Combined Resection of Liver and Hilar Bifurcation for Colorectal Liver Metastasis: A Single-Center Experience and Review of the Literature.

Introduction: Colorectal liver metastases (CRLM) infiltrating the hilar bifurcation is rarely described. We investigated the outcome of partial hepatectomy combined with resection of the hilar bifurcation. Methods: Data collection for patients who underwent resection for CRLM at our institution was performed prospectively from January 2008 to August 2021. Follow-up ended in August 2023. Patients with and without bile duct infiltration of CRLM were analyzed retrospectively. The primary endpoints were overall (OS) and recurrence-free survival (RFS). Results: A total of 1,156 liver resections were screened. Out of those, 18 were combined resections of the liver and the hilar bifurcation. Bile duct infiltration of CRLM was histologically proven in 5 of 18 cases. Preoperative mild obstructive jaundice occurred in 6 of 18 patients and was treated by drainage. Out of those, only 2 had a confirmed infiltration of the hilar bifurcation by CRLM. The median recurrence-free survival (RFS) was 10 months in those patients with bile duct infiltration compared to 9 months in those with no infiltration (p = 0.503). Conclusion: While CRLM is common, infiltration into the central biliary tract is rare. Tumor invasion of the biliary tree can cause jaundice, but jaundice does not necessarily mean tumor invasion. We have shown that combined resection of the liver and hilar bifurcation for CRLM is safe and infiltration of the bile duct by CRLM did not seem to have a significant effect on RFS or OS.

A CT-based radiomics tumor quality and quantity model to predict early recurrence after radical surgery for colorectal liver metastases.

PURPOSE: This study aimed to develop a tumor radiomics quality and quantity model (RQQM) based on preoperative enhanced CT to predict early recurrence after radical surgery for colorectal liver metastases (CRLM). METHODS: A retrospective analysis was conducted on 282 cases from 3 centers. Clinical risk factors were examined using univariate and multivariate logistic regression (LR) to construct the clinical model. Radiomics features were extracted using the least absolute shrinkage and selection operator (LASSO) for dimensionality reduction. The LR learning algorithm was employed to construct the radiomics model, RQQM (radiomics-TBS), combined model (radiomics-clinical), clinical risk score (CRS) model and tumor burden score (TBS) model. Inter-model comparisons were made using area under the curve (AUC), decision curve analysis (DCA) and calibration curve. Log-rank tests assessed differences in disease-free survival (DFS) and overall survival (OS). RESULTS: Clinical features screening identified CRS, KRAS/NRAS/BRAF and liver lobe distribution as risk factors. Radiomics model, RQQM, combined model demonstrated higher AUC values compared to CRS and TBS model in training, internal and external validation cohorts (Delong-test P < 0.05). RQQM outperformed the radiomics model, but was slightly inferior to the combined model. Survival curves revealed statistically significant differences in 1-year DFS and 3-year OS for the RQQM (P < 0.001). CONCLUSIONS: RQQM integrates both "quality" (radiomics) and "quantity" (TBS). The radiomics model is superior to the TBS model and has a greater impact on patient prognosis. In the absence of clinical data, RQQM, relying solely on imaging data, shows an advantage in predicting early recurrence after radical surgery for CRLM.

Viscoelastic properties of colorectal liver metastases reflect tumour cell viability.

BACKGROUND: Colorectal cancer is the third most common tumour entity in the world and up to 50% of the patients develop liver metastases (CRLM) within five years. To improve and personalize therapeutic strategies, new diagnostic tools are urgently needed. For instance, biomechanical tumour properties measured by magnetic resonance elastography (MRE) could be implemented as such a diagnostic tool. We postulate that ex vivo MRE combined with histological and radiological evaluation of CRLM could provide biomechanics-based diagnostic markers for cell viability in tumours. METHODS: 34 CRLM specimens from patients who had undergone hepatic resection were studied using ex vivo MRE in a frequency range from 500 Hz to 5300 Hz with increments of 400 Hz. Single frequency evaluation of shear wave speed and wave penetration rate as proxies for stiffness and viscosity was performed, along with rheological model fitting based on the spring-pot model and powerlaw exponent α, ranging between 0 (complete solid behaviour) and 1 (complete fluid behaviour). For histological analysis, samples were stained with H&E and categorized according to the degree of regression. Quantitative histologic analysis was performed to analyse nucleus size, aspect ratio, and density. Radiological response was assessed according to RECIST-criteria. RESULTS: Five samples showed major response to chemotherapy, six samples partial response and 23 samples no response. For higher frequencies (> 2100 Hz), shear wave speed correlated significantly with the degree of regression (p ≤ 0.05) indicating stiffer properties with less viable tumour cells. Correspondingly, rheological analysis of α revealed more elastic-solid tissue properties at low cell viability and major response (α = 0.43 IQR 0.36, 0.47) than at higher cell viability and no response (α = 0.51 IQR 0.48, 0.55; p = 0.03). Quantitative histological analysis showed a decreased nuclear area and density as well as a higher nuclear aspect ratio in patients with major response to treatment compared to patients with no response (all p < 0.05). DISCUSSION: Our results suggest that MRE could be useful in the characterization of biomechanical property changes associated with cell viability in CRLM. In the future, MRE could be applied in clinical diagnosis to support individually tailored therapy plans for patients with CRLM.

Microwave ablation for colorectal liver metastases with ultrasound fusion imaging assistance: a stratified analysis study based on tumor size and location.

PURPOSE: To investigate the efficacy of ultrasound fusion imaging-assisted microwave ablation (MWA) for patients with colorectal liver metastases (CRLM) based on stratified analysis of tumor size and location. METHODS: Patients with CRLM who underwent ultrasound fusion imaging-assisted MWA in our hospital between February 2020 and February 2023 were enrolled into this retrospective study. Ultrasound fusion imaging was used for detection, guidance, monitoring and immediate evaluation throughout the MWA procedures. Technical success, technique efficacy, local tumor progression (LTP), intrahepatic progression and overall survival (OS) were recorded and analyzed. The subgroup analysis of intrahepatic progression of MWA for CRLM was performed according to tumor size and location. RESULTS: A total of 51 patients with 122 nodules were enrolled. Both technical success and technique efficacy were acquired in all nodules. In a median follow-up period of 19 months, 2.5% of the nodules (3/122) were observed LTP. The 1-year and 2-year cumulative intrahepatic progression rates were 38.7% and 52.1% respectively. Patients were divided into subgroups according to tumor size (≥ 30 mm, n = 13; < 30 mm, n = 38) and tumor location (perivascular, n = 20; non-perivascular, n = 31 and subcapsular, n = 36; non-subcapsular, n = 15). The cumulative intrahepatic progression rates were similar between the subgroups regarding tumor size and perivascular location, while significantly higher in the subcapsular group than in the non-subcapsular group (p = 0.021). CONCLUSION: Ultrasound fusion imaging-assisted MWA exhibited satisfactory local efficacy for CRLM, especially for non-subcapsular tumors.

Assessing the performance of AI-assisted technicians in liver segmentation, Couinaud division, and lesion detection: a pilot study.

BACKGROUND: In patients with primary and secondary liver cancer, the number and sizes of lesions, their locations within the Couinaud segments, and the volume and health status of the future liver remnant are key for informing treatment planning. Currently this is performed manually, generally by trained radiologists, who are seeing an inexorable growth in their workload. Integrating artificial intelligence (AI) and non-radiologist personnel into the workflow potentially addresses the increasing workload without sacrificing accuracy. This study evaluated the accuracy of non-radiologist technicians in liver cancer imaging compared with radiologists, both assisted by AI. METHODS: Non-contrast T1-weighted MRI data from 18 colorectal liver metastasis patients were analyzed using an AI-enabled decision support tool that enables non-radiology trained technicians to perform key liver measurements. Three non-radiologist, experienced operators and three radiologists performed whole liver segmentation, Couinaud segment segmentation, and the detection and measurements of lesions aided by AI-generated delineations. Agreement between radiologists and non-radiologists was assessed using the intraclass correlation coefficient (ICC). Two additional radiologists adjudicated any lesion detection discrepancies. RESULTS: Whole liver volume showed high levels of agreement between the non-radiologist and radiologist groups (ICC = 0.99). The Couinaud segment volumetry ICC range was 0.77-0.96. Both groups identified the same 41 lesions. As well, the non-radiologist group identified seven more structures which were also confirmed as lesions by the adjudicators. Lesion diameter categorization agreement was 90%, Couinaud localization 91.9%. Within-group variability was comparable for lesion measurements. CONCLUSION: With AI assistance, non-radiologist experienced operators showed good agreement with radiologists for quantifying whole liver volume, Couinaud segment volume, and the detection and measurement of lesions in patients with known liver cancer. This AI-assisted non-radiologist approach has potential to reduce the stress on radiologists without compromising accuracy.

FASN promotes anoikis resistance in colorectal liver metastases through the ERK1/2 pathway.

PURPOSE: Colorectal cancer (CRC) is recognized as the third most common form of malignancy, with the liver frequently serving as the main site for metastasis. Anoikis resistance (AR) is critical in colorectal cancer liver metastases (CRLM). Fatty acid synthase (FASN), essential in lipid synthesis, mediates AR in many cancers. The present research examines the function of FASN in ERK1/2-mediated AR in CRLM and evaluates its therapeutic potential. METHODS: We performed scratch and migration experiment to evaluate the migration capacity of the LoVo cells. Flow cytometry was employed to identify cell apoptosis. The levels of FASN, p-ERK1/2, and proteins related to apoptosis was analyzed by Western blot. The mRNA level of FASN was determined by q-PCR after FASN silencing. In addition, we used an intrasplenic liver metastasis model of nude to assess the effect of FASN on CRLM. RESULTS: In vitro experiments showed that after FASN silencing, the cell apoptosis rate was increased, migration capability was notably decreased, the expression of p-ERK1/2, the proteins related to anti-apoptotic were significantly decreased, and the proteins related to apoptosis were significantly increased. In vivo experiments showed that AR significantly increased the number of liver metastatic foci, whereas FASN silencing significantly inhibited CRLM. CONCLUSION: These results suggest that FASN silencing suppressed AR through the ERK 1/2 pathway, which in turn suppressed CRLM.

Challenges and Opportunities for Precision Surgery for Colorectal Liver Metastases.

The incidence of colorectal cancer and colorectal liver metastases (CRLM) is increasing globally due to an interaction of environmental and genetic factors. A minority of patients with CRLM have surgically resectable disease, but for those who have resection as part of multimodal therapy for their disease, long-term survival has been shown. Precision surgery-the idea of careful patient selection and targeting of surgical intervention, such that treatments shown to be proven to benefit on a population level are the optimal treatment for each individual patient-is the new paradigm of care. Key to this is the understanding of tumour molecular biology and clinically relevant mutations, such as KRAS, BRAF, and microsatellite instability (MSI), which can predict poorer overall outcomes and a poorer response to systemic therapy. The emergence of immunotherapy and hepatic artery infusion (HAI) pumps show potential to convert previously unresectable disease to resectable disease, in addition to established systemic and locoregional therapies, but the surgeon must be wary of poor-quality livers and the spectre of post-hepatectomy liver failure (PHLF). Volume modulation, a cornerstone of hepatic surgery for a generation, has been given a shot in the arm with the advent of liver venous depletion (LVD) ensuring significantly more hypertrophy of the future liver remnant (FLR). The optimal timing of liver resection for those patients with synchronous disease is yet to be truly established, but evidence would suggest that those patients requiring complex colorectal surgery and major liver resection are best served with a staged approach. In the operating room, parenchyma-preserving minimally invasive surgery (MIS) can dramatically reduce the surgical insult to the patient and lead to better perioperative outcomes, with quicker return to function.

Ablation of Small Liver Metastases Presenting as Foci of Diffusion Restriction on MRI-Results from the Prospective Minimally Invasive Thermal Ablation (MITA) Study.

PURPOSE: Liver metastases presenting as small hyperintense foci on diffusion-weighted imaging (DWI) pose a therapeutic challenge. Ablation is generally not possible since these lesions are often occult on ultrasound and CT. The purpose of this prospective study was to assess if small liver metastases (≤10 mm) detected on DWI can be successfully localized and ablated with the Hepatic Arteriography and C-Arm CT-Guided Ablation technique (HepACAGA). MATERIALS AND METHODS: All consecutive patients with small liver metastases (≤10 mm), as measured on DWI, referred for ablation with HepACAGA between 1 January 2021, and 31 October 2023, were included. Re-ablations and ablations concomitant with another local treatment were excluded. The primary outcome was the technical success rate, defined as the intraprocedural detection and subsequent successful ablation of small liver metastases using HepACAGA. Secondary outcomes included the primary and secondary local tumor progression (LTP) rates and the complication rate. RESULTS: A total of 15 patients (26 tumors) were included, with liver metastases from colorectal cancer (73%), neuro-endocrine tumors (15%), breast cancer (8%) and esophageal cancer (4%). All 26 tumors were successfully identified, punctured and ablated (a technical success rate of 100%). After a median follow-up of 9 months, primary and secondary LTP were 4% and 0%, respectively. No complications occurred. CONCLUSION: In this proof-of-concept study, the HepACAGA technique was successfully used to detect and ablate 100% of small liver metastases identified on DWI with a low recurrence rate and no complications. This technique enables the ablation of subcentimeter liver metastases detected on MRI.

6,126 hepatectomies in 2022: current trend of outcome in Italy.

PURPOSE: Whether hospital volume affects outcome of patients undergoing hepatobiliary surgery, and whether the centralization of such procedures is justified remains to be investigated. The aim of this study was to analyze the outcome of liver surgery in Italy in relationship of hospital volume. METHODS: This is a nationwide retrospective observational study conducted on data collected by the National Italian Registry "Piano Nazionale Esiti" (PNE) 2023 that included all liver procedures performed in 2022. Outcome measure were case volume and 30-day mortality. Hospitals were classified as very high-volume (H-Vol), intermediate-volume (I-Vol), low-volume (L-Vol) and very low-volume (VL-VoL). A review on centralization process and outcome measures was added. RESULTS: 6,126 liver resections for liver tumors were performed in 327 hospitals in 2022. The 30-day mortality was 2.2%. There were 14 H-Vol, 19 I-Vol, 31 L-Vol and 263 VL-Vol hospitals with 30-day mortality of 1.7%, 2.2%, 2.6% and 3.6% respectively (P < 0.001); 220 centers (83%) performed less than 10 resections, and 78 (29%) centers only 1 resection in 2022. By considering the geographical macro-areas, the median count of liver resection performed in northern Italy exceeded those in central and southern Italy (57% vs. 23% vs. 20%, respectively). CONCLUSIONS: High-volume has been confirmed to be associated to better outcome after hepatobiliary surgical procedures. Further studies are required to detail the factors associated with mortality. The centralization process should be redesigned and oversight.

A critical appraisal of the current landscape of resectable BRAF mutated colorectal liver metastases: a systematic review.

BACKGROUND: Patients with surgically resectable BRAF-mutated colorectal liver metastases (CRLM) or limited extrahepatic disease constitute a highly selective subgroup among BRAF-mutated patients, characterized by a more indolent disease biology. This is evident in their suitability for surgical resection. However, initial studies from a decade ago presented a discouraging outlook for these patients, citing early, frequent, multifocal recurrences and a very limited median overall survival (OS) of less than two years. Our objective was to provide an updated, comprehensive, and critically assessed review of the current literature on the prognostic impact of BRAF variants in CRLM, as well as to explore optimal treatment strategies for these patients through a systematic search. METHODS: A systematic literature search of the Medline, Scopus, and CENTRAL databases for studies reporting long-term outcomes of patients with a known BRAF status was performed. RESULTS: A total of 386 unique studies were screened during the study selection process. After applying the exclusion criteria, a total of 18 studies published between 2012 and 2023 were deemed eligible for inclusion. CONCLUSIONS: In contrast to older studies, more recent studies, with larger sample sizes, have revealed that the rate of extrahepatic recurrence is comparable between BRAF-mutated and wild-type patients. Furthermore, they have reported significantly improved survival outcomes, with OS extending up to 52 months. Notably, patients with non-V600E BRAF mutations may even achieve outcomes comparable to those with wild-type BRAF CRLM. Additionally, a few recent studies have compared surgery and systemic therapies, indicating that surgery is associated with improved survival rates, even for patients with the V600E mutation. This challenges the previous belief that BRAF mutations are absolute contraindications to surgical treatment. Surgical denial for technically resectable patients may now be reserved for specific clinical scenarios, such as the presence of a BRAF V600E mutation and concurrent extrahepatic disease.

Health Economic Evaluation of Patients With Colorectal Liver Metastases Randomized to ALPPS or TSH: Analysis From the LIGRO Trial.

Objective: This is a preplanned, health economic evaluation from the LIGRO trial. One hundred patients with colorectal liver metastases (CRLM) and standardized future liver remnant <30% were randomized to associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) or two-staged hepatectomy (TSH). Summary Background Data: TSH, is an established method in advanced CRLM. ALPPS has emerged providing improved resection rate and survival. The health care costs and health outcomes, combining health-related quality of life (HRQoL) and survival into quality-adjusted life years (QALYs), of ALPPS and TSH have not previously been evaluated and compared. Methods: Costs and QALYs were compared from treatment start up to 2 years. Costs are estimated from resource use, including all surgical interventions, length of stay after interventions, diagnostic procedures and chemotherapy, and applying Swedish unit costs. QALYs were estimated by combining survival and HRQoL data, the latter being assessed with EQ-5D 3L. Estimated costs and QALYs for each treatment strategy were combined into an incremental cost-effectiveness ratio (ICER). Nonparametric bootstrapping was used to assess the joint distribution of incremental costs and QALYs. Results: The mean cost difference between ALPPS and TSH was 12,662€, [95% confidence interval (CI): -10,728-36,051; P = 0.283]. Corresponding mean difference in life years and QALYs was 0.1296 (95% CI: -0.12-0.38; P = 0.314) and 0.1285 (95% CI: -0.11-0.36; P = 0.28), respectively. The ICER was 93,186 and 92,414 for QALYs and life years as outcomes, respectively. Conclusions: Based on the 2-year data, the cost-effectiveness of ALPPS is uncertain. Further research, exploring cost and health outcomes beyond 2 years is needed.

Simulated deep CT characterization of liver metastases with high-resolution filtered back projection reconstruction.

Early diagnosis and accurate prognosis of colorectal cancer is critical for determining optimal treatment plans and maximizing patient outcomes, especially as the disease progresses into liver metastases. Computed tomography (CT) is a frontline tool for this task; however, the preservation of predictive radiomic features is highly dependent on the scanning protocol and reconstruction algorithm. We hypothesized that image reconstruction with a high-frequency kernel could result in a better characterization of liver metastases features via deep neural networks. This kernel produces images that appear noisier but preserve more sinogram information. A simulation pipeline was developed to study the effects of imaging parameters on the ability to characterize the features of liver metastases. This pipeline utilizes a fractal approach to generate a diverse population of shapes representing virtual metastases, and then it superimposes them on a realistic CT liver region to perform a virtual CT scan using CatSim. Datasets of 10,000 liver metastases were generated, scanned, and reconstructed using either standard or high-frequency kernels. These data were used to train and validate deep neural networks to recover crafted metastases characteristics, such as internal heterogeneity, edge sharpness, and edge fractal dimension. In the absence of noise, models scored, on average, 12.2% ( α = 0.012 ) and 7.5% ( α = 0.049 ) lower squared error for characterizing edge sharpness and fractal dimension, respectively, when using high-frequency reconstructions compared to standard. However, the differences in performance were statistically insignificant when a typical level of CT noise was simulated in the clinical scan. Our results suggest that high-frequency reconstruction kernels can better preserve information for downstream artificial intelligence-based radiomic characterization, provided that noise is limited. Future work should investigate the information-preserving kernels in datasets with clinical labels.

Drug-eluting beads transcatheter arterial chemoembolization combined with systemic therapy versus systemic therapy alone as first-line treatment for unresectable colorectal liver metastases.

Purpose: The purpose of this retrospective study was to compare the therapeutic efficacy and safety of drug-eluting bead transarterial chemoembolization (DEB-TACE) combined with systemic therapy to systemic therapy alone as first-line treatment for unresectable patients with colorectal liver metastases (CRLM). Methods: From December 2017 to December 2022, patients with unresectable CRLM who received systemic therapy with or without DEB-TACE as first-line treatment were included in the study. The primary endpoint was progression-free survival (PFS). Secondary endpoints were tumor response, conversion rate and adverse events. Results: Ninety-eight patients were enrolled in this study, including 46 patients who received systemic therapy combined with DEB-TACE (DEB-TACE group) and 52 patients who received systemic therapy alone (control group). The median PFS was elevated in the DEB-TACE group compared with the control group (12.1 months vs 8.4 months, p = 0.008). The disease control rate was increased in the DEB-TACE group compared with the control group (87.0% vs 67.3%, p = 0.022). Overall response rates (39.1% vs 25.0%; p = 0.133) and conversion rate to liver resection (33.8% vs 25.0%; p = 0.290) were no different between the two groups. The multivariate analysis showed that treatment options, size of liver metastasis, number of liver metastasis, synchronous metastases, and extrahepatic metastases were independent prognostic factor of PFS. Further subgroup analyses illustrated that PFS was beneficial with the DEB-TACE group in patients with age ≥ 60, male, left colon, synchronous metastases, bilobar, number of liver metastasis > 5, extrahepatic metastases, non-extrahepatic metastases, CEA level < 5 (ng/ml), and KRAS wild-type. No grade 4 or 5 toxicities related to DEB-TACE procedures were observed. Conclusion: In patients with unresectable CRLM, systemic chemotherapy with DEB-TACE as first-line treatment may improve progression-free survival and disease control rate outcomes over systemic chemotherapy alone with manageable safety profile.

Safety and feasibility of chemotherapy followed by liver transplantation for patients with definitely unresectable colorectal liver metastases: insights from the TransMet randomised clinical trial.

Background: Despite the increasing efficacy of chemotherapy (C), the 5-year survival rate for patients with unresectable colorectal liver metastases (CLM) remains around 10%. Liver transplantation (LT) might offer a curative approach for patients with liver-only disease, yet its superior efficacy compared to C alone remains to be demonstrated. Methods: The TransMet randomised multicentre clinical trial (NCT02597348) compares the curative potential of C followed by LT versus C alone in patients with unresectable CLM despite stable or responding disease on C. Patient eligibility criteria proposed by local tumour boards had to be validated by an independent committee via monthly videoconferences. Outcomes reported here are from a non-specified interim analysis. These include the eligibility of patients to be transplanted for non resectable colorectal liver metastases, as well as the feasibility and the safety of liver transplantation in this indication. Findings: From February 2016 to July 2021, 94 (60%) of 157 patients from 20 centres in 3 countries submitted to the validation committee, were randomised. Reasons for ineligibility were mainly tumour progression in 50 (32%) or potential resectability in 13 (8%). The median delay to LT after randomisation was 51 (IQR 30-65) days. Nine of 47 patients (19%, 95% CI: 9-33) allocated to the LT arm failed to undergo transplantation because of intercurrent disease progression. Three of the 38 transplanted patients (8%) were re-transplanted, one of whom (3%) died post-operatively from multi-organ failure. Interpretation: The selection process of potential candidates for curative intent LT for unresectable CLM in the TransMet trial highlighted the critical role of an independent multidisciplinary validation committee. After stringent selection, the feasibility of LT was 81%, as 19% had disease progression while on the waiting list. These patients should be given high priority for organ allocation to avoid dropout from the transplant strategy. Funding: No source of support or funding from any author to disclose for this work. The trial was supported by the Assistance Publique - Hôpitaux de Paris (AP-HP).

Conventional versus Hepatic Arteriography and C-Arm CT-Guided Ablation of Liver Tumors (HepACAGA): A Comparative Analysis.

PURPOSE: Hepatic Arteriography and C-Arm CT-Guided Ablation of liver tumors (HepACAGA) is a novel technique, combining hepatic-arterial contrast injection with C-arm CT-guided navigation. This study compared the outcomes of the HepACAGA technique with patients treated with conventional ultrasound (US) and/or CT-guided ablation. MATERIALS AND METHODS: In this retrospective cohort study, all consecutive patients with hepatocellular carcinoma (HCC) or colorectal liver metastases (CRLM) treated with conventional US-/CT-guided ablation between 1 January 2015, and 31 December 2020, and patients treated with HepACAGA between 1 January 2021, and 31 October 2023, were included. The primary outcome was local tumor recurrence-free survival (LTRFS). Secondary outcomes included the local tumor recurrence (LTR) rate and complication rate. RESULTS: 68 patients (120 tumors) were included in the HepACAGA cohort and 53 patients (78 tumors) were included in the conventional cohort. In both cohorts, HCC was the predominant tumor type (63% and 73%, respectively). In the HepACAGA cohort, all patients received microwave ablation. Radiofrequency ablation was the main ablation technique in the conventional group (78%). LTRFS was significantly longer for patients treated with the HepACAGA technique (p = 0.015). Both LTR and the complication rate were significantly lower in the HepACAGA cohort compared to the conventional cohort (LTR 5% vs. 26%, respectively; p < 0.001) (complication rate 4% vs. 15%, respectively; p = 0.041). CONCLUSIONS: In this study, the HepACAGA technique was safer and more effective than conventional ablation for HCC and CRLM, resulting in lower rates of local tumor recurrence, longer local tumor recurrence-free survival and fewer procedure-related complications.

Preoperative three-dimensional lung volumetry predicts respiratory complications in patients undergoing major liver resection for colorectal metastases.

Colorectal liver metastases (CRLM) are the predominant factor limiting survival in patients with colorectal cancer and liver resection with complete tumor removal is the best treatment option for these patients. This study examines the predictive ability of three-dimensional lung volumetry (3DLV) based on preoperative computerized tomography (CT), to predict postoperative pulmonary complications in patients undergoing major liver resection for CRLM. Patients undergoing major curative liver resection for CRLM between 2010 and 2021 with a preoperative CT scan of the thorax within 6 weeks of surgery, were included. Total lung volume (TLV) was calculated using volumetry software 3D-Slicer version 4.11.20210226 including Chest Imaging Platform extension ( http://www.slicer.org ). The area under the curve (AUC) of a receiver-operating characteristic analysis was used to define a cut-off value of TLV, for predicting the occurrence of postoperative respiratory complications. Differences between patients with TLV below and above the cut-off were examined with Chi-square or Fisher's exact test and Mann-Whitney U tests and logistic regression was used to determine independent risk factors for the development of respiratory complications. A total of 123 patients were included, of which 35 (29%) developed respiratory complications. A predictive ability of TLV regarding respiratory complications was shown (AUC 0.62, p = 0.036) and a cut-off value of 4500 cm3 was defined. Patients with TLV < 4500 cm3 were shown to suffer from significantly higher rates of respiratory complications (44% vs. 21%, p = 0.007) compared to the rest. Logistic regression analysis identified TLV < 4500 cm3 as an independent predictor for the occurrence of respiratory complications (odds ratio 3.777, 95% confidence intervals 1.488-9.588, p = 0.005). Preoperative 3DLV is a viable technique for prediction of postoperative pulmonary complications in patients undergoing major liver resection for CRLM. More studies in larger cohorts are necessary to further evaluate this technique.

Debulking Hepatectomy for Colorectal Liver Metastasis Conveys Survival Benefit.

(1) Background: Despite advances in surgical technique and systemic chemotherapy, some patients with multifocal, bilobar colorectal liver metastases (CRLM) remain unresectable. These patients may benefit from surgical debulking of liver tumors in combination with chemotherapy compared to chemotherapy alone. (2) Methods: A retrospective study including patients evaluated for curative intent resection of CRLM was performed. Patients were divided into three groups: those who underwent liver resection with recurrence within 6 months (subtotal debulked, SD), those who had the first stage only of a two-stage hepatectomy (partially debulked, PD), and those never debulked (ND). Kaplan-Meier survival curves and log-rank test were performed to assess the median survival of each group. (3) Results: 174 patients underwent liver resection, and 34 patients recurred within 6 months. Of the patients planned for two-stage hepatectomy, 35 underwent the first stage only. Thirty-two patients were never resected. Median survival of the SD, PD, and ND groups was 31 months, 31 months, and 19.5 months, respectively (p = 0.012); (4) Conclusions: Patients who underwent a debulking of CRLM demonstrated a survival benefit compared to patients who did not undergo any surgical resection. This study provides support for the evaluation of intentional debulking versus palliative chemotherapy alone in a randomized trial.

Personalized prediction of postoperative complication and survival among Colorectal Liver Metastases Patients Receiving Simultaneous Resection using machine learning approaches: A multi-center study.

BACKGROUND: To predict clinical important outcomes for colorectal liver metastases (CRLM) patients receiving colorectal resection with simultaneous liver resection by integrating demographic, clinical, laboratory, and genetic data. METHODS: Random forest (RF) models were developed to predict postoperative complications and major complications (binary outcomes), as well as progression-free survival (PFS) and overall survival (OS) (time-to-event outcomes) of the CRLM patients based on data from two hospitals. The models were validated on an external dataset from an independent hospital. The clinical utility of the models was assessed via decision curve analyses (DCA). RESULTS: There were 1067 patients included in survival prediction analyses and 1070 patients included in postoperative complication prediction analyses. The RF models provided an assessment of the model contributions of features for outcomes and suggested KRAS, BRAF, and MMR status were salient for the PFS or OS predictions. RF model of PFS showed that the Brier scores at 1-, 3-, and 5-year PFS were 0.213, 0.202 and 0.188; and the AUCs of 1-, 3- and 5-year PFS were 0.702, 0.720 and 0.743. RF model of OS revealed that Brier scores of 1-,3-, and 5-year OS were 0.040, 0.183 and 0.211; and the AUCs of 1-, 3- and 5-year OS were 0.737, 0.706 and 0.719. RF model for postoperative complication resulted in an AUC of 0.716 and a Brier score of 0.196. DCA curves clearly demonstrated that the RF models for these outcomes exhibited a superior net benefit across a wide range of threshold probabilities, signifying their favorable clinical utility. The RF models consistently exhibited robust performance in both internal cross-validation and external validation. The individualized risk profile predicted by the models closely aligned with the actual survival outcomes observed for the patients. A web-based tool (https://kanli.shinyapps.io/CRLMRF/) was provided to demonstrate the practical use of the prediction models for new patients in the clinical setting. CONCLUSION: The predictive models and a web-based tool for personalized prediction demonstrated a moderate predictive performance and favorable clinical utilities on several key clinical outcomes of CRLM patients receiving simultaneous resection, which could facilitate the clinical decision-making and inform future interventions for CRLM patients.

Are survival outcomes dependent on the tumour dose threshold of 139 Gy in patients with chemorefractory metastatic colorectal cancer treated with yttrium-90 radioembolization using glass particles? A real-world single-centre study.

OBJECTIVES: To compare the survival and objective response rate (ORR) of the patients receiving estimated tumour absorbed dose (ETAD) <140 Gy versus ETAD ≥140 Gy in patients with advanced chemorefractory colorectal carcinoma liver metastases (CRCLM) treated with yttrium-90 transarterial radioembolization (90Y TARE). METHODS: Between August 2016 and August 2023 adult patients with unresectable, chemorefractory CRCLM treated with 90Y TARE using glass particles, were retrospectively enrolled. Primary outcomes were overall survival (OS) and hepatic progression free survival (hPFS). Secondary outcome was ORR. RESULTS: A total of 40 patients with a mean age of 66.2 ± 7.8 years met the inclusion criteria. Mean ETAD for group 1 (ETAD <140 Gy) and group 2 (ETAD ≥140) were 131.2 ± 17.4 Gy versus 195 ± 45.6 Gy, respectively. The mean OS and hPFS for group 1 versus group 2 were 12 ± 10.3 months and 8.1 ± 9.3 months versus 9.3 ± 3 months and 7.1 ± 8.4 months, respectively and there were no significant differences (P = .181 and P = .366, respectively). ORR did not show significant difference between the groups (P = .432). CONCLUSION: In real-world practice, no significant difference was found in OS, hPFS, and ORR between patients who received ETAD <140 Gy versus ETAD ≥140 Gy in patients with CRCLM, in this series. ADVANCES IN KNOWLEDGE: This study demonstrated that increased tumour absorbed doses in radioembolization may not provide additional significant advantage for OS and hPFS for patients with CRCLM.