More than 50% of patients diagnosed with colorectal cancer (CRC) will develop liver metastases (CRCLM), which is the main cause of death for more than 60% of these patients. The aim of this study was to correlate the clinical and pathological characteristics of the primary CRC and CRCLM, with emphasis in predicting the histological growth pattern of the CRCLM.

Cohort of 73 patients with CRC. Analysis of clinical data and blinded pathological review was performed related with primary tumor and CRCLM features. The analysis was performed in SPSS (version 27) with a significance level of 5%.

A statistically significant association was found between tumor size and metastasis growth pattern (P = .002), with larger tumors giving rise to metastases with a nondesmoplastic growth pattern. Lymphovascular invasion (LVI) was associated with metachronous CRCLM (P = .043). In the absence of LVI, the time required for CRCLM to appear was significantly longer (P = .011). The number of metastases was significantly higher (P = .049) in tumors without LVI when compared to tumors with LVI. There was a statistically significant association between CRC high-grade inflammation and the desmoplastic metastases growth pattern of the CRCLM (P = .017).

The possibility of predicting the CRCLM histological growth pattern resorting to primary CRC characteristics would be useful for proper patient selection for surgery and adapting biological therapies.

KRAS mutation is a negative prognostic factor for colorectal liver metastases (CRLM). Thermal ablation (TA) is considered a valid alternative to liver resection (LR) for CRLM in selected cases. This study aims to investigate the influence of KRAS status on long-term outcomes of TA during LR.

This is a retrospective analysis of patients undergoing surgery for CRLM in two hepatobiliary centers. Patients were divided into two groups: LR or LR + TA, and long-term results were investigated according to KRAS status.

220 patients were included, of whom 74 (33.6%) were KRAS mutated. TA was performed in association with LR in 42 mutated (mKRAS) tumors (56.7%). Multivariate analysis in mKRAS patients showed that synchronous disease (p = 0.014), performing TA (p = 0.044), performing two or more TA (p = 0.032), and N2 status (p < 0.001) were independently associated with DFS. TA was more frequently associated with a liver-only recurrence, both in mutated and wt tumors, but with a higher risk in mKRAS (p = 0.013 vs. p = 0.048).

CRLM surgical treatment should be tailored to KRAS status because TA may potentially be less effective in mutated patients during surgical resection. This is even more important in the case of multiple ablations.

Histologic microscopic positive resection margin is a debated prognostic factor in patients resected for colorectal liver metastases. This study aimed to assess whether patients with R1 resection experience recurrence at the site of the resection (on-site recurrence) and to identify predictive factors for recurrence profiles in patients with R1 margins after resection of colorectal liver metastases.

All surgical colorectal liver metastasis resection cases with R1 parenchymal margin from September 2014 to March 2020 in our center were retrospectively included. Imaging was reviewed for each metastasis. All the analyses were performed per metastasis. Recurrence location was examined for each metastasis according to the site of the R1 margin and defined as on-site when recurrence was at the same place of the resected lesion. Prognostic factors for recurrence type were assessed using logistic regression.

Of 700 patients who underwent liver resection for colorectal liver metastases, 105 (15%) had at least 1 metastasis with R1 resection margin, representing 6.8% per metastasis. The median follow-up was 34 months. Overall recurrence occurred in 130 metastases (83.3%) with intrahepatic recurrence in 106 metastases (80.9%). On-site recurrence was observed for 49 metastases (31.4%) and isolated (without an additional recurrence site) for 20 metastases (12.8%). The on-site recurrence did not impact overall survival. Three predictive factors for on-site recurrence were found in the multivariate logistic regression: synchronous metastases, nonanatomic resection, and pathologic response tumor regression grade 4-5.

Intrahepatic localization of recurrence is more frequent than on-site recurrence after R1 parenchymal resection. Synchronous metastases, nonanatomic resection, and tumor regression grade 4-5 may impact the risk of on-site recurrence.

Systemic therapy, including liver resection, is crucial for treating metastatic liver tumors. Even when radical resection is successful, early recurrence of advanced or metastatic liver tumors may restrict subsequent treatment options, particularly if delayed liver function recovery (DLFR) occurs after hepatectomy. This study focused on DLFR after right hepatectomy for metastatic liver tumors.

This study involved a retrospective analysis of 78 patients who underwent right hepatectomy for metastatic liver tumors between 2007 and 2022. DLFR was defined as a modified albumin-bilirubin (mALBI) grade that was lower than that preoperatively or ≤ 2b at 3 months after surgery. Patient characteristics, surgical outcomes, and perioperative factors were compared between patients with and without DLFR. Overall survival (OS) was also assessed in patients with colorectal liver metastases.

The median age was 63, and 6 patients had ASA-PS ≥ 3. Of the primary tumors, 67 were colorectal cancer. The median preoperative indocyanine green retention rate at 15 min (ICG-R15) was 5.8%, and sarcopenia was present in 23 patients. Eight patients had complications of Clavien-Dindo grade ≥ 3a classification. DLFR occurred in 24 patients (30.7%). Univariate analysis identified ASA-PS ≥ 3, ICG-R15 ≥ 10%, sarcopenia, and grade ≥ 3a complications as significant factors. Multivariate analysis found ICG-R15 ≥ 10% (p = 0.021, HR = 4.352) and sarcopenia (p = 0.035, HR = 3.852) to be the predictors of DLFR. Three-year OS was worse in the DLFR group (p < 0.001).

Approximately 30% of patients developed DLFR following right hepatectomy. DLFR may adversely affect OS, and this risk should be carefully considered, particularly in patients with ICG-R15 > 10% or sarcopenia.

Surgeons may consider parenchymal-sparing hepatectomy (PSH) or major hepatectomy (MH) for patients with bilateral colorectal liver metastases (CLMs). This study aimed to evaluate the outcomes between PSH and MH for patients with extensive, bilateral CLMs.

A prospective database was queried for patients with ≥5 bilateral CLMs who underwent R0-intent initial single-stage hepatectomy (1998-2022). The outcomes were compared between patients who underwent PSH and those who underwent MH (≥3 Couinaud segments). The median follow-up was 49 months.

Among 206 patients, 90 (44%) underwent PSH, and 116 (56%) underwent MH. Although the PSH cohort had smaller tumors than the MH cohort (median: 2.0 vs 3.5 cm, respectively; P =.001), there were no differences in the treatment approach or mutational status. Patients who underwent PSH had lower rates of posthepatectomy liver insufficiency than those who underwent MH (1% vs 13%, respectively; P =.030). PSH increased significantly during the study period, and more patients who underwent PSH had margin-positive resections (47% in the PSH group vs 30% in the MH group; P =.02). Across the study period, 173 patients (84%) had recurrence. Local recurrence rates (35% in the PSH group vs 28% in the MH group), median recurrence-free survival (RFS: 7 months in the PSH group vs 9 months in the MH group), and hepatic-specific disease-free survival (DFS: 8 months in the PSH group vs 14 months in the MH group) were similar, regardless of approach (all P >.3). When stratified by tumor number (5-7, 8-10, or ≥11), the rates of PSH, margin-positive resection, and local recurrence were comparable. Overall survival was similar between the PSH and MH groups (median: 59 vs 47 months, respectively; P =.072).

PSH was associated with increased rates of positive margins for patients with high-volume bilateral CLMs who underwent R0-intent hepatectomy. However, hepatic-specific DFS and RFS were comparable with patients with similar disease who underwent MH.

Communicating vessels among hepatic veins in patients with tumors invading/compressing hepatic veins at their caval confluence facilitate new surgical solutions. Although their recognition by intraoperative ultrasound has been described, the possibility of preoperative detection still remains uncertain. We aimed to develop a model to predict their presence before surgery.

Patients with caval confluence-located tumors who underwent surgery between 2010 and 2022 were collected and analyzed. A total of 136 eligible patients were assigned randomly into the derivation (n = 96) and validation (n = 40) cohorts. Communicating vessels were recorded as visible or not considering the intraoperative ultrasound findings as reference. A predictive model was built and graphically represented as nomogram.

Of 136 patients included, 106 (78%) had communicating vessels. Of patients with communicating vessels, a parenchyma-sparing hepatectomy was performed in 98 (92%; 77% with hepatic vein amputation, 75/98). Of 30 patients without communicating vessels, all underwent an R1 vascular parenchyma-sparing hepatectomy. Operative mortality was nil. No liver congestion occurred. In the former, presence of communicating vessels at the intraoperative ultrasound was detected in 75 (78%) patients, whereas in the validation cohort it was detected in 31 (78%). No differences in the distribution of the variables were found in the 2 cohorts. The model included tumor size at the confluence, tumor number, degree of hepatic vein infiltration, and density of hepatic tissue at contrast-computed tomography, as predictors of communicating vessels in derivation cohort (discrimination was area under the receiver operating characteristic curve = 0.82).

Identification of communicating vessels in patients with tumors at the caval confluence opens new surgical options, expanding resectability. The present predictive model may play a useful role in facilitating surgical decision-making, developing and implementing surgical strategies, and guiding resectability improvement efforts.

Hepatocellular carcinoma (HCC) remains a significant global health challenge, with over 800,000 new cases diagnosed annually. This comprehensive review examines current surgical approaches and emerging multidisciplinary strategies in HCC treatment. While traditional surgical criteria, such as the Barcelona Clinic Liver Cancer (BCLC) staging system, have been relatively conservative, recent evidence from high-volume Asian centers supports more aggressive surgical approaches in carefully selected patients. The review discusses the evolution of selection criteria, including the new "Borderline Resectable HCC" classification system, which provides more explicit guidance for surgical decision-making. Technical innovations have significantly enhanced surgical precision, including three-dimensional simulation, intraoperative navigation systems, and the advancement of minimally invasive approaches. The review evaluates the ongoing debate between anatomical versus non-anatomical resection and examines the emerging role of robotic surgery. In liver transplantation, expanded criteria beyond the Milan criteria show promising outcomes, while the integration of novel biomarkers and imaging techniques improves patient selection. The role of preoperative and adjuvant therapies is increasingly important, with recent trials demonstrating the potential of immune checkpoint inhibitors combined with anti-VEGF agents in both settings. Despite these advances, postoperative recurrence remains a significant challenge. The review concludes that successful HCC treatment requires a personalized approach, integrating surgical expertise with emerging technologies and systemic therapies while considering individual patient factors and regional variations in practice patterns.

Carcinoembryonic antigen (CEA) levels may vary with administration and discontinuation of pre-hepatectomy chemotherapy in patients undergoing resection of colorectal cancer liver metastases (CLM). The prognostic significance of these changes, termed CEA dynamics, is unclear.

Consecutive patients undergoing hepatectomy for CLM (2001-2021) at a comprehensive cancer center were included. CEA dynamics were classified as CEA normal (CEA < 5 ng/mL before, during, and after chemotherapy), CEA decrease (elevated CEA levels that drop during and after chemotherapy), and CEA rebound (elevated CEA levels that drop during chemotherapy but rebound upon discontinuation). Recurrence-free (RFS), hepatic-specific disease-free (hDFS), and overall survival (OS) were compared across CEA dynamics groups.

Of 903 patients, 254 (28%) were CEA normal, 423 (47%) were CEA decrease, and 226 (25%) were CEA rebound. Median RFS was 15.9 months, median hDFS was not reached, and median OS was 11.9 years for CEA normal patients. By comparison, CEA decrease and CEA rebound patients had shorter median RFS (12.2 months, P = 0.002 and 7.4 months, P < 0.001, respectively), shorter median hDFS (29.1 months, P = 0.003 and 14.8 months, P < 0.001, respectively), and shorter median OS (7.1 years, P = 0.131, and 4.9 years, P < 0.001, respectively). On multivariable analysis, CEA rebound was an independent predictor of worse RFS [hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.16-1.93], hDFS (HR 1.39, 95% CI 1.03-1.88), and OS (HR 1.79, 95% CI 1.18-2.73). Among patients with CEA rebound, RAS-BRAF/TP53 comutation and multiple tumors predicted worse OS while APC mutation predicted improved OS.

CEA rebound between pre-hepatectomy chemotherapy discontinuation and CLM resection is associated with worse oncologic outcomes, particularly in patients with aggressive tumor biology, and may help frame patient and surgeon expectations ahead of CLM resection.

Laparoscopic parenchyma-sparing hepatectomy (PSH) is an effective treatment for colorectal liver metastases (CRLMs), but ensuring the safety and radicality of the procedure, particularly for deep-seated tumors, remains challenging. Surgical navigation technologies such as augmented reality navigation (ARN) and indocyanine green fluorescence imaging (ICG-FI) are increasingly utilized to guide surgery, yet their efficacy for CRLMs is unclear. This study aims to evaluate the short-term and long-term outcomes of ARN combined with ICG-FI-guided (ARN-FI) laparoscopic PSH for CRLMs.

Between January 2020 and December 2022, 89 consecutive patients who underwent laparoscopic PSH for CRLMs were included in the study. Patients were divided into an ARN-FI group ( n = 38) and a non-ARN-FI group ( n = 51) based on the use of ARN-FI. Inverse probability treatment weighting (IPTW) was used to balance baseline characteristics and minimize potential selection bias. Short-term and long-term outcomes were compared between the two groups. Cox regression analysis was conducted to identify risk factors associated with recurrence-free survival (RFS) and hepatic RFS.

After IPTW, there were 87 patients in the ARN-FI group and 89 patients in the non-ARN-FI group. Shorter parenchymal transection time, postoperative hospital stays, and wider margins were observed in the ARN-FI group. There was no significant difference in RFS or hepatic RFS between the groups. Mutant KRAS status was an independent risk factor for both RFS and hepatic RFS, while tumor diameter ≥ 5 cm and deep-seated location were risk factors for hepatic RFS. In the subgroup analysis of deep-seated tumors, the ARN-FI group also showed less intraoperative blood loss, a lower rate of strategy change, shorter postoperative recovery times, a higher R0 resection rate, and improved RFS and hepatic RFS.

In laparoscopic PSH for CRLMs, ARN-FI may improve surgical efficiency and accuracy. Especially for deep-seated tumors, it has the potential to reduce blood loss and attain higher R0 resection rates.

This study aims to assess the feasibility and short-term and intermediate-term technical success rate of the concept of systematic selective hepatic vein (HV) reconstruction for parenchyma-sparing hepatectomies (PSHs) in patients with colorectal liver metastases (CRLM) in accordance with stage 2a of the IDEAL framework.

The prospective case series of patients deemed eligible and operated on according to the concept.

All patients were treated by a single surgical team in three hospitals in Ukraine from June 2022 to November 2023.

The study included nine cases of resectable CRLM with at least one lesion located in the hepatocaval confluence with HV(s) invasion, for whom reconstruction of the HV(s) allowed for additional parenchyma preservation, being an alternative to major or extended hepatectomy.

Liver resections with different types of HVs reconstruction (primary closure, patching, end-to-end anastomosis with or without grafting) were performed after a thorough evaluation of the future liver remnant volume, volume of potentially additionally preserved parenchyma and possibility of future repeat hepatectomies.

Postoperative morbidity, short-term and long-term patency of the reconstructed vessels, and the volume of additionally preserved parenchyma were the focus.

Segmental resection was performed in four cases, two with graft interposition. Patch reconstruction was performed for three HVs and two inferior vena cava resections. Two cases required primary closure. No mortality was observed, while the major morbidity rate was 33%. The short-term and long-term patency of the reconstructed HVs was 88.9% and 66.7%, respectively. HV reconstructions allowed the preservation of additional parenchyma (mean 495.4 mL, 95% CI 350.2 to 640.7). A decision-making algorithm to be used within the described approach is proposed.

Selective HV reconstruction is a feasible approach for PSH for CRLM. Further studies are needed to compare this approach to convenient major hepatectomies.

This study was designed to assess computed tomography (CT)-based radiomics of colorectal liver metastases (CRLM), extracted from posttreatment scans in estimating pathologic treatment response to neoadjuvant therapy, and to compare treatment response estimates between CT-based radiomics and radiological response assessment by using RECIST 1.1 and CT morphologic criteria.

Patients who underwent resection for CRLM from January 2003-December 2012 at a single institution were included. Patients who did not receive preoperative systemic chemotherapy, or without adequate imaging, were excluded. Imaging characteristics were evaluated based on RECIST 1.1 and CT morphologic criteria. A machine-learning model was designed with radiomic features extracted from manually segmented posttreatment CT tumoral and peritumoral regions to identify pathologic responders (≥ 50% response) versus nonresponders. Statistical analysis was performed at the tumor level.

Eighty-five patients (median age, 62 years; 55 women) with 95 tumors were included. None of the subjectively evaluated imaging characteristics were associated with pathologic response (p > 0.05). Inter-reader agreement was substantial for RECIST categorical response assessment (K = 0.70) and moderate for CT morphological group response (K = 0.50). In the validation cohort, the machine learning model built with radiomic features obtained an area under the curve (AUC) of 0.87 and outperformed subjective RECIST assessment (AUC = 0.53, p = 0.01) and morphologic assessment (AUC = 0.56, p = 0.02).

Radiologist assessment of oligometastatic CRLM after neoadjuvant therapy using RECIST 1.1 and CT morphologic criteria was not associated with pathologic response. In contrast, a machine-learning model based on radiomic features extracted from tumoral and peritumoral regions had high diagnostic performance in assessing responders versus nonresponders.

With advances in chemotherapy, conversion surgery is often performed for initially unresectable colorectal cancer liver metastasis (CLM). However, unexpected posthepatectomy liver failure (PHLF) is sometimes associated with chemotherapy-associated liver injuries following long-term chemotherapy. We aimed to identify predictive factors for PHLF after conversion surgery for initially unresectable CLM.

We retrospectively identified 774 consecutive patients who underwent initial liver resections for histologically confirmed CLMs between 2010 and 2019 at our institute. We enrolled 107 patients with initially unresectable CLMs. Clinicopathological characteristics were evaluated to determine their association with PHLF. Logistic regression analysis was performed to analyze the predictors of PHLF.

Among the 107 patients, PHLF occurred in 15 cases (14%). Multivariate analysis revealed that splenomegaly during preoperative chemotherapy (> 135%) was an independent risk factor for PHLF (P = 0.002; odds ratio 14.30; 95% confidence interval 2.69-76.08). In the analysis limited to the splenomegaly group, lower platelet counts, increased blood loss and operative times, and large liver resection areas (> 100 cm2) were significant risk factors for PHLF (P = 0.018, 0.043, 0.020, and 0.024, respectively). Among them, a liver resection area > 100 cm2 can be calculated preoperatively and correlate with a complex hepatectomy.

These findings could help predict PHLF after conversion surgery and induction chemotherapy for initially unresectable CLMs. Careful decisions, including detailed procedures and timing of hepatectomy, should be made before conversion hepatectomy in patients who develop splenomegaly after induction chemotherapy and require complex hepatectomies with a large liver resection area.

The incidence of colorectal cancer and colorectal liver metastases (CRLM) is increasing globally due to an interaction of environmental and genetic factors. A minority of patients with CRLM have surgically resectable disease, but for those who have resection as part of multimodal therapy for their disease, long-term survival has been shown. Precision surgery-the idea of careful patient selection and targeting of surgical intervention, such that treatments shown to be proven to benefit on a population level are the optimal treatment for each individual patient-is the new paradigm of care. Key to this is the understanding of tumour molecular biology and clinically relevant mutations, such as KRAS, BRAF, and microsatellite instability (MSI), which can predict poorer overall outcomes and a poorer response to systemic therapy. The emergence of immunotherapy and hepatic artery infusion (HAI) pumps show potential to convert previously unresectable disease to resectable disease, in addition to established systemic and locoregional therapies, but the surgeon must be wary of poor-quality livers and the spectre of post-hepatectomy liver failure (PHLF). Volume modulation, a cornerstone of hepatic surgery for a generation, has been given a shot in the arm with the advent of liver venous depletion (LVD) ensuring significantly more hypertrophy of the future liver remnant (FLR). The optimal timing of liver resection for those patients with synchronous disease is yet to be truly established, but evidence would suggest that those patients requiring complex colorectal surgery and major liver resection are best served with a staged approach. In the operating room, parenchyma-preserving minimally invasive surgery (MIS) can dramatically reduce the surgical insult to the patient and lead to better perioperative outcomes, with quicker return to function.

Laparoscopic liver resection (LLR) has proved effective in the treatment of oligometastatic disease (1 or 2 colorectal liver metastases CRLM) with similar long-term outcomes and improved short-term results compared to open liver resection (OLR). Feasibility of parenchymal sparing LLR for high tumour burden diseases is largely unknown. Aim of the study was to compare short and long-term results of LLR and OLR in patients with ≥ 3 CRLM.

Patients who underwent first LR of at least two different segments for ≥ 3 CRLM between 01/2012 and 12/2021 were analysed. Propensity score nearest-neighbour 1:1 matching was based on relevant prognostic factors.

277 out of 673 patients fulfilled inclusion criteria (47 LLR and 230 OLR). After match two balanced groups of 47 patients with a similar mean number of CRLM (5 in LLR vs 6.5 in OLR, p = 0.170) were analysed. The rate of major hepatectomy was similar between the two group (10.6% OLR vs. 12.8% LLR). Mortality (2.1% OLR vs 0 LLR) and overall morbidity rates (34% OLR vs 23.4% LLR) were comparable. Length of stay (LOS) was shorter in the LLR group (5 vs 9 days, p = 0.001). No differences were observed in median overall (41.1 months OLR vs median not reached LLR) and disease-free survival (18.3 OLR vs 27.9 months LLR).

Laparoscopic approach should be considered in selected patients scheduled to parenchymal sparing LR for high tumour burden disease as associated to shorter LOS and similar postoperative and long-term outcomes compared to the open approach.

Approximately 70% of patients with colorectal liver metastases (CRLM) experiences intrahepatic recurrence after initial liver resection. This study assessed outcomes and hospital variation in repeat liver resections (R-LR).

This population-based study included all patients who underwent liver resection for CRLM between 2014 and 2022 in the Netherlands. Overall survival (OS) was collected for patients operated on between 2014 and 2018 by linkage to the insurance database.

Data of 7479 liver resections (1391 (18.6%) repeat and 6088 (81.4%) primary) were analysed. Major morbidity and mortality were not different. Factors associated with major morbidity included ASA 3+, major liver resection, extrahepatic disease, and open surgery. Five-year OS after repeat versus primary liver resection was 42.3% versus 44.8%, P = 0.37. Factors associated with worse OS included largest CRLM >5 cm (aHR 1.58, 95% CI: 1.07-2.34, P = 0.023), >3 CRLM (aHR 1.33, 95% CI: 1.00-1.75, P = 0.046), extrahepatic disease (aHR 1.60, 95% CI: 1.25-2.04, P = 0.001), positive tumour margins (aHR 1.42, 95% CI: 1.09-1.85, P = 0.009). Significant hospital variation in performance of R-LR was observed, median 18.9% (8.2% to 33.3%).

Significant hospital variation was observed in performance of R-LR in the Netherlands reflecting different treatment decisions upon recurrence. On a population-based level R-LR leads to satisfactory survival.

Minimally invasive caudate lobectomy, or even paracaval caudate resection, can be associated with significant bleeding due to its abutment of inferior vena cava (IVC), portal pedicle and hepatic veins.1-3 This risk can be magnified by cirrhosis as well as response to neoadjuvant therapy (a common phenomenon after excellent response to neoadjuvant chemotherapy), leading to obliteration or even fusion of the hepato-caval space.4-7 PATIENT: A 68-year-old female with stage IVa colorectal adenocarcinoma was found to have a single liver metastasis (3.8 × 3.1 cm) in the paracaval caudate lobe. The patient received four cycles of neoadjuvant chemotherapy, leading to inflammatory fusion of the hepato-caval space. Despite this, the patient underwent a safe laparoscopic Spiegel process resection.

Prior to surgery, three-dimensional liver and port site modeling was performed to optimize the understanding of the spatial relationship between the tumor, IVC, and portal-hepatic veins. Following inflow control of portal veinous branches, the fused hepato-caval space was dissected. The adhesions were then sharply dissected to mobilize the paracaval caudate lobe off the IVC. Using scissors rather than an energy device reduced the risk of inadvertent thermal injury to the IVC.

Preoperative virtual hepatectomy facilitates surgical planning, increasing the understanding of the tumor/vessel relationship and port placement. In case of a fused hepato-caval space, low central venous pressure and judicious management of short hepatic vein branches are the key for a successful dissection. Moreover, anticipation of a fused hepato-caval space and its strategic management are paramount when performing a minimally invasive caudate resection.

Colorectal cancer (CRC) is the 3rd most common malignancy with the liver being the most common site of metastases. The recurrence rate of colorectal liver metastases (CRLM) after liver resection (LR) is notably high, with an estimated 40% of patients experiencing recurrence within 6 months. In this context, we conducted a meta-analysis to synthesize and evaluate the reliability of evidence pertaining to prognostic factors associated with early recurrence (ER) in CRLM following LR.

Systematic searches were conducted from the inception of databases to July 14, 2023, to identify studies reporting prognostic factors associated with ER. The Quality in Prognostic Factor Studies (QUIPS) tool was employed to assess risk-of-bias for included studies. Meta-analysis was then performed on these prognostic factors, summarized by forest plots. The grading of evidence was based on sample size, heterogeneity, and Egger's P value.

The study included 24 investigations, comprising 12705 individuals, during an accrual period that extended from 2007 to 2023. In the evaluation of risk-of-bias, 22 studies were rated as low/moderate risk, while two studies were excluded because of high risk. Most of the studies used a postoperative interval of 6 months to define ER, with 30.2% (95% confidence interval [CI], 24.1-36.4%) of the patients experiencing ER following LR. 21 studies were pooled for meta-analysis. High-quality evidence showed that poor differentiation of CRC, larger and bilobar-distributed liver metastases, major hepatectomy, positive surgical margins, and postoperative complications were associated with an elevated risk of ER. Additionally, moderate-quality evidence suggested that elevated levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA199), lymph node metastases (LNM) of CRC, and a higher number of liver metastases were risk factors for ER.

This review has the potential to enhance the efficacy of surveillance strategies, refine prognostic assessments, and guide judicious treatment decisions for CRLM patients with high risk of ER. Additionally, it is essential to undertake well-designed prospective investigations to examine additional prognostic factors and develop salvage therapeutic approaches for ER of CRLM.

Early recurrence following hepatectomy for colorectal liver metastases (CLM) is associated with worse survival; yet, impact of further local therapy is unclear. We sought to evaluate whether local therapy benefits patients with early recurrence following hepatectomy for CLM.

Clinicopathologic and survival outcomes of patients managed with hepatectomy for CLM (1/2001-12/2020) were queried from a prospectively maintained database. Timing of recurrence was stratified as early (recurrence-free survival [RFS] < 6 months), intermediate (RFS 6-12 months), and later (RFS > 12 months). Local therapy was defined as ablation, resection, or radiation.

Of 671 patients, 541 (81%) recurred with 189 (28%) early, 180 (27%) intermediate, and 172 (26%) later recurrences. Local therapy for recurrence resulted in improved survival, regardless of recurrence timing (early 78 vs. 32 months, intermediate 72 vs. 39 months, later 132 vs. 65 months, all p < 0.001). Following recurrence, treatment with local therapy (hazard ratio [HR] = 0.24), liver and extrahepatic recurrence (HR = 1.81), RAS + TP53 co-mutation (HR = 1.52), and SMAD4 mutation (HR = 1.92) were independently associated with overall survival (all p ≤ 0.002). Among patients with recurrence treated by local therapy, patients older than 65 years (HR 1.79), liver and extrahepatic recurrence (HR 2.05), primary site or other recurrence (HR 1.90), RAS-TP53 co-mutation (HR 1.63), and SMAD4 mutation (HR 2.06) had shorter post-local therapy survival (all p ≤ 0.04).

While most patients recur after hepatectomy for CLM, local therapy may result in long-term survival despite early recurrence. Somatic mutational profiling may help to guide the multidisciplinary consideration of local therapy after recurrence.

The liver is the most frequent and often the only site of distant disease in colorectal cancer and, of all treatment protocols currently in use, resection is the most likely to result in long-term cure. Within the liver, tumour proximity to major vasculature and biliary structures poses a resection challenge, requiring a balance of achieving negative margins while preserving adequate vascular circulation and biliary drainage. The focus on parenchymal sparing resections are important but just as important may be the 'biological' behaviour of the tumour. In colorectal liver metastases (CRLM), biomarkers such as the Kirsten rat sarcoma oncogene homologue (KRAS) gene and histological growth patterns (HGPs) further improve the prognostication after resection. However, to date, the association between the KRAS status and HGPs in CRLM and their impact on resection margins around major vasculature or biliary structures in terms of overall survival and recurrence rates are unclear. The aim of this review was to explore the available evidence for the association between KRAS and HGPs in CRLM and attempt to define their impact on resection margins near major structures.

As tumors invade major abdominal veins, surgical procedures are transformed from simple and basic to complicated and challenging. In this narrative review, we focus on what is currently known and not known regarding the technical aspects of major abdominal venous resection and its reconstruction, patency, and oncologic benefit in a cross-cutting perspective.

A systematic literature search was performed in PubMed and Semantic Scholar from inception up to October 18, 2023. We reviewed 106 papers by title, abstract, and full text regarding resection or reconstruction of the inferior vena cava, hepatic vein confluence, portal vein (PV), and middle hepatic vein (MHV) tributaries in living donor liver transplantation (LDLT) in a cross-cutting perspective.

The oncologic benefit of aggressive hepatic vein resection with suitable reconstruction against adenocarcinoma remains unclear, and further studies are required to clarify this point. A superior mesenteric/PV resection is now a universal, indispensable, and effective procedure for pancreatic ductal adenocarcinoma. Although many case series using tailor-made autologous venous grafts have been reported, not only size mismatch but also additional surgical incisions and a longer operation time remain obstacles for venous reconstruction. The use of autologous alternative tissue remains only an alternative procedure because the patency rate of customized tubular conduit type to interpose or replace the resected vein is not known. Unlike arterial replacement, venous replacement using synthetic vascular grafts is still rarely reported and there are several inherent limitations except for reconstruction of tributaries of MHV in LDLT.

Various approaches to abdominal vein resection and replacement or reconstruction are technically feasible with satisfactory results. Synthetic vascular grafts may be appropriate but have a certain rate of complications.

The use of preoperative or "neoadjuvant" chemotherapy (NAC) has long been controversial for resectable colorectal liver metastases (CRLM). The European Society of Medical Oncology (ESMO) 2023 guidelines on metastatic colorectal cancer (CRC) indicate a combination of surgical/technical and oncologic/prognostic criteria as the two determinants for allocating patients to NAC or upfront hepatectomy. However, surgical and technical criteria have evolved, and oncologic prognostic criteria date from the pre-modern chemotherapy era and lack prospective validation. The traditional literature is interpreted as not supporting the use of NAC because several studies fail to demonstrate a benefit in overall survival (OS) compared to upfront surgery; however, OS may not be the most appropriate endpoint to consider. Moreover, the commonly quoted studies against NAC contain many limitations that may explain why NAC failed to demonstrate its value. The query of the recent literature focused primarily on other aspects than OS, such as surgical technique, the impact of side effects of chemotherapy, the histological growth pattern of metastases, or the detection of circulating tumor DNA, shows data that support a more widespread use of NAC. These should prompt a critical reappraisal of the use of NAC, leading to a more precise selection of patients who could benefit from it.

Colorectal cancer is the third most common cancer in the United States and the second most common cause of cancer-related death. Approximately 20-30% of patients will develop hepatic metastasis in the form of synchronous or metachronous disease. The treatment of colorectal liver metastasis (CRLM) has evolved into a multidisciplinary approach, with chemotherapy and a variety of locoregional treatments, such as ablation and portal vein embolization, playing a crucial role. However, resection remains a core tenet of management, serving as the gold standard for a curative-intent therapy. As such, the input of a dedicated hepatobiliary surgeon is paramount for appropriate patient selection and choice of surgical approach, as significant advances in the field have made management decisions extremely nuanced and complex. We herein aim to review the contemporary surgical management of colorectal liver metastasis with respect to both perioperative and operative considerations.

This study aimed to extract prognostic factors in patients undergoing neoadjuvant chemotherapy (NAC) for borderline resectable colorectal liver metastasis (BR-CRLM) (tumor size ≥5 cm, number of tumors ≥4, or resectable extrahepatic diseases) and assess validity of this strategy.

Since 2010, patients with BR-CRLM were treated with hepatectomy after six cycles of NAC. Prognostic factors of these patients were evaluated using clinicopathological data.

Of 650 patients who underwent initial hepatectomy for CRLM from 2010 to 2018, 246 BR-CRLM cases underwent hepatectomy after NAC (BR-NAC). The 5-year recurrence-free survival rate was 16.7% and the 5-year overall survival rate (5y-OS) was 52.9%. Number of tumors ≥6, carcinoembryonic antigen (CEA) level ≥25 ng/mL, tumor diameter ≥5 cm, and progressive disease (PD) after NAC were identified as independent poor prognostic factors for OS. Patients were divided into four groups according to the number of risk factors, and prognoses of the four groups were well stratified.

In patients with BR-NAC, number of tumors ≥6, CEA ≥25 ng/mL, tumor diameter ≥5 cm, and PD after NAC were independent poor prognostic factors. Patients with three or four risk factors showed poor prognosis and may need to switch chemotherapy.

Parenchyma- sparing liver resections are aimed at maximizing the possible preservation of parenchyma not affected by the tumor - a current trend in hepatopancreatobiliary surgery. On the other hand, a prerequisite for operations is to ensure their radicality. To effectively solve this problem, all diagnostic imaging methods available in the arsenal are used, which make it possible to comprehensively solve the issues of perioperative planning of the volume and technical features of the planned operation. Diagnostic imaging methods that allow intraoperative navigation through intraoperative, instrumentally based determination of the tumor border and resection plane have additional value. One of the methods of such mapping is ICG video fluorescence intraoperative navigation. An analysis of the clinical use of the domestic video fluorescent navigation system "MARS" for parenchymal-sparing resections of focal liver lesions is presented. An assessment was made of the dynamics of the distribution of the contrast agent during ICG videofluorescent mapping during parenchymal-sparing resection interventions on the liver, with the analysis of materials from histological examination of tissues taking into account three-zonal videofluorescent marking of the resection edge, performed using the domestic videofluorescence imaging system «MARS».

Colorectal cancer (CRC) is the third most common cancer, and nearly half of CRC patients experience metastases. Oligometastatic CRC represents a distinct clinical state characterized by limited metastatic involvement, demonstrating a less aggressive nature and potentially improved survival with multidisciplinary treatment. However, the varied clinical scenarios giving rise to oligometastases necessitate a precise definition, considering primary tumor status and oncological factors, to optimize treatment strategies. This review delineates the concepts of oligometastatic CRC, encompassing oligo-recurrence, where the primary tumor is under control, resulting in a more favorable prognosis. A comprehensive examination of multidisciplinary treatment with local treatments and systemic therapy is provided. The overarching objective in managing oligometastatic CRC is the complete eradication of metastases, offering prospects of a cure. Essential to this management approach are local treatments, with surgical resection serving as the standard of care. Percutaneous ablation and stereotactic body radiotherapy present less invasive alternatives for lesions unsuitable for surgery, demonstrating efficacy in select cases. Perioperative systemic therapy, aiming to control micrometastatic disease and enhance local treatment effectiveness, has shown improvements in progression-free survival through clinical trials. However, the extension of overall survival remains variable. The review emphasizes the need for further prospective trials to establish a cohesive definition and an optimized treatment strategy for oligometastatic CRC.

Parenchymal-sparing hepatectomy (PSH) is recommended in patients with colorectal liver metastases (CRLM). Based on the principle of PSH, to investigate the impact of anatomical resection (AR) and non-anatomic resection (NAR) on the outcome of CRLM and to evaluate the potential prognostic impact of three peritumoral imaging features.

Fifty-six patients who had abdominal gadoxetic acid-enhanced magnetic resonance imaging (MRI) before CRLM surgery were included in this retrospective research. Peritumoral early enhancement, peritumoral hypointensity on hepatobiliary phase (HBP), and biliary dilatation to the CRLM at MRI were evaluated. Survival estimates were calculated using the Kaplan-Meier method, and multivariate analysis was conducted to identify independent predictors of liver recurrence-free survival (LRFS), recurrence-free survival (RFS) and overall survival (OS).

NAR had a lower 3-year LRFS compared with AR (36.6% vs. 78.6%, p = 0.012). No significant differences were found in 3-year RFS (34.1% vs. 41.7%) and OS (61.7% vs. 81.3%) (p > 0.05). In NAR group, peritumoral early enhancement was associated with poor LRFS (p = < 0.001, hazard ratio [HR] = 6.260; 95% confidence interval [CI], 2.322,16.876]) and poor RFS (p = 0.035, HR =2.516; 95% CI, 1.069,5.919). No independent predictors of CRLM were identified in the AR group.

In patients with CRLM, peritumoral early enhancement was a predictor of LRFS and RFS after NAR according to the principle of PSH.

More than 50% of patients with colorectal cancer develop liver metastases. Hepatectomy is the preferred treatment for resectable liver metastases. This review provides a perspective on the utility and relevant prognostic factors of repeat hepatectomy in recurrent colorectal liver metastasis (CRLM).

The keywords "recurrent colorectal liver metastases", "recurrent hepatic metastases from colorectal cancer", "liver metastases of colorectal cancer", "repeat hepatectomy", "repeat hepatic resection", "second hepatic resection", and "prognostic factors" were used to retrieve articles published in the PubMed database up to August 2020. Additional articles were identified by a manual search of references from key articles.

Despite improvements in surgical methods and perioperative chemotherapy, recurrence remains common in 37%-68% of patients. Standards or guidelines for the treatment of recurrent liver metastases are lacking. Repeat hepatectomy appears to be the best option for patients with resectable metastases. The commonly reported prognostic factors after repeat hepatectomy were R0 resection, carcinoembryonic antigen level, the presence of extrahepatic disease, a short disease-free interval between initial and repeat hepatectomy, the number (> 1) and size (≥ 5 cm) of hepatic lesions, requiring blood transfusion, and no adjuvant chemotherapy after initial hepatectomy. The median overall survival after repeat hepatectomy ranged from 19.3 to 62 months, and the 5-year overall survival ranged from 21% to 73%. Chemotherapy can act as a test for the biological behavior of tumors with the goal of avoiding unnecessary surgery, and a multimodal approach involving aggressive chemotherapy and repeat hepatectomy might be the treatment of choice for patients with early recurrent CRLM.

Repeat hepatectomy is a relatively safe and effective treatment for resectable recurrent CRLM. The presence or absence of prognostic factors might facilitate patient selection to improve short- and long-term outcomes.

Updated knowledge about the rates of recurrence and time to recurrence following curative treatment of colorectal cancer is essential to secure better patient information on prognosis, to serve as a premise in the discussion on adjuvant chemotherapy, and help to properly scale the intensity and length of follow-up.

This is a population-based study investigating aspects on first recurrence after radical treatment of clinical stages I-III of colorectal cancer in Central-Norway during 2001-2015. To reveal any time-trends, data were stratified by the time periods 2001-2005, 2006-2010 and 2011-2015. The cumulative incidence of first recurrence was calculated, treating death of unrelated causes as a competing event. Multivariable Cox analyses were done to calculate cause specific hazard ratios (HR) for risk of recurrence.

At a minimum follow-up of six years, a first recurrence was detected in 1,113/5,556 patients at risk (20.0%). The recurrence rate was reduced from 23.6% in the first time period, through 20.0% in the second, and to 17.2% in the last, p < 0.001. The reduction applied to all tumor locations, to pathological disease stages II and III, to both gender, across different tumor differentiations, and to both elective and emergency surgery. In multivariable analyses time period, gender, disease stage, and tumor differentiation were significant determinants for risk of recurrence.

The rate of first recurrence after curative surgery for colorectal cancer was substantially reduced from 2001 to 2015. The reason for the reduction could not be attributed to a single factor only. A combined effect of several incremental improvements, such as an increased use of preoperative radiation for rectal cancers, improved adjuvant chemotherapy for colon cancer, and a reduced proportion of emergency surgery, is suggested.

The current high-level hepatectomy (HLH) is certified by the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS), comprising only anatomical hepatectomies above Couinaud's segmentectomy. This multicenter study aimed to identify the conditions of non-HLH that satisfy equivalent technical difficulties to HLH.

Between 2018 and 2021, 595 first open hepatectomies without biliary reconstruction (374 HLHs and 221 non-HLHs) were performed in the five institutions. Non-HLHs belonging to at least one of the three conditions; depth of hepatectomy ≥5 cm, number of resections ≥3 locations and at least one location with a depth of hepatectomy ≥3 cm, and hepatectomy involving the paracaval portion of the caudate lobe was proposed as the candidate for difficult non-HLH. The technical difficulty was estimated by the operative time and blood loss.

Difficult non-HLHs were neither associated with shorter operative time (373 min vs. 354 min, p = .184) nor lesser blood loss than those with HLHs (503 mL vs. 436 mL, p = .126). Postoperative complications such as Clavien-Dindo classification grade III or more were not significant between the two groups (18.6% vs. 13.4%, p = 0212).

Difficult non-HLHs were associated with no lesser technical difficulty than those with HLH.

Studies on the epidemiology of liver metastases (LM)-related mortality are rare. we aimed to describe the burden and trend of liver metastases in Pudong of Shanghai, which could be beneficial to cancer prevention.

We performed a retrospective population-based analysis of cancer mortality data with liver metastases in Shanghai Pudong from 2005 to 2021. Long-term trends in crude mortality rates (CMRs), age-standardized mortality rates worldwide, and rate of years of life lost (YLL) were analyzed by the Join-point regression model. In addition, we evaluate the impact of the demographic and nondemographic factors on the mortality of disease by the decomposition method.

Cancer with liver metastases accounted for 26.68% of all metastases. The CMR and age-standardized mortality rates by Segi's world population (ASMRW) of cancer with liver metastases were 15.12/105 person-years and 6.33/105 person-years, respectively. The YLL from cancer with liver metastases was 84 959.87 years, with the age group of 60-69 years having the highest YLL of 26 956.40 years. The top three cancer types in liver metastases are colorectal, gastric, and pancreatic cancer. The long-term trend of ASMRW significantly decreased by 2.31% per year ( P <0.05). The ASMRW and YLL rates of those over 45 decreased year by year. Particularly striking was the 70-79 age group. Although the overall mortality of cancer with liver metastases decreased, there was still a significant upward trend toward an increased mortality rate caused by cancer with liver metastases in aging patients.

Liver metastases were a common site of metastases in patients with cancers originating from the digestive system. The disease burden caused by cancer with liver metastases provides valuable evidence for cancer management.

The prognosis of intermediate- and advanced-stage hepatocellular carcinoma after liver resection should be comprehensively analyzed due to the high incidence of tumor recurrence and the availability of salvage therapy. This study evaluated the long-term outcome and salvageability in these patients after liver resection.

Data from consecutive patients with intermediate- and advanced-stage hepatocellular carcinoma who underwent initial liver resection from 2000 to 2016 were retrospectively reviewed. Analyses were performed in the setting of the initial liver resection and the recurrence(s). Active salvage therapy for recurrence was defined as the implementation of each therapy with curative intent-repeat surgery, ablative therapy, and liver transplantation.

Among the 1,013 liver resections for hepatocellular carcinoma, a total of 270 patients were eligible for this study (intermediate hepatocellular carcinoma, n = 134; advanced hepatocellular carcinoma, n = 136). The 5-year overall survival rates for intermediate and advanced-stage hepatocellular carcinoma were 49.7% and 36.8%, respectively; meanwhile, the actual recurrence rates excluding patients who died without recurrence were 94.7% and 90.7%, respectively. Active salvage therapy was performed in 43 (39.8%) patients with intermediate-stage hepatocellular carcinoma and 25 (23.4%) patients with advanced-stage hepatocellular carcinoma. Overall survival after initial liver resection, first active salvage therapy, and second/more active salvage therapy were comparable in both stages.

This study suggests that although liver resection alone may not yield remission in most patients with intermediate and advanced-stage hepatocellular carcinoma, active salvage therapy can potentially prolong survival. Further study to identify approaches to decrease recurrence rates and increase salvageability for these patients would be warranted.

The type of liver resection (anatomical resection, AR or non-anatomical resection, NAR) for colorectal liver metastases (CRLM) is subject to debate. The debate may persist because some prognostic factors, associated with aggressive tumor biological behavior, have been overlooked.

Our study aimed to investigate the characteristics of patients who would benefit more from anatomical resection for CRLM.

Seven hundred twenty-nine patients who underwent hepatic resection of CRLM were retrospectively collected from June 2012 to May 2019. Treatment effects between AR and NAR were compared in full subgroup analyses. Tumor relapse-free survival (RFS) was evaluated by a stratified log-rank test and summarized with the use of Kaplan-Meier and Cox proportional hazards methods.

Among 729 patients, 235 (32.2%) underwent AR and 494 (67.8%) underwent NAR. We showed favorable trends in RFS for AR compared with NAR in the patients with KRAS/NRAS/BRAF mutation (interaction P <0.001) or right-sidedness (interaction P <0.05). Patients who underwent AR had a markedly improved RFS compared with NAR in the cohorts of RAS/NRAS/BRAF mutation (median RFS 23.2 vs. 11.1 months, P <0.001) or right-sidedness (median RFS 31.6 vs. 11.5 months, P <0.001); upon the multivariable analyses, AR [gene mutation: hazard ratio (HR)=0.506, 95% CI=0.371-0.690, P <0.001; right-sidedness: HR=0.426, 95% CI=0.261-0.695, P =0.001) remained prognostic independently. In contrast, patients who underwent AR had a similar RFS compared with those who underwent NAR, in the cohorts of patients with gene wild-type tumors (median RFS 20.5 vs. 21.6 months, P =0.333). or left-sidedness (median RFS 15.8 vs. 19.5 months, P =0.294).

CRLM patients with gene mutation or right-sidedness can benefit more from AR rather than from NAR.

The efficacy of combining ablation and resection (CARe) in treating unresectable colorectal cancer liver metastases (CRLM) was well established. This study aimed to investigate the surgical and oncological outcomes of CARe strategy focusing on initially resectable CRLM.

A total of 971 patients with resectable CRLM from a retrospective database of 1414 CRLM patients were enrolled, including 120 in the CARe group and 851 in the hepatectomy alone group. Short- and long-term outcomes were compared between groups using propensity score matching analysis.

After propensity score matching, 96 matched pairs of patients from each group were included. General characteristics of primary tumour and liver metastases were not statistically different between the CARe group and hepatectomy alone group. Disease-free survival (p = 0.257), intrahepatic recurrence-free survival (p = 0.329), and overall survival (p = 0.358) were similar between the two groups. Patients in CARe group had significantly reduced rate of major hepatectomy (5.2% vs. 21.9%, p = 0.001), lower incidence of postoperative hepatic insufficiency (0.0% vs. 5.2%, p = 0.023), and shortened postoperative hospital stay (7 d vs. 8 d, p = 0.019). Multivariate analysis showed that surgical approach did not affect oncologic outcome; liver metastasis with diameter >3 cm was an independent prognostic factor for hepatic recurrence-free and disease-free survival, and RAS status and lymph node metastasis at the primary site were independent prognostic factors for overall survival.

For patients with resectable CRLM, CARe may be a better treatment strategy than hepatectomy alone, as it could avoid major hepatectomy and get better surgical outcomes, while providing the similar oncologic results.

The advantages of parenchymal-sparing resection (PSR) over anatomic resection (AR) of colorectal liver metastases (CRLM) remain controversial. Here, we aim to evaluate their safety and efficacy.

A systematic review and meta-analysis of short-term perioperative outcomes and long-term oncological outcomes for PSR and AR were performed by searching Pubmed, Embase, the Cochrane Library and Web of Science databases.

Twenty-two studies were considered eligible (totally 7228 patients: AR, n = 3154 (43.6%) vs. PSR, n = 4074 (56.4%)). Overall survival (OS, HR = 1.08, 95% CI: 0.95-1.22, P = 0.245) and disease-free survival (DFS, HR = 1.09, 95% CI: 0.94-1.28, P = 0.259) were comparable between the two groups. There were no significant differences in 3-year OS, 5-year OS, 3-year DFS, 5-year DFS, 3-year liver recurrence-free survival (liver-RFS) and 5-year liver-RFS. In terms of perioperative outcome, patients undergoing AR surgery were associated with prolonged operation time (WMD = 51.48 min, 95% CI: 29.03-73.93, P < 0.001), higher amount of blood loss (WMD = 189.92 ml, 95% CI: 21.39-358.45, P = 0.027), increased intraoperative blood transfusion rate (RR = 2.24, 95% CI: 1.54-3.26, P < 0.001), prolonged hospital stay (WMD = 1.00 day, 95% CI: 0.34-1.67, P = 0.003), postoperative complications (RR = 2.28, 95% CI: 1.88-2.77, P < 0.001), and 90-day mortality (RR = 3.08, 95% CI: 1.88-5.03, P < 0.001). While PSR surgery was associated with positive resection margins (RR = 0.77, 95% CI: 0.61-0.97, P = 0.024), intrahepatic recurrence (RR = 0.90, 95% CI: 0.82-0.98, P = 0.021) and repeat hepatectomy (RR = 0.64, 95% CI: 0.55-0.76, P < 0.001).

Considering relatively acceptable heterogeneity, PSR had better perioperative outcomes without compromising oncological long-term outcomes. However, these findings must be carefully interpreted, requiring more supporting evidence.

PROSPERO registration number: CRD42023445332.

In patients with colorectal liver metastases (CLM), surgery is potentially curative. The use of novel surgical techniques and complementary percutaneous ablation allows for curative-intent treatment even in marginally resectable cases. Resection is used as part of a multidisciplinary approach, which for nearly all patients will include perioperative chemotherapy. Small CLM can be treated with parenchymal-sparing hepatectomy (PSH) and/or ablation. For small CLM, PSH results in better survival and higher rates of resectability of recurrent CLM than non-PSH. For patients with extensive bilateral distribution of CLM, two-stage hepatectomy or fast-track two-stage hepatectomy is effective. Our increasing knowledge of genetic alterations allows us to use them as prognostic factors alongside traditional risk factors (e.g. tumor diameter and tumor number) to select patients with CLM for resection and guide surveillance after resection. Alteration in RAS family genes (hereafter referred to as "RAS alteration") is an important negative prognostic factor, as are alterations in the TP53, SMAD4, FBXW7, and BRAF genes. However, APC alteration appears to improve prognosis. RAS alteration, increased number and diameter of CLM, and primary lymph node metastasis are well-known risk factors for recurrence after CLM resection. In patients free of recurrence 2 y after CLM resection, only RAS alteration is associated with recurrence. Thus, surveillance intensity can be stratified by RAS alteration status after 2 y. Novel diagnostic instruments and tools, such as circulating tumor DNA, may lead to further evolution of patient selection, prognostication, and treatment algorithms for CLM.

As for resection for colorectal liver metastasis (CRLM), securing an adequate surgical margin is important for achieving a better prognosis. However, it is often difficult to achieve adequate margins for the resection of CRLM. So the current survival impact of sub-centi/millimeter surgical margins in hepatectomy for CRLM should be evaluated. In the current era of multidisciplinary treatment options, this review focused on the prognostic impact of a sub-centi/millimeter surgical margin width in hepatectomy for CRLM. We systematically reviewed retrospective studies that clearly described the surgical margin width for hepatectomy for CRLM. We selected studies conducted since 2000 that involved patients diagnosed as having CRLM. We focused on studies that investigated not only surgical margins, but also microscopic surgical curability such as R0 (microscopically complete resection) or R1 (microscopically incomplete resection), which clearly describe their definitions. Based on our literature review, 1, 2, or 5 mm was considered the minimum surgical margin width for hepatectomy for CRLM. Although a surgical margin width of 1 mm is acceptable for hepatectomy for CRLM, submillimeter margins, which are defined as R1 in many reports, are only acceptable for limited patients such as those who have undergone preoperative chemotherapy. Zero-mm margins are also acceptable in limited patients such as those who show a good response to preoperative chemotherapy. New chemotherapy agents have been reported to reduce the prognostic impact of a narrow surgical margin width. The incidence of margin recurrence, which is a major concern regarding R1 resection of CRLM, is about 20-30% according to the majority of earlier reports. As evaluations of the actual prognostic impact of the surgical margin remain difficult, further study is warranted.

A margin ≥ 1 mm is considered a standard resection margin for colorectal liver metastasis (CRLM). However, microscopic incomplete resection (R1) is not rare since aggressive surgical resection has been attempted in multiple and bilobar CRLM. This study aimed to investigate the prognostic impact of resection margins and perioperative chemotherapy in patients with CRLM.

A total of 368 of 371 patients who underwent simultaneous colorectal and liver resection for synchronous CRLM between 2006 and June 2017, excluding three R2 resections, were included in this study. R1 resection was defined as either abutting tumor on the resection line or involved margin in the pathological report. The patients were divided into R0 (n = 304) and R1 (n = 64) groups. The clinicopathological characteristics, overall survival, and intrahepatic recurrence-free survival were compared between the two groups using propensity score matching.

The R1 group had more patients with ≥ 4 liver lesions (27.3 vs. 50.0%, P < 0.001), higher mean tumor burden score (4.4 vs. 5.8%, P = 0.003), and more bilobar disease (38.8 vs. 67.2%, P < 0.001) than the R0 group. Both R0 and R1 groups showed similar long-term outcomes in the total cohort (OS, P = 0.149; RFS, P = 0.414) and after matching (OS, P = 0.097, RFS: P = 0.924). However, the marginal recurrence rate was higher in the R1 group than in the R0 group (26.6 vs. 16.1%, P = 0.048). Furthermore, the resection margin did not have a significant impact on OS and RFS, regardless of preoperative chemotherapy. Poorly differentiated, N-positive stage colorectal cancer, liver lesion number ≥ 4, and size ≥ 5 cm were poor prognostic factors, and adjuvant chemotherapy had a positive impact on survival.

The R1 group was associated with aggressive tumor characteristics; however, no effect on the OS and intrahepatic RFS with or without preoperative chemotherapy was observed in this study. Tumor biological characteristics, rather than resection margin status, determine long-term prognosis. Therefore, aggressive surgical resection should be considered in patients with CRLM expected to undergo R1 resection in this multidisciplinary approach era.

Liver resection is potentially curative for patients with colorectal liver metastasis, but an advanced understanding of tumor biology and improved adjuvant therapies have facilitated an ongoing evolution of metastatic resection, even in the setting of a significant metastatic disease burden. As indications for surgery have expanded, preferred techniques and timing have been debated. This commentary reviews the merits of anatomic versus non-anatomic approaches to colorectal liver metastasis resection, considering oncologic outcomes, overall survival, and conflicting theories in the pathophysiology of the metastatic liver spread.