Resection Of Colorectal Liver Metastases Research Articles

Repeat Hepatic Resection for Colorectal Liver Metastases, Assessment of Outcomes and Hospital Variation: A Nationwide Cohort Study

Repeat Hepatic Resection for Colorectal Liver Metastases, Assessment of Outcomes and Hospital Variation: A Nationwide Cohort Study

Tumor biology reflected by histological growth pattern is more important than surgical margin for the prognosis of patients undergoing resection of colorectal liver metastases.

The histological growth pattern (HGP) of colorectal liver metastases (CRLMs) reflects tumor biology and local infiltrating behavior. In patients undergoing surgery for CRLMs, we investigated whether HGP and surgical margin status interact when influencing prognosis. Clinicopathological data, margin status, and HGP were reviewed in patients who underwent resection of CRLMs. R1 margin was defined when cancer cells were present at any point along the margin. HGPs were scored according to international guidelines, identifying patients with desmoplastic (DHGP) or non-desmoplastic (non-DHGP) CRLMs. Among 299 patients, 16% had R1 resection and 81% had non-DHGP CRLMs. Non-DHGP was the only predictive factor for R1 resection (18.7% versus 7.4% in DHGP, p=0.04). Poorer 5-year overall survival was observed in both R1 and non-DHGP groups in univariate analysis (27.6% in R1 versus 45.6% in R0, p=0.026, and 37.2% in non-DHGP versus 59.2% in DHGP, p=0.013), whereas non-DHGP but not R1 remained associated with worse prognosis in multivariate analysis. In patients with non-DHGP, R1 margin has no prognostic impact. In patients undergoing resection of CRLMs, the prognostic value of poor tumor biology, such as in patients with non-DHGP, exceeds that of surgical radicality.

Negative Impact of Intraoperative Erythrocyte Transfusion on Overall Patient Survival after Resection for Colorectal Liver Metastases

Negative Impact of Intraoperative Erythrocyte Transfusion on Overall Patient Survival after Resection for Colorectal Liver Metastases

Perioperative Outcomes of Sinusoidal Obstruction Syndrome Underwent Liver Resection for Colorectal Metastases after Neoadjuvant Chemotherapy

Perioperative Outcomes of Sinusoidal Obstruction Syndrome Underwent Liver Resection for Colorectal Metastases after Neoadjuvant Chemotherapy

Tumor Burden Score Predicts 1-year Overall Survival after Curative Resection of Colorectal Liver Metastases

Tumor Burden Score Predicts 1-year Overall Survival after Curative Resection of Colorectal Liver Metastases

Vascular R1 in Parenchymal Sparing Liver Resections for Colorectal Liver Metastases: A Single Center Experience

Vascular R1 in Parenchymal Sparing Liver Resections for Colorectal Liver Metastases: A Single Center Experience

Importance of Resection Margin after Resection of Colorectal Liver Metastases in the Era of Modern Chemotherapy: A Population-based Cohort Study

Importance of Resection Margin after Resection of Colorectal Liver Metastases in the Era of Modern Chemotherapy: A Population-based Cohort Study

Laparoscopic versus Open Parenchymal Sparing Liver Resections for Colorectal Liver Metastases with High Tumour Burden: A Propensity Score Matched Analysis

Laparoscopic versus Open Parenchymal Sparing Liver Resections for Colorectal Liver Metastases with High Tumour Burden: A Propensity Score Matched Analysis

Local therapy improves survival for early recurrence after resection of colorectal liver metastases

Background: Early recurrence following hepatectomy for patients with colorectal liver metastases (CLM) is associated with worse survival. However, it is unclear whether local therapy improves outcomes. We hypothesized that local therapy benefits patients with recurrence following hepatectomy for CLM, regardless of timing of recurrent disease.

Splenic hypertrophy predicts liver-specific complications in patients undergoing major liver resection for colorectal liver metastases, after preoperative chemotherapy

Splenic hypertrophy predicts liver-specific complications in patients undergoing major liver resection for colorectal liver metastases, after preoperative chemotherapy

ICG Fluorescence Imaging for Real-time Margin Detection during Minimally Invasive Resections of Colorectal Liver Metastases (MIMIC) - A Multicenter Prospective Cohort Study

ICG Fluorescence Imaging for Real-time Margin Detection during Minimally Invasive Resections of Colorectal Liver Metastases (MIMIC) - A Multicenter Prospective Cohort Study

Preoperative CT-based Volumetry of the Lung Can Predict Postoperative Respiratory Complications in Patients Undergoing Major Liver Resection for Colorectal Metastases

Preoperative CT-based Volumetry of the Lung Can Predict Postoperative Respiratory Complications in Patients Undergoing Major Liver Resection for Colorectal Metastases

CSF1 expression associated with M2 macrophages and decreased survival in colorectal liver metastases

Background: Over half of patients with colorectal cancer develop liver metastases. A deeper understanding of the colorectal liver metastasis (CRLM)-specific tumor immune microenvironment is needed to improve therapeutic options. Within the tumor immune microenvironment, macrophages play a key role in tumor invasion and metastasis. Specifically, the M2 macrophage phenotype is known to be immunosuppressive, pro-tumorigenic, and is induced by CSF1 signaling. Using NanoString gene expression analysis on resected CRLM specimens, we previously identified that CSF1 was expressed at higher levels in patients with resected CRLM who had poor overall survival compared to those with better survival. Given these findings at the gene expression level, we hypothesized that tumors of patients with poor survival would have a higher prevalence of M2 macrophages. The aim of this study was to assess the M2 macrophage frequency in the tumor immune microenvironment of patients who underwent resection of CRLM.

Prognostic circulating proteomic biomarkers in colorectal liver metastases

The liver is the most common site of metastasis in colorectal cancer. Multimodal treatment, including liver resection, is potentially curative and prolongs survival for selected patients with colorectal liver metastases (CRLM). However, the treatment of CRLM remains challenging because recurrence is common, and prognosis varies widely between patients despite curative-intent treatment. Clinicopathological features and tissue-based molecular biomarkers, either alone or in combination, are insufficient for accurate prognostication. As most of the functional information in cells resides in the proteome, circulating proteomic biomarkers may be useful for rationalising the molecular complexities of CRLM and identifying potentially prognostic molecular subtypes. High-throughput proteomics has accelerated a range of applications including protein profiling of liquid biopsies for biomarker discovery. Moreover, these proteomic biomarkers may provide non-invasive prognostic information even before CRLM resection. This review evaluates recently discovered circulating proteomic biomarkers in CRLM. We also highlight some of the challenges and opportunities with translating these discoveries into clinical applications.

T cell receptor repertoire sequencing reveals chemotherapy-driven clonal expansion in colorectal liver metastases.

Colorectal liver metastasis (CLM) is a leading cause of colorectal cancer mortality, and the response to immune checkpoint inhibition (ICI) in microsatellite-stable CRC has been disappointing. Administration of cytotoxic chemotherapy may cause increased density of tumor-infiltrating T cells, which has been associated with improved response to ICI. This study aimed to quantify and characterize T-cell infiltration in CLM using T-cell receptor (TCR) repertoire sequencing. Eighty-five resected CLMs from patients included in the Oslo CoMet study were subjected to TCR repertoire sequencing. Thirty-five and 15 patients had received neoadjuvant chemotherapy (NACT) within a short or long interval, respectively, prior to resection, while 35 patients had not been exposed to NACT. T-cell fractions were calculated, repertoire clonality was analyzed based on Hill evenness curves, and TCR sequence convergence was assessed using network analysis. Increased T-cell fractions (10.6%vs. 6.3%) were detected in CLMs exposed to NACT within a short interval prior to resection, while modestly increased clonality was observed in NACT-exposed tumors independently of the timing of NACT administration and surgery. While private clones made up >90% of detected clones, network connectivity analysis revealed that public clones contributed the majority of TCR sequence convergence. TCR repertoire sequencing can be used to quantify T-cell infiltration and clonality in clinical samples. This study provides evidence to support chemotherapy-driven T-cell clonal expansion in CLM in a clinical context.

Circulating Tumor DNA: Towards More Individualized Treatment for Patients with Resectable Colorectal Cancer.

Despite curative-intent treatment, recurrence is common for patients with colorectal cancer (CRC). Currently, prediction of disease recurrence and prognostication following surgery is based upon vague clinical factors and more precise and dynamic biomarkers for risk stratification and treatment decisions are urgently needed. Circulating tumor DNA (ctDNA) is a promising biomarker for patients undergoing treatment for resectable CRC. In this review, we provide an overview of the data supporting current uses of ctDNA for CRC, including localized CRC and resectable colorectal liver metastases (CLM), as well as descriptions of important ongoing clinical trials using ctDNA in the care of patients with CRC. The detection of ctDNA following curative-intent therapy is associated with disease recurrence, and multiple trials are investigating its role in determining need and duration for adjuvant therapy for localized CRC. In addition, ctDNA reliably predicts prognosis for patients with CLM, with trials underway studying ctDNA-guided treatment sequencing and intensity. The detection of ctDNA is a sensitive and dynamic biomarker for disease recurrence in CRC. Many investigations are underway into ctDNA's potential role in surveillance and treatment algorithms, and it has the potential to become a critical biomarker to determine individualized strategies for treatment sequencing, choice, and duration of therapies.

Defining a textbook outcome for the resection of colorectal liver metastases

Textbook outcomes (TBO) are composite measures of care which may be superior in assessing quality compared to traditional methods. We aim to define TBOwhich are specific to surgical resection of colorectal liver metastases, and investigate their impact on survival. Single center analysis of all liver resections performed at our center from 2009 to 2020. A Cox model was used to identify perioperative outcomes which impacted on overall survival. These were retained with important postoperative outcomes to form a "TBO."The impact of a TBOon overall survival was investigated using Kaplan-Meier curve analysis. TBOwas achieved in 72.2% (197/273) of resections. Major morbidity (Clavien-Dindo ≥3) at 19.4% was the major limiting factor in not achieving a TBO. TBOwas associated with improved 3-year (77% vs. 55%), 5-year (60.7% vs. 42.5%), and median (93vs. 44 months) overall survival (log-rank test, p = 0.006). Multivariable analysis revealed age >65 years, American Society of AnaesthesiologistsGrade III-IV, and resection of >2 segments as factors predictive of not achieving a TBO. TBOis a useful composite measure in surgery for colorectal liver metastases. It can highlight areas which may be targeted for quality improvement and be useful as a tool to examine variation between centers. Achieving a TBOis associated with a significant improvement in survival.

Clearing Steatosis Prior to Liver Surgery for Colorectal Metastasis: A Narrative Review and Case Illustration.

Over recent years, non-alcoholic fatty liver disease (NAFLD) has become the most common liver disorder in the developed world, accounting for 20% to 46% of liver abnormalities. Steatosis is the hallmark of NAFLD and is recognized as an important risk factor for complication and death after general surgery, even more so after liver resection. Similarly, liver steatosis also impacts the safety of live liver donation and transplantation. We aim to review surgical outcomes after liver resection for colorectal metastases in patients with steatosis and discuss the most common pre-operative strategies to reduce steatosis. Finally, as illustration, we report the favorable effect of a low-caloric, hyper-protein diet during a two-stage liver resection for colorectal metastases in a patient with severe steatosis.

HPB P13 Does Socioeconomic deprivation affect outcomes in patients undergoing liver resection for Colorectal Liver metastases?

Abstract Background It is well documented that socioeconomic deprivation (SED) has an overall negative impact on health outcomes. Many studies have shown this in primary cancers. The effect of SED on outcomes in patients undergoing liver resection for colorectal liver metastases (CRLM) is not well documented. As these patients are already under follow up, it is likely that the impact of SED on outcomes will be diminished. It was our aim to evaluate the effect of SED on overall survival (OS) in patients undergoing liver resection for CRLM. Methods The STROCSS guideline for observational studies was followed to conduct a single-centre retrospective cohort study. The tertiary centre treats patients over a wide geographical area with a population of 2.2 million. All consecutive patients undergoing liver resection for CRLM between January 2013 and December 2020 were eligible for inclusion. Demographics, prognostic variables for CRLM, operative variables, pathological variables and overall survival was recorded. Data was censored at 31 December 2021. Follow up was complete and checked with the Clinical Portal electronic database and by contacting General practitioners. The Multiple Deprivation score, that is nationally recorded was used to determine socioeconomic deprivation status of each patient. Prognostic significance of socioeconomic deprivation was determined by Kaplan–Meier survival statistics and stepwise Cox proportional-hazards regression model. Results A total of 455 patients were eligible for inclusion; 237 patients were classed as least socioeconomically deprived and 218 patients as most socioeconomically deprived. Both cohorts were comparable in terms of baseline characteristics except for age (69 most deprived vs 72 Least deprived, P=0.004). Kaplan–Meier survival statistics showed that socioeconomic deprivation was associated with significantly lower probability of overall survival (HR: 1.55, 95% CI 1.23–1.95; Logrank test: P=0.0001). The stepwise Cox proportional-hazards regression analysis identified socioeconomic deprivation as predictor of OS (HR: 1.56, 95% CI 1.23–1.98, P=0.0003) alongside the following variables: ASA status 1 (HR: 0.43, 95% CI 0.19–0.94, P=0.0349), presence of extrahepatic disease (HR: 1.51, 95% CI 1.12–2.03, P=0.0075), number of tumours (HR: 1.07, 95% CI 1.01–1.13, P=0.0221), size of largest tumour (HR: 1.01, 95% CI 1.00–1.01, P=0.0003), extended hemihepatectomy (HR: 3.24, 95% CI 1.56–6.76, P=0.0018), and absence of recurrence (HR: 0.55, 95% CI 0.43–0.70, P<0.0001). Conclusions Socioeconomic deprivation reduces the probability of OS following liver resection for CRLM. This should be taken into account at different levels of health care planning for management of patients with CRLM including preoperative risk assessment, health care need assessment, and allocation of resources. Our study shows that the deleterious effects of SED extends to patients who are already in the healthcare system and therefore factors other than access to healthcare need further exploration.

HPB O01 Colorectal Liver Metastases and optimal follow-up: a systematic review

Abstract Background Colorectal cancer (CRC) is the third most common cancer worldwide. Approximately 42 000 new cases of CRC are diagnosed each year in the UK (1) (2). At diagnosis many patients (20–25%) already have colorectal liver metastases (CLRM) and further patients develop CRLM after their primary cancer is detected. Evidence suggests that survival rates for patients undergoing hepatectomy for CRLM are improving, however disease recurrence is still a problem with up to 70% recurring (3,4). Repeat resection has been shown to benefit patients with survival comparable to original hepatectomy (5,6). This highlights the importance of having a sensible and robust follow up plan for patients after hepatectomy for CRLM. On review of the literature, currently there is no clear consensus or recommendation surrounding the methods, intensity and duration of follow up for these patients. The aim of this systematic review was to report contemporary follow-up practices after curative hepatic resection for colorectal liver metastases and identify any potential oncological benefits. Methods A systematic review was conducted using PRISMA guidelines. Inclusion and exclusion criteria were set and searches were conducted between inception until 1st August 2020. Articles reporting follow up and outcomes for patients undergoing hepatectomy for CRLM were included. Data extraction was undertaken by two independent authors (AJ/AF) by reviewing full texts, any discrepancy was resolved by the senior author (SP). Outcomes included general demographics, method, frequency and duration of follow up. Reported survival and recurrence data was also collected (overall, disease-free and progression-free survival at 1, 3 and 5 years). Any further details of follow up recorded and these were classified as secondary outcomes, these included co-ordination with local hospitals, cost efficiency, patient reported outcomes and adaptability. Cost standardisation was performed using the Bank of England inflation calculator to account for the different years papers were published. Quality assessment was also performed using MINORS and CHEERS assessment methods. Results Twenty-two articles, totalling 8,384 included patients, published between 1994 and 2017 were included for data extraction. The most commonly used method of follow up was a CT scan (n=13), followed by physical examination (n=12). The most commonly used biochemical marker was CEA (n=11). The intensity of follow up was greater during first two years for majority of the articles. There was variation in the reported outcome measures, most commonly reported was overall survival, which ranged from 39% to 78.1% in the seventeen articles that reported it. The range of 1, 3, and 5 year survival were 63–94.7%, 45–65.1%, and 20–68% respectively. Co-ordination with local hospitals was reported in six articles, cost efficiency in six articles and patient reported outcomes were only described in three. The quality assessment using MINORS tool showed range of 4–10 for non-comparative and 5–16 for comparative studies and the CHEERS assessment for cost analysis showed a failure to meet many of the criteria. Conclusions This review has demonstrated the low quality evidence base on which surveillance after liver resection is based. Also shown is the large variation between the studies with regards to method and frequency of follow up. Based on this review and taking into account two previous systematic reviews in 2004 and 2012, we can conclude that further retrospective data will not be able to adequately answer questions around survival benefits of surveillance. Therefore, high quality, prospective studies focussing on endpoints that matter to patients should be the focus of future research.