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The Clinical Analysis on 30 cases of Patients with Non-Small cell Lung Cancer Treated by Percutaneous Targeted Cryoablation Therapy
Wu Qing, Wu Xueyong, Feng Jianping , Zhang Jiren


Department of Oncology, Jing'an Elder People Hospital , Shanghai (200040)
Oncology Center of PLA, Zhujiang Hospital, The First Military Medical University, Guangzhou

(Abstract) Object: to analyze the feasibility of Percutaneous Targeted Cryoablation Therapy for treatment of patients with lung cancer and its Influences on the Patients' Life-Span. Methods: CT or X-ray orientation and inducing, puncturing the skin to conduct the Argon-Helium prob orientation refrigeration. Results: All 30 cases are in smooth conditions during the operation without death. 94.4% get lower fever after the operation for 3-5 days , 16.7% has blood in the sputum, 10% (3 cases among the 30) has pneumothorax 20% (6 cases among 30) has thorax accumulated liquid and 3.3% (one case among 30) has thorax transplantation transferring. Based on CT re-examination, in the effective refrigeration zone, the result of CT show decreases significantly. 6 cases have got complete frozen, 19 cases' refrigeration range has exceeded 85% of the total cancer, as well as 5 cases' refrigeration range has surpassed 70% of the cancer. The shortest following-up period is three months and the longest is 12 months. Among the cases, 6 died and others are still been followed up. The clinical symptom has been improved obviously. Conclusion: Using the Cryocare surgery system orientation refrigeration through skin to treat lung cancer is feasible, effective with the advantages of less hurt and less syndrome. In addition, the refrigeration can be conducted repeatedly to elevate the effectiveness. This is the new treatment for the patients whose lung caner can not be cut or who are not willing the accept operation. However, the relatively high rudimental rate needs further improvement.

Key Words: Lung cancer, Cryocare surgery system, targeted cryoablation,

Cryocare surgery system is a new technology recently adopted in the world, which has made delightful success, among which using the technology to treat prostate cancer, lung cancer and so forth has been reported(1-2). The author, under the CT inducing, adopted this treatment to treat lung cancer the first time successfully in March of 2000. Until November of 2000, 30 operations have been adopted and the details are reported as following:

1 Clinical data
1.1 General Information
30 cases of Patients with Non-Small cell Lung Cancer (Male: 22 cases, Female: 8 cases). Ages: between 43 and 81. Average Age: 67. 9 cases of left higher lung cancer, 6 cases of left lower lung cancer, 4 cases of right higher lung cancer, 5 cases of middle lung cancer, 6 cases of right low lung cancer; 27 cases of surrounding lung cancer, 3 cases of central lung cancer, 23 cases of original bronchia lung cases, 1 case of left high lung lymph cancer, 6 cases of transferring lung cancer, 14 case of adenocarcinoma, 6 cases of squama lung cancer, 1 case of lung original lymph cancer, four cases of transferring adenocarcinoma and four cases with unclear pathologic diagnose. The largest cancer is 12×11×9 cm3 and the smallest is 2.5×3×3 cm3. TNM Period:1 case of ⅢA,4 case of ⅢB,25 case of Ⅳ,among which four cases have bone transfer. 8 cases of X-ray inducing and 22 cases of CT inducing.

1.2 Orientation Method
1.2.1 CT Orientation
Based on lung CT two-dimension and three-dimension pictures as well as X-ray picture, the cancer's size, shape and surroundings can be indicated. After comparison and calculation, the type, quantity and location of the cryoprob can be ensured and the specific spot can be confirmed. Theoretically, the operation range should exceed the brim of cancer. Refrigeration range should be beyond 1-1.5 cm of the cancer's brim. A plastic token will be stick a colorful sign will be drawn. Then, measure the specific direction, angle and depth as reference of the puncturing. All the puncturing points should be marked in this way one by one. (Diagram1-1 and diagram 1-2)

1.2.2 X-Ray Orientation
Our hospital adopts CT scan combined with X-ray picture orientation. The longitudinal axle of the cancer should be decided first, then the transverse axle. The point of interaction should be the puncturing point. A metal token should be put here, after adjustment, the token should be painted into color.

1.3 Operation Method
After local anaesthesia,the skin should cut with a depth of 0.5cm. Then the CT orientation picture should instruct the angle, direction and depth of puncturing till reaches the satisfactory level (Diagram 2). Introduce inducing steel wire to expand canal/ theca , then insert the cryoprob followed by the refrigeration stick. After the cryprob has been inserted completely, the cycles of "refrigeration-calefaction- refrigeration-calefaction" should be started off. Each time, the refrigeration duration is about 20 minutes. The lowest frozen temperature is approximate‐150℃ and the temperature of the cancer's brim is about -40℃. If the cancer is very huge, the second time refrigeration can be conducted after withdrawing the cryoprob 3-3.5 cm till the cancer thoroughly becomes a huge ice-ball. During calefaction, as soon as the cryoprob can be separated with the ice-ball, the cryoprob can be withdrawn. After withdrawing the cryoprob, the specialized hemostatic gauze should be used to jam the wound to avoid the bleeding. If the bleeding is significant, the protein gelatin can be injected.

2 The Results
All the 30 cases are in good conditions and no death during the operation. Six cases are frozen completely, 19 cases' refrigeration range is more than 85%, 5 cases' more than 70%. 94.4% of the cases get fever for 37-38.5 oC after operation. 16.7% get more blood in sputum after operation. 10% (3 cases among the 30) has pneumothorax. The compression rate of all the lungs with cancer is less than 20% and due to no symptom, the drainage was not conducted. 20% (6 cases among 30) has thorax accumulated liquid, among which 5 only get small amount. Based on reexamination, only one case has relatively more exuded liquid, which has be cured by twice thorax drainage. 3.3% (one case among 30) has thorax transplantation transferring. Following up: shorted 3 months and longest 12 months. Six cases died, among which 3 cases have pancoast, 2 cases have huge adenocarcinoma on the right lung (in IV stage),and one case of thorax transplantation transferring. The following up results indicate that 16 cases had chest-ache before operation, which has been obviously released in 9 cases or reduced in 7 cases after operation. 3 cases'(they all have pancoast comprehensive disease) chest -ache became serious again two months after the releasing.

3 Discussions
3.1The Feasibility Probe

This technology is a new targeted cryoablation therapy. Actually, the similar chemical treatment has accumulated mature experience.〔1〕。Because the prob only releases the effective materials on the tip and the pole longer than 3.5cm is insulated, the hurt on the lung is very limited. (2) The formation of the ice ball may have direction, therefore ,the operation can be controlled well. In all the 30 cases, the points' locations are all satisfactory as well as the actual refrigeration range is also decent (Diagram 3). The patients are in good conditions with less syndrome and short recovery time. On the same day of operation, the patient can walk and eat. (3) Based on animal experiment, the huge artery has "warm pool" effect, hen it has good anti-refrigeration ability. bronchia also has good low temperature enduring ability. So, it is even possible to cure the cancer, which has penetrated into important vessels/ bronchia. (4) This kind treatment has relatively lower requirement on the patients' lungs' functions. which makes is more applicable on original bronchia lung cancer, transferring lung cancer(with less than four transferred focuses), central lung cancer even on the patients, whose lung function has been partially destroyed. In addition, repeating the refrigeration will not add any risk of syndrome. It gives more patients chances. That after refrigeration, the cancer is irritated is still a rare phenomenon, which can not be drawn a conclusion on.

3.2 The Key Issue of the Orientation and Inducing
X-ray orientation: simple and the whole process of puncturing and refrigeration can be supervised. However, because of the shadow, the scalpel's location in the cancer is a little difficult to be detected. The accuracy is not as good as CT orientation. CT orientation and inducing has higher accuracy. Utilizing three-dimension technology, the profile and the specific point can be indicated clearly. It can indicate important vessels and bronchia clearly, but it is more expensive. However, the effectiveness of the operation is also related to the doctor's skill and experiences. The lack of three-dimension orientation system put negative effective on the operation's result.

3.3 Evaluation of the effectiveness
Currently, no over-all and objective evaluation criteria available. The author proposes the following standard with WHO criteria as reference:

3.3.1Clinical Evaluation Criteria
The effectiveness is directly related to the effective refrigeration range.(1)Complete cure: the refrigeration range goes beyond 1cm of the cancer brim, no obvious transferring. The effectiveness is similar to common surgery without obvious pains, which is easily accepted by the patient. Sometimes, if the cancer is too huge or the patient is in too bad health condition, the complete refrigeration cannot be conducted, this kind of case also belongs to the category of complete refrigeration. Also, the cases, which are completely cured after several times of refrigeration, also fall into the category of complete cure.

(2)Appeasement refrigeration: the refrigeration range can not cover the cancer tissues completely and still has the rudimental. Because big amount of the cancer has been killed, the volume of the cancer has reduced and the symptom has been improved. In addition, the immune system can be stimulated to avoid the cancer transferring. Appeasement Refrigeration can be classified into three types according to the size of the effective range ①Obvious effectiveness : the range is over 85%, the recent symptom has been improved significantly ②Effective: the range is over 65%, the clinical symptom has been improved, however, its influence on the life-span can not be detected yet and further observation is needed.③Useless The range is less than 45%, and the clinical symptom has not significant change as well as no active influence on the life-span. The above criteria is not mature yet. Due to the limitation of the following up time, the long term effectiveness can not be evaluated clearly yet. Here, only reference and discussion can be provided.

3.3.2 Photogragpical evaluation Criteria
Currently, the main index to judge the effectiveness is the CT indicator's change. If the CT indicator decreases obviously, we can judge that the cancer has been killed after refrigeration.(the reference index is 1.0Hu±20.7. However, further research on this point is needed.

4 . Syndrome and Prevention
The occurrence rate of pneumothorax is much lower than expectation (only 10%), because the refrigeration makes the cancer stick with the lung. The compression rate of all the lungs with cancer is less than 20% and due to no symptom, the drainage is not needed to be conducted. Reducing the puncturing times before refrigeration can decrease the occurrence rate of pneumothorax. No blood appearances in cough in the cases and only very limited blood can be found in sputum, which stops automatically one week later. The fever after operation is common, whose degree is connected with the refrigeration range. That after refrigeration, the cancer is irritated is still a rare phenomenon with a very low occurrence rate. Use puncturing needle to expand canal/ theca will be helpful to avoid the phenomenon. The occurrence of shock and sudden stop of heart-beaten is extremely rare.

5 Problems and Prospect
Due to the three-dimension technology and automatic orientation which should be adopted in the cryocare surgical system, have not been really applied clinically. Therefore, the accuracy of the operation rests more on the doctor's experience and subjective judgment. The difference of the cases is significant. Also the high rudimental rate is very common, which will put negative influence on the elevation of the operation's effectiveness. The breakthrough in the research of the orientation system will elevate the accuracy and comfort feelings of the operation, which makes the technique possibly to the mainstream treatment for lung cancer in the future.

REFERENCES
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( Paper was accepted at March, 2001)

 

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