Resection Of Liver Metastases Research Articles

The Effects of Primary Tumor Location on Survival after Liver Resection for Colorectal Liver Metastasis in the Mediterranean Population.

(1) Background: There is an abundance of literature available on predictors of survival for patients with colorectal liver metastases (CRLM) but minimal information available on the relationship between the primary tumor location and CRLM survival. The studies that focus on the primary tumor location and CRLM survival exhibit a great deal of controversy and inconsistency with regard to their results (some studies show statistically significant connections between the primary tumor location and prognosis versus other studies that find no significant relationship between these two factors). Furthermore, the majority of these studies have been conducted in the West and have studied more diverse and heterogenous populations, which may be a contributing factor to the conflicting results. (2) Methods: We included patients who underwent liver resection for CRLM between December 2004 and January 2019 at two university-affiliated medical centers in Israel: Carmel Medical Center (Haifa) and Rabin Medical Center (Petach Tikvah). Primary tumors located from the cecum up to and including the splenic flexure were labeled as right-sided primary tumors, whereas tumors located from the splenic flexure down to the anal verge were labeled as left-sided primary tumors. (3) Results: We identified a total of 501 patients. Of these patients, 225 had right-sided primary tumors and 276 had left-sided primary tumors. Patients with right-sided tumors were significantly older at the time of liver surgery compared to those with left-sided tumors (66.1 + 12.7 vs. 62 + 13.1, p = 0.002). Patients with left-sided tumors had slightly better overall survival rates than those with right-sided tumors. However, the differences were not statistically significant (57 vs. 50 months, p = 0.37 after liver surgery). (4) Conclusions: The primary tumor location does not significantly affect patient survival after liver resection for colorectal liver metastasis in the Mediterranean population.

PEGylated Fluorescent Anti-carcinoembryonic Antigen Antibody Labels Colorectal Cancer Tumors in Orthotopic Mouse Models

IntroductionColorectal cancer (CRC) patients often develop liver metastasis. However, curative resection of liver metastasis is not always possible due to poor visualization of tumor margins. The present study reports the characterization of a humanized anti-carcinoembryonic antigen monoclonal antibody conjugated to a PEGylated near-infrared dye, that targets and brightly labels human CRC tumors in metastatic orthotopic mouse models. MethodsThe hT84.66-M5A (M5A) monoclonal antibody was conjugated with a polyethylene glycol (PEG) chain that incorporated a near infrared (NIR) IR800 dye to establish M5A-IR800 Sidewinder (M5A-IR800-SW). Nude mice with CRC orthotopic primary tumors and liver metastasis both developed from a human CRC cell line, were injected with M5A-IR800-SW and imaged with the Pearl Trilogy Imaging System. ResultsM5A-IR800-SW targeted and brightly labeled CRC tumors, both in primary-tumor and liver-metastasis models. M5A-IR800-SW at 75 μg exhibited highly-specific tumor labeling in a primary-tumor orthotopic model with a median tumor-to-background ratio of 9.77 and in a liver-metastasis orthotopic model with a median tumor-to-background ratio of 7.23 at 96 h. The precise labeling of the liver metastasis was due to lack of hepatic accumulation of M5A-IR800-SW in the liver. ConclusionsM5A-IR800-SW provided bright and targeted NIR images of human CRC in orthotopic primary-tumor and liver-metastasis mouse models. The results of the present study suggest the clinical potential of M5A-IR800-SW for fluorescence-guided surgery including metastasectomies for CRC. The lack of hepatic NIR signal is of critical importance to allow for precise labeling of liver tumors.

Development of an Algorithm to Predict Recurrences After Resection of Liver Metastases in Patients With Metastatic Colorectal Cancer.

Hepatic recurrences after resection of metastatic lesions in advanced colorectal cancer (CRC) have an enormous impact on patient prognosis. Response evaluation criteria in solid tumor (RECIST) or morphologic response on computed tomography (CT) have been reported as surrogate prognostication markers. This study assessed a novel algorithm for the prognostication of liver metastasis treatment. Forty-seven patients with liver metastases from CRC who underwent liver resection after systemic chemotherapy were included. The CT values examined before and after chemotherapy were collected. The velocity of CT values (CTvΔ) was calculated, and the subjects were divided into CTvΔ_high and _low groups. Clinicopathological variables, recurrence-free survival (RFS), and overall survival (OS) were statistically compared between the two groups. In addition, the effect of the combined evaluation of CTvΔ and carcinoembryonic antigen (CEA) was evaluated. In univariate analyses, the hazard ratio (HR) for a recurrence after liver resection was relatively higher in the RECIST_stable disease (SD) or _progressive disease (PD) and the CTvΔ_low groups. In multivariate analysis, the HR was significantly higher in the CEA_high, the RECIST_SD or PD, and the CTvΔ_low groups. The RFS was significantly longer in the CTvΔ_high group. Furthermore, the combination of CTvΔ and CEA predicted the RFS and OS. Our algorithm using CTvΔ could be a useful tool to select patients suitable for liver resection of hepatic CRC metastases.

Outcomes after curatively intended treatment of limited peritoneal metastases and thermal ablation for liver metastases from colorectal cancer.

Peritoneal metastases (PM) and liver metastases (LM) are present simultaneously in up to 2 % of patients at the time of their colorectal cancer (CRC) diagnosis. Curatively intended treatment includes cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) combined with LM resection. A less invasive treatment for LM is ablation. We aimed to estimate overall survival (OS), disease-free survival (DFS) and postoperative data in patients managed simultaneously with CRS, HIPEC and radiofrequency ablation (RFA) as first choice. This was a retrospective national cohort study. All patients were treated at Aarhus University Hospital; the only CRS+HIPEC centre in Denmark. We included CRC patients managed with curative intent for simultaneously diagnosed PM and LM in the period January 2016- December 2021. LM was treated with RFA as first choice, if possible. Survival was calculated by the Kaplan-Meier method. A total of 25 patients were included, the median agewas 60 years (range 43-75 years) and 15 (60 %) were females. The median peritoneal cancer index was 7 (range 0-12), the median number of LM was 1 (range 1-3). Ablation was performed as the only treatment for LM in 18 (72 %) patients. After a median follow-up time of 17.1months (range4-36months), the median OS was 28.6months (95 % confidence interval (Cl) 15.8;36.1), 1-year OS was 84.0 % (95 % Cl 62.8;93.7). Median DFS was 6.1months (95 % Cl 4.0;10.3). Median LOS was ten days (range 5-26days). Both 30-day and 90-day mortality were 0 %. The selected treatment modality (RFA) for CRC patients with both LM and PM was safe. However, DFS was low. Further research is warranted to investigate if RFA is as effective as LM resection.

Postoperative pancreatic fistula after pancreaticoduodenectomy: if you lack knowledge of what to search for, you will be unable to locate what you desire.

Postoperative pancreatic fistula (POPF) is the most common and critical complication of pancreatoduodenectomy (PD). In this study, we aimed to define preoperative, perioperative, and postoperative conditions that may cause POPF and examine the predictive value of drain fluid amylase (DFA) values in showing the clinical severity of POPF. Between December 2018 and December 2019, 49 patients who underwent PD for malignant reasons by a single team were retrospectively analyzed. Patients with benign indications, vascular reconstruction, preoperative biliary drainage catheterization, resectable liver metastases, POPF that occurred after reoperation, and patients undergoing neoadjuvant oncological treatment were excluded from the study. The patients were divided into two groups developing (FP) and non-developing (FN) POPF. There was no difference between the groups in terms of gender (p=0.781), age (p=0.219), American Society of Anesthesiologists (ASA) score (p=0.338), and comorbidity status (p=0.219). The mean body mass index (BMI) kg/m2 values of the patients in the FN and FP groups were 25.2±4.0 kg/m2 and 27.4±2.6 kg/m2, respectively (p=0.042). An increased BMI increases the risk of POPF. Preoperative prognostic nutritional index (PNI) score (p=0.588), preoperative total bilirubin level (p=0.707), pancreatic duct diameter (p=0.334), pancreatic texture (p=0.334), operation time (p=0.659) do not pose a risk for POPF. Increased perioperative bleeding amounted to a risk for POPF (123.8±46.7 ml, 244.7±66.3 ml in FN and FP groups, respectively, p=0.024). Drain fluid amylase (DFA) values (p<0.001, p=0.043, p=0.019, respectively) were found to be high in patients with POPF on postoperative days 1, 4, and 7. Increased BMI and excess perioperative blood loss increase the risk of POPF. DFA level is an easily applicable method that provides early diagnosis for POPF.

Outcome after curative resection for colorectal cancer liver metastasis in Sri Lanka

Introduction: Colorectal cancer is the third most common cancer globally and in Sri Lanka. The liver is the commonest site of metastasis, developing in 25%-30%. Surgical resection and ablation are the only curative options available.Objective: To determine the clinical characteristics and treatment outcome in patients with colorectal cancer liver metastases.Method: Details of 73 patients with colorectal cancer liver metastases referred between 2010 and 2022 were reviewed. Demographic data, presentation, management of primary cancer and liver metastases, surgical outcome, recurrence free survival and overall survival were analyzed retrospectively.Results: The median age was 60 years (31-82) with a female predominance (n=39; 53.4%). Primary located in the left colon in 90.4% (n=66), presenting synchronously in 61.6% (n=45). Right hemi-liver (n=60; 82.2%) is more commonly involved with the caudate lobe alone involved in 1.4% (n=1). Segment VI is the commonest liver segment involved (n=39; 53.4%). Liver resection was performed in 45 patients (61.6%). 25 (55.6%) were major resections, and 6 (13.3%) were staged resections. The surgery group had a median recurrence-free survival of 24 (range=9.19-38.8) months and overall survival of 31 (range=14.51-47.50) months. 28 Patients who were offered palliative treatment had a poor overall survival of 16 (range=12.23-19.77) months (p &lt;0.05).Conclusion: Surgical resection was possible in 61.6% of patients giving superior survival outcomes.

Prognostic Impact of Tumor Markers (CEA and CA19-9) on Patients with Resectable Colorectal Liver Metastases Stratified by Tumor Number and Size: Potentially Valuable Biologic Markers for Preoperative Treatment.

Although patients with resectable colorectal liver metastasis (CLM), a population with good prognosis, have been treated with upfront surgery, some patients have had a poor prognosis. This study aimed to investigate biologic prognostic factors in patients with resectable CLMs. This single-center retrospective study enrolled consecutive patients who underwent liver resection for initial CLMs at the Cancer Institute Hospital between 2010 and 2020. The study defined CLMs as resectable (tumor size < 5cm; < 4 tumors; no extrahepatic metastasis) or borderline resectable (BR). Preoperative chemotherapy was administered to patients with BR CLMs. During the study period, 309 CLMs were classified as resectable without preoperative chemotherapy and 345 as BR with preoperative chemotherapy. For the 309 patients with resectable CLMs, the independent poor prognostic factors associated with overall survival in the multivariable analysis were high tumor marker levels (CEA ≥ 25ng/mL and/or CA19-9 ≥ 50U/mL; (hazard ratio [HR], 2.45; p = 0.0007), no adjuvant chemotherapy (HR, 1.69; p = 0.043), and age of 75 years or older (HR, 2.09; p = 0.012). The 5-year survival rates for the patients with high tumor marker (TM) levels (CEA ≥25 ng/mL and/or CA19-9 ≥50U/mL) were significantly worse than for those with low TM levels (CEA < 25 ng/mL and CA19-9 < 50U/mL) (55.3% vs. 81.1%; p <0.0001) and similar to the rate for those with BR CLMs (52.1%; p = 0.864). Postoperative adjuvant chemotherapy had an impact on prognosis only in the high-TM group (HR, 2.65; p = 0.007). High TM levels have a prognostic impact on patients with resectable CLMs stratified by tumor number and size. Perioperative chemotherapy improves long-term outcomes for patients with CLM and high TM levels.

Neoadjuvant chemotherapy versus upfront surgery as the initial treatment for patients with resectable, synchronous colorectal cancer liver metastases.

Although perioperative chemotherapy has been the standard treatment for colorectal cancer with resectable liver metastases (CRLM), studies that have compared neoadjuvant chemotherapy (NAC) and upfront surgery, especially in the setting of synchronous metastases are rare. We compared perioperative outcomes, overall survival (OS) and overall survival after recurrence (rOS) in a retrospective study of 281 total and 104 propensity score-matched (PSM) patients who underwent curative resection, with or without NAC, for synchronous CRLM, from 2006 to 2017. A Cox regression model was developed forOS. After PSM, 52 NAC and 52 upfront surgery patients with similar baseline characteristics were compared. Postoperative morbidity, mortality, and 5-year OS rate (NAC: 78.9%, surgery: 64.0%; p = 0.102) were similar between groups; however, the NAC group had better rOS (NAC: 67.3%, surgery: 31.5%; p = 0.049). Initial cancer stage (T4, N1-2), poorly differentiated histology, and >1 hepatic metastases were independent predictors of worse OS. Based on these factors, patients were divided into low-risk (≤1 risk factor, n = 115) and high-risk (≥2 risk factors, n = 166) groups. For high-risk patients, NAC yielded better OS than upfront surgery (NAC: 74.5%, surgery: 53.2%; p = 0.024). Although NAC and upfront surgery-treated patients had similar perioperative outcomes and OS, better postrecurrence survival was shown in patients with NAC. In addition, NAC may benefit patients with worse prognoses; therefore, physicians should consider patient disease risk before initiating treatment to identify patients who are most likely to benefit from chemotherapy.

Prognostic impact of R1 resection margin in synchronous and simultaneous colorectal liver metastasis resection: a retrospective cohort study

BackgroundA margin ≥ 1 mm is considered a standard resection margin for colorectal liver metastasis (CRLM). However, microscopic incomplete resection (R1) is not rare since aggressive surgical resection has been attempted in multiple and bilobar CRLM. This study aimed to investigate the prognostic impact of resection margins and perioperative chemotherapy in patients with CRLM.MethodsA total of 368 of 371 patients who underwent simultaneous colorectal and liver resection for synchronous CRLM between 2006 and June 2017, excluding three R2 resections, were included in this study. R1 resection was defined as either abutting tumor on the resection line or involved margin in the pathological report. The patients were divided into R0 (n = 304) and R1 (n = 64) groups. The clinicopathological characteristics, overall survival, and intrahepatic recurrence-free survival were compared between the two groups using propensity score matching.ResultsThe R1 group had more patients with ≥ 4 liver lesions (27.3 vs. 50.0%, P < 0.001), higher mean tumor burden score (4.4 vs. 5.8%, P = 0.003), and more bilobar disease (38.8 vs. 67.2%, P < 0.001) than the R0 group. Both R0 and R1 groups showed similar long-term outcomes in the total cohort (OS, P = 0.149; RFS, P = 0.414) and after matching (OS, P = 0.097, RFS: P = 0.924). However, the marginal recurrence rate was higher in the R1 group than in the R0 group (26.6 vs. 16.1%, P = 0.048). Furthermore, the resection margin did not have a significant impact on OS and RFS, regardless of preoperative chemotherapy. Poorly differentiated, N-positive stage colorectal cancer, liver lesion number ≥ 4, and size ≥ 5 cm were poor prognostic factors, and adjuvant chemotherapy had a positive impact on survival.ConclusionsThe R1 group was associated with aggressive tumor characteristics; however, no effect on the OS and intrahepatic RFS with or without preoperative chemotherapy was observed in this study. Tumor biological characteristics, rather than resection margin status, determine long-term prognosis. Therefore, aggressive surgical resection should be considered in patients with CRLM expected to undergo R1 resection in this multidisciplinary approach era.

Resection of primary colon cancer with and without resection of liver metastases: Propensity-score matched analysis.

e15580 Background: Studies show that attempts to treat liver metastases during or before primary colonic cancer resection may improve survival. We aimed to compare overall survival of patients with colon cancer and liver metastases who underwent primary tumor resection with/without resection of liver metastases. Methods: This retrospective cohort study included patients with stage IV colon adenocarcinoma and isolated liver metastases who underwent surgical resection, using data from the National Cancer Database between 2015-2019. Patients with metastases to other organs or who did not have primary tumor resection were excluded. The cohort was divided into Colectomy-only (resection of primary colonic cancer only) and Colectomy-plus (resection of primary tumor and liver metastases) groups. After comparing, significant baseline and treatment confounders were identified and groups were matched using the nearest neighbor, 1:1 propensity-score method. Primary outcome was overall survival; secondary endpoints were short-term mortality and 30-day unplanned readmission. Results: 6780 patients who underwent primary tumor only resection and 4082 who underwent primary tumor and liver metastases resection were included. Patients in the Colectomy-only group were significantly older (63.73±13.59 vs 59.56±13.32 years;p &lt; 0.001), more often male (56% vs 53.5%;p = 0.01), had more comorbidities (Charlson score 3: 4.4% vs 3.3%;p = 0.001) and right-sided colonic cancer (45.7% vs 43.2%;p = 0.002), shorter time before surgery (10 vs 30 days;p &lt; 0.001), and more laparoscopic surgery (40.4% vs 35%;p &lt; 0.001). Colectomy-only group patients had less chemotherapy (48.6% vs 50.7%, p = 0.04) and immunotherapy (34.1% vs 40.6%, p &lt; 0.001) whereas Colectomy-plus group patients had more neoadjuvant systemic therapy (18.8% vs 10.2%;p &lt; 0.001). Median overall survival of the Colectomy-plus group was significantly longer than Colectomy-only group (45.1 vs 24.4 months; p &lt; 0.001). After matching for significant confounders, 2038 patients were included in each group. There were no significant differences between the two groups in 30-day (3.8% vs 3.1%;p = 0.3) and 90-day mortality (7.7% vs 6.6%;p = 0.2). Colectomy-plus group patients had significantly higher 30-day unplanned readmissions (7.2% vs 5.3%, p = 0.02) and significantly longer median overall survival (41.5 vs 28.4 months, p &lt; 0.001). On Cox-regression analysis, resection of liver metastases and primary colonic tumor was associated with 33% mortality reduction (HR: 0.678, 95%CI: 0.618-0.745, p &lt; 0.001). Conclusions: Resection of colonic cancer liver metastasis with the primary tumor is associated with significant survival benefit and may prolong survival by approximately 12 months, versus primary tumor resection alone. Synchronous resection of the primary tumor and liver metastases should be considered as it appears to offer survival benefit.

Cell-free DNA fragmentation profiling for therapeutic response monitoring in metastatic colorectal cancer.

e15664 Background: Currently available circulating cell-free DNA (cfDNA) assays require deep-targeted sequencing to detect cancer-specific mutations at low mutant allele frequency (MAF) levels in the blood. Recently, we developed a tumor-agnostic, mutation-independent approach that utilizes low-coverage whole genome sequencing called DELFI (DNA evaluation of fragments for early interception) Tumor Fraction (DELFI-TF), a model designed to predict plasma tumor fractions based on genome-wide fragmentation-related features. Here, we report the results of DELFI-TF applied to a prospective cohort of patients with metastatic colorectal cancer (mCRC). Methods: Overall, 692 longitudinal plasma samples collected from 153 initially treatment-naive mCRC patients participating in the phase III CAIRO5 study (NCT02162563) were sequenced at low coverage and used for training and cross-validation. In patients with tumor-tissue-proven RAS/BRAF mutations, the tumor fractions were quantified as the cfDNA MAF of the RAS/BRAF variant measured by droplet digital PCR (ddPCR). Using fragment-sequencing statistics, a Bayesian regression model was trained against the MAF of the tumor-specific driver RAS/BRAF variant in all longitudinal timepoints to generate DELFI-TF scores. Changes in longitudinal DELFI-TF scores during first-line therapy (DELFI-TF slopes) were examined to predict treatment response and survival outcomes. Results: The DELFI-TF scores were strongly correlated with RAS/BRAF cfDNA MAF measured by ddPCR ( Pearson, r= 0.85, p&lt; 0.001). Baseline DELFI-TF correlated with dimensions of liver metastases reported in CT scans ( Pearson, r= 0.49, p&lt; 0.001) as well as clinical response, with pre-treatment levels significantly lower in patients with a later-confirmed partial or complete response ( Wilcoxon, p&lt; 0.05). Patients with low or negative DELFI-TF slopes presented with longer progression-free survival in the overall study population (13.4 months vs 10.4 months, HR = 2.03, 95% CI 1.25 to 3.32, Log-rank p&lt; 0.01) and in patients who experienced durable clinical benefit (16.7 months vs 13.3 months, HR = 2.24, 95% CI 1.1 to 4.55, Log-rank p= 0.023). Patients with low or negative DELFI-TF slopes also experienced significantly longer overall survival (59.4 months vs 29.1 months, HR = 3.05, 95% CI 1.58-5.90, Log-rank p&lt; 0.001). Tissue-informed focal and arm-level copy number changes were detected 4-12 weeks after liver metastases resection. Most patients detected as having a molecular relapse were diagnosed earlier than clinical recurrences identified by conventional imaging. Conclusions: DELFI-TF demonstrates the ability to use cfDNA fragmentomes to estimate cfDNA tumor burden with performance comparable to standard approaches for treatment response monitoring and clinical outcome prediction.

P-216 Surgical safety and oncological outcomes of laparoscopic liver resection for colorectal cancer liver metastasis in the Ukrainian state center

P-216 Surgical safety and oncological outcomes of laparoscopic liver resection for colorectal cancer liver metastasis in the Ukrainian state center

Nomogram predicting early recurrence defined by the minimum P value approach for colorectal liver metastasis patients receiving colorectal cancer resection with simultaneous liver metastasis resection: development and validation.

Simultaneous resections have been increasingly performed for colorectal liver metastasis patients. However, studies explored risk stratification for these patients are scarce. Among which, a clear definition of early recurrence remains controversial and models for predicting early recurrence in these patients are lacking. Colorectal liver metastasis patients who developed recurrence followed by simultaneous resection were enrolled. Early recurrence was determined by the minimum P value method, and patients were divided into an early recurrence group and late recurrence group. Standard clinical data were collected from each patient including demographics features, preoperative laboratory tests and postoperative regular follow-up results. All the data were accessed by clinicians and recorded accordingly. The nomogram for early recurrence was constructed in the training cohort and validated externally in the test cohort. The optimal value of early recurrence by the minimum P value method was 13 months. A total of 323 patients were included in the training cohort, of which 241 (74.6%) experienced early recurrence. Seventy-one patients were included in the test cohort, of which 49 (69.0%) experienced early recurrence. Significantly worse post-recurrence survival (median 27.0 vs. 52.8 months, P=0.00083) and overall survival (median 33.8 vs. 70.9 months, P<0.0001) were observed in patients with early recurrence in the training cohort. Positive lymph node metastases (P=0.003), tumour burden scores ≥4.09 (P=0.001), preoperative neutrophil-to-lymphocyte ratios ≥1.44 (P=0.006), preoperative blood urea nitrogen levels ≥3.55 µmol/L (P=0.017) and postoperative complications (P=0.042) were independently associated with early recurrence, and all these predictors were included in the nomogram. The nomogram for predicting early recurrence had a receiver operating characteristic curve of 0.720 in the training cohort and a receiver operating characteristic curve of 0.740 in the test cohort. The Hosmer-Lemeshow test and calibration curves showed acceptable model calibration in the training set (P=0.7612) and in the test set (P=0.8671). The decision curve analysis results for the training cohort and test cohort also indicated that the nomogram showed good clinical applicability. Our findings provide clinicians with new insights into accurate risk stratification for colorectal liver metastasis patients receiving simultaneous resection and contributing to the management of patients.

Correlation between recurrence-free survival and overall survival after upfront surgery for resected colorectal liver metastases.

The role of recurrence-free survival (RFS) as a valid surrogate endpoint for overall survival (OS) in patients who underwent upfront surgery for colorectal liver metastases remains uncertain. The aim of the study was to compare the two survival measures in a nationwide cohort of upfront resected colorectal liver metastasis. Data from patients with colorectal liver metastases without extrahepatic metastases who underwent curative surgery for liver metastases were retrieved from the Japanese nationwide database (data collection 2005-2007 and 2013-2014). RFS, OS, and survival after recurrence were estimated using the Kaplan-Meier method. The correlation (ρ) between RFS and OS was assessed using the rank correlation method combined with iterative multiple imputation, to account for censoring. As a secondary analysis, the correlation was evaluated according to adjuvant chemotherapy regimen. In sensitivity analysis, the pairwise correlation between RFS and OS was calculated. A total of 2385 patients with colorectal liver metastases were included. In the primary analysis, there was a moderately strong correlation between RFS and OS (ρ = 0.73, 95 per cent c.i. 0.70 to 0.76). The strength of the correlation was similar regardless of the adjuvant treatment regimen (oxaliplatin plus 5-fluorouracil: ρ = 0.72, 0.67 to 0.77; 5-fluorouracil alone: ρ = 0.72, 0.66 to 0.76; observation: ρ = 0.74, 0.69 to 0.78). The mean(s.d.) pairwise correlation coefficient between 3-year RFS and 5-year OS was 0.87(0.06). In surgically treated patients with colorectal liver metastases, there was a moderately strong correlation between RFS and OS, which was unaffected by the treatment regimen. Further validation using a trial-level analysis is required.

Laparoscopic and Open Liver Resections for Colorectal Cancer Liver Metastasis in the Ukrainian State Center.

Background Minimally invasive liver resections for metastatic colorectal cancer have been increasingly performed all over the world with promising results. We planned the current studyto review our experience on this matter and compare short- and long-term outcomes of laparoscopicliver resection (LLR) and open liver resection(OLR) in patients with colorectal cancer liver metastasis (CRLM). Materials and methods This is a single-center retrospective analysis of patients with CRLM who underwent laparoscopic (n=86) and open (n=96) surgical treatment for metastatic liver lesions between March 2016 and November 2022. Tumor characteristics, intra- and postoperative results, overall survival (OS), and disease-free survival (DFS)were analyzed and compared. Results LLR was associated with significantly shorter surgery duration (180 minutes versus 295 minutes, p=0.03). There was no significant difference in blood loss between the two groups (100 mL versus 350 mL, p=0.061). Additionally, the laparoscopic approach was associated with significantly shorter hospital stays (6 days versus 9 days, p=0.004). The rate of major complications (Clavien-Dindo classification ≥ 3) was lower in the LLR group (5.8% versus 16.6%, p=0.037). There was no mortality in the LLR group, and in the OLR group, one lethal case was induced by mesenteric thrombosis on the fifth postoperative day. We did not find a statistically significant difference in the OS rate between the two groups at one, three, and five years: 97.3%, 74.7%, and 43.4%, respectively,in the OLR group and 95.1%, 70.3%, and 49.5%,respectively,in the LLR group (p=0.53). DFS at one, three, and five years were 88.7%, 52.3%, and 25.5%,respectively, in the LLR group and 71.9%, 53.1%, and 19.3%, respectively, in the OLR group(p=0.66). Conclusions This study showed that laparoscopic liver surgery is a safe and effective method of CRLM treatment in our center. LLR was associated with a decrease in major morbidity, shorter surgery duration, and reduced postoperative hospital stay. Minimally invasive liver resections showed similar oncological outcomes to the open approach in terms of overall and disease-free survival.

Pre-operative exercise therapy suppresses colorectal liver metastases by triggering anti-tumor trained immunity of Kupffer cells

Abstract Hepatic recurrence after surgical resection of colorectal liver metastasis is the major cause of treatment failure. Pre-operative exercise therapy (PEx) has been shown to improve outcomes from major abdominal surgeries. We demonstrate that PEx significantly attenuates liver ischemia/reperfusion (I/R) injury by inducing an anti-inflammatory phenotype in Kupffer cells (KCs). However, the mechanisms by which PEx prevents surgery-induced hepatic recurrence remain unclear. Results: Four weeks of treadmill running significantly reduces I/R-induced hepatic metastatic tumor growth in mice compared to sedentary controls. Depletion of KCs substantially decreases I/R-induced tumor progression, indicating a pro-tumor role of KCs. Our scRNA-seq data reveal that PEx causes dramatic transcriptomic changes in KCs. A clear induction of trained immunity with noticeably higher levels of anti-tumor cytokines IFN-γ and TNF-α is observed in PEx-KCs. With scATAC-seq, we find that PEx triggers the chromatin accessibilities profile changes in KCs, which is associated with the metabolic reprogramming of itaconate/IRG1 pathway. Furthermore, PEx significantly changes the transcriptomic profile of polymorphonuclear myeloid-derived suppressive cells (PMN-MDSCs) in the tumor microenvironment (TME) and decreases them from forming neutrophil extracellular traps (NETs), which promote tumor progression. We identify the cell-cell interaction between KCs and PMN-MDSCs in the TME is significantly enriched after PEx, suggesting that PEx may facilitate KCs to modulate PMN-MDSCs. In summary, PEx ameliorates surgical stress-induced pro-tumorigenic inflammatory responses and sustains an anti-tumor immune microenvironment in the liver. Supported by grants from NIH (R01GM137203 for Hai Huang, R01CA214865 for Allan Tsung)

Survival outcomes for patients with colorectal cancer with synchronous liver only metastasis.

Colorectal cancer with synchronous liver-only metastasis is managed with a multimodal approach, however, optimal sequencing of modalities remains unclear. A retrospective review of all consecutive rectal or colon cancer cases with synchronous liver-only metastasis was conducted from the South Australian Colorectal Cancer Registry from 2006 to 2021. This study aimed to investigate how order and type of treatment modality affects overall survival. Data of over 5000 cases were analysed (n = 5244), 1420 cases had liver-only metastasis. There were a greater number of colon than rectal primaries (N = 1056 versus 364). Colonic resection was the preferred initial treatment for the colon cohort (60%). In the rectal cohort, 30% had upfront resection followed by 27% that had chemo-radiotherapy as 1st line therapy. For the colon cohort, there was an improved 5-year survival with surgical resection as initial treatment compared to chemotherapy (25% versus 9%, P < 0.001). In the rectal cohort, chemo-radiotherapy as the initial treatment was associated with an improved 5-year survival compared to surgery or chemotherapy (40% versus 26% versus 19%, P = 0.0015). Patients who were able to have liver resection had improved survival, with 50% surviving over 5 years compared to 12 months in the non-resected group (P < 0.001). Primary rectal KRAS wildtype patients who underwent liver resection and received Cetuximab had significantly worse outcomes compared to KRAS wildtype patients who did not (P = 0.0007). Where surgery is possible, resection of liver metastasis and primary tumour improved overall survival. Further research is required on the use of targeted treatments in patients undergoing liver resection.

Laparoscopic versus open resection of primary colorectal cancers and synchronous liver metastasis: a systematic review and meta-analysis

PurposeCombined resection of primary colorectal cancer and associated liver metastases is increasingly common. This study compares peri-operative and oncological outcomes according to surgical approach.MethodsThe study was registered with PROSPERO. A systematic search was performed for all comparative studies describing outcomes in patients that underwent laparoscopic versus open simultaneous resection of colorectal primary tumours and liver metastases. Data was extracted and analysed using a random effects model via Rev Man 5.3ResultsTwenty studies were included with a total of 2168 patients. A laparoscopic approach was performed in 620 patients and an open approach in 872. There was no difference in the groups for BMI (mean difference: 0.04, 95% CI: 0.63–0.70, p = 0.91), number of difficult liver segments (mean difference: 0.64, 95% CI:0.33–1.23, p = 0.18) or major liver resections (mean difference: 0.96, 95% CI: 0.69–1.35, p = 0.83). There were fewer liver lesions per operation in the laparoscopic group (mean difference 0.46, 95% CI: 0.13–0.79, p = 0.007). Laparoscopic surgery was associated with shorter length of stay (p < 0.00001) and less overall postoperative complications (p = 0.0002). There were similar R0 resection rates (p = 0.15) but less disease recurrence in the laparoscopic group (mean difference: 0.57, 95% CI:0.44–0.75, p < 0.0001).ConclusionSynchronous laparoscopic resection of primary colorectal cancers and liver metastases is a feasible approach in selected patients and does not demonstrate inferior peri-operative or oncological outcomes.

A prospective multicentre trial on survival after Microwave Ablation VErsus Resection for Resectable Colorectal liver metastases (MAVERRIC)

AimThis multi-centre prospective cohort study aimed to investigate non-inferiority in patients’ overall survival when treating potentially resectable colorectal cancer liver metastasis (CRLM) with stereotactic microwave ablation (SMWA) as opposed to hepatic resection (HR). MethodsPatients with no more than 5 CRLM no larger than 30 mm, deemed eligible for both SMWA and hepatic resection at the local multidisciplinary team meetings, were deliberately treated with SMWA (study group). The contemporary control group consisted of patients with no more than 5 CRLM, none larger than 30 mm, treated with HR, extracted from a prospectively maintained nationwide Swedish database. After propensity-score matching, 3-year overall survival (OS) was compared as the primary outcome using Kaplan-Meier and Cox regression analyses. ResultsAll patients in the study group (n = 98) were matched to 158 patients from the control group (mean standardised difference in baseline covariates = 0.077). OS rates at 3 years were 78% (Confidence interval [CI] 68–85%) after SMWA versus 76% (CI 69–82%) after HR (stratified Log-rank test p = 0.861). Estimated 5-year OS rates were 56% (CI 45–66%) versus 58% (CI 50–66%). The adjusted hazard ratio for treatment type was 1.020 (CI 0.689–1.510). Overall and major complications were lower after SMWA (percentage decrease 67% and 80%, p < 0.01). Hepatic retreatments were more frequent after SMWA (percentage increase 78%, p < 0.01). ConclusionSMWA is a valid curative-intent treatment alternative to surgical resection for small resectable CRLM. It represents an attractive option in terms of treatment-related morbidity with potentially wider options regarding hepatic retreatments over the future course of disease.

Surgery for colorectal liver metastases: Anatomic and non-anatomic approach

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