Sensitization Of Microwave Ablation For Hepatic Tumor Induced By Intratumoral Chemotherapeutic Drugs Injection

Objective Microwave ablation therapy for hepatic tumor has achieved satisfactory treatment responses. However, it is difficult to eradicate tumors bigger than 3cm in situ and conformably at one stroke. To achieve this aim, intratumoral chemotherapeutic drugs injection was used to sensitize hepatic tumor to microwave ablation.MATERIALS AND METHODSPart â… 1. Establishment of rabbit liver VX₂ tumor model by the coeliotomy: Nine New Zealand white rabbits were implanted with VX₂ tumor in two liver lobes by the coeliotomy. Ultrasound examinations were performed 17 days after implantation. At the same time exploratory laparotomy was performed to observe the results of implantation, the feature of tumor growth, and complications.2. Establishment of rabbit liver VX₂ tumor model under ultrasound guidance percutaneously: 40 New Zealand white rabbits were implanted with VX₂ tumor in two liver lobes under ultrasound guidance. Ultrasound examinations were performed 20³6 days after implantation. At the same time exploratory laparotomy was performed to observe the results of implantation, the feature of tumor growth, and complications.3. Comparison between the two methods: The results of the implantation, the feature of tumor growth, and complications were compared between two groups. Contrast sonography was performed in 3 rabbits with 4 tumors.Part â…¡1. To determine whether intratumoral distilled water injection followed bymicrowave ablation can increase ablation area: Seven New Zealand white rabbits with 10 rumors were treated with (1) microwave ablation alone (output power, 5W;time, 180s);(2) intratumoral injection of distilled water (volume, 0.5ml) immediately followed by microwave ablation. Pathologic examination and the resultant tumor destruction from each treatment were evaluated.2. To determine whether intratumoral chemotherapeutic drug injection can sensitize VX2 tumor to microwave ablation: 27 New Zealand white rabbits with 40 tumors treated with (a) microwave ablation alone (output power, 5W;time, 180s);(b) intratumoral cisplatin dissolved into distilled water injection alone (volume, 0.5 ml;total dose, 1.5mg);(c) intratumoral ultra-fluid lipiodol injection alone (volume, 0.5 ml);(d) intratumoral cisplatin dissolved into ultra-fluid lipiodol injection (volume, 0.5 ml;total dose, 1.5mg);(e) ultra-fluid lipiodol injection immediately followed by microwave ablation;(f) cisplatin injection immediately followed by microwave ablation;(g) intratumoral cisplatin dissolved in ultra-fluid lipiodol injection immediately followed by microwave ablation;(h) no treatment. Pathologic examination and the resultant tumor destruction from each treatment were evaluated. Part HITumor cell apoptotic indices in the residual tumor of the a^c group in the second part were compared with that of h group respectively by using TUNEL technique. ResultsPart I Tumors were successfully implanted in 12/18 (67%) in the groups by the coeliotomy, with the ectopic implantation rates of 4/16 (25%). Tumor size was (1.3xl.l)cm 18-19 days after implantation. The implantation time was about 20-30 minutes. Tumors successfully implanted varied from 16/30 (53%) to 38/50 (76%) in the groups under ultrasound guidance, with the ectopic implantation rates from 14% (6/44) to 25% (4/16). Tumor size was (0.7><0.5)cni 21-22 daysafter implantation, and (1.5xl.3)cm 31³8 days after implantation. The implantation time was about 12⁴0 minutes. There were no significant differences between two groups in the successfully in situ and ectopic implantation rate (the former, P=0.32;the later, P=0.62). The longitudinal and the transverse axis of tumors in the group by the coeliotomy 18-19 days after implantation were bigger than those under ultrasound guidance 21-22 days after implantation respectively (P=0.0001 each). There was no significant difference in the successful implantation rate of the left and right lobe between the two groups. Contrast sonography can show tumor distinctly. Coelio-adhesions, wound infection in abdominal walls and incisional hernia were often seen in the group by the coeliotomy, whereas implantation area can be chosen and celiac bleeding can be seen in the group under ultrasound guidance.Part II Coagulation area induced by the treatment of intratumoral distilled water injection immediately followed by microwave ablation was (87.49±6.57)mm2, while that of microwave ablation alone was (82.35±4.31)mm2 (P=0.18);Compared with the group of no treatment, microwave ablation, intratumoral lipiodol injection, and intratumoral cisplatin injection can destruct the tumor, and the destruction area was (82.35 + 4.3l)mm2^ (15.59+ 1.28)mm2> (23.27±3.96)mm2 respectively (P <0.0001 each). Cisplatin whatever dissolved in distilled water or lipiodol could sensitize tumor to microwave ablation, while lipiodol could not (P<0.0001, P<0.0001, and P=0.41 respectively). The destruction area was (145.13±7.00) mm2, (165.30±5.08) mm2, and (80.40±4.16) mm2 respectively. Lipiodol can sensitize rumor to cisplatin and the destruction area was (38.67±4.06) mm2 (PO.0001).Part HI Compared with the group of no treatment, tumor cell apoptotic indices increased significantly in the groups of microwave ablation, lipiodol, and cisplatin respectively (P<0.0001, P<0.0001, and P=0.0014). Conclusion 1. VX2 liver tumor established by the coeliotomy grows more rapidly than thatunder ultrasound guidance. VX2 liver tumor established by the coeliotomy can be used in the experimental study that therapeutic methods are performed without coeliotomy and the study period is short, while that under ultrasound guidance can be used in the experimental study that therapeutic methods are performed by the coeliotomy. Ultrasound examinations can be performed in monitoring the tumor growth, and contrast sonography can be performed if necessary.2. Coagulation area induced by the treatment of intratumoral distilled water injection immediately followed by microwave ablation was not significantly bigger than that of microwave ablation alone. Microwave ablation, lipiodol, and cisplatin can destruct the tumor. Cisplatin whatever dissolved into distilled water or lipiodol could sensitize tumor to microwave ablation, while lipiodol could not. Lipiodol can sensitize tumor to cisplatin.3. Microwave Ablation, lipiodol, and cisplatin can induce tumor cell apoptosis respectively.