Diagnosis Of Colorectal Liver Metastases Research Articles

Comprehensive data of 5085 patients newly diagnosed with colorectal liver metastasis between 2013 and 2017: Fourth report of a nationwide survey in Japan.

The Joint Committee for Nationwide Survey on colorectal liver metastasis (CRLM) was established to improve treatment outcomes in patients with CRLM. The aim of this study was to evaluate the transition in the characteristics and treatment strategies of patients with CRLM and to analyze the prognostic factors. The data of 5085 patients newly diagnosed between 2013 and 2017 were compared with those of 3820 patients from 2005 and 2007. In patients who underwent hepatectomy (n = 2759 and 2163), the number of CRLMs was significantly higher and in the 2013-2017 data than in the 2005-2007 data (median 2 vs. 1; p = .005). Overall survival (OS) rates after diagnosis of CRLM after hepatectomy were better in the 2013-2017 data than that in the 2005-2007 data (5-year OS, 62.4% vs. 56.7%, p < .001). Recurrence-free survival (RFS) after hepatectomy was comparable between the groups (5-year RFS, 30.5% vs. 30.7%; p = .068). Multivariate analyses identified age at diagnosis of CRLM ≥70 years, lymph node metastasis of primary lesion, preoperative carbohydrate antigen (CA) 19-9 value >100 U/mL, number of CRLM 2-4, and R2 resection as independent predictors of OS. Synchronous CRLM, concomitant extrahepatic metastasis, lymphatic invasion, lymph node metastasis of primary lesion, preoperative CA19-9 value >100 U/mL, number of CRLM 5-, and nonlaparoscopic approach were selected as that of RFS. Despite having a higher prevalence of advanced stage CRLM in the 2013-2017 patient population compared to the 2005-2007 cohort, prognostic outcomes demonstrably improved in the later period.

Tranexamic Acid in Patients Undergoing Liver Resection

Tranexamic acid reduces bleeding and blood transfusion in many types of surgery, but its effect in patients undergoing liver resection for a cancer-related indication remains unclear. To determine whether tranexamic acid reduces red blood cell transfusion within 7 days of liver resection. Multicenter randomized clinical trial of tranexamic acid vs placebo conducted from December 1, 2014, to November 8, 2022, at 10 hepatopancreaticobiliary sites in Canada and 1 site in the United States, with 90-day follow-up. Participants, clinicians, and data collectors were blinded to allocation. A volunteer sample of 1384 patients undergoing liver resection for a cancer-related indication met eligibility criteria and consented to randomization. Tranexamic acid (1-g bolus followed by 1-g infusion over 8 hours; n = 619) or matching placebo (n = 626) beginning at induction of anesthesia. The primary outcome was receipt of red blood cell transfusion within 7 days of surgery. The primary analysis included 1245 participants (mean age, 63.2 years; 39.8% female; 56.1% with a diagnosis of colorectal liver metastases). Perioperative characteristics were similar between groups. Red blood cell transfusion occurred in 16.3% of participants (n = 101) in the tranexamic acid group and 14.5% (n = 91) in the placebo group (odds ratio, 1.15 [95% CI, 0.84-1.56]; P = .38; absolute difference, 2% [95% CI, -2% to 6%]). Measured intraoperative blood loss (tranexamic acid, 817.3 mL; placebo, 836.7 mL; P = .75) and total estimated blood loss over 7 days (tranexamic acid, 1504.0 mL; placebo, 1551.2 mL; P = .38) were similar between groups. Participants receiving tranexamic acid experienced significantly more complications compared with placebo (odds ratio, 1.28 [95% CI, 1.02-1.60]; P = .03), with no significant difference in venous thromboembolism (odds ratio, 1.68 [95% CI, 0.95-3.07]; P = .08). Among patients undergoing liver resection for a cancer-related indication, tranexamic acid did not reduce bleeding or blood transfusion but increased perioperative complications. ClinicalTrials.gov Identifier: NCT02261415.

Radiological complete response with regorafenib for multiple lung metastases of ascending colon cancer: a case report

BackgroundRegorafenib is an oral diphenylurea multikinase inhibitor and currently approved for use following third-line therapy for metastatic colorectal cancer (CRC) patients. Only one case has previously been reported of metastatic CRC showing a complete response (CR) to regorafenib.Case presentationA 68-year-old Japanese man underwent laparoscopy-assisted ileocecal resection and D3 lymphadenectomy due to his ascending colon cancer. Eighteen months after surgery, a laparoscopic hepatic left lateral segmentectomy was performed due to a liver tumor, and a pathological diagnosis of colorectal liver metastasis was made. Three months after the second surgery, contrast-enhanced computed tomography (CT) revealed multiple lung metastases. The patient had undergone 18 courses of the FOLFOX + bevacizumab chemotherapy regimen as their first-line therapy and 11 courses of the FOLFIRI + ramucirumab chemotherapy regimen as their second-line therapy. As their third-line therapy, the patient was administered the regorafenib chemotherapy regimen. We evaluated the chemotherapy treatment’s effect on the lung tumors by CT after 3, 7, 11, and 17 courses of the regorafenib chemotherapy regimen, finding that the lung tumors had shrunk with time; thus, each tumor was considered a partial response (PR) based on the RECIST guidelines. After 21 courses of the regorafenib chemotherapy regimen, the chemotherapy was discontinued in response to the patient’s wishes. Even at 1 and 3 months after the discontinuation of the chemotherapy, CT revealed that the lung tumors had shrunk, with each considered a PR. Furthermore, 9 months after the discontinuation of the chemotherapy, CT revealed scarring of the lung tumors. This was considered a CR, rather than a PR. The patient remains disease-free 18 months after the discontinuation of chemotherapy.ConclusionsIn this paper, we present the second case of radiological CR with regorafenib for multiple lung metastases of ascending colon cancer. Currently, there is no consensus on a treatment strategy for patients with radiological CR.

Probe-based confocal laser endomicroscopy for real-time evaluation of colorectal liver metastasis in resected surgical specimens

Probe-based confocal laser endomicroscopy (pCLE) enables real-time examination of tissue structure. This study investigated pCLE with or without fluorescein sodium for the intraoperative diagnosis of colorectal liver metastasis (CLM) and detection of surgical margins. Thirty-four specimens of CLM and adjacent noncancerous tissue were obtained from 21 patients and examined by pCLE between May 2017 and March 2018. Images were obtained both without and with fluorescein sodium applied to the cut surface and compared with hematoxylin and eosin-stained tissue. Fluorescence intensity (FI) was measured by luminance-analysis software. Without external fluorophores, pCLE visualized 91.2% of CLM tissues as an irregular structure with low autofluorescence and 90.5% of noncancerous liver tissues as a regular structure with high autofluorescence. The median FI was significantly lower in cancer than in benign tissue in patients without chemotherapy [70.4 (51.6–110) vs. 48.3 (39.0–59.4), p = 0.002] and with chemotherapy [67.9 (54.6–89.2) vs. 48.6 (28.8–82.1), p < 0.001]. The border was clearly visible; pCLE with fluorescein sodium clearly showed their morphologies. In summary, our study demonstrated real-time pCLE distinguished CLM and noncancerous tissue by differences in structure and FI regardless of prehepatectomy chemotherapy. Fluorescein spray facilitated clear visualization of differences in the morphology.

C-Met-Targeting 19F MRI Nanoparticles with Ultralong Tumor Retention for Precisely Detecting Small or Ill-Defined Colorectal Liver Metastases.

Precisely detecting colorectal liver metastases (CLMs), the leading cause of colorectal cancer-associated mortality, is extremely important. 1H MRI with high soft tissue resolution plays a key role in the diagnosing liver lesions; however, precise detecting CLMs by 1H MRI is a great challenge due to the limited sensitivity. Even though contrast agents may improve the sensitivity, due to their short half-life, repeated injections are required to monitor the changes of CLMs. Herein, we synthesized c-Met-targeting peptide-functionalized perfluoro-15-crown-5-ether nanoparticles (AH111972-PFCE NPs), for highly sensitive and early diagnosis of small CLMs. The size, morphology and optimal properties of the AH111972-PFCE NPs were characterized. c-Met specificity of the AH111972-PFCE NPs was validated by in vitro experiment and in vivo 19F MRI study in the subcutaneous tumor murine model. The molecular imaging practicability and long tumor retention of the AH111972-PFCE NPs were evaluated in the liver metastases mouse model. The biocompatibility of the AH111972-PFCE NPs was assessed by toxicity study. AH111972-PFCE NPs with regular shape have particle size of 89.3 ± 17.8 nm. The AH111972-PFCE NPs exhibit high specificity, strong c-Met-targeting ability, and precise detection capability of CLMs, especially small or ill-defined fused metastases in 1H MRI. Moreover, AH111972-PFCE NPs could be ultralong retained in metastatic liver tumors for at least 7 days, which is conductive to the implementation of continuous therapeutic efficacy monitoring. The NPs with minimal side effects and good biocompatibility are cleared mainly via the spleen and liver. The c-Met targeting and ultralong tumor retention of AH111972-PFCE NPs will contribute to increasing therapeutic agent accumulation in metastatic sites, laying a foundation for CLMs diagnosis and further c-Met targeted treatment integration. This work provides a promising nanoplatform for the future clinical application to patients with CLMs.

Clinical Significance of Liver MR Imaging.

MRI is widely used in clinical practice for detecting liver diseases. Since the introduction of gadoxetic acid, MRI has become the most effective modality for the detection and characterization of focal liver lesions. According to previous meta-analyses, the area under the receiver operating characteristic curve (AUROC) was 0.97-0.99 for the diagnosis of small hepatocellular carcinoma (≥ 2 cm) by gadoxetic-acid-enhanced MRI. Moreover, the AUROC for the diagnosis of colorectal liver metastases was significantly high (0.98). Despite gadoxetic acid's drawbacks, its clinical utility outweighs them, making it the contrast agent of choice in routine liver MRIs. Moreover, clinically, liver MRI has become more prevalent for a quantitative assessment. Liver fibrosis can be evaluated using MR elastography; whereas, hepatic steatosis and iron overload can be evaluated using proton density fat fraction, with high accuracy and reproducibility. This article reviewed the usefulness of liver MRI, which can be a comprehensive imaging modality in clinical practice.

Comprehensive data of 4502 patients newly diagnosed with colorectal liver metastasis between 2015 and 2017, and prognostic data of 2427 patients newly diagnosed with colorectal liver metastasis in 2013 and 2014: Third report of a nationwide survey in Japan.

To improve treatment outcomes in patients with colorectal liver metastasis (CRLM), the Joint Committee for Nationwide Survey on CRLM was established by the Japanese Society for Cancer of the Colon and Rectum and the Japanese Society of Hepato-Biliary-Pancreatic Surgery. The aim of the study was to evaluate transition in the characteristics and treatment strategy in CRLM patients and analyze prognostic factors using large-scale data. The present study summarizes the data of patients newly diagnosed between 2015 and 2017 and presents prognostic data of patients newly diagnosed in 2013 and 2014. Survival curves were generated by the Kaplan-Meier method and compared by log-rank test. Multivariate analyses were carried out using Cox proportional hazard modeling. The data of 4502 patients newly diagnosed with CRLM between 2015 and 2017 and the prognostic data of 2427 patients diagnosed in 2013 and 2014 are included. Regarding the 2013 and 2014 prognostic data, the 5-year overall survival (OS) rates of patients who underwent hepatectomy alone was 59.8%. Multivariate analyses identified age at diagnosis of CRLM ≥70 years, concomitant extrahepatic metastasis at diagnosis of CRLM, tumor depth of primary lesion ≥subserosa/pericolic or perirectal tissue, mutant KRAS status, number of CRLM ≥5, maximum diameter of CRLM >5 cm, and surgical curability R1/R2 as independent predictors of OS. Analysis of the latest nationwide database of patients diagnosed with CRLM revealed changes in patients and oncological characteristics, a transition in treatment strategy, and different independent prognosticators to those reported previously.

Contrast-Enhanced Ultrasound With SonoVue and Sonazoid for the Diagnosis of Colorectal Liver Metastasis After Chemotherapy.

To compare the diagnostic efficacy of SonoVue and Sonazoid contrast-enhanced ultrasound (CEUS) in correctly detecting and characterizing colorectal liver metastasis (CRLM) after chemotherapy. Patients with CRLMs treated with chemotherapy and subsequently scheduled for hepatic resection were prospectively enrolled from April 2020 to January 2021. Lesions detected by SonoVue or Sonazoid CEUS were recorded as and characterized as metastases or non-metastatic lesions respectively. Histopathology or intraoperative ultrasound with MRI were the reference standard. A total of 348 focal liver lesions in 42 patients were investigated, including 297 CRLMs and 51 non-metastatic lesions. SonoVue showed significantly higher diagnostic accuracy (64.7% versus 54.0%; P<.001) and sensitivity (63.3% versus 50.5%; P<.001) in the diagnosis of CRLMs than Sonazoid, both methods presented with similar specificity (72.5% versus 74.5%; P=1.0). Forty metastases appeared non-hypoenhancing (hyperenhancing or isoenhancing) in the late phase and postvascular phase of Sonazoid CEUS and were mischaracterized as benign lesions. SonoVue performed significantly better than Sonazoid in the diagnosis of CRLMs after chemotherapy.

Optimal cytoreductive LIVER surgery for unresectable colorectal liver metastases: A prospective observational study.

3570 Background: Patients with multiple colorectal liver metastases (CLM) involving all the hepatic segments are currently not eligible for potentially curative liver surgery. Transplantation is a promising alternative but graft shortage and stringent selection criteria limit its accessibility. Owing to the improving efficacy of chemotherapy, the impossibility to resect all the initial metastatic sites could lead to revisit the role of optimal cytoreductive liver surgery (CLS) aiming to treat by resection ± radiofrequency, all the macroscopic residual tumors after a good response to chemotherapy. Although validated for ovarian cancer and peritoneal carcinomatosis, this strategy remains unexplored in CLM. Our objective was to evaluate the outcome of this strategy in patients with definitively unresectable CLM. Methods: Within a prospective monocentric study, we enrolled for debulking surgery, between 2017 and 2021, all consecutive patients with multinodular unresectable CLM involving all segments on initial imaging and consequently ineligible for a curative surgery either after a one or two-stage hepatectomy. These patients should have a strong response to chemotherapy ( &gt; 50 % on RECIST criteria) for at least a 3-month period and no or limited extrahepatic disease, to be included. End-points of the analysis were overall and disease-free survival at 3 years. Results: Among 26 patients considered for this strategy, optimal CLS could be achieved in 21 patients after a median interval of 10 months from CLM diagnosis. The median number of lesions was 11 (7 - 26) on initial imaging. Four patients (19%) had synchronous lung metastases. Liver-first strategy was undertaken in 19 patients (90%). Postoperative complications (Grade ≥ III) occured in 5 patients (24%). One patient died within 90-day after operation from intra-abdominal hemorrage while on anticoagulation therapy. After a median follow-up of 25 months from hepatectomy, the 3-year OS rates was 85%. Median survival was not reached at the time of the analysis. Of the 4 (19%) patients with complete pathological response on the liver specimen, 3 developed recurrence. A total of 17 patients (81%) developed recurrence after a median time of 10,5 months from hepatectomy. Among them, repeat hepatectomy could be undertaken in four patients. The survival time to surgical failure (recurrence untreatable with curative intent) was 32% and 16% at 2 and 3 years. At last follow-up, seven patients (33%) are alive and recurrence-free. Conclusions: The promising results of this prospective series suggest that CLS may be worthy in patients with diffuse CLM non curatively treatable by surgery but responding well to chemotherapy. This strategy should however be reserved to hyperselected patients, super responders, eligible for an optimal resection of all the macroscopic residual tumors, and confimed by other expert centers, to be definitively validated.

Multi-institutional analysis of outcomes for thermosphere microwave ablation treatment of colorectal liver metastases: the SMAC study

ObjectivesOligometastatic colorectal cancer benefits of locoregional treatments but data concerning microwave ablation (MWA) are limited and interactions with systemic therapy are still debated. The aim of this study is to evaluate safety and effectiveness of Thermosphere™ MWA (T-MWA) of colorectal liver metastases (CLM) and factors affecting local tumor progression-free survival (LTPFS).MethodsIn this multi-institutional retrospective study (January 2015–September 2019), patients who underwent T-MWA for CLM were enrolled. Complications according to SIR classification were collected, primary efficacy and LTP were calculated. Analyzed variables included CLM size at diagnosis and at ablation, CLM number, ablation margins, intra-segment progression, chemotherapy before ablation (CBA), variations in size (ΔSDIA-ABL), and velocity of size variation (VDIA-ABL) between CLM diagnosis and ablation. Uni/multivariate analyses were performed using mixed effects Cox model to account for the hierarchical structure of data, patient/lesions.ResultsOne hundred thirty-two patients with 213 CLM were evaluated. Complications were reported in 6/150 procedures (4%); no biliary complications occurred. Primary efficacy was achieved in 204/213 CLM (95.7%). LTP occurred in 58/204 CLM (28.4%). Six-, twelve-, and eighteen-month LTPFS were 88.2%, 75.8%, and 69.9%, respectively. At multivariate analysis, CLM size at ablation (p = 0.00045), CLM number (p = 0.046), ablation margin < 5 mm (p = 0.0035), and intra-segment progression (p < 0.0001) were statistically significant for LTPFS. ΔSDIA-ABL (p = 0.63) and VDIA-ABL (p = 0.38) did not affect LTPFS. Ablation margins in the chemo-naïve group were larger than those in the CBA group (p < 0.0001).ConclusionT-MWA is a safe and effective technology with adequate LTPFS rates. Intra-segment progression is significantly linked to LTPFS. CBA does not affect LTPFS. Anticipating ablation before chemotherapy may take the advantages of adequate tumor size with correct ablation margin planning.Key Points• Thermosphere™-Microwave ablation is a safe and effective treatment for colorectal liver metastases with no registered biliary complications in more than 200 ablations.• Metastases size at time of ablation, intra-segment progression, and minimal ablation margin < 5 mm were found statistically significant for local tumor progression-free survival.• Chemotherapy before ablation modifies kinetics growth of the lesions but deteriorates ablation margins and does not significantly impact local tumor progression-free survival.

Biomarkers in colorectal liver metastases: Rising complexity and unknown clinical significance?

Surgical resection of the liver is the standard treatment for colorectal liver metastases, but 70% of patients still experience recurrence, resulting in limited survival. Molecular biomarkers promise guidance within the selection process of individualized treatment and provide better prognostic forecasting of recurrence and response to treatment. Presently, most investigated biomarkers include mutations of KRAS, BRAF, TP53, PIK3CA, APC, expression of Ki‐67, and microsatellite instability. As some colorectal cancer tumors exhibit more than one molecular target, in line with a rising number of potential biomarkers, the complexity of their clinical implementation is rising steadily. Therefore, it is important to approach new insights into molecular biomarkers with explicit caution to their clinical applicability and significance, as there are contradictory results arising from multiple available studies and meta‐analyses. This review helps to shed light on the complexity of promising biomarkers in both the prognosis and diagnosis of colorectal liver metastases.

Assessment of Textbook Outcome in Laparoscopic and Open Liver Surgery

Textbook outcome (TO) is a composite measure that captures the most desirable surgical outcomes as a single indicator, yet to date TO has not been defined and assessed in the field of laparoscopic liver resection (LLR) and open liver resection (OLR). To obtain international agreement on the definition of TO in liver surgery (TOLS) and to assess the incidence of TO in LLR and OLR in a large international multicenter database using a propensity-score matched analysis. Patients undergoing LLR or OLR for all liver diseases between January 2011 and October 2019 were analyzed using a large international multicenter liver surgical database. An international survey was conducted among all members of the European-African Hepato-Pancreato-Biliary Association (E-AHPBA) and International Hepato-Pancreato-Biliary Association (IHPBA) to reach agreement on the definition of TOLS. The rate of TOLS was assessed for LLR and OLR before and after propensity-score matching. Factors associated with achieving TOLS were investigated. Textbook outcome, with TOLS defined as the absence of intraoperative incidents of grade 2 or higher, postoperative bile leak grade B or C, severe postoperative complications, readmission within 30 days after discharge, in-hospital mortality, and the presence of R0 resection margin. A total of 8188 patients (4559 LLR; median age, 65 years [interquartile range, 55-73 years]; 2529 were male [55.8%] and 3629 OLR; median age, 64 years [interquartile range, 56-71 years]; 2204 were male [60.7%]) were included in the analysis of whom 69.1% achieved TOLS; 74.8% for LLR and 61.9% for OLR (P < .001). On multivariable analysis, American Society of Anesthesiologists grade III, previous abdominal surgery, histological diagnosis of colorectal liver metastases (odds ratio [OR], 0.656 [95% CI, 0.457-0.940]; P = .02), cholangiocarcinoma, non-CRLM, a tumor size of 30 mm or more, minor resection of posterior/superior segments (OR, 0.716 [95% CI, 0.577-0.887]; P = .002), anatomically major resection (OR, 0.579 [95% CI, 0.418-0.803]; P = .001), and nonanatomical resection (OR, 0.612 [95% CI, 0.476-0.788]; P < .001) were associated with a worse TOLS rate after LLR. For OLR, only histological diagnosis of cholangiocarcinoma (OR, 0.360 [95% CI, 0.214-0.607]; P < .001) and a tumor size of 30 mm or more (30-50 mm = OR, 0.718 [95% CI, 0.565-0.911]; P = .01; 50.1-100 mm = OR, 0.729 [95% CI, 0.554-0.960]; P = .02; >10 cm = OR, 0.550 [95% CI, 0.366-0.826]; P = .004) were associated with a worse TOLS rate. In this multicenter study, TOLS was found to be a useful tool for assessing patient-level hospital performance and may have utility in optimizing patient outcomes after LLR and OLR.

A new rapid diagnostic system with ambient mass spectrometry and machine learning for colorectal liver metastasis.

BackgroundProbe electrospray ionization-mass spectrometry (PESI-MS) can rapidly visualize mass spectra of small, surgically obtained tissue samples, and is a promising novel diagnostic tool when combined with machine learning which discriminates malignant spectrum patterns from others. The present study was performed to evaluate the utility of this device for rapid diagnosis of colorectal liver metastasis (CRLM).MethodsA prospectively planned study using retrospectively obtained tissues was performed. In total, 103 CRLM samples and 80 non-cancer liver tissues cut from surgically extracted specimens were analyzed using PESI-MS. Mass spectra obtained by PESI-MS were classified into cancer or non-cancer groups by using logistic regression, a kind of machine learning. Next, to identify the exact molecules responsible for the difference between CRLM and non-cancerous tissues, we performed liquid chromatography-electrospray ionization-MS (LC-ESI-MS), which visualizes sample molecular composition in more detail.ResultsThis diagnostic system distinguished CRLM from non-cancer liver parenchyma with an accuracy rate of 99.5%. The area under the receiver operating characteristic curve reached 0.9999. LC-ESI-MS analysis showed higher ion intensities of phosphatidylcholine and phosphatidylethanolamine in CRLM than in non-cancer liver parenchyma (P < 0.01, respectively). The proportion of phospholipids categorized as monounsaturated fatty acids was higher in CRLM (37.2%) than in non-cancer liver parenchyma (10.7%; P < 0.01).ConclusionThe combination of PESI-MS and machine learning distinguished CRLM from non-cancer tissue with high accuracy. Phospholipids categorized as monounsaturated fatty acids contributed to the difference between CRLM and normal parenchyma and might also be a useful diagnostic biomarker and therapeutic target for CRLM.

Implementation of hepatic artery infusion (HAI) chemotherapy for unresectable colorectal liver metastases (CRLM): The University of Miami experience.

96 Background: In patients with unresectable liver-confined CRLM, regional chemotherapy via HAI in combination with modern systemic chemotherapy (CT) can achieve hepatic disease control and expand surgical resectability. We describe patient selection and early outcomes following implementation of a HAI program at our tertiary referral academic center. Methods: We analyzed demographics, previous systemic treatment, primary tumor location, molecular profiling, extent of hepatic/extrahepatic disease, perioperative HAI outcomes (toxicity, conversion to resection/ablation, radiographic response), and overall survival (OS) in CRLM patients selected for HAI treatment (01/2018—06/2020) after multidisciplinary review. Results: Of 35 patients with unresectable CRLM (primary: colon, n = 24; rectum, n = 11) selected for HAI, 57% were heavily pre-treated (with at least 2 lines of pre-HAI systemic chemotherapy), 71% had a Fong clinical risk score ≥3, 86% presented with synchronous disease, 80% had bilobar metastasis, and 86% had &gt; 5 tumors. All tumors were microsatellite stable, with 20% harboring KRAS/NRAS mutations and none had class I/II BRAF mutations. HAI was initiated at a median 14 (IQR 3, 64) months after CRLM diagnosis, and administered for a median of 7 (range 2, 16) cycles; 91% of patients (31/34) received concurrent HAI and systemic chemotherapy. Although most (69%) patients experienced some degree of hepatic toxicity during HAI therapy resulting in FUDR dose reduction and steroid administration, biliary sclerosis requiring intervention was observed in only 3 (9%) of patients. The overall perioperative morbidity was 17%, and there were no surgical-related 90-day mortalities following HAI pump placement. Excluding patients who initiated HAI treatment within the last 3 months of the study period (n = 3), 13 of 32 patients (41%) were rendered disease-free in the liver following complete resection and/or ablation in combination with HAI/systemic chemotherapy; in the remaining 19 patients (59%), hepatic progression-free survival was 7.3 months (IQR 4, 12). At a median follow-up of 11.2 months, post-HAI median OS for the overall cohort was 12.3 (IQR 7, 20) months. Patients undergoing complete resection/ablation demonstrated improved survival compared with those with progressive disease (median 20 vs 12 months, respectively). Conclusions: Implementation of a HAI program for multimodality liver-directed management of unresectable CRLM is feasible and is associated with meaningful clinical outcomes unlikely to be achieved with systemic therapy alone in heavily pre-treated patients.

Aggressive recurrences determine oncologic outcomes after resection of liver metastases from primary right colon cancer: Results of a case-control study

BackgroundDespite recent studies suggest that, among patients operated on for colorectal liver metastases (CLM), the primary tumor location may impact on postoperative survivals, results are still contrasting. Objectiveevaluating survivals (overall (OS) and (DFS)) following liver resection of CLM from Right colon Cancer (RcC-CLM) versus Left colon Cancer (LcC-CLM), among patients undergoing preoperative chemotherapy (pCHT), identifying survival predictors, and investigating impact of recurrent disease pattern and management on survival. MethodsAmong 727 patients operated for CLM(1989–2016), after excluding patients with primary transverse colon/rectum tumor and patients not receving pCHT, 297 patients were identified. Among them, 81 with RcC-CLM were matched 1:1 with LcC-CLM, according to CLM number and diameter, disease-free interval between primary tumor and CLM diagnosis, primary tumor N-status, and the presence of extrahepatic disease. ResultsOverall, 66.7% of patients had multiple CLM, 21% had CLM>5 cm, 82.7% had DFI<12 months, 67.9% had N+ primary tumor, and 11.1% had extrahepatic disease at time of hepatectomy. RcC-CLM patients were similar to LcC-CLM in terms of demographic, clinical, perioperative, and pathologic characteristics. Patients operated for RcC-CLM, compared to LcC-CLM, had significantly shorter 5y-DFS(18% versus 39%) and 5y-OS(38% vs 65%). At multivariate analysis, being operated for RcC-CLM, compared to LcC-CLM, was the strongest predictor of recurrence (Hazard Ratio:2.265,p < .001) and death (HR:2.234,p = .001). Among 107 patients experiencing recurrent disease, curative recurrence resection was associated with higher 5y-OS(64% vs 17%; p < .001). However, recurrence resection was less frequently feasible among RcC-CLM(26%) patients, compared to LcC-CLM(44%,p = .05). Conclusionsresection of RcC-CLM, compared to LcC-CLM, is associated with worse survivals, probably related to a different pattern of recurrence precluding recurrence resection among RcC-CLM patients.

Liver resection surgery compared with thermal ablation in high surgical risk patients with colorectal liver metastases: the LAVA international RCT.

Although surgical resection has been considered the only curative option for colorectal liver metastases, thermal ablation has recently been suggested as an alternative curative treatment. There have been no adequately powered trials comparing surgery with thermal ablation. Main objective - to compare the clinical effectiveness and cost-effectiveness of thermal ablation versus liver resection surgery in high surgical risk patients who would be eligible for liver resection. Pilot study objectives - to assess the feasibility of recruitment (through qualitative study), to assess the quality of ablations and liver resection surgery to determine acceptable standards for the main trial and to centrally review the reporting of computed tomography scan findings relating to ablation and outcomes and recurrence rate in both arms. A prospective, international (UK and the Netherlands), multicentre, open, pragmatic, parallel-group, randomised controlled non-inferiority trial with a 1-year internal pilot study. Tertiary liver, pancreatic and gallbladder (hepatopancreatobiliary) centres in the UK and the Netherlands. Adults with a specialist multidisciplinary team diagnosis of colorectal liver metastases who are at high surgical risk because of their age, comorbidities or tumour burden and who would be suitable for liver resection or thermal ablation. Thermal ablation conducted as per local policy (but centres were encouraged to recruit within Cardiovascular and Interventional Radiological Society of Europe guidelines) versus surgical liver resection performed as per centre protocol. Pilot study - patients' and clinicians' acceptability of the trial to assist in optimisation of recruitment. Primary outcome - disease-free survival at 2 years post randomisation. Secondary outcomes - overall survival, timing and site of recurrence, additional therapy after treatment failure, quality of life, complications, length of hospital stay, costs, trial acceptability, and disease-free survival measured from end of intervention. It was planned that 5-year survival data would be documented through record linkage. Randomisation was performed by minimisation incorporating a random element, and this was a non-blinded study. In the pilot study over 1 year, a total of 366 patients with colorectal liver metastases were screened and 59 were considered eligible. Only nine participants were randomised. The trial was stopped early and none of the planned statistical analyses was performed. The key issues inhibiting recruitment included fewer than anticipated patients eligible for both treatments, misconceptions about the eligibility criteria for the trial, surgeons' preference for one of the treatments ('lack of clinical equipoise' among some of the surgeons in the centre) with unconscious bias towards surgery, patients' preference for one of the treatments, and lack of dedicated research nurses for the trial. Recruitment feasibility was not demonstrated during the pilot stage of the trial; therefore, the trial closed early. In future, comparisons involving two very different treatments may benefit from an initial feasibility study or a longer period of internal pilot study to resolve these difficulties. Sufficient time should be allowed to set up arrangements through National Institute for Health Research (NIHR) Research Networks. Current Controlled Trials ISRCTN52040363. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 21. See the NIHR Journals Library website for further project information.

Impact of primary tumor location on survival following colorectal liver metastases resection

Background: Despite recent studies suggest that, among patients operated on for colorectal liver metastases (CLM), the primary tumor location (right versus left colon) may impact on postoperative survivals, Results are still contrasting. Objective: To evaluate survivals (overall(OS) and disease-free(DFS)) following liver resection of CLM from Right colon Cancer(RcC-CLM) versus Left colon Cancer(LcC-CLM), among patients undergoing preoperative chemotherapy. Methods: Among 727 patients operated on for CLM(1989-2016), following exclusion of patients with primary tumor located in the transverse colon or rectum and of patients not receving preoperative chemotherapy, 297 patients were identified. Among them, 81 operated for RcC-CLM were matched 1:1 with 81 operated for LcC-CLM, according to CLM number and diameter, disease-free interval(DFI) between primary tumor and CLM diagnosis, tumor N-status, and the presence of extrahepatic disease. Results: Overall, 66.7% of patients had multiple CLM, 21% had CLM>5 cm, 82.7% had DFI<12 months, 67.9% had N+ primary tumor, and 11.1% had extrahepatic disease at time of hepatectomy. RcC-CLM patients were similar to LcC-CLM in terms of demographic, clinical, perioperative, and pathologic characteristics. Patients operated for RcC-CLM, compared to LcC-CLM, had significantly shorter 5y-DFS(18% versus 39%) and 5y-OS(38% vs 65%). At multivariate analysis, being operated for RcC-CLM, compared to LcC-CLM, was the strongest predictor of recurrence(Hazard Ratio:2.265,p<.001) and death(HR:2.234,p=.001). In case of recurrence, recurrent disease resection was less frequent among RcC-CLM(26%), compared to LcC-CLM (44%,p=.05) and was associated with longer 5y-OS(64% vs 17%;p<.001). Conclusions: RcC-CLM, compared to LcC-CLM, are associated with worse survivals, probably related to a different pattern of recurrence precluding recurrence resection among RcC-CLM patients.

Capabilities of &lt;sup&gt;18&lt;/sup&gt;F-FDG PET/CT in the differential diagnosis of colorectal liver metastases

Aim. To study the capabilities of &lt;sup&gt;18&lt;/sup&gt;F -FDG PET/CT in the differential diagnosis of colorectal liver metastases. Materials and methods . A retrospective analysis of &lt;sup&gt;18&lt;/sup&gt;F -FDG PET/CT data of 126 patients with colorectal cancer was carried out. The final diagnosis of colorectal cancer was established based on the analysis of morphological material obtained from the primary tumor. The metastatic or benign origins of the liver foci was confirmed by histological examination or by the results of radiation examination (dynamic observation). Sensitivity and specificity of this method were determined using ROC analysis using the SUV as a numerical classifier. Results . Colorectal liver metastases were detected in 51 (40.5%) patients. Advanced extrahepatic tumor process was detected in 25 (19.8%) cases. There were no progression in 50 (39.7%) patients. Benign tumors were detected in 22 patients with colorectal cancer: in 10 cases coupled with liver metastases, in 12 – without them. Totally 166 focal liver lesions were found: 125 (75.3%) metastases and 41 (24.7%) benign tumors. According to ROC analysis, sensitivity and specificity of &lt;sup&gt;18&lt;/sup&gt;F -FDG PET/CT with SUV ≥ 3.0 in the diagnosis of liver metastases were 84.8% and 97.6% respectively, the area under the ROC curve – 0.893 (95% CI 0.836–0.936 , p &lt; 0.0001), positive predictive value and negative predictive value were – 99.1% and 67.8%, respectively. Conclusion. &lt;sup&gt;18&lt;/sup&gt;F-FDG PET/CT is a highly informative imaging method in the differential diagnosis of colorectal liver metastases larger than 10 mm. The use of quantitative data processing with a threshold value SUV ≥ 3.0 allows to achieve high sensitivity and specificity of the method.

Splenic volume as a biomarker of hepatic damage after chemotherapy in patients with resected colorectal liver metastases (CRLM).

Chemotherapy-associated liver injury (CALI) is a matter of concern for hepatobiliary surgeons as it can entail postoperative liver failure after an extensive hepatectomy. Recent studies have taken special interest in liver function parameters which can correlate with CALI to decrease this adverse event. Therefore, the current study investigates the usefulness of splenic volume as a biomarker of CALI through a portal hypertension mechanism, in patients with colorectal liver metastases (CRLM). We carried out a study in patients with CRLM operated on between 2009 and 2014 in our center. All samples of healthy liver were graded for non-alcoholic fatty liver disease (NAFLD) and sinusoidal obstructive syndrome. Computarized tomography scans for spleen volumetry were analyzed for each patient at CRLM diagnosis, after neoadjuvant chemotherapy, 1 and 6months after resection. A group of 65 consecutive patients with CRLM of large bowel adenocarcinoma submitted to liver resection were included. Patients receiving neoadjuvant chemotherapy had a greater spleen volume increase than those who did not receive treatment (p = 0.053), finding a statistically significant spleen growth in patients with NAFLD (p = 0.036). There was no correlation between spleen enlargement and postoperative complications or average stay. However, survival was decreased in patients with spleen growth and CALI. Patients who receive neoadjuvant chemotherapy for liver metastasis surgery have a greater splenic volume increase, which correlates with NAFLD and a lower survival.

VEROnA Protocol: A Pilot, Open-Label, Single-Arm, Phase 0, Window-of-Opportunity Study of Vandetanib-Eluting Radiopaque Embolic Beads (BTG-002814) in Patients With Resectable Liver Malignancies.

BackgroundTransarterial chemoembolization (TACE) is the current standard of care for patients with intermediate-stage hepatocellular carcinoma (HCC) and is also a treatment option for patients with liver metastases from colorectal cancer. However, TACE is not a curative treatment, and tumor progression occurs in more than half of the patients treated. Despite advances and technical refinements of TACE, including the introduction of drug-eluting beads-TACE, the clinical efficacy of TACE has not been optimized, and improved arterial therapies are required.ObjectiveThe primary objectives of the VEROnA study are to evaluate the safety and tolerability of vandetanib-eluting radiopaque embolic beads (BTG-002814) in patients with resectable liver malignancies and to determine concentrations of vandetanib and the N-desmethyl metabolite in plasma and resected liver following treatment with BTG-002814.MethodsThe VEROnA study is a first-in-human, open-label, single-arm, phase 0, window-of-opportunity study of BTG-002814 (containing 100 mg vandetanib) delivered transarterially, 7 to 21 days before surgery in patients with resectable liver malignancies. Eligible patients have a diagnosis of colorectal liver metastases, or HCC (Childs Pugh A), diagnosed histologically or radiologically, and are candidates for liver surgery. All patients are followed up for 28 days following surgery. Secondary objectives of this study are to evaluate the anatomical distribution of BTG-002814 on noncontrast-enhanced imaging, to evaluate histopathological features in the surgical specimen, and to assess changes in blood flow on dynamic contrast-enhanced magnetic resonance imaging following treatment with BTG-002814. Exploratory objectives of this study are to study blood biomarkers with the potential to identify patients likely to respond to treatment and to correlate the distribution of BTG-002814 on imaging with pathology by 3-dimensional modeling.ResultsEnrollment for the study was completed in February 2019. Results of a planned interim analysis were reviewed by a safety committee after the first 3 patients completed follow-up. The recommendation of the committee was to continue the study without any changes to the dose or trial design, as there were no significant unexpected toxicities related to BTG-002814.ConclusionsThe VEROnA study is studying the feasibility of administering BTG-002814 to optimize the use of this novel technology as liver-directed therapy for patients with primary and secondary liver cancer.Trial RegistrationClinicalTrial.gov NCT03291379; https://clinicaltrials.gov/ct2/show/NCT03291379International Registered Report Identifier (IRRID)DERR1-10.2196/13696