Resection Of Colorectal Liver Metastases Research Articles

Liver Resection With Extrahepatic Disease: A Population-Based Analysis of Thoughtful Selection.

The oncologic benefit of liver resection for colorectal liver metastases (CRLM) in the setting of concurrent extrahepatic disease (EHD) is controversial. We performed a population-based, cross-sectional study to determine the practice patterns and overall survival (OS) of patients with CRLM + EHD who underwent liver resection. Patients with CRLM + EHD were identified using the California Cancer Registry from 2000 to 2019. Records were linked to the Office of Statewide Health Planning Inpatient Database. Patient demographics, clinical characteristics, and survival were compared between CRLM + EHD patients with and without liver resection. Of 170 978 patients with CRLM, 62 003 (36%) had concurrent EHD (CRLM + EHD). In all, 3736 (6%) of CRLM + EHD underwent liver resection compared to 22% of patients with liver limited CRLM. Compared to CRLM + EHD without liver resection, CRLM + EHD with resection were younger, had fewer comorbidities, received higher frequencies of perioperative chemotherapy, and were more likely to have only a single site of EHD rather than multiple sites. Median OS was significantly higher for CRLM + EHD with resection compared to without (52 vs. 27 months, HR 0.46 [95% CI 0.44-0.47], p < 0.001). Regarding the location of EHD, this survival benefit was observed with liver resection for lung, peritoneal, intraabdominal lymph nodes, ovarian, and bone metastases. In a large population-based setting, subsets of CRLM + EHD patients that undergo liver resection are associated with prolonged survival. These results support surgery with thoughtful patient selection to optimize survival outcomes in this population.

Preoperative identification of early extrahepatic recurrence after hepatectomy for colorectal liver metastases: A machine learning approach.

Machine learning (ML) may provide novel insights into data patterns and improve model prediction accuracy. The current study sought to develop and validate an ML model to predict early extra-hepatic recurrence (EEHR) among patients undergoing resection of colorectal liver metastasis (CRLM). Patients with CRLM who underwent curative-intent resection between 2000 and 2020 were identified from an international multi-institutional database. An eXtreme gradient boosting (XGBoost) model was developed to estimate the risk of EEHR, defined as extrahepatic recurrence within 12months after hepatectomy, using clinicopathological factors. The relative importance of factors was determined using Shapley additive explanations (SHAP) values. Among 1410 patients undergoing curative-intent resection, 131 (9.3%) patients experienced EEHR. Median OS among patients with and without EEHR was 35.4months (interquartile range [IQR] 29.9-46.7) versus 120.5months (IQR 97.2-134.0), respectively (p<0.001). The ML predictive model had c-index values of 0.77 (95% CI, 0.72-0.81) and 0.77 (95% CI, 0.73-0.80) in the entire dataset and the validation data set with bootstrapping resamples, respectively. The SHAP algorithm demonstrated that T and N primary tumor categories, as well as tumor burden score were the three most important predictors of EEHR. An easy-to-use risk calculator for EEHR was developed and made available online at: https://junkawashima.shinyapps.io/EEHR/. An easy-to-use online calculator was developed using ML to help clinicians predict the chance of EEHR after curative-intent resection for CRLM. This tool may help clinicians in decision-making related to treatment strategies for patients with CRLM.

Comparing Open, Laparoscopic and Robotic Liver Resection for Metastatic Colorectal Cancer-A Systematic Review and Network Meta-Analysis.

Colorectal liver metastases (CRLM) can be surgically managed through open resections (OLR), laparoscopic resections (LLR), or robotic liver resections (RLR). However, there is ongoing uncertainty regarding the safety and effectiveness of minimally invasive approaches like LLR and RLR. This study aims to clarify these issues by conducting a network meta-analysis (NMA) to compare outcomes across OLR, LLR and RLR for patients with CRLM. Following the PRISMA-NMA guidelines, the meta-analysis included 13 studies with a combined total of 6582 patients. Of these, 50.6% underwent LLR, 45.3% underwent OLR, and 4.1% underwent RLR. The analysis found no significant differences in R0 resection rates between LLR (odds ratio [OR] 1.03, 95% confidence interval [CI]: 0.84-1.26) and RLR (OR 1.57, 95% CI: 0.98-2.51) when compared to OLR. Additionally, there were no significant differences in disease-free survival (DFS) and overall survival (OS) at 1, 3, and 5 years. Despite these findings, both LLR and RLR were associated with reduced postoperative complication rates (RLR: OR 0.52, 95% CI: 0.32-0.86; LLR: OR 0.50, 95% CI: 0.37-0.68). However, patients undergoing LLR were more likely to require conversion to open surgery compared to those undergoing RLR (OR: 12.46, 95% CI: 2.64-58.67). Furthermore, RLR was associated with a reduced need for blood transfusions (OR: 0.13, 95% CI: 0.05-0.32), and LLR resulted in shorter hospital stays (mean difference: -6.66 days, 95% CI: -11.6 to -1.88 days). This study demonstrates the oncological safety of LLR and RLR approaches for CRLM relative to OLR, with enhanced perioperative outcomes anticipated following minimally invasive resections of CRLM.

Evaluating Combinations of Biological and Clinicopathologic Factors Linked to Poor Outcomes in Resected Colorectal Liver Metastasis: An External Validation Study.

Recent studies have suggested that certain combinations of KRAS or BRAF biomarkers with clinical factors are associated with poor outcomes and may indicate that surgery could be "biologically" futile in otherwise technically resectable colorectal liver metastasis (CRLM). However, these combinations have yet to be validated through external studies. We conducted a systematic search to identify these studies. The overall survival (OS) of patients with these combinations was evaluated in a cohort of patients treated at 11 tertiary centers. Additionally, the study investigated whether using high-risk KRAS point mutations in these combinations could be associated with particularly poor outcomes. The recommendations of four studies were validated in 1661 patients. The first three studies utilized KRAS, and their validation showed the following median and 5-year OS: (1) 30 months and 16.9%, (2) 24.3 months and 21.6%, and (3) 46.8 months and 44.4%, respectively. When analyzing only patients with high-risk KRAS mutations, median and 5-year OS decreased to: (1) 26.2 months and 0%, (2) 22.3 months and 15.1%, and (3) not reached and 44.9%, respectively. The fourth study utilized BRAF, and its validation showed a median OS of 10.4 months, with no survivors beyond 21 months. The combinations of biomarkers and clinical factors proposed to render surgery for CRLM futile, as presented in studies 1 (KRAS high-risk mutations) and 4, appear justified. In these studies, there were no long-term survivors, and survival was similar to that of historic cohorts with similar mutational profiles that received systemic therapies alone for unresectable disease.

New definition of borderline resectable colorectal liver metastasis based on prognostic outcomes.

Although surgical resection is the curative treatment for colorectal liver metastases (CRLM), the efficacy of neoadjuvant chemotherapy (NAC) has been discussed due to recent remarkable advances in chemotherapy. The definition of borderline resectable (BR) is most important, where neoadjuvant chemotherapy should be administered. This study aimed to examine a new definition of BR CRLM based on the results of the treatment outcomes. This study included 127 patients who underwent liver resection for CRLM after exclusion of conversion cases between April 2010 and December 2023. Upfront resection was performed for synchronous and single liver metastasis or metachronous liver metastases. NAC was administered for multiple synchronous liver metastases. In order to find a new definition of BR, we examined the prognostic factors obtained from the treatment outcomes. CA19-9 level > 37.0 was the only prognostic factor in the upfront group [hazard ratio (HR) 2.386, 95% CI, 1.583-4.769; p = 0.049]. in the NAC group, a maximum tumor diameter ˃3 cm (HR 2.248, 95% CI 1.038-4,867, p = 0.040), CA19-9 level > 37.0 (HR 2.239, 95% CI 1.044-4.800, p = 0.038), and a right-sided primary tumor in the colon (HR 2.770, 95% CI 1.284-5.988, p = 0.009) were identified as significant prognostic factors. In cases of CRLM, patients with CA19-9 levels > 37.0, or CA19-9 level with < 37.0 but with a primary tumor in the right colon or a maximum tumor diameter of > 3cm can be defined as BR CRLM and should be treated with NAC.

Computed Tomography-Based Radiomics with Machine Learning Outperforms Radiologist Assessment in Estimating Colorectal Liver Metastases Pathologic Response After Chemotherapy.

This study was designed to assess computed tomography (CT)-based radiomics of colorectal liver metastases (CRLM), extracted from posttreatment scans in estimating pathologic treatment response to neoadjuvant therapy, and to compare treatment response estimates between CT-based radiomics and radiological response assessment by using RECIST 1.1 and CT morphologic criteria. Patients who underwent resection for CRLM from January 2003-December 2012 at a single institution were included. Patients who did not receive preoperative systemic chemotherapy, or without adequate imaging, were excluded. Imaging characteristics were evaluated based on RECIST 1.1 and CT morphologic criteria. A machine-learning model was designed with radiomic features extracted from manually segmented posttreatment CT tumoral and peritumoral regions to identify pathologic responders (≥ 50% response) versus nonresponders. Statistical analysis was performed at the tumor level. Eighty-five patients (median age, 62 years; 55 women) with 95 tumors were included. None of the subjectively evaluated imaging characteristics were associated with pathologic response (p > 0.05). Inter-reader agreement was substantial for RECIST categorical response assessment (K = 0.70) and moderate for CT morphological group response (K = 0.50). In the validation cohort, the machine learning model built with radiomic features obtained an area under the curve (AUC) of 0.87 and outperformed subjective RECIST assessment (AUC = 0.53, p = 0.01) and morphologic assessment (AUC = 0.56, p = 0.02). Radiologist assessment of oligometastatic CRLM after neoadjuvant therapy using RECIST 1.1 and CT morphologic criteria was not associated with pathologic response. In contrast, a machine-learning model based on radiomic features extracted from tumoral and peritumoral regions had high diagnostic performance in assessing responders versus nonresponders.

Proteogenomic Characterization of Early Intrahepatic Recurrence after Curative-Intent Treatment of Colorectal Liver Metastases.

Clinical and pathological factors are insufficient to accurately identify patients at risk of early recurrence after curative-intent treatment of colorectal liver metastases (CRLM). This study aimed to identify candidate prognostic proteogenomic biomarkers for early intrahepatic recurrence after curative-intent resection of CRLM. Patients diagnosed with intrahepatic recurrence within 6 months of liver resection were categorized as the "early recurrence" group, while those who achieved a recurrence-free status for 10 years were designated as "durable remission". Comprehensive genomic and proteomic profiling of fresh frozen samples from these prognostically distinct groups was performed using the TruSight Oncology 500 assay and label-free data-dependent acquisition liquid chromatography-mass spectrometry. Genetic alterations were identified in 117 of the 523 profiled genes in patients with early recurrence. The most common somatic mutations linked to early recurrence were TP53 (88%), APC (71%), KRAS (38%), and SMAD4 (21%). SMAD4 alterations were absent in samples from patients with a durable remission. Calponin-2, versican core protein, glutathione peroxidase 3, fibulin-5, and amyloid-β precursor protein were upregulated more than 2-fold in early recurrence. Exploratory analysis of these proteogenomic biomarkers suggests that SMAD4, calponin-2, and glutathione peroxidase 3 may have the potential to predict early recurrence, enabling improved prognostication and precision oncology in CRLM.

Resection of colorectal liver metastases with second-line aflibercept plus FOLFIRI: Results from the RESECTION prospective French cohort

AimTo evaluate R0/R1 resection rate in patients with colorectal liver metastases (CLM) treated with aflibercept plus FOLFIRI after failure of a prior oxaliplatin-based regimen in daily clinical practice. MethodsThis French, multicentre, prospective, observational cohort (NCT05178745) included patients with CLM (alone or predominant; up to 5 lung nodules <2 cm allowed) initiating aflibercept/FOLFIRI every 2 weeks per physician choice. Primary endpoint was R0/R1 resection rate. Secondary endpoints included overall survival (OS), progression-free survival (PFS), radiological and pathological responses, and safety. ResultsA total of 137 patients (median age 65 years, RAS/BRAF mutant 57%/9%) were enrolled at 22 French sites. CLM (median 4) were synchronous in 82%, bilobar in 71% and located in liver only in 54%. Overall, 17% of patients had R0/R1 resection (21% for patients with liver-only disease). A major pathological response per Blazer score was observed in 55% of resected patients, along with significantly longer OS (median 34.8 vs 9.1 months, p<0.0001) and PFS (median 11.4 vs 4.9 months, p<0.0001) compared to non-resected patients. Post-operative complications occurred in 17% of patients (all Dindo-Clavien grade I-II) with no post-operative deaths. Overall, 34% had grade ≥3 adverse events, mainly general health deterioration and diarrhea. ConclusionsResults suggest that aflibercept plus FOLFIRI, after failure of a prior oxaliplatin-based regimen, allows R0/R1 resection of CLM in almost 20% of patients with a major pathological response in most cases and a median OS prolonged by more than 3-fold versus non-resected patients.

Patterns of recurrence after curative intent hepatic resection for colorectal liver metastasis

BackgroundImproved surgical techniques and more intensive systemic therapy have increased the number of patients with oligometastatic colorectal cancer eligible for resection, but a significant percentage of these cases will ultimately recur. Furthermore, distinct recurrence patterns have been associated with different outcomes. MethodsData for 195 patients who underwent curative-intent colorectal liver metastasis (CRLM) resection between 2016 and 2022 at Johns Hopkins Hospital were retrospectively collected. Cox regression univariate and multivariate analyses identified features associated with survival outcomes. Association between risk factors and site of recurrences was conducted via logistic regression with initial recurrences grouped into intrahepatic-only, extrahepatic-only, and concurrent intra- and extrahepatic recurrence. ResultsThe 1- and 2-year recurrence-free survival (RFS) rates were 46% and 22%, respectively. The 1- and 2-year overall survival (OS) rates were 95% and 88%, respectively. The median OS was 71.7 months. Multivariate analysis identified age <60 years, N2 nodal status, R1 liver margin, and higher preoperative carcinoembryonic antigen as top prognostic factors for worse RFS. Additionally, patients with left-sided primary tumors had a higher risk of intrahepatic-only recurrence, whereas mutant KRAS was associated with a higher risk of extrahepatic recurrence with or without liver recurrence. ConclusionThese results from a recent cohort of patients treated with current standard-of-care therapies identify features associated with elevated risk and specific patterns of recurrence. These insights into CRLM recurrence patterns support a larger prospective study to identify subgroups of patients who may require additional therapies to prevent recurrence.

Classification of Neoadjuvant Therapy Response in Patients With Colorectal Liver Metastases Using Contrast-Enhanced Ultrasound—With Histological Pathology as the Gold Standard

ObjectiveTo evaluate the response to neoadjuvant therapy in patients with colorectal liver metastases (CRLMs) using ultrasound(US) and contrast-enhanced ultrasound(CEUS), with correction to the tumor regression grade (TRG) of pathological results. MethodsThis study included patients with resectable CRLMs admitted from February to December 2022. After at least 4 cycles neoadjuvant therapy, all the patients received US and CEUS examinations within two weeks before hepatectomy. CEUS clips were postprocessed with color parameter imaging (CPI) and microflow imaging (MFI) analysis. Logistic regression analyses were used to develop an evaluation Nomogram. Ultrasound-based model was constructed to discriminate between the response (TRG1/2/3) and nonresponse (TRG4/5) groups at the lesion level. The model's predictive ability was evaluated using the C index and calibration curve, with decision curve analysis assessing the Nomogram's added value. ResultsThe study analyzed 105 CRLM lesions (the lesion with the highest diameter analyzed for each patient), with 43.8% showing a response to therapy. Univariate analysis identified calcification on US (p = 0.039), CEUS enhancement degree (p < 0.001), CEUS enhancement pattern (p<0.001), CEUS washout type (p < 0.001), CEUS necrosis (p < 0.001), CPI feeding artery (p = 0.003) and MFI pattern (p < 0.001) were significantly associated with TRG. The multivariate analysis showed CEUS enhancement pattern (p = 0.026), CEUS washout type (p = 0.018) and CEUS necrosis (p = 0.005) were independently associated with the neoadjuvant therapy response. A Nomogram with the three independent predictors was developed, with an AUC of 0.898. ConclusionThe ultrasound-based model provided accurate evaluation of pathological tumor response to preoperative chemotherapy in patients with CRLM, and may help to decide the individualized treatment strategy.

Chromosomal instability is associated with prognosis and efficacy of bevacizumab after resection of colorectal cancer liver metastasis

Introduction Individualized treatment of colorectal cancer liver metastases (CRLM) remains challenging due to differences in the severity of metastatic disease and tumour biology. Exploring specific prognostic risk subgroups is urgently needed. The current study aimed to investigate the prognostic value of chromosomal instability (CIN) in patients with initially resectable CRLM and the predictive value of CIN for the efficacy of bevacizumab. Methods Ninety-one consecutive patients with initially resectable CRLM who underwent curative liver resection from 2006 to 2018 at Sun Yat-sen University Cancer Center were selected for analysis. CIN was evaluated by automated digital imaging systems. Immunohistochemistry (IHC) was performed to detect interleukin-6 (IL-6), vascular endothelial growth factor A (VEGFA) and CD31 expression in paraffin-embedded specimens. Recurrence-free survival (RFS) and overall survival (OS) were analysed using the Kaplan–Meier method and Cox regression models. Results Patients with high chromosomal instability (CIN-H) had a worse 3-year RFS rate (HR, 1.953; 95% CI, 1.001–3.810; p = 0.049) and a worse 3-year OS rate (HR, 2.449; 95% CI, 1.150–5.213; p = 0.016) than those with low chromosomal instability (CIN-L). CIN-H was identified as an independent prognostic factor for RFS (HR, 2.569; 95% CI, 1.078–6.121; p = 0.033) and OS (HR, 3.852; 95% CI, 1.173–12.645; p = 0.026) in the multivariate analysis. The protein levels of IL-6, VEGFA and CD31 were upregulated in patients in the CIN-H group compared to those in the CIN-L group in both primary tumour and liver metastases tissues. Among them, 22 patients with recurrent tumours were treated with first-line bevacizumab treatment and based on the clinical response assessment, disease control rates were adversely associated with chromosomal instability (p = 0.043). Conclusions Our study showed that high chromosomal instability is a negative prognostic factor for patients with initially resectable CRLM after liver resection. CIN may have positive correlations with angiogenesis through expression of IL-6–VEGFA axis and be used as a potential predictor of efficacy of bevacizumab.

549P Combined morphometric immune signatures define the prognosis of patients with resectable colorectal liver metastases

549P Combined morphometric immune signatures define the prognosis of patients with resectable colorectal liver metastases

Survival benefit of adjuvant chemotherapy based on molecular residual disease detection in resected colorectal liver metastases: subgroup analysis from CIRCULATE-Japan GALAXY

The prognostic role of circulating-tumor DNA (ctDNA)-based molecular residual disease (MRD) detection and its utility for postsurgical risk-stratification has been reported in colorectal cancer. In this study, we explored the use of ctDNA-based MRD detection in patients with colorectal liver metastases (CLM), for whom the survival benefit of adjuvant chemotherapy (ACT) after surgical resection remains unclear. Patients with CLM without extrahepatic disease from GALAXY study (UMIN000039205) were included. The disease-free survival (DFS) benefit of ACT was evaluated in MRD-positive and -negative groups after adjusting for age, gender, number and size of liver metastases, RAS status, and previous history of oxaliplatin for primary cancer. ctDNA was detected using a personalized, tumor-informed 16-plex mPCR-NGS assay. ctDNA-based MRD status was evaluated 2 to 10 weeks after curative surgery, before the start of ACT. Among 6,061 patients registered in GALAXY, 190 surgically resected CLM patients without any preoperative chemotherapy were included with a median follow-up of 24 (1-48) months. ctDNA positivity in the MRD window was 32.1% (61/190). ACT was administered to 25.1% (48/190) of patients. In the MRD-positive group, 24-month DFS was higher for patients treated with ACT (33.3% vs. not reached, adjusted HR: 0.07, P <0.0001); whereas no benefit of ACT was seen in the MRD-negative group (24-month DFS: 72.3% vs. 62.2%, adjusted HR: 0.68, P =0.371). Multivariate analysis showed that the size of liver metastases (HR: 3.94, P =0.031) was prognostic of DFS in the MRD-positive group. However, in the MRD-negative group, none of the clinicopathological factors were prognostic of DFS. Our data suggest that ACT may offer notable clinical benefits in MRD-positive patients with CLM. MRD status-based risk-stratification could be potentially incorporated in future clinical trials for CLM.

Robotic surgery for colorectal liver metastases (CRLM): A systematic literature review with meta-analysis.

Colorectal Cancer (CRC) is the third most prevalent cancer (10.2%) with the second highest mortality (9.2%).[1] Up to 14.5% of patients present with synchronous metastases and 12.8% will develop metachronous metastases within 5 years. The treatment for these metastases is resection. [2] In this study we perform a systematic search of the literature about robotic versus laparoscopic liver resections of colorectal liver metastases (CLRM). We include 16 studies. We describe the patient and tumor characteristics. We also describe operation characteristics (rate of major resections, operation time, usage and duration of Pringle, conversion rate, complication rate, R0 margin rate, estimated blood loss, length of stay, mortality and recurrence. Using this data we perform a meta-analysis: no significant difference in operation time was found between robotic and laparoscopic liver resections. There was significantly lower conversion rate, significantly higher R0 margin rate, significantly lower blood loss in the robotic group. We conclude that robotic surgery is promising in the therapy of CRLM. In the future there is need for RCT to compare robotic versus laparoscopic liver surgery for CRLM. Furthermore a longer follow-up is needed.

Cytoreductive Surgery With Hyperthermic Intraperitoneal Chemotherapy and Liver Resection is a Treatment Option for Patients With Peritoneal and Liver Metastases From Colorectal Cancer.

Colorectal cancer frequently metastasize to the liver and peritoneum, and is associated with a poor prognosis. In selected patients, a benefit in overall survival (OS) was shown for both peritoneal metastases (PM-CRC) offered cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), and colorectal liver metastases (CLM) treated with surgical resection. However, the presence of CLM was considered a relative contraindication to CRS-HIPEC, causing a paucity in outcome data in this patient group. Patient with PM-CRC having CRS-HIPEC at a single national center between 2007 and 2023, with additional intervention for CLM, were included (previous curative treatment for extra-peritoneal and extra-hepatic metastases was allowed). Three groups were defined: CLM before CRS-HIPEC (preCRS-HIPEC); CLM resected simultaneously with CRS-HIPEC (simCRS-HIPEC); CLM after CRS-HIPEC (postCRS-HIPEC), aiming to retrospectively analyze outcomes. Fifty-seven patients were included and classified as: preCRS-HIPEC (n=11), simCRS-HIPEC (n=29), and postCRS-HIPEC (n=17). Median peritoneal cancer index (PCI) was 8, 13 patients had severe complications (Clavien-Dindo ≥3), and no 90-day mortality. Median OS was 48 months after CRS-HIPEC. PCI was a predictor of OS (HR 1.11, P<0.001). We observed no difference in short or long-term outcomes between intervention groups. This study demonstrate that patients with CLM having CRS-HIPEC had comparable OS to reports on CRS-HIPEC only, likely explained by a low PCI. Simultaneous CLM resection did not increase the risk of severe complications. In this national cohort, CRS-HIPEC and CLM intervention offers long-term survival, suggesting that this treatment may be offered to selected patients with PM-CRC and CLM.

The association between histopathological growth patterns with tumor budding and poorly differentiated clusters in colorectal liver metastasis treated with preoperative systemic therapy.

The liver's unique cellular structure makes it a frequent site for metastatic cancer. In colorectal liver metastasis (CRLM), surgical resection is essential for long-term survival. Histopathological growth patterns (HGPs) in CRLM, including desmoplastic and nondesmoplastic patterns, provide critical prognostic information. Tumor budding (TB) and poorly differentiated clusters (PDCs), indicators of aggressive cancer behavior, are evaluated using standardized histological scoring systems and are linked to epithelial-mesenchymal transition. This study explored the correlation between HGPs, TB, and PDCs in CRLM. Archived data from Thammasat University Hospital, including resected CRLM specimens, were analyzed. This study evaluated 51 CRLM resection specimens treated with preoperative systemic therapy, finding most to be nondesmoplastic with low TB and grade 1 PDC. Desmoplastic growth was significantly more prevalent in cases receiving preoperative chemotherapy than those that did not. Higher 3-year mortality was noted in nondesmoplastic groups and those with higher TB and tumor regression grade (TRG) scores. Significant correlations were observed between HGPs, TB, and PDCs, despite challenges in assessing these parameters due to issues with noncancer cells, extracellular mucin, bile ductular proliferation, and retraction artifacts. This study underscores the prognostic significance of HGPs, TB, PDCs, and TRG scores in CRLM, highlighting the need for precise histopathological evaluation for more accurate prognostic implications.

Prognostic implications of margin status in association with systemic treatment in a cohort study of patients with resection of colorectal liver metastases.

This study investigates the impact of margin status after colorectal liver metastasis (CLM) resection on outcomes of patients after neoadjuvant treatment versus those who underwent upfront resection. An international collaborative database of CLM patients who underwent surgical resection was used. Proportional hazard regression models were created for single and multivariable models to assess the relationship between independent measures and median overall survival (mOS). R1 was associated with worse OS in the neoadjuvant group (mOS: 51.8 m for R0 vs. 26.0 m for R1; HR: 2.18). In the patients who underwent upfront surgery, R1 was not associated with OS. (mOS: 46.7 m for R0 vs. 42.6 m for R1). When patients with R1 in each group were stratified by adjuvant treatment, there was no significant difference in the neoadjuvant group, while in the upfront surgery group with R1, adjuvant treatment was associated with significant improvement in OS (mOS: 42.6 m for adjuvant vs. 25.0 m for no adjuvant treatment; HR: 0.21). R1 is associated with worse outcomes in the patients who receive neoadjuvant treatment with no significant improvement with the addition of adjuvant therapy, likely representing an aggressive tumor biology. R1 did not impact OS in patients with upfront surgery who received postoperative chemotherapy.

Patterns and Predictors of Recurrence After Curative Resection of Colorectal Liver Metastasis (CRLM).

Our study aims to determine the predictors and patterns of relapses after curative colorectal liver metastasis (CRLM) resection. A single-centre, retrospective study of CRLM patients operated between 2010 and 2022 was performed. The site of first recurrence was either hepatic (marginal (≤ 1cm) or extramarginal), extrahepatic, or both. Factors that predicted relapse patterns and overall survival were determined by multivariable Cox regression analysis with backward elimination of variables. The study consisted of 258 patients, with a similar proportion of synchronous (144; 56%) and metachronous(114; 43%) metastasis. At a 43-month median follow-up, 156 patients (60.4%) developed recurrences with 33 (21.1%) in the liver, 62(24.03%) extra-hepatic recurrences, and 58 (22.48%) having both. Isolated marginal liver relapses were seen in seven (9.89%) liver recurrence patients. The median overall and relapse-free survivals were 38months (30-54) and 13months (11-16), respectively. The 3-year liver-relapse-free survival was 54.4% (44.9-60.6). Size of liver metastases > 5cm (HR 2.06 (1.34-3.17), involved surgical margins (HR 2.16 (1.27-3.68)), and adjuvant chemotherapy (HR 1.89 (1.07-3.35)) were predictors of hepatic recurrences. Node positivity of primary (HR 1.61 (1.02-2.56)), presence of baseline extra-hepatic metastases (HR 0.30 (0.18-0.51)), size of liver metastases > 5cm (HR 2.02 (1.37-2.99)), poorly differentiated histology (HR 2.25 (1.28-3.49)), presence of LVI (HR 2.25 (1.28-3.94)), and adjuvant chemotherapy (HR 2.15 (1.28-3.61)) were predictors of extra-hepatic recurrences. The study found majority relapses occurred at extrahepatic sites whilst isolated marginal recurrences were few. The consistent predictors of recurrence were size and inability to deliver adjuvant therapy. A tailored adjuvant therapy might improve outcomes after liver metastasectomy in colorectal cancers.

Combined Resection of Liver and Hilar Bifurcation for Colorectal Liver Metastasis: A Single-Center Experience and Review of the Literature

Introduction: Colorectal liver metastases (CRLM) infiltrating the hilar bifurcation is rarely described. We investigated the outcome of partial hepatectomy combined with resection of the hilar bifurcation. Methods: Data collection for patients who underwent resection for CRLM at our institution was performed prospectively from January 2008 to August 2021. Follow-up ended in August 2023. Patients with and without bile duct infiltration of CRLM were analyzed retrospectively. The primary endpoints were overall (OS) and recurrence-free survival (RFS). Results: A total of 1,156 liver resections were screened. Out of those, 18 were combined resections of the liver and the hilar bifurcation. Bile duct infiltration of CRLM was histologically proven in 5 of 18 cases. Preoperative mild obstructive jaundice occurred in 6 of 18 patients and was treated by drainage. Out of those, only 2 had a confirmed infiltration of the hilar bifurcation by CRLM. The median recurrence-free survival (RFS) was 10 months in those patients with bile duct infiltration compared to 9 months in those with no infiltration (p = 0.503). Conclusion: While CRLM is common, infiltration into the central biliary tract is rare. Tumor invasion of the biliary tree can cause jaundice, but jaundice does not necessarily mean tumor invasion. We have shown that combined resection of the liver and hilar bifurcation for CRLM is safe and infiltration of the bile duct by CRLM did not seem to have a significant effect on RFS or OS.

Evolution and current trends in the management of colorectal cancer liver metastasis.

Metastatic colorectal cancer (mCRC) is a major cause of cancer-related death, with a 5-year relative overall survival of up to 20%. The liver is the most common site of distant metastasis in colorectal cancer (CRC), with about 50% of CRC patients metastasizing to their liver over the course of their disease. Complete liver resection is the primary modality of treatment for resectable colorectal cancer liver metastasis (CRLM), with an overall 5-year survival rate of up to 58%. However, only 15% to 20% of patients with CRLM are deemed suitable for resection at presentation. For unresectable diseases, the median survival of patients remains low even with the best chemotherapy. In recent decades, the management of CRLM has continued to evolve with the expansion of resection criteria, novel targeted systemic therapies, and improved locoregional therapies. However, due to the heterogeneity of the CRC patient population, the optimal evaluation of treatment options for CRLM remains complex. Therefore, effective management requires a multidisciplinary team to help define resectability and devise a personalized treatment approach, from the initial diagnosis to the final treatment.