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Objectives: Hyper- or isointensity in the hepatobiliary phase (HBP) of gadoxetic acid-enhanced MRI has high specificity for focal nodular hyperplasia (FNH) but may be present in hepatocellular adenoma and carcinoma (HCA/HCC). This study aimed to identify imaging characteristics differentiating FNH and HCA/HCC. Materials and methods: This multicenter retrospective cohort study included patients with pathology-proven FNH or HCA/HCC, hyper-/isointense in the HBP of gadoxetic acid-enhanced MRI between 2010 and 2020. Diagnostic performance of imaging characteristics for the differentiation between FNH and HCA/HCC were reported. Univariable analyses, multivariable logistic regression analyses, and classification and regression tree (CART) analyses were conducted. Sensitivity analyses evaluated imaging characteristics of B-catenin-activated HCA. Results: In total, 124 patients (mean age 40 years, standard deviation 10 years, 108 female) with 128 hyper-/isointense lesions were included. Pathology diagnoses were FNH and HCA/HCC in 64 lesions (50%) and HCA/HCC in 64 lesions (50%). Imaging characteristics observed exclusively in HCA/HCC were raster and atoll fingerprint patterns in the HBP, sinusoidal dilatation on T2-w, hemosiderin, T1-w in-phase hyperintensity, venous washout, and nodule-in-nodule partification in the HBP and T2-w. Multivariable logistic regression and CART additionally found a T2-w scar indicating FNH, less than 50% fat, and a spherical contour indicating HCA/HCC. In our selected cohort, 14/48 (29%) of HCA were B-catenin activated, most (13/14) showed extensive hyper-/isointensity, and some had a T2-w scar (4/14, 29%).Conclusion: If the aforementioned characteristics typical for HCA/HCC are encountered in lesions extensively hyper- to isointense, further investigation may be warranted to exclude B-catenin-activated HCA. Clinical relevance: Hyper- or isointensity in the HBP of ga

Hepatocellular carcinoma (HCC) comprises 75 to 85% of all primary liver cancers. Current guidelines recommend a biannual HCC surveillance using ultrasound (US) for high-risk patients. However, due to its low sensitivity for detection of early-stage HCC lesions, there is an urgency for more sensitive surveillance tools. Here, we describe the potential of a short MRI surveillance (SMS) protocol for HCC, including axial T1-weighted in-out phase, fat-saturated T2-weighted, and diffusion-weighted sequences. In this prospective, multicenter, patient cohort study, patients will be recruited from existing HCC surveillance cohorts of six medical centers in The Netherlands. Surveillance patients who undergo biannual US, will be invited for SMS on the same day for 3 years. In case of a suspicious finding on either US or SMS, patients will be invited for a full MRI liver protocol including gadolinium-based contrast agent intravenous injection within 2 weeks. To our knowledge, this will be the first study to perform a head-to-head comparison with a paired US-MRI design. We hypothesize that the sensitivity of SMS for detection of early-stage HCC will be higher than that of US leading to improved survival of surveillance patients through timely HCC diagnosis. Furthermore, we hypothesize that the SMS-HCC protocol will prove cost-effective. Relevance statement The US sensitivity for detecting early-stage HCC has been reported to be less than 50%. We expect that the proposed SMS will detect at least twice as many early-stage HCC lesions and therefore prove to be cost-effective. Key points • The low sensitivity of US necessitates better imaging tools for HCC screening. • This is the first study with a paired US-MRI design. • This design will allow a head-to-head comparison in both diagnostics and patient-acceptance. • We expect that SMS can contribute to a higher survival rate. Graphical Abstract: (Figure presented.)

Histopathological growth patterns (HGPs) are independent prognosticators for colorectal liver metastases (CRLM). Currently, HGPs are determined postoperatively. In this study, we evaluated radiomics for preoperative prediction of HGPs on computed tomography (CT), and its robustness to segmentation and acquisition variations. Patients with pure HGPs [i.e. 100% desmoplastic (dHGP) or 100% replacement (rHGP)] and a CT-scan who were surgically treated at the Erasmus MC between 2003–2015 were included retrospectively. Each lesion was segmented by three clinicians and a convolutional neural network (CNN). A prediction model was created using 564 radiomics features and a combination of machine learning approaches by training on the clinician’s and testing on the unseen CNN segmentations. The intra-class correlation coefficient (ICC) was used to select features robust to segmentation variations; ComBat was used to harmonize for acquisition variations. Evaluation was performed through a 100 × random-split cross-validation. The study included 93 CRLM in 76 patients (48% dHGP; 52% rHGP). Despite substantial differences between the segmentations of the three clinicians and the CNN, the radiomics model had a mean area under the curve of 0.69. ICC-based feature selection or ComBat yielded no improvement. Concluding, the combination of a CNN for segmentation and radiomics for classification has potential for automatically distinguishing dHGPs from rHGP, and is robust to segmentation and acquisition variations. Pending further optimization, including extension to mixed HGPs, our model may serve as a preoperative addition to postoperative HGP assessment, enabling further exploitation of HGPs as a biomarker., ImPhys/Medical Imaging, ImPhys/Computational Imaging

Background: In unresectable pCCA, the standard of care is palliative chemotherapy. We investigated the feasibility and safety of adding stereotactic body radiation therapy (SBRT) after chemotherapy. Methods: Patients with unresectable pCCA, stage T1-T4N0-N1M0, ECOG 0-1, having finished 6–8 cycles of cisplatin and gemcitabine without disease progression were eligible. SBRT was planned in 15 fractions of 3.0–4.5 Gy. The primary endpoints were feasibility (defined as completing SBRT as planned) and toxicity, evaluated within 3 months after SBRT (CTCAE v4.03). A conventional “3 + 3” design was used, corresponding to a sample size of 6 patients. Dose-limiting toxicity (DLT) was defined as grade ≥ 4 hepatobiliary or grade ≥ 3 gastrointestinal toxicity. The secondary endpoints, measured from the start of radiotherapy, were local control, progression-free survival, overall survival, and quality of life (QoL). ClinicalTrials.gov identifier: NCT03307538. Results: Six patients were enrolled between November 2017 and March 2020. SBRT was delivered as planned. All patients were treated with 60Gy (15 × 4.0Gy). No SBRT-related DLT was observed. The most common grade ≥ 3 toxicity was cholangitis (n = 5). The median follow-up was 14 months. The 12-month local control rate was 80%. We observed no substantial changes in QoL. Conclusion: In patients with unresectable pCCA with stable disease after palliative chemotherapy, adding SBRT is feasible and safe. The observed local control merits an additional evaluation of effectiveness.

Histopathological growth patterns (HGPs) are independent prognosticators for colorectal liver metastases (CRLM). Currently, HGPs are determined postoperatively. In this study, we evaluated radiomics for preoperative prediction of HGPs on computed tomography (CT), and its robustness to segmentation and acquisition variations. Patients with pure HGPs [i.e. 100% desmoplastic (dHGP) or 100% replacement (rHGP)] and a CT-scan who were surgically treated at the Erasmus MC between 2003–2015 were included retrospectively. Each lesion was segmented by three clinicians and a convolutional neural network (CNN). A prediction model was created using 564 radiomics features and a combination of machine learning approaches by training on the clinician’s and testing on the unseen CNN segmentations. The intra-class correlation coefficient (ICC) was used to select features robust to segmentation variations; ComBat was used to harmonize for acquisition variations. Evaluation was performed through a 100 × random-split cross-validation. The study included 93 CRLM in 76 patients (48% dHGP; 52% rHGP). Despite substantial differences between the segmentations of the three clinicians and the CNN, the radiomics model had a mean area under the curve of 0.69. ICC-based feature selection or ComBat yielded no improvement. Concluding, the combination of a CNN for segmentation and radiomics for classification has potential for automatically distinguishing dHGPs from rHGP, and is robust to segmentation and acquisition variations. Pending further optimization, including extension to mixed HGPs, our model may serve as a preoperative addition to postoperative HGP assessment, enabling further exploitation of HGPs as a biomarker.

Background: Low skeletal muscle mass is associated with increased postoperative morbidity and worse survival following resection for perihilar cholangiocarcinoma (PHC). We investigated the predictive value of skeletal muscle mass and density for overall survival (OS) of all patients with suspected PHC, regardless of treatment. Methods: Baseline characteristics and parameters regarding disease and treatment were collected from all patients with PHC from 2002 to 2014. Skeletal muscle mass and density were measured at the level of the third lumbar vertebra on CT. The association between skeletal muscle mass and density with OS was investigated using the Kaplan-Meier method and Cox survival. Results: Median OS in 233 included patients did not differ between those with and without low skeletal muscle mass (p = 0.203), whereas a significantly different median OS (months) was observed between patients with low (HR 7.0, 95% CI 4.7-9.3) and high (HR 12.1, 95% CI 8.1-16.1) skeletal muscle density (p = 0.004). Low skeletal muscle density was independently associated with decreased OS (HR 1.78, 95% CI 1.03-3.07, p = 0.040) within the first 6 months but not after 6 months (HR 0.68, 95% CI 0.44-1.07, p = 0.093), after adjusting for age, tumour size and suspected peritoneal or other distant metastases on imaging. Conclusion: A time-dependent effect of skeletal muscle density on OS was found in patients with PHC, regardless of subsequent treatment. Low skeletal muscle density may identify patients at risk for early death.