探讨纳米刀消融术联合吉西他滨在局部进展期胰腺癌(LAPC)治疗中的安全性及临床疗效。

回顾性分析2014年1月至2017年9月间解放军火箭军特色医学中心肝胆外科收治的64例LAPC患者临床资料，其中纳米刀消融联合吉西他滨治疗24例(联合组)和单药吉西他滨化疗40例(对照组)。监测2组患者治疗前与治疗后1、3、5、7、14、30 d的血清淀粉酶、肌酸激酶、乳酸脱氢酶水平，观察治疗前及治疗后7、14、30、60、90 d肿瘤标志物CA19-9水平变化趋势；记录2组治疗中出现的相关性并发症情况；CT影像结合实体瘤评价标准对比治疗前与治疗后90 d的肿瘤体积改变；治疗后通过复诊和电话方式随访16个月，经Kaplan-Meier曲线分析2组患者近期生存状况。对数据采用重复测量方差分析、t检验及χ²检验。

治疗前联合组血清淀粉酶[(41.25±20.77) U/L]和对照组[(48.82±18.25) U/L]比较，差异无统计学意义(t＝－1.525，P＝0.132)；治疗后1 d，联合组患者血清淀粉酶[(402.71±254.74) U/L]呈现一过性升高，随后逐渐下降，治疗后14 d[(40.03±18.96) U/L]和治疗后30 d[(35.76±16.02) U/L]分别与治疗前相比，差异均无统计学意义(t＝0.213、1.025；P＝0.833、0.311)；对照组治疗过程中各监测时间点血清淀粉酶水平比较，差异无统计学意义(F＝5.793，P＝0.058)。联合组与对照组患者治疗过程中，各监测时间点肌酸激酶水平比较，差异均无统计学意义(F＝2.330、1.718, P＝0.065、0.117)；乳酸脱氢酶水平比较，差异均无统计学意义(F＝1.240、1.804, P＝0.302、0.137)。联合组治疗后7 d患者肿瘤标志物CA19-9水平出现一过性升高，随后呈下降趋势，治疗后90 d [(114.43±40.61) U/mL]与治疗前[(190.81±100.46) U/mL]相比，差异有统计学意义(t＝3.453，P＝0.002)；对照组CA19-9水平于治疗后14 d持续上升，治疗后90 d [(494.57±94.08) U/mL]与治疗前[(212.22±81.34) U/mL]相比，差异有统计学意义(t＝－14.358，P<0.05)。联合组所有患者(100.0%)消融术中均出现术区肌肉震颤，2例(8.3%)患者出现一过性血压升高，治疗后3例(12.5%)患者出现轻度胰腺炎体征，未出现出血、穿孔、胰瘘等严重并发症。对照组中12例(30.0%)患者出现消化道不良反应，9例(22.5%)表现为骨髓抑制症状。联合组治疗后90 d肿瘤体积[(14.17±12.65) cm³]小于对照组[(26.93±17.42) cm³]，差异有统计学意义(t＝－3.123，P＝0.003)，联合组肿瘤缓解20例(83.3%)明显优于对照组14例(35.0%)，差异有统计学意义(χ²＝14.072，P<0.05)。随访表明，联合组平均生存时间为(11.3±3.7)个月，对照组为(7.6±3.4)个月，联合组患者生存情况优于对照组，差异有统计学意义(t＝8.130，P＝0.004)。

纳米刀消融术联合吉西他滨化疗可有效控制胰腺肿瘤的局部进展，延长生存期，值得临床推广。

To investigate the safety and clinical efficacy of nano-knife ablation combined with gemcitabine in the treatment of locally advanced pancreatic cancer (LAPC).

From January 2014 to September 2017, the clinical data of 64 patients with LAPC admitted to the Department of Hepatobiliary Surgery, Rocket Army Characteristic Medical Center of PLA were retrospectively analyzed. Among them, 24 patients in the nano-knife ablation combined with gemcitabine treatment (combined group) and 40 patients in the single drug gemcitabine chemotherapy (control group). Serum amylase, creatine kinase and lactate dehydrogenase levels were monitored before and 1, 3, 5, 7, 14 and 30 days after treatment in the two groups. To observe the change trend of CA19-9, a tumor marker, before and 7, 14, 30, 60 and 90 days after treatment. Relevant complications in the two groups were recorded. The volume changes of tumors before and 90 days after treatment were compared between CT images and solid tumors evaluation criteria. After treatment, follow-up visits and telephone calls were conducted for 16 months. The short-term survival of the two groups was analyzed by Kaplan-Meier curve. Data were analyzed with repeated measurements of variance analysis, t test and chi-square test.

Before treatment, serum amylase in the combined group [(41.25±20.77) U/L] was compared with the control group [(48.82±18.25) U/L], the difference was not statistically significant (t=-1.525, P=0.132). One day after treatment, the serum amylase in the combined group [(402.71±254.74) U/L] showed a transient increase, and then gradually decreased. There were no statistically significant differences between 14 days after treatment [(40.03±18.96) U/L] and 30 days after treatment [(35.76±16.02) U/L] compared with that before treatment (t=0.213, 1.025; P=0.833, 0.311). There was no significant difference in serum amylase levels of the control group at each monitoring time point (F=5.793, P=0.058). There was no significant difference in creatine kinase level between the two groups at each monitoring time point (F=2.330, 1.718; P=0.065, 0.117), and no significant difference in lactate dehydrogenase level between the two groups (F=1.240, 1.804; P=0.302, 0.137). Seven days after treatment, the level of CA19-9 in the combined group showed a transient increast, and then showd a downward trend, and there was significant difference within 90 days after treatment [(114.43±40.61) U/mL]compared with before treatment [(190.81±100.46) U/mL](t=3.453, P=0.002). The level of CA19-9 in the control group continued to rise 14 days after treatment. The difference was statistically significant within 90 days after treatment [(494.57±94.08) U/mL] compared with before treatment [(212.22±81.34) U/mL](t=-14.358, P<0.05). All patients (100.0%) during the ablation surgery in the combined group had muscle tremor in the operation area, 2 patients (8.3%) had transient blood pressure rise, 3 patients (12.5%) had mild signs of pancreatitis after operation, and no severe complications such as hemorrhage, perforation and pancreatic fistula occurred. In the control group, 12 patients (30.0%) had gastrointestinal adverse reactions, and 9 patients (22.5%) had bone marrow suppression symptoms. The tumor volume of the combined group [(14.17±12.65) cm³] was smaller than that of the control group [(26.93±17.42) cm³] at the time of 90 days after treatment, and the difference was statistically significant (t=-3.123, P=0.003). Twenty cases (83.3%) in the combined group were significantly better than 14 cases (35.0%) in the control group (χ²= 14.072, P<0.05). The follow-up showed that the average survival time of the combined group was (11.3±3.7) months and that of the control group was (7.6±3.4) months. The survival of the combined group was better than that of the control group, the difference was statistically significant (t=8.130, P=0.004).

Nano-knife ablation combined with gemcitabine chemotherapy can effectively control the local progress of pancreatic cancer and prolong survival time, which is worthy of clinical promotion.