CT增强扫描和MRI诊断小肝癌的应用价值

吕天甫 黄勇 王永新 沈宗朝 李天良

·临床论著·

CT增强扫描和MRI诊断小肝癌的应用价值

吕天甫*黄勇 王永新 沈宗朝 李天良

（西双版纳州人民医院放射科，云南 景洪 666100）

探讨CT增强扫描和MRI诊断小肝癌的应用价值。选择2016年1月至2019年7月在我院接受治疗的疑似小肝癌患者97例进行研究。入组后患者均由同一组医护人员行CT增强扫描及MRI检测。以病理检查为金标准，对各检测方法与联合检测的诊断效能进行分析，并对比各诊断效能指标。97例患者中共63例患者（64.95%）经病理学检查确诊为小肝癌。CT增强扫描对小肝癌诊断价值与金标准诊断结果一致性尚可（Kappa=0.445，P<0.05），灵敏度、特异度、准确度、阳性预测值、阴性预测值分别为77.78%（49/63）、67.65%（23/34）、74.23%（72/97）、81.67%（49/60）、62.16%（23/37）。MRI对小肝癌诊断价值与金标准诊断结果一致性尚可（Kappa=0.449，P<0.05），灵敏度、特异度、准确度、阳性预测值、阴性预测值分别为71.43%（45/63）、73.53%（25/34）、72.16%（70/97）、83.33%（45/54）、58.14%（25/43）。联合检测对小肝癌诊断价值与金标准诊断结果一致性较高（Kappa=0.795，P<0.05），灵敏度、特异度、准确度、阳性预测值、阴性预测值分别为90.48%（57/63）、85.29%（29/34）、88.66%（86/97）、91.94%（57/62）、82.86%（29/35）。联合检测在诊断灵敏度、特异度准确度及阴性预测值方面均明显高于CT增强扫描与MRI检测（P<0.05），三组阳性预测值对比差异无统计学意义（P>0.05）。CT增强扫描机MRI对小肝癌均具有较高的诊断价值，两者联合使用可显著提高诊断效能。

CT增强扫描；MRI；小肝癌；诊断价值

小肝癌也称为亚临床肝癌或早期肝癌，临床上多指肝细胞癌中单个癌结节最大直径在3 cm以内或两个癌结节直径和在3 cm以内的患者，此类患者临床尚无明显症状[1-3]。小肝癌血供充足，若能在发病早期发现病灶并根据其血供特点制订合适的治疗方案有助于提高治疗成功率[4-5]。因小肝癌患者症状隐匿，单靠临床症状难以诊断，对于该病的诊断临床上仍以病理检查为金标准，但该检查床上较大，因小肝癌患者症状不明显部分患者不愿意配合进行穿刺取样而致其临床应用受到一定限制[6]。随着影像学技术的不断发展，CT、MRI、超声等方法均被证实可用于肝癌的早期诊断，其中CT增强扫描与MRI为临床常用的肝癌早期诊断方法，但关于上述两种方法联合使用对小肝癌诊断方面的研究较少，因此本研究旨在通过分析CT增强扫描和MRI诊断小肝癌的应用价值，以期为该方法的临床应用提供参考依据。

1 资料与方法

1.1 一般资料

选择2016年1月至2019年7月在我院接受治疗的疑似小肝癌患者97例进行研究。纳入标准：①患者均有明确的肝硬化或慢性肝炎病史，经超声检查为疑似小肝癌；②神志清醒，智力正常，可配合进行相关检查；③患者已获知情同意。排除标准：①检查前接受过肝脏手术或介入治疗；②15d 内未接受过CT及MRI检查；③对造影剂过敏；④妊娠期及哺乳期妇女；⑤不愿意配合进行穿刺或手术病理检者；⑥合并心、肺、肾等重要脏器严重疾病；⑦合并其他恶性肿瘤。

1.2 方法

入组后患者均由同一组具5年以上临床经验的医护人员进行相关检查。

1.2.1 CT增强扫描

采用GE64排VCT进行检测，患者仰卧，双臂上举，腹部放松，对膈顶至髂嵴部位进行动态增强扫描，扫描前禁食4~5 h，前20 min饮水500 ml，经外周静脉注入碘佛醇注射液100 ml，流速为3.0 ml·s-1。扫描参数：电压120 kv，电流240 mA，层厚3 mm，矩阵512×512，先平扫后进行动态增强扫描。动脉期延迟30 s，静脉期延迟60 s，平衡期延迟120 s，结束后对原始数据图像重建。

1.2.2 MRI检查

以西门子1.5T Avanto MRI进行检测，患者仰卧，双臂上举，胸线圈，扫描范围同CT增强扫描，扫描时嘱屏气，扫描参数：层厚6 mm，间隔1 mm，对横断面、冠状面及矢状面分别行平行扫描，序列：T1W1：TR 400~500 ms，TE 15 ms，T2W2： TR 3500 ms，TE 105 ms。平扫后经右肘静脉推注钆喷酸葡胺，扫描序列为T1W1。

1.2.3 评价标准

由2~4名具高级技术职称的专家对CT及MRI图像进行诊断，将最终达成一致的结果以手术或穿刺病理检查结果为金标准，参照《原发性肝癌规范化病理诊断指南（2015年版）》[7]的相关规定进行诊断，计算各诊断效能指标。

1.3 统计学方法

采用SPSS22.0统计学软件进行数据分析，灵敏度=真阳性例数/（真阳性例数+假阴性例数）×100%，特异度=真阴性例数/（真阴性例数+假阳性例数）×100%，准确度=（真阳性例数+真阴性例数）/试验组总病例数×100%，阳性预测值=真阳性例数/（真阳性例数+假阳性例数）×100%，阴性预测值=真阴性例数/（真阴性例数+假阴性例数）×100%。

计数资料以例或率（n（%））表示，采用X检验，一致性分析采用Kappa一致性检验，Kappa<0.40认为一致性较差，Kappa值0.40~0.75认为一致性尚可，Kappa值0.75以上认为一致性良好，均以P<0.05认为差异具有统计学意义。

2 结果

2.1 一般资料

97例患者中男58例，女39例；年龄25~61岁，平均43.02±5.17岁；58例有明确的肝硬化史，34例为慢性肝炎患者；78例患者甲胎蛋白（Alpha Fetoprotein，AFP）等检查异常。

临床表现：乏力纳呆43例，上腹部胞胀54例，肝区隐痛60例，恶心呕吐38例，持续低烧33例。共63例患者（64.95%）经病理学检查，确诊为小肝癌。

2.2 CT增强扫描对小肝癌诊断价值

CT增强扫描对小肝癌诊断价值与金标准诊断结果一致性尚可（Kappa=0.445，P=0.000），灵敏度、特异度、准确度、阳性预测值、阴性预测值分别为77.78%（49/63）、67.65%（23/34）、74.23%（72/97）、81.67%（49/60）、62.16%（23/37），见表1。

表1 CT增强扫描对小肝癌诊断价值（例）

2.3 MRI对小肝癌诊断价值

MRI对小肝癌诊断价值与金标准诊断一致性尚可（Kappa=0.449，P=0.000），灵敏度、特异度、准确度、阳性预测值、阴性预测值分别为71.43%（45/63）、73.53%（25/34）、72.16%（70/97）、83.33%（45/54）、58.14%（25/43），见表2。

表2 MRI对小肝癌诊断价值（例）

2.4 联合检测对小肝癌诊断价值

联合检测对小肝癌诊断价值与金标准一致性尚可（Kappa=0.795，P=0.000），灵敏度、特异度、准确度、阳性预测值、阴性预测值分别为90.48%（57/63）、85.29%（29/34）、88.66%（86/97）、91.94%（57/62）、82.86%（29/35），见表3。

表3 联合检测对小肝癌诊断价值（例）

2.5 不同诊断方法诊断效能指标对比

联合检测在诊断灵敏度、特异度准确度及阴性预测值高于CT增强扫描与MRI检测（P<0.05），三组阳性预测值无显著差异（P>0.05），见表4。

表4 不同诊断方法诊断效能指标对比（例）

图1 代表性肝右叶小肝癌CT结果

注：A：CT平扫可见低密度病灶；B：CT动脉期早期扫描见病灶强化；C：CT动脉晚期可见病灶明显比周围肝组织明显；D-CT门静脉期肝脏强化密度增高，肿瘤内造影剂已开始下降。

图2 代表性肝右叶小肝癌MRI结果

注：A：肝右叶小肝癌T1信号相等或稍低，T2信号高，B-E：增强扫描动脉期明显增强，门静脉期和延迟期信号低，小肝癌包膜完整，延迟期环状增强，呈一动态过程；黄色箭头表示病灶位置。

3 讨论

肝癌为临床常见的恶性肿瘤，其病灶大小与分化程度密切相关，分化程度越高体积越大，相应病情也更为复杂，若在小肝癌阶段进行手术治疗可有效显著提高患者治愈率[8-9]。因小肝癌临床症状体征不明显，对其早期诊断难度较大，组织病理学检查虽为当前对肝癌诊断的金标准，但必须通过手术或穿刺取样，对患者创伤较大且在取样过程中容易出现针道出血、针道恶性转移等风险，因而临床上需谨慎使用[10-11]。

CT增强扫描应范围大、分辨率高、扫描速度快等优势而常用于腹部疾病的诊断，增强扫描可进一步明确肝脏病变的定位、定性及病灶与周围组织的关系。本研究结果显示：CT增强扫描对小肝癌诊断价值与金标准诊断结果一致性尚可，灵敏度、特异度、准确度、阳性预测值、阴性预测值均较高。可能肝脏癌变组织多由肝动脉供血，通过扫描过程中对对比剂流动情况进行分析，可有效获取病灶周围血供情况而加强对肝癌的诊断价值，根据对比剂显影时段在动脉期时进入动脉，此时大部分病灶明显强化而出现高密度灶，脉期进入肝门静脉，此时肝实质强度最高，病灶强化程度下降，在动脉期高密度灶变为低密度灶[12]。但因CT扫描对病变部位及周围正常组织的关系辨识能力弱，界限较为模糊而容易误诊，加上CT检查有一定的辐射而不利于患者健康[13]。MRI对于高软组织的分辨率高，可多层次多方位成像且无放射性而常被用于多种恶性肿瘤的早期诊断[14]。本研究结果显示：MRI对小肝癌诊断价值与金标准诊断结果一致性尚可，灵敏度、特异度、准确度、阳性预测值、阴性预测值较高。病灶部位在TIWI多表现为低信号，T2W1则表现为高信号或稍高信号，增强后信号更为清晰，可有效区分肝脏组织及病灶组织而减少误诊的发生。同时MRI无电离辐射损伤，通过扫描获得原生3D图像后不需重建图像矩阵就可获得清晰图像，加上该方法对于软组织的分辨率较高，可精确反映病变情况，CT增强扫描与MRI联合使用可互为补充，使诊断的准确性进一步提高[15]。

综上所述，CT增强及MRI对小肝癌均具有较高的诊断价值，两者联合使用可显著提高诊断效能。因本研究为单中心研究，样本量有限，取得的结果可能有一定的偏差，下步将扩大样本量增加指标进行进一步深入研究。

1 Zhou JN, Zeng Q, Wang HY, et al. MicroRNA-125b attenuates epithelial-mesenchymal transitions and targets stem-like liver cancer cells through small mothers against decapentaplegic 2 and 4[J]. Hepatology, 2015, 62(3): 801-815.

2 Zhou K, Nguyen LH, Miller JB, et al. Modular degradable dendrimers enable small RNAs to extend survival in an aggressive liver cancer model[J]. Proc Natl Acad Sci U S A, 2016, 113(3): 520-525.

3 Zhen L, Nan Y, Yao J, et al. Targeting docetaxel-PLA nanoparticles simultaneously inhibit tumor growth and liver metastases of small cell lung cancer[J]. Int J Pharm, 2015, 494(1): 337-345.

4 Ruobing Liu, Kaiyan Li, Hongchang Luo, et al. Ultrasound-guided percutaneous microwave ablation for small liver cancers adjacent to large vessels: long-term outcomes and strategies[J]. OTM, 2017, 3(2): 57-64.

5 Cheng Z, Li X, Ding J. Characteristics of liver cancer stem cells and clinical correlations[J]. Cancer Lett, 2016, 379(2): 230-238.

6 He S, Hu B, Li C, et al. PDXliver: a database of liver cancer patient derived xenograft mouse models[J]. Bmc Cancer, 2018, 18(1): 550-556.

7 中国抗癌协会肝癌专业委员会. 原发性肝癌规范化病理诊断指南(2015年版)[J]. 中华肝胆外科杂志, 2015, 21(3): 865-872.

8 Ling YM, Chen JY, Guo L, et al. β-defensin 1 expression in HCV infected liver/liver cancer: an important role in protecting HCV progression and liver cancer development[J]. Sci Rep, 2017, 7(1): 13404-13410.

9 Seto K, Sakabe T, Itaba N, et al. A Novel Small-molecule WNT Inhibitor, IC-2, Has the Potential to Suppress Liver Cancer Stem Cells[J]. Anticancer Res, 2017, 37(7): 3569-3579.

10 Zhang, Xu. Application of dual-source CT perfusion imaging and MRI for the diagnosis of primary liver cancer[J]. Oncol Lett, 2017, 14(5): 5753-5758.

11 Wang SY. Real-time fusion imaging of liver ultrasound[J]. J Ultras Med, 2017, 25(1): 9-11.

12 Tanaka O, Nishigaki Y, Hayashi H, et al. The advantage of iron-containing fiducial markers placed with a thin needle for radiotherapy of liver cancer in terms of visualization on MRI: an initial experience of Gold Anchor[J]. Radiol Case Rep, 2017, 12(2): 416-421.

13 Chen Q, Shang W, Zeng C, et al. Theranostic imaging of liver cancer using targeted optical/MRI dual-modal probes[J]. Oncotarget, 2017, 8(20): 32741-32751.

14 Su Q, Bi S, Yang X, et al. Prioritization of liver MRI for distinguishing focal lesions[J]. Science China Life Sciences, 2017, 60(1): 28-34.

15 Zamboglou C, Thomann B, Koubar K, et al. Focal dose escalation for prostate cancer using 68 Ga-HBED-CC PSMA PET/CT and MRI: a planning study based on histology reference[J]. Radiat Oncol, 2018, 13(1): 81-89.

Value of CT enhanced scan and MRI in diagnosis of small hepatocellular carcinoma

Lv Tian-fu*, Huang Yong, Wang Yong-xin, Shen Zong-chao, Li Tian-liang

(Department of Radiology, The People’s Hospital of Xishuangbanna, Jinghong 666100, Yunnan)

To investigate the value of CT enhanced scan and MRI in the diagnosis of small hepatocellular carcinoma.A total of 97 patients with suspected small hepatocellular carcinoma admitted to our hospital from January 2016 to July 2019 were enrolled. After enrollment, the two groups of patients were examined with CT enhanced scan and MRI by the same group of medical staff. Pathological examination was used as the gold standard. And the diagnostic efficacy was analyzed. And each diagnostic performance index was compared.A total of 63 (64.95%) patients in 97 patients were diagnosed as small hepatocellular carcinoma by pathological examination. CT-enhanced scan was consistent with the diagnostic value of small-scale hepatocellular carcinoma (Kappa=0.445, P<0.05). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 77.78% (49/63), 67.65% (23/34), 74.23% (72/97), 81.67% (49/60), and 62.16% (23/37), respectively. The diagnostic value of MRI for small hepatocellular carcinoma was consistent with the pathological examination gold standard diagnosis (Kappa=0.449, P<0.05). The sensitivity, specificity, accuracy, positive predictive value and negative predictive value were 71.43% (45/63), 73.53% (25/34), 72.16% (70/97), 83.33% (45/54), 58.14% (25/43), respectively. The diagnostic value of combined detection for small hepatocellular carcinoma was consistent with the gold standard diagnosis (Kappa=0.795, P<0.05). The sensitivity, specificity, accuracy, positive predictive value and negative predictive value were 90.48% (57/63), 85.29% (29/34), 88.66% (86/97), 91.94% (57/62), 82.86% (29/35), respectively. The combined detection was significantly higher than the CT enhanced scan and MRI test (P<0.05) in the diagnostic sensitivity, specificity accuracy and negative predictive value. There was no significant difference in the positive predictive value between the three groups (P>0.05).CT-enhanced scanner MRI has a high diagnostic value for small hepatocellular carcinoma. The combination of these two can significantly improve the diagnostic efficiency.

CT Enhanced Scan; MRI; Small Liver Cancer; Diagnostic Value

Teprotumumab for the Treatment of Active Thyroid Eye Disease.

Douglas RS, Kahaly GJ, Patel A, et al.

BACKGROUND:

Thyroid eye disease is a debilitating, disfiguring, and potentially blinding periocular condition for which no Food and Drug Administration-approved medical therapy is available. Strong evidence has implicated the insulin-like growth factor I receptor (IGF-IR) in the pathogenesis of this disease.

METHODS:

In a randomized, double-masked, placebo-controlled, phase 3 multicenter trial, we assigned patients with active thyroid eye disease in a 1: 1 ratio to receive intravenous infusions of the IGF-IR inhibitor teprotumumab (10 mg per kilogram of body weight for the first infusion and 20 mg per kilogram for subsequent infusions) or placebo once every 3 weeks for 21 weeks; the last trial visit for this analysis was at week 24. The primary outcome was a proptosis response (a reduction in proptosis of ≥2 mm) at week 24. Prespecified secondary outcomes at week 24 were an overall response (a reduction of ≥2 points in the Clinical Activity Score plus a reduction in proptosis of ≥2 mm), a Clinical Activity Score of 0 or 1 (indicating no or minimal inflammation), the mean change in proptosis across trial visits (from baseline through week 24), a diplopia response (a reduction in diplopia of ≥1 grade), and the mean change in overall score on the Graves' ophthalmopathy-specific quality-of-life (GO-QOL) questionnaire across trial visits (from baseline through week 24; a mean change of ≥6 points is considered clinically meaningful).

RESULTS:

A total of 41 patients were assigned to the teprotumumab group and 42 to the placebo group. At week 24, the percentage of patients with a proptosis response was higher with teprotumumab than with placebo (83% [34 patients] vs. 10% [4 patients], P<0.001), with a number needed to treat of 1.36. All secondary outcomes were significantly better with teprotumumab than with placebo, including overall response (78% of patients [32] vs. 7% [3]), Clinical Activity Score of 0 or 1 (59% [24] vs. 21% [9]), the mean change in proptosis (-2.82 mm vs. -0.54 mm), diplopia response (68% [19 of 28] vs. 29% [8 of 28]), and the mean change in GO-QOL overall score (13.79 points vs. 4.43 points) (P≤0.001 for all). Reductions in extraocular muscle, orbital fat volume, or both were observed in 6 patients in the teprotumumab group who underwent orbital imaging. Most adverse events were mild or moderate in severity; two serious events occurred in the teprotumumab group, of which one (an infusion reaction) led to treatment discontinuation.

CONCLUSIONS:

Among patients with active thyroid eye disease, teprotumumab resulted in better outcomes with respect to proptosis, Clinical Activity Score, diplopia, and quality of life than placebo; serious adverse events were uncommon.

(From N Engl J Med. 2020, 382(4): 341-352.)

吕天甫，男，主治医师，主要从事影像诊断工作，Email：lvtianfuyou@126. com。

（2019-10-29）