RU2231991C2 - Method for treating unresectable primary and metastatic hepatic tumors - Google Patents

Abstract

FIELD: medicine, oncology.

SUBSTANCE: primary focus or cancer metastases into liver from other organs should be simultaneously once affected with high-frequency thermodestruction at 120 kHz current frequency at 100 V tension and 1 A current power through umbrella-like nondisposable electrodes. Seance duration of high-frequency electric impact corresponds to 2-3 min.

EFFECT: higher efficiency of therapy.

7 dwg, 1 ex, 1 tbl

Description

The invention relates to medicine, namely to oncology, and can be used for intracavitary, high-frequency thermotherapy of primary and metastatic liver tumors when radical surgical treatment is not possible due to the prevalence of the process and associated clinical diseases.

The well-known “Method of high-frequency thermal destruction (Fedorov VD and others. The first experience of clinical use of ultrasound-controlled intraoperative and percutaneous high-frequency treatment of metastatic liver tumors with needle perfused electrodes. G. Actual issues of diagnosis and surgical treatment of metastatic liver cancer. - M., 2001 G., S. 171-172), the essence of which is the conversion of high-frequency energy supplied to the tumor center with a needle electrode into heat. In this case, the tumor tissue is an integral part of the electrical high-frequency (375 kHz) circuit due to low-resistance contact with the adhesive neutral electrode of a large surface. Inside the tumor zone, resistor heating raises the temperature from 56 to 70-100 ° C, which leads to the formation of coagulation necrosis. High-frequency needle electrodes with a diameter of 1.2 mm have a perforated working part at its distal end 15 mm, equipped with an isotonic NaCl solution with an automatically set speed of 60-80 ml / h. The needle has teflon insulation except for the perforated part. The duration of a session of thermal action on tumor foci of the liver with an energy power of 40-60 W is 3 to 20 minutes, depending on the size of the foci and the data that control the process of ultrasound investigation (ultrasound). High-frequency energy supplied to the needle tip was produced by a computer-controlled generator Elekrotom ® 106 NETT, Berchtold GmbH & Co Tuttlmgen (Germany). The method was used to treat 3 patients with various focal liver lesions, the size of the foci ranged from 2 to 4 cm. The method was used intraoperatively and transdermally. The effectiveness of treatment was evaluated by ultrasound and morphological examination of biopsy specimens. Two observations revealed complete destruction of tissues in the form of coagulation necrosis and detritus. During the observation period of 1.5 months, the sizes of the treated foci did not increase, and one patient showed pronounced signs of changes in cancer cells in the form of wrinkling.

The disadvantages of the above method of high-frequency thermal destruction are: the size of the tumor is limited to 2-4 cm in diameter, insufficient tissue necrosis is observed, no changes were observed according to morphological studies beyond the border of the tumor, although it is known that peripheral tumor cells are usually located outside the main focus.

The well-known “Method of radiofrequency exposure to primary and metastatic liver tumors” (see Radiofreguency Ablation of Unresectable Primary and Metastatic Hepatic Malignances. Results in 123 Patients. Steven A. Curiey et al. Reprinted from ANNALS OG SURGERY. Vol.230 N 1 Guly 1999 p. 2-3), selected by us as a prototype.

During the operation, under the control of ultrasonography, a radiofrequency needle was inserted into the affected area for treatment. In this case, the radio-frequency exposure system of the generator 2000 manufactured by Radio Fherapeutics Corp. was used. Mountain (View Ca), the system contains a generator that supplies 100 V with a current frequency of 300-1250 kHz, a unipolar needle-shaped single electrode, an indifferent electrode attached to the patient’s skin. The needle electrode 12-15 cm long has insulation, a cannula containing ten individual curved needles, a handle, and when the needle electrode is inserted into the liver tumor, the needles open in the tip of the electrode in the form of an umbrella. For tumors <3.0 cm in diameter, the umbrella portion of the electrode opens in the center of the tumor. The place of introduction of the needle electrode is controlled by ultrasound. With more extensive liver lesions, an umbrella electrode is placed in the posterior space (under ultrasonographic control) between the tumor and normal tissue, parenchyma of the liver, moved with an interval of 2.5-3.0 cm relative to the tumor. The optimal position of the electrode allows the destruction of the tumor in at least 1 cm of the normal tissue from the liver parenchyma. The initial applied voltage during treatment is 50 V, then increases by 10 V in 1, 2, 3 and 4 minutes to a maximum voltage of 90 B. The treatment continues until the peak voltage, after which the voltage is turned off, indicating a growing tissue resistance when coagulation necrosis occurs . After a 20-second pause, the voltage returns to 75% of the maximum and then drops, reaching a peak. Thus, each tumor or region with a large tumor is treated with two phases of exposure to high-frequency energy, before removing the umbrella electrode, change its position. By means of ultrasonography, control and measurement of the exposure zone, an increase in echogeneticity in accordance with tissue coagulation are carried out. During surgery with RFA at 90 V, between 2–3 minutes, vascularization of the flow and obstruction of the hepatic artery and portal hepatic vein were observed. Relief occurred when the shutdown, increasing the size of the zone of coagulation necrosis. After treatment, acute or short-term complications were observed in all patients, scanning or radiography of the chest was performed to identify residual or recurrent tumors in the treatment areas to further monitor the development of new hepatic or extrahepatic metastases.

Radio frequency exposure is an effective, well-tolerated treatment method for patients. However, there is a risk of developing recurrent tumors and the occurrence of metastases, which requires further improvement of the treatment method.

The aim of the invention is to increase the effectiveness of treatment and prevent the further spread of the malignant process, the occurrence of relapse in inoperable liver cancer.

This goal is achieved by the fact that the primary focus or cancer metastases to the liver from other organs is subjected to simultaneous single exposure to a high-frequency thermal destruction generator with a current frequency of 120 kHz, at a voltage of 100 V and a current strength of 1 ampere through reusable umbrella electrodes of various sizes, resulting in necrobiotic processes within the tumor, and beyond its border, at a distance of up to 10 cm, with developing hyperthermia up to 70-80 ° C, dystrophic cytoreductive changes in the liver tissue, as well as in zhnyh peripheral tumor cells.

The invention "A method for the treatment of primary, unresectable and metastatic liver tumors" is new, as it is unknown from the level of medicine in the field of high-frequency thermotherapy of liver tumors.

The novelty of the invention is as follows:

1. A lower current frequency of 120 kHz is used than with known methods of treatment with high-frequency thermotherapy, due to which, in addition to the necrotic effect achieved by using the appropriate diameter of the tumor size of the selected umbrella electrode, hyperthermia is also achieved (up to 70-80 ° C) at the periphery of the tumor up to 10 cm, which is confirmed by us experimentally. This temperature has a fatal cytoreductive effect on tumor cells outside the main focus. It is known that the cytoreductive effects of hyperthermia appear even at a temperature of 50-55 ° C. The minimum temperature capable of destroying malignant tissue is heating in the range of 50-55 ° C, at which the denaturation of cytoplasmic proteins occurs (see Neurat Bailey, Mathematics in Biology and Medicine. M., 1970).

2. The proposed effect allows, therefore, to treat patients with a larger than known tumor diameter (up to 7-10 cm) and has a prophylactic effect on the local distribution of liver tumors.

3. The duration of the session of high-frequency electrical exposure is not long and is 2-3 minutes.

4. During the therapy session, it is possible to control the interstitial temperature of the liver using a standard simple electrothermometer.

5. The proposed method is more economical, simple, does not require re-execution of therapy sessions, can be applied in medical institutions of various levels.

The invention "A method for the treatment of primary, unresectable and metastatic liver tumors" is industrially applicable and can be used in healthcare both in specialized oncology hospitals, and in the general medical network, in cancer research institutes.

The effectiveness of the proposed method is verified experimentally.

Piglet (3 months old, weighing 35 kg) under intravenous anesthesia performed supramedian laparotomy. After turning on the apparatus of high-frequency destruction (Fig. 1), an umbrella electrode with a diameter of 3 cm is introduced into the liver (Figs. 2, 3). The duration of high-frequency exposure was 2-3 minutes at a voltage of 100 V, sequentially at 4 different points at a distance of 8-10 cm (figure 4). An interstitial temperature of the liver at a depth of 3-4 cm was determined with a needle electrothermometer at a distance of 1-3-5-8 cm from the point of introduction (Fig. 5) of the umbrella electrode.

After completion of the experiment, the animal was withdrawn from the experiment by the simultaneous administration of 1 g of sodium thiopental and 12 mg of arduan intramuscularly.

The area of introduction of the electrode and adjacent around the liver tissue were excised and subjected to histological examination.

Experiment Results

In all 3 zones of the introduction of the umbrella electrode after 3 minutes in a diameter of 3 cm (that is, corresponding to the diameter of the electrode) there were external signs of coagulation necrosis - the tissues became whitish, tight to the touch, and did not bleed. The temperature of the liver directly in the area of necrosis immediately after turning off the apparatus was 100-120 ° C; 1 cm from the necrosis zone 82 ° C; 3 cm - 76 ° C; 5 cm - 68 ° C; 10 cm - 61 ° C.

Histological examination directly in the zone of localization of the umbrella electrode showed signs of destruction of tissue necrosis, and along the periphery from 1 to 10 cm there was a varying degree of degeneration, necrobiotic tissue disorders with the presence of vascular thrombosis, hemorrhage, and vacuolization of cells.

Thus, studies have shown that high-frequency hyperthermia in the proposed mode leads to necrotic changes directly in the localization zone of the “whiskers” of the umbrella electrode, and beyond it causes an increase in temperature, leading to significant changes in the liver cells, causing the death of their intracellular apparatus. These data can be extrapolated to the tumor process, since the resistance of tumor cells to temperature is lower than in healthy ones. G.Kim S.A. showed that already 30-minute hyperthermia of transplantable melanoma at a temperature of + 42 ° C leads to the death of some tumor cells while maintaining skin integrity (see Local tumor hyperthermia in combination with radiation therapy, Malignant Cutaneous Lesions (Cancer, 1977). the data served as the basis for their transfer to the conditions of the clinic.

An example of the implementation of the “Method for the treatment of primary unresectable and metastatic liver tumors” in the clinic on the patient.

As an example, we present a clinical observation, b-naya A., born in 1976, medical history N 1284/0. I entered the Department of Preventive Oncology, Laparoscopic and General Surgery, RNII on January 17, 02, with complaints of enlarged liver and pain in the right upper quadrant.

As a result of a clinical examination, including FGDS, biochemical studies, tumor markers, ultrasound, CT, the diagnosis was made: liver cancer of a multifocal type (cholangiocarcinoma), T ₃ N _o M _o , st. IV, cl. column IV.

Ultrasound of the abdominal cavity from 01/17/02: the liver has clear contours, pr. Share 13.0, lion. a proportion of 8.3 cm, a parenchyma of increased echo density, in both lobes there are multiple focal formations of reduced echo density. Conclusion: multiple focal liver damage.

The same picture was revealed on CT (Fig.6).

01/25/02, the operation was performed: upper median laparotomy, high-frequency thermal destruction of the tumor nodes of the liver, catheterization of the umbilical vein, drainage of the abdominal cavity.

Protocol of operation N 20

Under E.T.N. upper-median anesthesia L≈20 cm, the abdominal cavity is opened. During the audit, large lesions of ⌀ 5 cm were found in the liver in the IV segment, ⌀ 4 cm in the II and III segments, and ⌀ 5 cm in the V and VI. In addition, there are small tumor nodes up to 1 cm across the entire surface of the liver. Biopsy taken. Tumor nodes in the segments were subjected to a high-frequency cytoreductive effect for 3 min, signs of coagulation necrosis were observed in the zone of introduction of the umbrella electrode. Measurement of t ° C on the periphery and in the tumor revealed an increase to 80-100 ° C.

When histological examination N 634151 answer: adenocarcinoma.

P / o period went smoothly, the patient was discharged in satisfactory condition 12.02.02

The patient was re-admitted for the control study 05/20/02, the General condition is satisfactory. No complaints of pain.

The table shows the tests obtained during the examination.

Ultrasound data from 07/11/02: in the I, IV, VI segments of the liver, a hyperechoic formation with central zones of fibrosis is located (Fig. 7).

Thus, 6 months after high-frequency thermal degradation, the general condition of the patient is satisfactory, there are no complaints, in the foci exposed, there is fibrosis and the absence of their growth.

The technical and economic efficiency of the “Method for the treatment of primary unresectable and metastatic liver tumors” consists in necrotizing unresectable primary and multiple liver tumors, preventing their further local spread due to hyperthermic, cytoreductive high-frequency exposure.

Claims (1)

A method for the treatment of unresectable primary and metastatic liver tumors, including intraoperative open or laproscopic high-frequency electrical exposure, characterized in that the primary lesion or cancer metastases to the liver from other organs are subjected to a single instantaneous exposure to high-frequency thermal destruction with a frequency of 120 kHz at 100 V and current 1 And, through reusable umbrella electrodes, the duration of a session of high-frequency electrical exposure is 2-3 minutes.

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