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.

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.

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 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.

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.

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.

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).

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.

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 ).

Introduction and Objective  It is unclear if the length of the time interval to initiation of adjuvant radiation therapy (RT) after endoscopic endonasal surgery affects reconstruction outcomes. In this study we present our experience with adjuvant RT after endoscopic endonasal procedures, to determine if the time to RT after surgery impacts post-RT reconstruction complication rates. Methods  A retrospective cohort study of 164 patients who underwent endoscopic endonasal surgery between 1998 and 2021 was conducted. Using Cox proportional hazard ratios (HRs), we evaluated several variables and the complications that occurred during the 1-year period after starting RT. Results  Seventy-eight (47.5%) and eighty-six patients (52.5%) received RT before and after the sixth postoperative week, respectively. The overall post-RT complication rates were 28%, most of these were severe infections ( n  = 20, 12.2%) and delayed CSF leak ( n  = 4, 2.5%). There was no significant difference in the post-RT complications between the patients who received postoperative RT before or after the sixth operative week (HR: 1.13; 95% confidence interval: 0.63-2.02; p = 0.675 ). Univariate analysis demonstrated negative impact associated with smoking history ( p = 0.015 ), the use of neoadjuvant chemotherapy ( p = 0.0001 ), and the use of photon therapy ( p = 0.012 ); and we found a positive impact with the use of multilayer reconstruction techniques (overall, p = 0.041 ; with fat, p = 0.038 ; and/or fascia graft, p = 0.035 ). After a multivariate analysis only, smoking history was an independent risk factor for post-RT complications ( p = 0.012 ). Conclusion  Delaying RT for more than 6 weeks after endoscopic endonasal surgery does not provide a significant benefit for reconstruction outcomes. However, special attention may be warranted in patients with smoking history who have received neoadjuvant chemotherapy, or in patients who will receive photon-based RT after surgery as these groups were found to have increased complication rates post-RT.

The prognostic implications of the RAS status in colorectal cancer liver metastasis (CRLM) remain unclear. This study investigated the prognostic significance of RAS status after curative hepatectomy, focusing on surgical controllability.

This retrospective study included liver-only CRLM patients who underwent the first hepatectomy between 2015 and 2022 at the National Cancer Center Hospital. Recurrence-free survival (RFS), surgically controllable period (SCP), and overall survival (OS) were compared between RAS wild-type (RAS-wt) and mutant (RAS-mt) patients. Multivariate analyses were conducted to identify independent prognostic factors for each outcome and independent risk factors for less than 1 year SCP.

A total of 150 patients were evaluated, comprising 63 patients with RAS-mt status. There was no significant difference in RFS between RAS-mt and RAS-wt (7.00 vs. 8.03 months, p = 0.48). RAS-mt patients exhibited worse SCP (11.80 vs.21.13 months, p < 0.001) and OS (44.03 vs. 70.03 months, p < 0.001) compared to RAS-wt. Multivariate analysis identified RAS-mt as an independent prognostic factor for both OS (hazard ratio [HR]: 3.37, p < 0.001) and SCP (HR: 2.20, p < 0.001), and as an independent risk factor for less than 1 year of SCP (odds ratio, 2.31; p = 0.03).

CRLM with RAS mutations should be considered for strict surgical indications with preoperative chemotherapy and thorough examination, considering the possibility of short SCP.

Colorectal cancer (CRC) is a complex and genetically heterogeneous disease presenting a specific metastatic pattern, with the liver being the most common site of metastasis. Around 20%-25% of patients with CRC will develop exclusively hepatic metastatic disease throughout their disease history. With its specific characteristics and therapeutic options, liver-limited disease (LLD) should be considered as a specific entity. The identification of these patients is particularly relevant in view of the growing interest in liver transplantation in selected patients with advanced CRC. Identifying why some patients will develop only LLD remains a challenge, mainly because of a lack of a systemic understanding of this complex and interlinked phenomenon given that cancer has traditionally been investigated according to distinct physiological compartments. Recently, multidisciplinary efforts and new diagnostic tools have made it possible to study some of these complex issues in greater depth and may help identify targets and specific treatment strategies to benefit these patients. In this review we analyze the underlying biology and available tools to help clinicians better understand this increasingly common and specific disease.

Liver cancer is a leading cause of cancer deaths worldwide. Surgical resection of superficial hepatic lesions is increasingly guided by the disrupted bile excretion of the fluorescent dye indocyanine green (ICG). To extend this approach to deeper lesions, a dedicated bimodal tracer that facilitates both fluorescence guidance and radioguidance was developed. Methods: A tracer comprising a methylated cyanine-5 (Cy5) fluorescent dye and a mercaptoacetyltriserine chelate (hHEPATO-Cy5) was synthesized and characterized. Cellular uptake and excretion were evaluated in hepatocyte cultures (2-dimensional culture and in vitro lesion model), using a fluorescent bile salt, MitoTracker dye, and methylated Cy5 as a control. After radiolabeling, the pharmacokinetics of 99mTc-hHEPATO-Cy5 were assessed in mice over 24 h (percentage injected dose and percentage injected dose per gram of tissue, SPECT/CT imaging and fluorescence imaging). The ability to provide real-time fluorescence guidance during robot-assisted hepatobiliary surgery was evaluated in a porcine model using ICG as a reference. Results: The unique molecular signature of hHEPATO-Cy5 promotes hepatobiliary excretion. In vitro studies on hepatocytes showed that where methylated Cy5 remained internalized, hHEPATO-Cy5 showed fast clearance (10 min) similar to that of fluorescent bile salt. In vivo use of 99mTc-hHEPATO-Cy5 in mice revealed liver accumulation and rapid biliary clearance. The effectiveness of bile clearance was best exemplified by the 2-orders-of-magnitude reduction in count rate for the gallbladder (P = 0.008) over time. During hepatobiliary surgery in a porcine model, hHEPATO-Cy5 enabled fluorescence-based lesion identification comparable to that of ICG. Conclusion: The bimodal 99mTc-hHEPATO-Cy5 provides an effective means to identify liver lesions. Uniquely, it helps overcome the shortcomings of fluorescence-only approaches by allowing for an extension to in-depth radioguidance.

This study aimed to assess the prognostic value of total tumor volume (TTV) for early recurrence (within 6 months) and overall survival (OS) in patients with colorectal liver metastases (CRLM), treated with induction systemic therapy followed by complete local treatment.

Patients with initially unresectable CRLM from the multicenter randomized phase 3 CAIRO5 trial (NCT02162563) who received induction systemic therapy followed by local treatment were included. Baseline TTV and change in TTV as response to systemic therapy were calculated using the CT scan before and the first after systemic treatment, and were assessed for their added prognostic value. The findings were validated in an external cohort of patients treated at a tertiary center.

In total, 215 CAIRO5 patients were included. Baseline TTV and absolute change in TTV were significantly associated with early recurrence (P = 0.005 and P = 0.040, respectively) and OS in multivariable analyses (P = 0.024 and P = 0.006, respectively), whereas RECIST1.1 was not prognostic for early recurrence (P = 0.88) and OS (P = 0.35). In the validation cohort (n = 85), baseline TTV and absolute change in TTV remained prognostic for early recurrence (P = 0.041 and P = 0.021, respectively) and OS in multivariable analyses (P < 0.0001 and P = 0.012, respectively), and showed added prognostic value over conventional clinicopathological variables (increase C-statistic, 0.06; 95 % CI, 0.02 to 0.14; P = 0.008).

Total tumor volume is strongly prognostic for early recurrence and OS in patients who underwent complete local treatment of initially unresectable CRLM, both in the CAIRO5 trial and the validation cohort. In contrast, RECIST1.1 did not show prognostic value for neither early recurrence nor OS.

Despite the increasing use of immunotherapy in treating various cancer types, there is still limited understanding of its impact on surgical complications. We used a national database to examine the difference in surgical outcomes for rectal cancer patients who received standard neoadjuvant chemoradiation plus neoadjuvant immunotherapy and patients who received neoadjuvant chemoradiation only.

This retrospective cohort study used the National Cancer Database (NCDB). We selected patients aged 18-90 with T1-3, N1-2, and M0 rectal cancer who underwent curative-intent surgery between 2010 and 2020. We performed a 1:1 propensity match to control for patient age, sex, Charlson-Deyo comorbidity index, surgical approach, and tumor site. Our primary outcome was difference in surgical outcomes (hospital length of stay, unplanned 30-day readmission, 30-day mortality) between the two groups. Secondary outcomes included days from diagnosis to surgery and pathologic outcomes.

Our study included 26 229 patients, of which 126 received immunotherapy in addition to chemoradiation and 26 103 received only chemoradiation. In our matched population of 125 pairs of patients, patients who received immunotherapy and chemoradiation underwent surgery later compared to patients who only received chemoradiation (median 245 vs. 144 days, p < 0.001). There were no significant differences in median length of stay (5 vs. 5 days, p = 0.202), unplanned 30-day readmission (7 vs. 9, p = 0.617), and 30-day mortality (0 vs. 1, p = 1.000) between the two groups.

Neoadjuvant immunotherapy for rectal cancer is not associated with adverse surgical outcomes. This work can help clinicians optimize treatment protocols and move closer toward strategies tailored to specific patient profiles.

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.

Despite decreased incidence rates in average-age onset patients in high-income economies, colorectal cancer is the third most diagnosed cancer in the world, with increasing rates in emerging economies. Furthermore, early onset colorectal cancer (age ≤50 years) is of increasing concern globally. Over the past decade, research advances have increased biological knowledge, treatment options, and overall survival rates. The increase in life expectancy is attributed to an increase in effective systemic therapy, improved treatment selection, and expanded locoregional surgical options. Ongoing developments are focused on the role of sphincter preservation, precision oncology for molecular alterations, use of circulating tumour DNA, analysis of the gut microbiome, as well as the role of locoregional strategies for colorectal cancer liver metastases. This overview is to provide a general multidisciplinary perspective of clinical advances in colorectal cancer.

By presenting the most up-to-date findings and incorporating the latest evidence, this article seeks to present a comprehensive guide for navigating the complexities inherent in the management of colorectal liver metastasis. It aims to serve as a valuable resource offering clinicians and healthcare professionals an understanding of the diverse modalities and approaches available for treating this challenging and multifaceted disease. In an era of rapidly evolving medical knowledge, this article examines the latest insights to make informed decisions in the realm of colorectal liver metastasis management. The article does not only highlight the up-to-date knowledge but also provides the evidence for existing therapeutic strategies. This practical tool provides evidence-based recommendations to clinicians, thereby contributing to the ongoing advancement of effective treatment strategies for this challenging disease.

Thermal ablation is routinely used for solitary colorectal liver metastases (SCLM), but the added value of adjuvant systemic therapy in SCLM remains unclear. This study aimed to compare the long-term outcomes for SCLM treated by ablation alone (AB) versus ablation plus systemic therapy (AS).

This multicenter retrospective study using nationwide data from fourteen institutions between October 2010 and May 2023, 369 patients with initial SCLM smaller than 5 cm, no extrahepatic metastases, and colorectal cancer R0 resection treated by thermal ablation were included. The crude analysis was used to analyze eligible cases between the two groups. The propensity score matching to control for potential confounders in each matched group. Subgroup analyses were performed to identify specific survival benefits.

61.2% (226/369) of eligible patients were treated with AS and 38.8% (143/369) with AB. During the median follow-up period of 8.8 years, 1-/3-/5-year DFS/OS rates did not differ between the two groups, when analyzed via propensity score matching ( P =0.52/0.08). Subgroup analysis revealed that AS was significantly associated with better OS than AB in patients with plasma CEA >5 ug/l ( P =0.036), T (III-IV) category of primary cancer ( P =0.034), or clinical risk score (1-2) ( P =0.041). In each matched group, the authors did find a significant difference in drug-related adverse events ( P <0.001) between AS group (24.1%, 28/116) and AB group (0.0%, 0/116).

For patients with plasma CEA >5 ug/l, T (III-IV) category of primary cancer, or clinical risk score (1-2), thermal ablation plus systemic therapy appeared to be associated with improved overall survival. Thermal ablation was equally effective in disease-free survival for treating SCLM, whether with or without adjuvant systemic therapy.

This review addresses the current landscape of colorectal cancer (CRC) with a focus on liver metastases, the third most common cancer globally. It explores recent findings in treatment strategies, emphasizing the dynamic interplay between surgery, systemic chemotherapy, and local therapies for synchronous colorectal liver metastases (CRLMs).

Highlighting the role of advanced imaging, the review underscores the significance of contrast-enhanced MRI in surgical planning for CRLMs. Surgical resection remains a primary choice for resectable cases, with considerations for oncologic scoring systems and tumor biology. Perioperative systemic chemotherapy plays a pivotal role, especially in conversion therapy for initially unresectable CRLMs. The review also explores various local therapies, including radiofrequency ablation, microwave ablation, stereotactic body radiotherapy, hepatic arterial infusional chemotherapy, selective internal radiation therapy, and transarterial chemoembolization for unresectable cases. A comprehensive approach, integrating surgery, systemic chemotherapy, and local therapies, is crucial for managing synchronous CRLMs. Surgical resection and perioperative chemotherapy are key players, guided by considerations of tumor biology and scoring systems. For unresectable cases, local therapies offer viable alternatives, emphasizing the need for tailored treatments. Multidisciplinary collaboration among medical oncologists, surgeons, and radiologists is essential. Ongoing research will refine treatment approaches, while emerging technologies hold promise for further advancements in managing colorectal liver metastases.