Colorectal Liver Metastasis Lesions Research Articles

Classification of Neoadjuvant Therapy Response in Patients With Colorectal Liver Metastases Using Contrast-Enhanced Ultrasound—With Histological Pathology as the Gold Standard

ObjectiveTo evaluate the response to neoadjuvant therapy in patients with colorectal liver metastases (CRLMs) using ultrasound(US) and contrast-enhanced ultrasound(CEUS), with correction to the tumor regression grade (TRG) of pathological results. MethodsThis study included patients with resectable CRLMs admitted from February to December 2022. After at least 4 cycles neoadjuvant therapy, all the patients received US and CEUS examinations within two weeks before hepatectomy. CEUS clips were postprocessed with color parameter imaging (CPI) and microflow imaging (MFI) analysis. Logistic regression analyses were used to develop an evaluation Nomogram. Ultrasound-based model was constructed to discriminate between the response (TRG1/2/3) and nonresponse (TRG4/5) groups at the lesion level. The model's predictive ability was evaluated using the C index and calibration curve, with decision curve analysis assessing the Nomogram's added value. ResultsThe study analyzed 105 CRLM lesions (the lesion with the highest diameter analyzed for each patient), with 43.8% showing a response to therapy. Univariate analysis identified calcification on US (p = 0.039), CEUS enhancement degree (p < 0.001), CEUS enhancement pattern (p<0.001), CEUS washout type (p < 0.001), CEUS necrosis (p < 0.001), CPI feeding artery (p = 0.003) and MFI pattern (p < 0.001) were significantly associated with TRG. The multivariate analysis showed CEUS enhancement pattern (p = 0.026), CEUS washout type (p = 0.018) and CEUS necrosis (p = 0.005) were independently associated with the neoadjuvant therapy response. A Nomogram with the three independent predictors was developed, with an AUC of 0.898. ConclusionThe ultrasound-based model provided accurate evaluation of pathological tumor response to preoperative chemotherapy in patients with CRLM, and may help to decide the individualized treatment strategy.

Detection of Liver Lesions in Colorectal Cancer Patients Using 18F-FDG PET/CT Dual-Time-Point Scan Imaging.

The aim of this study was to evaluate the diagnostic performance of dual-time-point fluorine-18-fluorodeoxyglucose positron emission computed tomography/computed tomography (18F-FDG PET/CT) compared to conventional early imaging for detecting colorectal liver metastases (CRLM) in colorectal cancer (CRC) patients. One hundred twenty-four consecutive CRC patients underwent dual-time-point imaging scans on a retrospective basis. Histopathological confirmation and/or clinical follow-up were accepted as the gold standard. Standard uptake values (SUV), signal-to-noise ratio (SNR), retention index (RI), tumor-to-normal liver ratio (TNR), and lesion sizes were measured for early and delayed PET scans. The diagnostic performance of early and delayed images was calculated on a per-patient basis and compared using McNemar's test. Among the 124 patients, 57 (46%) had CRLM, 6 (4.8%) had benign lesions, and 61 (49.2%) had no concerning lesions detected. Smaller CRLM lesions (<5 cm3) showed significantly higher uptake in the delayed scans relative to early imaging (p < 0.001). The SUV and TNR increased significantly in delayed imaging of all metastatic lesions (p < 0.001). The retention index of all CRLM was high (40.8%), especially for small lesions (54.8%). A total of 177 lesions in delayed images and 124 in standard early images were identified. In a per-patient analysis, delayed imaging had significantly higher sensitivity (100% vs. 87.7%) and specificity (91.0% vs. 94.0%) compared to early imaging (p-value = 0.04). The detection of liver lesions using dual-time-point PET/CT scan improves the sensitivity and specificity for the detection of colorectal liver metastasis.

Surgical approach to microwave and radiofrequency liver ablation for hepatocellular carcinoma and colorectal liver metastases less than 5cm: a systematic review and meta-analysis.

Primary hepatocellular carcinoma (HCC) and colorectal liver metastases (CRLM) represent the two most common malignant neoplasms of the liver. The objective of this study was to assess outcomes of surgical approaches to liver ablation comparing laparoscopic versus percutaneous microwave ablation (MWA), and MWA versus radiofrequency ablation (RFA) in patients with HCC or CRLM lesions smaller than 5cm. A systematic review was conducted across seven databases, including PubMed, Embase, and Cochrane, to identify all comparative studies between 1937 and 2021. Two independent reviewers screened for eligibility, extracted data for selected studies, and assessed study bias using the modified Newcastle Ottawa Scale. Random effects meta-analyses were subsequently performed on all available comparative data. From 1066 records screened, 11 studies were deemed relevant to the study and warranted inclusion. Eight of the 11 studies were at high or uncertain risk for bias. Our meta-analyses of two studies revealed that laparoscopic MW ablation had significantly higher complication rates compared to a percutaneous approach (risk ratio = 4.66; 95% confidence interval = [1.23, 17.22]), but otherwise similar incomplete ablation rates, local recurrence, and oncologic outcomes. The remaining nine studies demonstrated similar efficacy of MWA and RFA, as measured by incomplete ablation, complication rates, local/regional recurrence, and oncologic outcomes, for both HCC and CRLM lesions less than 5cm (p > 0.05 for all outcomes). There was no statistical subgroup interaction in the analysis of tumors < 3cm. The available comparative evidence regarding both laparoscopic versus percutaneous MWA and MWA versus RFA is limited, evident by the few studies that suffer from high/uncertain risk of bias. Additional high-quality randomized trials or statistically matched cohort studies with sufficient granularity of patient variables, institutional experience, and physician specialty/training will be useful in informing clinical decision making for the ablative treatment of HCC or CRLM.

The role of R0/R1vasc resection in the treatment of patients affected by marginal resectable colorectal liver metastases: A pairwise propensity score match analysis

Increasingly, patients with multiple colorectal liver metastases (CRLM) are surgically treated. R1par surgery remains one of the negative prognostic factors for overall survival (OS). According to our data on R1 in main intrahepatic vascular contact (MVC), we investigate the oncological outcome of patients with multiple bilobar disease with bilateral MVC (BC), compared to patients with unilateral MVC (UC) and patients with disease and no MVC (NC). This single-institution study included patients who underwent hepatectomy for multiple (≥ 4) bilobar CRLM lesions from 2004-2019. Three-hundred-fifty-five patients meet the inclusion criteria. One-hundred-thirty-two patients with R1par resection were excluded. Three groups were defined: NC, UC, BC. After pairwise propensity score match 145 patients were analyzed. No differences between groups were observed in the preoperative variables. Increased surgical time, hilar clamping, and blood loss were reported in the BC group. Postoperative minor morbidity, liver failure rate, overall and local recurrences were higher in the BC group. BC patients were more likely to be re-resected. Cumulative OS 3-5 years survival in NC, UC, BC were 54%-40%, 49%-35%, 57%-24% (p < 0.91). At multivariate analysis, factors influencing OS, were N status of the primitive lesions, RAS status, and repeated hepatectomy. Patients with BC and lesions ≥ 4 are generally considered unresectable or suitable for staged hepatectomy. This retrospective study shows that these patients can be submitted to the so called enhanced-one-staged hepatectomy with the same oncological results, however surgical complexity, postoperative minor morbidity and postoperative liver failure are increased.

Prospective Non-Randomized Study of Intraoperative Assessment of Surgical Resection Margin of Colo-Rectal Liver Metastases.

Introduction: More than 50% of patients with colorectal cancer (CRC) develop liver metastases during the natural course of disease. Surgical resection is currently the most potentially curative method in the treatment of colorectal liver metastases (CRLM). The goal of surgery is to achieve a negative resection margin (RM) of at least 1 mm, which provides the best prognosis for patients. The RM can be assessed by the pathologist of the resected liver specimen (RLS) and by the surgeon intraoperatively. The aim of this research paper is to determine the degree of agreement on intraoperative assessment of the RM by the surgeon and histopathological RM assessment by the pathologist.Material and methods: This prospective non-randomized double-blind study was approved by the Ethics Committee of the Oncology Institute of Vojvodina and registered on ClinicalTrials.gov #NCT04634526. The study was conducted at the Oncology Institute of Vojvodina, Sremska Kamenica, Serbia. An experienced hepatobiliary surgeon assessed RM for every specimen intra-operatively, immediately after CRLM resection. Resected CRLM lesions were analyzed by two experienced pathologists. These data were compared with pathological RM assessment as a “gold standard”. RM of 1 mm or more was rated as negative RM (RM-). Disease-free survival (DFS) and recurrence rate was calculated by RM status defined by surgeon and by pathologist.Results: From 01 January 2015 to 31 August 2019, 98 patients were enrolled in the study. There were 219 RLS with 245 CRLM. The surgeon registered positive RM (RM+) of <1mm in 41 (18.7%) RLS. Taking the result of the histopathological assessment (HPA) as the “gold standard”, it was determined that RM was true positive in 32 (14.6%) cases. False positive RM was found in 9 (4.1%) cases. False negative RM was found in 20 (9.1%) cases. True negative RM was found in 158 (72.2%) cases. Sensitivity of surgical assessment (SA) of RM+ was 61.5% (32/52). Specificity of SA of RM+ was 94.6% (158/167). The positive predictive value (PPV) was 78.0% (32/41), while the negative predictive value (NPV) was 88.8% (158/178). The overall accuracy of the RM+ SA was 86.8% (190/219). There was no statistically significant difference in the assessment of RM+ per RLS by surgeon and pathologists (p=0.061), but it was significant when analyses per patients was performed (p=0.017). Recurrence rate for RM+ patients was 48.1% (13/27, p=0.05) for SA and 35.0% (14/40, p=0.17) for HPA. Three year DFS for RM- and RM+ was 66.5% and 27.9% (p=0.04), respectively, by SA, and 64.8% and 42.1% (p=0.106), respectively, by HPA.Conclusion: Intraoperative assessment of RM- by surgeon of RLS is clinically meaningful. There is not a statistically significant difference in the assessment of RM+ by surgeon and pathologists per RLS, but it was statically significant on a per patient basis. RM determined by surgeon has better prognostic impact on recurrence rate and 1- and 3-year DFS than standard histopathological assessment.

Size of the Largest Colorectal Liver Metastasis Is an Independent Prognostic Factor in the Neoadjuvant Setting

BackgroundUp to 50% of patients diagnosed with colorectal cancer develop metastases during the course of their disease. Surgical resection remains the only curative treatment option for colorectal liver metastases (CRLM), frequently in conjunction with neoadjuvant chemotherapy. This study sought to determine if the pathologic size of the largest CRLM impacted disease-free survival (DFS) and disease-specific survival (DSS) in the setting of neoadjuvant chemotherapy. MethodsAll patients diagnosed with CRLM who underwent neoadjuvant chemotherapy for liver resection at the Massachusetts General Hospital between 2004 and 2016 were reviewed. The median size of the largest liver lesion was used as the cutoff for grouped evaluation. ResultsA total of 214 patients were included. Median follow-up was 100.0 mo (interquartile range 68.9-133.8 mo). The median size of the largest lesion was 21 mm. Patients with lesions ≥21 mm exhibited significantly worse median DFS (12.5 mo versus 16.6 mo; P = 0.033) and median DSS (71.3 mo versus 103.5 mo; P = 0.038). CRLM lesions ≥21 mm were associated with poorer DFS on univariate analysis (hazard ratio (HR) = 1.42, 95% confidence interval (CI) 1.03-1.95 P = 0.033) and multivariable analysis (HR = 1.58, 95% CI 1.07-2.35, P = 0.023). CRLM lesions ≥21 mm were also independently associated with poorer DSS after liver resection on univariate analysis (HR = 1.51, 95% CI 1.02-2.24; P = 0.037) and multivariable analysis (HR = 1.98, 95% CI: 1.27-3.07; P = 0.002). ConclusionsThe size of the largest CRLM is an important prognostic factor for both DFS and DSS after neoadjuvant therapy and serves as a useful indicator of tumor biology.

Long-term outcomes of patients undergoing hepatectomy for bilateral multiple colorectal liver metastases-a propensity score matching analysis

Objective: Liver is the most common site of distant metastasis in colorectal cancer patients. Currently, surgical resection of colorectal liver metastasis (CRLM) still remains the most curative therapeutic option which is associated with long-term survival. However, the outcome of CRLM patients with bilobar multiple lesions has been reported to be extremely poor due to the complex techniques of the surgery and the difficulties to achieve a negative resection margin. In this study, postoperative long-term outcome in patients with bilobar versus unilobar multiple CRLM undergoing surgical resection were compared and the prognostic factors of CRLM were analyzed. Methods: A retrospective cohort study was performed. The clinicopathological data were collected retrospectively from patients with multiple CRLM who received liver resection between January 2002 and November 2018 at our department. Inclusion criteria: (1) All CRLM lesions were confirmed by preoperative enhanced CT or MRI and enhanced ultrasonography. (2) All CRLM lesions were resectable either initially or converted by systemic treatments. The CRLM patients were considered as resectable, if their extrahepatic diseases were able to be completely removed. (3) Sufficient remnant liver volume was required to maintain normal liver function, which was defined by the ratio of remnant liver volume to total liver volume (RLV-TLV), of greater than 30% in general or 40% for the patients undergoing chemotherapy. (4) Medical records and follow-up information were intact. Those undergoing multiple operations after recurrence, with R2 resection, or with a single CRLM lesion were excluded. Patients were divided into bilobar and unilobar group according to tumor distribution. One-to-one propensity score matching (PSM) was performed to balance the covariates between the bilobar group and unilobar group. After PSM, the differences in long-term outcomes between the two groups were compared. Results: A total of 491 patients met the inclusion criteria, 344 (69.6%) with bilobar and 147 (30.4%) with unilobar CRLM. In the propensity-score-matched population (bilobar, 143; unilobar, 143), baseline characteristics were similar between the two groups. The 1-, 3-, and 5-year overall survival rates in the bilobar group were 91.6%, 52.1%, and 35.3% respectively, compared with 93.7%, 56.8%, and 43.8% in the unilobar group, and the difference was not statistically significant (P=0.204). The 1-, 3-, and 5-year recurrence-free survival rates in the bilobar group were 45.7%, 33.7%, and 33.7% respectively, compared with 62.5%, 44.1%, and 42.1% in the unilobar group, and the difference was not statistically significant (P=0.075). No significant difference was found in liver-only recurrence (45.6% in bilobar vs. 53.3% in unilobar, P=0.543). Univariate analysis showed that N stage of primary tumor, diameter of the largest liver metastases, carcinoembyonic antigen level, RAS gene status and clinical risk score (CRS) were significantly associated with the prognosis of CRLM (all P<0.05). Multivariate analysis indicated that diameter of largest liver metastases > 5 cm (HR=1.888, 95% CI: 1.251-2.848, P=0.002), CRS≥3 (HR=1.552,95% CI:1.050-2.294, P=0.027) and RAS gene mutation (HR=1.561, 95% CI: 1.102-2.212, P=0.012) were independent risk factors of poor overall survival after hepatectomy. Conclusions: Tumor distribution may not affect the prognosis of multiple CRLM after resection. Surgical removal in patients with bilobar multiple CRLM provides comparable long-term survival to unilobar multiple CRLM.

A comparison of microwave thermosphere versus radiofrequency thermal ablation in the treatment of colorectal liver metastases

BackgroundMicrowave thermosphere ablation (MTA) is a new generation technology. The aim of this study was to compare the efficacy of MTA and radiofrequency ablation (RFA) in achieving local tumor control in patients with colorectal liver metastasis (CRLM). MethodsThis was a retrospective study of a prospective ablation database. Fifty-four patients with 155 CRLM lesions underwent RFA and 51 patients with 121 lesions underwent MTA. Patients were managed by a multidisciplinary team. Clinical and oncologic data were analyzed. Kaplan–Meier and Cox Proportional Hazards model were used for statistical analysis. ResultsDemographics were similar between the two groups. Total ablation and operative times were significantly shorter in MTA group (19 vs. 37 mins, p < 0.001, 154 vs. 202 mins, p = 0.009). With a similar hospital stay (median 1), 90-day morbidity was similar (8 vs. 10%, p = 0.848), without mortality. Local recurrence (LR) rate per lesion was 20% in RFA and 10% in MTA group (p = 0.020). On Cox Proportion Hazards model, ablation modality and tumor size were independent predictors of LR. ConclusionsThis is the first study comparing the efficacy of RFA and MTA on CRLM. The results suggest that compared to RFA, MTA improves local tumor control, while significantly shortening operative time.

Prognostic Significance of c-erbB-2 and Vascular Endothelial Growth Factor in Colorectal Liver Metastases

The prognostic value of c-erbB-2 and vascular endothelial growth factor (VEGF) expression in colorectal liver metastases (CLM) is unclear. The purpose of this study was to clarify the relationship of c-erbB-2 and VEGF with the clinicopathological parameters and the survival results in CLM. For 44 patients who had undergone liver resection for CLM at Fudan University Cancer Hospital from 2000 to 2007, the expression of c-erbB-2 and VEGF in CLM and the corresponding primary cancer specimens were evaluated immunohistochemically. The correlations among c-erbB-2 and VEGF, clinicopathologic factors, and survival were then statistically analyzed. Positive expression rates of c-erbB-2 and VEGF in CLM lesions were 38.64% and 52.72%, respectively. The expression of c-erbB-2 and VEGF in CLM were similar to that of corresponding primary tumor. c-erbB-2 expression correlated with number of metastatic lesions and the distribution of liver metastases. The expression of VEGF correlated with the size of liver metastatic lesion and distribution of liver metastases. A statistically significant association between the expression of c-erbB-2 and VEGF in both CLM and primary tumor was noted. Univariate analysis showed that VEGF was a prognostic factor. However, on multivariate analysis, expression of VEGF was not an independent prognostic marker. Patients with both negative expression of c-erbB-2 and VEGF expression had a better outcome than others. VEGF might be a statistically significant prognostic factor. The combined analysis of c-erbB-2 and VEGF is of added prognostic value. An association exists between c-erbB-2 and VEGF. However, further studies are required to confirm this issue.