CLINICAL EFFECTS OF ELECTROCHEMICAL THERAPY IN THE
TREATMENT OF MIDDLE AND LATE STAGE LIVER CANCER
Xin Yu-Ling, Peng Ze-Bin China-Japan Friendship Hospital, Beijing 100029

Abstract:   From 1987 to 1991, 165 cases of middle and late stage liver cancer received electrochemical therapy (ECT). There were 108 male and 57 female patients with the age of 33 to 78 years old. 125 were primary liver cancer and 40 metastatic cancer. Among them, 26 cases were diagnosed as stage II, and 89 in stage III, 50 in stage IV. 83 cases costumers were Located in the right lobe of the liver, 56 in the left lobe and the other 26 cases were multiple lesions in both lobes. Total number of tumors were 211. The

number of tumors in diameter of4.0—6.0 cm, 6.1—1.0 cm, 7.1—~8.0 cm, 8. 1—~9.0 cm, 9.1—10.0 cm and over 10.0 cm were 26, 58, 51, 32, 25 and 19, respectively. Under the guide of ultrasonography and CT, electrodes were inserted into tumor mass. The number of electrodes was determined according to the tumor size. The distance between two electrodes was 2.0 to 2.5 cm. Voltage used was 6.0—8.0 V. and current 60—80 mA. Electric quantity was 100 coulomb per 1.0 cm diameter of tumor mass. All patients were followed up for three months after ECT. According to UICC criteria, there were 36 (21.8%) in CR, 65 (39.4%) in PR, 35 (21.2%) in NC and 29 (17.6%) in PD. The 1 to 5 years survival rates were 56.9%, 29.6%, 13.9%, 10.3% and 5.4%, respectively.Key words: electrochemical therapy liver cancer

lt is no doubt that liver cancer has high mortality and morbidity and the survival time of the patient is not more than six months. lt is said that about millions people died of the disease annually in the world. Liver cancer threatens human health and life severally. Although surgical management is the first choice in treatment of liver cancer, only 15—20 percent can be operated on, because most of the patients are diagnosed at late stage. Invasive therapy has been helpful to the remission of the disease, yet it still has some limitations in clinical use. In recent ten years, we have treated late stage liver cancer with electrochemical therapy (ECT) and obtained satisfactory results.

Clinical data

From 1987 to 1991, 165 cases of liver cancer underwent electrochemical therapy (ECT) in our hospital. There were 125 primary cases and 40 metastatic cases according to clinical symptoms, ultrasonography and laboratory tests. 98 of the group were diagnosed by needle biopsy. There were 108 male and 57 female patients with an average age of 49.5 years (33—78 years).

Location of tumors: There were 56 cases located in the left lobe, 83 in the right lobe and 26 cases were multiple lesions (in both lobes). The total number of tumors were 211, including 64 in the left lobe, 102 in the right lobe and 45 in both lobes. 5 of 56 cases in the left lobe and 9 of 83 cases in the right lobe were multiple metastatic lesions.

Diameter of tumors: The diameter of tumors was in range of4.0—15,Ocm. The number of tumors in diameter of 4.0—6.0 cm, 6.1—7.0 cm, 7.1—8.0 cm, 8.1—9.0 cm, 9.0—10.0 cm and over 10.0 cm were 26, 58, 51, 32, 25 and 19, respectively. There were 76 cases had tumors with diameter more than 8.1 cm.

Clinical stage: There were no cases at stage 1 in this group. 26 patients were diagnosed at stage II (T2NOMO), and 89 at stage III (T3N1MO) and 50 at stage IV (T4NOMO). See Table-1.

Table- 1. TNM stage of the patients

There were 84.2 % (139/165) of the patients at stage UI and IV who were not suitable to Operation or ineffective to radio-or chemotherapy.

AFP was tested by ELISA in 116 cases before and after ECT. lt was indicated that the positive rate of AFP decreased from 86.2% (100/116) to 31.9% (37/116) and the value of AFP also decreased significantly. There was significant difference between the weak positive rates before and after ECT. See Table-2.

Table-2. The value of AFP before and after ECT

Indications

1. ECT is suitable for patients over 70 years old or have hypofunction of some organs (liver, kidney, heart, lung), thus can not receive surgical operation. 2. The diameter costumer mass is more than 8.0 cm or metastatic cases to whom chemotherapy is not effective. 3. Liver cancer accompanied by metastasis in abdominal lymph nodes, skeleton, lung and other organs.

Contraindications

1.   Tumor invading the portal or accompanied by tumor thrombus in the portal vein and venae cava inferior. 2. Patient L~ too weak to eat food or suffered with cachexia, jaundice and ascites. 3. Though adequate treatments, remote metastatic lesion is not controlled.

Method

There are two types of ECT instrument, BK93 and ZAY-6B. Different electrodes, specially made of platinum, can be used according to different lesions. Hard needle-like electrode is made 15 cm in length and 0.7 cm in diameter. Elastic soft electrode, 20 cm in length and 0.7 cm in diameter, is winded to a spiral-shaped needle with platinum wire 0.3 cm in diameter. According to different locations of tumours and condition of patients, two methods of inserting electrodes were used: 1. Percutaneous ECT. With sterilization and local anesthesia, electrodes were inserted to tumor mass accurately through the skin under the guide of ECT or ultrasonography. lt was used mostly in treatment costumers in the left lobe. 2. Laparotomy ECT. Electrodes were inserted to tumor mass under direct vision during laparotomy. lt was used mostly in treatment of massive tumor in the right lobe or multiple lesions. Because the right lobe of the liver is in deep location and adjacent to the lung and the colon, this way is helpful to insert electrodes properly so that injury to other organs can be avoided. After insertion, electrodes were connected with the instrument to start treatment.

Our experience demonstrated that the radius of killing area around each electrode is about 3.0 cm, thus the distance between two electrodes inserted should be about 2.5cm. Hence, based on this principle, die number of electrodes needed could be determined according to die size costumer. Generally, voltage was

8.0—10.0 V and current 80-100 mA. Electric quantity needed in treatment was about 100 coulombs per

1.0 cm diameter costumer. Treatment time for such a quantity was 15 to 20 minutes.

The mechanism of ECT is electrolysis and electrophoresis of die direct current electricity which may kill tumor tissue directly. The direct current applied to tumor will change die movement of various electrolytes and pH level around electrodes (pH 1-2 around anode and 12-14 around cathode). This significant change of pH value will make malignant tissue necrotic so that electrolytes (Cv, H+, 02) released from necrotic tissue may result in protein denaturation. These chemical changes need a period of time. lt was indicated that clinical effectiveness with relative bw voltage (6—~8 V) and weak current (80‘-~100 mA) and bong treatment time(25 min for 100 coulombs) was better than that with higher voltage (9~10 V) and current(100-150 mA) and shorter time (15 min for 100 coulombs).

Results

1. ECT is safe and effective in treatment of middle and late stage liver cancer. There were no dead cases and severe complications in this group. According to the effective standard for liver cancer established by UICC in 1988, there were 21.8 % CR (36/165), 39.4 % PR (65/165), 21.2 % NC (351165) and 17.6 % PD (29/165) in one year after the treatment. The total effective rate was 61.2 % (CR+PR, 101/165). See Table-3. The effective rate of metastatic liver cancer was 70.0 % which was higher than that (58.4%) of primary liver cancer (P<0.05).

The factors which influenced the short-term effectiveness included the right choice of indications and proper location of electrodes. In this group, 35 of 83 cases with tumor in the right lobe of the liver underwent ECT with percutaneous insertion. Due to the ribs and the adjacent organs, it was difficult to insert electrodes properly. Other 48 in 83 cases underwent laparotomy so that the right number and accurate localization of electrodes could be determined according to the shape and size of tumors under direct vision. And also, the doctor could change the location of electrodes during treatment if necessary. So the results of these two methods were different. See Table-4. The effective rate (71.1%) of 135 cases with tumors in diameter less than 8.0 cm was better than that (43.4%) of cases with tumors in diameter over 8.0 cm (P<0.0l).

Table-3. The short-term effectiveness

 Table-4. Comparison of effectiveness of percutaneous and laparotomy ECT

2.   The long-term effectiveness:

The average survival time was 18.4 months. The one-year mortality was 30.9 % (51/165). The two to five year survival rates were 24.8 % (41/165), 12.7 % (2 1/165), 10.3 % (17/165) and 4.8 (8/165), respectively. The survival rate was related to clinical types (primary or metastatic) and clinical stage. The 1,3,5 year survival rates offstage II were 100 %‚ 61.5 % and 30.7 %‚ respectively. But those rates offstage III were only 60.6 %‚ 13.9 % and 1.1 %‚ respectively. No cases in stage IV lived more than two years. See Table-5.

Complications

No severe complications occurred during the treatment. 32 patients complained of upright abdominal pain and fever (about 38.0 °C) the next day after ECT. White blood cell count was in a range of 8 x 1 0—~ 10 x 1 0/L. The diagnosis was local peritonitis which was cured by use of antibiotics. One patient with a huge tumor mass in the left lobe of the liver underwent percutaneous ECT and suffered with abdominal pain and general tenderness with high fever (about 39.0 °C) the next day. The diagnosis was thought to be peritonitis due to bleeding so laparotomy was done. But no blood was found and there was about 180 ml black necrotic liquid around the wound which had no tumor cell by pathological test. The patient was cured.

Discussion

1. The total effective rate of 165 patients with liver cancer was 61.2% and the 1, 3 and 5-year survival rates were 6 1.9%, 13.9% and 5.4%, respectively. The average survival time was 18.4 months. lt indicated that the effectiveness of ECT was only the next to Operation but better than other conservative therapies.

2. ECT is easy, safe and less traumatic. lt is a new approach to patients with middle and late stage liver cancer to whom surgical management is inadequate or radiation and chemotherapy are not effective. And also, this method is helpful to prolong the survival time.

3. We suggest that combined Treatments be helpful to improve the clinical effectiveness of middle and late stage liver cancer, especially the huge massive cases. ECT combined with TAl may be the trend in treatment of the huge massive liver cancer. Chinese traditional herbs and biological agents are useful to improve the immunity and life quality of patients.

Typical cases:

Case 1: A 67-year-old male patient with the history of chronic hepatitis for ten years complained of the pain in the hepatic region and poor appetite with the lose of body weight in Jan. 1991. He was found to have a bw echo mass in the right lobe of the liver. CT showed that the size of the mass was about 8.6 x 9.5cm. The value of AFP was 1189 ugfL. The diagnosis was primary liver cancer. Because of hepatic dysfunction, operation was inadequate so percutaneous ECT was done. Under local anesthesia and the guide of CT, twelve electrodes (4 anodes and 8 cathodes) were inserted into the mass. Voltage was 8.0 V and current 110 mA. Electric quantity needed was 1100 coulombs. The patient felt pain in the liver region and body temperature was 38.3 °C the next day after ECT. These symptoms disappeared two weeks later. The value of AFP dropped to 300 ~g/L and the size of mass decreased significantly. The patient was discharged and had follow-up examination for five months. The tumor disappeared completely and AFP was 80 uxg/L.

Case 2: A 58-year-old patient had the colectomy because of carcinoma of colon in 1990. But in 1992, he felt slight pain in the hepatic area and CT showed that there were two metastatic lesions in the liver, the 6.5 x 5.6 cm one in the left lobe and 4.8 x 4.2 cm in the right lobe. Laparotomy ECT was done. Three anodes and six cathodes were inserted in the left tumor and two anodes and four cathodes in the right tumor. Voltage was 9.0 V and current 135 mA. Electric quantity was 1200 coulombs. The patient recovered normally and took Chinese traditional drugs for six months. Repeated CT found that the lesion in the right lobe disappeared and the lesion in the left lobe decreased by 2/3 of the original size which disappeared completely one year later.