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肝细胞癌影像学检查临床适用性评价
Evaluation of the clinical applicability of imaging examinations in hepatocellular carcinoma
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吕晗, 王振常, 刘晓清, 等. 影像学检查的临床适用性评价: 基于循证医学证据,合理选择检查方法[J]. 中华外科杂志, 2020, 58(11): 831-834. DOI:10.3760/cma.j.cn112139-20200604-00433.
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陈耀龙, 王小琴, 王琪, 等. 遵循指南报告规范提升指南报告质量[J]. 中华内科杂志, 2018, 57(3): 168-170. DOI:10.3760/cma.j.issn.0578-1426.2018.03.003.
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The quality of reporting practice guidelines is often poor, and there is no widely accepted guidance or standards for such reporting in health care. The international RIGHT (Reporting Items for practice Guidelines in HealThcare) Working Group was established to address this gap. The group followed an existing framework for developing guidelines for health research reporting and the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) Network approach. It developed a checklist and an explanation and elaboration statement. The RIGHT checklist includes 22 items that are considered essential for good reporting of practice guidelines: basic information (items 1 to 4), background (items 5 to 9), evidence (items 10 to 12), recommendations (items 13 to 15), review and quality assurance (items 16 and 17), funding and declaration and management of interests (items 18 and 19), and other information (items 20 to 22). The RIGHT checklist can assist developers in reporting guidelines, support journal editors and peer reviewers when considering guideline reports, and help health care practitioners understand and implement a guideline.
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陈耀龙, 杨克虎, 王小钦, 等. 中国制订/修订临床诊疗指南的指导原则(2022 版)[J]. 中华医学杂志, 2022, 102(10): 697-703. DOI:10.3760/cma.j.cn112137-20211228-02911.
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姜之歆, 刘柳, 李光宇, 等. 基于估时作业成本法的医院超声造影诊断肝占位的成本研究[J]. 医学与社会, 2023, 36(6):74-79. DOI:10.13723/j.yxysh.2023.06.014.
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Medical imaging techniques are important in the management of many patients with liver disease. Unenhanced ultrasound examinations sometimes identify focal abnormalities in the liver that may require further investigation, primarily to distinguish liver cancers from benign abnormalities. One important factor in selecting an imaging test is the ability to provide a rapid diagnosis. Options for additional imaging investigations include computed tomography (CT) and/or magnetic resonance imaging (MRI) and biopsy when the diagnosis remains uncertain. CT and MRI usually require referral with associated waiting time and are sometimes contraindicated. The use of contrast agents may improve the ability of ultrasound to distinguish between liver cancer and benign abnormalities and, because it can be performed at the same appointment as unenhanced ultrasound, more rapid diagnoses may be possible.To compare the clinical effectiveness and cost-effectiveness of contrast-enhanced ultrasound (CEUS) using SonoVue(®) with that of contrast-enhanced computed tomography (CECT) and contrast-enhanced magnetic resonance imaging (CEMRI) for the assessment of adults with focal liver lesions (FLLs) in whom previous liver imaging is inconclusive.Eight bibliographic databases including MEDLINE, EMBASE, Cochrane Database of Systematic Reviews and Database of Abstracts of Reviews of Effects were searched from 2000 to September/October 2011. Research registers and conference proceedings were also searched.Systematic review methods followed published guidance. Risk of bias was assessed using a modified version of the QUADAS-2 tool. Results were stratified by clinical indication for imaging (characterisation of FLLs detected on ultrasound surveillance of cirrhosis patients, detection of liver metastases, characterisation of incidentally detected FLLs, assessment of treatment response). For incidental FLLs, pooled estimates of sensitivity and specificity, with 95% CIs, were calculated using a random-effects model. For other clinical indications a narrative summary was used. The cost-effectiveness of CEUS was modelled separately for the three main clinical applications considered [characterisation of FLLs detected on ultrasound surveillance of cirrhosis patients, detection of liver metastases in patients with colorectal cancer (CRC), characterisation of incidentally detected FLLs].Of the 854 references identified, 19 (describing 18 studies) were included in the review. Hand searching of conference proceedings identified a further three studies. Twenty of the 21 studies included in the systematic review were diagnostic test accuracy studies. Studies in cirrhosis patients reported varying estimates of test performance. There was no consistent evidence of a significant difference in performance between imaging modalities. It was unclear whether or not CEUS alone is adequate to rule out hepatocellular carcinoma (HCC) for FLLs of < 30 mm; one study indicated that CEUS may be better at ruling out HCC for FLLs of 11-30 mm [very small FLLs (< 10 mm) excluded]. There was no consistent evidence of a difference in test performance between imaging modalities for the detection of metastases; CEUS alone may be adequate to rule out liver metastases in colorectal cancer. In patients with incidentally detected FLLs, the pooled estimates of sensitivity for any malignancy using CEUS and CECT were 95.1% and 94.6%, respectively, and the corresponding specificity estimates were 93.8% and 93.1% respectively. One study comparing CEUS with CEMRI reported similar sensitivity and lower specificity for both modalities. In the surveillance of cirrhosis, CEUS was as effective as but £379 less costly than CECT. CEMRI was £1063 more costly than CEUS and gained 0.022 QALYs. In the detection of liver metastases from CRC, CEUS cost £1 more than CECT, and at a lifetime time horizon they yielded equal QALYs. CEMRI was dominated by CECT. In the characterisation of incidentally detected FLLs, CEUS was slightly more effective than CECT and CEMRI (by 0.0002 QALYs and 0.0026 QALYs respectively) and less costly (by £52 and £131 respectively).There were a number of methodological issues specific to the studies included in this review. The main indication for liver imaging in the populations considered is likely to be to rule out primary liver cancer or metastases. Therefore, patient-level analyses of test performance are of particular interest. Some of the studies included in this review reported per-patient analyses; however, no study clearly stated how results were defined (e.g. was the presence of any positive lesion regarded as a positive test for the whole patient). In addition, a number of studies reported data for one lesion per patient (treated as per-patient data in this assessment). These studies generally selected the largest lesion or the lesion 'most suspicious for malignancy' for inclusion in analyses, with the consequence that estimates of test performance may have been exaggerated. The applicability of studies included in this review may be limited, as the majority of imaging studies were interpreted by multiple, experienced operators and the prevalence of malignancy in included studies appeared higher than might be expected in clinical practice. The cost-effectiveness analyses did not take into account the potential benefits of reduced anxiety that may arise from potentially shorter waiting times associated with SonoVue CEUS.SonoVue CEUS could provide similar diagnostic performance to other imaging modalities (CECT and CEMRI) for the assessment of FLLs. Economic analyses indicated that CEUS was a cost-effective replacement for CEMRI. The use of CEUS instead of CECT was considered cost-effective in the surveillance of cirrhosis and the characterisation of incidentally detected FLLs, with similar costs and effects for the detection of liver metastases from CRC. Further research is needed to compare the effects of different imaging modalities (SonoVue CEUS, CECT, CEMRI) on therapeutic planning, treatment and clinical outcomes. Future test accuracy studies should provide standardised definitions of a positive imaging test, and compare all three imaging modalities in the same patient group.PROSPERO: CRD42011001694.The National Institute for Health Research Health Technology Assessment programme.
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To determine the feasibility of spectral computed tomography (CT) in the differentiation of focal liver lesions from hepatocellular carcinoma (HCC) using a network meta-analysis (NMA).The review was completed in accordance with PRISMA guidelines. Searches of three medical databases were performed. A total of nine articles were found for the qualitative synthesis. The meta-analysis was performed on five studies for the normalised iodine concentration (NIC; which is the iodine concentration in the lesion divided by the iodine concentration in the aorta) and the lesion-normal parenchyma iodine ratio (LNR; which is the iodine concentration in the lesion divided by the iodine concentration in the non-tumour hepatic parenchyma) on portal venous and arterial phase images due to sufficient data.Spectral CT can be used to differentiate HCC from hepatic haemangioma (HH), focal nodular hyperplasia (FNH), regenerative nodules, neuroendocrine tumours (NETs), abscesses, and angiomyolipoma (AML). Hepatic metastases versus abscess and FNH versus HH could also be differentiated. The NMA demonstrated that HCC, NETs, and regenerative nodules could be differentiated due to lower quantitative iodine values. FNH, AML, and HH all had higher values.Spectral CT shows promise in differentiating focal liver lesions. Studies with larger sample sizes are warranted. Future studies should be performed comparing benign lesions using quantitative markers.Copyright © 2023 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
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We investigated the effect of iodinated contrast medium concentration on increased neoplastic lesion enhancement and its direct relation to diagnostic efficacy in biphasic spiral computed tomography for detection of hepatocellular carcinoma.A pilot, single-center, randomized, double-blind, crossover, comparative study was performed and included 22 participants. Each patient underwent two separate biphasic contrast-enhanced spiral computed tomographic examinations. Scans were performed with iomeprol containing 400 (iomeprol 400) or 300 (iomeprol 300) mg of iodine per milliliter (Iomeron, Bracco Imaging SpA, Milan, Italy) with a 2- to 12-day window scan; patients were given an equal total dose of 45 g of iodine at a fixed injection rate of 4 mL/s. Comparison included assessment of quantitative and qualitative parameters.Lesion density and lesion-to-liver contrast increased more markedly with the higher concentration of contrast medium during the arterial phase (p = 0.0016 and 0.0005, respectively). There was no significant difference in any parameter between the two concentrations during the portal phase. Number of lesions detected during the arterial phase increased from 37 with iomeprol 300 to 42 with iomeprol 400; in the portal phase, the respective numbers were 34 and 36.Even though a small number of patients was examined, our study suggests that, in patients with cirrhosis, an increased concentration of iodine improves liver-to-lesion contrast and may improve the detection of hepatocellular carcinoma.
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Gadobenate and gadoxetate are hepatobiliary magnetic resonance imaging (MRI) contrast agents. We intraindividually compared these two agents for the characterization of focal liver lesions (FLLs).A total of 140 adult subjects were randomized to undergo two 3-T MRI exams separated by 7-14 days, one with 0.05 mmol/kg gadobenate and one with 0.025 mmol/kg gadoxetate. For both exams, we acquired the same unenhanced T1-weighted, T2-weighted, and diffusion-weighted sequences, followed by contrast-enhanced T1-weighted sequences during the dynamic and hepatobiliary phases (HBP) (at 20 min for gadoxetate, at 120 min for gadobenate). Three experienced unaffiliated readers independently evaluated each exam in blinded, randomized order for lesion nature (benign/malignant) and specific lesion diagnosis. McNemar test, Wald tests. paired t-tests and κ statistics were used.A total of 208 FLLs (108 malignant and 100 benign) were confirmed at final diagnosis. Sensitivity and specificity for malignant/benign differentiation ranged from 91.6% to 99.1% and from 87.5% to 90.5% for gadobenate, and from 86.0% to 91.6% and from 79.7% to 83.6% for gadoxetate. Significantly (p ≤ 0.025) higher values for gadobenate were determined for all diagnostic performance parameters except for sensitivity and negative predictive value for one reader. Significantly (p < 0.001) greater accuracy and confidence for specific lesion diagnosis was achieved with gadobenate for two of three blinded readers. Interreader agreement for malignant/benign differentiation was better with gadobenate (κ = 0.91 versus κ = 0.72).Gadobenate was superior to gadoxetate for the differentiation and diagnosis of malignant and benign FLLs for two of three readers. Further confirmatory studies that include a wider representation of different types of FLLs are warranted.Better diagnostic performance and greater confidence in the characterization of FLLs with gadobenate might improve patient management decisions and timings, and potentially lead to better patient outcomes.Better diagnostic performance for the differentiation of FLLs was achieved with gadobenate for two of three readers. Reader confidence for lesion diagnosis was greater with gadobenate. Superior dynamic phase imaging with gadobenate was crucial for accurate lesion diagnosis.© 2025. The Author(s).
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Society guidelines differ in their recommendations for surveillance to detect early-stage hepatocellular carcinoma (HCC) in patients with cirrhosis. We compared the performance of surveillance imaging, with or without alpha fetoprotein (AFP), for early detection of HCC in patients with cirrhosis.Two reviewers searched MEDLINE and SCOPUS from January 1990 through August 2016 to identify published sensitivity and specificity of surveillance strategies for overall and early detection of HCC. Pooled estimates were calculated and compared using the DerSimonian and Laird method for a random effects model. The study was conducted in accordance with Preferred Reporting Items for Systematic Review and Meta-analysis guidelines.Thirty-two studies (comprising 13,367 patients) characterized sensitivity of imaging with or without AFP measurement for detection of HCC in patients with cirrhosis. Ultrasound detected any stage HCC with 84% sensitivity (95% confidence interval [CI] 76%-92%), but early-stage HCC with only 47% sensitivity (95% CI 33%-61%). In studies comparing ultrasound with vs without AFP measurement, ultrasound detected any stage HCC with a lower level of sensitivity than ultrasound plus AFP measurement (relative risk [RR] 0.88; 95% CI 0.83-0.93) and early-stage HCC with a lower level of sensitivity than ultrasound plus AFP measurement (RR 0.81; 95% CI 0.71-0.93). However, ultrasound alone detected HCC with a higher level of specificity than ultrasound plus AFP measurement (RR 1.08; 95% CI 1.05-1.09). Ultrasound with vs without AFP detected early-stage HCC with 63% sensitivity (95% CI 48%-75%) and 45% sensitivity (95% CI 30%-62%), respectively (P = .002). Only 4 studies evaluated computed tomography or magnetic resonance image-based surveillance, which detected HCC with 84% sensitivity (95% CI 70%-92%).We found ultrasound alone has a low sensitivity to detect early stage HCC in patients with cirrhosis. Addition of AFP to ultrasound significantly increases sensitivity of early HCC detection in clinical practice.Copyright © 2018. Published by Elsevier Inc.
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Current practice guidelines recommend the use of ultrasound (US) as an initial surveillance tool for hepatocellular carcinoma (HCC) in patients with liver cirrhosis. Patients with liver cirrhosis, however, frequently have coarse liver parenchyma, masking the presence of tiny nodules during B-mode US. Contrast-enhanced US (CEUS) with Sonazoid has a long-lasting, stable Kupffer phase, which makes it possible to scan the entire liver to depict small lesions. In addition, defect reperfusion imaging (reinjection imaging) enables to determine whether the detected nodule is HCC or not. This prospective, multicenter, randomized, controlled trial was conducted to demonstrate the usefulness of Kupffer phase surveillance in the detection of small HCC compared to B-mode US.A total of 23 institutions joined this study. In total, 656 patients with hepatitis B- or C-related liver cirrhosis were randomized either to the B-mode US surveillance group ( = 313) or the Kupffer phase CEUS with Sonazoid surveillance group ( = 309). The primary endpoint was the maximum size of HCC at the time of the first detection. Secondary endpoints included time to HCC detection, number of tumors, and Barcelona Clinic Liver Cancer stage at the first detection, and sensitivity, specificity, and accuracy of each method in the diagnosis, and the cumulative detection rate of HCC.The mean HCC size at the first detection was significantly smaller in the CEUS (13.0 ± 4.1 mm; = 28) than in the B-mode US group (16.7 ± 4.1 mm; = 26) (p = 0.011). Of the 38 patients with HCV cirrhosis diagnosed with HCC by US alone, mean tumor size at the first detection was significantly smaller in the 20 patients diagnosed by CEUS alone than in the 18 diagnosed by B-mode US alone (12.7 ± 3.1 vs. 17.6 ± 7.0 mm, = 0.012). In contrast, among the 16 patients with HBV cirrhosis diagnosed by US alone, mean tumor size at the first detection was similar in the 8 patients diagnosed by CEUS alone and the 8 diagnosed by B-mode US (13.6 ± 6.0 vs. 14.5 ± 2.7 mm, = 0.715).Kupffer phase CEUS surveillance with Sonazoid is extremely useful for the early detection and confirmation of HCC using a reinjection technique. Kupffer phase CEUS with Sonazoid contrast combined with the reinjection technique is, therefore, recommended as first-line screening tool for HCC in patients with liver cirrhosis, especially those with very coarse liver parenchyma.Copyright © 2019 by S. Karger AG, Basel.
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Biannual ultrasonography (US) is a current recommendation for hepatocellular carcinoma (HCC) surveillance in a high-risk group. The sensitivity of US, however, has been low in patients with a high risk of developing HCC. We aimed to compare sensitivity for HCC of biannual US and two-phase low-dose computed tomography (LDCT) in patients with a high risk of HCC.In this prospective single-arm study, participants with an annual risk of HCC greater than 5% (based on a risk index of ≥2.33) and who did not have a history of HCC were enrolled from November 2014 to July 2016. Participants underwent paired biannual US and two-phase LDCT 1-3 times. Two-phase LDCT included arterial and 3-min delayed phases. The sensitivity, specificity, and positive predictive value of HCC detection using US and two-phase LDCT were compared using a composite algorithm as a standard of reference.Of the 139 enrolled participants, 137 underwent both the biannual US and two-phase LDCT at least once and had follow-up images. Among them, 27 cases of HCC (mean size: 14 ± 4 mm) developed in 24 participants over 1.5 years. Two-phase LDCT showed a significantly higher sensitivity (83.3% [20/24] vs. 29.2% [7/24], < 0.001) and specificity (95.6% [108/113] vs. 87.7% [99/113], =0.03) than US. A false-positive result was reported in 14 participants at US and 5 participants at two-phase LDCT, resulting in a significantly higher positive predictive value of two-phase LDCT (33.3% [7/21] vs. 80% [20/25], < 0.001).Patients with a risk index ≥2.33 showed a high annual incidence of HCC development in our study, and two-phase LDCT showed significantly higher sensitivity and specificity for HCC detection than US.Copyright © 2020 by S. Karger AG, Basel.
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Current recommendations for patients with cirrhosis are to undergo surveillance for hepatocellular carcinoma (HCC) with ultrasonography (US) every 6 months. However, the sensitivity of US screening to detect early-stage HCC is suboptimal. Magnetic resonance imaging (MRI) with liver-specific contrast may detect additional HCCs missed by US in high-risk patients with cirrhosis.To compare the HCC detection rate of US and MRI in patients with cirrhosis who are at high risk for HCC.A prospective surveillance study of 407 patients with cirrhosis and an estimated annual risk of HCC greater than 5% who underwent 1 to 3 biannual screening examinations with paired US and liver-specific contrast-enhanced MRI at a tertiary care hospital between November 2011 and August 2014. All patients were followed-up with dynamic computed tomography (CT) at 6 months after the study. The confirmation of HCC was based on the results of histologic examination and/or typical CT images of HCC.HCC detection rates and false-positive findings of US vs MRI.A total of 407 eligible patients received 1100 screenings with paired US and MRI. Hepatocellular carcinomas were diagnosed in 43 patients: 1 detected by US only, 26 by MRI only, 11 by both, and 5 were missed by both. The HCC detection rate of MRI was 86.0% (37/43), significantly higher than the 27.9% (12/43) of US (P < .001). Magnetic resonance imaging showed a significantly lower rate of false-positive findings than US (3.0% vs 5.6%; P = .004). Of the 43 patients with HCC, 32 (74.4%) had very early-stage HCC (a single nodule <2 cm), and 29 (67.4%) received curative treatments. The 3-year survival rate of the patients with HCC (86.0%) was not inferior to those without HCC (94.2%; hazard ratio, 2.26; 95% CI, 0.92-5.56; P = .08).In patients with cirrhosis at high-risk of HCC, screening that used MRI with liver-specific contrast resulted in a higher HCC detection rate and lower false-positive findings compared with US. With MRI screening, most of the cancers detected were at very early stage, which was associated with a high chance of curative treatments and favorable survival of patients. Whether surveillance with MRI would reduce mortality from HCC in high-risk patients requires further investigation.clinicaltrials.gov Identifier: NCT01446666.
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Current recommendations for the surveillance of HCC are based on the semiannual liver ultrasound (with or without serum alpha-fetoprotein) in patients with cirrhosis and in subgroups with chronic hepatitis B infection. However, the sensitivity of this strategy is suboptimal for the detection of early-stage tumors, especially in obese patients, due to interoperator variability and poor adherence. The detection rate of focal liver lesions is excellent with MRI, making it the best alternative candidate for surveillance. However, performing a full contrast-enhanced MRI is unrealistic because of limited availability and health economics. Abbreviated MRI (AMRI) corresponds to the acquisition of a limited number of sequences with a high detection rate. The theoretical benefits of AMRI are a reduced acquisition time (≤10 min) with improved time-effectiveness and cost-effectiveness compared with conventional MRI, and greater accuracy than ultrasound. Numerous protocols may be performed, including T1-weighted, T2-weighted, and DWI sequences, with or without contrast administration. Although published studies report promising per-patient results, they should be interpreted with caution. Indeed, most studies were simulated, retrospectively reviewing a subset of sequences in relatively small populations who underwent a full MRI. They also included groups that were not representative of screening populations. In addition, most were published by Asian groups, with at-risk populations that were different from Western populations. There are no existing longitudinal studies that directly compare the different AMRI approaches or AMRI to ultrasound. Finally, it is possible that 1 approach will not fit all patients and that strategies should be tailored to the risk of HCC, in particular in relation to the cost and availability of AMRI. Several trials are ongoing to evaluate these questions.
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Ultrasonography (US) is recommended for HCC surveillance in high-risk patients but has limited performance in detecting early-stage HCC. We aimed to compare the diagnostic performance of biannual US and annual non-contrast abbreviated magnetic resonance imaging (NC-AMRI) as HCC surveillance modalities in high-risk patients.This prospective, multicenter cohort study enrolled participants with an estimated annual risk of HCC greater than 5% between October 2015 and April 2017. Participants underwent six rounds of HCC surveillance at 6-month intervals, with both US and NC-AMRI at rounds 1, 3, and 5, and only US at rounds 2, 4, and 6. The sensitivity, diagnostic yield (DY), and false referral rate (FRR) for HCC detection by US and NC-AMRI were compared.In total, 208 participants underwent 980 US and 516 NC-AMRI examinations during 30 months of follow-up. Among them, 34 HCCs were diagnosed in 31 participants, with 20 (64.5%) classified as very early-stage and 11 (35.5%) as early-stage HCC. The sensitivity of annual NC-AMRI (71.0%, 22/31) was marginally higher than that of biannual US (45.2%, 14/31; p = 0.077). NC-AMRI showed a significantly higher DY than US (4.26% vs. 1.43%, p <0.001), with a similar FRR (2.91% vs. 3.06%, p = 0.885). A simulation of alternating US and NC-AMRI at 6-month intervals yielded a sensitivity of 83.9% (26/31), significantly exceeding that of biannual US (p = 0.006).Annual NC-AMRI showed a marginally higher sensitivity than biannual US for HCC detection in high-risk patients. The DY of annual NC-AMRI was significantly higher than that of biannual US, without increasing the FRR. Thus, alternating US and NC-AMRI at 6-month intervals could be an optimal surveillance strategy for high-risk patients.Current guidelines permit the use of magnetic resonance imaging (MRI) as a surveillance tool for hepatocellular carcinoma in patients in whom ultrasonography (US) is inadequate. However, the specific indications, imaging sequences, and intervals for MRI surveillance remain unclear. In our study, we found that annual non-contrast abbreviated MRI exhibited marginally higher sensitivity and significantly better diagnostic yield than biannual US in patients at high risk of hepatocellular carcinoma. Alternating US and non-contrast abbreviated MRI at 6-month intervals led to significantly improved sensitivity compared to biannual US, making it a potentially optimal surveillance strategy for high-risk patients.NCT02551250.Copyright © 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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Background Hepatobiliary phase (HBP) hypointense nodules without arterial phase hyperenhancement (APHE) at gadoxetic acid-enhanced MRI may indicate hepatocellular carcinoma (HCC) or nonmalignant cirrhosis-associated nodules. Purpose To assess the distribution of pathologic diagnoses of HBP hypointense nodules without APHE at gadoxetic acid-enhanced MRI and to evaluate clinical and imaging features in differentiating their histologic grades. Materials and Methods This retrospective multicenter study included pathologic analysis-confirmed HBP hypointense nodules without APHE (≤30 mm) in patients with chronic liver disease or cirrhosis screened between January 2008 and June 2016. Central pathologic review by 10 pathologists determined final histologic grades as progressed HCC, early HCC, high-grade dysplastic nodule (DN), and low-grade DN or regenerative nodule. Gadoxetic acid-enhanced MRI features were analyzed by three radiologists. Multivariable logistic regression analyses with elastic net regularization were performed to identify clinical and imaging features for differentiating histologic grades. Results There were 298 patients (mean age, 59 years ± 10; 226 men) with 334 nodules evaluated, and progressed HCCs were diagnosed in 44.0% (147 of 334), early HCCs in 20.4% (68 of 334), high-grade DNs in 27.5% (92 of 334), and low-grade DNs or regenerative nodules in 8.1% (27 of 334). Serum α-fetoprotein level 100 ng/mL or greater (odds ratio, 2.7; =.01) and MRI features including well-defined margin (odds ratio, 5.5; =.003), hypointensity at precontrast T1-weighted imaging (odds ratio, 3.2; <.001), intermediate hyperintensity at T2-weighted imaging (odds ratio, 3.4; <.001), and restricted diffusion (odds ratio, 1.9; =.04) were independent predictors for progressed HCC at multivariable analysis. Conclusion In patients at high risk for hepatocellular carcinoma (HCC), hepatobiliary phase hypointense nodules without arterial phase hyperenhancement at gadoxetic acid-enhanced MRI corresponded mainly to progressed HCCs, early HCCs, and high-grade dysplastic nodules. High α-fetoprotein level and some imaging features at MRI helped to differentiate progressed HCC from lower grade nodules. © RSNA, 2020 See also the editorial by Motosugi in this issue.
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中华人民共和国国家卫生健康委员会医政司. 原发性肝癌诊疗指南(2024年版)[J]. 中国实用外科杂志, 2024, 44(4):361-386. DOI:10.19538/j.cjps.issn1005-2208.2024.04.01.
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Multiphasic computed tomography (CT) and magnetic resonance imaging (MRI) are both used for noninvasive diagnosis of hepatocellular carcinoma (HCC) in patients with cirrhosis. To determine if there is a relative diagnostic benefit of one over the other, we synthesized evidence regarding the relative performance of CT, extracellular contrast-enhanced MRI, and gadoxetate-enhanced MRI for diagnosis of HCC in patients with cirrhosis. We also assessed whether liver biopsy versus follow-up with the same versus alternative imaging is best for CT-indeterminate or MRI-indeterminate liver nodules in patients with cirrhosis. We searched multiple databases from inception to April 27, 2016, for studies comparing CT with extracellular contrast-enhanced MRI or gadoxetate-enhanced MRI in adults with cirrhosis and suspected HCC. Two reviewers independently selected studies and extracted data. Of 33 included studies, 19 were comprehensive, while 14 reported sensitivity only. For all tumor sizes, the 19 comprehensive comparisons showed significantly higher sensitivity (0.82 versus 0.66) and lower negative likelihood ratio (0.20 versus 0.37) for MRI over CT. The specificities of MRI versus CT (0.91 versus 0.92) and the positive likelihood ratios (8.8 versus 8.1) were not different. All three modalities performed better for HCCs ≥2 cm. Performance was poor for HCCs <1 cm. No studies examined whether adults with cirrhosis and an indeterminate nodule are best evaluated using biopsy, repeated imaging, or alternative imaging. Concerns about publication bias, inconsistent study results, increased risk of bias, and clinical factors precluded support for exclusive use of either gadoxetate-enhanced or extracellular contrast-enhanced MRI over CT.CT, extracellular contrast-enhanced MRI, or gadoxetate-enhanced MRI could not be definitively preferred for HCC diagnosis in patients with cirrhosis; in patients with cirrhosis and an indeterminate mass, there were insufficient data comparing biopsy to repeat cross-sectional imaging or alternative imaging. (Hepatology 2018;67:401-421).© 2017 by the American Association for the Study of Liver Diseases.
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To perform a systematic review and meta-analysis of the diagnostic performance of computed tomography (CT) and magnetic resonance (MR) imaging as noninvasive modalities for evaluating hepatocellular carcinoma (HCC) in patients with chronic liver disease.A search of the MEDLINE, EMBASE, and Cochrane Library databases was performed to identify studies providing per-patient or per-lesion diagnostic accuracies of multidetector CT and MR imaging for HCCs in patients with chronic liver disease. Studies published from January 2000 to December 2012 that used a reference standard based on histopathologic findings and/or findings at follow-up were included. Summary estimates of diagnostic accuracy were obtained by using a random-effects model with further exploration with meta-regression and subgroup analyses.Forty studies (six on multidetector CT, 22 on MR imaging, and 12 on both CT and MR imaging) were included. The studies evaluated a total of 1135 patients with multidetector CT and 2489 patients with MR imaging. The overall per-patient sensitivity of MR imaging was 88% (95% confidence interval [CI]: 83%, 92%), with a specificity of 94% (95% CI: 85%, 98%). The overall per-lesion sensitivity of MR imaging was higher than that of multidetector CT when the paired data of the 11 available studies were pooled (80% vs 68%, P =.0023). Gadoxetic acid-enhanced MR imaging showed significantly higher per-lesion sensitivity than MR imaging performed with other contrast agents (87% vs 74%, P =.03). Per-lesion sensitivity was significantly lower for HCCs smaller than 1 cm than that for HCCs 1 cm or larger (P <.001 for CT, P =.02 for MR imaging) and for those in explanted livers (P =.04 for CT, P <.001 for MR imaging).MR imaging showed higher per-lesion sensitivity than multidetector CT and should be the preferred imaging modality for the diagnosis of HCCs in patients with chronic liver disease.© RSNA, 2015 Online supplemental material is available for this article.
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程燕霞, 付左骏, 周颖. 肝癌超声造影特征及与临床分期、微血管侵犯的相关性研究[J]. 浙江医学, 2024, 46(12): 1309-1313. DOI:10.12056/j.issn.1006-2785.2024.46.12.2024-56.
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侯宝华, 简志祥, 孙建, 等. B型超声检查在肝癌切除术中的临床应用[J]. 南方医科大学学报, 2007, 27(7): 1039-1040. DOI:10.3321/j.issn:1673-4254.2007.07.036.
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Background: The aim of this study was to evaluate the performance and the impact of contrast-enhanced intraoperative ultrasound (CE-IOUS) on intraoperative decision-making, as there is still no standardized protocol for its use. Therefore, we retrospectively analyzed multiple CE-IOUS performed in hepato-pancreatic-biliary surgery with respect to pre- and postoperative imaging and histopathological findings. Methods: Data of 50 patients who underwent hepato-pancreatic-biliary surgery between 03/2022 and 03/2024 were retrospectively collected. CE-IOUS was performed with a linear 6–9 MHz multifrequency probe connected to a high-resolution device. The ultrasound contrast agent used was a stabilized aqueous suspension of sulphur hexafluoride microbubbles. Results: In total, all 50 lesions indicated for surgery were correctly identified. In 30 cases, CE-IOUS was used to localize the primary lesion and to define the resection margins. In the remaining 20 cases, CE-IOUS identified an additional lesion. Fifteen of these findings were identified as malignant. In eight of these cases, the additional malignant lesion was subsequently resected. In the remaining seven cases, CE-IOUS again revealed an inoperable situation. In summary, CE-IOUS diagnostics resulted in a high correct classification rate of 95.7%, with positive and negative predictive values of 95.2% and 100.0%, respectively. Conclusions: CE-IOUS shows excellent performance in describing intraoperative findings in hepato-pancreatic-biliary surgery, leading to a substantial impact on intraoperative decision-making.
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| [31] |
The goal of the study described here was to define the predictive value of pre-operative clinical information and contrast-enhanced ultrasound (CEUS) imaging characteristics in combined hepatocellular-cholangiocarcinoma (CHC) patients with microvascular invasion (MVI). Seventy-six patients with pathologically confirmed CHC were enrolled in this study, comprising 18 patients with MVI-positive status and 58 with MVI-negative CHC nodules. The pre-operative clinical data and CEUS imaging features were retrospectively analyzed. Univariate and multivariate analyses were performed to identify the potential predictors of MVI in CHC. Recurrence-free survival (RFS) after hepatectomy was compared between patients with different MVI status using the log-rank test and Kaplan-Meier survival curves. Univariate analysis indicated that the following parameters of patients with CHC significantly differed between the MVI-positive and MVI-negative groups (p<0.05): tumor size, α-fetoprotein ≥400 ng/mL, enhancement patterns in arterial phase and marked washout during the portal venous phase on CEUS. On multivariate logistic regression analysis, only the CEUS characteristics of heterogeneous enhancement (odds ratio = 6.807; 95% confidence interval [CI]: 1.099, 42.147; p = 0.039) and marked washout (odds ratio = 4.380; 95% CI: 1.050,18.270; p = 0.043) were identified as independent predictors of MVI in CHC. The combination of the two risk factors in predicting MVI achieved a better diagnostic performance than each parameter alone, with an area under the receiver operating characteristic curve of 0.736 (0.622, 0.830). After hepatectomy, CHC patients with MVI exhibited earlier recurrence compared with those without MVI (hazard ratio = 1.859; 95% CI: 0.8699-3.9722, p = 0.046). The CEUS imaging features of heterogeneous enhancement in the arterial phase and marked washout during the portal venous phase were the potential predictors of MVI in CHC. Aside from that, CHC patients with MVI had an earlier recurrence rate than those without MVI after surgery.Copyright © 2022. Published by Elsevier Inc.
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| [32] |
孔雅露, 汤红, 徐安丽. 超声引导下穿刺活检诊断鉴别早期肝癌价值评价[J]. 影像研究与医学应用, 2019, 3(16):189-190. DOI:CNKI:SUN:YXYY.0.2019-16-124.
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| [33] |
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| [34] |
薛静, 杜廷伟, 王运昌, 等. US-CT/MRI融合成像在肝癌患者超声引导下射频消融治疗中的应用价值分析[J]. 中国CT和MRI杂志, 2019, 17(12):77-80. DOI:10.3969/j.issn.16725131.2019.12.025.
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彭梓婷, 石统东. 超声造影引导射频消融治疗肝癌疗效的Meta分析[J]. 重庆医学, 2024, 53(10): 1548-1552. DOI:10.3969/j.issn.1671-8348.2024.10.019.
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| [36] |
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| [37] |
<b><i>Background:</i></b> Contrast-enhanced ultrasound (CEUS) with second-generation contrast agents performed 1 month after hepatocellular carcinoma (HCC) treatment is almost as sensitive as contrast-enhanced computed tomography (CECT) in depicting the residual tumor. However, the efficacy of CEUS performed early after the procedure is still debated. <b><i>Aim:</i></b> We evaluated the diagnostic accuracy (DA) of CEUS for the assessment of tumor response shortly after locoregional therapy in patients with unresectable HCC. <b><i>Methods:</i></b> Ninety-four patients with 104 HCC lesions who were scheduled to receive percutaneous ethanol injection, radiofrequency ablation, transcatheter arterial chemoembolization, or combined treatment were enrolled in this study. With CECT at 1-month as the reference standard, the DA of CEUS performed 48-h after the procedure was evaluated. Patients were followed-up to look for tumor or disease progression. <b><i>Results:</i></b> Based on CECT findings, 43/104 lesions were diagnosed as having residual viability after 1 month. CEUS performed 48 h after treatment detected residual tumor in 34/43 nodules with treatment failure at CECT with a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 79.1, 96.7, 94.4, 86.8, and 89%, respectively. There was a high degree of concordance between CEUS and CECT (kappa coefficient = 0.78). A hyperemic halo was detectable in 35 lesions without a statistically significant difference between concordant and discordant cases. In patients with uninodular disease responders according to 48 h CEUS had a significantly longer mean overall survival and time to progression compared to nonresponders. <b><i>Conclusion:</i></b> CEUS performed 48 h after treatment can be considered a reliable modality for the evaluation of the real extent of necrosis and has prognostic value in the assessment of HCC.
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| [38] |
王玉, 宣之东, 郑雪, 等. 超声造影对原发性肝癌数字减影血管造影引导下肝动脉化疗栓塞治疗的疗效评估价值[J]. 现代生物医学进展, 2020, 20(6): 1185-1188. DOI:10.13241/j.cnki.pmb.2020.06.042.
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This study reviewed the literature to directly evaluate the diagnostic performance of contrast-enhanced ultrasonography (CEUS) versus contrast-enhanced computed tomography (CECT) for assessing residual tumors of hepatocellular carcinoma treated with transarterial chemoembolization.PubMed, Embase, the Cochrane Library, and the China National Knowledge Infrastructure were searched through April 30, 2017. The pooled sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and summary receiver operating characteristic curve were calculated and compared to examine the diagnostic performance of CEUS versus CECT.A total of 11 studies, including 421 patients and 491 nodules were analyzed. The pooled diagnostic performances of CEUS versus CECT were as follows: (1) sensitivity (95% confidence interval), 0.97 (0.95-0.99) versus 0.72 (0.67-0.76); (2) specificity, 0.86 (0.74-0.94) versus 0.99 (0.95-1.00); (3) positive predictive value, 0.97 (0.95-0.99) versus 1.00 (0.98-1.00); (4) negative predictive value, 0.90 (0.83-0.95) versus 0.51 (0.44-0.58); (5) positive likelihood ratio, 7.79 (4.73-12.82) versus 12.50 (5.74-27.20); (6) negative likelihood ratio, 0.05 (0.03-0.09) versus 0.35 (0.26-0.48); (7) diagnostic odds ratio, 150.56 (57.03-397.49) versus 35.54 (14.89-84.83); and (8) area under the summary receiver operating characteristic curve, 0.9875 versus 0.9239. The sensitivity and negative predictive value of CEUS were significantly higher than those of CECT (both P < .001). The specificity and positive predictive value of CECT were significantly higher than those of CEUS (both P < .05).Contrast-enhanced US, with better sensitivity and negative predictive value versus CECT, was an effective method for exclusion of residual tumors after transarterial chemoembolization. Contrast-enhanced CT, with higher specificity than CEUS, is a valid approach for identifying residual tumors.© 2018 by the American Institute of Ultrasound in Medicine.
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| [40] |
To assess and compare the diagnostic value of contrast-enhanced MRI (CEMRI) and contrast-enhanced CT (CECT) for evaluating the response of hepatocellular carcinoma (HCC) after transarterial chemoembolisation (TACE).
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| [41] |
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| [42] |
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| [43] |
Intravenous contrast-enhanced ultrasound (CEUS), using the second-generation ultrasound contrast agent SonoVue, has been widely used in adults. In 2016, it was approved for pediatric applications by the American Food and Drug Administration (FDA). However, it has not been approved by the Chinese Food and Drug Administration (CFDA). The objective of the study was to evaluate the safety and effectiveness of CEUS in children prospectively at a single center in China. A total of 312 cases of Chinese children were enrolled in clinical trials. Contrast agent was given intravenously with two different doses, including 2.4 ml/time and 0.03 ml/kg. All CEUS was performed for evaluating adverse effect and the diagnostic accuracy compared with the pathology and enhanced CT. All 312 subjects underwent CEUS successfully. The dose of contrast agent for CEUS was 2.4 ml between November 2015 and June 2016, which was modified to 0.03 ml/kg between July 2016 and April 2019, according to the recommendation of the FDA. With the two different doses of the contrast agent, the heart rate, respiration rate, oxygen saturation, and blood pressure of the participants had no statistically significant difference (> 0.05) before and after administration. The blood pressure had been significantly decreased in participants who received combined anesthetic administration. Following 600 intravenous injections of the CEUS, there were three cases of transient rash and three cases of hypotension (n = 6, 1.92%). The six recovered quickly after receiving intravenous methylprednisolone and epinephrine. Most of the studies were performed for evaluating renal microcirculation and assisting renal biopsy (192/312 [61.5%]), which together had a 98.9% effectiveness in the identification of pathology in the specimens. Some studies were conducted to identify a mass in the liver, retroperitoneum, abdominal cavity, kidneys, testicles, thyroid, and so on (99/312 [31.4%]), which had a 97.6% accuracy. The other studies were conducted to identify trauma, vascular malformation, infection, hemorrhage, and so on (21/312 [6.73%]), which had a similar accuracy to enhanced CT. The adverse effects of CEUS in children are similar to that in adults. The results indicate that it is safe to use SonoVue for CEUS in pediatric patients.Copyright © 2019 Mao, Xia, Chen, Gao, Yang, Li, Wang, Mai, Liu, Wen, Gan, Song, Wei, Yang, Wu, Yang, Yu, Yu, Fan, Tao, Feng, Lin and Liu.
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