CT-guided percutaneous marking of small pulmonary nodules with [99mTc]Tc-Macrosalb is very accurate and allows minimally invasive lung-sparing resection: a single-centre quality control.

PURPOSE: The detection of small lung nodules in thoracoscopic procedure is difficult when the lesions are not located within the outer border of the lung. In the case of ground-glass opacities, it is often impossible to palpate the lesion. Marking lung nodules using a radiotracer is a known technique. We analysed the accuracy and safety of the technique and the potential benefits of operating in a hybrid operating room. METHODS: 57 patients, including 33 (58%) females with a median age of 67 years (range 21-82) were included. In 27 patients, we marked and resected the lesion in a hybrid room. In 30 patients, the lesion was marked at the department of radiology the day before resection. [99mTc]Tc-Macrosalb (Pulmocis®) was used at an activity of 1 MBq in the hybrid room and at an activity of 3 MBq the day before to get technical feasible results. Radioactivity was detected using the Neoprobe® detection system. RESULTS: Precise detection and resection of the nodules was possible in 95% of the lesions and in 93% of the patients. Complete thoracoscopic resection was possible in 90% of the patients. Total conversion rate was 10%, but conversion due to failure of the marking of the nodule was observed in only 5% of the patients. Histology revealed 28 (37%) primary lung cancers, 24 (32%) metastases and 21 (28%) benign lesions. In 13 (23%) patients, minor complications were observed. None of them required additional interventions. CONCLUSION: The radio-guided detection of small pulmonary nodules is very accurate and safe after CT-guided injection of [99mTc]Tc-Macrosalb. Performing the operation in a hybrid room has several logistic advantages and allows using lower technetium-99m activities. The technique allows minimally invasive lung sparing resection and prevents overtreatment of benign and metastatic lesions.

Non-hypervascular hepatobiliary phase hypointense lesions detected in patients with hepatocellular carcinoma: a post hoc analysis of SORAMIC trial to identify risk factors for progression.

OBJECTIVES: To identify clinical and imaging parameters associated with progression of non-hypervascular hepatobiliary phase hypointense lesions during follow-up in patients who received treatment for hepatocellular carcinoma. METHODS: A total of 67 patients with 106 lesions were identified after screening 538 patients who underwent gadoxetic acid-enhanced MRI within the SORAMIC trial. All patients were allocated to the trial treatment according to the trial scheme, and 61 of 67 patients received systemic treatment with sorafenib (either alone or combined with locoregional therapies) during the trial period. Follow-up images after treatment according to trial scheme were reviewed for subsequent hypervascularization or > 1 cm size increase. The correlation between progression and several imaging and clinical parameters was assessed using univariable and multivariable analyses. RESULTS: On a median 178 (range, 48-1072) days follow-up period, progression was encountered in 18 (16.9%) lesions in 12 (17.9%) patients. In univariable analysis size > 12.6 mm (p = 0.070), ECOG-PS (p = 0.025), hypointensity at T1-weighted imaging (p = 0.028), hyperintensity at T2-weighted imaging (p < 0.001), hyperintensity at DWI images (p = 0.007), and cirrhosis (p = 0.065) were correlated with progression during follow-up. Hyperintensity at T2 images (p = 0.011) was an independent risk factor for progression in multivariable analysis, as well as cirrhosis (p = 0.033) and ECOG-PS (p = 0.030). CONCLUSIONS: Non-hypervascular hepatobiliary phase hypointense lesions are associated with subsequent progression after treatment in patients with HCC. T2 hyperintensity, diffusion restriction, cirrhosis, and higher ECOG-PS could identify lesions with increased risk. These factors should be considered for further diagnostic evaluation or treatment of such lesions. KEY POINTS: • Non-hypervascular hepatobiliary phase hypointense lesions have considerable risk of progression in patients with hepatocellular carcinoma receiving treatment. • T2 hyperintensity, cirrhosis, ECOG-PS, and hyperintensity at DWI are associated with increased risk of progression. • Non-hypervascular hepatobiliary phase hypointense lesions should be considered in the decision-making process of locoregional therapies, especially in the presence of these risk factors.

Stimulatory MAIT cell antigens reach the circulation and are efficiently metabolised and presented by human liver cells.

OBJECTIVE: Mucosal-associated invariant T (MAIT) cells are the most abundant T cells in human liver. They respond to bacterial metabolites presented by major histocompatibility complex-like molecule MR1. MAIT cells exert regulatory and antimicrobial functions and are implicated in liver fibrogenesis. It is not well understood which liver cells function as antigen (Ag)-presenting cells for MAIT cells, and under which conditions stimulatory Ags reach the circulation. DESIGN: We used different types of primary human liver cells in Ag-presentation assays to blood-derived and liver-derived MAIT cells. We assessed MAIT cell stimulatory potential of serum from healthy subjects and patients with portal hypertension undergoing transjugular intrahepatic portosystemic shunt stent, and patients with inflammatory bowel disease (IBD). RESULTS: MAIT cells were dispersed throughout healthy human liver and all tested liver cell types stimulated MAIT cells, hepatocytes being most efficient. MAIT cell activation by liver cells occurred in response to bacterial lysate and pure Ag, and was prevented by non-activating MR1 ligands. Serum derived from peripheral and portal blood, and from patients with IBD stimulated MAIT cells in MR1-dependent manner. CONCLUSION: Our findings reveal previously unrecognised roles of liver cells in Ag metabolism and activation of MAIT cells, repression of which creates an opportunity to design antifibrotic therapies. The presence of MAIT cell stimulatory Ags in serum rationalises the observed activated MAIT cell phenotype in liver. Increased serum levels of gut-derived MAIT cell stimulatory ligands in patients with impaired intestinal barrier function indicate that intrahepatic Ag-presentation may represent an important step in the development of liver disease.

Prognostic value of baseline imaging and clinical features in patients with advanced hepatocellular carcinoma.

AIMS: To investigate the prognostic value of baseline imaging features for overall survival (OS) and liver decompensation (LD) in patients with hepatocellular carcinoma (HCC). DESIGN: Patients with advanced HCC from the SORAMIC trial were evaluated in this post hoc analysis. Several radiological imaging features were collected from baseline computed tomography (CT) and magnetic resonance imaging (MRI) imaging, besides clinical values. The prognostic value of these features for OS and LD (grade 2 bilirubin increase) was quantified with univariate Cox proportional hazard models and multivariate Least Absolute Shrinkage and Selection Operator (LASSO) regression. RESULTS: Three hundred and seventy-six patients were included in this study. The treatment arm was not correlated with OS. LASSO showed satellite lesions, atypical HCC, peritumoral arterial enhancement, larger tumour size, higher albumin-bilirubin (ALBI) score, liver-spleen ratio <1.5, ascites, pleural effusion and higher bilirubin values were predictors of worse OS, and higher relative liver enhancement, smooth margin and capsule were associated with better OS. LASSO analysis for LD showed satellite lesions, peritumoral hypointensity in hepatobiliary phase, high ALBI score, higher bilirubin values and ascites were predictors of LD, while randomisation to sorafenib arm was associated with lower LD. CONCLUSIONS: Imaging features showing aggressive tumour biology and poor liver function, in addition to clinical parameters, can serve as imaging biomarkers for OS and LD in patients receiving sorafenib and selective internal radiation therapy for HCC.

Addition of Y-90 radioembolization increases tumor response and local disease control in hepatocellular carcinoma patients receiving sorafenib.

PURPOSE: To compare the treatment response and progression-free survival (PFS) in advanced hepatocellular carcinoma (HCC) patients who received sorafenib treatment either alone or combined with radioembolization (RE). METHODS: Follow-up images of the patients treated within a multicenter phase II trial (SORAMIC) were assessed by mRECIST. A total of 177 patients (73 combination arm [RE + sorafenib] and 104 sorafenib arm) were included in this post-hoc analysis. Response and progression characteristics were compared between treatment arms. Survival analyses were done to compare PFS and post-progression survival between treatment arms. Multivariate Cox regression analysis was used to compare survival with factors known to influence PFS in patients with HCC. RESULTS: The combination arm had significantly higher objective response rate (61.6% vs. 29.8%, p < 0.001), complete response rate (13.7% vs. 3.8%, p = 0.022), and a trend for higher disease control rate (79.2% vs. 72.1%, p = 0.075). Progression was encountered in 116 (65.5%) patients and was more common in the sorafenib arm (75% vs. 52.0%, p = 0.001). PFS (median 8.9 vs. 5.4 months, p = 0.022) and hepatic PFS were significantly better in the combination arm (9.0 vs. 5.7 months, p = 0.014). Multivariate analysis confirmed the treatment arm as an independent predictor of PFS. CONCLUSION: In advanced HCC patients receiving sorafenib, combination with RE has an additive anticancer effect on sorafenib treatment resulting in a higher and longer tumor response. However, the enhanced response did not translate into prolonged survival. Better patient selection and superselective treatment could improve outcomes after combination therapy.

Correlation of liver enhancement in gadoxetic acid-enhanced MRI with liver functions: a multicenter-multivendor analysis of hepatocellular carcinoma patients from SORAMIC trial.

OBJECTIVES: To evaluate the correlation between liver enhancement on hepatobiliary phase and liver function parameters in a multicenter, multivendor study. METHODS: A total of 359 patients who underwent gadoxetic acid-enhanced MRI using a standardized protocol with various scanners within a prospective multicenter phase II trial (SORAMIC) were evaluated. The correlation between liver enhancement on hepatobiliary phase normalized to the spleen (liver-to-spleen ratio, LSR) and biochemical laboratory parameters, clinical findings related to liver functions, liver function grading systems (Child-Pugh and Albumin-Bilirubin [ALBI]), and scanner characteristics were analyzed using uni- and multivariate analyses. RESULTS: There was a significant positive correlation between LSR and albumin (rho = 0.193; p < 0.001), platelet counts (rho = 0.148; p = 0.004), and sodium (rho = 0.161; p = 0.002); and a negative correlation between LSR and total bilirubin (rho = -0.215; p < 0.001) and AST (rho = -0.191; p < 0.001). Multivariate analysis confirmed independent significance for each of albumin (p = 0.022), total bilirubin (p = 0.045), AST (p = 0.031), platelet counts (p = 0.012), and sodium (p = 0.006). The presence of ascites (1.47 vs. 1.69, p < 0.001) and varices (1.55 vs. 1.69, p = 0.006) was related to significantly lower LSR. Similarly, patients with ALBI grade 1 had significantly higher LSR than patients with grade 2 (1.74 ± 0.447 vs. 1.56 ± 0.408, p < 0.001); and Child-Pugh A patients had a significantly higher LSR than Child-Pugh B (1.67 ± 0.44 vs. 1.49 ± 0.33, p = 0.021). Also, LSR was negatively correlated with MELD-Na scores (rho = -0.137; p = 0.013). However, one scanner brand was significantly associated with lower LSR (p < 0.001). CONCLUSIONS: The liver enhancement on the hepatobiliary phase of gadoxetic acid-enhanced MRI is correlated with biomarkers of liver functions in a multicenter cohort. However, this correlation shows variations between scanner brands. KEY POINTS: • The correlation between liver enhancement on the hepatobiliary phase of gadoxetic acid-enhanced MRI and liver function is consistent in a multicenter-multivendor cohort. • Signal intensity-based indices (liver-to-spleen ratio) can be used as an imaging biomarker of liver function. • However, absolute values might change between vendors.

Persistent acute cholecystitis after cholecystostomy - increased mortality due to treatment approach?

BACKGROUND: Percutaneous cholecystostomy (PC) is a treatment option for acute cholecystitis (AC) in cases where cholecystectomy (CCY) is not feasible due to limited health conditions. The use of PC remains questionable. The aim was to retrospectively analyse the outcome of patients after PC. METHODS: All patients who underwent PC for AC at a tertiary referral hospital over 10 years were included. Descriptive statistics, analysed mortality with and without CCY after PC, and a multivariable logistic regression for potential confounder and a landmark sensitivity analysis for immortal time bias were used. RESULTS: Of 158 patients, 79 were treated with PC alone and 79 had PC with subsequent CCY. Without CCY, 48% (38 patients) died compared to 9% with CCY. In the multivariable analysis CCY was associated with 85% lower risk of mortality. The landmark analysis was compatible with the main analyses. Direct PC-complications occurred in 17% patients. Histologically, 22/75 (29%) specimens showed chronic cholecystitis, and 76% AC. CONCLUSION: Due to the high mortality rate of PC alone, performing up-front CCY is proposed. PC represents no definitive treatment for AC and should remain a short-term solution because of the persistent inflammatory focus. According to these findings, almost all specimens showed persistent inflammation.

Response prediction of hepatocellular carcinoma undergoing transcatheter arterial chemoembolization: unlocking the potential of CT texture analysis through nested decision tree models.

OBJECTIVES: To investigate if nested multiparametric decision tree models based on tumor size and CT texture parameters from pre-therapeutic imaging can accurately predict hepatocellular carcinoma (HCC) lesion response to transcatheter arterial chemoembolization (TACE). MATERIALS AND METHODS: This retrospective study (January 2011-September 2017) included consecutive pre- and post-therapeutic dynamic CT scans of 37 patients with 92 biopsy-proven HCC lesions treated with drug-eluting bead TACE. Following manual segmentation of lesions according to modified Response Evaluation Criteria in Solid Tumors criteria on baseline arterial phase CT images, tumor size and quantitative texture parameters were extracted. HCCs were grouped into lesions undergoing primary TACE (VT-lesions) or repeated TACE (RT-lesions). Distinct multiparametric decision tree models to predict complete response (CR) and progressive disease (PD) for the two groups were generated. AUC and model accuracy were assessed. RESULTS: Thirty-eight of 72 VT-lesions (52.8%) and 8 of 20 RT-lesions (40%) achieved CR. Sixteen VT-lesions (22.2%) and 8 RT-lesions (40%) showed PD on follow-up imaging despite TACE treatment. Mean of positive pixels (MPP) was significantly higher in VT-lesions compared to RT-lesions (180.5 vs 92.8, p = 0.001). The highest AUC in ROC curve analysis and accuracy was observed for the prediction of CR in VT-lesions (AUC 0.96, positive predictive value 96.9%, accuracy 88.9%). Prediction of PD in VT-lesions (AUC 0.88, accuracy 80.6%), CR in RT-lesions (AUC 0.83, accuracy 75.0%), and PD in RT-lesions (AUC 0.86, accuracy 80.0%) was slightly inferior. CONCLUSIONS: Nested multiparametric decision tree models based on tumor heterogeneity and size can predict HCC lesion response to TACE treatment with high accuracy. They may be used as an additional criterion in the multidisciplinary treatment decision-making process. KEY POINTS: • HCC lesion response to TACE treatment can be predicted with high accuracy based on baseline tumor heterogeneity and size. • Complete response of HCC lesions undergoing primary TACE was correctly predicted with 88.9% accuracy and a positive predictive value of 96.9%. • Progressive disease was correctly predicted with 80.6% accuracy for lesions undergoing primary TACE and 80.0% accuracy for lesions undergoing repeated TACE.

Consensus report from the 8th International Forum for Liver Magnetic Resonance Imaging.

OBJECTIVES: The 8th International Forum for Liver Magnetic Resonance Imaging (MRI), held in Basel, Switzerland, in October 2017, brought together clinical and academic radiologists from around the world to discuss developments in and reach consensus on key issues in the field of gadoxetic acid-enhanced liver MRI since the previous Forum held in 2013. METHODS: Two main themes in liver MRI were considered in detail at the Forum: the use of gadoxetic acid for contrast-enhanced MRI in patients with liver cirrhosis and the technical performance of gadoxetic acid-enhanced liver MRI, both opportunities and challenges. This article summarises the expert presentations and the delegate voting on consensus statements discussed at the Forum. RESULTS AND CONCLUSIONS: It was concluded that gadoxetic acid-enhanced MRI has higher sensitivity for the diagnosis of hepatocellular carcinoma (HCC), when compared with multidetector CT, by utilising features of hyperenhancement in the arterial phase and hypointensity in the hepatobiliary phase (HBP). Recent HCC management guidelines recognise an increasing role for gadoxetic acid-enhanced MRI in early diagnosis and monitoring post-resection. Additional research is needed to define the role of HBP in predicting microvascular invasion, to better define washout during the transitional phase in gadoxetic acid-enhanced MRI for HCC diagnosis, and to reduce the artefacts encountered in the arterial phase. Technical developments are being directed to shortening the MRI protocol for reducing time and patient discomfort and toward utilising faster imaging and non-Cartesian free-breathing approaches that have the potential to improve multiphasic dynamic imaging. KEY POINTS: • Gadoxetic acid-enhanced MRI provides higher diagnostic sensitivity than CT for diagnosing HCC. • Gadoxetic acid-enhanced MRI has roles in early-HCC diagnosis and monitoring post-resection response. • Faster imaging and free-breathing approaches have potential to improve multiphasic dynamic imaging.

Comparison of glucagon-like peptide-1 receptor (GLP-1R) PET/CT, SPECT/CT and 3T MRI for the localisation of occult insulinomas: evaluation of diagnostic accuracy in a prospective crossover imaging study.

PURPOSE: Benign insulinomas are the most prevalent cause of endogenous hyperinsulinaemic hypoglycaemia (EHH) in adults, and because of their small size are difficult to localise. The purpose of the study was to test the diagnostic accuracy and clinical impact of glucagon-like peptide-1 receptor (GLP-1R) PET/CT using 68Ga-DOTA-exendin-4 in consecutive adult patients referred for localisation of insulinomas. The results were compared with 111In-DOTA-exendin-4 SPECT/CT, study-MRI and previously performed external CT and/or MRI (prior external CT/MRI). METHODS: We prospectively enrolled patients with neuroglycopenic symptoms due to EHH. GLP-1R PET/CT, SPECT/CT and study-MRI were performed in a randomised, crossover order within 3-4 days. The reference standard was surgery with histology and treatment outcome. RESULTS: From January 2014 until March 2017, 52 patients were recruited. All imaging and invasive procedures before recruitment identified suspicious lesions in 46.2% of patients. GLP-1R PET/CT, SPECT/CT and study-MRI detected suspicious lesions in 78.8%, 63.5% and 63.4% of patients, respectively. In 38 patients, conclusive histology was available for final analysis. Accuracy (95% confidence interval) for PET/CT, SPECT/CT, study-MRI and prior external CT/MRI was 93.9% (87.8-97.5%), 67.5% (58.1-76.0%), 67.6% (58.0-76.1%) and 40.0% (23.9-57.9%), respectively (all P values < 0.01, except comparison of SPECT/CT and study-MRI with a P value = 1.0). Impact on clinical management was 42.3%, 32.7% and 33.3% for PET/CT, SPECT/CT and study-MRI, respectively. Percentage reading agreement was 89.5%, 75.7%, and 71.1% for PET/CT, SPECT/CT and study-MRI, respectively. CONCLUSION: 68Ga-DOTA-exendin-4 PET/CT performed significantly better than 111In-DOTA-exendin-4 SPECT/CT and MRI in the localisation of benign insulinomas and should be considered in patients where localisation fails with CT/MRI ( ClinicalTrials.gov , NCT02127541).

Cost evaluation of gadoxetic acid-enhanced magnetic resonance imaging in the diagnosis of colorectal-cancer metastasis in the liver: Results from the VALUE Trial.

OBJECTIVES: To assess the costs of diagnostic workup and surgery of three strategies for patients with colorectal cancer liver-metastases (CRCLM): gadoxetic-acid-enhanced MRI (Gd-EOB-DTPA-MRI), MRI with extracellular contrast-media (ECCM-MRI) or contrast-enhanced MDCT (CE-MDCT). METHODS: The within-trial cost evaluation was modelled as a decision-tree to calculate the cost of diagnosis and surgery. The model used clinical outcomes and resource utilization data from a prospective randomized multicentre study. Analyses were performed for the 354-patient safety population from eight participating countries. RESULTS: The diagnostic workup cost using Gd-EOB-DTPA-MRI upfront resulted in savings compared to ECCM-MRI in all countries except Thailand (difference <2 %). Compared to CE-MDCT, initial imaging with Gd-EOB-DTPA-MRI was less costly in all countries except Korea and Spain (differences 4 and 8 %, respectively). Significantly more patients in the Gd-EOB-DTPA-MRI group were eligible for surgery (39.3 % (48/122) vs. 31.0 % (36/116) and 26.7 % (31/116) for ECCM-MRI and CE-MDCT, respectively), allowing more patients to undergo potentially curative surgery, but resulting in higher treatment costs for the strategy starting with Gd-EOB-DTPA-MRI. CONCLUSIONS: The benefits of Gd-EOB-DTPA-MRI due to less additional imaging and similar diagnostic workup costs in the three groups suggest that Gd-EOB-DTPA-MRI should be the preferred initial imaging procedure to evaluate hepatic resectability in patients with CRCLM. KEY POINTS: • Diagnostic imaging cost to evaluate resectability was similar among the groups • Cost for imaging was rather small compared to the cost of surgery • Significantly more patients in the Gd-EOB-DTPA-MRI arm were eligible for surgery • Gd-EOB-DTPA-MRI is recommended for evaluating hepatic resectability in patients with CRCLM.

Consensus report from the 7th International Forum for Liver Magnetic Resonance Imaging.

OBJECTIVES: Liver-specific MRI is a fast-growing field, with technological and protocol advancements providing more robust imaging and allowing a greater depth of information per examination. This article reports the evidence for, and expert thinking on, current challenges in liver-specific MRI, as discussed at the 7th International Forum for Liver MRI, which was held in Shanghai, China, in October 2013. METHODS: Topics discussed included the role of gadoxetic acid-enhanced MRI in the differentiation of focal nodular hyperplasia from hepatocellular adenoma and small hepatocellular carcinoma (HCC) from small intrahepatic cholangiocarcinoma (in patients with chronic liver disease), the differentiation of low-grade dysplastic nodule (DN) from pre-malignant high-grade DN and early HCC, and treatment planning and assessment of treatment response for patients with HCC and colorectal liver metastasis. Optimization of the gadoxetic acid-enhanced MRI protocol to gain robust arterial and hepatobiliary phase images was also discussed. RESULTS AND CONCLUSIONS: Gadoxetic acid-enhanced MRI demonstrates added value for the detection and characterization of focal liver lesions and shows promise in a number of new indications, including regional liver functional assessment and patient monitoring after therapy; however, more data are needed in some areas, and further developments are needed to translate cutting-edge techniques into clinical practice. KEY POINTS: Liver-specific MRI is a fast-growing field, with many technological and protocol advancements. Gadoxetic acid-enhanced MRI demonstrates value for detecting and characterizing focal liver lesions. Gadoxetic acid-enhanced MRI shows promise in regional functional assessment and patient monitoring. Further developments are needed to translate cutting-edge techniques into clinical practice.

Pilot randomized trial of selective internal radiation therapy vs. chemoembolization in unresectable hepatocellular carcinoma.

BACKGROUND & AIMS: To compare selective internal radiation therapy (SIRT) with transarterial chemoembolization (TACE), the standard-of-care for intermediate-stage unresectable, hepatocellular carcinoma (HCC), as first-line treatment. METHODS: SIRTACE was an open-label multicenter randomized-controlled pilot study, which prospectively compared primarily safety and health-related quality of life (HRQoL) changes following TACE and SIRT. Patients with unresectable HCC, Child-Pugh ≤B7, ECOG performance status ≤2 and ≤5 liver lesions (≤20 cm total maximum diameter) without extrahepatic spread were randomized to receive either TACE (at 6-weekly intervals until tumour enhancement was not observed on MRI or disease progression) or single-session SIRT (yttrium-90 resin microspheres). RESULTS: Twenty-eight patients with BCLC stage A (32.1%), B (46.4%) or C (21.4%) received either a mean of 3.4 (median 2) TACE interventions (N = 15) or single SIRT (N = 13). Both treatments were well tolerated. Despite SIRT patients having significantly worse physical functioning at baseline, at week-12, neither treatment had a significantly different impact on HRQoL as measured by Functional Assessment of Cancer Therapy-Hepatobiliary total or its subscales. Both TACE and SIRT were effective for the local control of liver tumours. Best overall response-rate (RECIST 1.0) of target lesions were 13.3% and 30.8%, disease control rates were 73.3% and 76.9% for TACE and SIRT, respectively. Two patients in each group were down-staged for liver transplantation (N = 3) or radiofrequency ablation (N = 1). CONCLUSIONS: Single-session SIRT appeared to be as safe and had a similar impact on HRQoL as multiple sessions of TACE, suggesting that SIRT might be an alternative option for patients eligible for TACE.

Hepatic steatosis: effect on hepatocyte enhancement with gadoxetate disodium-enhanced liver MR imaging.

PURPOSE: To investigate the effect of hepatic steatosis on enhancement of liver parenchyma with gadoxetate disodium-enhanced MR imaging. MATERIALS AND METHODS: Gadoxetate disodium-enhanced MR images of 166 patients were analyzed. Liver-spleen contrast and liver-spleen relative enhancement ratio on three-dimensional gradient echo T1-weighted images with fat suppression 20 minutes after injection of gadoxetate disodium were evaluated in correlation with fat signal fraction using the Pearson correlation coefficient and also compared between patients with normal liver parenchyma (n = 115) and with liver steatosis (n = 51) using the Student t-test. RESULTS: The liver-spleen contrast at hepatobiliary phase showed inverse correlations with the fat signal fraction (r = -0.36; P < 0.01), while the liver-spleen relative enhancement ratio showed no statistical correlation with the fat signal fraction (P = 0.80). The liver-spleen contrast in the group with steatotic liver was significantly lower than that in the group with normal livers (P < 0.001). There was no significant difference in the relative enhancement ratio between the two groups (P = 0.85). CONCLUSION: Our results may suggest that hepatic steatosis does not affect the uptake of gadoxetate disodium into hepatocytes and are considered crucial as background knowledge in extending the use of gadoxetate disodium-enhanced MR imaging to quantitate liver function.

Diagnostic accuracy of dynamic gadoxetic-acid-enhanced MRI and PET/CT compared in patients with liver metastases from neuroendocrine neoplasms.

PURPOSE: To evaluate the diagnostic accuracy of dynamic-contrast-enhanced (DCE) MRI in comparison to both (18)F-FDG- and (68)Ga-DOTATATE-PET/CT in patients with liver metastases of neuroendocrine neoplasms (NEN). MATERIALS AND METHODS: Thirty-two patients with hepatic metastases from NEN were examined both in DCE-MRI and positron emission tomography/computed tomography (PET/CT), using either (18)F-fluorodeoxyglucose ((18)F-FDG) or (68)Ga-DOTATATE as tracer. DCE-MRI was performed at 3 Tesla with Gd-EOB-DTPA acquiring 48 slices every 2.2 s for 5 min. Three regions of interest (ROIs) representing liver background and liver metastases were defined in fat-saturated T1w three-dimensional GRE MRI sequences in the hepatobiliary phase. Corresponding ROIs were then defined in the DCE-MRI- and in the PET/CT-dataset. Area under the curve (AUC) was calculated for the differentiation between metastases and liver background for DCE-MRI and PET-CT parameters. RESULTS: AUC was very high for SUVmean (mean standardized uptake value) derived from (68)Ga-DOTATATE- (AUC = 0.966), and (18)F-FDG-PET/CT (AUC = 0.989). For DCE-MRI parameters, arterial flow fraction and intracellular uptake fraction showed the highest AUCs (AUC = 0.826, AUC = 0.819, respectively). The combination of those two had an AUC of 0.949. The combination of DCE-MRI and PET-CT parameters resulted in the highest AUC. CONCLUSION: Both PET/CT parameters and DCE-MRI perfusion parameters show a high diagnostic accuracy in the distinction between liver metastases and liver tissue. Our data suggest that both modalities provide complementary information.

Combination of antiangiogenic therapy using the mTOR-inhibitor everolimus and low-dose chemotherapy for locally advanced and/or metastatic pancreatic cancer: a dose-finding study.

Pancreatic adenocarcinomas are associated with a poor survival prognosis. Besides curative surgical resection, only limited therapies with modest impact are available. New evidence suggests that the mammalian target of rapamycin pathway may be involved in the pathogenesis of neuroendocrine tumors, and breast and renal cell cancer. The phase I study described here was therefore designed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of escalating doses of the mammalian target of rapamycin inhibitor everolimus in combination with gemcitabine in patients with advanced pancreatic cancer. Eligible patients had histologically confirmed locally advanced and/or metastatic pancreatic carcinoma and were administered 5 mg everolimus every second day (cohort 1, 2, 3) or 5 mg daily (cohort 4, 5) in combination with escalating low-dose gemcitabine. It was found that if two patients showed DLTs, MTD was reached and gemcitabine dose escalation was stopped at this level. Twenty-seven patients were enrolled in the study (cohort 1: n=3; cohort 2: n=4; cohort 3: n=6; cohort 4: n=7; cohort 5: n=7) and received a maximum 600 mg gemcitabine/week. In cohort 5, two of the six patients experienced DLTs (grade 3 liver toxicity lasting for>7 days). MTD was measured as 400 mg/m/week gemcitabine plus 5 mg/day everolimus. The MTD of a low-dose gemcitabine treatment in combination with everolimus was determined and no new safety concerns were identified in patients with advanced pancreatic cancer.

A Retrospective Cohort Analysis of Transarterial Chemoembolization for Hepatocellular Cancer at a Tertiary Center in Switzerland.

Background/Objectives: International guidelines recommend transarterial chemoembolization (TACE) for intermediate-stage hepatocellular carcinoma (HCC). However, it is used outside these recommendations and has proven beneficial in prolonging survival. Since the role of TACE outside BCLC stage B is unclear, the present study analyzed the results of TACE performed at a tertiary center in Switzerland for different treatment groups, and aims to highlight the treatment outcomes for these groups. Methods: This retrospective cohort study includes 101 HCC patients undergoing TACE at our center. Patients were further subdivided into groups according to therapy combinations (therapies applied before and after index TACE). Kaplan-Meier survival curves were calculated for the Barcelona Center for Liver Cancer (BCLC) subgroups. Results: After TACE, the median survival was 28.1 months for BCLC 0, 31.5 months for BCLC A, 20.5 months for BCLC B, 10.8 for BCLC C, and 7.5 months for BCLC D. A lesion size larger than 55 mm was negatively associated with survival (HR 2.8, 95% CI 1.15-6.78). Complications occurred after TACE procedures: Clavien-Dindo I + II = 30, Clavien-Dindo > 3 = 2. Conclusions: TACE was performed in a substantial part of our cohort outside of routinely used treatment guidelines. The combination of the survival data and complication rate in these patients suggests it was a safe and beneficial strategy. Furthermore, our data show that in our cohort, the survival benefit associated with TACE was restricted to patients with a lesion size smaller than 55 mm.

Safety and efficacy of Holmium-166 selective internal radiotherapy of primary and secondary liver cancer confirmed by real-world data.

Purpose: Holmium-166 has emerged as a promising option for selective internal radiotherapy (SIRT) for hepatic malignancies, but data on routine clinical use are lacking. The purpose of this study was to describe the safety and effectiveness of Holmium-166 SIRT in real-world practice through retrospective analysis of a multicenter registry. Methods: Retrospective analysis was conducted on Holmium-166 SIRT procedures performed between July 15, 2019, and July 15, 2021, across seven European centers. Treatment planning, treatment realization and post-treatment follow-up were conducted according to routine local practice. Safety and effectiveness data were extracted from the patients' health records. Primary endpoint analysis was assessed for the entire study population with separate analysis for subgroups with hepatocellular carcinoma, metastatic colorectal cancer and intrahepatic cholangiocarcinoma. Results: A total of 167 SIRT procedures in 146 patients (mean age 66 ± 11 years, 68% male) were retrospectively evaluated. Most common tumor entities were hepatocellular carcinoma (n=55), metastatic colorectal cancer (n=35), intrahepatic cholangiocarcinoma (n=19) and metastatic neuroendocrine tumors (n=10). Nine adverse events grade ≥ 3 according to Common Terminology Criteria for Adverse Events were recorded, including one fatal case of radioembolization-induced liver disease. Response rates and median overall survival for the above mentioned subgroups were comparable to results from previous Holmium-166 trials as well as to results from Yttrium-90 registries. Conclusion: This study confirms that the safety and effectiveness of Holmium-166 SIRT derived from prospective trials also applies in routine clinical practice, reinforcing its potential as a viable treatment option for primary and secondary liver cancer.

Skeletal muscle quality predicts overall survival in advanced liver hepatocellular carcinoma treated with SIRT and sorafenib: A subanalysis of the SORAMIC trial.

BACKGROUND AND AIMS: Our purpose was to assess the impact of muscle quality on overall survival (OS) in patients with advanced HCC. METHODS: This is a subanalysis of the SORAMIC trial. Overall, 363 patients were included. The SIRT/Sorafenib treatment group comprised 182 patients and the sorafenib group 181 patients. Myosteatosis was defined as skeletal muscle density (SMD) < 41 HU for patients with a body mass index up to 24.9 kg/m2 and <33 HU for patients with a body mass index ≥25 kg/m2. Albumin-gauge score was calculated as follows: serum albumin (g/dL) × SMD (HU). To assess the impact of muscle quality on clinical variables and OS, a Cox regression model was used. Hazard ratios are presented together with 95 % confidence intervals (95 % CI). Kaplan-Meier curves were used for survival analysis. RESULTS: In the SIRT/sorafenib cohort, low albumin-gauge score was an independent predictor of worse OS, HR = 1.74, CI 95% (1.16-2.62), p = 0.01. In the sorafenib cohort, muscle quality parameters did not predict OS. In alcohol-induced HCC (n = 129), myosteatosis independently predicted OS, HR = 1.85, CI 95% (1.10; 3.12), p = 0.02. In viral-induced HCC (n = 99), parameters of muscle quality did not predict OS. In patients with NASH/Non-alcoholic fatty liver disease (NAFLD) induced HCC, albumin-gauge score was a strong independent predictor of worse OS in the subgroup undergoing combined treatment with SIRT and sorafenib, HR = 9.86, CI 95% (1.12; 86.5), p = 0.04. CONCLUSIONS: Myosteatosis predicts independently worse OS in patients with alcohol-induced HCC undergoing combined treatment with SIRT and sorafenib. In patients with NASH/NAFLD induced HCC undergoing treatment with SIRT and sorafenib, albumin-gauge score predicts independently worse OS. IMPACT AND IMPLICATIONS: Associations between parameters of muscle quality and OS are different in accordance to the treatment strategy and etiology of HCC. These findings highlight the prognostic potential of skeletal muscle quality in patients with advanced HCC.