a method for future liver remnant volume (FLRV) increase. The aim of the study was to evaluate the positivite and negativite aspects of the method in clinical practice. PVE with aHSC application was used in 32 patients with colorectal liver metastases and insufficient FLRV. Preoperative number of colorectal liver metastases (CLMs) was 5.2±3.6, CLMs volume 70.1±102.3 mm3 Results: FLRV growth occurred after 2-3 weeks in 31 (96.9%) patients, with volume increase from 528.2±170.5 to 715.4±143.3 ml (p=0.0001). Postoperative thirty days mortality, morbidity was 0% and 3.1%, respectively. Insufficient FLRV growth occurred in one patient. R0 liver resection was performed in 27(87.1%) patients. CLMs volume progression was in 5 (15.6%) patients from 680.0±59.4 to 723.1±57.1 ml (p=0.01). One and two-year overall survival were 88% and 62.9% respectively. Six and twelve-month recurrence-free survival rates were 50.7% and 39.6% respectively. PVE with aHSC application is a safe and useful method for FLRV growth. It significantly increases secondary CLMs resectability. However, it can cause CLMs progression. Liver resection should, therefore, be performed as soon as possible after achieving optimal increase of FLRV.

Long-term Results of Surgery for Colorectal Liver Metastases in Terms of Primary Tumour Location and Clinical Risk Factors.

The aim of the study was to evaluate the influence of primary tumour location and clinical risk factors for long-term results of surgery for colorectal liver metastases (CLMs). Overall survival (OS) and recurrence-free survival (RFS) were evaluated in 636 patients. Patients were divided by tumour location (right-/left-sided colorectal cancer: RCRC/LCRC; rectal cancer), and age, gender, number and size of CLMs, type of liver surgery and interval from primary operation were evaluated. One-, 3- and 5-year OS and RFS were independent of primary tumour location (p<0.59). CLM diameter was negatively associated with OS for the whole cohort (p<0.002), and RCRC (p<0.03) and LCRC (p<0.04) groups, as well as for RFS of those with LCRC (p<0.04). CLM number was negatively associated with RFS for the whole cohort (p<0.0001), RCRC (p<0.02), LCRC (p<0.0001) and RC (p<0.02). Radiofrequency ablation and combined procedures led to worse OS for the whole cohort (p<0.03), and to worse RFS for the whole cohort (p<0.0003) and for those with LCRC (p<0.03). A shorter interval between primary colorectal cancer surgery and CLMs procedure was risky for poor OS and RFS of patients with CLMs from RCRC (p<0.05), LCRC (p<0.05) and RC (p<0.02). Primary tumour location together with clinical risk factors are important for long-term results of surgery CLMs.

Failure to cure colorectal liver metastases patients quantified the impact of the liver surgical specialist

Presenter: Eduardo Vega MD | Saint Elizabeth's Medical Center, Tufts University Background: A multidisciplinary team that involves a liver surgical specialist (LSS) is a critical factor in providing optimal oncologic care for patients with colorectal liver metastases (CRLM). Lack of LSS may lead to a failure-to-cure in patients with possibly resectable CRLM. This study aimed to quantify the failure to cure rate due to non-inclusion of LSS Methods: All patients who underwent chemotherapy with palliative intent for CRLM at a community oncology network between 2014-2018 were identified from a prospectively maintained cancer registry. Two LSS blinded towards patient management and outcome, reviewed pretreatment imaging and assigned each scan a newly developed resectability score. Nominal Group Technique and independent scores were combined to determine feasibility of curative intent resection. Interobserver agreement was calculated with Kappa Statistic. Results: This study included 49 palliative CRLM patients. Demographic factors were: 29 (59%) male, median age 68 (IQR 58-75), 9 (18%) rectal primary, 22 (70%) receiving oxaliplatin-base chemotherapy. Of 45 (91%) with CRLM, 3 had left-sided metastases only. The median number of CRLM was 8 (IQR 2-8). Agreement on resectability was 21 patients (45%). A lower median number of CRLM was found in the group considered to be resectable by LSS (2 vs 8; p=0.001). Of those, 6 had lung metastases and 1 peritoneal carcinomatosis. Of the unresectable patients, 10 had unresectable lung metastases with associated mediastinal metastases, ovarian and peritoneal carcinomatosis or bone metastases. Substantial agreements was found between liver surgeons (Kappa=0.814). Conclusion: Almost fifty percent of patients with tumors deemed unresectable by non-LSS providers were considered potentially resectable upon independent liver surgeon review. Despite the rapid evolution of the systemic treatment for CRLM, inclusion of a LSS may result in the highest immediate impact on cure rate. Mandatory inclusion of LSS, akin to other countries, may significantly impact survival of patients with 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.

Histopathological growth patterns and positive margins after resection of colorectal liver metastases

BackgroundHistopathological growth patterns (HGPs) of colorectal liver metastases (CRLM) may be an expression of biological tumour behaviour impacting the risk of positive resection margins. The current study aimed to investigate whether the non-desmoplastic growth pattern (non-dHGP) is associated with a higher risk of positive resection margins after resection of CRLM. MethodsAll patients treated surgically for CRLM between January 2000 and March 2015 at the Erasmus MC Cancer Institute and between January 2000 and December 2012 at the Memorial Sloan Kettering Cancer Center were considered for inclusion. ResultsOf all patients (n = 1302) included for analysis, 13% (n = 170) had positive resection margins. Factors independently associated with positive resection margins were the non-dHGP (odds ratio (OR): 1.79, 95% confidence interval (CI): 1.11–2.87, p = 0.016) and a greater number of CRLM (OR: 1.15, 95% CI: 1.08–1.23 p < 0.001). Both positive resection margins (HR: 1.41, 95% CI: 1.13–1.76, p = 0.002) and non-dHGP (HR: 1.57, 95% CI: 1.26–1.95, p < 0.001) were independently associated with worse overall survival. ConclusionPatients with non-dHGP are at higher risk of positive resection margins. Despite this association, both positive resection margins and non-dHGP are independent prognostic indicators of worse overall survival.

84P - Comprehensive evaluation of relapse risk (CERR) score for colorectal liver metastases development and validation

BackgroundTo modify the tumor burden score (TBS) and to develop a comprehensive and practical prognostic scoring system among Chinese patients with colorectal liver metastases (CRLM). Methods787 adult patients who underwent curative-intent liver resection for CRLM were identified from Zhongshan Hospital in Shanghai, China between June 2010 and January 2018. Tumor relapse-free survival (RFS) was the main outcomes. TBS was modified with geometric algorithms. The Cox regression model was used to identify independent predictors of prognosis. Time-dependent AUC, calibration curve, and C-index were employed to validate the predictive ability of a survival model. ResultsModified TBS (mTBS) was established by a mathematical equation (parameters were CRLM size, CRLM number, and unilobar/bilobar metastasis). mTBS model (AUC=0.62 at 33 Month) out-performed TBS model (AUC=0.54 at 33 Month) in predicting RFS (P=.002). Five preoperative predictors of worse RFS were identified and were incorporated into CERR score: KRAS/NRAS/BRAF mutated tumor (score 1 point); node-positive primary (1 point); extrahepatic disease (1 point); CEA level >200 ng/ml or CA 19-9 >200 U/mL (1 point); mTBS between 5 and 11 (1 point) or 12 and over (2 points). Patients undergoing hepatectomy for CRLM were stratified by CERR score into risk groups: high-risk group (CERR score 4 or more) had a 3-year RFS rate of 9.77%; medium-risk group (CERR score 2-3) had a 3-year RFS rate of 21.96%; low-risk group (CERR score 0-1) had a 3-year RFS rate of 39.90%. The CERR score model was further validated using internal bootstrap validation, and the discriminatory capacity of the CERR score was significantly superior to that of the Fong score and that of the Genetic and Morphological Evaluation (GAME) score. ConclusionsModified TBS should be promoted. The CERR score is a powerful prognostic tool that can help to determine the optimal clinical management strategies. Legal entity responsible for the studyZhongshan Hospital. FundingThe National Natural Science Foundation of China. DisclosureAll authors have declared no conflicts of interest.

563P - Comprehensive evaluation of recurrence risk (CERR) score for colorectal liver metastases: Development and validation

BackgroundFor colorectal liver metastases (CRLM), some key prognostic factors— KRAS/NRAS/BRAF, location of primary tumor, and CA19-9—were identified for recurrence and survival but were rarely included in prognostic scoring system analysis. Besides, tumor burden score (TBS) is a prognostic indicator capturing the cumulative impact CRLM size and CRLM number, but TBS does not take spatial factor—unilobar or bilobar metastasis—into account. Methods787 patients undergoing hepatic resection of CRLM were included and were divided into training and validation groups. Modified TBS (mTBS) was established by a mathematical equation (parameters were CRLM size, CRLM number, and unilobar/bilobar metastasis). In the training group, the Cox proportional hazards model was used to identify independent predictors of prognosis; these factors were combined into the Comprehensive Evaluation of Recurrence Risk (CERR) score. The score was compared with Fong score and “Genetic and Morphological Evaluation” (GAME) score and validated in the validation group. Some indices (including C-index, iAUC, Akaike information criterion, net reclassification index, and integrated discrimination improvement) were calculated to compare the discriminatory capacities of three prognostic scoring systems. ResultsmTBS (AUC 0.617) out-performed TBS (AUC 0.568) in predicting recurrence-free survival (RFS) (P=0.006). Five preoperative predictors of worse RFS were identified and were incorporated into CERR score: KRAS/NRAS/BRAF mutated tumor (1 point); node-positive primary (1 point); extrahepatic disease (1 point); CEA >200ng/ml or CA19-9 >200U/mL (1 point); mTBS between 5 and 11 (1 point) or 12 and over (2 points). Patients undergoing hepatectomy for CRLM were stratified by CERR score into risk groups: high-risk group (CERR score 4 or more) had a 3-year RFS rate of 9.77%; medium-risk group (CERR score 2-3) had a 3-year RFS rate of 21.96%; low-risk group (CERR score 0-1) had a 3-year RFS rate of 39.90%. The validation group showed that the discriminatory capacity of the CERR score was superior to that of the Fong score and the GAME score. ConclusionsThe CERR score is a prognostic tool that can be used to determine optimal clinical management strategies. Legal entity responsible for the studyZhongshan Hospital, Fudan University, Shanghai, China. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Intraoperative Ultrasound Staging for Colorectal Liver Metastases in the Era of Liver-Specific Magnetic Resonance Imaging: Is It Still Worthwhile?

Background To assess the efficacy of intraoperative ultrasound (IOUS) compared with liver-specific magnetic resonance imaging (MRI) in patients with colorectal liver metastases (CRLMs). Methods From January 2010 to December 2017, 721 patients underwent MRI as a part of preoperative workup within 1 month before hepatectomy and were considered for the study. Early intrahepatic recurrence (relapse at cut surface excluded) was assessed 6 months after the resection and was considered as residual disease undetected by IOUS and/or MRI. IOUS and MRI performance was compared on a patient-by-patient basis. Long-term results were also studied. Results A total of 2845 CRLMs were detected by MRI, and the median number of CRLMs per patient was 2 (1–31). Preoperative chemotherapy was administered in 489 patients (67.8%). In 177 patients, 379 new nodules were intraoperatively found and resected. Among 379 newly identified nodules, 317 were histologically proven CRLMs (11.1% of entire series). The median size of new CRLMs was 6 ± 2.5 mm. Relationships between intrahepatic vessels and tumors differed between IOUS and MRI in 128 patients (17.7%). The preoperative surgical plan was intraoperatively changed for 171 patients (23.7%). Overall, early intrahepatic recurrence occurred in 8.7% of cases. To assess the diagnostic performance, 24 (3.3%) recurrences at the cut surface were excluded; thus, 5.4% of early relapses were considered for analysis. The sensitivity of IOUS was superior to MRI (94.5% vs 75.1%), while the specificity was similar (95.7% vs 95.9%). Multivariate analysis at the hepatic dome or subglissonian and mucinous histology revealed predictive factors of metastases missing at MRI. The 5-year OS (52.1% vs 37.8%, p=0.006) and DF survival (45.1% vs 33%, p=0.002) were significantly worse among patients with new CRLMs than without. Conclusions IOUS improves staging in patients undergoing resection for CRLMs even in the era of liver-specific MRI. Intraoperative detection of new CRLMs negatively affects oncologic outcomes.

The Disease-Free Interval Between Resection of Primary Colorectal Malignancy and the Detection of Hepatic Metastases Predicts Disease Recurrence But Not Overall Survival

IntroductionThe disease-free interval (DFI) between resection of primary colorectal cancer (CRC) and diagnosis of liver metastases is considered an important prognostic indicator; however, recent analyses in metastatic CRC found limited evidence to support this notion.ObjectiveThe current study aims to determine the prognostic value of the DFI in patients with resectable colorectal liver metastases (CRLM).MethodsPatients undergoing first surgical treatment of CRLM at three academic centers in The Netherlands were eligible for inclusion. The DFI was defined as the time between resection of CRC and detection of CRLM. Baseline characteristics and Kaplan–Meier survival estimates were stratified by DFI. Cox regression analyses were performed for overall (OS) and disease-free survival (DFS), with the DFI entered as a continuous measure using a restricted cubic spline function with three knots.ResultsIn total, 1374 patients were included. Patients with a shorter DFI more often had lymph node involvement of the primary, more frequently received neoadjuvant chemotherapy for CRLM, and had higher number of CRLM at diagnosis. The DFI significantly contributed to DFS prediction (p =0.002), but not for predicting OS (p =0.169). Point estimates of the hazard ratio (95% confidence interval) for a DFI of 0 versus 12 months and 0 versus 24 months were 1.284 (1.114–1.480) and 1.444 (1.180–1.766), respectively, for DFS, and 1.111 (0.928–1.330) and 1.202 (0.933–1.550), respectively, for OS.ConclusionThe DFI is of prognostic value for predicting disease recurrence following surgical treatment of CRLM, but not for predicting OS outcomes.

Outcomes of enhanced one-stage ultrasound-guided hepatectomy for bilobar colorectal liver metastases compared to those of ALPPS: a multicenter case-match analysis

BackgroundIn case of bilobar colorectal liver metastases (CLM) associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been proposed. Enhanced one-stage ultrasound-guided hepatectomy (e-OSH) may represent a further solution for these patients. Aim of this study was to compare by case-match analyses the outcome of ALPPS and e-OSH. MethodsBetween 2012 and 2017, patients undergoing ALPPS for bilobar CLM were matched 1:2 with patients receiving e-OSH. Patients were matched according to the Fong Score (1–3/4–5), the number of CLM (3–7/≥8), the number of CLM in the left liver (1–2/≥3) and preoperative chemotherapy. All the patients in the e-OSH group had a right -sided major vascular contact. The main endpoints of the study were perioperative outcomes, overall (OS) and disease-free survival (DFS). ResultsSeventy-eight patients were selected (26 ALPPS and 52 e-OSH) based on matching process. The two treatments differed significantly in major morbidity (26.9% ALPPS vs 7.7% e-OSH, p = 0.017). Median OS (31.7 vs 32.6 months) and DFS (10.6 vs 7.8 months) were comparable between the two groups. ConclusionsThis study demonstrates that ALPPS and e-OSH for bilobar CLM achieve comparable long-term results, despite higher morbidity reported after ALPPS. These findings should drive to reposition e-OSH in managing these patients.

Contrast-enhanced intra-operative ultrasound as a clinical decision making tool during surgery for colorectal liver metastases: The ULIIS study

BackgroundDetecting more colorectal liver metastases (CRLMs) during surgery may help optimise strategy and improve outcomes. Our objective was to determine clinical utility (CU) of contrast-enhanced intra-operative ultrasound (CE-IOUS) using sulphur hexafluoride microbubbles during CRLM surgery. MethodA prospective phase II trial performed at two comprehensive cancer research centres. Patients operated for CRLMs were eligible and assessable if intra-operative ultrasound (IOUS) and CE-IOUS had been performed and pathological results were available and/or 3-month imaging. CU was defined as the justified change in planned surgical strategy or procedure using CE-IOUS. ResultsOut of the 68 patients enrolled, 54 were eligible and assessable. 43 patients underwent pre-operative chemotherapy. The median number of CRLMs was 2 (range, 1–11). Pre-operative staging was performed using MRI. IOUS allowed identification of 45 new CRLMs in 13 (24.7%) patients. Compared to IOUS, CE-IOUS allowed identification of 10 additional CRLMs in 9 (16.7%) patients. Surgery was altered and justified in 4 patients only, leading to a CU rate of 7.70% (95 CI, [3.2, 18.6]). No missing CRLMs were identified by CE-IOUS. ConclusionsAlthough the primary endpoint was not met for one protocol violation, secondary endpoints indicate that CE-IOUS has an intermediate added-value for surgeons treating CRLMs. Trial registrationNCT01880554 (https://clinicaltrials.gov/).

Outcomes of ALPPS for bilateral colorectal liver metastases compared to those of one-stage parenchymal sparing hepatectomy: a multicenter case-match analysis

Introduction: About 30% of patients with colorectal liver metastases (CRLM) are not initially resectable due to the extent of hepatic disease. When the future liver remnant (FLR) is regarded to be not sufficient, classic two stage hepatectomy or associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) can be performed to get increase of the FLR. One-stage ultrasound-guided parenchymal-sparing hepatectomy (OSH) may represent an alternative strategy for these patients. Method: A retrospective analysis of patients enrolled within the ALPPS Italian Registry between 2005 and 2017 was performed. Patients undergoing ALPPS for ≥3 bilateral CRLM were matched 1:2 with patients receiving a OSH at Humanitas Research Hospital. Patients were matched according to the Fong Score (1-2/3/4-5); the contact of CRLM with major intrahepatic vessels; the number of CRLM (3-7/≥8); the number of CRLM in the left liver (< /≥3); and the response to preoperative chemotherapy. The main end points of the study were perioperative outcomes, overall (OS) and disease-free survival (DFS). Results: Eighty-one patients were selected (27 ALPPS and 54 OSH) based on matching process. Demographic and tumor characteristics were similar between the two groups. The two treatments differed significantly in major morbidity (29.6% ALPPS vs 7.4% OSH, p=0.017) but with similar mortality rate (7.4% vs 1.8%, p=0.256). Median OS (31.7 vs 31.4 months) and DFS (7.2 vs 7.3 months) were comparable between the two groups. Conclusions: This case-match study demonstrates that ALPPS and OSH for bilateral CRLM achieve comparable OS and DFS, despite higher morbidity rates reported after ALPPS.

Prospective Evaluation of Intrahepatic Microscopic Occult Tumor Foci in Patients with Numerous Colorectal Liver Metastases

Background: Patients with numerous colorectal liver metastases (CLM) have high risk of early recurrence after liver resection (LR). The presence of intrahepatic occult microscopic metastases missed by imaging has been hypothesized, but it has never been assessed by pathology analyses. Methods: All patients with > 10 CLM who underwent LR between September 2015 and September 2016 were considered. A large sample of liver without evidence of disease (“healthy liver”) was taken from the resected specimen and sent to the pathologist. One mm-thick sections were analyzed. Any metastasis, undetected by preoperative and intraoperative imaging, but identified by the pathologist was classified as occult microscopic metastasis. Results: Ten patients were prospectively enrolled (median number of CLM n = 15). In a per-lesion analysis, the sensitivity of computed tomography and magnetic resonance imaging was 91 and 98% respectively. The pathology examination confirmed all the CLM. All patients had an adequate sample of “healthy liver” (median number of examined blocks per sample n = 14 [5–33]). No occult microscopic metastases were detected. After a median follow-up of 15 months, 5 patients were disease-free. Recurrence was hepatic and bilobar in all patients. Conclusions: Clinically relevant occult microscopic disease in patients with numerous CLM is excluded. These results support the indication to resection in such patients and exclude the need for de principe major hepatectomy to increase the completeness of surgery.