Optimized treatment parameter by computer simulation for high-intensity focused ultrasound treatment of uterine adenomyosis: Short-term and long-term results.

This study aimed to investigate the efficacy and safety of using optimized parameters obtained by computer simulation for ultrasound-guided high-intensity focused ultrasound (HIFU) treatment of uterine adenomyosis in comparison with conventional parameters. We retrospectively assessed a single-institution, prospective study that was registered at Clinical Research Information Service (CRiS) of Republic of Korea (KCT0003586). Sixty-six female participants (median age: 44 years) with focal uterine adenomyosis were prospectively enrolled. All participants were treated with a HIFU system by using treatment parameters either for treating uterine fibroids (Group A, first 20 participants) or obtained via computer simulation (Group B, later 46 participants). To assess the treatment efficacy of HIFU, qualitative indices, including the clinically effective dysmenorrhea improvement index (DII), were evaluated up to 3 years after treatment, whereas quantitative indices, such as the nonperfused volume ratio and adenomyosis volume shrinkage ratio (AVSR), on MRI were evaluated up to 3 months after treatment. Quantitative/qualitative indices were compared between Groups A and B by using generalized linear mixed effect model. A safety assessment was also performed. Results showed that clinically effective DII was more frequently observed in Group B than in Group A (odds ratio, 3.69; P = 0.025), and AVSR were higher in Group B than in Group A (least-squares means, 21.61; P = 0.001). However, two participants in Group B developed skin burns at the buttock and sciatic nerve pain and required treatment. In conclusion, parameters obtained by computer simulation were more effective than the conventional parameters for treating uterine adenomyosis by using HIFU in terms of clinically effective DII and AVSR. However, care should be taken because of the risk of adverse events.

Characterization of hepatobiliary phase hypointense nodules without arterial phase hyperenhancement on gadoxetic acid-enhanced MRI via contrast-enhanced ultrasound using perfluorobutane.

PURPOSE: Hepatobiliary phase (HBP) hypointense nodules without arterial phase hyperenhancement (APHE) on gadoxetic acid-enhanced MRI (GA-MRI) may be nonmalignant cirrhosis-associated nodules or hepatocellular carcinomas (HCCs). We aimed to characterize HBP hypointense nodules without APHE on GA-MRI by performing contrast-enhanced ultrasound using perfluorobutane (PFB-CEUS). METHODS: In this prospective, single-center study, participants at high-risk of HCC having HBP hypointense nodules without APHE at GA-MRI were enrolled. All participants underwent PFB-CEUS; if APHE and late, mild washout or washout in the Kupffer phase were present, the diagnosis of HCC was established according to the v2022 Korean guidelines. The reference standard consisted of histopathology or imaging. The sensitivity, specificity, and positive/negative predictive values of PFB-CEUS for detecting HCC were calculated. Associations between clinical/imaging features and the diagnosis of HCC were evaluated with logistic regression analyses. RESULTS: In total, 67 participants (age, 67.0 years ± 8.4; 56 men) with 67 HBP hypointense nodules without APHE (median size, 1.5 cm [range, 1.0-3.0 cm]) were included. The prevalence of HCC was 11.9% (8/67). The sensitivity, specificity, and positive and negative predictive values of PFB-CEUS for detecting HCC were 12.5%(1/8), 96.6%(57/59), 33.3%(1/3) and 89.1%(57/64), respectively. Mild-moderate T2 hyperintensity on GA-MRI (odds ratio, 5.756; P = 0.042) and washout in the Kupffer phase on PFB-CEUS (odds ratio, 5.828; P = 0.048) were independently associated with HCC. CONCLUSION: Among HBP hypointense nodules without APHE, PFB-CEUS was specific for detecting HCC, which had a low prevalence. Mild-moderate T2 hyperintensity on GA-MRI and washout in the Kupffer phase on PFB-CEUS may be useful to detect HCC in those nodules.

Low dose of contrast agent and low radiation liver computed tomography with deep-learning-based contrast boosting model in participants at high-risk for hepatocellular carcinoma: prospective, randomized, double-blind study.

OBJECTIVE: To investigate the image quality and lesion conspicuity of a deep-learning-based contrast-boosting (DL-CB) algorithm on double-low-dose (DLD) CT of simultaneous reduction of radiation and contrast doses in participants at high-risk for hepatocellular carcinoma (HCC). METHODS: Participants were recruited and underwent four-phase dynamic CT (NCT04722120). They were randomly assigned to either standard-dose (SD) or DLD protocol. All CT images were initially reconstructed using iterative reconstruction, and the images of the DLD protocol were further processed using the DL-CB algorithm (DLD-DL). The primary endpoint was the contrast-to-noise ratio (CNR), the secondary endpoint was qualitative image quality (noise, hepatic lesion, and vessel conspicuity), and the tertiary endpoint was lesion detection rate. The t-test or repeated measures analysis of variance was used for analysis. RESULTS: Sixty-eight participants with 57 focal liver lesions were enrolled (20 with HCC and 37 with benign findings). The DLD protocol had a 19.8% lower radiation dose (DLP, 855.1 ± 254.8 mGy·cm vs. 713.3 ± 94.6 mGy·cm, p = .003) and 27% lower contrast dose (106.9 ± 15.0 mL vs. 77.9 ± 9.4 mL, p < .001) than the SD protocol. The comparative analysis demonstrated that CNR (p < .001) and portal vein conspicuity (p = .002) were significantly higher in the DLD-DL than in the SD protocol. There was no significant difference in lesion detection rate for all lesions (82.7% vs. 73.3%, p = .140) and HCCs (75.7% vs. 70.4%, p = .644) between the SD protocol and DLD-DL. CONCLUSIONS: DL-CB on double-low-dose CT provided improved CNR of the aorta and portal vein without significant impairment of the detection rate of HCC compared to the standard-dose acquisition, even in participants at high risk for HCC. KEY POINTS: • Deep-learning-based contrast-boosting algorithm on double-low-dose CT provided an improved contrast-to-noise ratio compared to standard-dose CT. • The detection rate of focal liver lesions was not significantly differed between standard-dose CT and a deep-learning-based contrast-boosting algorithm on double-low-dose CT. • Double-low-dose CT without a deep-learning algorithm presented lower CNR and worse image quality.

Abbreviated MRI for Secondary Surveillance of Recurrent Hepatocellular Carcinoma After Presumed Curative Treatment.

BACKGROUND: Little is known about the performance of abbreviated MRI (AMRI) for secondary surveillance of recurrent hepatocellular carcinoma (HCC) after curative treatment. PURPOSE: To evaluate the detection performance of AMRI for secondary surveillance of HCC after curative treatment. STUDY TYPE: Retrospective. POPULATION: A total of 243 patients (183 men and 60 women; median age, 65 years) who underwent secondary surveillance for HCC using gadoxetic acid-enhanced MRI after more than 2 year of disease-free period following curative treatment, including surgical resection or radiofrequency ablation (RFA). FIELD STRENGTH/SEQUENCE: A 3.0 T/noncontrast AMRI (NC-AMRI) (T2-weighted fast spin-echo, T1-weighted gradient echo, and diffusion-weighted images), hepatobiliary phase AMRI (HBP-AMRI) (T2-weighted fast spin-echo, diffusion-weighted, and HBP images), and full-sequence MRI ASSESSMENT: Four board-certified radiologists independently reviewed NC-AMRI, HBP-AMRI, and full-sequence MRI sets of each patient for detecting recurrent HCC. STATISTICAL TESTS: Per-lesion sensitivity, per-patient sensitivity and specificity for HCC detection at each set were compared using generalized estimating equation. RESULTS: A total of 42 recurred HCCs were confirmed in the 39 patients. The per-lesion and per-patient sensitivities did not show significant differences among the three image sets for either reviewer (P ≥ 0.358): per-lesion sensitivity: 59.5%-83.3%, 59.5%-85.7%, and 59.5%-83.3%, and per-patient sensitivity: 53.9%-83.3%, 56.4%-85.7%, and 53.9%-83.3% for NC-AMRI, HBP-AMRI, and full-sequence MRI, respectively. Per-lesion pooled sensitivities of NC-AMRI, HBP-AMRI, and full-sequence MRI were 72.6%, 73.2%, and 73.2%, with difference of -0.6% (95% confidence interval: -6.7, 5.5) between NC-AMRI and full-sequence MRI and 0.0% (-6.1, 6.1) between HBP-AMRI and full-sequence MRI. Per-patient specificity was not significantly different among the three image sets for both reviewers (95.6%-97.1%, 95.6%-97.1%, and 97.6%-98.5% for NC-AMRI and HBP-AMRI, respectively; P ≥ 0.117). DATA CONCLUSION: NC-AMRI and HBP-AMRI showed no significant difference in detection performance to that of full-sequence gadoxetic acid-enhanced MRI during secondary surveillance for HCC after more than 2-year disease free interval following curative treatment. Based on its good detection performance, short scan time, and lack of contrast agent-associated risks, NC-AMRI is a promising option for the secondary surveillance of HCC. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.

Sonazoid™ versus SonoVue® for Diagnosing Hepatocellular Carcinoma Using Contrast-Enhanced Ultrasound in At-Risk Individuals: A Prospective, Single-Center, Intraindividual, Noninferiority Study.

OBJECTIVE: To determine whether Sonazoid-enhanced ultrasound (SZUS) was noninferior to SonoVue-enhanced ultrasound (SVUS) in diagnosing hepatocellular carcinoma (HCC) using the same diagnostic criteria. MATERIALS AND METHODS: This prospective, single-center, noninferiority study (NCT04847726) enrolled 105 at-risk participants (71 male; mean age ± standard deviation, 63 ± 11 years; range, 26-86 years) with treatment-naïve solid hepatic nodules (≥ 1 cm). All participants underwent same-day SZUS (experimental method) and SVUS (control method) for one representative nodule per participant. Images were interpreted by three readers (the operator and two independent readers). All malignancies were diagnosed histopathologically, while the benignity of other lesions was confirmed by follow-up stability or pathology. The primary endpoint was per-lesion diagnostic accuracy for HCC pooled across three readers using the conventional contrast-enhanced ultrasound diagnostic criteria, including arterial phase hyperenhancement followed by mild (assessed within 2 minutes after contrast injection) and late (≥ 60 seconds with a delay of 5 minutes) washout. The noninferiority delta was -10%p. Furthermore, different time delays were compared as washout criteria in SZUS, including delays of 2, 5, and > 10 minutes. RESULTS: A total of 105 lesions (HCCs [n = 61], non-HCC malignancies [n = 19], and benign [n = 25]) were evaluated. Using the 5-minutes washout criterion, per-lesion accuracy of SZUS pooled across the three readers (72.4%; 95% confidence interval [CI], 64.1%-79.3%) was noninferior to that of SVUS (71.4%; 95% CI, 63.1%-78.6%), meeting the statistical criterion for non-inferiority (difference of 0.95%p; 95% CI, -3.8%p-5.7%p). The arterial phase hyperenhancement combined with the 5-minutes washout criterion showed the same sensitivity as that of the > 10-minutes criterion (59.0% vs. 59.0%, p = 0.989), and the specificities were not significantly different (90.9% vs. 86.4%, p = 0.072). CONCLUSION: SZUS was noninferior to SVUS for diagnosing HCC in at-risk patients using the same diagnostic criteria. No significant improvement in HCC diagnosis was observed by extending the washout time delay from 5 to 10 minutes.

Feasibility and safety of a novel 3D-printed biodegradable biliary stent in an in vivo porcine model: a preliminary study.

To assess the feasibility and safety of a novel 3D-printed biodegradable biliary stent using polycaprolactone (PCL) in an in vivo porcine model. In this animal study using domestic pigs, biodegradable radiopaque biliary stents made of polycaprolactone (PCL) and barium sulfate were produced using 3D printing and surgically inserted into the common bile duct (CBD) of pigs (stent group, n = 12). Another five pigs were allocated to the control group that only underwent resection and anastomosis of the CBD without stent insertion. To check the position and status of the stents and stent-related complications, follow-up computed tomography (CT) was performed every month. The pigs were sacrificed 1 or 3 months after surgery, and their excised CBD specimens were examined at both the macroscopic and microscopic levels. Three pigs (one in the stent group and two in the control group) died within one day after surgery and were excluded from further analysis; the remaining 11 in the stent group and 3 in the control group survived the scheduled follow-up period (1 month, 5 and 1; and 3 months, 6 and 2 in stent and control groups, respectively). In all pigs, no clinical symptoms or radiologic evidence of biliary complications was observed. In the stent group (n = 11), stent migration (n = 1 at 3 months; n = 2 at 1 month) and stent fracture (n = 3 at 2 months) were detected on CT scans. Macroscopic evaluation of the stent indicated no significant change at 1 month (n = 3) or fragmentation with discoloration at 3 months (n = 5). On microscopic examination of CBD specimens, the tissue inflammation score was significantly higher in the stent group than in the control group (mean ± standard deviation (SD), 5.63 ± 2.07 vs. 2.00 ± 1.73; P = 0.039) and thickness of fibrosis of the CBD wall was significantly higher than that of the control group (0.46 ± 0.12 mm vs. 0.21 ± 0.05 mm; P = 0.012). Despite mild bile duct inflammation and fibrosis, 3D-printed biodegradable biliary stents showed good feasibility and safety in porcine bile ducts, suggesting their potential for use in the prevention of postoperative biliary strictures.

Additional value of superb microvascular imaging of ultrasound examinations to evaluate focal liver lesions.

PURPOSE: To evaluate the additional value of superb microvascular imaging (SMI) to characterize focal liver lesions (FLLs). METHOD: Between July 2020 and December 2020, 70 patients (39 men and 31 women; mean age [± standard deviation], 61.1 ± 10.1 years) with FLLs were prospectively enrolled and underwent B-mode ultrasound (US), color Doppler imaging (CDI), power Doppler imaging (PDI), and SMI examinations on the same day. All the malignant FLLs were confirmed by histological diagnosis, while the benign FLLs were confirmed by typical imaging features at contrast-enhanced CT and/or MRI. Tumor vascularity scores in CDI, PDI, and SMI were graded using a 5-point scale. For tumors in which vascularity was detected on SMI, tumor vascular pattern on SMI was assessed in each lesion. The diagnostic performance of a combination of B-mode US and SMI, based on vascular pattern on SMI, was compared to B-mode US alone to diagnose malignant lesions; and hemangiomas. RESULTS: Seventy FLLs (34 benign [31 hemangiomas, 3 focal nodular hyperplasias] and 36 malignant tumors [16 hepatocellular carcinomas, 10 cholangiocarcinomas, 10 metastases]) were enrolled. Tumor vascularity score in SMI was significantly higher than those in CDI and PDI (P < 0.001). Using a combination of B-mode US and SMI, the diagnostic performance was improved from 0.867 and 0.834 to 0.945 and 0.921 (P = 0.035 and 0.112) to diagnose malignant tumors and from 0.896 and 0.853 to 0.975 and 0.987 (P = 0.027 and 0.006) to diagnose hemangiomas by reviewers 1 and 2, respectively. CONCLUSIONS: SMI provides higher sensitivity than CDI and PDI to detect tumor vascularity, and a combination of B-mode US and SMI can improve the characterization of FLLs when vascular pattern of tumor is considered.

Performance of LI-RADS Version 2018 on CT for Determining Eligibility for Liver Transplant According to Milan Criteria in Patients at High Risk for Hepatocellular Carcinoma.

BACKGROUND. LI-RADS has been investigated primarily in terms of detection of hepatocellular carcinoma (HCC), with less attention given to its performance, particularly on CT, in determining eligibility for liver transplant (LT). OBJECTIVE. The purpose of our study was to assess the performance of LI-RADS version 2018 (v2018) on CT for the diagnosis of HCC and determination of LT eligibility according to the Milan criteria (MC). METHODS. This retrospective study included 136 patients (110 men, 26 women; mean age, 53.9 ± 8.1 [SD] years) at high-risk for HCC who underwent liver protocol CT within 3 months before LT between January 2010 and December 2018. Two radiologists independently reviewed CT examinations using LI-RADS v2018; Organ Procurement and Transplantation Network (OPTN) classes were constructed from the LI-RADS interpretations. Histopathologic analysis of liver explants served as the reference standard for determining the presence of HCC and LT eligibility based on MC. Diagnostic performance was evaluated. Overall survival (OS) was assessed based on medical record review. RESULTS. Based on histopathologic evaluation of liver explants in the 136 patients, 27 patients had no malignancy, 77 were eligible for LT due to HCC within MC, and 32 were unsuitable for LT (i.e., HCC beyond MC in 16 patients, HCC with macrovascular invasion in 12, non-HCC malignancy in four). LR-5 exhibited per-lesion sensitivity and PPV for HCC of 55.9% and 92.8%, respectively, for reader 1 and 39.8% and 86.5% for reader 2. When considering LR-5 observations to represent HCC in assessing MC, LI-RADS had accuracy for determining LT eligibility of 92.7% for reader 1 and 85.3% for reader 2; OPTN criteria had accuracy for determining LT eligibility of 89.0% for reader 1 and 84.4% for reader 2. Five-year OS for patients within MC versus 5-year OS for patients unsuitable for LT was 92.2 months versus 56.0 months for LI-RADS, 92.6 months versus 47.6 months for OPTN criteria, and 93.3 months versus 55.1 months for histopathologic assessment of liver explants. CONCLUSION. LI-RADS v2018, as evaluated on CT in high-risk patients, shows high PPV for HCC detection and high accuracy for determining LT eligibility based on MC. LT eligibility based on preoperative LI-RADS evaluation is associated with post-LT survival. CLINICAL IMPACT. These findings support the use of LI-RADS on CT in assessing eligibility in patients who are candidates for LT.

Diagnostic criteria of perfluorobutane-enhanced ultrasonography for diagnosing hepatocellular carcinoma in high-risk individuals: how is late washout determined?

PURPOSE: The aim of this study was to investigate the optimal washout criteria of perfluorobutane-enhanced ultrasonography (PFB-US) for the diagnosis of hepatocellular carcinoma (HCC) in high-risk individuals. METHODS: Participants at risk of HCC with treatment-naïve solid hepatic observations (≥1 cm) who underwent PFB-US from March 2019 to September 2020 were prospectively recruited. Arterial phase hyperenhancement (APHE), washout time, and washout degree were evaluated. The diagnosis of HCC was made by non-rim APHE with late and mild washout. The per-lesion diagnostic performance for diagnosing HCC using different cutoffs for late washout (50, 55, 60, 65, and 70 seconds postcontrast) and the different time windows for determining washout (until 2, 3, 4, 5, 6, 7, 8, 9, and 10 minutes postcontrast) were compared using the McNemar test. RESULTS: In total, 101 participants with 113 observations (mean size, 33.5±2.8 mm; HCCs [n=82], non-HCC malignancies [n=16], benign [n=15]) were evaluated. Non-rim APHE was observed in 86.6% (71/82) of HCCs. As the cutoff time for late washout increased, the specificity increased to 100% (95% confidence interval [CI], 88.8% to 100%) at the 60-second cutoff with 62.2% sensitivity (95% CI, 50.8% to 72.7%). When the time window for determining washout became wider, the sensitivity and accuracy increased until 6 minutes, with 100% specificity at all times. CONCLUSION: Determining washout within 6 minutes after contrast injection with a 60-second cutoff for late washout showed the highest sensitivity without losing specificity for diagnosing HCC using PFB-US in individuals at high risk.

Early response evaluation of doxorubicin-nanoparticle-microbubble therapy in orthotopic hepatocellular carcinoma rat model using contrast-enhanced ultrasound and intravoxel incoherent motion-diffusion MRI.

PURPOSE: This study aimed to apply doxorubicin-loaded nanoparticle microbubble (Dox-NP-MB) therapy in an orthotopic rat model of hepatocellular carcinoma (HCC) and investigate the utility of contrast-enhanced ultrasound (CEUS) and intravoxel incoherent motion diffusion-weighted magnetic resonance imaging (IVIM-DWI) for response evaluation. METHODS: Twenty-eight N1S1 HCC model rats were treated with either Dox-NP-MB (group [G] 1, n=8), doxorubicin (Dox) alone (G2, n=7), nanoparticle microbubbles alone (G3, n=7), or saline (G4, control, n=6) on days 0 and 7, and were sacrificed on day 11. IVIM-DWI and CEUS were performed before each treatment and before euthanasia. Efficacy was estimated by the percentage of tumor volume growth inhibition compared with control. Toxicity was assessed by body weight changes and blood tests. Post-treatment changes in IVIM-DWI and CEUS parameters were analyzed. RESULTS: Tumor volume growth was inhibited by 48.4% and 90.2% in G1 and G2 compared to G4, respectively. Compared to G2, G1 had a significantly lower degree of body weight change (median, 91.0% [interquartile range, 88.5%-97.0%] vs. 88.0% [82.5%-88.8%], P<0.05) and leukopenia (1.75×103 cells/µL [1.53-2.77] vs. 1.20×103 cells/µL [0.89-1.51], P<0.05). After the first treatment, an increase in peak enhancement, wash-in rate, and wash-in perfusion index on CEUS was observed in G3 and G4 but suppressed in G1 and G2; the apparent diffusion coefficients, true diffusion coefficients, and perfusion fractions significantly increased in G1 and G2 compared to baseline (P<0.05). CONCLUSION: Dox-NP-MB showed reduced Dox toxicity. Early changes in some CEUS and IVIM-DWI parameters correlated with the therapeutic response.

Development of a predictive model for extragastric recurrence after curative resection for early gastric cancer.

BACKGROUND: Stratification of patients who undergo curative resection for early gastric cancer (EGC) is warranted due to the heterogeneity in the risk of developing extragastric recurrence (EGR). Therefore, we aimed to stratify the need for postoperative surveillance for EGR detection in patients with EGC by developing a model for predicting EGR-free survival. METHODS: This retrospective cohort study included patients who underwent postoperative surveillance after curative resection of EGC (n = 4149). Cox proportional hazard models were used to identify predictors to build a model for predicting EGR-free survival. Bootstrap-corrected c-index and calibration plots were used for internal and external (n = 2148) validations. RESULTS: A risk-scoring system was constructed using variables significantly associated with EGR-free survival: pathologic T stage (pT1b[sm1], hazard ratio [HR] 4.928; pT1b[sm2], HR 5.235; pT1b[sm3], HR 7.748) and N stage (pN1, HR 4.056; pN2, HR 9.075; pN3, HR 30.659). Patients were dichotomized into a very-low-risk group or a low-or-greater-risk group. The 5-year EGR-free survival rates differed between the two groups (99.9 vs. 97.3%). The discriminative performance of the model was 0.851 (Uno's c-index) and 0.751 in the internal and external cohorts, respectively. The calibration slope was 0.916 and 1.131 in the internal and external cohorts, respectively. CONCLUSIONS: Our model for predicting EGR-free survival based on the pathologic T and N stages may be useful for stratifying patients who have undergone curative surgery for EGC. The results suggest that patients in the very-low-risk group may be spared from postoperative surveillance considering their extremely high EGR-free survival rate.

Prediction of residual tumor and overall survival after first-line surgery in patients with pancreatic ductal adenocarcinoma using preoperative magnetic resonance imaging findings.

BACKGROUND: Complete resection is the only potentially curative treatment in patients with pancreatic ductal adenocarcinoma (PDA) and is associated with a longer overall survival (OS) than incomplete resection of tumor. Hence, prediction of the resection status after surgery would help predict the prognosis of patients with PDA. PURPOSE: To predict residual tumor (R) classification and OS in patients who underwent first-line surgery for PDA using preoperative magnetic resonance imaging (MRI). MATERIAL AND METHODS: In this study, 210 patients with PDA who underwent MRI and first-line surgery were randomly categorized into a test group (n=150) and a validation group (n=60). The R classification was divided into R0 (no residual tumor) and R1/R2 (microscopic/macroscopic residual tumor). Preoperative MRI findings associated with R classification and OS were assessed by using logistic regression and Cox proportional hazard models. In addition, the prediction models for the R classification and OS were validated using calibration plots and C statistics. RESULTS: On preoperative MRI, portal vein encasement (odds ratio 4.755) was an independent predictor for R1/R2 resection (P=0.040). Tumor size measured on MRI (hazard ratio [HR] per centimeter 1.539) was a predictor of OS, along with pathologic N1 and N2 stage (HR 1.944 and 3.243, respectively), R1/R2 resection (HR 3.273), and adjuvant chemoradiation therapy (HR 0.250) (P<0.050). Calibration plots demonstrated satisfactory predictive performance. CONCLUSION: Preoperative MRI was valuable for predicting R1/R2 resection using portal vein encasement. Tumor size measured on MRI was useful for the prediction of OS after first-line surgery for PDA.

Noninvasive assessment of hepatic steatosis using a pathologic reference standard: comparison of CT, MRI, and US-based techniques.

PURPOSE: The present study compared the performance of computed tomography (CT), magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF), controlled attenuation parameter (CAP), grayscale ultrasonography (US), and attenuation imaging (ATI) for the diagnosis of hepatic steatosis (HS). METHODS: In total, 120 prospectively recruited patients who underwent hepatic resection between June 2018 and June 2020 were retrospectively analyzed. CT, MRI-PDFF, CAP, grayscale US, and ATI were performed within 3 months before surgery. Diagnostic performance for HS ≥5% and HS >33% was compared using the area under the curve (AUC) of receiver operating characteristic curves. Histopathologic examinations served as the reference standard for the degree of HS. RESULTS: For detecting HS ≥5%, MRI-PDFF (AUC, 0.946) significantly outperformed CT, CAP and grayscale US (AUC, 0.807, 0.829, and 0.761, respectively) (P<0.01 for all). ATI (AUC, 0.892) was the second-best modality and significantly outperformed grayscale US (P=0.001). In pairwise comparisons, there were no significant differences between the AUC of ATI and the values of MRI-PDFF, CT, or CAP (P=0.133, P=0.063, and P=0.150, respectively). For detecting HS >33%, all the modalities provided good diagnostic performance without significant differences (AUC, 0.887-0.947; P>0.05 for all). CONCLUSION: For detecting HS ≥5%, MRI-PDFF was the best imaging modality, while ATI outperformed grayscale US. For detecting HS >33%, all five imaging tools demonstrated good diagnostic performance.

Tumor volume measured using MR volumetry as a predictor of prognosis after surgical resection of single hepatocellular carcinoma.

PURPOSE: To evaluate the clinical value of tumor volume-measurement using magnetic resonance (MR) volumetry for predicting prognosis after surgical resection of single small-to-medium-sized hepatocellular carcinoma (HCC) (≤5cm). METHOD: This retrospective study included 162 consecutive patients who underwent preoperative gadoxetic acid-enhanced MRI and subsequent surgical resection for single HCC (≤5cm). Tumor volume was measured at hepatobiliary phase of MR images using semi-automated three-dimensional volumetric software program. Recurrence-free survival (RFS) and overall survival (OS) were estimated using Kaplan-Meier method. The Cox-proportional-hazard-model was used to evaluate clinical, pathologic, and radiologic prognostic factors. A minimal p-value approach based on log-rank test statistics was used to obtain the optimal-cutoff tumor volume for predicting RFS and OS. Inter-examiner reproducibility of MR volumetric measurements was assessed using intraclass correlation coefficient (ICC) and coefficient of variance (CV). RESULTS: After a median follow-up of 84.4 months (range, 2.8-126.5), HCC recurrence occurred in 69 (42.6%) patients and twenty-four (14.8%) patients died with estimated 5-year OS of 90.8%. Larger tumor volume was significantly associated with poor RFS(P = 0.018) and poor OS(P = 0.005) in multivariate analysis. For predicting RFS and OS after surgery, the optimal-cutoff of tumor volume was set at 4.0 mL and 4.0 mL, respectively, with larger volume ≥4.0 mL was significantly associated with poor RFS (hazard ratio[HR], 1.84, P = 0.023) and poor OS (HR, 2.66, P = 0.033). Inter-examiner reproducibility of tumor volume-measurement using MR-volumetry showed ICC of 0.980 and CV of 3.9%. CONCLUSIONS: Tumor volume-measurement using MR-volumetry is clinically feasible and reproducible, and can help predict RFS and OS after resection of single small-to-medium-sized HCC.

Gadoxetate-enhanced MRI Features of Proliferative Hepatocellular Carcinoma Are Prognostic after Surgery.

Background Hepatocellular carcinomas (HCCs) are heterogeneous neoplasms, and the prognosis varies based on the subtype. Two broad molecular classes of HCC have been proposed: a proliferative and a nonproliferative class. Purpose To evaluate the gadoxetate-enhanced MRI findings of the proliferative class HCC and its prognostic significance after surgery. Materials and Methods This retrospective cohort study evaluated patients with surgically resected treatment-naive single HCC (≤5 cm) who underwent hepatic resection from January 2010 through February 2013 and preoperative gadoxetate-enhanced MRI. A Cox proportional hazards model was used to determine the predictive factors for overall survival (OS), intrahepatic distant recurrence, and extrahepatic metastasis (EM). The mean follow-up period was 75.5 months ± 30.2 (standard deviation). Multivariable logistic regression was performed to determine factors associated with proliferative class HCC. Results A total of 158 patients (mean age, 57 years ± 11; 128 men and 30 women) were evaluated. Forty-two of the 158 HCCs (26.6%) were proliferative class HCCs (17 macrotrabecular-massive HCCs, 14 keratin 19-positive HCCs, 10 scirrhous HCCs, and one sarcomatoid HCC). The proliferative class was associated with worse OS (hazard ratio [HR], 3.1; 95% CI: 1.5, 6.0; P = .01) and higher rates of intrahepatic distant recurrence (HR, 1.83; 95% CI: 1.1, 2.9; P = .01) and EM (HR, 9.97; 95% CI: 3.2, 31.4; P < .001). Rim arterial phase hyperenhancement (APHE) at gadoxetate-enhanced MRI (odds ratio [OR], 6.35; 95% CI: 1.9, 21.7; P = .01) and high serum α-fetoprotein (>100 ng/mL) (OR, 4.18; 95% CI: 1.64, 10.7; P = .01) were independent predictors for proliferative HCC. The presence of rim APHE was associated with poor OS (HR, 2.4; 95% CI: 1.2, 4.9; P = .02) and higher rates of EM (HR, 7.4; 95% CI: 2.5, 21.7; P < .01). Conclusion The proliferative class of hepatocellular carcinoma (HCC) is an independent factor for poor overall survival with increased rates of intrahepatic and extrahepatic metastasis. Rim arterial phase hyperenhancement at gadoxetate-enhanced MRI may help to identify proliferative class HCC and predict poor overall survival and an increased incidence of extrahepatic metastasis. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Krinsky and Shanbhogue in this issue.

Predictors of conversion surgery in patients with pancreatic cancer who underwent neoadjuvant or palliative FOLFIRINOX treatment using baseline and follow-up CT.

PURPOSE: We aimed to evaluate the predictive factors of conversion surgery in pancreatic adenocarcinoma (PAC) after neoadjuvant or palliative FOLFIRINOX using baseline and follow-up CT. METHODS: We retrospectively included 189 patients who had undergone more than 4 cycles of FOLFIRINOX. We reviewed baseline CT (B-CT), 1st follow-up CT (1st-CT), and the preoperative or last follow-up CT (L-CT) and determined tumor size changes according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Extra-pancreatic perineural invasion (EPNI) and resectability using NCCN 2019 guideline were evaluated. Subgroup analysis by baseline resectability was performed. RESULTS: B-CT included resectable (n = 25, 23.2%), borderline (n = 55, 29.1%), locally advanced (n = 44, 23.3%), and metastatic (n = 65, 34.4%) PAC. Seventy-four patients had undergone surgery (39.2%) with an 83.8% (62/74) R0 resection. For operability, resectable status at L-CT (hazard ratio (HR) 65.5; 95% confidence interval (CI) 5.0-865; P = 0.002), RECIST (partial response) at 1st-CT (HR 3.6; 95% CI 1.1-11.7; P = 0.032), and baseline borderline resectability (HR 8.6; 95% CI 1.6-46.4; P = 0.013) were important predictors. Based on a size reduction cut-off of 22.2%, the area under the receiver operating characteristic (ROC) curve (Az) was 0.761 (sensitivity = 70.3%, specificity = 74.8%). In subgroup analysis, RECIST (partial response) at 1st-CT was a significant predictor of locally advanced PAC (HR 32; 95% CI 4.5-227, P 0.001), and the optimal cut-off was 22.2% (Az = 0.914; sensitivity = 100%, specificity = 75%). Baseline tumor size ([Formula: see text] 4 cm) (HR 5.6, 95% CI 1.3-24.3, P = 0.022) and unresectable status at 1st-CT (HR 4.8, 95% CI 1.1-20.6, P = 0.035) were significantly associated with margin-positive resection. CONCLUSION: Both baseline and follow-up CT findings are useful to predict conversion surgery for PAC after FOLFIRINOX.

Superb microvascular imaging technology of ultrasound examinations for the evaluation of tumor vascularity in hepatic hemangiomas.

PURPOSE: This study aimed to investigate and categorize the diverse features of hepatic hemangiomas on superb microvascular imaging (SMI) in a relatively large prospective study. METHODS: In this prospective study, 70 patients with 92 hepatic hemangiomas were consecutively enrolled. All nodules were radiologically confirmed with the typical imaging features of hepatic hemangiomas on dynamic computed tomography (CT) or magnetic resonance imaging (MRI). Using SMI, all lesions were evaluated and categorized into subgroups according to the flow pattern on SMI. Differences in the frequencies of SMI patterns according to lesion size and enhancement patterns on dynamic CT or MRI were also compared. RESULTS: In 67.4% (62/92) of hemangiomas, tumor vascularity was detected using SMI, while 32.6% (30/92) did not show any signal on the SMI examination, and the absence of an SMI signal was not shown in rapidly enhancing hemangiomas (0% [0/30] vs. 100% [30/30], P=0.002) and was more frequent in lesions <2 cm than in lesions ≥2 cm (44.0% [22/50] vs. 2.7% [8/42], P=0.011). In hepatic hemangiomas in which vascularity was detected (n=62), the strip rim pattern was the most common SMI pattern of hepatic hemangiomas (48.4%, 30/62), followed by the nodular rim pattern involving spotty dot-like engorged vessels (37.1%, 23/62). CONCLUSION: The evaluation of the inner vascularity of hepatic hemangiomas with SMI was feasible for most hemangiomas, especially in larger (≥2 cm) or rapidly enhancing hemangiomas. The most frequent SMI patterns of hepatic hemangiomas were the strip rim pattern and nodular rim pattern.

Preoperative assessment of the resectability of pancreatic ductal adenocarcinoma on CT according to the NCCN Guidelines focusing on SMA/SMV branch invasion.

OBJECTIVES: For patients with pancreatic adenocarcinoma (PAC), adequate determination of disease extent is critical for optimal management. We aimed to evaluate diagnostic accuracy of CT in determining the resectability of PAC based on 2020 NCCN Guidelines. METHODS: We retrospectively enrolled 368 consecutive patients who underwent upfront surgery for PAC and preoperative pancreas protocol CT from January 2012 to December 2017. The resectability of PAC was assessed based on 2020 NCCN Guidelines and compared to 2017 NCCN Guidelines using chi-square tests. Overall survival (OS) was estimated using the Kaplan-Meier method and compared using log-rank test. R0 resection-associated factors were identified using logistic regression analysis. RESULTS: R0 rates were 80.8% (189/234), 67% (71/106), and 10.7% (3/28) for resectable, borderline resectable, and unresectable PAC according to 2020 NCCN Guidelines, respectively (p < 0.001). The estimated 3-year OS was 28.9% for borderline resectable PAC, which was significantly lower than for resectable PAC (43.6%) (p = 0.004) but significantly higher than for unresectable PAC (0.0%) (p < 0.001). R0 rate was significantly lower in patients with unresectable PAC according to 2020 NCCN Guidelines (10.7%, 3/28) than in those with unresectable PAC according to the previous version (31.7%, 20/63) (p = 0.038). In resectable PAC, tumor size ≥ 3 cm (p = 0.03) and abutment to portal vein (PV) (p = 0.04) were independently associated with margin-positive resection. CONCLUSIONS: The current NCCN Guidelines are useful for stratifying patients according to prognosis and perform better in R0 prediction in unresectable PAC than the previous version. Larger tumor size and abutment to PV were associated with margin-positive resection in patients with resectable PAC. KEY POINTS: • The updated 2020 NCCN Guidelines were useful for stratifying patients according to prognosis. • The updated 2020 NCCN Guidelines performed better in the prediction of margin-positive resection in unresectable cases than the previous version. • Tumor size ≥ 3 cm and abutment to the portal vein were associated with margin-positive resection in patients with resectable pancreatic adenocarcinoma.

Added value of [68Ga]Ga-DOTA-TOC PET/CT for characterizing pancreatic neuroendocrine neoplasms: a comparison with contrast-enhanced CT and/or MRI in a large study cohort.

OBJECTIVES: To investigate an additional value of [68Ga]Ga-DOTA-TOC PET/CT for characterizing suspected pancreatic neuroendocrine neoplasms (NENs) in a large study cohort. METHODS: This retrospective study included 167 patients who underwent [68Ga]Ga-DOTA-TOC PET/CT for suspected pancreatic NENs detected by contrast-enhanced CT (n = 153) and/or MRI (n = 85). Two board-certified radiologists independently reviewed CT and/or MRI as well as [68Ga]Ga-DOTA-TOC PET/CT and scored the probability of NEN on a 5-point scale. Radiologists' diagnostic performances with and without [68Ga]Ga-DOTA-TOC PET/CT were compared using pathologic findings as the standard of reference. RESULTS: All 167 patients were pathologically diagnosed with NENs (n = 131) or non-NENs (n = 36) by surgery (n = 93) or biopsy (n = 74). The non-NEN group included focal pancreatitis (n = 7), gastrointestinal stromal tumor (n = 6), serous cystadenoma (n = 5), metastatic renal cell carcinoma (n = 4), intrapancreatic accessory spleen (n = 4), ductal adenocarcinoma (n = 3), solid pseudopapillary neoplasm (n = 2), intraductal papillary mucinous carcinoma (n = 1), adenosquamous carcinoma (n = 1), schwannoma (n = 1), paraganglioma (n = 1), and solitary fibrous tumor (n = 1). Radiologists' diagnostic performance significantly improved after the addition of [68Ga]Ga-DOTA-TOC PET/CT (AUC of CT: 0.737 vs. 0.886 for reviewer 1 [p = 0.0004]; 0.709 vs. 0.859 for reviewer 2 [p = 0.0002], AUC of MRI: 0.748 vs. 0.872 for reviewer 1 [p = 0.023]; 0.670 vs. 0.854 for reviewer 2 [p = 0.001]). [68Ga]Ga-DOTA-TOC PET/CT significantly improved sensitivity (CT: 87.4% vs. 96.6% for reviewer 1 [p = 0.001]; 74.8% vs. 92.5% for reviewer 2 [p = 0.0001], MRI: 86.9% vs. 98.4% for reviewer 1 [p = 0.016]; 70.5% vs. 91.8% for reviewer 2 [p = 0.002]). CONCLUSIONS: [68Ga]Ga-DOTA-TOC PET/CT provided an additional value over conventional CT or MRI for the characterization of suspected pancreatic NENs. KEY POINTS: • [68Ga]Ga-DOTA-TOC PET/CT could provide additional value over conventional CT and/or MRI for the exact characterization of suspected pancreatic NENs by increasing AUC values and sensitivity. • Diagnostic improvement was significant, especially in NENs showing an atypical enhancement pattern. • The inter-observer agreement was improved when [68Ga]Ga-DOTA-TOC PET/CT was added to CT and/or MRI.

Reducing Pain by Artificial Ascites Infusion During Radiofrequency Ablation for Subcapsular Hepatocellular Carcinoma.

PURPOSE: To evaluate therapeutic effects of artificial ascites (AA) infusion in patients with subcapsular hepatocellular carcinoma (HCC) treated with radiofrequency ablation (RFA) and to determine whether this infusion can reduce pain. METHODS AND MATERIALS: From 2011 to 2016, 123 patients with treatment-naïve single subcapsular HCC (≤ 2.5 cm) who underwent RFA were retrospectively included. Patients were divided into two groups according to AA infusion. After RFA, medical records were used to analyze pain scores during a 24-h period and to determine the opioid used that compared using Mann-Whitney U test. We also conducted subgroup analysis of the patients with HCCs located adjacent to parietal peritoneum. After follow-up period, we analyzed local tumor progression (LTP) and recurrence-free survival using Kaplan-Meier method. RESULTS: AA was infused in 76 patients (61.8%, 76/123). Pain score using numeric rating scale (NRS) was significantly lower in AA infusion group than in control group (2.54 ± 2.8 vs. 3.66 ± 3.2, p = 0.048). Dose of opioids used was not significantly different between two groups (1.62 ± 3.4 mg vs. 1.66 ± 3 mg, p = 0.698). However, in subgroup analysis (N = 45), NRS score and dose of opioids used were significantly lower in AA infusion group (p = 0.03, p = 0.032, respectively). LTP rate was not significantly different between two groups (p = 0.673). CONCLUSION: AA infusion was an effective and safe way to reduce pain when performing RFA for subcapsular HCC. In particular, in patients with subcapsular HCC adjacent to parietal peritoneum, dose of opioid to use pain control was significantly lower with AA infusion.