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胆管癌(cholangiocarcinoma, CCA)是一种起源于胆管上皮的恶性肿瘤,发病率约为(1~2)/10万人[1]。根据解剖位置,CCA可分为肝内胆管癌(intrahepatic CCA, iCCA)、肝门部胆管癌(perihilar CCA, pCCA)和远端胆管癌(distal cholangiocarcinoma, dCCA),后两者属于肝外胆管癌(extrahepatic CCA, EHCC)。迄今为止,根治性切除仍然是早期EHCC最有效的治疗方法。由于大多数EHCC就诊时已处于晚期[2-3],接受根治性切除的比例仅为20%~35%[4-5]。此外,49%~64%的EHCC病人术后发生复发或转移[6]。因此,EHCC的预后较差,pCCA和dCCA的5年总生存率(OS)约为11%~41%和27%~37%[7]。
对于不能行根治性切除的晚期EHCC病人,姑息治疗方式包括姑息性胆肠内引流术、经皮肝或经内镜胆道支架置入、射频消融术、放化疗、分子靶向治疗等[8-9]。经姑息性手术(PS)或胆道支架植入等途径行胆道引流可使病人恢复胆汁循环,从而减轻病人症状,提高生活质量及延长生存时间[10]。对于晚期EHCC病人,通过何种途径行胆道引流疗效更好的研究,目前国内外报道很少。本研究比较自膨式金属支架联合导管载入式125I粒子(self-expandable metallic stent combined with catheter loaded iodine-125 seeds, SEMS-CL-125I)及PS治疗晚期EHCC的疗效。
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选择2014年1月至2018年6月在我科住院的晚期EHCC病人。纳入标准:(1)病理诊断为pCCA或DCCA,经多学科讨论后认为不适合做根治性切除;(2)病人不能耐受或不愿行根治性切除;(3)首次接受SEMS-CL-125I(SEMS-CL-125I组)或胆囊切除联合胆管空肠吻合术(PS组)。排除标准:(1)良性胆道疾病;(2)远处转移;(3)既往因EHCC接受过手术、内镜下胆道支架植入或化疗等治疗;(4)随访等资料不完整。最终纳入101例病人。其中,SEMS-CL-125I组67例,男47例,女20例,年龄>70岁41例,pCCA 28例;PS组34例,男27例,女7例,年龄>70岁15例,pCCA 28例。2组性别、年龄、肿瘤部位、血清总胆红素(TBIL)、直接胆红素(DBIL)、丙氨酸氨基转移酶(ALT)、天冬氨酸转氨酶(AST)、白蛋白(ALB)、糖类抗原19-9(CA19-9)和癌胚抗原(CEA)等差异均无统计学意义(P>0.05),具有可比性。本研究遵守赫尔辛基宣言[11],并通过蚌埠医学院第一附属医院伦理委员会的批准。
变量 总体 SEMS-CL-125I组
(n=67)PS组
(n=34)Z P 性别(男/女) 74/27 47/20 27/7 0.99* 0.05 年龄(≥70/ < 70)/岁 56/45 41/26 15/19 2.66* 0.05 肿瘤部位(pCCA/dCCA) 36/65 28/39 8/26 3.28* 0.05 CA19-9/ (ng/mL) 278.9(62.5~797.8) 293.0(72.5~989.8) 128.6(34.9~471.0) 1.61 0.05 CEA/(ng/mL) 4.2(2.6~6.4) 4.0(2.4~6.1) 4.3(2.8~6.7) 0.82 0.05 ALT/(U/L) 125(81~248) 131(92~239) 104(58~269) 1.00 0.05 AST/(U/L) 133(80.5~169) 137(97~191) 166(61~167) 1.72 0.05 TBIL/(μmol/L) 221(127~319) 244(150~343) 178(99~293) 1.67 0.05 DBIL/(μmol/L) 182.0(106.9~284.8) 194.8(121.7~298.8) 142.8(80.4~234.4) 1.74 0.05 ALB/(g/L) 34.2(31.4~37.7) 33.6(31.1~37.2) 35.1(32.9~39.9) 1.60 0.05 *示χ2值 表 1 基线资料比较
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SEMS-CL-125I组67例均成功置入胆道支架和125I粒子。SEMS-CL-125I的具体操作过程已在前文进行描述[12-14]。PS组行姑息性手术。2组病人均进行随访,随访截止至2019年6月或死亡。随访内容:术后1、3、6个月行血清肿瘤标志物、生化常规、腹部B超、CT检查。
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采用秩和检验、χ2检验、方差分析和q检验。
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与术前相比,2组病人术后1、3、6个月血清TBIL、ALT、AST水平均降低,而ALB均升高,差异有统计学意义(P < 0.05)。SEMS-CL-125I组术后1个月ALB水平显著高于PS组(P < 0.05)(见表 2)。
分组 n 术前 术后1月 术后3月 术后6月 P F MS组内 ALT/(U/L) SEMS-CL-125I组 67 169.16±106.71 46.93±29.67** 37.81±29.72** 41.75±37.47** < 0.01 74.50 3 638.650 PS组 34 163.12±140.72 56.06±35.62** 40.38±15.56** 48.20±28.44** < 0.01 20.50 5 530.460 t — 0.24 1.36 0.47 0.88 — — — P — 0.05 0.05 0.05 0.05 — — — AST/(U/L) SEMS-CL-125I组 67 152.76±91.04 54.72±30.87** 41.22±34.11** 44.70±45.01** < 0.01 61.10 3 107.660 PS组 34 120.41±65.09 51.48±29.97** 35.50±13.18** 47.80±24.75** < 0.01 33.80 1 480.300 t — 1.84 0.50 0.94 0.37 — — — P — 0.05 0.05 0.05 0.05 — — — TBIL/(U/L) SEMS-CL-125I组 67 250.01±132.09 39.82±32.79** 17.63±22.01** 17.53±10.93** < 0.01 179.0 0 4 781.710 PS组 34 212.42±144.91 54.25±48.47** 15.16±10.95** 23.29±16.76** < 0.01 48.80 5 937.260 t — 1.31 1.77 0.62 2.08 — — — P — 0.05 0.05 0.05 0.05 — — — ALB/(g/L) SEMS-CL-125I组 67 34.45±4.87 39.07±3.83** 40.72±3.39** 39.86±3.32** < 0.01 34.50 15.225 PS组 34 35.80±4.38 36.60±5.58 39.65±2.09** 39.28±2.66* < 0.01 41.90 15.441 t — 1.36 2.61 1.68 0.88 — — — P — 0.05 0.05 0.05 0.05 — — — 与同组术前比较*P<0.05,**P<0.01 表 2 2组术后1、3、6个月血清中ALT、AST、TBIL及ALB的变化情况
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SEMS-CL-125I组67例中术后有12例(17.9%)出现并发症,其中胰腺炎或血清淀粉酶升高6例,严重电解质紊乱3例,胆道感染3例。PS组术后12例(35.3%)出现并发症,其中吻合口瘘5例,切口感染4例,切口裂开1例,伤口出血1例,胃瘫1例。2组均未发生粒子放射相关的并发症。2组术后总体并发症差异无统计学意义(χ2=3.76,P>0.05)。与PS组病人的住院时间17~23 d相比,SEMS-CL-125I组12~18 d明显缩短(χ2=4.02,P < 0.01);与PS组病人的住院费用42 912~59 874元相比,SEMS-CL-125I组32 147~41 067元明显减少(χ2=6.06,P < 0.01)。
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2组病人均获得了完整的随访,最长随访时间为30个月。SEMS-CL-125I组中分别有33例(49.3%)、12例(17.9%)及2例(3.0%)于术后6个月、12个月及18个月重新植入新鲜的125I粒子。至随访终点,SEMS-CL-125I组病死44例(65.7%),PS组病死24例(70.6%)。与PS组相比,SEMS-CL-125I组病人OS显著改善(中位生存时间14个月和10个月,P < 0.05)(见图 1)。SEMS-CL-125I组病人1年、2年OS率分别为65.0%和40.0%,而PS组则分别为20.7%和18.1%。肿瘤部位pCCA病人SEMS-CL-125I组可显著改善OS(P < 0.05),而在dCCA中2组OS差异无统计学意义(P>0.05)(见图 2)。术前TBIL、CA19-9、ALB和治疗方法是与术后OS相关的主要因素(见表 3)。
变量 OR(95%CI) P 性别(男/女) 1.040(0.654-1.652) >0.05 年龄(≥70/ < 0岁) 1.227(0.787-1.911) >0.05 肿瘤部位(pCCA/dCCA) 1.174(0.749-1.841) >0.05 CA19-9 (H vs L) 1.960(1.239-3.101) < 0.01 CEA (H vs L) 1.208(0.761-1.916) >0.05 ALT (H vs L) 1.027(0.655-1.610) >0.05 AST (H vs L) 1.145(0.689-1.901) >0.05 TBIL (H vs L) 1.762(1.124-2.762) < 0.05 ALB (L vs H) 1.757(1.111-2.779) < 0.05 治疗方法 1.640(1.030-2.611) < 0.05 (PS vs SEMS-CL-125I) 表 3 影响病人术后OS的单因素分析
胆道支架联合125I粒子置入与姑息性手术治疗晚期胆管癌的疗效比较
Comparison of therapeutic effect of biliary stent combined with 125I particle implantation and palliative surgery in the treatment of advanced cholangiocarcinoma
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摘要:
目的比较自膨式金属支架联合导管载入式125I粒子(SEMS-CL-125I)与姑息性手术(PS)治疗晚期肝外胆管癌(EHCC)的疗效。 方法选择SEMS-CL-125I(SEMS-CL-125I组,n=67)或PS(PS组,n=34)治疗的晚期EHCC病人,比较2组术后并发症、住院时间、住院费用和总体生存率(OS)的差异。 结果与术前相比,2组病人术后1、3、6个月血清TBIL、ALT、AST水平均降低,而ALB均升高(P < 0.05)。SEMS-CL-125I组术后1个月ALB水平显著高于PS组(P < 0.05)。2组术后总体并发症差异无统计学意义(P>0.05)。与PS组相比,SEMS-CL-125I组病人的住院时间明显缩短,住院费用明显减少(P < 0.01),OS显著改善(P < 0.05)。术前TBIL、CA19-9、ALB和治疗方法是与术后OS相关的主要因素。 结论对于晚期EHCC病人,与PS相比,SEMS-CL-125I显著缩短了住院时间,降低了住院费用,延长了生存时间,值得临床推广和应用。 -
关键词:
- 肝外胆管癌 /
- 自膨式金属支架 /
- 导管载入式125I粒子 /
- 姑息性手术
Abstract:ObjectiveTo compare the efficacy of self-expanding metal stent combined with catheter loaded 125I particle (SEMS-CL-125I) and palliative surgery (PS) in the treatment of advanced extrahepatic cholangiocarcinoma (EHCC). MethodsPatients with advanced EHCC treated with SEMS-CL-125I (SEMS-CL-125I group, n=67) or PS (PS group, n 34) were selected.The postoperative complications, hospitalization time, hospitalization expenses and overall survival rate (OS) between the two groups were compared. ResultsCompared with that before operation, the levels of TBIL, ALT and AST in the two groups decreased at 1, 3 and 6 months after operation, while ALB increased (P < 0.05).The level of ALB in SEMS-CL-125I group was significantly higher than that in PS group at 1 month after operation (P < 0.05).There was no significant difference in postoperative complications between the two groups (P>0.05).Compared with PS group, The hospitalization time, hospitalization expenses and OS in SEMS-CL-125I group were significantly shorter than those in PS group (P < 0.01), and OS was significantly improved (P < 0.05).Preoperative TBIL, CA19-9, ALB and treatment method were the main factors related to postoperative OS. ConclusionsCompared with PS, SEMS-CL-125I significantly shortens the hospitalization time, reduces the hospitalization expenses and prolongs the survival time of patients with advanced EHCC, which is worthy of clinical promotion and application. -
表 1 基线资料比较
变量 总体 SEMS-CL-125I组
(n=67)PS组
(n=34)Z P 性别(男/女) 74/27 47/20 27/7 0.99* 0.05 年龄(≥70/ < 70)/岁 56/45 41/26 15/19 2.66* 0.05 肿瘤部位(pCCA/dCCA) 36/65 28/39 8/26 3.28* 0.05 CA19-9/ (ng/mL) 278.9(62.5~797.8) 293.0(72.5~989.8) 128.6(34.9~471.0) 1.61 0.05 CEA/(ng/mL) 4.2(2.6~6.4) 4.0(2.4~6.1) 4.3(2.8~6.7) 0.82 0.05 ALT/(U/L) 125(81~248) 131(92~239) 104(58~269) 1.00 0.05 AST/(U/L) 133(80.5~169) 137(97~191) 166(61~167) 1.72 0.05 TBIL/(μmol/L) 221(127~319) 244(150~343) 178(99~293) 1.67 0.05 DBIL/(μmol/L) 182.0(106.9~284.8) 194.8(121.7~298.8) 142.8(80.4~234.4) 1.74 0.05 ALB/(g/L) 34.2(31.4~37.7) 33.6(31.1~37.2) 35.1(32.9~39.9) 1.60 0.05 *示χ2值 表 2 2组术后1、3、6个月血清中ALT、AST、TBIL及ALB的变化情况
分组 n 术前 术后1月 术后3月 术后6月 P F MS组内 ALT/(U/L) SEMS-CL-125I组 67 169.16±106.71 46.93±29.67** 37.81±29.72** 41.75±37.47** < 0.01 74.50 3 638.650 PS组 34 163.12±140.72 56.06±35.62** 40.38±15.56** 48.20±28.44** < 0.01 20.50 5 530.460 t — 0.24 1.36 0.47 0.88 — — — P — 0.05 0.05 0.05 0.05 — — — AST/(U/L) SEMS-CL-125I组 67 152.76±91.04 54.72±30.87** 41.22±34.11** 44.70±45.01** < 0.01 61.10 3 107.660 PS组 34 120.41±65.09 51.48±29.97** 35.50±13.18** 47.80±24.75** < 0.01 33.80 1 480.300 t — 1.84 0.50 0.94 0.37 — — — P — 0.05 0.05 0.05 0.05 — — — TBIL/(U/L) SEMS-CL-125I组 67 250.01±132.09 39.82±32.79** 17.63±22.01** 17.53±10.93** < 0.01 179.0 0 4 781.710 PS组 34 212.42±144.91 54.25±48.47** 15.16±10.95** 23.29±16.76** < 0.01 48.80 5 937.260 t — 1.31 1.77 0.62 2.08 — — — P — 0.05 0.05 0.05 0.05 — — — ALB/(g/L) SEMS-CL-125I组 67 34.45±4.87 39.07±3.83** 40.72±3.39** 39.86±3.32** < 0.01 34.50 15.225 PS组 34 35.80±4.38 36.60±5.58 39.65±2.09** 39.28±2.66* < 0.01 41.90 15.441 t — 1.36 2.61 1.68 0.88 — — — P — 0.05 0.05 0.05 0.05 — — — 与同组术前比较*P<0.05,**P<0.01 表 3 影响病人术后OS的单因素分析
变量 OR(95%CI) P 性别(男/女) 1.040(0.654-1.652) >0.05 年龄(≥70/ < 0岁) 1.227(0.787-1.911) >0.05 肿瘤部位(pCCA/dCCA) 1.174(0.749-1.841) >0.05 CA19-9 (H vs L) 1.960(1.239-3.101) < 0.01 CEA (H vs L) 1.208(0.761-1.916) >0.05 ALT (H vs L) 1.027(0.655-1.610) >0.05 AST (H vs L) 1.145(0.689-1.901) >0.05 TBIL (H vs L) 1.762(1.124-2.762) < 0.05 ALB (L vs H) 1.757(1.111-2.779) < 0.05 治疗方法 1.640(1.030-2.611) < 0.05 (PS vs SEMS-CL-125I) -
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