CT增強(qiáng)掃描和MRI診斷小肝癌的應(yīng)用價(jià)值

呂天甫 黃勇 王永新 沈宗朝 李天良

·臨床論著·

CT增強(qiáng)掃描和MRI診斷小肝癌的應(yīng)用價(jià)值

呂天甫*黃勇 王永新 沈宗朝 李天良

（西雙版納州人民醫(yī)院放射科，云南 景洪 666100）

探討CT增強(qiáng)掃描和MRI診斷小肝癌的應(yīng)用價(jià)值。選擇2016年1月至2019年7月在我院接受治療的疑似小肝癌患者97例進(jìn)行研究。入組后患者均由同一組醫(yī)護(hù)人員行CT增強(qiáng)掃描及MRI檢測。以病理檢查為金標(biāo)準(zhǔn)，對各檢測方法與聯(lián)合檢測的診斷效能進(jìn)行分析，并對比各診斷效能指標(biāo)。97例患者中共63例患者（64.95%）經(jīng)病理學(xué)檢查確診為小肝癌。CT增強(qiáng)掃描對小肝癌診斷價(jià)值與金標(biāo)準(zhǔn)診斷結(jié)果一致性尚可（Kappa=0.445，P<0.05），靈敏度、特異度、準(zhǔn)確度、陽性預(yù)測值、陰性預(yù)測值分別為77.78%（49/63）、67.65%（23/34）、74.23%（72/97）、81.67%（49/60）、62.16%（23/37）。MRI對小肝癌診斷價(jià)值與金標(biāo)準(zhǔn)診斷結(jié)果一致性尚可（Kappa=0.449，P<0.05），靈敏度、特異度、準(zhǔn)確度、陽性預(yù)測值、陰性預(yù)測值分別為71.43%（45/63）、73.53%（25/34）、72.16%（70/97）、83.33%（45/54）、58.14%（25/43）。聯(lián)合檢測對小肝癌診斷價(jià)值與金標(biāo)準(zhǔn)診斷結(jié)果一致性較高（Kappa=0.795，P<0.05），靈敏度、特異度、準(zhǔn)確度、陽性預(yù)測值、陰性預(yù)測值分別為90.48%（57/63）、85.29%（29/34）、88.66%（86/97）、91.94%（57/62）、82.86%（29/35）。聯(lián)合檢測在診斷靈敏度、特異度準(zhǔn)確度及陰性預(yù)測值方面均明顯高于CT增強(qiáng)掃描與MRI檢測（P<0.05），三組陽性預(yù)測值對比差異無統(tǒng)計(jì)學(xué)意義（P>0.05）。CT增強(qiáng)掃描機(jī)MRI對小肝癌均具有較高的診斷價(jià)值，兩者聯(lián)合使用可顯著提高診斷效能。

CT增強(qiáng)掃描；MRI；小肝癌；診斷價(jià)值

小肝癌也稱為亞臨床肝癌或早期肝癌，臨床上多指肝細(xì)胞癌中單個(gè)癌結(jié)節(jié)最大直徑在3 cm以內(nèi)或兩個(gè)癌結(jié)節(jié)直徑和在3 cm以內(nèi)的患者，此類患者臨床尚無明顯癥狀[1-3]。小肝癌血供充足，若能在發(fā)病早期發(fā)現(xiàn)病灶并根據(jù)其血供特點(diǎn)制訂合適的治療方案有助于提高治療成功率[4-5]。因小肝癌患者癥狀隱匿，單靠臨床癥狀難以診斷，對于該病的診斷臨床上仍以病理檢查為金標(biāo)準(zhǔn)，但該檢查床上較大，因小肝癌患者癥狀不明顯部分患者不愿意配合進(jìn)行穿刺取樣而致其臨床應(yīng)用受到一定限制[6]。隨著影像學(xué)技術(shù)的不斷發(fā)展，CT、MRI、超聲等方法均被證實(shí)可用于肝癌的早期診斷，其中CT增強(qiáng)掃描與MRI為臨床常用的肝癌早期診斷方法，但關(guān)于上述兩種方法聯(lián)合使用對小肝癌診斷方面的研究較少，因此本研究旨在通過分析CT增強(qiáng)掃描和MRI診斷小肝癌的應(yīng)用價(jià)值，以期為該方法的臨床應(yīng)用提供參考依據(jù)。

1 資料與方法

1.1 一般資料

選擇2016年1月至2019年7月在我院接受治療的疑似小肝癌患者97例進(jìn)行研究。納入標(biāo)準(zhǔn)：①患者均有明確的肝硬化或慢性肝炎病史，經(jīng)超聲檢查為疑似小肝癌；②神志清醒，智力正常，可配合進(jìn)行相關(guān)檢查；③患者已獲知情同意。排除標(biāo)準(zhǔn)：①檢查前接受過肝臟手術(shù)或介入治療；②15d 內(nèi)未接受過CT及MRI檢查；③對造影劑過敏；④妊娠期及哺乳期婦女；⑤不愿意配合進(jìn)行穿刺或手術(shù)病理檢者；⑥合并心、肺、腎等重要臟器嚴(yán)重疾??；⑦合并其他惡性腫瘤。

1.2 方法

入組后患者均由同一組具5年以上臨床經(jīng)驗(yàn)的醫(yī)護(hù)人員進(jìn)行相關(guān)檢查。

1.2.1 CT增強(qiáng)掃描

采用GE64排VCT進(jìn)行檢測，患者仰臥，雙臂上舉，腹部放松，對膈頂至髂嵴部位進(jìn)行動態(tài)增強(qiáng)掃描，掃描前禁食4~5 h，前20 min飲水500 ml，經(jīng)外周靜脈注入碘佛醇注射液100 ml，流速為3.0 ml·s-1。掃描參數(shù)：電壓120 kv，電流240 mA，層厚3 mm，矩陣512×512，先平掃后進(jìn)行動態(tài)增強(qiáng)掃描。動脈期延遲30 s，靜脈期延遲60 s，平衡期延遲120 s，結(jié)束后對原始數(shù)據(jù)圖像重建。

1.2.2 MRI檢查

以西門子1.5T Avanto MRI進(jìn)行檢測，患者仰臥，雙臂上舉，胸線圈，掃描范圍同CT增強(qiáng)掃描，掃描時(shí)囑屏氣，掃描參數(shù)：層厚6 mm，間隔1 mm，對橫斷面、冠狀面及矢狀面分別行平行掃描，序列：T1W1：TR 400~500 ms，TE 15 ms，T2W2： TR 3500 ms，TE 105 ms。平掃后經(jīng)右肘靜脈推注釓噴酸葡胺，掃描序列為T1W1。

1.2.3 評價(jià)標(biāo)準(zhǔn)

由2~4名具高級技術(shù)職稱的專家對CT及MRI圖像進(jìn)行診斷，將最終達(dá)成一致的結(jié)果以手術(shù)或穿刺病理檢查結(jié)果為金標(biāo)準(zhǔn)，參照《原發(fā)性肝癌規(guī)范化病理診斷指南（2015年版）》[7]的相關(guān)規(guī)定進(jìn)行診斷，計(jì)算各診斷效能指標(biāo)。

1.3 統(tǒng)計(jì)學(xué)方法

采用SPSS22.0統(tǒng)計(jì)學(xué)軟件進(jìn)行數(shù)據(jù)分析，靈敏度=真陽性例數(shù)/（真陽性例數(shù)+假陰性例數(shù)）×100%，特異度=真陰性例數(shù)/（真陰性例數(shù)+假陽性例數(shù)）×100%，準(zhǔn)確度=（真陽性例數(shù)+真陰性例數(shù)）/試驗(yàn)組總病例數(shù)×100%，陽性預(yù)測值=真陽性例數(shù)/（真陽性例數(shù)+假陽性例數(shù)）×100%，陰性預(yù)測值=真陰性例數(shù)/（真陰性例數(shù)+假陰性例數(shù)）×100%。

計(jì)數(shù)資料以例或率（n（%））表示，采用X檢驗(yàn)，一致性分析采用Kappa一致性檢驗(yàn)，Kappa<0.40認(rèn)為一致性較差，Kappa值0.40~0.75認(rèn)為一致性尚可，Kappa值0.75以上認(rèn)為一致性良好，均以P<0.05認(rèn)為差異具有統(tǒng)計(jì)學(xué)意義。

2 結(jié)果

2.1 一般資料

97例患者中男58例，女39例；年齡25~61歲，平均43.02±5.17歲；58例有明確的肝硬化史，34例為慢性肝炎患者；78例患者甲胎蛋白（Alpha Fetoprotein，AFP）等檢查異常。

臨床表現(xiàn)：乏力納呆43例，上腹部胞脹54例，肝區(qū)隱痛60例，惡心嘔吐38例，持續(xù)低燒33例。共63例患者（64.95%）經(jīng)病理學(xué)檢查，確診為小肝癌。

2.2 CT增強(qiáng)掃描對小肝癌診斷價(jià)值

CT增強(qiáng)掃描對小肝癌診斷價(jià)值與金標(biāo)準(zhǔn)診斷結(jié)果一致性尚可（Kappa=0.445，P=0.000），靈敏度、特異度、準(zhǔn)確度、陽性預(yù)測值、陰性預(yù)測值分別為77.78%（49/63）、67.65%（23/34）、74.23%（72/97）、81.67%（49/60）、62.16%（23/37），見表1。

表1 CT增強(qiáng)掃描對小肝癌診斷價(jià)值（例）

2.3 MRI對小肝癌診斷價(jià)值

MRI對小肝癌診斷價(jià)值與金標(biāo)準(zhǔn)診斷一致性尚可（Kappa=0.449，P=0.000），靈敏度、特異度、準(zhǔn)確度、陽性預(yù)測值、陰性預(yù)測值分別為71.43%（45/63）、73.53%（25/34）、72.16%（70/97）、83.33%（45/54）、58.14%（25/43），見表2。

表2 MRI對小肝癌診斷價(jià)值（例）

2.4 聯(lián)合檢測對小肝癌診斷價(jià)值

聯(lián)合檢測對小肝癌診斷價(jià)值與金標(biāo)準(zhǔn)一致性尚可（Kappa=0.795，P=0.000），靈敏度、特異度、準(zhǔn)確度、陽性預(yù)測值、陰性預(yù)測值分別為90.48%（57/63）、85.29%（29/34）、88.66%（86/97）、91.94%（57/62）、82.86%（29/35），見表3。

表3 聯(lián)合檢測對小肝癌診斷價(jià)值（例）

2.5 不同診斷方法診斷效能指標(biāo)對比

聯(lián)合檢測在診斷靈敏度、特異度準(zhǔn)確度及陰性預(yù)測值高于CT增強(qiáng)掃描與MRI檢測（P<0.05），三組陽性預(yù)測值無顯著差異（P>0.05），見表4。

表4 不同診斷方法診斷效能指標(biāo)對比（例）

圖1 代表性肝右葉小肝癌CT結(jié)果

注：A：CT平掃可見低密度病灶；B：CT動脈期早期掃描見病灶強(qiáng)化；C：CT動脈晚期可見病灶明顯比周圍肝組織明顯；D-CT門靜脈期肝臟強(qiáng)化密度增高，腫瘤內(nèi)造影劑已開始下降。

圖2 代表性肝右葉小肝癌MRI結(jié)果

注：A：肝右葉小肝癌T1信號相等或稍低，T2信號高，B-E：增強(qiáng)掃描動脈期明顯增強(qiáng)，門靜脈期和延遲期信號低，小肝癌包膜完整，延遲期環(huán)狀增強(qiáng)，呈一動態(tài)過程；黃色箭頭表示病灶位置。

3 討論

肝癌為臨床常見的惡性腫瘤，其病灶大小與分化程度密切相關(guān)，分化程度越高體積越大，相應(yīng)病情也更為復(fù)雜，若在小肝癌階段進(jìn)行手術(shù)治療可有效顯著提高患者治愈率[8-9]。因小肝癌臨床癥狀體征不明顯，對其早期診斷難度較大，組織病理學(xué)檢查雖為當(dāng)前對肝癌診斷的金標(biāo)準(zhǔn)，但必須通過手術(shù)或穿刺取樣，對患者創(chuàng)傷較大且在取樣過程中容易出現(xiàn)針道出血、針道惡性轉(zhuǎn)移等風(fēng)險(xiǎn)，因而臨床上需謹(jǐn)慎使用[10-11]。

CT增強(qiáng)掃描應(yīng)范圍大、分辨率高、掃描速度快等優(yōu)勢而常用于腹部疾病的診斷，增強(qiáng)掃描可進(jìn)一步明確肝臟病變的定位、定性及病灶與周圍組織的關(guān)系。本研究結(jié)果顯示：CT增強(qiáng)掃描對小肝癌診斷價(jià)值與金標(biāo)準(zhǔn)診斷結(jié)果一致性尚可，靈敏度、特異度、準(zhǔn)確度、陽性預(yù)測值、陰性預(yù)測值均較高?？赡芨闻K癌變組織多由肝動脈供血，通過掃描過程中對對比劑流動情況進(jìn)行分析，可有效獲取病灶周圍血供情況而加強(qiáng)對肝癌的診斷價(jià)值，根據(jù)對比劑顯影時(shí)段在動脈期時(shí)進(jìn)入動脈，此時(shí)大部分病灶明顯強(qiáng)化而出現(xiàn)高密度灶，脈期進(jìn)入肝門靜脈，此時(shí)肝實(shí)質(zhì)強(qiáng)度最高，病灶強(qiáng)化程度下降，在動脈期高密度灶變?yōu)榈兔芏仍頪12]。但因CT掃描對病變部位及周圍正常組織的關(guān)系辨識能力弱，界限較為模糊而容易誤診，加上CT檢查有一定的輻射而不利于患者健康[13]。MRI對于高軟組織的分辨率高，可多層次多方位成像且無放射性而常被用于多種惡性腫瘤的早期診斷[14]。本研究結(jié)果顯示：MRI對小肝癌診斷價(jià)值與金標(biāo)準(zhǔn)診斷結(jié)果一致性尚可，靈敏度、特異度、準(zhǔn)確度、陽性預(yù)測值、陰性預(yù)測值較高。病灶部位在TIWI多表現(xiàn)為低信號，T2W1則表現(xiàn)為高信號或稍高信號，增強(qiáng)后信號更為清晰，可有效區(qū)分肝臟組織及病灶組織而減少誤診的發(fā)生。同時(shí)MRI無電離輻射損傷，通過掃描獲得原生3D圖像后不需重建圖像矩陣就可獲得清晰圖像，加上該方法對于軟組織的分辨率較高，可精確反映病變情況，CT增強(qiáng)掃描與MRI聯(lián)合使用可互為補(bǔ)充，使診斷的準(zhǔn)確性進(jìn)一步提高[15]。

綜上所述，CT增強(qiáng)及MRI對小肝癌均具有較高的診斷價(jià)值，兩者聯(lián)合使用可顯著提高診斷效能。因本研究為單中心研究，樣本量有限，取得的結(jié)果可能有一定的偏差，下步將擴(kuò)大樣本量增加指標(biāo)進(jìn)行進(jìn)一步深入研究。

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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.)

呂天甫，男，主治醫(yī)師，主要從事影像診斷工作，Email：lvtianfuyou@126. com。

（2019-10-29）