The cancer journey of a young patient who presented with an obstructing metastatic (Stage 4) colon cancer is described. The addition of bevacizumab to an established chemotherapy regimen of 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX) ameliorated their chemotherapy-associated liver injury (CALI). This improvement in liver quality was demonstrated non-invasively with multi-parametric magnetic resonance imaging (mpMRI). Both the response to chemotherapy and the improvement in liver quality provided by additional bevacizumab allowed this patient with initially unresectable synchronous colorectal liver metastases to undergo resection of their bowel primary, followed by an extended liver resection, uncomplicated by post-hepatectomy liver failure (PHLF). They had subsequent planned ablative therapy with stereotactic ablative radiotherapy (SABR) to a residual central metastasis, and are currently disease free. This case illlustrates the importance of a multi-modal, multidisciplinary and individualised approach to patients' cancer care.

Reliable and modern information on primary evaluation, treatment, and long-term survival rates for patients with colorectal cancer (CRC) metastases are needed. Whether synchronous CRC metastases carry a worse prognosis than metachronous is still debated.

Population-based study on 7,950 CRC patients from Central Norway, 2001- 2015. Of these, 1,843 (23.2%) had synchronous metastases and of radically operated patients with stage I-III disease 1,117 (20.1%) developed metachronous metastases. The treatment strategies and outcomes for patients with metastases were analyzed, stratified by three consecutive 5-year periods.

Median and 3-year survival for patients with synchronous metastases were 11 months and 16.4%, compared to 17 months and 29.4% with metachronous metastases, p < 0.001 and p < 0.001, respectively. The subsets receiving supportive care only, had a median survival of 3-4 months. Patients with synchronous metastases and primary palliative chemotherapy had a median survival of 15 months compared to 18 months with metachronous metastases, p < 0.001. Neither groups improved survival across the study period. The 5-year survival for the 342/1,843 (18.6%) patients with synchronous metastases and curative intent treatment was 41.8% compared to 43.6% for the corresponding 422/1,117 (37.8%) patients with metachronous metastases, log-rank p = 0.281. Survival significantly improved for both these groups across the study period.

A key determinant of better survival for patients with metachronous CRC metastases compared to synchronous was a significantly higher proportion treated with curative intent. Survival for both patients with synchronous and metachronous metastases taken collectively steadily improved during the study period, driven by the increased proportions and improved survival for the subsets with curative intent treatment.

Neoadjuvant chemotherapy (NAC) treatment has appeared as a promising alternative to upfront surgery to improve efficacy outcomes in non-metastatic colon cancer, but the findings are still controversial. Considering this ongoing debate, we conducted a systematic review and meta-analysis of randomized controlled trials to assess the benefit of NAC in high-risk stage II and stage III colon cancer.

We searched PubMed, Embase, and Cochrane for clinical trials evaluating NAC in non-metastatic colon cancer. Random and fixed effects models were employed for statistical analyses in Review Manager software version 5.4. Moreover, to evaluate the heterogeneity, I2 statistics were used.

A total of 1248 patients from 4 clinical trials were included. The NAC group demonstrated a 38 % reduction in the risk of death. (HR 0.62; 95 % CI 0.41-0.92; I2 = 0 %), and a 21 % reduction in the risk of disease recurrence (HR 0.79; 95 % CI 0.65-0.96; I2 = 0 %). Additionally, the NAC group had higher R0 resection, with an increase of 80 % in the odds compared to upfront surgery (OR 1.80; 95 % CI 1.24-2.61; I² = 0 %). Pathological complete response and major pathologic response (PCR) were achieved in 5.9.% % and 36.2 %, respectively. Patients with proficient mismatch repair achieved a higher PCR rate and a consistent reduction in the risk of recurrence compared to the overall population, with proportions of 6.3 % and 32 %, respectively. Also, there was no significant addition to the toxicity profile in the NAC arm.

Our systematic review and meta-analysis support the feasibility and survival benefits of neoadjuvant chemotherapy for high-risk stage II and III colon cancer.

Colorectal liver metastases (CRLM) are a major indication for liver surgery in Europe, highlighting the need for standardized knowledge and training in surgical oncology. The European Society of Surgical Oncology (ESSO) has updated its core curriculum to provide a structured framework for education. Previous publications have addressed pancreatic, hepatocellular, and biliary tract cancers to support candidates preparing for the European Board of Surgery Qualification (EBSQ) exams in Surgical Oncology and Hepato-Pancreato-Biliary Surgery. However, a dedicated guide for CRLM remains absent. This article aims to fill that gap by offering a structured reference on CRLM, covering epidemiology, staging, genetics, and diagnosis of metastatic colorectal cancer. It also outlines multidisciplinary treatment strategies, including systemic, surgical, interventional, and palliative approaches. A structured literature review was conducted using PubMed to identify the most updated (inter)national management guidelines, prioritizing recent multicentre studies, systematic reviews, and meta-analyses published from January 2020 to January 2025. By bridging the gap between the ESSO core curriculum and detailed subspecialty training, this guide provides an essential resource for hepatobiliary surgeons and surgical oncologists. It serves as a valuable tool for those preparing for board examinations while promoting a standardized approach to CRLM education and management across Europe.

Currents guidelines recommend chemotherapy with or without biologic agents for asymptomatic stage IV colon cancer treatment, whereas primary tumor resection is reserved for symptomatic tumors or resectable metastases. However, US treatment patterns are understudied. Our study aims to identify real-world treatment patterns for asymptomatic metastatic colon cancer.

Adults with asymptomatic metastatic colon cancer were identified in the 2014 Surveillance, Epidemiology, and End Results Patterns of Care database and categorized into 6 groups: chemotherapy with or without biologic agents, chemotherapy with or without biologic agents with primary tumor resection and metastasectomy, chemotherapy with or without biologic agents and primary tumor resection alone, primary tumor resection only, no treatment, or other treatments. Multinomial logistic regression was used to examine factors associated with receiving each treatment modality. Cox proportional hazard models were used to assess the relationships between treatments and survival.

Among 1,717 weighted patient cases, 28% received chemotherapy with or without biologic agents, 23% chemotherapy with or without biologic agents with primary tumor resection, 12% chemotherapy with or without biologic agents with primary tumor resection and metastasectomy, 12% primary tumor resection only, 23% no treatment, and 2% other treatment. Younger patients were more likely to receive chemotherapy with or without biologic agents with primary tumor resection and metastasectomy than chemotherapy with or without biologic agents alone (odds ratio, 3.32; 95% confidence interval, 1.3-8.6) and less likely to undergo no treatment (odds ratio, 0.05; 95% confidence interval, 0.02-0.17). Patients treated by chemotherapy with or without biologic agents with primary tumor resection and metastasectomy had the greatest median survival of 61 months, whereas those with no treatment had a 1-month median survival.

Almost one quarter of patients with asymptomatic stage IV colon cancer received no treatment. Meanwhile, 12% of patients underwent curative systemic and surgical treatment, which was associated with a median survival of 5 years, validating reported outcomes of this approach by institutional studies. These data provide an important benchmark for future interventions pertaining to asymptomatic patients with stage IV colon cancer.

The liver is an important metastatic organ that contains many innate immune cells, yet little is known about their role in anti-metastatic defense. We investigated how invariant natural killer T (iNKT) cells influence colorectal cancer-derived liver metastasis using different models in immunocompetent mice. We found that hepatic iNKT cells promote metastasis by creating a supportive niche for disseminated cancer cells. Mechanistically, iNKT cells respond to disseminating cancer cells by producing the fibrogenic cytokines interleukin-4 (IL-4) and IL-13 in a T cell receptor-independent manner. Selective abrogation of IL-4 and IL-13 sensing in hepatic stellate cells prevented their transdifferentiation into extracellular matrix-producing myofibroblasts, which hindered metastatic outgrowth of disseminated cancer cells. This study highlights a novel tumor-promoting axis driven by iNKT cells in the initial stages of metastasis.

The assessment of resectability in patients with colorectal cancer (CRC) and multiple liver metastases is primarily a technical decision. However, in cases with unfavourable tumor biology, the clinical benefit of surgery remains limited. Further research is needed to identify additional factors influencing oncological outcomes in these patients to better guide the decision-making process. The aim of this study was to investigate the association of tumor burden score (TBS) and oncological outcome in CRC patients with multiple bilobar metastases.

Five hundred twenty-one consecutive patients who underwent liver resections for CRC liver metastases between January 2002 and January 2024 were identified from the National Cancer Institute (Kyiv, Ukraine) prospective database and analysed retrospectively.

The median and 5-year overall survival in cohorts with TBS clusters < 3, ≥ 3-9 and ≥ 9 was 116.2 months, 50.3 months and 29.7 months; and 75.7%, 42.4% and 41.6%, respectively (P < 0.001). TBS index has shown high prognostic specificity and sensitivity for postoperative morbidity with AUC 0.97 on the ROC curve. The multivariate Cox regression model has shown that the TBS clusters have a significant negative impact on overall survival particularly in cohorts with TBS ≥ 3-9 (HR: 2.8, 95% CI: 1.7-4.8, P = 0.0001) and TBS ≥ 9 (HR: 1.4, 95% CI: 1.31-1.46, P = 0.005).

In this Ukranian population-based study of patients with resectable CRC liver metastases, high TBS was associated with poorer overall survival.

Clinically significant posthepatectomy liver failure (PHLF B+C) remains the main cause of mortality after major hepatic resection. This study aimed to establish an aspartate aminotransferase to platelet ratio combined with an albumin-bilirubin grade (APRI+ALBI), based multivariable model (MVM) to predict PHLF and compare its performance to indocyanine green clearance (ICG-R15 or ICG-PDR) and albumin-ICG evaluation (ALICE).

A total of 12,056 patients from the National Surgical Quality Improvement Program database were used to generate a MVM to predict PHLF B+C. The model was determined using stepwise backwards elimination. The performance of the model was tested using receiver operating characteristic curve analysis and validated in an international cohort of 2525 patients. In 620 patients, the APRI+ALBI MVM, trained in the National Surgical Quality Improvement Program cohort, was compared with the MVM's based on other liver function tests (ICG clearance, ALICE) by comparing the areas under the curve (AUC).

A MVM including APRI+ALBI, age, sex, tumor type, and extent of resection was found to predict PHLF B+C with an AUC of 0.77, with comparable performance in the validation cohort (AUC: 0.74). In direct comparison with other MVM's based on more expensive and time-consuming liver function tests (ICG clearance, ALICE), the APRI+ALBI MVM demonstrated equal predictive potential for PHLF B+C. A smartphone application for the calculation of the APRI+ALBI MVM was designed.

Risk assessment through the APRI+ALBI MVM for PHLF B+C increases preoperative predictive accuracy and represents a universally available and cost-effective risk assessment before hepatectomy, facilitated by a freely available smartphone app.

The benefit of simultaneous curative resection in patients with colorectal liver metastases has been unclear. Adjuvant chemotherapy is still considered an effective and priority treatment for advanced-stage colorectal patients.

We retrospectively collected patients with colorectal liver metastases from January 2012 to October 2023 at the Guangxi Medical University Cancer Hospital. The baseline information was compared between a simultaneous curative resection group and a palliative treatment group. Propensity score matching with a 1:1 ratio was applied to develop comparable cohorts of curative resection and palliative treatment resection. Kaplan-Meier survival and Cox regression analyses were performed to determine the impact of curative resection on survival of colorectal liver metastasis patients. Prognostic nomogram and a web-version calculator were developed based on the multivariate Cox regression method. Then, the concordance index (C-index), receiver operating characteristic, calibration plots, and decision curves analysis were applied to evaluate the prognostic performance of the nomogram.

A total of 716 patients with colorectal liver metastases were enrolled in the study, of whom 131 patients received curative resection. There was no significant difference in terms of baseline information between the curative resection group and the palliative treatment group after propensity score matching. Multivariable Cox regression analysis showed that curative resection was an independent prognostic factor affecting overall survival (P = .001, hazard ratio = 1.95, 95% confidence interval 1.30-2.91). Compared with patients who did not receive curative resection, patients who received simultaneous curative resection had a significant improvement in overall survival before and after propensity score matching (P < .0001 and P = .0047, respectively). Overall survival nomogram showed excellent predictive performance with the C-indexes of 0.686 (95% confidence interval 0.556-0.792). The areas under the receiver operating characteristic curves were 0.75 (95% confidence interval 64.43-96.05), 0.75 (67.22-82.58), and 0.76 (66.10-85.98) for predicting 1-, 3-, and 5-year survival, respectively. The calibration plots and decision curves analysis also indicated the good predictability of the predictive nomogram. Finally, subgroup analysis further demonstrated a favorable impact of curative resection on overall survival in colorectal liver metastasis patients after propensity score matching.

Simultaneous curative resection may improve the overall survival of patients with colorectal liver metastases and is an independent and effective indicator for predicting overall survival. The nomogram may provide a personalized treatment strategy.

Optimal prognostic stratification for colorectal liver metastases (CRLM) patients undergoing surgery with neoadjuvant therapy (NAT) remains elusive. This study aimed to develop and validate dual-time-point radiomic models for CRLM prognosis prediction using pre- and post-NAT imaging features.

Radiomic features were extracted from four MRI sequences in 100 cases of CRLM patients who underwent NAT and radical resection. RAD scores were generated, and clinical/pathologic variables were incorporated into uni- and multivariate Cox regression analyses to construct prognosis models. Time-ROC, time-C index, decision curve analysis (DCA), and calibration curves assessed the predictive performance of Fong score and pre- and post-NAT models for overall survival (OS) and disease-free survival (DFS) in a testing set.

The final models included four variables for OS and three variables for DFS. The post-NAT models outperformed the pre-NAT models in time-ROC, time-C index, calibration, and DCA analysis, except for the 1-year DFS area under the curve (AUC). The Fong score models underperformed. The post-NAT OS RAD score effectively stratified patients into prognostic subgroups.

The radiomic models incorporating pre- and post-NAT MRI features and clinical/pathologic variables effectively stratified CRLM patients prognositically. The post-NAT models demonstrated superior performance.

There is no standard surgical management for rectal cancer with synchronous resectable liver metastases. The aim of this study was to assess the oncologic outcomes of an adaptative and individualized strategy considering the extension of both tumoral sites in the management of rectal cancer with synchronous resectable liver metastases.

From 2011 to 2020, all consecutive patients treated for low/midrectal cancer with resectable synchronous resectable liver metastases in 4 French centers were included. The choice of strategy was not systematic but tailored on a case-by-case basis to the extension of rectal cancer and liver metastases, prioritizing the most advanced site. The success of the strategy was defined as complete resection of both tumor sites.

Among 83 included patients, most had locally advanced rectal cancer (cT3T4 = 96%) and a median of 3 liver metastases. Forty patients underwent a rectum-first strategy, 31 a liver-first strategy, and 12 a simultaneous resection strategy. Complete resection rate of both sites was 82%. After a 43-month follow-up, median overall survival was 58 months. One- and 3-year survival rates were 94% and 73%, with no difference between strategies (P = .650). In multivariate analysis, the only prognostic factor for overall survival was complete resection of both sites (P = .011, hazard ratio, 0.321; 95% confidence interval, 0.135-0.768), with a median overall survival of 72 months in these patients.

Extent-based tailored strategy for rectal cancer with synchronous resectable liver metastases, on the basis of disease extension, allows high rates of complete resection and favorable long-term survival outcomes. This individualized approach maximizes potential for curative outcomes in patients with metastatic rectal cancer.

To improve prognosis of patients with synchronous colorectal liver metastasis (CRLM), we constructed a nomogram model to improve outcome through risk stratification and decision support.

The 389 CRLM patients (273 training set and 116 validation set at a ratio of 7: 3) receiving systematic chemotherapy and synchronously resection with/without radiofrequency ablation (RFA) were retrospectively investigated. Overall survival (OS) and recurrence free survival (RFS) were mainly endpoint. A normo-gram model was conduct. The receiver operating characteristic (ROC) curve, decision curve analysis (DCA), C-index and calibration curve were performed to assess stablity and efficacy of model. The prognosis was evaluated based on Kaplan-Meier (KM) curve.

A total of 389 CRLM patients were included. The median OS and RFS times were 70.20 months (95% CIs: 57.73, 82.68) and 11.70 months (95% CIs: 9.75, 13.65), respectively. These patients were divided into training set and validation set at a ratio of 7: 3. In training set, 1, 3, and 5-year survival rate of OS was 97.38%, 71.18%, and 54.56% as well as RFS was 52.57%, 22.65%, and 21.12%, respectively. Cox model showed that hospital day, R0 resection, RFA, only neoadjuvant chemotherapy and CRS score were independent prognostic factors for CRLM patients. The patients were divided into high-risk group and low-risk group based on cut-off value of score calculated by model. The KM curves were statistically different between two groups (P < 0.01). The ROC curve, DCA and calibration curve showed a good prediction efficacy. the C-index of OS and RFS were 0.72 and 0.68, respectively, which were also verified in the validation set (OS, 0.71; RFS, 0.65).

A good prediction model was developed and validated to assess the prognoses of CRLM patients. Systematic chemotherapy and R0 resection could benefit patients' survival and improve prognosis.

Visceral obesity (VO), associated with excessive visceral adipose tissue (VAT), has been extensively studied in cancer. However, whether low VAT can predict the prognosis of colorectal liver metastases (CRLM) undergoing neoadjuvant chemotherapy (NAC) remains unknown.

This multicentre real-world cohort study analysed data from initially resectable CRLM patients who received NAC. The predictive effect of VAT on progression-free survival (PFS) and overall survival (OS) was evaluated using restricted cubic splines (RCS). VAT was categorized into low/normal VAT and VO groups using X-tile. The prognostic differences were further assessed through Kaplan-Meier (KM) analysis. The impact of changes in VAT (ΔVAT) after NAC was evaluated.

Among 1524 CRLM patients, 1105 patients (72.51%) were under 65 years old, with a median VAT of 84.00 (36.24-148.00) cm2. Of all patients, 804 (52.76%) were female. A U-shaped nonlinear relationship was observed between VAT and both PFS/OS (p < 0.001). Compared with the normal VAT, both low VAT and VO groups showed worsened PFS and OS (p < 0.05). The 3-year PFS rate was 31.6%, 69.0% and 42.0% in the low, normal VAT and VO groups (p < 0.05). The 3-year OS rate was 76.4%, 88.9% and 79.4% in the low, normal VAT and VO groups (p < 0.05). There was also a nonlinear relationship between VAT and NAC-related adverse events, objective response rate and postoperative complications (p < 0.001). An increase in ΔVAT in the low VAT group was associated with better PFS and OS (p < 0.05). In the VO group, both increases and decreases in ΔVAT were associated with worsened PFS and OS (p < 0.05).

This study is the first to reveal that low VAT and VO can predict PFS and OS in CRLM patients undergoing NAC. Baseline VAT and ΔVAT may serve as important indicators for risk stratification and personalized treatment in CRLM patients.

Hepatic arterial infusion (HAI) chemotherapy, first introduced in the 1980s, has gained recognition as an effective locoregional treatment for colorectal liver metastasis (CRLM). Initially used for unresectable liver metastases, HAI's application has expanded to the adjuvant setting following hepatic resection, with early studies indicating improved hepatic disease-free survival. Recent research demonstrates that combining HAI with modern systemic therapies enhances conversion to resectability and prolongs both recurrence-free and overall survival, even in heavily pretreated patients with diverse RAS mutational statuses. Personalization through approaches like microsatellite instability status and dose modifications further optimize outcomes. However, the complexity of HAI requires expertise across multidisciplinary teams, limiting its widespread adoption to specialized centers. Ongoing clinical trials continue to investigate HAI's role in CRLM management, highlighting its potential to become a cornerstone of liver-directed therapy. We explore how HAI chemotherapy, in combination with personalized medicine, can advance treatment strategies for metastatic colorectal cancer.

The Eastern Canadian Gastrointestinal Cancer Consensus Conference was an annual meeting that was held in St. John's, Newfoundland and Labrador, from 26 to 28 September 2024. This included experts in medical oncology, radiation oncology, surgical oncology, nuclear medicine, and general practitioners in oncology (GPO) from across the eastern Canadian provinces who are involved in the management of patients with gastrointestinal malignancies. This consensus statement generated by the conference addresses multiple topics, including the management of localized rectal cancer, liver-limited colorectal cancer, systemic therapy for advanced biliary tract cancers, radioligand therapy for gastroenteropancreatic neuroendocrine tumors (GEP-NETs), systemic therapy for pancreatic and midgut well-differentiated NETs, and systemic therapy for HER2-positive gastroesophageal cancers.

There is still no consensus as to whether patients with upfront resectable synchronous colorectal liver metastases (sCRLM) should receive neoadjuvant treatment prior to liver surgery. Two randomized controlled trials have assessed the role of peri-operative chemotherapy in sCRLM; neither have shown a survival benefit in the neoadjuvant group. The aim of this population-based study was to examine overall survival in patients treated with neoadjuvant chemotherapy and hepatectomy compared to patients who had upfront surgery.

This is a retrospective observational study between 2009 and 2017 containing data extracted from two Swedish national registries. Descriptive statistics and Cox regression analyses were employed.

In total, 2072 patients with sCRLM were treated with liver surgery between 2009 and 2017. A majority (n = 1238, 60%) were treated with neoadjuvant chemotherapy, and 834 patients (40%) had upfront surgery. Patients in the upfront surgery group were older (median age 70 compared to 65 years, p ≤ 0.001). Median overall survival in the upfront surgery group was 26 months (95% CI 23-29 months) compared to 57 months (95% CI 42-48 months) in the neoadjuvant group, log rank p ≤ 0.001. In the multivariable Cox regression analysis, age ≥ 70 years (HR 1.46, 95% CI 1.25-1.70), T category of primary cancer (HR 1.41, 95% CI 1.09-1.84), lymphatic spread of primary cancer (HR 1.68, 95% CI 1.41-1.99), and number of liver metastases (six or more metastases resulted in HR 2.05, 95% CI 1.38-3.01) negatively influenced overall survival. By contrast, adjuvant therapy was protective (HR 0.80, 95% CI 0-69-0.94), whereas neoadjuvant treatment compared to upfront surgery did not influence overall survival (HR 1.04, 95% CI 0.86-1.26).

Neoadjuvant treatment in sCRLM did not confer a survival benefit compared to upfront surgery.

We aimed to define borderline resectable colorectal liver metastases (CRLM) based on the analysis of risk factors for early surgical failure and investigate the efficacy of neoadjuvant chemotherapy in these patients.

This was a retrospective analysis of a multi-institutional cohort of patients diagnosed with technically resectable CRLM. Early surgical failure within 6 months of liver surgery was defined as ESF6. We classified CRLM into three grades (A, B, and C) according to the definition of the Japanese Society for Cancer of the Colon and Rectum.

Among the 249 patients with technically resectable CRLM, 46 (18.5%) developed ESF6. The survival rate of these patients was significantly lower than that of the patients without ESF6. In the multivariate analysis of synchronous CRLM patients, no neoadjuvant chemotherapy, Grade B/C, and Charlson comorbidity index ≥ 3 were independent predictors of ESF6. Among patients with synchronous and Grade B/C CRLM, ESF6 rates, surgical failure-free survival, and overall survival in the neoadjuvant chemotherapy group were significantly better relative to the upfront surgery group.

Patients with synchronous and Grade B/C CRLM are at a high risk of early surgical failure, have a poor long-term prognosis, and can be defined as borderline resectable and good candidates for neoadjuvant chemotherapy.

Colorectal cancer most commonly metastasizes to the liver. While various treatment strategies have been developed, surgical management of these patients has vital implications on the prognosis and survival of this group of patients. There remains a need for a consensus guideline regarding the surgical evaluation and management of patients with colorectal liver metastases (CRLM).

This review article is a consensus guideline established by the members of the AHPBA Professional Standards Committee, as an amalgamation of existent literature and a guide to surgeons managing this complex disease.

These guidelines reports the benefits and shortcomings of various diagnostic modalities including imaging and next-generation sequencing in the management of patients with CRLM. While surgery has established survival benefits in patients with resectable disease, this report notes the importance of treatment sequencing with non-surgical modalities as well as between colon and liver resection. Finally, the guidelines address the various treatment modalities for patients with unresectable disease, that may have significant impact on survival.

CRLM is a complex diagnosis which warrants multidisciplinary approach with early surgical involvement in both assessment and management of the disease, to optimize patient outcomes and survival.

Colorectal cancer (CRC) frequently metastasizes to the liver and lungs, leading to poor prognosis. Advances in chemotherapy, minimally invasive surgery, and perioperative care have expanded adjuvant chemotherapy (AC) regimens and eligibility for AC. However, the impact of AC after curative resection of distant metastases on recurrence and prognosis remains uncertain. This study evaluated the role of AC in CRC liver and lung metastases, focusing on cases with curative resection based on the latest studies published in the past five years.

This systematic review followed PRISMA guidelines. Literature searches of Medline and Cochrane Library (2019-2023) identified studies on AC or observation after curative resection of CRC metastases, reporting outcomes such as overall survival (OS) and disease-free survival (DFS). Data analysis was performed using Review Manager and R software, with results expressed as hazard ratios (HR) and 95% confidence intervals (CI).

Seven studies met the eligibility criteria, including one randomized controlled trial and six retrospective studies, encompassing 1580 patients who underwent curative resection (R0) for CRC metastases. This meta-analysis showed a positive trend in OS for the AC group compared to that for the surgery-alone group (HR 0.86, 95% CI: 0.73-1.01; p = 0.06), but the difference was insignificant. AC significantly improved DFS (HR 0.81, 95% CI: 0.66-0.99; p = 0.04). Subgroup analysis indicated that AC significantly improved DFS and tended to improve OS for liver metastasis. In contrast, AC did not improve OS in cases of lung metastasis.

This meta-analysis suggests that AC demonstrated significant positive effects on DFS. Moreover, AC could contribute to improvements in OS. These findings, supported by the latest research, reinforce the recommendation of AC as a valuable strategy for improving both recurrence and survival outcomes in patients with curatively resected distant CRC metastases.

Background: Colorectal cancer is the second most common type of cancer and a leading cause of cancer-related deaths worldwide. Approximately 15% of the patients with colorectal cancer will already have liver metastases (CRLMs) at diagnosis. Luckily, the advances in chemotherapy regimens during the past few decades have led to increased rates of disease regression that could even render an originally unresectable disease resectable. In certain patients with CRLMs, the hepatic lesions are missing on preoperative imaging after neoadjuvant chemotherapy. These patients can undergo surgery with or without resection of the sites of the disappearing liver metastases (DLMs). In this systematic review, we assess the recurrence rate of the DLMs that were left unresected as well as the complete pathologic response of those resected. Methods: A literature search was conducted in PubMed for studies including patients with CRLMs who received neoadjuvant chemotherapy and had DLMs in preoperative imaging. Two independent reviewers completed the search according to the PRISMA checklist. Results: Three hundred and twenty-six patients with 1134 DLMs were included in our review. A total of 47 out of 480 DLMs (72.29%) that were removed had viable tumor cells in postoperative histology. One hundred and forty-five tumors could not be identified intraoperatively and were removed based on previous imaging, with thirty (20.69%) of them presenting viable cancer cells. Four hundred and sixty-five lesions could not be identified and were left in place. Of them, 152 (32.69%) developed local recurrence within 5 years. Of note, 34 DLMs could not be categorized as viable or non-viable tumors. Finally, DLMs that were identifiable intraoperatively had a higher possibility of viable tumors compared to non-identifiable ones (72.29% vs. 20.69%, respectively). Conclusions: Disappearing liver metastases that are left unresected have an increased possibility of recurrence. Patients receiving neoadjuvant treatment for CRLMs may have better survival chances after resecting all the DLM sites, either identifiable intraoperatively or not.

Approximately 50% of colorectal cancer patients develop liver metastases. Hepatic metastases represent the most common cause of colorectal cancer-related mortality. Metastasectomy, if possible, represents the most effective treatment strategy; 20% of patients will be cured and more than 50% survive at least 5 years. Nuances to treatment planning hinge on whether patients present with resectable disease upfront, whether the future liver remnant is adequate, and whether the primary tumor, if present, is colon versus rectal in origin. This article discusses considerations impacting our approach to patients with colorectal liver metastases and the role for various multimodal treatment options.

Blood loss and subsequent red blood cell transfusions are common in liver surgery. Hypovolaemic phlebotomy is associated with decreased red blood cell transfusion in observational studies. This trial aimed to investigate whether hypovolaemic phlebotomy is superior to usual care in reducing red blood cell transfusions in patients undergoing liver resection.

PRICE-2 was a multicentre, single-blind, superiority randomised controlled trial. Patients at a higher risk of blood loss undergoing liver resection for any indication at four Canadian academic tertiary-care hospitals were randomised to receive hypovolaemic phlebotomy or usual care. Hypovolaemic phlebotomy consisted of the removal of 7-10 mL/kg of whole blood, without volume replacement, before liver transection. Patients were randomised centrally using permuted blocks of randomly variable length, stratified by centre. The randomisation sequence was computer-generated by an independent statistician. Surgeons, patients, and outcome assessors were masked to treatment allocation. The primary outcome was perioperative red blood cell transfusion to 30 days post-randomisation, analysed in all randomly assigned patients who underwent liver resection. PRICE-2 trial was registered with ClinicalTrials.gov (NCT03651154) and is completed.

Between Oct 1, 2018, and Jan 13, 2023, 486 individuals were randomly assigned to receive hypovolaemic phlebotomy (n=245) or usual care (n=241). 22 individuals in the hypovolaemic phlebotomy group and 18 in the usual care group did not undergo liver resection and were thus excluded from the primary analysis population. 223 patients were included in the hypovolaemic phlebotomy group (mean age 61·4 years [SD 13·0]; 137 [61%] men) and 223 in the control group (62·1 years [12·1]; 114 [51%]). 17 (8%) of 223 patients allocated to hypovolaemic phlebotomy and 36 (16%) of 223 patients allocated to usual care had a perioperative red blood cell transfusion by 30 days (difference -8·8 percentage points [95% CI -14·8 to -2·8]; adjusted risk ratio [aRR] 0·47 [95% CI 0·27 to 0·82]). Severe complications to 30 days occurred in 37 (17%) patients allocated to hypovolaemic phlebotomy and 36 (16%) allocated to usual care (aRR 1·06 [95% CI 0·70-1·61]). Overall complications to 30 days occurred in 135 (61%) of 223 patients allocated to hypovolaemic phlebotomy and 116 (52%) of 223 patients allocated to usual care (1·08 [0·92-1·25]). There was no postoperative mortality to 90 days.

In patients undergoing liver resection, hypovolaemic phlebotomy reduced perioperative red blood cell transfusion and improved operative conditions, with no statistically significant increase in the incidence of complications compared with usual care. Hypovolaemic phlebotomy should be considered for routine use in patients undergoing liver resection at higher risk of bleeding.

Canadian Institutes of Health Research (PJT-156108).

Perioperative chemotherapy has emerged as a critical component in managing resectable colorectal liver metastases (CRLM), aiming to improve long-term survival, although data supporting its use remains controversial. This narrative review explores the current state of perioperative chemotherapy in patients with resectable CRLM, focusing on its role in different oncological risk categories. The review highlights ongoing controversies, such as optimal patient selection and the role of post- versus preoperative treatment in specific scenarios.

Hepatic artery infusion (HAI) chemotherapy, particularly with floxuridine (FUDR), has previously shown effectiveness in improving recurrence-free survival (RFS) in colorectal cancer (CRC) patients with colorectal liver metastases (CRLM). Nonetheless, its adjuvant use alongside modern systemic chemotherapy remains unevaluated.

The HARVEST trial is an open-label, randomized, controlled study conducted from May 2018 to August 2021. CRC patients with resectable primary tumors and CRLM were recruited and randomized to receive standard systemic chemotherapy only (non-HAI group) or in combination with HAI-FUDR (HAI group). However, due to a FUDR manufacturing shortage, the study was terminated early after enrolling 92 patients. The primary endpoint was the 3-year RFS rate, with secondary endpoints including overall survival (OS), liver-specific RFS, and adverse events.

Of the 92 randomized patients, 77 were included in the modified intention-to-treat analysis. Three-year RFS rates were comparable between the HAI (N = 38) and non-HAI (N = 39) groups (31.4 % vs. 34.4 %; P = 0.28). However, improved 1-year RFS and a longer expected five-year OS were observed in the HAI group. While exploratory subgroup analysis suggested potential RFS benefits for patients with multiple liver metastases, RAS/BRAF mutations, and positive postoperative ctDNA methylation, multivariable analysis did not identify these as independent factors. Safety analysis showed comparable chemotherapy-related adverse events, except for a higher occurrence of ALT elevation in the HAI group.

While our study showed no significant difference in three-year RFS, adjuvant chemotherapy intensification with HAI-FUDR is feasible and may offer early benefits in RFS and long-term OS. Nonetheless, a larger sample size is needed for validation and identifying which patient subgroup might benefit from this regimen.

ClinicalTrials.gov: NCT03500874.

The management of synchronous metastatic rectal cancer (SMRC) is complex and multimodal, involving chemotherapy, surgery and/or radiotherapy. The aim of this study was firstly to confirm the efficacy of the induction FOLFIRINOX, and secondly to evaluate the different therapeutic strategies and outcomes of patients.

This French study combined data from a prospective FFCD trial and a multicenter cohort. Patients included had SMRC and had undergone induction triplet chemotherapy. Two groups of patients were defined according to the resectability of metastases at baseline: resectable (Res) and unresectable (URes). The primary endpoint was the objective response rate.

146 patients were included in 16 French centers and 65 patients in the FFCD1102 trial. In overall population the median age of patients was 59 years, 86% of tumors were of the lower or middle rectum, 33% were well-differentiated, 53% were RAS mutated and 7% BRAF mutated. Triplet induction was associated with 80% of objective response and 92% of disease control. After the induction phase, 69% and 48% of patients of Res and URes groups underwent rectal surgery, and secondary metastases resection was done in 79% and 39% of patients, respectively. Median overall survival (OS) for Res was 56.3 months (95% CI: 22.54-NA). Median OS for URes who had or not secondary metastases resection were 45.1 months (95% CI: 39.89-NA) and 21.1 months (95% CI 17.31-27.1), respectively. Patients with BRAF mutated tumors were more likely to have unresectable disease, and had worse survivals than the patients with RAS mutated or RAS/BRAF wild-type.

Triplet induction chemotherapy is a treatment of choice in selected patients with SMRC, allowing to adapt the therapeutic strategy to the response and invasiveness of the various sites.

The management of metastatic rectal cancer is essentially based on three main therapeutic approaches: surgery, radiotherapy/chemoradiotherapy and chemotherapy. Induction triplet chemotherapy appears as a good choice for fit and young patients. It allows to adapt the therapeutic strategy to the response and invasiveness of the various sites. In this study dedicated to patients undergoing treatment for rectal cancer with synchronous metastases, FOLFIRINOX-based induction chemotherapy was associated with objective response rate of 77% and disease control rate of 92%. These results are similar with those of the FFCD 1102 trial and confirm the efficacy of induction chemotherapy with FOLFIRINOX with or without targeted therapy in these patients in daily routine practice. Surgery for metastases is a key factor in determining patient's outcome and triplet induction chemotherapy, associated with high response rates, enables a significant percentage of patients to undergo surgery and appears therefore to be a treatment of choice, particularly for patients whose disease is unresectable at baseline.

The combination of preoperative chemotherapy and surgical treatment has been shown to significantly enhance the prognosis of colorectal cancer with liver metastases (CRLM) patients. Nevertheless, as a result of variations in clinicopathological parameters, the prognosis of this particular group of patients differs considerably. This study aimed to develop and evaluate Cox proportional risk regression model and competing risk regression model using two patient cohorts. The goal was to provide a more precise and personalized prognostic evaluation system.

We collected information on individuals who had a pathological diagnosis of colorectal cancer between 2000 and 2019 from the Surveillance, Epidemiology, and End Results (SEER) Database. We obtained data from patients who underwent pathological diagnosis of colorectal cancer and got comprehensive therapy at the hospital between January 1, 2010, and June 1, 2022. The SEER data collected after screening according to the inclusion and exclusion criteria were separated into two cohorts: a training cohort (training cohort) and an internal validation cohort (internal validation cohort), using a random 1:1 split. Subgroup Kaplan-Meier (K-M) survival analyses were conducted on each of the three groups. The data that received following screening from the hospital were designated as the external validation cohort. The subsequent variables were chosen for additional examination: age, gender, marital status, race, tumor site, pretreatment carcinoembryonic antigen level, tumor size, T stage, N stage, pathological grade, number of tumor deposits, perineural invasion, number of regional lymph nodes examined, and number of positive regional lymph nodes. The primary endpoint was median overall survival (mOS). In the training cohort, we conducted univariate Cox regression analysis and utilized a stepwise regression approach, employing the Akaike information criterion (AIC) to select variables and create Cox proportional risk regression models. We evaluated the accuracy of the model using calibration curve, receiver operating characteristic curve (ROC), and area under curve (AUC). The effectiveness of the models was assessed using decision curve analysis (DCA). To evaluate the non-cancer-related outcomes, we analyzed variables that had significant impacts using subgroup cumulative incidence function (CIF) and Gray's test. These analyses were used to create competing risk regression models. Nomograms of the two models were constructed separately and prognostic predictions were made for the same patients in SEER database.

This study comprised a total of 735 individuals. The mOS of the training cohort, internal validation cohort, and QDU cohort was 55.00 months (95%CI 46.97-63.03), 48.00 months (95%CI 40.65-55.35), and 68.00 months (95%CI 54.91-81.08), respectively. The multivariate Cox regression analysis revealed that age, N stage, presence of perineural infiltration, number of tumor deposits and number of positive regional lymph nodes were identified as independent prognostic risk variables (p < 0.05). In comparison to the conventional TNM staging model, the Cox proportional risk regression model exhibited a higher C-index. After controlling for competing risk events, age, N stage, presence of perineural infiltration, number of tumor deposits, number of regional lymph nodes examined, and number of positive regional lymph nodes were independent predictors of the risk of cancer-specific mortality (p < 0.05).

We have developed a prognostic model to predict the survival of patients with synchronous CRLM who undergo preoperative chemotherapy and surgery. This model has been tested internally and externally, confirming its accuracy and reliability.

The contemporary management of patients with colorectal cancer and synchronous liver metastases is complex. This study appraises the recommendations made by national/international guidelines for the diagnosis and management of patients with synchronous liver metastases from colorectal cancer.

A systematic review of national and international guidelines published between 2011 and 2024 was carried out using PubMed, OvidSP and Guidelines International Network databases. The quality of guidelines was evaluated using the Appraisal of Guidelines for Research & Evaluation II (AGREE II) instrument. Guidelines were assessed for the quality of advice for specific scenarios. The protocol was registered with PROSPERO (CRD42021243744).

The search strategy returned ninety unique articles with 11 guidelines eligible for inclusion. Of these, one (9 %) guideline defined 'synchronous disease' at outset, eight (73 %) recommended neoadjuvant chemotherapy as first intervention. Seven (64 %) guidelines supported synchronous hepatic resection with colectomy. One (9 %) recommended against synchronous surgery.

This study demonstrates important variations between international clinical guidelines on diagnostic workup and management of synchronous liver metastases in colorectal cancer. [167 words].

Post-hepatectomy liver failure (PHLF) is the first cause of death after major hepatectomy, and future liver remnant (FLR) volume is the main factor predicting PHLF. Liver venous deprivation (LVD) via portal and hepatic vein embolization has been suggested to induce a better hypertrophy of the FLR than portal vein embolization. The aim of this retrospective multicentric study was to assess safety, feasibility and efficacity of LVD in a French national multicentric register.

Between 2016 and 2023, LVD was performed in 7 expert centers, for patients with liver malignancies requiring major hepatectomy with an FLR percentage of total liver volume (FLR%) ≤25% for a healthy liver or <30% for a diseased liver. FLR volumetry was assessed before and 4 weeks after the procedure.

One hundred and ninety-two patients were included in the study. The technical success rate was 100% and severe complication rate post-LVD was 2.6% (5/192). The FLR% increased by 61.7% over an average of 27±9.7 days. Major hepatectomy was performed 40 days after LVD on 161 (83.8%) patients. Hepatectomy was not performed on 31 (16.2%) patients, mostly because of oncological progression. Severe postoperative complications (Clavien-Dindo grade ≥ IIIA) occurred in 21.1% (34/161) of patients. Postoperative mortality rate was 4.3% (7/161).

This study is the largest to confirm that LVD is a safe, reproducible, efficient technique that induces rapid major FLR growth. However, this new technique needs to be standardized and harmonized between centers to ensure uniform results.

The regenerative capacities of the liver and improvements in surgical techniques have expanded the possibilities of resectability. Liver resection is often the only curative treatment for primary and secondary malignancies, despite the risk of post-hepatectomy liver failure (PHLF). This serious complication (with a 50% mortality rate) can be avoided by better assessment of liver volume and function of the future liver remnant (FLR).

The aim of this review was to understand and assess clinical, biological, and imaging predictors of PHLF risk, as well as the various hypertrophy techniques, to achieve an adequate FLR before hepatectomy.

We reviewed the state of the art in liver regeneration and FLR hypertrophy techniques.

The use of new biological scores (such as the aspartate aminotransferase/platelet ratio index + albumin-bilirubin [APRI+ALBI] score), concurrent utilization of 99mTc-mebrofenin scintigraphy (HBS), or dynamic hepatocyte contrast-enhanced MRI (DHCE-MRI) for liver volumetry helps predict the risk of PHLF. Besides portal vein embolization, there are other FLR optimization techniques that have their indications in case of risk of failure (e.g., associating liver partition and portal vein ligation for staged hepatectomy, liver venous deprivation) or in specific situations (transarterial radioembolization).

There is a need to standardize volumetry and function measurement techniques, as well as FLR hypertrophy techniques, to limit the risk of PHLF.

The prognostic value of baseline variant allele frequency (VAF) in circulating tumor DNA (ctDNA) of colorectal cancer liver metastases (CRLM) patients after curative resection was rarely investigated.

A single-center prospective study was performed to investigate the prognostic impact of baseline VAF in ctDNA and matched tumor tissues of CRLM patients after curative resection between May 2019 and May 2021 by the Illumina NovoSeq 6000 platform. The relationship of the tumor burden score (TBS) and the VAF in ctDNA and matched tumor tissues was evaluated by the Pearson correlation method. The survival curves of recurrence-free survival (RFS) and overall survival (OS) were plotted. Factors associated with RFS were calculated using Cox regression analysis, and an integrated prognostic model using significant baseline variables was proposed.

There were 121 patients with baseline ctDNA and matched tumor tissues enrolled in the study. A total of 417 mutations spanning 20 genes were identified in baseline tumor tissues of 119/121 (98.3 %) cases. The overall mutations in tumor tissues were completely covered by ctDNA in 52 of 121(43.0 %) patients. Baseline VAF in ctDNA but not in tumor tissues was significantly correlated to TBS of CRLM (R = 0.36, p < 0.001). Significantly longer RFS but not OS was observed in patients with lower VAF in ctDNA compared to those with higher one (p < 0.001 and p = 0.33 respectively). Multivariate Cox regression analysis showed higher VAF in baseline ctDNA was an independent risk factor for RFS. An integrated prognostic model including baseline metastasis location and VAF in ctDNA outperformed the traditional CRS model in predicting RFS.

Baseline VAF in ctDNA but not in tumor tissues influenced RFS of CRLM patients after curative resection.

The significance of resection of para-aortic lymph node metastasis in colorectal cancer is controversial.

To clarify the prognosis of colorectal cancer after para-aortic lymph node metastasis resection.

Multicenter retrospective study.

Thirty-six institutions in Japan participated in this study. Database and medical records at each institution were used for data collection.

Patients with resected and pathologically proven para-aortic lymph node metastasis of colorectal cancer between 2010 and 2015 were included.

Overall survival after para-aortic lymph node metastasis resection, recurrence-free survival, and recurrence patterns after R0 resection of para-aortic lymph node metastasis.

A total of 133 patients were included in the primary analysis population in this study. The 5-year overall survival rate (95% CI) was 41.0% (32.0-49.8), and the median survival (95% CI) was 4.1 (3.4-4.7) years. Independent prognostic factors for overall survival were the pathological T stage (pT4 vs pT1- 3, adjusted HR: 1.91, p = 0.006), other organ metastasis (present vs absent, adjusted HR: 1.98, p = 0.005), time to metastases (synchronous vs metachronous adjusted HR: 2.02, p = 0.02), and the number of para-aortic lymph node metastasis (3 or more vs less than 3, adjusted HR: 2.13, p = 0.001). The 5-year recurrence-free survival rate (95% CI) was 21.1% (13.5-29.7), with a median (95% CI) of 1.2 (0.9-1.4) years. The primary tumor location (left- vs right-sided colon, adjusted HR: 4.77, p = 0.01; rectum vs right-sided colon, adjusted HR: 5.27, p = 0.006), other organ metastasis (present vs absent, adjusted HR: 1.90, p = 0.03), number of para-aortic lymph node metastases (3 or more vs less than 3, adjusted HR: 2.20, p = 0.001), and hospital volume (less than 10 vs 10 or more, adjusted HR: 2.18, p = 0.02) were identified as independent prognostic factors for recurrence-free survival. Para-aortic lymph node recurrence was the most common at 33.3%.

Selection bias cannot be ruled out because of the retrospective nature of the study.

Less than 3 para-aortic lymph node metastases were a favorable prognostic factor for overall and recurrence-free survival. However, para-aortic lymph node metastases were considered to be a systemic disease, and the significance of resection was limited. See Video Abstract .

ANTECEDENTES:La importancia de la resección de metástasis en los ganglios linfáticos paraaórticos (PALNM) en el cáncer colorrectal (CCR) es controvertida.OBJETIVO:Aclarar el pronóstico del CCR después de la resección PALNM.DISEÑO:Estudio retrospectivo multicéntrico.ENTORNO CLINICO:Treinta y seis instituciones en Japón participaron en este estudio.PACIENTES:Pacientes con PALNM de CCR resecado y patológicamente probado entre 2010 y 2015.FUENTES DE DATOS:Base de datos y registros médicos de cada institución.PRINCIPALES MEDIDAS DE RESULTADO:Supervivencia general (SG) después de la resección PALNM, supervivencia libre de recurrencia (SLR) y patrones de recurrencia después de la resección R0 de PALNM.RESULTADOS:Se incluyó un total de 133 pacientes en la población de análisis primario de este estudio. La tasa de SG a 5 años (intervalo de confianza [IC] del 95 %) fue del 41,0 % (32,0, 49,8) y la mediana de supervivencia (IC del 95 %) fue de 4,1 (3,4, 4,7) años. Los factores de pronóstico independientes para la SG fueron el estadio T patológico (pT4 vs. pT1-3, índice de riesgo ajustado [aHR]: 1,91, p = 0,006), metástasis en otros órganos (presente vs. ausente, aHR: 1,98, p = 0,005), tiempo hasta las metástasis (síncronas vs. metacrónicas, aHR: 2,02, p = 0,02) y número de PALNM (≥3 vs. <3, aHR: 2,13, p = 0,001). La tasa de SLR a 5 años (IC del 95%) fue del 21,1% (13,5, 29,7), con una mediana (IC del 95%) de 1,2 (0,9, 1,4) años. La ubicación del tumor primario (colon del lado izquierdo vs. derecho, aHR: 4,77, p = 0,01; recto vs. colon del lado derecho, aHR: 5,27, p = 0,006), metástasis en otros órganos (presente vs. ausente, aHR: 1,90, p = 0,03), el número de PALNM (≥3 vs. <3, aHR: 2,20, p = 0,001) y el volumen hospitalario (<10 vs. ≥10, aHR: 2,18, p = 0,02) se identificaron como independientes factores pronósticos del SLR. La recurrencia de los ganglios linfáticos paraaórticos fue la más común con un 33,3%.LIMITACIONES:No se puede descartar un sesgo de selección debido a la naturaleza retrospectiva del estudio.CONCLUSIONES:Menos de tres PALNM fue un factor pronóstico favorable tanto para la SG como para la SLR. Sin embargo, las PALNM se consideraron una enfermedad sistémica y la importancia de la resección fue limitada. (Traducción- Dr. Francisco M. Abarca-Rendon ).