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Treatment of Liver Tumors by Targeted Ar-He Cryoablation:
Song huazhi Yi fengtao Zhang yuxing Liu ying
Centre of Ar-He Knife, Wuhan General Hospital of PLA, Wuhan


[Abstract] Object To investigate the effective treatment for liver tumors(especially for advanced liver tumors) and indications with targeted Ar-He cryosuigical system. Methods Using local anesthesia,under B-ultrasonography or computer tomography monitoring,97 patients were selected for percutaneous targeted Ar-he cryoablation. Results In 97 patients, 76 cases were followed up for 3-6 months,15 cases(19.6%)were died;21 cases were followed up for 7-12 months,4 cases(19.1%)were died. Complications: hemorrhage 3 cases(3.26%); aching of liver 44 cases(45.6%);fever 50 cases(51.1%). Conclusion Percutaneous targeted Ar-He cryoablation in treatment of patients with liver tumors (especially with irresectable advanced liver tumors) is an effective treatment. If the treatment by targeted Ar-He cryoablation combines with interventional chemotherapy for liver tumors, it is significant to alleviate patients` pain, to prolong patients` survival time and to improve patients` living quality. It is advisable in extensive clinical practice.
[key words] Liver tumor Targeted cryoablation Cryocare surgical system


Clinical data
During Aug.2000~Nov.2001,97 cases of patients with liver cancer were treated by
Percutaneous targeted Ar-He cryoablation. Among them, 76 cases were male and 21
Female. Age of patients is between 36 and 74, the average age was 49. The diagnosis of 88 cases were primary carcinoma and 9 cases metastatic carcinoma in liver .The minimal volume of tumor was 2.38×1.81cm, the maximal 13×12cm, and the average volume was 6.5×4.8cm. 72 cases were hepatocellular carcinoma,17cases cholangiocarcinoma and 8 cases adenocarcinoma. Among them, 12 cases multiple (more than 2 foci ),54 cases massive type, 11 cases diffuse type and 20 cases combined portal cancer embolus.

Equipment

Cryocare surgery system(Ar-He knife) made in U.S., with 4 especially probs
made as 2,3,5,8 mm in diameter. TOSHIBA SSA -220A ultrasonic diagnostic apparatus.
Methods(1-3)
1. Preoperative examination of blood routine, blood coagulation mechanism, liver function and renal function. Corresponding treatment is needed if something abnormal. Targeted Ar-He cryoablation can?t be given until the result is or near normal.

2. The day before operation, with B-ultrasonography and CT, determine the locality and depth lf operation ,and mark on the skin. Preoperative fast for 12 hours and IM 10mg tranquilizer 30 minutes preoperation.

3. According to different locality of tumors ,patients take supine position, oblique position or lateral recumbent position. Establish venous passage,connect electrocardiographic monitoring system and give oxygen inhalation if necessary. Prepare operative instruments such as surgical knife handle, blade,suture and suture and suture needle and so on.

4. Routine sterilization for filed of operation and drape .According to preoperative location,again use B-ultrasonography to decide route of entry and depth .It?s difficult to form a big ice ball encysted the whole massive or dissymmetric tumor and oeave 1cm safe border. So it?s necessary to decide several directions of entry at the same time for operation. After local anesthesia, made a small skin incision ,separate a little with blood vessel forceps, enlarge the incision, and under B-ultrasonography monitoring ,insert the

superconductive knife into target area. For tumor smaller than 2cm in diameter, it?s better to use puncture probe for location owing to influence of respiration. The parient is told to hold breath for a while to ensure the accuracy .Be careful to avoid hemorrhage due to blind puncture.

Intraoperative B-ultrasonography monitors the volume of the ice ball and the relationship between the ice ball and blood vessels or bile duct. Once the ice ball is near blood vessels or bile duct, stop refrigeration and immediately rewarm. Colsely observe the patient change of respiration,blood pressure and pulse .If something abnormal, stop refrigeration and give expectant treatment. After refrigeration,take out superconductive knives,pack hemostat, give suture and gauze and fix with abdominal belt.
Give postoperative measurment of blood pressure and pulse once every hour,keep in bed for 12 hours, give routine treatment with antibiotic, hemostat and hepatinica and give hydration treatment for those with wide range of refrigeration.

Results
Among the 97 patients, 3 cases(3.1%) had complicated hemorrhage (2 cases intraoperative and 1 case 6 hours postoperative ), and 2 cases hemostasis by hepatic artery embolism and 1 case by local pressing;50 cases(51.6%) had postoperative fever with temperature 37.60C-390C; and 44cases (45.4%) had mild or moderate hepatalgia. No case had megalgia or damage of blood vessels or bile duct. For these 97 cases, 78 cases (80.4%) were followed up for 3~6 months with 15 cases (19.2%) dead; 21 cases for 7~12 months with 4 cases (19%) dead. 4 cases died from hemorrhage of digestive tract; 9 cases from hepatic failure; 5 cases from hepato-renal syndrome and 1 case from intrahepatic

hemorrhage. Tumors shrank 1-2cm for 45 cases, about 3cm for 11 cases and about 1/2 for 15 cases (for example: fig1-2). No cases of tumor disappearing completely, but CT scan showing the tumor tissue have lost growth activity after cryotherapy. 17 cases without any change and 6 cases with tumor larger than preoperation.
Discussion

Ⅰ. Mechanism for treatment of liver caner by targeted Ar-He knife entered medical market since late 1999?s in China(1). This epuipment has 4 or 8 insulated superconductive knives pyretogenic independently, which can output high-pressure ordinary temperature argon (cold medium) or high-pressure ordinary temperature helium (heat medium). With refrigeration only on the edge and ordinary temperature on the handle, Ar-He knife is a microtraumatic targeted cryosurgery apparatus using helium to unfreeze. It can adjust the volume of ice ball by computer so as not to damage normal tissues around. Using argon as cold medium, the edge of Ar-He superconductive knife quickly expands (Joule-Thomson effect) to make tissues refrigerate rapidly. In a few seconds the temperature drops to 1400C-1500C below zero, then helium makes the temperature rise to 200C -400C in a short period of time, which make tumor tissues coagulation necrosis. Intracellular cryolites formed by quick refrigeration extend to all celltlar tissues through intercellular bridge, causing a kind of "domino effect". Intracellular and extracellular cryolites, dehyration and rupture of tissues, and damage of blood vessels cause cytohypoxia and cell death(2-4).
Ⅱ.Concrete operation

1. Read carefully the examination results of CT and B-ultrasonography to make clear the volume and locality of tumor and the relationship between tumors and intrahepatic blood vessels and duct.With B-ultrasonography and CT , locate the tumor and mark the location on the skin the day before operation.

2. For the tumor near high position of diaphragm,it?sbetter to operate from costal margin, through part of the normal hepatic tissues to the tumor ,to avoid damaging the diaphragm or pleura (causing complicated hemopleura )by directly operating vertically from the tumor . For tumors near hepatic surface ,refrigeration may cause capsular hemorrhage of liver . It?s better to refrigerate under direct vision for hemostasis .With percutaneous refrigeration,it?s also necessary to enter focus through part of normal tissues in order to reduce hemorrhagic chances .The 3 hemorrhage cases were all with tumors near hepatic surface.

3. Preoperative and intraoperative location must be accurate under B-ultrasonography. After deciding the locality of focus, insert one or several superconductive knives into target area in accordance with volume and appearance of tumors. Insert gently ,especially for tumors near high position diaphragm, to avoid injuring the diaphragm and entering the thoracic cavity. Refrigerate immediately superconductive knife reached the target area. Don?tmove the knife around ,otherwise it may hurt the liver and cause intrahepatic hemorrhage.(3-5)
Ⅲ.Determination of refrigerated range

The refrigerated range of tumors has positive correlation with prognosis. In principle the refrigerated range should be 1-2cm in diameter larger than tumor,but in fact it?s difficult to do so because of volume of tumors or multiple. The range should be determined with the volume of tumors and hepato-renal function situation of patient. Of patient. For single tumor smaller than 5cm, with normal hepato-renal function,the ice ball should be lauger than 6cm in diameter; for tumor larger than 5cm, especially with abnormal hepatorenal function, the ice ball shouldn?t be larger than the tumor, otherwise normal hepatictissues may be damaged and postoperative hepatic or real failure can be easily to happen; fou tumors larger than 10cm it?s better to refrigerate twice (2/3 for the first time and 1/3 for the second a week later ); for tumors near diaphragmatic or hepatic surface, the ice ball shouldn?t be overlarge tumors, refrigerate once for all if less than 4 foci, and refrigerate fractionally for over 5 foci.
Ⅳ.Combination with interventional chemotherapy(1,6)

The treatment by targeted Ar-He cryoablation combined with interventionmal chemotherapy is especially effective for patients with intermediate or advanced hepatic carcinoma. Whether the treatment by targeted Ar-He cryoablation should be before or after the interventional chemotherapy? How long is the intermission? Isembolism necessary? No agreement has yet been reached.We think that it is more appropriate to carry out the treatment by targeted Ar-He cryoablation before interventional chemotherapy. After treatment by targed Ar-He cryoablation, the greater part of tumor is necrotic and the load is lightened, so that the dosage can be reduced, therapeutic effect increased and side effects such as digestive tract tract reaction, arrest of bone marrow, etc. of interventional chemotherapy can be reduced. For interventional chemotherapy after targeted Ar-He cryoablation treatment itself can damage vascular endothelio and intravascular crystal to make vascular block and tumors ischemic necrosis. Furthermore, many patients with liver
Cancer are complicated with hepato-cirrhosis. There?s fibrosis change after Ar-He cryoablation treatment and embolism can worsen hepato-cirrhosis and portal hypertension, causingsecondary digestive tract hemorrhage. The interventional chemotherapy should be carried out 7-10 days after Ar-He cryoablation treatment. Too short intermission may influence healing of Ar-He knife trauma.
Ⅴ.Complications and treatment

The common complications after Ar-He cryoablation treatment are fever, hepatalgia, hepatic or renal failure and intrahepatic hemorrhage. The fever begins 3 days afer operation with temperature 37.5-38.80C and lasts about 5 days. IM bupleurum 4ml for temperature below 38.80C and IV dexamethasone 5mg for temperature above 38.50C .Take indomethacin 25mg for hepatalgia. Cases with intrahepatic hemorrhage should be under B-ultrasonography in emergency department to make clear hemorrhage situation. For small amount of hemorrhage with little influence on blood pressure, dicynone or paminomethyl beozoic acid can be used through IV. For large amount of hemorrhage with decline of blood pressure, immediately give hepatic arteriography and hepatic artery embolism. For the 3 cases with hermorrhage, 2 cases were hemostasis by hepatic artery embolism and 1case by local pressing.
For larger tumors, especially cases with hepatic and renal insufficiency, a lot of sphacelus absorbed and ejected after refrigeration can cause hepatic or renal failure. For these patients, give hydration treatment postoperation and small dose (2-5mg per day) of dexamethasone and intensify hepatic protecion.

The treatment by targeted Ar-He cryoablation combined with interventional chemotherapy is especially effective for patients with intermediate or advanced hepatic carcinoma, It is of great significance to alleviate patients? pain, prolong patients? lifetime and improve patients? life quality. It is advisable in extensive clinical practice.
References
1. Seming Wang, Jiren Zhang. Qiuping Reng, et al. The treatment of irresectable Liver Tumors by percutaneous targeted Ar-He Cryoablation. International Journal of Modern Cancer Therapy.2000;3:16-18
2. Leef,Bahn DK.Mcllugh TA,Onid GM,LeeFT Jr.US-guided percutanepus cryoablation of prostate cancer.Rachnology 1994;192 769 776.
3. Nakada SY,Lee I Jr,Warner Nj,Chosy SC,Moon ID.Laparoscopic cryosurgery of the kidney in the poreine model,an actue feasibility study,Urology(in press).
4. Gage A A.Current progess in cryosurgery.Cryobiology 1988,25:483-486
5. Rand RW,Rand RP,Eggerding FA,et al .Cryolumpectomy for breast cancer:an experimenta study,cryobiology 1985,22.307-318.
6. zhangjiren et al. Targeted Cryablation Technology for treatment of Cancer. 2001,P47( in press)
( Paper was accepted at March, 2002)


 

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