RECIST 1.1 versus clinico-radiological response assessment for locally advanced cervical cancer: implications on interpreting survival outcomes of future trials.

OBJECTIVE: To investigate differences in standard clinico-radiological evaluation versus Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 for reporting survival outcomes in patients with locally advanced cervical cancer treated with chemoradiation and brachytherapy. METHODS: Between November 2017 and March 2020, patients recruited in cervical cancer trials were identified. MRI at diagnosis and at least one follow-up imaging was mandatory. Disease-free survival and progression-free survival were determined using standard evaluation (clinical examination and symptom-directed imaging) and RECIST 1.1. Agreement between criteria was estimated using κ value. Sensitivity analysis was done to test the sensitivity, specificity, and accuracy of RECIST 1.1 in detecting response to treatment. RESULTS: Sixty-nine eligible patients had at least one target lesion. Thirty-three patients (47.8%) had pathological lymph nodes. Of these 33 patients, RECIST 1.1 classified only 18% (6/33) as 'target nodal lesions' and the remaining nodes as 'non-target'. There were 6 (8.7%) and 8 (11.6%) patients with disease events using RECIST 1.1 and standard evaluation, respectively. The disease-free survival at 12, 18, and 24 months using RECIST 1.1 was 94.2%, 91.2%, 91.2%, and with standard evaluation was 94.2%, 89.7%, and 88.2%, respectively (p=0.58). Whereas, progression-free survival at 12, 18, and 24 months using RECIST 1.1 and standard evaluation were same (94.2%, 91.2%, and 91.2%, respectively). The κ value was 0.84, showing strong agreement in assessing disease-free survival, although an absolute difference of 3% between endpoint assessment methodologies. RECIST 1.1 had a sensitivity of 75% (95% CI 34.91% to 96.81%), specificity of 100% (95% CI 94.13% to 100%), and accuracy of 97.1% (95% CI 89.92% to 99.65%). CONCLUSIONS: The study showed 1.5% and 3% difference in disease-free survival at 18 and 24 months and no difference in progression-free survival between RECIST 1.1 and standard evaluation in a patient cohort with low event rate.

Automated Assessment of T2-Weighted MRI to Differentiate Malignant and Benign Primary Solid Liver Lesions in Noncirrhotic Livers Using Radiomics.

RATIONALE AND OBJECTIVES: Distinguishing malignant from benign liver lesions based on magnetic resonance imaging (MRI) is an important but often challenging task, especially in noncirrhotic livers. We developed and externally validated a radiomics model to quantitatively assess T2-weighted MRI to distinguish the most common malignant and benign primary solid liver lesions in noncirrhotic livers. MATERIALS AND METHODS: Data sets were retrospectively collected from three tertiary referral centers (A, B, and C) between 2002 and 2018. Patients with malignant (hepatocellular carcinoma and intrahepatic cholangiocarcinoma) and benign (hepatocellular adenoma and focal nodular hyperplasia) lesions were included. A radiomics model based on T2-weighted MRI was developed in data set A using a combination of machine learning approaches. The model was internally evaluated on data set A through cross-validation, externally validated on data sets B and C, and compared to visual scoring of two experienced abdominal radiologists on data set C. RESULTS: The overall data set included 486 patients (A: 187, B: 98, and C: 201). The radiomics model had a mean area under the curve (AUC) of 0.78 upon internal validation on data set A and a similar AUC in external validation (B: 0.74 and C: 0.76). In data set C, the two radiologists showed moderate agreement (Cohen's κ: 0.61) and achieved AUCs of 0.86 and 0.82. CONCLUSION: Our T2-weighted MRI radiomics model shows potential for distinguishing malignant from benign primary solid liver lesions. External validation indicated that the model is generalizable despite substantial MRI acquisition protocol differences. Pending further optimization and generalization, this model may aid radiologists in improving the diagnostic workup of patients with liver lesions.

Impact of EUS in liver transplantation workup for patients with unresectable perihilar cholangiocarcinoma.

BACKGROUND AND AIMS: For a highly selected group of patients with unresectable perihilar cholangiocarcinoma (pCCA), liver transplantation (LT) is a treatment option. The Dutch screening protocol comprises nonregional lymph node (LN) assessment by EUS, and whenever LN metastases are identified, further LT screening is precluded. The aim of this study is to investigate the yield of EUS in patients with pCCA who are potentially eligible for LT. METHODS: In this retrospective, nationwide cohort study, all consecutive patients with suspected unresectable pCCA who underwent EUS in the screening protocol for LT were included from 2011 to 2021. During EUS, sampling of a "suspicious" nonregional LN was performed based on the endoscopist's discretion. The primary outcome was the added value of EUS, defined as the number of patients who were precluded from further screening because of malignant LNs. RESULTS: A total of 75 patients were included in whom 84 EUS procedures were performed, with EUS-guided tissue acquisition confirming malignancy in LNs in 3 of 75 (4%) patients. In the 43 who underwent surgical staging according to the protocol, nonregional LNs with malignancy were identified in 6 (14%) patients. Positive regional LNs were found in 7 patients in post-LT-resected specimens. CONCLUSIONS: Our current EUS screening for the detection of malignant LNs in patients with pCCA eligible for LT shows a limited but clinically important yield. EUS with systematic screening of all LN stations, both regional and nonregional, and the sampling of suspicious lymph nodes according to defined and set criteria could potentially increase this yield.

18 F-FDG PET/MRI for restaging esophageal cancer after neoadjuvant chemoradiotherapy.

PURPOSE: The purpose of this study was to investigate whether 18F-fluorodeoxyglucose ( 18 F-FDG) PET/MRI may potentially improve tumor detection after neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer. METHODS: This was a prospective, single-center feasibility study. At 6-12 weeks after nCRT, patients underwent standard 18 F-FDG PET/computed tomography (CT) followed by PET/MRI, and completed a questionnaire to evaluate burden. Two teams of readers either assessed the 18 F-FDG PET/CT or the 18 F-FDG PET/MRI first; the other scan was assessed 1 month later. Maximum standardized uptake value corrected for lean body mass (SUL max ) and mean apparent diffusion coefficient (ADC mean ) were measured at the primary tumor location. Histopathology of the surgical resection specimen served as the reference standard for diagnostic accuracy calculations. When patients had a clinically complete response and continued active surveillance, response evaluations until 9 months after nCRT served as a proxy for ypT and ypN (i.e. 'ycT' and 'ycN'). RESULTS: In the 21 included patients [median age 70 (IQR 62-75), 16 males], disease recurrence was found in the primary tumor in 14 (67%) patients (of whom one ypM+, detected on both scans) and in locoregional lymph nodes in six patients (29%). Accuracy (team 1/team 2) to detect yp/ycT+ with 18 F-FDG PET/MRI vs. 18 F-FDG PET/CT was 38/57% vs. 76/61%. For ypN+, accuracy was 63/53% vs. 63/42%, resp. Neither SUL max (both scans) nor ADC mean were discriminatory for yp/ycT+ . Fourteen of 21 (67%) patients were willing to undergo a similar 18 F-FDG PET/MRI examination in the future. CONCLUSION: 18 F-FDG PET/MRI currently performs comparably to 18 F-FDG PET/CT. Improvements in the scanning protocol, increasing reader experience and performing serial scans might contribute to enhancing the accuracy of tumor detection after nCRT using 18 F-FDG PET/MRI. TRIAL REGISTRATION: Netherlands Trial Register NL9352.

FAPI PET versus FDG PET, CT or MRI for Staging Pancreatic-, Gastric- and Cholangiocarcinoma: Systematic Review and Head-to-Head Comparisons of Diagnostic Performances.

INTRODUCTION: There is a pressing demand for the development of cancer-specific diagnostic imaging tools, particularly for staging of pancreatic-, gastric- or cholangiocarcinoma, as current diagnostic imaging techniques, including CT, MRI and PET using FDG, are not fully adequate. The novel PET-tracer "FAPI" has the potential to visualize even small tumour deposits employing the tumour-specific expression of fibroblast-activating protein (FAP) in malignant cells. METHODS: We performed a systematic review to select studies investigating the use of FAPI PET for staging pancreatic-, gastric- and cholangiocarcinoma (PROSPERO CRD42022329512). Patient-wise and lesion-wise comparisons were performed for primary tumour (T), lymph nodes (N), organ metastases (M) and peritoneal carcinomatosis (PC). Maximum standardized uptake values (SUVmax) and tumour-to-background ratios (TBR) were compared between PET using FAPI versus FDG (if reported). RESULTS: Ten articles met the inclusion criteria. In all studies, FAPI PET showed superiority over FDG-PET/CT/MRI for the detection of T, N, M and PC, both in the patient-wise and in lesion-wise comparisons (when performed). Additionally, higher SUVmax and TBRmax values were reported for use of FAPI compared to FDG. CONCLUSIONS: The positive results of this review warrant prospective clinical studies to investigate the accuracy and clinical value of FAPI PET for diagnosing and staging patients with pancreatic-, gastric- and cholangiocarcinoma.

Socioeconomic differences in participation and diagnostic yield within the Dutch national colorectal cancer screening programme with faecal immunochemical testing.

BACKGROUND: CRC mortality rates are higher for individuals with a lower socioeconomic status (SES). Screening could influence health inequalities. We therefore aimed to investigate SES differences in participation and diagnostic yield of FIT screening. METHODS: All invitees in 2014 and 2015 in the Dutch national CRC screening programme were included in the analyses. We used area SES as a measure for SES and divided invitees into quintiles, with Quintile 1 being the highest SES. Logistic regression analysis was used to compare the participation rate, positivity rate, colonoscopy uptake, positive predictive value (PPV) and detection rate across the SES groups. RESULTS: Participation to FIT screening was significantly lower for Quintile 5 (67.0%) compared to the other Quintiles (73.0% to 75.1%; adjusted OR quintile 5 versus quintile 1: 0.73, 95%CI: 0.72-0.74), as well as colonoscopy uptake after a positive FIT (adjusted OR 0.73, 95%CI: 0.69-0.77). The detection rate per FIT participant for advanced neoplasia gradually increased from 3.3% in Quintile 1 to 4.0% in Quintile 5 (adjusted OR 1.20%, 95%CI 1.16-1.24). As a result of lower participation, the yield per invitee was similar for Quintile 5 (2.04%) and Quintile 1 (2.00%), both being lower than Quintiles 2 to 4 (2.20%-2.28%). CONCLUSIONS: Screening has the potential to reduce health inequalities in CRC mortality, because of a higher detection in participants with a lower SES. However, in the Dutch screening programme, this is currently offset by the lower participation in this group.

Study protocol for a multicentre nationwide prospective cohort study to investigate the natural course and clinical outcome in benign liver tumours and cysts in the Netherlands: the BELIVER study.

INTRODUCTION: Benign liver tumours and cysts (BLTCs) comprise a heterogeneous group of cystic and solid lesions, including hepatic haemangioma, focal nodular hyperplasia and hepatocellular adenoma. Some BLTCs, for example, (large) hepatocellular adenoma, are at risk of complications. Incidence of malignant degeneration or haemorrhage is low in most other BLTCs. Nevertheless, the diagnosis BLTC may carry a substantial burden and patients may be symptomatic, necessitating treatment. The indications for interventions remain matter of debate. The primary study aim is to investigate patient-reported outcomes (PROs) of patients with BLTCs, with special regards to the influence of invasive treatment as compared with the natural course of the disease. METHODS AND ANALYSIS: A nationwide observational cohort study of patients with BLTC will be performed between October 2021 and October 2026, the minimal follow-up will be 2 years. During surveillance, a questionnaire regarding symptoms and their impact will be sent to participants on a biannual basis and more often in case of invasive intervention. The questionnaire was previously developed based on PROs considered relevant to patients with BLTCs and their caregivers. Most questionnaires will be administered by computerised adaptive testing through the Patient-Reported Outcomes Measurement Information System. Data, such as treatment outcomes, will be extracted from electronic patient files. Multivariable analysis will be performed to identify patient and tumour characteristics associated with significant improvement in PROs or a complicated postoperative course. ETHICS AND DISSEMINATION: The study was assessed by the Medical Ethics Committee of the University Medical Center Groningen and the Amsterdam UMC. Local consultants will provide information and informed consent will be asked of all patients. Results will be published in a peer-reviewed journal. STUDY REGISTRATION: NL8231-10 December 2019; Netherlands Trial Register.

A multicentre retrospective analysis on growth of residual hepatocellular adenoma after resection.

BACKGROUND & AIMS: Hepatocellular adenoma (HCA) is a benign liver tumour that may require resection in select cases. The aim of this study was to the assess growth of residual HCA in the remnant liver and to advise on an evidence-based management strategy. METHOD: This multicentre retrospective cohort study included all patients with HCA who underwent surgery of HCA and had residual HCA in the remnant liver. Growth was defined as an increase of >20% in transverse diameter (RECIST criteria). Data on patient and HCA characteristics, diagnostic work-up, treatment and follow-up were documented and analysed. RESULTS: A total of 134 patients were included, one male. At diagnosis, median age was 38yrs (IQR 30.0-44.0) and median BMI was 29.9 kg/m2 (IQR 24.6-33.3). After resection, median number of residual sites of HCA was 3 (IQR 2-6). Follow-up of residual HCA showed regression in 24.6%, stable HCA in 61.9% and growth of at least one lesion in 11.2%. Three patients (2.2%) developed new HCA that were not visible on imaging prior to surgery. Four patients (3%, one male) underwent an intervention as growth was progressive. No statistically significant differences in clinical characteristics were found between patients with growing residual or new HCA versus those with stable or regressing residual HCA. CONCLUSION: In patients with multiple HCA who undergo resection, growth of residual HCA is not uncommon but interventions are rarely needed as most lesions stabilize and do not show progressive growth. Surveillance is indicated when residual HCA show growth after resection, enabling intervention in case of progressive growth.

Response to Letter: Intrapatient Comparison of the Hepatobiliary Phase of Gd-BOPTA and Gd-EOB-DTPA in the Differentiation of HCA From FNH.

LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY STAGE: 3 J. Magn. Reson. Imaging 2020;52:1281-1282.

Growth of hepatocellular adenoma during pregnancy: A prospective study.

BACKGROUND & AIMS: The presence of hepatocellular adenoma (HCA) in pregnant women requires special consideration, as it has been reported to carry the risk of growth and clinically significant haemorrhage. In this prospective study we assessed aspects of growth of HCA <5 cm during pregnancy. METHODS: This was a multicentre prospective cohort study in pregnant women with suspected HCA <5 cm on imaging. Definitive HCA diagnosis was established by MRI with hepatobiliary contrast agents (LCE-MRI), preferably before pregnancy. If at study inclusion a definitive diagnosis was lacking, LCE-MRI was performed after giving birth. Growth of the adenoma (defined as an increase of >20%) was closely monitored with ultrasound examinations throughout pregnancy. RESULTS: Of the 66 women included, 18 were excluded from analysis because postpartum LCE-MRI did not confirm the diagnosis of HCA and showed the lesion to be focal nodular hyperplasia. The remaining 48 women, with an HCA confirmed by LCE-MRI, were followed during 51 pregnancies. Median age was 30 years (IQR 27-33) and median body mass index 31.9 kg/m2 (IQR 26.3-36.6). Growth of HCA was seen in 13 of the pregnancies (25.5%); the median increase was 14 mm (IQR 8-19). One woman whose HCA grew to >70 mm successfully underwent transarterial embolization at week 26 of pregnancy to prevent further growth. The other 50 pregnancies proceeded without complications. CONCLUSION: This study suggests that an HCA <5 cm confers minimal risk to a pregnant woman and none to her child. HCA increased in size during a quarter of pregnancies, so we recommend close monitoring with ultrasound examinations, enabling intervention if needed. In light of the large proportion of misdiagnosed HCA, LCE-MRI should be performed to prevent unnecessary anxiety in women with a benign liver lesion. LAY SUMMARY: The presence of hepatocellular adenoma in pregnant women requires special consideration, as it carries the risk of growth and haemorrhage. In this study we followed 48 patients with hepatocellular adenoma <5 cm during 51 pregnancies and found that a hepatocellular adenoma during pregnancy confers minimal risk to the pregnant woman and none to her child.

Incidence of Interval Colorectal Cancer After Negative Results From First-Round Fecal Immunochemical Screening Tests, by Cutoff Value and Participant Sex and Age.

BACKGROUND & AIMS: We evaluated the incidence of interval cancers between the first and second rounds of colorectal cancer (CRC) screening with the FOB-Gold fecal immunochemical test (FIT), and the effects of different cutoff values and patient sex and age. METHODS: We collected data from participants in a population-based CRC screening program in the Netherlands who had a negative result from a first-round of FIT screening. We calculated the cumulative incidence of interval cancer after a negative result from a FIT and the sensitivity of the FIT for detection of CRC at a low (15 µg Hb/g feces) and high (47 µg Hb/g feces) cutoff value. RESULTS: Among the 485,112 participants with a negative result from a FIT, 544 interval cancers were detected; 126 were in the 111,800 participants with negative results from a FIT with the low cutoff value and 418 were in the 373,312 FIT participants with negative results from a FIT with the high cutoff value. The mean age of participants tested with the low cutoff value was 72.0 years and the mean age of participants tested the high cutoff value was 66.7 years. The age-adjusted 2-year cumulative incidence of interval cancer after a negative result from a FIT were 9.5 per 10,000 persons at the low cutoff value vs 13.8 per 10,000 persons at the high cutoff value (P < .005). The age-adjusted sensitivity of the FIT for CRC were 90.5% for the low cutoff value vs 82.9% for the high cutoff (P < .0001). The FIT identified men with CRC with 87.4% sensitivity and women with CRC with 82.6% sensitivity (P < .001). CONCLUSIONS: In an analysis of data from a FIT population-based screening program in the Netherlands, we found that incidence of interval CRC after a negative result from a FIT to be low. Although the sensitivity of detection of CRC decreased with a higher FIT cutoff value, it remained above 80%.

The second round of the Dutch colorectal cancer screening program: Impact of an increased fecal immunochemical test cut-off level on yield of screening.

The Dutch colorectal cancer (CRC) screening program started in 2014, inviting the target population biennially to perform a fecal immunochemical test (FIT). We obtained prospectively collected data from the national screening information-system to present the results of the second round (2016) and evaluate the impact of increasing the FIT cut-off halfway through the first round from 15 to 47 µg Hb/g feces on outcomes in the second round. Second round screening was done with a 47 µg Hb/g feces FIT cut-off. Participants were classified based on first round participation status as either FIT (15,47) or FIT (47,47) participants, and previous nonparticipants. In total, 348,891 (75.9%) out of 459,740 invitees participated in the second round. Participation rates were 93.4% among previous participants and 21.0% among previous non-participants. FIT(47,47) participants had a significantly higher detection rate of AN (15.3 vs. 10.4 per 1,000 participants) compared to FIT(15,47) participants in the second round, while their cumulative detection rate of AN over two rounds was significantly lower (45.6 vs. 52.6 per 1,000 participants). Our results showed that participation in the Dutch CRC screening program was consistently high and that second round detection rates depended on the first round FIT cut-off. The cumulative detection over two rounds was higher among FIT(15,47) participants. These findings suggest that a substantial part of, but not all the missed findings in the first round due to the increased FIT cut-off were detected in the subsequent round.

Development and Validation of a Model to Predict Regression of Large Size Hepatocellular Adenoma.

INTRODUCTION: Surgery is advocated in hepatocellular adenomas (HCA) >5 cm that do not regress to <5 cm after 6-12 months. The aim of this study was to develop a model for these patients, estimating the probability of HCA regression to <5 cm at 1 and 2 years follow-up. METHODS: Data were derived from a multicenter retrospective cohort of female patients diagnosed with HCA >5 cm at first follow-up. Potential predictors included age, body mass index, and HCA diameter at diagnosis (T0), HCA-subtype (hepatocyte nuclear factor 1α inactivated HCA, inflammatory-HCA, unclassified HCA) and "T0-T1 regression-over-time" (percentage of regression between T0 and first follow-up (T1) divided by weeks between T0 and T1). Cox proportional hazards regression was used to develop a multivariable model with time to regression of HCA < 5 cm as outcome. Probabilities at 1 and 2 years follow-up were calculated. RESULTS: In total, 180 female patients were included. Median HCA diameter at T0 was 82.0 mm and at T1 65.0 mm. Eighty-one patients (45%) reached the clinical endpoint of regression to <5 cm after a median of 34 months. No complications occurred during follow-up. In multivariable analysis, the strongest predictors for regression to <5 cm were HCA diameter at T0 (logtransformed, hazard ratio (HR) 0.05), T0-T1 regression-over-time (HR 2.15) and HCA subtype inflammatory-HCA (HR 2.93) and unclassified HCA (HR 2.40), compared to hepatocyte nuclear factor 1α inactivated HCA (reference). The model yielded an internally validated c-index of 0.79. DISCUSSION: In patients diagnosed with HCA > 5 cm that still exceed 5 cm at first follow-up, regression to <5 cm can be predicted at 1 and 2 years follow-up using this model. Although external validation in an independent population is required, this model may aid in decision-making and potentially avoid unnecessary surgery.

Quality Monitoring of a FIT-Based Colorectal Cancer Screening Program.

BACKGROUND: Quality assessment is crucial for consistent program performance of colorectal cancer (CRC) screening programs using fecal immunochemical test for hemoglobin (FIT). However, literature on the consistency of FIT performance in laboratory medicine was lacking. This study examined the consistency of FIT in testing positive or detecting advanced neoplasia (AN) for different specimen collection devices, lot reagents, and laboratories. METHODS: All participants with a FIT sample with a cutoff concentration of 47 µg Hb/g feces in the Dutch CRC screening program in 2014 and 2015 were included in the analyses. Multivariable logistic regression analyses were performed to estimate the odds ratios of collection devices, reagents, and laboratories on testing positive or detecting AN and positive predictive value (PPV). RESULTS: In total, 87519 (6.4%) of the 1371169 participants tested positive. Positivity rates and detection rates of AN differed between collection devices and reagents (all P < 0.01). In contrast, PPVs were not found to vary between collection devices, reagents, or laboratories (all P > 0.05). Positivity rates showed a small difference for laboratories (P = 0.004) but not for detection rates of AN. Size of the population affected by the deviating positivity rates was small (0.1% of the total tested population). CONCLUSIONS: Variations were observed in positivity and detection rates between collection devices and reagents, but there was no detected variation in PPV. Although the overall population effect of these variations on the screened population is expected to be modest, there is room for improvement.

Evaluation of T2-W MR imaging and diffusion-weighted imaging for the early post-treatment local response assessment of patients treated conservatively for cervical cancer: a multicentre study.

OBJECTIVES: To compare MR imaging with or without DWI and clinical response evaluation (CRE) in the local control evaluation of cervical carcinoma after radiotherapy. METHODS: In a multicentre university setting, we prospectively included 107 patients with primary cervical cancer treated with radiotherapy. Sensitivity and specificity for CRE and MR imaging (with pre-therapy MR imaging as reference) (2 readers) were evaluated using cautious and strict criteria for identifying residual tumour. Nested logistic regression models were constructed for CRE, subsequently adding MR imaging with and without DWI as independent variables, as well as the pre- to post-treatment change in apparent diffusion coefficient (delta ADC). RESULTS: Using cautious criteria, CRE and MR imaging with DWI (reader 1/reader 2) have comparable high specificity (83% and 89%/95%, respectively), whereas MR imaging without DWI showed significantly lower specificity (63%/53%) than CRE. Using strict criteria, CRE and MR imaging with DWI both showed very high specificity (99% and 92%/95%, respectively), whereas MR imaging without DWI showed significantly lower specificity (89%/77%) than CRE. All sensitivities were not significantly different. Addition of MR imaging with DWI to CRE has statistically significant incremental value in identifying residual tumour (reader 1: estimate, 1.06; p = 0.001) (reader 2: estimate, 0.62; p = 0.02). Adding the delta ADC did not have significant incremental value in detecting residual tumour. CONCLUSIONS: DWI significantly increases the specificity of MR imaging in the detection of local residual tumour. Furthermore, MR imaging with DWI has significant incremental diagnostic value over CRE, whereas adding the delta ADC has no incremental diagnostic value. KEY POINTS: • If MR imaging is used for response evaluation, DWI should be incorporated • MR imaging with DWI has diagnostic value comparable/complementary to clinical response evaluation • Inter-reader agreement is moderate to fair for two experienced radiologist readers • Quantitative measurements of ADC early post-therapy have limited diagnostic value.

Intrapatient Comparison of the Hepatobiliary Phase of Gd-BOPTA and Gd-EOB-DTPA in the Differentiation of Hepatocellular Adenoma From Focal Nodular Hyperplasia.

BACKGROUND: Current imaging guidelines do not specify the preferred hepatobiliary contrast agent when differentiating hepatocellular adenoma (HCA) from focal nodular hyperplasia (FNH) on MRI. PURPOSE: To analyze intrapatient differences in the hepatobiliary phase (HBP) after use of both gadobenate dimeglumine (Gd-BOPTA) and gadoxetic acid (Gd-EOB-DTPA)-enhanced MRI to differentiate HCA from FNH. STUDY TYPE: Retrospective. POPULATION: Patients who underwent both Gd-BOPTA and Gd-EOB-DTPA-enhanced MRI, including 33 patients with 82 lesions (67 HCA; 15 FNH), with a step-down reference standard of pathology, 20% regression, identical appearance to earlier biopsied lesions, and stringent imaging findings. FIELD STRENGTH/SEQUENCE: 1.5T and 3T HBP of Gd-BOPTA and Gd-EOB-DTPA-enhanced MRI, precontrast fat-suppressed T1 -weighted sequence. ASSESSMENT: Signal intensities relative to the surrounding liver in the HBP were assessed by two observers. STATISTICAL TESTS: Sensitivity and specificity of HCA diagnosis were calculated for both contrast agents. Interobserver agreement was evaluated using Cohen's kappa; differences in degree of certainty for scoring a lesion were calculated by means of the Wilcoxon signed rank test. Differences in signal intensity between Gd-BOPTA and Gd-EOB-DTPA were calculated using McNemar's test. RESULTS: Almost perfect agreement was found between observers for scored signal intensities with both contrast agents. In 30 of the 82 lesions (37%) a difference was observed between contrast agents in the HBP, with Gd-EOB-DTPA proving correct in all but one of the discordant lesions. When distinguishing HCA from FNH, Gd-BOPTA showed a sensitivity of 46% (31/67) and a specificity of 87% (13/15), while the sensitivity and specificity of Gd-EOB-DTPA was 85% (57/67) and 100% (15/15), respectively. A risk of misclassifying HCA as FNH typically occurs for Gd-BOPTA when lesions are intrinsically hyperintense (P < 0.005). DATA CONCLUSION: The HBP of Gd-EOB-DTPA shows superior accuracy in ruling out HCA in comparison with Gd-BOPTA, especially when the lesion is intrinsically hyperintense on T1 -weighted imaging. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;49:700-710.

Can point shear wave elastography differentiate focal nodular hyperplasia from hepatocellular adenoma.

PURPOSE: Focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) are liver tumors that require different management. We assessed the potential of point shear wave elastography (pSWE) to differentiate FNH from HCA and the interobserver and intraobserver reliability of pSWE in the examination of these lesions and of native liver tissue (NLT). METHODS: The study included 88 patients (65 FNH, 23 HCA). pSWE was performed by two experienced liver sonographers (observers 1 [O1] and 2 [O2]) and acquired within the lesion of interest and NLT. Group differences, optimal cutoff for characterization and interobserver reliability was assessed with Mann-Whitney-U, area under the ROC curce (AUROC) and intraclass correlation coefficient (ICC). Intraobserver reliability in NLT was assessed in 20 healthy subjects using ICC. RESULTS: Median stiffness was significantly higher in FNH than in HCA (7.01 kPa vs 4.98 kPa for O1 (P = 0.017) and 7.68 kPa vs 6.00 kPa for O2 (P = 0.031)). A cutoff point for differentiation between the two entities could not be determined with an AUROC of 0.67 (O1) and 0.69 (O2). Interobserver reliability was good for lesion- stiffness (ICC = 0.86) and poor for NLT stiffness (ICC = 0.09). In healthy subjects, intraobserver reliability for NLT-stiffness was poor for O1 (ICC = 0.23) and moderate for O2 (ICC = 0.62). CONCLUSION: This study shows that pSWE cannot reliably differentiate FNH from HCA. Interobserver and intraobserver reliability for pSWE in NLT were insufficient. Interpretation of results gained with this method should be done with great caution.