Evaluation of sorafenib for hepatocellular carcinoma by contrast-enhanced ultrasonography: A pilot study

AIM: To determine the usefulness of arrival time parametric imaging (AtPI) using contrast-enhanced ultrasonography (CEUS) with Sonazoid in evaluating early response to sorafenib for hepatocellular carcinoma (HCC).METHODS: Fourteen advanced HCC patients who received sorafenib 400/800 mg/d for at least 4 wk and were followed up by CEUS were enrolled in this study. CEUS was performed before treatment and 2 and 4 wk after treatment, and images of the target lesion in the arterial phase were recorded for each patient. The images were analyzed by AtPI. Color mapping (CM) images obtained by AtPI were compared before and after the treatment. In these CM images, the mean arrival time of the contrast agent in the region of interest from the starting point [mean time (MT)] was calculated. In each patient, differences between MT before and MT 2 and 4 wk after the treatment were compared with responses evaluated 4-8 wk after the treatment by dynamic computed tomography (CT), and statistical analysis was performed. Modified response evaluation criteria in solid tumors was used for the response evaluation.RESULTS: In CM images both 2 and 4 wk after the treatment, delays in the arrival time of the contrast agent were noted in 8 of the 14 patients. In the other 6 patients, no color changes were observed in the tumor, or red and/or yellow increase, suggesting a decrease in blood flow velocity between images 2 and 4 wk after the treatment and those before the treatment. Dynamic CT could be performed 4-8 wk after the treatment in 13 of the 14 patients. Median differences in the MT were 1.13 s and 1.015 s, 2 and 4 wk after the treatment, respectively, in the 8 patients who showed stable disease (SD)/partial response (PR) on dynamic CT. Median differences in the MT were -0.39 s and -0.95 s, 2 and 4 wk after the treatment, respectively, in the 5 patients who showed progressive disease (PD). Differences in the median MT between SD/PR and PD groups were significant 2 and 4 wk after the treatment with P = 0.019 and P = 0.028, respectively.CONCLUSION: AtPI by CEUS using Sonazoid is suggested to be useful for evaluating early responses to sorafenib.     

Small hepatic nodules (< or =2 cm) in cirrhosis patients: characterization with contrast-enhanced ultrasonography.

AIM: We evaluated the efficacy of contrast-enhanced ultrasonography (CEUS) for the characterization of small hepatic nodules (< or =2 cm) in cirrhosis patients. PATIENTS AND METHODS: Thirty cirrhosis patients with 30 hepatic nodules (1-2 cm) were enrolled in this study. Eighteen hepatic nodules were hepatocellular carcinomas (HCC) and 12 were benign lesions. CEUS was performed using microbubble contrast (Levovist). With surrounding hepatic parenchyma as a reference, two characteristics of hepatic nodules, including arterial phase enhancement (AE) and the absence of delayed phase enhancement (ADE), were evaluated as criteria for the diagnosis of HCC. A radiologist independently reviewed the dynamic computed tomographies (CT) of 26 hepatic nodules. RESULTS: CEUS showed AE in 15 nodules (13 HCC and two benign) and ADE in 17 lesions (14 HCC and three benign). For HCC, the coincidental AE of both CEUS and dynamic CT was 40%. Using both AE and ADE for HCC diagnosis, the sensitivity, specificity, accuracy, positive predictive value and negative predictive values were 55.6%, 91.7%, 70%, 90.9% and 57.9%, respectively. When using either AE or ADE for HCC diagnosis, the same parameters were 94.4%, 66.7%, 83.3%, 81% and 88.9%, respectively. One benign hepatic nodule with both AE and ADE was diagnosed as HCC 29 months after the CEUS study. CONCLUSIONS: A combination of characteristics of AE and ADE as determined by CEUS was highly specific for small HCCs in cirrhosis patients. Concurrent delayed phase imaging is useful in the diagnosis of small hypovascular HCCs.     

Efficacy of platinum analogue for advanced hepatocellular carcinoma unresponsive to transcatheter arterial chemoembolization with epirubicin

Aim:  Hepatocellular carcinoma (HCC) often shows resistance to transcatheter arterial chemoembolization (TACE). Such patients often have a poor prognosis and are unresponsive to other forms of therapy. The aim of this retrospective study was to determine the response to TACE using platinum analogues in patients deemed resistant to TACE using epirubicin.
Methods:  We studied 152 consecutive patients with advanced HCC resistant to TACE using epirubicin. All cases were treated with platinum analogue using transcatheter arterial chemotherapy with or without embolization.
Results:  Computed tomography at 3 months after therapy showed complete response (CR) in 6 patients (4.0%), partial response (PR) in 28 (18%), stable disease (SD) in 35 (23%), and progressive disease (PD) in 83 (55%). The cumulative survival rates for PR/CR patients who received platinum analogue-transcatheter arterial chemotherapy with or without embolization (81.8% at first year, 53.9% at second year, and 33.1% at third year) were significantly higher than those of SD/PD patients (36.6%, 17.5% and 7.4%, respectively) ( P  < 0.001). The 50% survival period was extended almost 1.4 year in PR/CR patients who received platinum analogue-transcatheter arterial chemotherapy with or without embolization.
Conclusion:  Our retrospective study is the first to report the efficacy of platinum analogues for advanced HCC unresponsive to TACE using epirubicin.     

Preoperative chemoradiotherapy in cancer of the thoracic esophagus

Surgery with or without adjuvant radiotherapy (RT) is the standard treatment of esophageal cancer. Preoperative radio- and chemotherapy (CT) have been introduced to improve prognosis. We report a phase II prospective non-randomized trial of preoperative RT (42 Gy/25) plus CT (cisplatin 20 mg/mq/day plus 5-fluorouracil 600 mg/mq/day, 1-5 weeks) for the treatment of thoracic esophageal cancer. From 1993, 50 patients were enrolled (40 men and 10 women, mean age 57 years, range 30-75 years). Squamous cell carcinoma accounted for 90% of cases; 10% were adenocarcinoma. Downstaging of the disease was obtained in 77.3% of cases; there were 13 (29.5%) complete responses (CR) and 21 (47.7%) partial responses (PR). Median survival was 28 and 25 months, respectively, for CR and partial response (PR) plus stable disease (SD) and progressive disease (PD) (P = 0.05). Progressive-free median survival was 22 and 17 months, respectively, for CR and PR + SD + PD (P = 0.08). Multimodal treatment of esophageal cancer showed promising results, although not significant, in terms of survival and disease progression for patients achieving a complete pathologic response.     

Computed tomography perfusion in evaluating the therapeutic effect of transarterial chemoembolization for hepatocellular carcinoma

AIM： To prospectively assess the changes in parameters of computed tomography （CT） perfusion pre- and post-transarterial chemoembolization （TACE） of hepatocellular carcinoma （HCC） in different treatment response groups, and to correlate the changes with various responses of HCC to TACE. METHODS： Thirty-nine HCC patients underwent CT perfusion examinations pre-（1 d before TACE） and post-treatment （4 wk after TACE）. The response evaluation criteria for solid tumors （RECIST） were referred to when treatment responses were distributed. Wilcoxon-signed ranks test was used to compare the differences in CT perfusion parameters pre- and post- TACE for different response groups.
RESULTS： Only one case had treatment response to CR and the CT perfusion maps of post-treatment lesion displayed complete absence of signals. In the PR treatment response group, hepatic artery perfusion （HAP）, hepatic arterial fracture （HAF） and hepatic blood volume （HBV） of viable tumors post-TACE were reduced compared with pre-TACE （P = 0.001, 0.030 and 0.001, respectively）. In the SD group, all CT perfusion parameters were not significantly different pre- and post-TACE. In the PD group, HAP, HAl=, portal vein perfusion （PVP） and hepatic blood flow （HBF） of viable tumors post-TACE were significantly increased compared with pre-TACE （P = 0.005, 0.012, 0.035 and 0.005, respectively）.
CONCLUSION： Changes in CT perfusion parameters of viable tumors are correlated with different responses of HCC to TACE. Therefore, CT perfusion imaging is a feasible technique for monitoring response of HCC to TACE.     

Utility of contrast-enhanced ultrasonography with Sonazoid in radiofrequency ablation for hepatocellular carcinoma

Background and Aims: Kupffer imaging in contrast‐enhanced ultrasonography (CEUS) with Sonazoid, which lasts for 60 min or longer, may be useful in ultrasound‐guided percutaneous tumor ablation. The utility of Sonazoid in radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) was investigated in this study. Methods: We analyzed a total of 716 HCC nodules that were detected on dynamic computed tomography in 316 patients. Detectability of these nodules was compared between CEUS and conventional ultrasonography. The effectiveness in the treatment was assessed by comparing the mean numbers of treatment sessions of RFA in patients treated with CEUS and that in historical controls matched for tumor and background conditions. Results: Detectability of tumor nodule was 83.5% in conventional ultrasonography and 93.2% in CEUS (P = 0.04). Sixty‐nine nodules in 52 patients were additionally detected with CEUS. The number of additionally detected tumor nodules was positively correlated with serum albumin level (P = 0.016). The number of RFA sessions was 1.33 ± 0.45 with CEUS as compared to 1.49 ± 0.76 in the historical controls (P = 0.0019). Conclusions: CEUS with Sonazoid is useful for HCC detection in patients with a well‐conserved liver function reservoir. The decrease in RFA session numbers indicated the utility of Sonazoid in RFA treatment of HCC.     

Usefulness of contrast-enhanced ultrasonography with abdominal virtual ultrasonography in assessing therapeutic response in hepatocellular carcinoma treated with radiofrequency ablation.

OBJECTIVE: Contrast-enhanced computed tomography (CECT) is regarded as the gold standard for assessing the efficacy of radiofrequency ablation (RFA) against hepatocellular carcinoma (HCC). We evaluated the efficacy of virtual ultrasonography (VUS) with contrast-enhanced ultrasonography (CEUS) vs. CECT for assessing the response to RFA. MATERIALS AND METHODS: Study 1: The therapeutic responses in 22 patients with 26 HCC nodules were assessed by CEUS with VUS as well as by CECT. The efficacy of treatment was based on whether the safety margin was greater than 5 mm after RFA. Study 2: In seven patients with seven HCC nodules, the nodules were treated by RFA and the therapeutic efficacy was assessed by CEUS with VUS. The number of RFA sessions was assessed. RESULTS: Compared with CECT, CEUS with VUS had a specificity of 77%, a sensitivity of 91.6%, and an accuracy of 84%. When the therapeutic response to RFA was analyzed by CECT only, 1.86 +/- 0.69 assessments (mean) were required, while when response was assessed by CEUS with VUS, 1.14 +/- 0.38 CECT assessments were required (P = 0.03). CONCLUSION: CEUS with VUS is effective in assessing the therapeutic response to RFA of HCC. Moreover, the number of CECT scans required is reduced by this approach.     

立体定向放疗治疗老年单发肝细胞肝癌近期疗效分析

目的探讨立体定向放疗治疗老年单发肝细胞肝癌（hepatocellular carcinoma, HCC）的近期疗效及安全性。 方法选取浙江大学医学院附属第一医院收治的22例老年HCC患者（均为单发肝内病灶且肿瘤最大径<5 cm）,均行立体定向放疗,放疗后1、3、6个月行肝脏增强MRI检查评价近期疗效（分为完全缓解、部分缓解、局部稳定、局部进展）和不良反应（主要包括骨髓抑制、肝功能损伤、放射性胃肠炎、放射性肝病等）。 结果与放疗前比较,放疗后1、3、6个月的HCC病灶均显著缩小（t=6.211、4.824、4.209,均P<0.01）。随访期内总有效率相对稳定,放疗后1、3、6个月的近期总有效率（完全缓解率+部分缓解率）分别为81.8%、77.3%、72.7%。治疗及随访期间主要不良反应为骨髓抑制、肝功能损伤、放射性胃肠炎,患者均能耐受。 结论立体定向放疗治疗老年单发HCC效果良好,不良反应可耐受。     

Cost-effectiveness analysis on the surveillance for hepatocellular carcinoma in liver cirrhosis patients using contrast-enhanced ultrasonography

Aim: Sonazoid is a new contrast agent for ultrasonography (US). Contrast‐enhanced ultrasonography (CEUS) using Sonazoid enables Kupffer imaging, which improves the sensitivity of hepatocellular carcinoma (HCC) detection. However, there are no studies on the cost‐effectiveness of HCC surveillance using Sonazoid. Methods: We constructed a Markov model simulating the natural history of HCV‐related liver cirrhosis (LC) patients, and compared three strategies (no surveillance, US surveillance and CEUS surveillance). The transition probability and cost data were obtained from published data. The simulation and analysis were performed using TreeAge pro 2009 software. Results: When compared to the no surveillance group, the US and CEUS surveillance groups increased the life expectancy by 1.67 and 1.99 quality‐adjusted life‐years (QALY), respectively, and the incremental cost effectiveness ratio (ICER) were 17 296 $US/QALY and 18 384 $US/QALY, respectively. These results were both less than the commonly‐accepted threshold of $US 50 000/QALY. Even if the CEUS surveillance group was compared with the US surveillance group, the ICER was $US 24 250 and thus cost‐effective. Sensitivity analysis showed that the annual incidence of HCC and CEUS sensitivity were two critical parameters. However, when the annual incidence of HCC is more than 2% and/or the CEUS sensitivity is more than 80%, the ICER was also cost‐effective. Conclusions: Contrast‐enhanced ultrasonography surveillance for HCC is a cost‐effective strategy for LC patients and gains their longest additional life years, with similar degree of ICER in the US surveillance group. CEUS surveillance using Sonazoid is expected to be used not only in Japan, but also world‐wide.     

Hepatocellular carcinoma after ablation:The imaging follow-up scheme

Percutaneous ablation using thermal or chemical methods has been widely used in the treatment of hepatocellular carcinoma (HCC).Nowadays,contrast-enhanced imaging modalities such as computed tomography (CT),magnetic resonance imaging (MRI),and contrast-enhanced ultrasound (CEUS) are widely used to evaluate local treatment response after ablation therapies.CEUS is gaining increasing attention due to its characteristics including real-time scanning,easy performance,lack of radiation,wide availability,and lack of allergy reactions.Several studies have documented that CEUS is comparable to CT or MRI in evaluating local treatment efficacy within 1 mo of treatment.However,little information is available regarding the role of CEUS in the followup assessment after first successful ablation treatment.Zheng et al found that in comparison with contrastenhanced computed tomography (CECT),the sensitivity,specificity,positive predictive value,negative predictive value and overall accuracy of CEUS in detecting local tumor progression (LTP) were 67.5%,97.4%,81.8%,94.4% and 92.3%,respectively,and were 77.7%,92.0%,92.4%,76.7% and 84.0%,respectively for the detection of new intrahepatic recurrence.They concluded that the sensitivity of CEUS in detecting LTP and new intrahepatic recurrence after ablation is relatively low in comparison with CECT,and CEUS cannot replace CECT in the follow-up assessment after percutaneous ablation for HCC.These results are meaningful and instructive,and indicated that in the follow-up period,the use of CEUS alone is not sufficient.In this commentary,we discuss the discordance between CT and CEUS,as well as the underlying mechanisms involved.We propose the combined use of CT and CEUS which will reduce false positive and negative results in both modalities.We also discuss future issues,such as an evidence-based ideal imaging follow-up scheme,and a cost-effectiveness analysis of this imaging follow-up scheme.     

Efficacy of chemotherapy or chemo‐anti‐PD‐1 combination after failed anti‐PD‐1 therapy for relapsed and refractory hodgkin lymphoma: A series from lysa centers

Anti‐PD‐1 therapy provides high response rates in Hodgkin lymphoma (HL) patients who have relapsed or are refractory (R/R) to autologous stem cell transplantation (ASCT) and brentuximab vedotin (BV), but median progression free survival (PFS) is only one year. The efficacy of treatment following anti‐PD‐1 is not well known. We retrospectively investigated the efficacy of salvage therapies for unsatisfactory response to anti‐PD‐1 therapy, assessed by PET‐CT according to the Lugano criteria, in 30 R/R HL patients. Patients were highly pretreated before anti‐PD‐1 (70% received ASCT and 93% BV). Unsatisfactory responses to anti‐PD1 therapy were progressive disease (PD) (n = 24) and partial response (PR) (n = 6). For the 24 PD patients, median anti‐PD‐1 related PFS was 7.5 months (95%CI, 5.7‐11.6); 17 received subsequent CT alone (Group 1) and 7 received CT in addition to anti‐PD‐1 (Group 2). 16/24 patients (67%) obtained an objective response. In the 15 patients treated with the same CT, twelve obtained PR or complete response (CR). In Group 1, there were 7 CR (41%), 3 PR (18%), and 7 PD (41%). In Group 2, there were 4 CR (57%), 2 PR (29%), and 1 SD (14%). No unexpected toxicity was observed. Six patients who achieved response proceeded to allogeneic SCT. With a median follow‐up of 12.1 months (7‐14.7), the median PFS following the initiation of CT was 11 months (95% CI 6.3‐not reached) and the median of overall survival was not reached. These observations in highly pretreated HL patients suggest that anti‐PD‐1 therapy might re‐sensitize tumor cells to CT.     

USEFUL ENDOSCOPIC ULTRASONOGRAPHY TO ASSESS THE EFFICACY OF NEOADJUVANT THERAPY FOR ADVANCED ESOPHAGEAL CARCINOMA: BASED ON THE RESPONSE EVALUATION CRITERIA IN SOLID TUMORS

Objective: The aim of the present study was to assess the usefulness of endoscopic ultrasonography (EUS) for evaluating the efficacy of neoadjuvant therapy for advanced esophageal carcinoma based on the Response Evaluation Criteria in Solid Tumors (RECIST). Patients and Methods: Sixty‐two patients with advanced esophageal carcinoma underwent surgical resection after neoadjuvant therapy. The maximal tumor thickness was measured by EUS before and after neoadjuvant therapy, and the percent reduction was compared with the pathological response. Based on the RECIST, PD‐SD (progressive disease‐stable disease) was defined as < 30% reduction of tumor thickness on EUS, PR (partial response) as ≥ 30% reduction of tumor thickness, and CR (complete response) as no detectable tumor (100%). Results: The percent reduction of the thickness of Grade 0–1, Grade 2 and Grade 3 tumor was 11.5 ± 21.0%, 48.2 ± 17.0% and 74.9 ± 21.1%, respectively. There were significant differences in the extent of reduction among the three groups. Based on the RECIST, 80% of Grade 0–1 cases, 91% of Grade 2 cases and 22% of Grade 3 cases were PD‐SD, PR, and CR according to EUS, respectively. EUS correctly identified 80% of non‐responders and 94% of responders. Conclusions: The percentage reduction of tumor thickness on EUS closely reflected the pathological evaluation. EUS evaluation based on the RECIST seems to be useful for monitoring neoadjuvant therapy in patients with esophageal carcinoma.     

微波消融序贯化疗治疗晚期非小细胞肺癌的免疫学效应观察

目的探讨冷循环微波消融序贯化疗治疗晚期非小细胞肺癌（NSCLC）的近期疗效和免疫学效应。方法对58例晚期NSCLC行微波凝固治疗,1周后序贯化疗（方案为多烯紫杉醇75mg／m2＋顺铂30mg／m2,1～3d,21天为一周期,4周期为一疗程）,治疗前后采血检测免疫指标,胸部增强CT动态观察前后变化。结果58例NSCLC微波凝固治疗7d后细胞毒性T淋巴细胞（CTL）活性升高30例,升高率51．7％。1周后增强CT显示90％的肿块有10％-50％不同程度的缩小,完全坏死率达100％者36例、达80％以上者5例。化疗1疗程后行CT评价,完全缓解（CR）5．2％（3／58）、部分缓解（PR）34．5％（20／58）、病变稳定（SD）51．7％（30／58）、病变进展（PD）8．6％（5／58）;微波凝固序贯化疗患者临床获益率达91．4％。随访最短6月,最长24月,中位生存时间为13．2月,1年生存率为49．3％。结论CT引导下冷循环微波消融系统治疗肺癌是一种安全、有效的肿瘤局部治疗手段。微波凝固治疗即可降低肿瘤负荷,还可提高机体免疫,提高综合治疗的疗效。     

Transarterial embolization ablation of hepatocellular carcinoma with a lipiodol-ethanol mixture

AIM: To determine the safety and effectiveness of transarterial embolization ablation (TEA) of hepatocellular carcinoma (HCC) with a lipiodol-ethanol mixture. METHODS: Between January 1 and December 31, 2009, 15 patients with HCC (13 men/two women, aged 38-75 years) accepted TEA treatment and were enrolled in this study, including five newly diagnosed patients and 10 with refractory disease. Two months after TEA, angiography and contrast computed tomography (CT) were performed, and responses were assessed using a modified version of Response Evaluation Criteria in Solid Tumors (RECIST version 1.1). The follow-up period was to June 30, 2010. RESULTS: Every new case was treated once. Angiography was performed immediately after TEA, and showed that the tumor-feeding vessels were completely embolized and that lipiodol was densely deposited inside tumors. Two months after treatment, contrast CT showed no enhanced lesions. Alpha fetoprotein levels returned to normal in four patients and markedly decreased in another. mean ± SD survival after treatment was 10.8 ± 4.5 mo. All five patients survived during the follow-up period. Ten patients with refractory disease were treated a total of 14 times. Angiography immediately after TEA showed that blood flow to the tumors was obviously decreased in all cases, and contrast CT showed obvious depositions of lipiodol. Two months after treatment, the tumors had shrunk (6/10) or were stable (3/10). One had progressed after 2 mo and died of tumor rupture 3 mo after TEA. mean ± SD survival after treatment was 8.6 ± 4.3 mo; two patients survived during the follow-up period. Adverse effects included reversible hepatic decompensation, upper abdominal pain, and fever. CONCLUSION: TEA is an effective therapy for patients with HCC and might be more effective than transcather arterial chemoembolization for treating refractory disease.     

Improved diagnosis of well‐differentiated hepatocellular carcinoma with gadolinium ethoxybenzyl diethylene triamine pentaacetic acid‐enhanced magnetic resonance imaging and Sonazoid contrast‐enhanced ultrasonography

Aim: Two new imaging modalities have been developed recently that are directed at the focal liver lesions: gadolinium ethoxybenzyl diethylene triamine pentaacetic acid (Gd‐EOB‐DTPA)‐enhanced magnetic resonance imaging (MRI) and Sonazoid contrast‐enhanced ultrasonography (CEUS). We investigated the usefulness of these modalities for the diagnosis of small (<2 cm), well‐differentiated hepatocellular carcinoma (HCC). Methods: A total of 15 nodules from 13 patients, which were histologically diagnosed as well‐differentiated HCC, were subjected to this study. Lesions that showed hypervascularity in the arterial phase and washout in the portal or late non‐hemodynamic phase were regarded as HCC in the dynamic studies of all imaging modalities. Results: By multidetector computed tomography (MDCT), six of 15 (40%) nodules were diagnosed as HCC. Gd‐EOB‐DTPA‐enhanced MRI diagnosed HCC in nine of the 15 (60%) nodules. Of the nine nodules that were not diagnosed by MDCT, four could be diagnosed by Gd‐EOB‐DTPA‐enhanced MRI. In Sonazoid CEUS, 10 of 15 nodules (67%) were diagnosed as HCC. Four of nine nodules that could not be diagnosed as HCC by MDCT, were diagnosed by Sonazoid CEUS. A total of 11 of the 15 (73%) nodules were diagnosed as HCC by Gd‐EOB‐DTPA‐enhanced MRI and Sonazoid CEUS in addition to MDCT. Conclusion: Gd‐EOB‐DTPA‐enhanced MRI and Sonazoid CEUS had greater diagnostic value for small, well‐differentiated HCC than did conventional MDCT.     

表柔比星药物洗脱微球肝动脉化疗栓塞术治疗不可手术切除的原发性肝癌患者临床疗效和安全性分析

目的 探讨采用表柔比星药物洗脱微球肝动脉化疗栓塞术(DEB-TACE)治疗不可手术切除的原发性肝癌(PLC)患者的临床疗效和安全性。方法 2016年1月～2019年6月我院收治的78例不可手术切除是PLC患者,其中接受TACE治疗42例,接受表柔比星DEB-TACE治疗36例。根据RECIST评估临床疗效,比较两组治疗相关不良事件。随访2年,采用Log-Rank检验比较生存率。结果 DEB-TACE治疗组完全缓解(CR)、部分缓解(PR)、稳定(SD)和疾病进展(PD)率分别为16.7%、66.7%、13.9%和2.8%,客观缓解(OR)率为83.3%,而TACE治疗组分别为2.4%、52.4%、3 3.3%和11.9%,OR率为54.8%,差异显著(P<0.05);术后,DEB-TACE治疗组1级和2级腹痛分别为11.1%和3 3.3%,与TACE治疗组的30.9%和14.3%比,差异显著(P<0.05),1级恶心呕吐发生率为27.8%,显著高于TACE治疗组的9.5%,差异显著(P<0.05);在治疗结束后随访2年,TACE组和DEB-TACE组1 a生存率分别为...     

Assessment of metastatic liver disease in patients with primary extrahepatic tumors by contrast-enhanced sonography versus CT and MRI

AIM: To evaluate contrast-enhanced ultrasonography (CEUS) using SonoVue(?) in the detection of liver metas-tases in patients with known extrahepatic primary tumors versus the combined gold standard comprising CT, MRI and clinical/histological data. METHODS: It is an international multicenter study, and there were 12 centres and 125 patients (64 males, 61 females, aged 59±11 years) involved, with 102 patients per protocol. Primary tumors were colorectal in 35%, breast in 27%, pancreatic in 17% and others in 21%. CEUS using SonoVue(?) was employed with a low-mechanical-index technique and contrast-specific software using Siemens Elegra, Philips HDI 5000 and Acuson Sequoia; continuous scanning for at least five minutes. RESULTS: CEUS with SonoVue(?) increased significantly the number of focal liver lesions detected versus unen-hanced sonography. In 31.4% of the patients, more lesions were found after contrast enhancement. The total numbers of lesions detected were comparable with CEUS (55), triple-phase spiral CT (61) and MRI with a liver-specific contrast agent (53). Accuracy of detection of metastatic disease (i.e. at least one metastatic lesion) was significantly higher for CEUS (91.2%) than for un-enhanced sonography (81.4%) and was similar to that of triple-phase spiral CT (89.2%). In 53 patients whose CEUS examination was negative, a follow-up examination 3-6 months later confirmed the absence of metastatic lesions in 50 patients (94.4%). CONCLUSION: CEUS is proved to be reliable in the detection of liver metastases in patients with known extra-hepatic primary tumors and suspected liver lesions.     

Clinically Useful Diagnostic Tool of Contrast Enhanced Ultrasonography for Focal Liver Masses: Comparison to Computed Tomography and Magnetic Resonance Imaging

Background/Aims

To evaluate the diagnostic value of contrast (SonoVue®) enhancement ultrasonography (CEUS) and to compare this method with computed tomography (CT) and magnetic resonance imaging (MRI) in evaluating liver masses.

Methods

CEUS (n=50), CT (n=47), and MRI (n=43) were performed on 50 liver masses in 48 patients for baseline mass characterization. The most likely impression for each modality and the final diagnosis, based on the combined biopsy results (n=14), angiography findings (n=36), and clinical course, were determined. The diagnostic value of CEUS was compared to those of CT and MRI.

Results

The final diagnosis of the masses was hepatocellular carcinoma (n=43), hemangioma (n=3), benign adenoma (n=2), eosinophilic abscess (n=1), and liver metastasis (n=1). The overall diagnostic agreement with the final diagnosis was substantial for CEUS, CT, and MRI, with κ values of 0.621, 0.763, and 0.784, respectively. The sensitivity, specificity, and accuracy were 83.3%, 87.5%, and 84.0%, respectively, for CEUS; 95.0%, 87.5%, and 93.8%, respectively, for CT; and 94.6%, 83.3%, and 93.0%, respectively for MRI. After excluding the lesions with poor acoustic sonographic windows, the sensitivity, specificity, and accuracy for CEUS were 94.6%, 87.5%, and 93.3%, respectively, with a κ value of 0.765.

Conclusions

If an appropriate acoustic window is available, CEUS is comparable to CT and MRI for the diagnosis of liver masses.     

Contrast-enhanced ultrasound: Improving the preoperative staging of hepatocellular carcinoma and guiding individual treatment

AIM: To investigate the clinical role of contrast-enhanced ultrasound (CEUS) combined with contrast-enhanced computed tomography (CE-CT) or magnetic resonance imaging to improve the preoperative staging of hepatocellular carcinoma (HCC) and guide surgical decision-making.METHODS: Sixty-nine patients who underwent liver resection for HCC in our center were enrolled prospectively in the study. CEUS and CE-CT/MRI were performed before surgery. Intraoperative ultrasound (IOUS) was carried out after liver mobilization. Lesions depicted by each imaging modality were counted and mapped. To investigate the impact of tumor size on the study, we divided the patients into two groups, the “Smaller group”(S-group, ≤ 5 cm in diameter) and the “Larger-group” (L-group, > 5 cm in diameter). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of CE-CT/MRI, CEUS, IOUS, CEUS+CE-CT/MRI and the tumor node metastasis staging of tumors were calculated and compared. Changes in the surgical strategy as a result of CEUS and IOUS were analyzed.RESULTS: One hundred and twenty-seven nodules, comprising 94 HCCs confirmed by histopathology and 33 benign lesions confirmed by histopathology and follow-up, were identified in 69 patients. The overall diagnostic sensitivity rates of CE-CT/MRI, CEUS, IOUS and CEUS+ CE-CT/MRI were 78.7%, 89.4%, 89.4% and 89.4%, respectively. There was a significant difference between CEUS + CE-CT/MRI and CE-CT/MRI (P = 0.046). Combining CEUS with CT or MRI increased, the diagnostic specificity compared with CT/MRI, CEUS and IOUS, and this difference was statistically significant (100%, 72.7%, 97.0%, and 69.7%, P = 0.004, P = 0.002, P = 0.002, respectively). The diagnostic accuracy was significantly higher for CEUS + CT/MRI compared with CT/MRI (92.1% vs 77.2%, P = 0.001). The TNM staging of tumors based on CEUS + CE-CT/MRI approximated to the final pathological TNM staging (P = 0.977). There was a significant difference in the accuracy of TNM staging when comparing CEUS + CE-CT/MRI with CE-CT/MRI (P = 0.002). Before surgery, strategies were changed in 15.9% (11/69) of patients as a result of CEUS. Finally, only 5.7% (4/69) of surgical strategies were changed because of IOUS findings. In the S-group, CEUS revealed 12 false positive lesions, including seven false positive lesions that were diagnosed by preoperative imaging examinations and five by IOUS. In contrast, in the L-group, IUOS revealed eight new malignant lesions; six of these lesions were true HCCs that were also identified by preoperative CEUS.CONCLUSION: CEUS combined with CT or MRI improves the accuracy of preoperative staging for hepatocellular carcinoma and may help to guide individualized treatment for patients with HCC. CEUS may better identify non-malignant lesions in patients with small tumors and discover new malignant lesions in patients with large tumors.     

肝细胞癌患者TACE治疗前后血清miR-145水平变化及其临床意义

目的 探讨肝细胞癌(HCC)患者在经导管动脉化疗栓塞术(TACE)治疗前后血清microRNA-145(miR-145)水平变化及其临床意义。方法 2013年1月～2015年12月我院收治的72例HCC患者和同期60例健康体检者,采用qRT-PCR法检测血清miR-145水平,采用ROC曲线分析血清miR-145和甲胎蛋白(AFP)预测不良预后的价值。结果 在治疗1个月末,16例(22.2 %)为PR,13例(18.1%)为SD,43例(59.7 %)为PD;HCC组血清miR-145水平为(0.59±0.25),显著低于对照组【(1.02±0.28),P＜0.05】,术后1个月,HCC患者血清miR-145水平为(0.81±0.26),显著高于术前(P＜0.05);不同性别、年龄、肿瘤直径、肿瘤分化、癌栓和Child-Pugh分级患者血清miR-145水平无显著性差异(P＞0.05),而不同TNM分级和术前AFP水平患者之间差异显著(P＜0.05); PD组血清miR-145水平为(0.86±0.21),显著高于PR组或SD组【分别为(0.62±0.19)和(0.75±0.19),P＜0.05】;随访3年,28例(38.9%)患者死亡,其中高miR-14 水平患者3 a生存率为75.6 %,显著高于低水平患者的41.9 %(x²=8.765,P＜0.05);血清miR-145、AFP和miR-145联合AFP预测HCC不良预后的曲线下面积分别为0.871、0.851和0.942,两者联合预测的敏感度为91.7 %,准确度为90.2%。结论 TACE术后检测血清miR-145水平可能预示HCC患者预后较好。