Short-Term Efficacy of Celiac Plexus Block Combined with Interstitial Permanent Implantation of 125I Seeds in Treatment of Advanced Pancreatic Cancer
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摘要:目的
探讨腹腔神经丛阻滞术联合125I粒子组织间植入治疗晚期胰腺癌(不可手术切除的局部晚期和转移性胰腺癌)的近期疗效。
方法选取100例CT引导下125I粒子组织间植入联合腹腔神经丛阻滞术治疗的晚期胰腺癌患者作为研究对象。术后第7天、1个月和3个月评估疼痛缓解情况和肿瘤标志物CA19-9的变化以及术后3个月通过CT评估肿瘤大小的变化。
结果100例患者术后三个月,完全缓解(CR)12例,部分缓解(PR) 78例,疾病稳定(SD) 5例,疾病进展(PD)5例。CA19-9明显下降(P<0.01),肿瘤长短径之和明显缩小(P<0.01)。治疗前100例患者均属重度疼痛(视觉疼痛模拟量表(VAS):7~10分),术后3个月有59例患者疼痛消失(VAS:0分),35例患者轻度疼痛(VAS:1~3分),6例患者中度疼痛(VAS:4~6分),疼痛缓解率100%。
结论腹腔神经丛阻滞术联合125I粒子组织间植入对晚期胰腺癌患者的近期疗效较好且能有效改善患者近期疼痛。
Abstract:ObjectiveTo investigate the short-term efficacy of celiac plexus block combined with the interstitial permanent implantation of 125I seeds in the treatment of advanced pancreatic cancer (inoperable locally advanced and metastatic pancreatic cancers).
MethodsA total of 100 patients with advanced pancreatic cancer were selected and treated with celiac plexus block combined with the interstitial permanent implantation of 125I seeds under CT guidance. Pain relief and changes in the tumor marker CA19-9 were assessed on the seventh day, the first and third months after surgery. In the third month after surgery, tumor size was assessed by CT.
ResultsAmong the 100 patients with advanced pancreatic cancer, complete response (CR) was found in 12 cases, partial response (PR) in 78 cases, stable disease in five cases, and progression of disease in five cases three months after surgery. The CA19-9 level and the sum of short and long tumor diameters were significantly decreased (both P<0.01). A total of 100 patients had severe pain before treatment (visual analogue scale (VAS)): 7–10 points), 59 patients reported pain disappearance (VAS: 0 points), 35 patients had mild pain (VAS: 1–3 points), and six patients experienced moderate pain (VAS: 4–6 points) in the third month after treatment. The pain relief rate was 100%.
ConclusionCeliac plexus block combined with the interstitial permanent implantation of 125I seeds has good short-term efficacy and can effectively improve short-term pain in patients with advanced pancreatic cancer.
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Key words:
- Pancreatic cancer /
- Celiac plexus block /
- 125I particles
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0 引言
胰腺癌被称为“癌中之王”,具有起病隐匿、进展迅猛和预后极差等特点,5年生存率仅为12%[1-2]。早期胰腺癌患者的首选治疗方案为手术切除,但大多数患者诊断时已属晚期,仅有15%~20%的患者有机会接受手术[3]。放化疗是丧失手术机会的胰腺癌患者的主要治疗手段,但疗效并不理想[4]。
放射性125I粒子近距离放射治疗肿瘤的原理为通过放射治疗计划系统制定治疗方案,将放射性粒子植入到肿瘤组织间,利用放射线粒子产生的射线对肿瘤进行持续性、低剂量照射,使肿瘤得到最大照射而周围正常组织受到尽可能小的照射[5]。腹腔神经丛阻滞术是指将药物(如无水乙醇、糖皮质激素或利多卡因)注入腹腔神经丛,使腹腔神经节发生慢性坏死,从而达到止痛的目的[6]。有研究表明放射性125I粒子近距离放疗联合化疗可以缓解胰腺癌患者的疼痛并控制肿瘤局部进展[7-8]。但是,关于腹腔神经丛阻滞术联合125I粒子组织间植入对晚期胰腺癌患者的近期疗效尚不十分清楚,就此我们对2013年3月至2022年10月就诊于黄冈市中心医院的100例晚期胰腺癌患者进行了回顾性分析。
1 资料与方法
1.1 研究对象
选取2013年3月—2022年10月在黄冈市中心医院行CT引导经皮穿刺组织学活检证实为胰腺癌、并在CT引导下行腹腔神经丛阻滞术联合125I粒子组织间植入治疗的100例未手术的患者作为研究对象。其中,男性59例,女性41例,年龄35~72岁,平均年龄55. 59±11.4岁,病灶最大直径2.4~10.8 cm。100例患者的临床资料见表1。本研究经黄冈市中心医院伦理委员会审批。
表 1 100例晚期胰腺癌患者的临床资料Table 1 Clinical data of 100 patients with advanced pancreatic cancerClinical features n(%) Gender Male 59(59) Female 41(41) Age(years) ≤60 59(59) >60 41(41) TNM stage T3 47(47) T4 53(53) N0 12(12) N1 41(41) N2 47(47) M0 18(18) M1 82(82) Tumor site Pancreatic head 35(35) Pancreatic body 23(23) Pancreatic tail 42(42) Tumor size(cm) 2–4 39(39) >4 61(61) 1.2 CT引导下腹腔神经丛阻滞术联合125I粒子组织间植入
术前给患者行腹部CT,将结果输入治疗计划系统,画出治疗靶区,并算出需要植入的粒子数目以及计划好粒子的空间排布,制定好治疗方案。患者俯卧于CT检查床,常规心电监护,建立静脉通道。在体表贴上定位栅,行腹部CT平扫确定胰腺穿刺进针路径、角度及深度。消毒铺巾后,按照TPS制定的方案,通过穿刺引导针将125I粒子均匀植入病灶内,CT复查粒子排布效果满意。术者、助手和护士三方确认粒子无遗失。穿刺针通过肾与第一腰椎的椎旁间隙到达胰头后方(注意不要损伤到肾动脉及腹主动脉),将调配好的组织液(无水乙醇20 ml,利多卡因30 ml,地塞米松10 ml及碘克沙醇5 ml)缓慢推注,复查评估,组织液于腹膜后间隙弥散良好。
1.3 仪器设备
穿刺定位使用西门子SOMATOM Spirit双层螺旋CT,评估疗效使用GE西门子64排螺旋CT,放射性粒子治疗计划系统由北京飞天兆业科技有限公司提供。6711型125I放射性粒子源由北京原子高科有限公司提供,平均光子能量27~35 keV,活度0.8 mCi,组织穿透力1.7 cm,半衰期为57.6天,粒子源出厂前经检漏实验、活度测量并标定。全封闭防辐射粒子枪及专用植入针均由珠海和佳公司生产。
1.4 疗效和疼痛评价标准
依据实体瘤疗效评价标准(RECIST 1.1标准)评价疗效,分为完全缓解(CR)、部分缓解(PR)、疾病稳定(SD)和疾病进展(PD) 。
采用视觉疼痛模拟量表(visual analogue scale, VAS)评估疼痛程度,分为无疼痛(0分)、轻度疼痛(1~3分)、中度疼痛(4~6分)和重度疼痛(7~10分)。
1.5 观察指标
记录术后第7天、1个月和3个月患者的疼痛缓解情况。术后3个月,对比患者治疗前后的肿瘤体积和肿瘤标志物CA19-9变化,评估疗效。
1.6 统计学方法
利用GraphPad Prism9. 0对数据进行分析,正态分布计量资料采用$ \bar{x} $ ± s 表示,联合治疗前后两组间的疗效比较采用t检验。P<0.05为差异有统计学意义。
2 结果
2.1 联合治疗对胰腺癌病灶的控制
按照实体瘤临床疗效评价标准(RECIST1.1版),通过PET-CT、ECT和增强CT/MRI等影像学检查评估了所有患者联合治疗3个月后的可测量和不可测量病灶以及特殊部位病灶情况。联合治疗3个月后,CR 12例(12%),PR 78例(78%),SD 5例(5%),PD 5例(5%),联合治疗的有效率(CR+PR)达90%,见图1A~F。术后3个月的肿瘤长短径之和相比于术前明显缩小(P=
0.000965 ),见图1G。100例患者术后 3个月的血清CA19-9浓度显著下降(P=0.000033 ),见图1H。图 1 联合治疗3个月后肿瘤病灶大小(典型病例)和CA19-9的变化Figure 1 Changes in tumor lesion size (typical case) and CA19-9 after three months of combined treatmentA, B: A 50-year-old woman presented with a 3.5 cm×4 cm mass around the abdominal trunk three months after palliative treatment for pancreatic cancer, and PET-CT indicated progression; C–E: A dorsal approach was made with an abdominal plexus block followed by the implantation of 125I particles between tumor tissues; F: After three months of combined treatment, the pancreatic cancer lesion had drastically reduced; G: Changes in the sum of the short and long tumor diameters after three months of combined treatment; H: Changes in the tumor marker CA19-9 after three months of combined treatment.2.2 联合治疗对胰腺癌患者疼痛的控制
腹腔神经丛阻滞术联合125I粒子组织间植入治疗前所有患者均为重度疼痛,VAS评分均值为8.65分;术后第7天所有患者的疼痛情况均好转,VAS评分均值降至5.18分;术后1个月,疼痛控制率得到进一步提高,VAS评分均值为4.08分;术后3个月,VAS评分均值降至0.90分,见图2。
2.3 联合治疗后不良反应或并发症
治疗后常见的术后并发症包括:穿刺损伤胰管所致的胰瘘、胃肠道症状、术后腹水、粒子移位、感染、大量出血和乳糜瘘等。本研究中的100例患者术后有9例患者出现感染,但体温均未超过38.5℃;13例患者出现轻度的胃肠道反应(恶心呕吐、腹泻);3例患者出现胰瘘;7例患者出现术后出血。以上患者经过积极的对症支持治疗后都得到恢复。
3 讨论
众所周知,由于胰腺癌起病极其隐匿、恶性程度高且进展迅速,多数患者诊断时已经无法进行肿瘤根治性手术[9-10]。因此,我们十分有必要探索出新的能够改善胰腺癌患者生存期和生活质量的治疗手段。
作为一种放射治疗的新兴模式,125I 粒子植入因其安全有效、便捷等优势已经被广泛应用于多种实体瘤(胰腺癌、肝癌、肺癌等)的治疗[11-12]。尽管125I 粒子植入治疗胰腺癌具备独特的优势,但由于胰腺癌恶性程度高以及125I 粒子植入治疗自身存在的不足导致单一125I 粒子植入的治疗效果并不理想[13]。因此,有部分科研工作者已经开始寻求125I 粒子植入联合其他治疗方式来提高胰腺癌的治疗效果。张丽娟等[14]通过随机对照试验对125I 粒子植入联合小柴胡汤与单一125I 粒子植入治疗胰腺癌的临床疗效进行了对比,结果发现联合治疗组患者的生活质量评分和卡氏体力状况(KPS)评分及有效率(68.75% vs. 31.25%)均显著高于单一125I 粒子植入组。闫一洋等[15]通过回顾性分析47例125I粒子植入联合腹腔热灌注化疗的晚期胰腺癌患者的临床资料,结果提示联合治疗能够有效缓解患者的疼痛和控制肿瘤局部进展。
腹腔神经丛阻滞术自Kappis于1914年首次提出后[16],经过百余年的发展,此技术已从最初的麻醉医生盲穿或借助X线引导穿刺到如今借助超声内镜、CT和MRI引导穿刺[17]。腹腔神经丛阻滞术不仅相对安全,而且有效地缓解了胰腺癌患者的疼痛,极大改善了患者的生活质量[18]。
本研究表明,腹腔神经丛阻滞术联合125I粒子组织间植入治疗100例晚期胰腺癌患者3个月后,肿瘤病灶明显缩小,所有患者的血清CA19-9浓度也显著下降。此外,联合治疗前100例患者均属重度疼痛,术后第7天所有患者的疼痛都得到了较好缓解,术后三个月时中度疼痛患者6例,轻度疼痛患者35例,59例患者疼痛消失,疼痛缓解率达100%。
需要指出的是,尽管本研究的联合治疗方案对晚期胰腺癌患者显示出非常好的近期临床疗效,但是我们并不确定远期临床疗效是否也如此。另外,本研究只是将晚期胰腺癌患者治疗前后的病灶大小、血清CA19-9浓度以及疼痛进行对比,而不是将晚期胰腺癌患者随机分组后设置实验组和对照组来评估联合治疗的疗效。虽然我们的研究缺乏队列进行对照说明单独腹腔神经丛阻滞术或单独125I粒子组织间植入是否可以达到联合治疗类似的效果,但是相关研究表明单独腹腔神经丛阻滞术仅能缓解胰腺癌患者的疼痛症状,没有缩瘤效应[19-21]。刘颖等[13,22]进行了单纯125I粒子对胰腺癌疗效的研究,上述研究报道的疗效劣于本研究联合治疗的效果。综上所述:腹腔神经丛阻滞术联合125I粒子组织间植入治疗晚期胰腺癌近期疗效优于单独治疗。最后,本研究100例患者虽然未进行手术,但在初诊时经胰腺增强CT或增强MRI检查并经活检病理确诊后,继续完善了胸腹部、盆腔增强CT或增强MRI、ECT以及PET-CT,综合各项检查结果评估出患者的TNM分期。少数TNM分期困难的病例进行了MDT会诊(肿瘤科、影像科、外科和核医学科等),综合各科医生讨论后的意见确定患者的TNM分期。
综上所述,放射性125I粒子近距离放疗联合腹腔神经丛阻滞术或许可作为改善晚期胰腺癌患者生存期和生活质量的推荐治疗方案。
Competing interests: The authors declare that they have no competing interests.利益冲突声明:所有作者均声明不存在利益冲突。作者贡献:柯尊乾、尹志红、周冬:临床数据的分析和论文撰写朱晓东、聂豪:临床数据的收集胡水红、曾勇:论文修订邹佳华:课题思路的提出及设计研究方案 -
表 1 100例晚期胰腺癌患者的临床资料
Table 1 Clinical data of 100 patients with advanced pancreatic cancer
Clinical features n(%) Gender Male 59(59) Female 41(41) Age(years) ≤60 59(59) >60 41(41) TNM stage T3 47(47) T4 53(53) N0 12(12) N1 41(41) N2 47(47) M0 18(18) M1 82(82) Tumor site Pancreatic head 35(35) Pancreatic body 23(23) Pancreatic tail 42(42) Tumor size(cm) 2–4 39(39) >4 61(61) -
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