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Targeted-Cryoablation for Solid Tumor: A Clinical Analysis of 41 Cases

Zhang Zongcheng, Jiang Jianxiao, Li Kaibin.
Department of Oncology, 2nd Hospital of Zhaoqing, Guangdong 526060, P R China
[Abstract] Forty-one solid tumor patients, who had lost their radical excision chance, were treated with cryosurgery in our hospital from April, 2001 to December, 2001. Preoperatively, the tumor diameter of 8 patients were smaller than 5cm, 25 ranged from 5cm to 10cm, 8 were larger than 10cm. The CEA value of 16 cases were higher than 250μg/L, AFP in 8 cases higher than 400ug/L. Open cryosurgery (5 cases), percutaneous cryoablation(31 cases), and superficial cryosurgery directly(5 cases) were performed. Fever after operation in different extent was observed in all patients. No death, liver rupture or hemorrhage, biliary fistula, skin frostbite, infection and puncture resulted implantation metastasis during and post-operation were presented. Pneumothorax occurred in two lung cancer patients during percutaneous cryoablation. Postoperatively, abnormal serum content of AFP and CEA decreased. Multicolour B-ultrasound and CT scan revealed that the blood flow of tumor vessel decreased and the tumor size reduced gradually. The quality of life in 35 patients improved obviously. The short-term effect was prominent, but the forward effect needs further study.

[Key Words] Solid tumor, Cryosurgery, Cryoablation
The paper presented 41 patients suffered from solid tumor who had lost their radical excision chance, were treated by cryosurgery between April, 2001 and December, 2001.

1 Clinical Materials
1.1 General material. Forty-one patients were enrolled in the group, male 33 and female 8 respectively. Age ranged from 38 to 86 years, averaged 57 years old. There were 18 cases of lung cancer, 10 hepatic cell carcinoma, 3 metastatic liver cancer, 2 prostate cancer, 3 skin squamous cell carcinoma, 1 fibrosarcoma in left leg, 1 tongue root squamous cell carcinoma, 1 left chest mesothelioma, 1 liver angioma, and 1 penis tumor complicated bilateral groin lymphatic metastasis. All patients were diagnosed through pathology, image, and tumor marker. Preoperatively, the tumor diameter of 8 patients were smaller than 5cm, 25 ranged from 5cm to 10cm, 8 were larger than 10cm. The CEA value of 16 cases were higher than 250μg/L, AFP in 8 cases higher than 400ug/L, and the Karnofsky score varied from 50 to 70(average 60).

1.2 Instrument & equipment. Endocare Cryocare System( 4 knifes 2mm、3mm、5mm、8mm); A suit of self-made stainless human trunk localizer (see the chart).

2. Cryosurgery methods
Directly freezing after abdominal incision or thoracotomy were performed in 5 patients. Inclined incision at submarginal of right rib were used in 4 liver tumor patients. After abdomen was exposed, cut the round ligament of liver, confirmed the location, size and number of tumor and made it exposure completely. To get the best freezing effect, puncture to the scheduled target point should be guided by B-ultrasound when the tumor locate in the deep of the liver. An appropriate cryoprobe(selected based on the tumor size, localization, and the scheduled ice ball size), was introduced into the tumor through normal hepatic tissue. Multi- time & point freezing were chosen for big tumor to make the ice ball overlay the whole tumor or 1cm beyond the tumor border may as well. Right rib interspace inclined incision thoracotomy was performed for one lung cancer patient. During the operation, one or more cryoprobe were inserted into the rim of the tumor. The operator should block off mediastinal organs with hands like heart, big blood vessel and main bronchus, and pay attention to avoid injuring bronchus, bronchial blood vessels and normal lung tissues. Close thorax drainage was placed and connected to water-covered bottle when cryosurgery closed.
Percutaneous cryosurgery were performed for 31 cases. Local anesthesia plus intravenous anesthesia were used for operation. Two liver cancer cryoablation were guided by B-ultrasound after localized by CT scan. Self-made stainless trunk localizer and CT monitor were introduced into the process of puncturing for 8 liver cancer, while it improved the once success rate greatly. Puncture monitored under CT were achieved for 17 lung cancer, 1 left thorax mesothelioma, 2 prostate cancer, and 1 liver angioma. When the needle reached at the target point, import a guide steel wire, and then withdraw the needle and introduce in a tube dilator with sheath. Confirmed the depth, reserved the outer sheath and insert needle-shape cryoprobe to the tumor. The freezing time and the necessity of another freezing were decided on the size of tumor. Generally, 2 freezing cycles 15 mins (20 min for lung cancer) each is needed. Observe the iceball size by CT or B-ultrasound. When the temperature resumed to 15°C, pull out the probe and filled in hemostatic gauze.
Direct freezing 5 superficial tumors. They were 3 cases skin squamous cell carcinoma, 1 fibrosarcoma in left leg, 1 tongue root squamous cell carcinoma, and 1 penis tumor complicated bilateral groin lymphatic metastasis. Needle-shape cryoprobe were pressed tight to the tumor or inserted into the tumor for freezing directly according to CT image. Warm water constantly dripping to protect the surrounding normal skin.

3. Result
Hospitalization time of the group ranged from 5 to 20 days, and average 13 days. There were no death, liver rupture and hemorrhage, biliary fistula, skin frostbite, infection and puncture resulted implantation metastasis during and post- operation. pneumothorax occurred in 2 percutaneous cryoablation patients after operation. Fever in different degree can be observed in all patients. The AFP value in 8 patients whose serum content of AFP was higher than normal decreased. Those 16 CEA abnormal patients decreased prominently, especially 10 patients back to normal level. One month after surgery, the systemic condition improved. Karnofsky score advanced to 60~90, average 70. CT scan revealed tumor necrosis, CT value decreased obviously from 30Hu to -20Hu below and without enhancement sign. Three months postoperatively, CT scan showed the tumor size obviously reduced. Especially, the wounded area of a male patient suffered from abdominal skin squamous cell carcinoma dwindled from 25cm to 5cm 5 month after cryosurgery. The quality of life in 35 patients improved prominently. Postoperatively follow-up study show the short-term effect were prominent, but the forward effect needs further study.

4. Discussion
4.1 Mechanism of cryosurgery for treating solid tumor. 4-probe Cryosurgery System is manufactured by American Endocare Corporation utilizing outer space rocket controlled and guided technology. It matches 2mm, 3mm, 5mm, 8mm insert-type cryoprobe. The iceball can be controlled between 3cm to 8cm according to the diameter of the cryoprobe. The temperature will drop to -160°C in one minute, and can rise up to 40°C quickly, and even can complete cold-heat-cold-heat multi-cycle. In the course of freezing, ice crystal formed in the cytoplasm could result in tissue necrosis. The efficacy of freezing lies on the freezing speed. In the course of temperature drop off, rapid freezing water molecule in cytoplasm inflate the cell suddenly, leading to cell membrane rupture and cellular necrosis. At the same time, protein, the main component of cell, degenerate rapidly under super low temperature. The tumor, enriched with blood vessel, undergo anoxia and ischemia because of vessel wall hurt and thrombosis. So cryosurgery plays a withering effect on the tumor. The specific antigen produced by necrotic tumor cells enter into blood circulation, stimulate immune system constantly to produce antibody, and bring forth immune reaction to suppress tumor's further development.

4.2 Patients selection. At present, tumor radical resection is still the most effectively and first choice for treating parenchymatous tumor. But most patients had lost their radical resection chance when they came to see a doctor. Cryosurgery had become a most vital choice of treatment for these patients. Indications: 1. Parenchymatous tumor who had lost its radical resection chance. 2. The principal part of tumor did not invade big blood vessel and luminal organ such as esophagus, intestine, heart, and aorta, etc. 3. Karnofsky score must excess 50. Function of vital organs like heart, lung, liver, and kidney must be normal. Bleeding & clotting mechanism must be in normal range.

4.3 Therapeutical effect evaluation.
Short- & long-term curative effect evaluation of cryosurgery must comply with the criterion established by WHO. Besides the change of tumor size, CT value and PET can also be introduced in short-term curative effect evaluation.

4.4 General therapy postoperatively. Cryosurgery is just a kind of local therapy, the systemic therapy after operation is absolutely necessarily. For example, lipiodol interventional embolism for liver cancer, interventional bronchial artery perfusion chemotherapy for lung cancer, and internal iliac artery perfusion chemotherapy for cervix cancer are important methods after cryosurgery. It also can cooperate with systemic chemotherapy, immunotherapy, biotherapy and radiotherapy.

4.5 Complications' prophylaxis and treatment. It is important to prevent and treat complications after cryosurgery. It is necessary for the operator to manipulate correctly and control the contraindication of patient selection. At the beginning, pneumothorax occurred in a lung cancer patient during percutaneous cryoablation because of unskilled manipulation, and the patient had to perform thoracotomy before cryosurgery. The most common complications is hemorrhage caused by puncture percutaneously. At this moment, the needle should stay at the former location. If it is pulled out, blood may bleeding into abdominal cavity. Go on to insert cryoprobe in order to stop bleeding by freezing. After withdrawing cryoprobe, glutin sponge and hemostatic gauze should be filled in the puncture channel. As draw the catheter sheath, hemostatics must be filled into the bleeding point, and eventually pull out the sheath when stop bleeding. The wound should be tightened with bellyband for 24 hours after operation. During the process of percutaneous puncture for lung cancer patients, it is important to prevent gas communication intra- and outer- thorax. Not only does pneumothorax lead to dyspnea, but also make the tumor shift and fail to puncture because of lung compressed. In freezing course of freezing prostate cancer and cervix carcinoma, bladder must be rinsed continuously with warm water to prevent hurt bladder, ureter, and urethra. If it is possible, temperature probe must be used to monitor tissue temperature surround the corresponding organ and when the temperature drop to low 0℃, cryosurgery must stop. In the course of cryosurgery, pay attention to heat preservation and cold shock prophylaxis. With the help of anestheitst, ECG monitoring and deal with any unexpected condition as soon as possible is necessary.

References
1. Wang SM, Zhang JR, Peng QP, et al. The treatment of irresectable liver tumors by percutaneous targeted Ar-He cryoablation. International Journal of Modern Cancer Therapy. 2000; 3(1): 16-18
2. Steele G Jr. Cryoablation in hepatic surgery. Semin liver Dis 1994;14;120 125.
3. Morrs DL, Horton.AC, Dilley A V, et al. The treatment of hepatic metastasis by cryotherapy and regional cytotoxic perfusion.Gut,1993,34:1156.
( Paper was accepted at March, 2002)

 

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