Management Of Colorectal Liver Metastases Research Articles

New trends in surgery for colorectal liver metastasis

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

Impact of neoadjuvant chemotherapy on short-term outcomes after simple and complex minimally invasive minor hepatectomy for colorectal liver metastases: A propensity-score matched and coarsened exact matched study

BackgroundIn the last three decades, minimally invasive liver resection has been replacing conventional open approach in liver surgery. More recently, developments in neoadjuvant chemotherapy have led to increased multidisciplinary management of colorectal liver metastases with both medical and surgical treatment modalities. However, the impact of neoadjuvant chemotherapy on the surgical outcomes of minimally invasive liver resections remains poorly understood. MethodsA multicenter, international, database of 4998 minimally invasive minor hepatectomy for colorectal liver metastases was used to compare surgical outcomes in patients who received neoadjuvant chemotherapy with surgery alone. To correct for baseline imbalance, propensity score matching, coarsened exact matching and inverse probability treatment weighting were performed. Results2546 patients met the inclusion criteria. After propensity score matching there were 759 patients in both groups and 383 patients in both groups after coarsened exact matching. Baseline characteristics were equal after both matching strategies. Neoadjuvant chemotherapy was not associated with statistically significant worse surgical outcomes of minimally invasive minor hepatectomy. ConclusionNeoadjuvant chemotherapy had no statistically significant impact on short-term surgical outcomes after simple and complex minimally invasive minor hepatectomy for colorectal liver metastases.

Prognosis of a Heterogeneous TRG Pathological Response to Neoadjuvant Chemotherapy in Patients who Undergo Resection for Colorectal Liver Metastases.

Optimal management of colorectal liver metastasis (CRLM) is based on a combination of chemotherapy and surgical resection. The tumor regression grade (TRG) score is a histological scoring system to evaluate response to chemotherapy. The prognosis of a heterogeneous response in cases of multiple metastases has not been evaluated according to the TRG score. All patients who underwent liver resection for multiple CRLM after neoadjuvant chemotherapy in two tertiary centers from January 2015 to April 2019 were retrospectively included. Oncological characteristics and outcome between TRG 1-2-3 (good response group), TRG 4-5 (poor response group) and heterogeneous TRG (good and poor TRG among different lesions within the same patient) groups were compared. Among the 327 patients included, 134 (41.0%) had good response (TRG 1-2-3), 120 (36.7%) had poor response (TRG 4-5), and 73 (22.3%) had heterogeneous response. The type and number of cycles of chemotherapy, k-Ras mutational status, and tumor number or size did not differ between the three groups. Use of irinotecan-based and anti-VEGF neoadjuvant therapy was associated with better TRG response [irinotecan-based: hazard ratio (OR) = 1.744; p = 0.045; anti-VEGF neoadjuvant therapy: 2.054; p = 0.005). Overall survival (OS) was higher in the 1-2-3 TRG group than in the heterogeneous TRG group (2-year OS = 81.3% vs. 60.3%, respectively; p = 0.003) and the 4-5 TRG group (2-year OS = 81.3% vs. 55.0%, respectively; p = 0.012) and similar between the heterogeneous and 4-5 TRG groups. The proportion of heterogeneous pathological response according to TRG is 22.3%, and the prognosis is comparable to that of poor pathological response.

Contemporary Surgical Management of Colorectal Liver Metastases.

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.

Multimodal Management of Colorectal Liver Metastases: State of the Art.

Liver is the most common site of colorectal cancer (CRC) metastases. Treatment of CRC liver metastases (CRLM) includes different strategies, prevalently based on the clinical and oncological intent. Valid approaches in liver-limited or liver-prevalent disease include surgery, percutaneous ablative procedures (radiofrequency ablation, microwave ablation), intra-arterial perfusional techniques (chemo-embolization, radio-embolization) as well as stereotactic radiotherapy. Systemic treatments, including chemotherapy, immunotherapy and other biological agents, are the only options for patients with no chance of locoregional approaches. The use of chemotherapy in other settings, such as neoadjuvant, adjuvant or conversion therapy of CRLM, is commonly accepted in the clinical practice, although data from several clinical trials have been mostly inconclusive. The optimal integration of all these strategies, when applicable and clinically indicated, should be ever considered in patients affected by CRLM based on clinical evidence and multidisciplinary experience. Here we revised in detail all the possible therapeutic approaches of CRLM focusing on the current evidences, the studies still in progress and the often contradictory data.

Integration of Next-Generation Sequencing in the Surgical Management of Colorectal Liver Metastasis.

Hepatic resection remains the treatment of choice for colorectal liver metastases. The advancement of surgical technique and use of perioperative systemic therapy has expanded the number and complexity of patients eligible for surgical resection. In recent years, investigation into gene mutations, such as RAS/RAF pathway, have led to targeted therapies that have significantly improved outcomes. Next-generation sequencing allows analysis of large number of genes that may have potential prognostic relevance in the clinical setting. This review summarizes the current applications of next-generation sequencing technology in metastatic colorectal cancer, focusing on its prognostic implications on patient management.

Colorectal cancer liver metastasis: genomic evolution and crosstalk with the liver microenvironment.

Colorectal cancer (CRC) patients frequently develop liver metastases, which are the major cause of cancer-related mortality. The molecular basis and management of colorectal liver metastases (CRLMs) remain a challenging clinical issue. Recent genomic evidence has demonstrated the liver tropism of CRC and the presence of a stricter evolutionary bottleneck in the liver as a target organ compared to lymph nodes. This bottleneck challenging CRC cells in the liver is organ-specific and requires adaptation not only at the genetic level, but also at the phenotypic level to crosstalk with the hepatic microenvironment. Here, we highlight the emerging evidence on the clonal evolution of CRLM and review recent insights into the molecular mechanisms orchestrating the bidirectional interactions between metastatic CRC cells and the unique liver microenvironment.

Pushing the Limits of Surgical Resection in Colorectal Liver Metastasis: How Far Can We Go?

Colorectal cancer is the third most common cancer worldwide, and up to 50% of all patients diagnosed will develop metastatic disease. Management of colorectal liver metastases (CRLM) has been constantly improving, aided by newer and more effective chemotherapy agents and the use of multidisciplinary teams. However, the only curative treatment remains surgical resection of the CRLM. Although survival for surgically resected patients has shown modest improvement, this is mostly because of the fact that what is constantly evolving is the indication for resection. Surgeons are constantly pushing the limits of what is considered resectable or not, thus enhancing and enlarging the pool of patients who can be potentially benefited and even cured with aggressive surgical procedures. There are a variety of procedures that have been developed, which range from procedures to stimulate hepatic growth, such as portal vein embolization, two-staged hepatectomy, or the association of both, to technically challenging procedures such as simultaneous approaches for synchronous metastasis, ex-vivo or in-situ perfusion with total vascular exclusion, or even liver transplant. This article reviewed the major breakthroughs in liver surgery for CRLM, showing how much has changed and what has been achieved in the field of CRLM.

Surgical management of colorectal liver metastases—a practical clinical approach

Summary Background Despite the remarkable advances that have been made in the management of colorectal cancer over recent years, the optimal treatment for colorectal liver metastases (CRLM) remains a controversial matter. Undoubtedly, such a complex disease requires a multidisciplinary approach, in which close collaboration between all specialists involved in its management is of utmost importance. Methods A literature search was conducted in PubMed. There was no limit set to the date of publication. The main focus of the literature review is to provide a comprehensive summary of the current multidisciplinary management of CRLM while highlighting the surgical approach. Results Assessment of resectability, evaluation of the patient’s fitness, and discussion of clinicopathological features all play a vital role in finding the most suitable treatment strategy for CRLM patients, who should all be timely discussed in the multidisciplinary tumor board, in order to decide upon the optimal therapy sequence, operative time window, and postoperative treatment. Conclusion Although hepatic resection remains the only potentially curative treatment strategy for patients with CRLM, a multidisciplinary approach is essential for optimal treatment. A clear definition of treatment goal (curative vs. palliative) at the time of disease diagnosis determines the further therapeutic course. Preoperative estimation of liver functional reserve is a key factor in the decision-making process for CRLM resectability.

Surgical and Interventional Management of Liver Metastasis.

Colorectal cancer is one of the most common cancers diagnosed worldwide. While the incidence of colorectal cancer has been declining since the adoption of screening colonoscopy, the findings of liver metastasis are still found in up to 25% of patients at diagnosis. The management of liver metastasis has evolved over the past two to three decades, and survival rates have improved secondary to improved systemic therapy, surgical options, and local therapies. In this article, we aim to review the available surgical and ablative options for management of colorectal liver metastasis, as well as appropriate imaging and patient selection.

Cohort study of long-term survival and recurrence patterns following operative management of colorectal liver metastasis - is follow-up beyond 5years warranted?

To evaluate the patterns of overall survival (OS) and recurrence following surgical resection of colorectal liver metastases (CRLM). In compliance with STROCSS guideline, a single-centre retrospective cohort study was conducted. All consecutive patients undergoing resection of CRLM between 2003 and 2019 were considered eligible for inclusion. The outcome measures included OS, recurrence-free survival (RFS), recurrence rate, time to recurrence (TTR) and longest TTR. Statistical analyses included simple descriptive statistics and Kaplan-Meier survival statistics. We included 486 liver resections in 472 patients. The estimated median OS and RFS were 5.1years and 3.1years, respectively. The probability of 1-year, 3-year, 5-year and 10-year OS was 93%, 69%, 50% and 34%, respectively. The probability of 1-year, 3-year, 5-year and 10-year RFS was 81%, 50%, 34% and 33%, respectively. Recurrence occurred in 56% (271/486) of patients, and the median TTR was 1.6years (IQR: 0.8-2.7) with longest TTR of 4.8years. Although there were no recurrences in the 66 patients that entered the 6th year, the 95% CI for true rate of recurrence in the population given these data is 0-5.4%. Our results suggest that recurrences that occur after operative management of CRLM are almost certain to occur within the first 5years even for patients surviving longer than 5years. This does not disprove the requirement for follow up beyond 5years. However, based on this data, we have altered our follow up from 10 to 6years. The need for the 6th year of follow up will be reassessed in light of further observations.

The Role of Biomarkers in the Management of Colorectal Liver Metastases.

Simple SummaryColorectal cancer remains one of the most significant sources of cancer-related morbidity and mortality worldwide. The liver is the most common site of metastatic spread. Multiple modalities exist to manage and potentially cure patients with metastatic colorectal cancer. However, reliable biomarkers to assist with clinical decision-making are limited. Recent advances in genomic sequencing technology have greatly expanded our knowledge of colorectal cancer carcinogenesis and significantly reduced the cost and timing of the investigation. In this article, we discuss the current utility of biomarkers in the management of colorectal cancer liver metastases.Surgical management combined with improved systemic therapies have extended 5-year overall survival beyond 50% among patients with colorectal liver metastases (CRLM). Furthermore, a multitude of liver-directed therapies has improved local disease control for patients with unresectable CRLM. Unfortunately, a significant portion of patients treated with curative-intent hepatectomy develops disease recurrence. Traditional markers fail to risk-stratify and prognosticate patients with CRLM appropriately. Over the last few decades, advances in molecular sequencing technology have greatly expanded our knowledge of the pathophysiology and tumor microenvironment characteristics of CRLM. These investigations have revealed biomarkers with the potential to better inform management decisions in patients with CRLM. Actionable biomarkers such as RAS and BRAF mutations, microsatellite instability/mismatch repair status, and tumor mutational burden have been incorporated into national and societal guidelines. Other biomarkers, including circulating tumor DNA and radiomic features, are under active investigation to evaluate their clinical utility. Given the plethora of therapeutic modalities and lack of evidence on timing and sequence, reliable biomarkers are needed to assist clinicians with the development of patient-tailored management plans. In this review, we discuss the current evidence regarding biomarkers for patients with CRLM.

Implications of RAS Mutations on Oncological Outcomes of Surgical Resection and Thermal Ablation Techniques in the Treatment of Colorectal Liver Metastases.

Simple SummaryModern management of colorectal liver metastases (CRLM) requires a thorough knowledge of tumor biology and oncogenes mutations. RAS mutations are of paramount interest for the indication of targeted therapies and is increasingly considered as a negative prognostic factor for patients undergoing surgical resection or ablation for CRLM. Several studies discussed the results of specific technical considerations according to RAS mutational status on the oncological outcomes after surgical resection/ablation for CRLM. We reviewed the available data on the real impact of RAS mutations on the prognosis with special regard to the need of a tailored surgical (ablation) approach according to tumoral biology.Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related death. More than 50% of patients with CRC will develop liver metastases (CRLM) during their disease. In the era of precision surgery for CRLM, several advances have been made in the multimodal management of this disease. Surgical treatment, combined with a modern chemotherapy regimen and targeted therapies, is the only potential curative treatment. Unfortunately, 70% of patients treated for CRLM experience recurrence. RAS mutations are associated with worse overall and recurrence-free survival. Other mutations such as BRAF, associated RAS /TP53 and APC/PIK3CA mutations are important genetic markers to evaluate tumor biology. Somatic mutations are of paramount interest for tailoring preoperative treatment, defining a surgical resection strategy and the indication for ablation techniques. Herein, the most relevant studies dealing with RAS mutations and the management of CRLM were reviewed. Controversies about the implication of this mutation in surgical and ablative treatments were also discussed.

Laparoscopic Compared with Open Liver Resection in the Management of Colorectal Liver Metastases

Introduction: Laparoscopic liver resection (LLR) is increasingly adopted in the management of colorectal liver metastases (CRLM). This study compares perioperative and oncologic outcomes in LLR and open resection (OLR) for CRLM. Methods: Consecutive patients undergoing hepatectomy between 2009-2019 for CRLM at a single tertiary referral centre were prospectively studied. Univariable and multivariable logistic and Cox proportional hazards regression analysis was performed to determine the independent impact of operative approach on perioperative and oncologic outcome. Results: 273 patients were studied. LLR patients were more likely to be ASA-3 (58.0% vs 34.5%, P=0.016), older (65.4±9.4 vs 61.4±10.9 years, P=0.016) and have a greater Charlson comorbidity index (4.6±1.5 vs 4.0±1.4, P=0.008). LLR patients had less bilobar disease (18.0% vs 44.4%, P=0.001), were less likely to undergo major hepatectomy (6.0% vs 36.8%, P<0.001) or portal vein embolization (0.0% vs 10.8%, P=0.015), with increased non-anatomical resection (76.1% vs 66.0%, P=0.016). R0 resection rates were similar (86.0% vs 91.0%, P=0.310). Length of stay (median 7-days in both groups, P=0.313), readmission (4.0% vs 8.6%,P=0.275), and 30-day mortality (0.0% vs 1.8%, P=0.340) were equivalent. On multivariable analysis, major liver resection (OR2.70 [95%CI 1.46- 5.01], P=0.002), but not LLR (P=0.221), independently predicted major postoperative morbidity. Overall survival was similar between groups on univariable (median 47.0 vs 44.0 months, P=0.384) and multivariable analysis (P=0.152). Conclusion: LLR is feasible and safe with outcomes that are at least equivalent to open surgery. LLR may facilitate surgical resection for CRLM among patients with significant baseline comorbidity and anaesthetic risk.

Role of liver transplantation in the management of colorectal liver metastases: Challenges and opportunities.

The liver is the most common site of colorectal cancer metastasis. Complete resection of the metastatic tumor is currently the only treatment modality available with a potential for cure. However, only 20% of colorectal liver metastases (CRLM) are considered resectable at the time of presentation. Liver transplantation (LT) has been proposed as an alternative oncologic treatment for patients with unresectable CRLM. This review summarizes the published experiences of LT in the setting of unresectable CRLM from the previous decades and discusses the challenges and future horizons in the field. Contemporary experiences that come mostly from countries with broader access to liver grafts are also explored and their promising findings in terms of overall survival (OS) and disease-free survival (DFS) are outlined along with their study design and methods. The rationale of establishing specific patient selection criteria and the dilemmas around immunosuppressive regimens in patients undergoing LT for CRLM are also highlighted. Additionally, this review describes the findings of studies comparing LT vs chemotherapy alone and LT vs portal vein embolization plus resection for CRLM in terms of OS and DFS. Last but not least, we present current perspectives and ongoing prospective trials that try to elucidate the role of LT for CRLM.

Narrative review of the role of yttrium-90 selective internal radiation therapy in the surgical management of colorectal liver metastases.

The management of colorectal liver metastasis (CRLM) is complicated and benefits from a multidisciplinary team approach. Liver-directed therapy has been emerging as a modality for better progression-free control. In its early years, selective internal radiation therapy (SIRT) with yttrium-90 (Y-90) was confined as an end-of-line therapy. However, literature has supported other roles including: a first-line treatment for CRLM alone or in combination with systemic chemotherapy; an adjunct to second or third-line chemotherapy; and a salvage treatment for chemo-refractory disease. Although future liver remnant (FLR) hypertrophy may take 3-12 months, the SIRT effect on loco-regional disease control has rendered it to be a useful tool in some pathologies with certain strategic goals. This paper reviews the use of SIRT with Y-90 in a surgical treatment pathway. This includes: (I) an element of multidisciplinary treatment of low-volume CRLMs, (II) convert an R1 to R0 resection by sterilizing the margins of tumor near critical structures, and (III) radiation lobectomy to induce contralateral hypertrophy in order to aid in a safer resection. There are many opportunities to validate the role of SIRT as a first-line therapy along with surgical resection including an umbrella clinical trial design.

Open versus laparoscopic liver resection of colorectal metastases: a meta-analysis of matched patient populations.

In recent years, the management of colorectal liver metastases (CRLM) has evolved significantly. Laparoscopic liver resection is increasingly being performed, despite a lack of major randomized controlled trial evidence or widespread international consensus. The objective of this review was to compare the short- and long-term outcomes following open and laparoscopic CRLM resection. A systematic review of comparative matched population studies was performed. Evaluated endpoints included surgical outcomes and survival outcomes. Twelve studies were included in this review, reporting on 3095 patients. R0 (negative margins) rates were higher in the laparoscopic CRLM group (89.3% versus 86.9%). In addition, laparoscopic resection was associated with less blood loss (486 mls versus 648 mls, p ≤ 0.0001*) and reduced blood transfusion rates (6.7% vs. 12.2%, OR 2.13, 95% CI 1.08-4.19, p = 0.03*). Major complication rates were higher in the open CRLM group (12.5% vs. 8.1%, OR 1.74, 95% CI 1.30-2.33, p = 0.03*), as was overall hospital length of stay (median 7 versus 5.5days, p = 0.001*). Perioperative mortality was similar between both groups, and there was no significance in 5-year overall survival for open or laparoscopic CRLM resection groups (58% and 61% respectively). Laparoscopic CRLM resection is associated with less blood loss, lower transfusion rates, major complications, and overall hospital length of stay with comparable oncological outcome.

Combined liver resection and radiofrequency ablation for bilobar multiple colorectal liver metastasis

Combined liver resection and radiofrequency ablation for bilobar multiple colorectal liver metastasis

Locoregional Therapies for Colorectal Cancer Liver Metastases: Options Beyond Resection

Colorectal cancer was the third most common malignancy worldwide in 2018, and most patients present with or develop distant metastases. Colorectal liver metastases are most commonly observed because of the vascular drainage of the colon and superior rectum. Current guidelines recommend surgical resection as first-line treatment; however, 80% to 90% of patients with colorectal liver metastases are ineligible for primary resection. For patients with unresectable disease, a multidisciplinary treatment approach is favored, incorporating systemic therapy and a toolbox of local ablative therapies. These treatments either aim at cytoreduction to enable a conversion to surgical resectability or control of disease progression and spread. Each of these treatments carries unique outcomes and risk profiles, thereby contributing to an individualized treatment strategy for patients with colorectal liver metastases. This review summarizes evidence on hepatic artery infusion, stereotactic body radiation therapy, thermal ablation, transarterial chemoembolization with drug-eluding beads, and transarterial radioembolization for treatment of colorectal liver metastases. Results of large-scale prospective and retrospective studies and international guidelines are discussed to provide detailed background on the current and prospective use of local ablative techniques in management of colorectal liver metastases.

Risk stratification and goal of systemic therapy for successful surgical management of colorectal liver metastases: Oncological optimization.

For patients with stage IV colorectal cancer (CRC), curative-intent surgery has actively been performed for expecting prolonged survival outcomes. However, because the population with stage IV CRC is considerably heterogeneous, optimal selection of surgical candidate is inevitable to maximize survival outcomes. In the era of effective chemotherapy, there is an increasing need for a strategic use of chemotherapy as a part of multidisciplinary treatment to expand surgical indications and enhance the clinical outcomes. However, since the fate of each patient is difficult to predict at initial presentation, our clinical practice is rather "tailored", considering the anatomy, oncological behavior of tumor, response to chemotherapy, and patient's physical status. Given that surgery is the only treatment option for expecting cure of colorectal liver metastases (CLM), the main purpose of chemotherapy for potentially/marginally resectable disease is to clarify the likelihood of surgical benefit through testing the behavior of the tumor and to select an appropriate candidate for surgery. This process of clinical decision is actually optimization of the initial population for surgery through the optimization of treatment for each patient. In this article, theoretical bases of multidisciplinary management for CLM were revisited and the concept of "oncological optimization" underling our clinical decision was discussed.