Metastasis is a hallmark of cancer and the leading cause of cancer-related mortality. However, the mechanism underlying liver metastasis in colorectal cancer (CRC) remains incompletely understood. This study explores the role of long non-coding RNA (lncRNA) SLERT in promoting CRC liver metastasis by downregulating HUNK expression.

SLERT expression levels in CRC tissues were analyzed and correlated with patient survival outcomes. Functional assays, including migration and invasion assays, were performed to assess the impact of SLERT knockdown and overexpression on metastatic behavior. Mechanistic studies examined SLERT's interaction with the RNA-binding protein RBM15 and its effect on HUNK mRNA stability. The subcellular localization of SLERT was also determined.

SLERT was significantly upregulated in CRC tissues and associated with poor survival outcomes. Silencing SLERT inhibited CRC cell migration and invasion, whereas its overexpression enhanced these metastatic properties. Mechanistically, SLERT interacted with RBM15, impairing its ability to stabilize HUNK mRNA, leading to decreased HUNK expression and increased metastatic potential. SLERT was primarily localized in the cytoplasm, indicating its active role in gene regulation within the tumor microenvironment.

LERT promotes liver metastasis in CRC by downregulating HUNK expression through RBM15-mediated mRNA destabilization. These findings suggest that SLERT could serve as a diagnostic biomarker and therapeutic target. Targeting SLERT or restoring HUNK expression may provide novel strategies to combat CRC liver metastasis and improve patient prognosis.

This study aimed to investigate the impact of the mutational status of multiple genes on survival in Chinese patients with colorectal liver metastases (CRLM) undergoing liver resection.

This study included 519 Chinese patients undergoing curative liver resection for CRLM between 2011 and 2021 and had genomic sequencing data of 620 genes available for analysis. The genes associated with overall survival (OS) were identified using Cox regression analyses. The patients were stratified according to a novel scoring system based on the number of genes with a deleterious status (mutation or wild type), and OS was compared among the groups. The prognostic capacity of the scoring system was assessed using Harrell's C-index.

Twelve genes were mutated in more than 10% of the patients. RAS mutation, SMAD4 mutation, and APC wild-type status were significantly associated with worse OS. A scoring system was built based on the mutational status of RAS, SMAD4, and APC. Higher scores were significantly associated with worse OS (HR > 1, p < 0.05, for any two groups), and the patients with a score of 3 had poor survival with a median OS of only 17.1 months. The scoring system demonstrated moderate discriminative capacity (Harrell's C-index = 0.627).

In Chinese patients, the mutational status of RAS, SMAD4, and APC was significantly associated with survival after CRLM resection. The three-gene scoring system provided information on prognostic stratification for survival, which can be used to improve precision surgery for CRLM.

Incisional hernia (IH) after open liver surgery is a well-recognized complication. The clinical importance of IH detected on computed tomography in terms of objective abdominal wall discomfort and impairment of quality of life (QoL) is less well known.

Patients who underwent curative surgery for colorectal liver metastases between 2010 and 2015 at a single center and were alive in February 2017 were asked to complete a ventral hernia pain questionnaire and the EORTC QLQ-C30 QoL questionnaire.

A total of 105 patients (80%) completed the questionnaires. Forty-three patients (42%) developed IH. The majority (77%) of IHs were < 2.5 cm. Patients who had an IH before liver surgery developed a new IH to a greater extent (P = 0.001). There were no significant differences regarding abdominal wall symptoms and QoL between patients with and without IH. However, about half (48%) of all patients had abdominal wall symptoms after a median follow-up of 34 months.

Radiologically detected IH after open liver surgery has low clinical importance. About half of all patients who underwent liver surgery experienced abdominal wall symptoms a long after surgery, but these symptoms were not related to IH.

Over the last decade, multiple clinical trials have demonstrated a survival benefit for liver transplantation in colorectal cancer with liver metastases. Additionally, advances in donor organ preservation have expanded organ availability affording the opportunity to expand indications for liver transplantation, such as colorectal cancer with unresectable liver metastases. Current data support comparable overall survival (OS) for liver transplantation for colorectal cancer with liver metastases compared with general liver transplantation recipients. Supported by this data, in the United States, allocation policy is changing to include deceased donor livers for patients with unresectable colorectal cancer liver metastases. Available studies to date demonstrate improved outcomes with primary tumor R0 resection, 6-12 months of pretransplantation chemotherapy, and careful radiologic restaging (including positron emission tomography/computed tomography) to confirm lack of extrahepatic disease. A response to pretransplantation chemotherapy is a key predictor of long-term outcomes and progression during chemotherapy appears to be a contraindication to proceeding to transplant. A carcinoembryonic antigen level ≤80 µg/L and largest liver tumor dimension <5.5 cm are both associated with improved progression-free and OS in the available literature. Liver transplantation for colorectal cancer with unresectable liver metastases is associated with longer progression-free and OS compared with chemotherapy alone. Patient selection based on imaging, laboratory, and clinical findings is critical to identify patients most likely to benefit. Liver transplantation should be considered at all centers with an active transplant program to improve outcomes for patients with advanced colorectal cancer.

The role of laparoscopic liver resection (LLR) for intrahepatic cholangiocarcinoma (ICC) remains debated. This study aimed to evaluate the short- and long-term outcomes of LLR vs. open liver resection (OLR) in ICC stratified by tumor burden score (TBS). ICC patients who underwent LLR or OLR were included from a multicenter database between July 2009 and October 2022. Patients were stratified into two cohorts based on whether the TBS was > 5.3. A 1:3 propensity score matching (PSM) analysis was performed between LLR and OLR in each cohort. Cox regression analysis was used to identify prognostic factors for ICC. A total of 626 patients were included in this study, 304 and 322 patients were classified into the low- and high-TBS groups, respectively. In the low-TBS group, after PSM, LLR was associated with less blood loss, lower CCI, fewer complications and shorter hospital stay (all p < 0.05). Kaplan-Meier curves revealed that LLR had better OS (p = 0.032). Multivariate Cox regression analysis showed that surgical procedure was an independent prognostic factor for ICC (HR: 0.445; 95% CI: 0.235-0.843; p = 0.013). In the high-TBS group, after PSM, LLR were associated with reduced blood loss, lower CCI, fewer complications and shorter hospital stay (all p < 0.05), while OS (p = 0.98) and DFS (p = 0.24) were similar between the two groups. TBS is an important prognostic factor for ICC. LLR is a safe and feasible option for ICC and leads to faster postoperative recovery. LLR can offer ICC a comparable and even better long-term prognosis than OLR.

The combination of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAb) and doublet chemotherapy is the standard first-line treatment for patients with wild-type RAS/BRAF metastatic colorectal cancer (mCRC). Some patients may require secondary resection after first-line treatment. However, it remains unclear whether targeted therapy should be continued after liver resection. To investigate whether targeted therapy can be spared after secondary resection, we retrospectively analyzed data from the Taiwan National Health Insurance Research Database for patients with wild-type KRAS mCRC who received first-line anti-EGFR mAb plus doublet chemotherapy. Between 2013 and 2018, 5694 mCRC patients were screened, with 174 meeting the eligibility criteria and being enrolled in this study. Among them, 153 patients continued anti-EGFR mAb after secondary resection. These patients demonstrated a significant improvement in overall survival (OS) but not in time to treatment failure. Postresection anti-EGFR mAb conferred OS benefits compared to no anti-EGFR mAb (43.17 vs. 31.41 months; P = 0.0064). When stratified by assessment period, OS was longer in patients assessed between 2016 and 2018 than in those assessed between 2012 and 2015 (not reached vs. 39.87 months; P = 0.1819). However, no significant difference was observed in time to treatment failure when stratified by assessment period or primary tumor location. A multivariate analysis revealed that postresection anti-EGFR mAb was an independent predictor of prolonged OS. In conclusion, for mCRC patients who have undergone secondary resection after first-line anti-EGFR mAb plus doublet chemotherapy, continuing anti-EGFR mAb may significantly extend OS, regardless of the primary tumor location.

Machine learning (ML) may provide novel insights into data patterns and improve model prediction accuracy. The current study sought to develop and validate an ML model to predict early extra-hepatic recurrence (EEHR) among patients undergoing resection of colorectal liver metastasis (CRLM).

Patients with CRLM who underwent curative-intent resection between 2000 and 2020 were identified from an international multi-institutional database. An eXtreme gradient boosting (XGBoost) model was developed to estimate the risk of EEHR, defined as extrahepatic recurrence within 12 months after hepatectomy, using clinicopathological factors. The relative importance of factors was determined using Shapley additive explanations (SHAP) values.

Among 1410 patients undergoing curative-intent resection, 131 (9.3%) patients experienced EEHR. Median OS among patients with and without EEHR was 35.4 months (interquartile range [IQR] 29.9-46.7) versus 120.5 months (IQR 97.2-134.0), respectively (p < 0.001). The ML predictive model had c-index values of 0.77 (95% CI, 0.72-0.81) and 0.77 (95% CI, 0.73-0.80) in the entire dataset and the validation data set with bootstrapping resamples, respectively. The SHAP algorithm demonstrated that T and N primary tumor categories, as well as tumor burden score were the three most important predictors of EEHR. An easy-to-use risk calculator for EEHR was developed and made available online at: https://junkawashima.shinyapps.io/EEHR/.

An easy-to-use online calculator was developed using ML to help clinicians predict the chance of EEHR after curative-intent resection for CRLM. This tool may help clinicians in decision-making related to treatment strategies for patients with CRLM.

Histopathological growth patterns are one of the strongest prognostic factors in patients with resected colorectal liver metastases. Development of an efficient, objective and ideally automated histopathological growth pattern scoring method can substantially help the implementation of histopathological growth pattern assessment in daily practice and research. This study aimed to develop and validate a deep-learning algorithm, namely neural image compression, to distinguish desmoplastic from non-desmoplastic histopathological growth patterns of colorectal liver metastases based on digital haematoxylin and eosin-stained slides.

The algorithm was developed using digitalized whole-slide images obtained in a single-centre (Erasmus MC Cancer Institute, the Netherlands) cohort of patients who underwent first curative intent resection for colorectal liver metastases between January 2000 and February 2019. External validation was performed on whole-slide images of patients resected between October 2004 and December 2017 in another institution (Radboud University Medical Center, the Netherlands). The outcomes of interest were the automated classification of dichotomous hepatic growth patterns, distinguishing between desmoplastic hepatic growth pattern and non-desmoplatic growth pattern by a deep-learning model; secondary outcome was the correlation of these classifications with overall survival in the histopathology manual-assessed histopathological growth pattern and those assessed using neural image compression.

Nine hundred and thirty-two patients, corresponding to 3.641 whole-slide images, were reviewed to develop the algorithm and 870 whole-slide images were used for external validation. Median follow-up for the development and the validation cohorts was 43 and 29 months respectively. The neural image compression approach achieved significant discriminatory power to classify 100% desmoplastic histopathological growth pattern with an area under the curve of 0.93 in the development cohort and 0.95 upon external validation. Both the histopathology manual-scored histopathological growth pattern and neural image compression-classified histopathological growth pattern achieved a similar multivariable hazard ratio for desmoplastic versus non-desmoplastic growth pattern in the development cohort (histopathology manual score: 0.63 versus neural image compression: 0.64) and in the validation cohort (histopathology manual score: 0.40 versus neural image compression: 0.48).

The neural image compression approach is suitable for pathology-based classification tasks of colorectal liver metastases.

The liver is affected by two groups of malignant tumours: primary liver cancers and liver metastases. Liver metastases are significantly more common than primary liver cancer, and five-year survival after radical surgical treatment of liver metastases ranges from 28% to 50%, depending on primary cancer site. However, R0 resection (resection for cure) is not feasible in most people; therefore, other treatments have to be considered in the case of non-resectability. One possible option is based on the concept that the blood supply to hepatic tumours originates predominantly from the hepatic artery. Transarterial chemoembolisation (TACE) of the peripheral branches of the hepatic artery can be achieved by administering a chemotherapeutic drug followed by vascular occlusive agents and can lead to selective necrosis of the cancer tissue while leaving normal liver parenchyma virtually unaffected. The entire procedure can be performed without infusion of chemotherapy and is then called bland transarterial embolisation (TAE). These procedures are usually applied over a few sessions. Another possible treatment option is systemic chemotherapy which, in the case of colorectal cancer metastases, is most commonly performed using FOLFOX (folinic acid, 5-fluorouracil, and oxaliplatin) and FOLFIRI (folinic acid, 5-fluorouracil, and irinotecan) regimens applied in multiple sessions over a long period of time. These therapies disrupt the cell cycle, leading to death of rapidly dividing malignant cells. Current guidelines determine the role of TAE and TACE as non-curative treatment options applicable in people with liver-only or liver-dominant metastatic disease that is unresectable or non-ablatable, and in people who have failed systemic chemotherapy. Regarding the treatment modalities in people with colorectal cancer liver metastases, we found no systematic reviews comparing the efficacy of TAE or TACE versus systemic chemotherapy.

To evaluate the beneficial and harmful effects of transarterial embolisation (TAE) or transarterial chemoembolisation (TACE) compared with systemic chemotherapy in people with liver-dominant unresectable colorectal cancer liver metastases.

We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, and three additional databases up to 4 April 2024. We also searched two trials registers and the European Medicines Agency database and checked reference lists of retrieved publications.

We included randomised clinical trials assessing beneficial and harmful effects of TAE or TACE versus systemic chemotherapy in adults (aged 18 years or older) with colorectal cancer liver metastases.

We used standard Cochrane methods. Our primary outcomes were all-cause mortality; overall survival (time to mortality); and any adverse events or complications. Our secondary outcomes were cancer mortality; health-related quality of life; progression-free survival; proportion of participants dying or surviving with progression of the disease; time to progression of liver metastases; recurrence of liver metastases; and tumour response measures (complete response, partial response, stable disease, and progressive disease). For the purpose of the review and to perform necessary analyses, whenever possible, we converted survival rates to mortality rates, as this was our primary outcome. For the analysis of dichotomous outcomes, we used the risk ratio (RR); for continuous outcomes, we used the mean difference; and for time to event outcomes, we calculated hazard ratios (HRs), all with 95% confidence intervals (CI). We used the standardised mean difference with 95% CIs when the trials used different instruments. We used GRADE to assess the certainty of evidence for each outcome. We based our conclusions on outcomes analysed at the longest follow-up.

We included three trials with 118 participants randomised to TACE versus 120 participants to systemic chemotherapy. Four participants were excluded; one due to disease progression prior to treatment and three due to decline in health. The trials reported data on one or more outcomes. Two trials were performed in China and one in Italy. The trials differed in terms of embolisation techniques and chemotherapeutic agents. Follow-up ranged from 12 months to 50 months. TACE may reduce mortality at longest follow-up (RR 0.86, 95% CI 0.79 to 0.94; 3 trials, 234 participants; very low-certainty evidence), but the evidence is very uncertain. TACE may have little to no effect on overall survival (time to mortality) (HR 0.61, 95% CI 0.37 to 1.01; 1 trial, 70 participants; very low-certainty evidence), any adverse events or complications (3 trials, 234 participants; very low-certainty evidence), health-related quality of life (2 trials, 154 participants; very low-certainty evidence), progression-free survival (1 trial, 70 participants; very low-certainty evidence), and tumour response measures (presented as the overall response rate) (RR 1.81, 95% CI 1.11 to 2.96; 3 trials, 234 participants; very low-certainty evidence), but the evidence is very uncertain. No trials reported cancer mortality, proportion of participants dying or surviving with progression of the disease, and recurrence of liver metastases. We found no trials comparing the effects of TAE versus systemic chemotherapy in people with colorectal cancer liver metastases.

The evidence regarding effectiveness of TACE versus systemic chemotherapy in people with colorectal cancer liver metastases is of very low certainty and is based on three trials. Our confidence in the results is limited due to the risk of bias, inconsistency, indirectness, and imprecision. It is very uncertain whether TACE confers benefits with regard to reduction in mortality, overall survival (time to mortality), reduction in adverse events or complications, improvement in health-related quality of life, improvement in progression-free survival, and tumour response measures (presented as the overall response rate). Data on cancer mortality, proportion of participants dying or surviving with progression of the disease, and recurrence of liver metastases are lacking. We found no trials assessing TAE versus systemic chemotherapy. More randomised clinical trials are needed to strengthen the body of evidence and provide insight into the benefits and harms of TACE or TAE in comparison with systemic chemotherapy in people with liver metastases from colorectal cancer.

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.

To describe the treatment patterns and survival status of advanced gastric cancer (AGC) in China in the past two decades, and objectively evaluate the impact of standardized Chinese medicine (CM) treatment on the survival of AGC patients.

This multicenter registry designed and propensity score analysis study described the diagnosis characteristics, treatment-pattern development and survival status of AGC from 10 hospitals in China between January 1, 2000 and July 31, 2021. Overall survival (OS) was evaluated between non-CM cohort (standard medical treatment) and CM cohort (integrated standard CM treatment ≥3 months). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to adjust any difference in average outcomes for bias.

A total of 2,001 patients histologically confirmed locally advanced and/or metastasis stomach and gastroesophageal junction adenocarcinoma were enrolled. Among them, 1,607 received systemic chemotherapy, 215 (10.74%) accepted molecular targeted therapy, 44 (2.2%) received checkpoint inhibitor therapy, and 769 (38.43%) received CM. Two-drug regimen was the main choice for first-line treatment, with fluoropyrimidine plus platinum as the most common regimen (530 cases, 60.09%). While 45.71% (16 cases) of patients with HER2 amplification received trastuzumab in first-line. The application of apatinib increased (33.33%) in third-line. The application of checkpoint inhibitors has increased since 2020. COX analysis showed that Lauren mixed type (P=0.017), cycles of first-line treatment >6 (P=0.000), CM (P=0.000), palliative gastrectomy (P=0.000), trastuzumab (P=0.011), and apatinib (P=0.008) were independent prognostic factors for the OS of AGC. After PSM and IPTW, the median OS of CM cohort and non-CM cohort was 18.17 and 12.45 months, respectively (P<0.001).

In real-world practice for AGC in China, therapy choices consisted with guidelines. Two-drug regimen was the main first-line choice. Standardized CM treatment was an independent prognostic factor and could prolong the OS of Chinese patients with AGC. (Registration No. NCT02781285).

Surgical resection of colorectal cancer liver metastasis (CRLM) has been associated with improved survival in these patients. The purpose of this study was to investigate the usefulness of liver metastasectomy, also finding independent factors related to survival after liver metastasectomy.

In a retrospective study, all patients with CRLM who underwent resection of liver metastases between 2012 and 2022 at Imam Khomeini Hospital Complex in Tehran, Iran, were enrolled. All patients were actively followed based on clinicopathologic and operative data.

A total of 248 patients with a median follow-up time of 46 months (Range, 12 to 122) were studied. Eighty-six patients (35.0%) underwent major hepatectomy, whereas 160 (65.0%) underwent minor hepatectomy. The median overall survival was 43 months (Range, 0 to 122 months), with estimated 1-, 3- and 5-year overall survival rates of 91%, 56%, and 42%, respectively. Multivariate analysis demonstrated that a metastasis size > 6 cm, major hepatectomy, rectum as the primary tumor site, and involved margin (< 1 mm) were independent factors associated with decreased overall survival (OS).

Surgical resection is an effective treatment for patients with CRLM that is associated with relatively favorable survival. A negative margin of 1 mm seems to be sufficient for oncological resection.

Colorectal liver metastasis (CRLM) is a disease entity that warrants special attention due to its high frequency and potential curability. Identification of "high-risk" patients is increasingly popular for risk stratification and personalization of the management pathway. Traditional regression-based methods have been used to derive prediction models for these patients, and lately, focus has shifted to artificial intelligence-based models, with employment of variable supervised and unsupervised techniques. Multiple endpoints, like overall survival (OS), disease-free survival (DFS) and development or recurrence of postoperative complications have all been used as outcomes in these studies. This review provides an extensive overview of available clinical prediction models focusing on the prognosis of CRLM and highlights the different predictor types incorporated in each model. An overview of the modelling strategies and the outcomes chosen is provided. Specific patient and treatment characteristics included in the models are discussed in detail. Model development and validation methods are presented and critically appraised, and model performance is assessed within a proposed framework.

Colorectal cancer is the second most common cause of cancer death in the United States, and up to half of patients develop colorectal liver metastases (CRLMs). Notably, somatic genetic mutations, such as mutations in RAS, BRAF, mismatch repair (MMR) genes, TP53, and SMAD4, have been shown to play a prognostic role in patients with CRLM. This review summarizes and appraises the current literature regarding the most relevant somatic mutations in surgically treated CRLM by not only reviewing representative studies, but also providing recommendations for areas of future research. In addition, advancements in genetic testing and an increasing emphasis on precision medicine have led to a more nuanced understanding of these mutations; thus, more granular data for each mutation are reviewed when available. Importantly, such knowledge can pave the way for precision medicine with the ultimate goal of improving patient outcomes.

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.

This study evaluated the feasibilities and outcomes following four-dimensional magnetic resonance imaging (4D-MRI) assisted stereotactic body radiation therapy (SBRT) for unresectable colorectal liver metastases (CRLMs). From March 2018 to January 2022, we identified 76 unresectable CRLMs patients with 123 lesions who received 4D-MRI guided SBRT in our institution. 4D-MRI simulation with or without abdominal compression was conducted for all patients. The prescription dose was 50-65 Gy in 5-12 fractions. The image quality of computed tomography (CT) and MRI were compared using the Clarity Score. Clinical outcomes and toxicity profiles were evaluated. 4D-MRI improved the image quality compared with CT images (mean Clarity Score: 1.67 vs 2.88, P < 0.001). The abdominal compression reduced motions in cranial-caudal direction (P = 0.03) with two phase T2 weighted images assessing tumor motion. The median follow-up time was 12.5 months. For 98 lesions assessed for best response, the complete response, partial response and stable disease rate were 57.1 %, 30.6 % and 12.2 %, respectively. The local control (LC) rate at 1 year was 97.3 %. 46.1 % of patients experienced grade 1-2 toxicities and only 2.6 % patients experienced grade 3 hematologic toxicities. The 4D-MRI technique allowed accurate target delineation and motion tracking in unresectable CRLMs patients. Favorable LC rate and mild toxicities were achieved. This study provided evidence for using 4D-MRI assisted SBRT as an alternative treatment in unresectable CRLMs.

Liver transplantation (LT) has significantly transformed the prognosis of patients with end-stage liver disease and hepatocellular carcinoma (HCC). The traditional epidemiology of liver diseases has undergone a remarkable shift in indications for LT, marked by a decline in viral hepatitis and an increase in metabolic dysfunction-associated steatotic liver disease (MASLD), along with expanded indications for HCC. Recent advancements in surgical techniques, organ preservation and post-transplant patients' management have opened new possibilities for LT. Conditions that were historically considered absolute contraindications have emerged as potential new indications, demonstrating promising results in terms of patient survival. While these expanding indications provide newfound hope, the ethical dilemma of organ scarcity persists. Addressing this requires careful consideration and international collaboration to ensure equitable access to LT. Multidisciplinary approaches and ongoing research efforts are crucial to navigate the evolving landscape of LT. This review aims to offer a current overview of the primary emerging indications for LT, focusing on acute-on-chronic liver failure (ACLF), acute alcoholic hepatitis (AH), intrahepatic and perihilar cholangiocarcinoma (i- and p-CCA), colorectal liver metastasis (CRLM), and neuroendocrine tumor (NET) liver metastases.

Surgical resection is still considered the optimal treatment for colorectal liver metastasis (CRLM). Although laparoscopic and robotic surgery demonstrated their reliability especially in referral centers, the comparison between perioperative outcomes of robotic liver resection (RLR) and open (OLR) liver resection are still debated when performed in referral centers for robotic surgery, not dedicated to HPB. Our study aimed to verify the efficacy and safety of perioperative outcomes after RLR and OLR for CRLM in an HUB&Spoke learning program (H&S) between a high volume center for liver surgery and high volume center for robotic surgery.

We analyzed prospective databases of Pineta Grande Hospital (Castel Volturno) and Robotic Surgical Units (Foligno-Spoleto and Arezzo) from 2011 to 2021. A 1:1 propensity score matching (PSM) was performed according to baseline characteristics of patients, solitary/multiple CRLM, anterolateral/posterosuperior location.

383 patients accepted to be part of the study (268 ORL and 115 RLR). After PSM, 45 patients from each group were included. Conversion rate was 8.89 %. RLR group had a significantly lower blood loss (226 vs. 321 ml; p=0.0001), and fewer major complications (13.33 % vs. 17.78 %; p=0.7722). R0 resection was obtained in 100% of OLR (vs.95.55%, p =0.4944. Hospital stay was 8.8 days in RLR (vs. 15; p=0.0001).Conclusion: H&S represents a safe and effective program to train general surgeons also in Hepatobiliary surgery providing R0 resection rate, blood loss volume and morbidity rate superimposable to referral centers. Furthermore, H&S allow a reduction of health mobility with consequent money saving for patients and institutions.

CRC with liver metastases is a major contributor to cancer-related mortality. Despite advancements in liver resection techniques, patient survival remains a concern due to high recurrence rates. This study seeks to uncover prognostic biomarkers that predict overall survival in patients undergoing curative hepatic resection for CRC liver metastases.

Prospectively collected serum samples from a cohort of 49 patients who received curative hepatic resection for CRC liver metastases were studied. The patients are part of a cohort, previously analyzed for perioperative complications (see methods). Various preoperative serum markers, clinical characteristics, and factors were analyzed. Univariate and multivariate Cox regression analyses were conducted to determine associations between these variables and disease-free survival as well as overall survival.

For disease-free survival, univariate analysis highlighted the correlation between poor outcomes and advanced primary tumor stage, high ASA score, and synchronous liver metastases. Multivariate analysis identified nodal-positive primary tumors and synchronous metastases as independent risk factors for disease-free survival. Regarding overall survival, univariate analysis demonstrated significant links between poor survival and high preoperative IL-8 levels, elevated neutrophil-lymphocyte ratio (NLR), and presence of metastases in other organs. Multivariate analysis confirmed preoperative IL-8 and having three or more liver metastases as independent risk factors for overall survival. The impact of IL-8 on survival was particularly noteworthy, surpassing the influence of established clinical factors.

This study establishes preoperative IL-8 levels as a potential prognostic biomarker for overall survival in patients undergoing curative liver resection for CRC liver metastases. This study underscores the importance of incorporating IL-8 and other biomarkers into clinical decision-making, facilitating improved patient stratification and tailored treatment approaches. Further research and validation studies are needed to solidify the clinical utility of IL-8 as a prognostic marker.

Microwave ablation (MWA) is a treatment modality for colorectal liver metastases (CRLM). While potentially curative, more information is needed on factors that contribute to long-term local tumour control. The prospective multicentre observational study CIRSE Emprint Microwave Ablation Registry aims to prospectively collect real-world technical data and clinical outcomes on patients treated with MWA in CRLM.

Eligible patients are adults with up to 9 local treatment naïve CRLM of ≤ 3 cm completely treatable with either MWA alone or MWA with resection and/or radiotherapy within 8 weeks. Data are collected, at baseline, every 3 months until 12 months, and thereafter every 6 months until the end of the study. The primary outcome measure is local tumour control. Secondary outcome measures are overall survival, (hepatic-) disease-free survival, time-to-progression untreatable by ablation, systemic therapy vacation, safety, and quality of life. Covariates related to the primary outcome measure will be assessed using a stratified log-rank test and an univariable Cox proportional hazard regression. A sample size of 500 patients with 750 lesions produces a two-sided 95% confidence interval with a precision equal to 0.057.

Between September 2019 and December 2022, 500 patients have been enrolled with at least 976 treated tumours.

The prospective observational CIEMAR study will provide valuable insights into the real-world use of MWA, helping in the future patient selection and clarifying factors that may contribute to long-term local tumour control.

NCT03775980.

Colorectal cancer (CRC) is the second most common cause of cancer-related deaths in the US. Thermal ablation (TA) can be a comparable alternative to partial hepatectomy for selected cases when eradication of all visible tumor with an ablative margin of greater than 5 mm is achieved. This systematic review and meta-analysis aimed to encapsulate the current clinical evidence concerning the optimal TA margin for local cure in patients with colorectal liver metastases (CLM).

MEDLINE, EMBASE, and the CENTRAL databases were systematically searched from inception until 1 May 2023, in accordance with the PRISMA Guidelines. Measure of effect included the risk ratio (RR) with 95% confidence interval (CI) using the random-effects model.

Overall, 21 studies were included, comprising 2005 participants and 2873 ablated CLMs. TA with margins less than 5 mm were associated with a 3.6 times higher risk for LTP (n = 21 studies, RR: 3.60; 95% CI: 2.58-5.03; p-value < 0.001). When margins less than 5 mm were additionally confirmed by using 3D software, a 5.1 times higher risk for LTP (n = 4 studies, RR: 5.10; 95% CI: 1.45-17.90; p-value < 0.001) was recorded. Moreover, a thermal ablation margin of less than 10 mm but over 5 mm remained significantly associated with 3.64 times higher risk for LTP vs. minimal margin larger than 10 mm (n = 7 studies, RR: 3.64; 95% CI: 1.31-10.10; p-value < 0.001).

This meta-analysis solidifies that a minimal ablation margin over 5 mm is the minimum critical endpoint required, whereas a minimal margin of at least 10 mm yields optimal local tumor control after TA of CLMs.

An estimated 25% of patients with colorectal cancer (CRC) present with distant metastases at the time of diagnosis, the most common site being the liver. Although prior studies have reported that a simultaneous approach to resections in these patients can lead to increased rates of complications, emerging literature shows that minimally invasive surgical (MIS) approaches can mitigate this additional morbidity. This is the first study utilizing a large national database to investigate colorectal and hepatic procedure-specific risks in robotic simultaneous resections for CRC and colorectal liver metastases (CRLM). Utilizing the ACS-NSQIP targeted colectomy, proctectomy, and hepatectomy files, 1,721 patients were identified who underwent simultaneous resections of CRC and CRLM from 2016 to 2021. Of these patients, 345 (20%) underwent resections by an MIS approach, defined as either laparoscopic (n = 266, 78%) or robotic (n = 79, 23%). Patients who underwent robotic resections had lower rates of ileus compared to those who had open surgeries. The robotic group had similar rates of 30-day anastomotic leak, bile leak, hepatic failure, and post-operative invasive hepatic procedures compared to both the open and laparoscopic groups. The rate of conversion to open (8% vs. 22%, p = 0.004) and median LOS (5 vs. 6 days, p = 0.022) was significantly lower for robotic compared to laparoscopic group. This study, which is the largest national cohort of simultaneous CRC and CRLM resections, supports the safety and potential benefits of a robotic approach in these patients.

Early detection of severe complications may reduce morbidity and mortality in patients undergoing hepatic resection. Therefore, we prospectively evaluated a panel of inflammatory blood markers for their value in predicting postoperative complications in patients undergoing liver surgery.

A total of 139 patients undergoing liver resections (45 wedge resections, 49 minor resections, and 45 major resections) were prospectively enrolled between August 2017 and December 2018. Leukocytes, CRP, neutrophil-lymphocyte ratio (NLR), thrombocyte-lymphocyte ratio (TLR), bilirubin, INR, and interleukin-6 and -8 (IL-6 and IL-8) were measured in blood drawn preoperatively and on postoperative days 1, 4, and 7. IL-6 and IL-8 were measured using standardized immunoassays approved for in vitro diagnostic use in Germany. ROC curve analysis was used to determine predictive values for the occurrence of severe postoperative complications (CDC ≥ 3).

For wedge and minor resections, leukocyte counts at day 7 (AUC 0.80 and 0.82, respectively), IL-6 at day 7 (AUC 0.74 and 0.73, respectively), and CRP change (∆CRP) at day 7 (AUC 0.72 and 0.71, respectively) were significant predictors of severe postoperative complications. IL-8 failed in patients undergoing wedge resections, but was a significant predictor of severe complications after minor resections on day 7 (AUC 0.79), had the best predictive value in all patients on days 1, 4, and 7 (AUC 0.72, 0.72, and 0.80, respectively), and was the only marker with a significant predictive value in patients undergoing major liver resections (AUC on day 1: 0.70, day 4: 0.86, and day 7: 0.92). No other marker, especially not CRP, was predictive of severe complications after major liver surgery.

IL-8 is superior to CRP in predicting severe complications in patients undergoing major hepatic resection and should be evaluated as a biomarker for patients undergoing major liver surgery. This is the first paper demonstrating a feasible implementation of IL-8 analysis in a clinical setting.

Bilobar liver metastases from colorectal cancer pose a challenge for obtaining a satisfactory oncological outcome with an adequate future liver remnant. This study aimed to assess the clinical and pathological determinants of overall survival and recurrence-free survival among patients undergoing surgical clearance of bilobar liver metastases from colorectal cancer.

A retrospective international multicentre study of patients who underwent surgery for bilobar liver metastases from colorectal cancer between January 2012 and December 2018 was conducted. Overall survival and recurrence-free survival at 1, 2, 3 and 5 years after surgery were the primary outcomes evaluated. The secondary outcomes were duration of postoperative hospital stay, and 90-day major morbidity and mortality rates. A prognostic nomogram was developed using covariates selected from a Cox proportional hazards regression model, and internally validated using a 3:1 random partition into derivation and validation cohorts.

A total of 1236 patients were included from 70 centres. The majority (88 per cent) of the patients had synchronous liver metastases. Overall survival at 1, 2, 3 and 5 years was 86.4 per cent, 67.5 per cent, 52.6 per cent and 33.8 per cent, and the recurrence-free survival rates were 48.7 per cent, 26.6 per cent, 19.2 per cent and 10.5 per cent respectively. A total of 25 per cent of patients had recurrent disease within 6 months. Margin positivity and progressive disease at liver resection were poor prognostic factors, while adjuvant chemotherapy in margin-positive resections improved overall survival. The bilobar liver metastases from colorectal cancer-overall survival nomogram was developed from the derivation cohort based on pre- and postoperative factors. The nomogram's ability to forecast overall survival at 1, 2, 3 and 5 years was subsequently validated on the validation cohort and showed high accuracy (overall C-index = 0.742).

Despite the high recurrence rates, overall survival of patients undergoing surgical resection for bilobar liver metastases from colorectal cancer is encouraging. The novel bilobar liver metastases from colorectal cancer-overall survival nomogram helps in counselling and informed decision-making of patients planned for treatment of bilobar liver metastases from colorectal cancer.

Colorectal cancer (CRC) is the second leading cause of cancer deaths in Spain. Metastatic disease is present in 15-30% of patients at diagnosis and up to 20-50% of those with initially localized disease eventually develop metastases. Recent scientific knowledge acknowledges that this is a clinically and biologically heterogeneous disease. As treatment options increase, prognosis for individuals with metastatic disease has steadily improved over recent decades. Disease management should be discussed among experienced, multidisciplinary teams to select the most appropriate systemic treatment (chemotherapy and targeted agents) and to integrate surgical or ablative procedures, when indicated. Clinical presentation, tumor sidedness, molecular profile, disease extension, comorbidities, and patient preferences are key factors when designing a customized treatment plan. These guidelines seek to provide succinct recommendations for managing metastatic CRC.

Surveillance of stage IV colorectal cancer (CRC) after curative-intent metastasectomy can be effective for detecting asymptomatic recurrence. Guidelines for various forms of surveillance exist but are supported by limited evidence. We aimed to determine the most cost-effective strategy for surveillance following curative-intent metastasectomy of stage IV CRC. We performed a decision analysis to compare four active surveillance strategies involving clinic visits and investigations elicited from National Comprehensive Cancer Network (NCCN) recommendations. Markov model inputs included data from a population-based cohort and literature-derived costs, utilities, and probabilities. The primary outcomes were costs (2021 Canadian dollars) and quality-adjusted life years (QALYs) gained. Over a 10-year base-case time horizon, surveillance with follow-ups every 12 months for 5 years was most economically favourable at a willingness-to-pay threshold of CAD 50,000 per QALY. These patterns were generally robust in the sensitivity analysis. A more intensive surveillance strategy was only favourable with a much higher willingness-to-pay threshold of approximately CAD 425,000 per QALY, with follow-ups every 3 months for 2 years then every 12 months for 3 additional years. Our findings are consistent with NCCN guidelines and justify the need for additional research to determine the impact of surveillance on CRC outcomes.

Twenty percent of colorectal cancer liver metastases (CLMs) are initially resectable with a 5-year survival rate of 25%-40%. Perioperative folinic acid, 5-fluorouracil, oxaliplatin (FOLFOX) increases progression-free survival (PFS). In advanced disease, the addition of targeting therapies results in an overall survival (OS) advantage. The aim of this study was to evaluate panitumumab and FOLFIRI as perioperative therapy in resectable CLM.

Patients with previously untreated, wild-type Rat sarcoma virus (RAS), and resectable CLM were included. Preoperative four and postoperative eight cycles of panitumumab and folinic acid, 5-fluorouracil, irinotecan (FOLFIRI) were administered. Primary objectives were efficacy and safety. Secondary endpoints included PFS and OS.

We enrolled 36 patients in seven centers in Austria (intention-to-treat analyses, 35 patients). There were 28 men and seven women, and the median age was 66 years. About 91.4% completed preoperative therapy and 82.9% underwent liver resection. The R0 resection rate was 82.7%. Twenty patients started and 12 patients completed postoperative chemotherapy. The objective radiological response rate after preoperative therapy was 65.7%. About 20% and 5.7% of patients had stable disease and progressive disease, respectively. The most common grade 3 adverse events were diarrhea, rash, and leukopenia during preoperative therapy. One patient died because of sepsis, and one had a pulmonary embolism grade 4. After surgery, two patients died because of hepatic failure. Most common grade 3 adverse events during postoperative therapy were skin toxicities/rash and leukopenia/neutropenia, and the two grade 4 adverse events were stroke and intestinal obstruction. Median PFS was 13.2 months. The OS rate at 12 and 24 months were 85.6% and 73.3%, respectively.

Panitumumab and FOLFIRI as perioperative therapy for resectable CLM result in a radiological objective response rate in 65.7% of patients with a manageable grade 3 diarrhea rate of 14.3%. Median PFS was 13.2 months, and the 24-month OS rate was 73.3%. These data are insufficient to widen the indication of panitumumab from the unresectable setting to the setting of resectable CLM.

Colorectal cancer liver metastasis (CRLM) is one of the leading causes of death among patients with colorectal cancer (CRC). Although immunotherapy has demonstrated encouraging outcomes in CRC, its benefits are minimal in CRLM. The complex immune landscape of the hepatic tumour microenvironment is essential for the development of a premetastatic niche and for the colonisation and metastasis of CRC cells; thus, an in-depth understanding of these mechanisms can provide effective immunotherapeutic targets for CRLM. This review summarises recent studies on the immune landscape of the tumour microenvironment of CRLM and highlights therapeutic prospects for targeting the suppressive immune microenvironment of CRLM.

To determine the long-term outcomes of radiofrequency ablation with respect to overall survival, disease-free survival, and complications in patients with colorectal cancer liver metastases. Additionally, we sought to examine whether various patient- and treatment-related characteristics were associated with prognosis.

Fifty-nine patients with colorectal cancer liver metastases who had undergone percutaneous radiofrequency ablation treatment were included in this study. A total of 138 lesions were treated with radiofrequency ablation in the first and second sessions. Tumor diameters ranged from 10 to 60 mm (mean, 2.45 mm). Treatment efficacy, complications, and overall survival and disease-free survival were analyzed.

The primary success rate of radiofrequency ablation was 94.4%. At the end of the first month, the residual disease was detected in 12 lesions, 10 of which underwent secondary radiofrequency ablation treatment, resulting in a cumulative secondary success rate of 98.4%. The 1-, 3-, and 5-year overall survival rates in 59 patients with colorectal cancer liver metastases were 94.9%, 52.5%, and 40.6%, respectively. The median survival was 42 months in patients with metastasis size of ≤3 cm, while it was 25 months in patients with metastasis size of >3 cm (P = .001). The 1-, 3-, and 5-year disease-free survival rates were 44%, 10.2%, and 6.7%, respectively. Metastatic tumor status (solitary or multiple) was a significant prognostic factor in determining overall survival and disease-free survival; furthermore, extrahepatic recurrence during follow-up was a prognostic factor affecting overall survival. Minor complications developed in four radiofrequency ablation procedures (6.7%).

Radiofrequency ablation remains a safe and effective treatment option improving survival in select cases of colorectal cancer liver metastases.

An estimated 25% of patients with colorectal cancer (CRC) present with distant metastases at the time of diagnosis, the most common site being the liver. Controversy exists regarding the safety of a simultaneous versus staged approach to resections in these patients, but reports have shown that minimally invasive surgery (MIS) approaches can mitigate morbidity. This is the first study utilizing a large national database to investigate colorectal and hepatic procedure-specific risks in robotic simultaneous resections for CRC and colorectal liver metastases (CRLM). Utilizing the ACS-NSQIP targeted colectomy, proctectomy, and hepatectomy files, 1,550 patients were identified who underwent simultaneous resections of CRC and CRLM from 2016-2020. Of these patients, 311 (20%) underwent resections by an MIS approach, defined as an either laparoscopic (n = 241, 78%) or robotic (n = 70, 23%). Patients who underwent robotic resections had lower rates of ileus compared to those who had an open surgery. The robotic group had similar rates of 30-day anastomotic leak, bile leak, hepatic failure, and post operative invasive hepatic procedures compared to both the open and laparoscopic groups. The rate of conversion to open was significantly lower for robotic compared to laparoscopic group (9% vs. 22%, p = 0.012). This report is the largest study to date of robotic simultaneous CRC and CRLM resections reported in the literature and supports the safety and potential benefits of this approach.

Complimentary use of Liver directed therapies (LDTs) with systemic chemotherapy has improved oncologic outcomes in colorectal liver metastasis (CRLM). We analysed institutional results of multimodality management.

Retrospective analysis of prospectively maintained database of CRLM patients managed with LDT including surgical resection, Ablation, Transarterial chemoembolization (TACE) or Transarterial radioembolization (TARE) between November 2011 to March 2020. Management plan was decided in multidisciplinary meeting. Resectable tumours underwent surgical resection or ablation or both in some cases. Borderline resectable or unresectable disease was treated with down staging chemotherapy or TACE/TARE followed by resection or ablation. All patients received adjuvant chemotherapy. Factors influencing survival were analysed.

Out of total 375 patients, surgery alone was done in 191 (50.93%) patients while surgery with other LDT in 26 patients (6.93%). Ablation alone was done in 100 (26.66%) whereas TACE/TARE were done as standalone treatment in 21 (5.6%) and 7 (1.86%) patients respectively. TACE + ablation was done in 28 (7.46%) and TARE + ablation was done in 2(0.53%) patients.5-year Overall Survival(OS) was 49.8% while Event free survival(EFS) was 21.4%. The median OS and EFS for surgical group was significantly better than non-surgical group (78 V/s 39 months; p<0.05 and 20 V/s 15 months p <0.005). The resectable (78 months) group had better median OS as compared to borderline resectable and Unresectable group (39 months and 29 months). Male gender, resectable disease and surgical intervention were associated with improved OS.

Although surgery remains the mainstay of treatment, complementary use of non-surgical LDT with systemic therapy offers possibility of good outcomes in advanced liver limited disease. Our experience highlights the impact of multidisciplinary care in optimizing CRLM treatment.

Over the past two decades of successive clinical trials in metastatic colorectal cancer (CRC), the median overall survival of both control and experimental arms has steadily improved. However, the incremental change in survival for metastatic CRC patients not treated on trial has not yet been quantified. We performed a retrospective review of 1420 patients with de novo metastatic CRC who received their primary treatment at the University of Texas M.D. Anderson Cancer Center (UTMDACC) from 2004 through 2019. Median OS was roughly stable for patients diagnosed between 2004 and 2012 (22.6 months) but since has steadily improved for those diagnosed in 2013 to 2015 (28.8 months), and 2016 to 2019 (32.4 months). Likewise, 5-year survival rate has increased from 15.7% for patients diagnosed from 2004 to 2006 to 26% for those diagnosed from 2013 to 2015. Notably, survival improved for patients with BRAFV600E mutant as well as microsatellite unstable (MSI-H) tumors. Multivariate regression analysis identified surgical resection of liver metastasis (HR = 0.26, 95% CI, 0.19-0.37), use of immunotherapy (HR = 0.44, 95% CI, 0.29-0.67) and use of third line chemotherapy (regorafenib or trifluridine/tipiracil, HR = 0.74, 95% CI, 0.58-0.95), but not year of diagnosis (HR = 0.99, 95% CI, 0.98-1), as associated with better survival, suggesting that increased use of these therapies are the drivers of the observed improvement in survival.