高强度聚焦超声治疗肝癌的免疫学效应及影像学评估

Immune modulation and focused ultrasound imaging for patients with hepatocellular carcinoma

目的 对高强度聚焦超声（HIFU）治疗原发性肝癌的免疫学效应以及影像学评估手段进行初步探讨.方法 选取63例接受HIFU治疗的肝癌患者作为病例组,另选39例健康志愿者作为对照组,记录63例患者在HIFU治疗前后的免疫学指标,并与健康对照组进行比较;病例组治疗后3个月,将临床疗效较好的患者分入有效组,疗效不佳的患者分入无效组,记录所有患者治疗前与治疗后3个月的临床疗效指标,并比较有效组和无效组患者的免疫学指标和临床疗效指标;比较病例组中巨块型患者和结节型患者的治疗有效率;记录治疗前后所有病例组患者病灶的超声造影检查（CEUS）及CT检查.结果 治疗前,病例组患者的血清热休克蛋白（HSP-70）和干扰素γ（IFN-γ）与白介素10（IL-10）的比值（IFN-γ/IL-10）分别为（18.78±4.53） ng/ml和（1.25±0.29）,明显低于健康对照组[（20.26±4.16） ng/ml、（1.79±0.31）],而病例组的转化生长因子β（TGF-β）为（1.38 ±0.27） ng/ml,明显高于健康对照组[（1.10±0.17）ng/ml],组间差异均有统计学意义（P＜0.01）.经HIFU治疗后1周和治疗后3个月,病例组患者的HSP-70[（21.93±5.28）和（20.71±4.66） ng/ml]、1FN-γ/IL-10[（1.68±0.34）和（1.49±0.28）]及TGF-β[（1.19 ±0.25）和（1.24±0.23）ng/ml]等免疫学指标均较组内治疗前明显好转（P＜0.05）;病例组患者治疗前后的上述免疫学指标均差于健康对照组（P＜0.05）.经HIFU治疗后3个月,病例组患者的目测类比法（VAS）评分[（3.53±0.86）分]和卡氏行为状态（KPS）评分[（79.12±20.49）分]以及血清总胆红素（TBIL）[（26.42±10.29） μmol/L]和甲胎蛋白（AFP）值[（84.82±21.51） ng/ml]均明显优于组内治疗前[（4.02±1.14）分和（68.94±18.35）分;（37.28±14.62） μmol/L和（265.39±87.45） ng/ml],且差异均有统计学意义（P＜0.05）.病例组中,治疗有效组患者的全部上述指标均明显优于无效组（P＜0.05）.另外,病例组中,巨块型患者的临床治疗总有效率为87.5％,明显高于结节型患者的66.67％,但二者之间的差异并无统计学意义（P＞0.05）;影像学指标（CEUS和CT）显示HIFU治疗后肿瘤病灶血供消失,体积缩小.结论 HIFU能有效治疗原发性肝癌,同时能增强患者体内抗肿瘤免疫应答;相较于结节型患者,HIFU对于巨块型患者的疗效可能更好;CEUS可实时评估HIFU疗效.

Objective To evaluate immune modulation and the utility of high intensity focused ultrasound （HIFU） imaging for patients with hepatocellular carcinoma.Methods Sixty-three patients with hepatocellular carcinoma were treated using HIFU.Another 39 healthy volunteers served as a control group.A variety of immunological indexes were recorded before and after the treatment and 3 months later.The patients demonstrating good curative effect formed an effective group and those with poor curative effect were the ineffective group.The immunological and clinical indexes of the effective and ineffective groups were compared.The efficacy of the treatment for patients with giant blocks was compared with that for patients with nodular lesions.Contrast-enhanced ultrasono grams （CEUSs） and CT scans of the patients before and after HIFU were recorded.Results All of the immunological indexes [HSP,IFN-γ/IL-10 and TGF-β] were significantly better 1 week and 3 months after treatment than before treatment.Though all of course remained worse than those of the healthy controls throughout.The average indices in the effective group were also of course significantly better than those of the ineffective group,since that is how the groups were defined.Three months after the treatment had ended,self-reported pain,quality of life [Karnosky performance status],total bilirubin and tumor markers were all significantly better than before treatment.And there too the indexes of the effective group were still significantly better than those of the ineffective group.Efficacy was not significantly better among patients with giant blocks （87.5%） than among patients with nodular lesions （66.67%）.The CEUS and CT images showed that after HIFU,blood supply to the neoplastic lesions had disappeared,and tumor volume had decreased.Conclusions HIFU is an effective treatment for hepatocellular carcinoma.It can improve patients＇ anti-tumor response.CEUS can be used to assess quickly the curative effect of HIFU.