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Clinical eveluation on Argon-Helium Targeted ablation Therapy for Treatment of Liver Cancer

Wu Qing, Zhang Jiren,

Department of Oncology, Jing'an Elder People Hospital, Shanghai

Oncology Center of PLA, Zhujiang Hospital, The First Military Medical University, Guangzhou

(Abstract) Object: to eveluate effectiveness as well as the syndrome by observing the patients treated by Endocare cryosurgery system. Methods: by the means of CT and B ultra short wave orientation and inducing, percutaneous Argon and Helium targeted ablation for treatment of liver cancer, using Crycare surgery system. Results: the patients are in good conditions during and after the operation, can recover soon, have no bleeding as well as the gallbladder will not be hurt or damaged. After the operation, 85% of the patients get fever and the low fever continue 2-7 day. The change of liver chemical enzyme is 81%(36 cases among 44) as well as the occurrence rate of the reactive thorax hydrocele is 20.4% (9 cases among 44). Among the 9 hydrocele cases, two have two-side thorax hydrocele, one has an abscess below the diaphragm, which has been cured by drainage. The occurrence rate of the lag reactive alimentary canal bleeding is 5.4% (two cases among 44) and among the two cases, one is dead ; therefore the mortality of the operation is 2.2% (one case among 44) . After the operation, based-on the follow-up whose duration is between 5 and 18 months, 15 cases are dead and the survival rate after one year is 65.9% as well as the one-year survival rate of the entire refrigeration patients is 90% ( 9 cases among 10). Conclusion: percutaneous Ar-He targeted ablation therapy is feasible, safety, effective with less syndrome and less hurt; however, the rudimental rate of the cancer is relatively high, which needs further improvement.

Key Words: Liver Cancer, Percutaneous targeted ablation Therapy

The incidence rate of liver cancer is relatively high in China; however, the operation-cutting rate is comparatively low as well as the recrudescent rate is high. Therefore, the comprehensive curative effect is not satisfactory. In recent tow years, foreign countries adopts the new argon and helium superconductor cryocare surgical system (in short form: Argon and Helium Scalpel) that punctures through the liver skin and directly refrigerates the cancer, and has made significant effectiveness. Zhang Jiren, Wang Senming and other people have successfully conducted this methods to cure liver cancer via B ultra short wave inducing(1). During the period between January 2000 and February of 2001, our hospital, adopting CT orientation and B ultra shot wave inducing, treated liver cancer 44 cases by percutaneous Ar-He targeted cryoablation therapy. The details are reported as the following.

1. The clinic data

1.1 General information: 44 patients with liver cancer, were treated by percutaneous Ar-He targeted cryoablation therapy, including 27 male cases; 17 female cases. The oldest one is 72 years old, the youngest is 34 as well as the average age is 59.2 years old. Among the 44 cases, there are original liver cancer 32 cases and transferring liver cancer 12 cases. The 44 cases totally accepted refrigeration 51 times, among which, 3 cases were frozen in the process of ventrotomy and 41 cases were treated through oriented refrigeration, including three cases of being frozen twice as well as two cases of being frozen three times. The biggest size of the cancer is 12×10× 9cm3 and the smallest is 3.4×2.6×3.6cm3. Among the cases, 11 cases' cancer entangles together with the liver cover film, two cases' pylori veins are embolized by cancer, four cases have slight liver ascites, 38 cases' liver function level is Child A as well as 6 cases' liver function level is B. The phases of the cancer: Ib phase: one case, IIa phase 16 cases, IIb phase 12 cases as well as IIIa phase 3 cases. During the operation, 3 cases only used one incision, 23 cases used 2 incisions, 14 cases used three incisions as well as 11 cases used four incisions.

1.2 Applicable Field of the Treatment: Original liver cancer with the diameter ≤12cm or the volume of the cancer occupies less than 50% of the liver's volume; the number of the focuses of the original cancer is ≤3个, the number of the focuses of the transferred cancer should be more than 4 or 5, in addition, the focuses of the original cancer should been cut already; the patients who have light or middle level hepatocirrhosis and the liver function level is Child A or B;the patients with original liver cancer which has transferred out of the liver; however, the cancer has been cut through operation or refrigeration; huge cancer, which has harmed the celiac veins, also can be treated by refrigeration; if the pylori veins are embolized by cancer, the refrigeration should be conducted together with the "liver artery & pylori vein bio-pumping operation" to avoid the validity of the simple refrigeration.

1.3 The taboo, namely the cases who are suitable for the treatment: Patients with significant icterus or ascites, which can not be alleviated by treatment; the patients whose liver function level is Child C;the patients who have serious hepatocirrhosis and high blood pressure of pylori veins; the cancer's volume has excess 60% of the liver's entire volume or the caner has extensively transferred; the patients whose cruor functions are abnormal or who have bleeding tendencies.

1.4 The designing and orientation of the refrigeration: the authors of this article adopt CT orientation method to judge the size, shape, location, circumstance of the cancer via the three-dimension image demonstrated by CT. After overall comparison and measuring, the site, layer, type of the "cold scalpel", angle, depth will be decided. Then, the puncture spots will be marked one by one (please refer to diagram 1). All the refrigeration is conducted after abdomen has been opened by operation and B ultra short wave shall play the roles of exploring direction and inducing.

1.5 The procedures of the operation
Local anesthesia with 0.5% Lidocaine or allo-propyl-hydroxybenene 2mg/kg. Referring to the three-dimension image, under the inducing of B ultra short wave, the doctors adopt Sholder technique to puncture the site and conduct the refrigeration. The cycle of refrigeration- temperature restoring-refrigeration will be repeated twice. In each time, the refrigeration period should last 15 minutes. If the cancer is significantly large, two more cycles can be adopted with withdrawing the cryoprob 3-3.5 cm till the cancer is totally frozen and decomposed. After withdrawing the cryoprob, the specialized bleeding stanching bolt should be used immediately in case the bleeding will happen. If necessary, the protein blood coagulant should be injected. Basically, no stitch is needed after operation.

2 The Result of the Operation:
During and after the operation, the patients are in good conditions, can recover very soon, can eat food immediately and can walk on the next day. There are no liver film cracking cases, no gallbladder leaking cases and no transplanting transferring cases. After the refrigeration, AFP of 43.4% of the patients recover to the normal level (14 among the 32 cases), and AFP level of 16 patients has got significant dropping (16 cases among 32). Only 0.62% of the patients have not got any changes in the term of AFP (2 cases among 32). 85% of the cases get fever after the operations, which lasts 2 to 7 days; the liver function change was found to be 81% (36 cases among 44), which lasts approximately one week; the occurrence rate of the reactive thorax hydrocele is 20.4% (9 cases among 44), among which two have two-side thorax hydrocele as well as one has an abscess below the diaphragm, which has been cured by drainage.The occurrence rate of the lag reactive alimentary canal bleeding is 5.4% (two cases among 44) and among the two cases, one is dead ; therefore the mortality of the operation is 2.2% (one case among 44). 10 cases are entire refrigeration ones and two of them are huge cancers, which are refrigerated three times and the cancers are eliminated eventually. 19 cases' refrigeration area surpasses 85% if the tatol area, 13 cases surpass 75% of the total area, as well only 2 cases' refrigeration area is less than 60% of the total. Based-on the follow-up whose duration is between 5 and 18 months, 15 cases are dead and the survival rate after one year is 65.9% as well as the one-year survival rate of the entire refrigeration patients is 90% ( 9 cases among 10).

3.Conlusion:
Percutaneous targeted cryoablation therapy for treatment of liver cancer is feasible, safety, effective with less syndrome and less liver hurt. Combining with chemotherapy and radiotherapy, It will promot the progress of clinical oncology.

4.Discusstion

The effectiveness of the treatment is closely related to the operation designing, orientation and the inducing methods. Currently, there is not itself three-dimension designing system available. Therefore, the designing and the orientation more depend on CT or B ultrasound scan the personal experiences and ability, which leads to the differences. The weakness of the designing, the inaccuracy of the orientation will lower the effectiveness of the operation directly. Therefore, different methods should be adopted according to different actual situations. The authors' experiences are presented as the following: the designing based on CT two dimension diagram will be more accurate than the B ultra short wave based ones. Even some operations can be induced by CT to improve the effectiveness and to reduce the syndrome. Currently, the negative effect of the patient's respirations on the operation can not overcome well yet; however, patient can hold his breath temporarily to solve the problem. Some patients who easily get refrigeration syndrome or are not suitable for accepting the operation through the "orientation refrigeration" can be treated by B ultra inducing refrigeration during the process of celiotomy operation.
The syndrome and its effects: The serious one is the massive haemorrhage and the lag reactive alimentary bleeding, which possibly cause death. Especially the lag reactive alimentary bleeding, its cause has not been clearly, may be connection with the satuation of patient, such as serious hepatocirrhosis, pylori veins high blood pressure, the decrease of the liver's storage ability as well as the too large scale of frozen range for huge cancers. The common symptom is: bleeding is found in two weeks after the operation, the exhaustion of the liver functions, icterus as well as massive ascites. According to the report of Fred T.Lee(5), the occurrence rate of the lag reactive alimentary bleeding is 1%; in our cases, the occurrence rate is 4.5% (2 cases among 44). The two cases are both suffered from the serious hepatocirrhosis and the sizes of their cancers are 9-10cm. The cases both happened at the begging stage of our research. Later, since huge cancers are refrigerated by several times and the patients with serious hepatocirrhosis pylori veins high blood pressure are not allowed to be treated by this kind of operation, the lag reactive alimentary bleeding never occurs. The massive haemorrhage has not happened in our researched cases. However, the authors believe the massive haemorrhage has the connection with piercing the blood vessel in the process of puncturing, which can be averted by adopting the puncturing directions. cryoprob direct insert on the artery may cause the massive hemorrhage; therefore, it will be avoided in operation. The above syndrome will put negative effects on the refrigeration's effectiveness. The feverl is relation with the range of refrigeration.it is only the normal reaction.
The evaluation of the effectiveness: Currently, it is hard to evaluate the long period effectiveness. Different data groups indicate the different TNM stages and syndrome of the cases. The distinctions between the one-year survival rates in different groups are various. In our cases, the one-year survival rate of the entire frozen cases is much higher than it of the rudimental cancer cases. Two years after the operation, the health conditions of the two groups are significantly different. If the cancer rudimental rate is less than 15%, the improvement of the patient's health condition is significant with the weight increase and AFP declining. If the cancer rudimental rate is more than 65%, the improvement of the patient's health condition is hard to be identified.

Based on the clinical observation, the authors propose our own opinion: the refrigeration can be divided into two categories: eradicative refrigeration and appeasement refrigeration. Eradicative refrigeration refers to the cases whose refrigeration range exceeds the brim the cancer more than 1 cm, without cancer transferring and without rudimental cancer. Appeasement refrigeration refers to the cases with rudimental cancer. The refrigeration range of the appeasement treatment should exceed 85% of the cancer's volume; otherwise the effectiveness will not be significant. In addition, to select the reasonable comprehensive treatment scheme also contributes to the effectiveness of the refrigeration. Emphasis should be put on the comprehensiveness of the treatment. According the authors' experiences, combining withchemotherapy may helpful for elevating the survival rate as well as reducing the recurring or transferring after cryotherapy.


REFERENCES
1.Wang Xuehao ,The Treatment Selection of the Middle or Late Stage Liver Cancers in Surgery     Theories and Practice 2000 Volume 5
2.Yang Jiahai, Chen Han and Wu Mengchao The Resecting of the Huge Liver Cancers (attached by 86   cases) in Practical Surgery Magazine 1999,19
3.Senming Wang,Jiren,Zhang,The treament of irresectable liver tumors by percutaneous targeted Ar-He  crgoablation International journal of Modern Cancer Therapy Vol,3No.1(2000)pp16~18
4.Deng Xiaojun Using the "Argon and Helium Scalpel" Ultra Low Temperature Combined with Liver    Artery & Pylori Veins Pumping Operation to Treat Liver Cancer Combined with Pylori Vein Cancer   Embolism in China General Surgery Magazine,2001. Volume 10, Page 179 to 181
5.Fred T.Lee,Jr,et al Hepatic Cryosurgery with Interacperativ US Guidance.Scanlan          Radiology,Vol.202,No.3 pp624~632 March,1997
 (Manuscrpt was accepted at July, 2001)

 

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