RU2463026C1 - Method of electrochemical lysis and photodynamic therapy of choroidal melanoma - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, and can be used in ophthalmology for electrochemical lysis and photodynamic therapy of choroidal melanomas (CM). 2 hours after PS introduction on tumour zone on sclera applied and sewn to it is electrode-anode, made in form of net from platinum wire with hole in the centre and corresponding in shape to shape of tumour base projection on sclera, in size being 1 mm smaller than tumour base on entire perimetre; laser light conductor with diffuser, made on entire length of intratumour part of light conductor, is introduced through anode hole into tumour structure transsclerally, with platinum insert-cathode being located on distal end of light conductor; after that, electrochemical lysis of tumour is performed, then by means of laser light conductor intrastromal irradiation of tumour with laser radiation with wavelength, corresponding to maximum of PS absorption of light irradiation, is performed.

EFFECT: invention ensures reduction of trauma by electrochemical laser and photodynamic therapy of choroidal melanoma, complete tumour destruction, prevention of metastases.

2 cl, 1 ex

Description

The invention relates to medicine and can be used in ophthalmology for electrochemical lysis and photodynamic therapy of choroid melanomas (MX) of equatorial localization with a prominence of more than 4 mm.

One of the promising treatments for MX is photodynamic therapy (PDT). The PDT method is based on the selective accumulation of the introduced systemic photosensitizer (PS) in the vessels and stroma of the tumor, which upon subsequent laser irradiation with a wavelength corresponding to the absorption peak of this PS leads to phototoxic damage to the vascular system of the neoplasm and the death of tumor cells that accumulate PS.

It is known that PS accumulates in tumor cells with a fast cell cycle (fast metabolic processes). If there are cells in the tumor tissue that, at the time of treatment, the drug had not captured or accumulated in small quantities, the chances of their effective destruction are significantly reduced. In addition, the effectiveness of PDT is limited by the height of the MX (not more than 4.6 mm).

Thus, it is necessary to look for treatment methods based on a combination of PDT with other effective methods of treating malignant neoplasms.

Electrochemical lysis (ECL) has no similar PDT efficacy limitations on tumor height. In addition, it was found that during ECL, the microvascular bed of the neoplasm is blocked, and in the cathode field the capillaries are blocked as a result of electroosmotic fluid transfer, and in the anode field due to microthromboses (Matveev N.L., Kaplan MA, Borsukov AV Methods and techniques for the use of electrochemical lysis in the treatment of neoplasms: Recommendations for interventional radiologists, hepatobiliary surgeons, oncologists. - 2005. - P.14). Therefore, ECL can contribute to blocking within the tumor of PS circulating in the vascular bed.

A known method of electrochemical destruction and photodynamic therapy of choroid melanoma (RF patent No. 2336059), including electrochemical destruction and photodynamic therapy of intraocular neoplasm.

The disadvantages of this method are increased invasiveness due to the need for intratumoral administration of several electrodes and a fiber.

The objective of the invention is to increase the efficiency of electrochemical lysis and photodynamic therapy of choroid melanoma.

The technical result is to reduce the morbidity of electrochemical lysis and photodynamic therapy of choroid melanoma, the complete destruction of the tumor, the prevention of metastasis.

The technical result is achieved by the fact that in the method of electrochemical lysis and photodynamic therapy of choroid melanoma, including intravenous administration of a chlorine-type photosensitizer (PS) at a dose of 0.8-1.0 mg / kg for 10 minutes, electrochemical lysis and photodynamic therapy of intraocular neoplasm, according to the invention, 2 hours after the introduction of the FS on the area of the projection of the tumor on the sclera, an electrode is applied and hemmed to it - an anode made in the form of a grid of platinum wire with a hole in the center and in shape corresponding etstvuyuschy shaped projection on the base of the tumor sclera, and size - less base Tumor 1 mm around the perimeter; through the hole of the anode, a laser fiber with a diffuser, made for the entire length of the intratumoral part of the fiber, is transsclerally inserted into the tumor structure, while a platinum insert - cathode is located at the distal end of the fiber; then, electrochemical lysis of the tumor is carried out with a charge of 12-18 C (the charge passed through the conductor during the lysis) for 20 minutes, after which an intrastromal irradiation of the tumor with laser radiation with a wavelength corresponding to the maximum absorption of PS light radiation is performed using a laser fiber capacity of 20-30 mW for 5 minutes.

The technical result is achieved due to the fact that:

1. The proposed system of electrodes and a fiber, where one electrode in the form of a grid is placed on the sclera, and a fiber is inserted inside the tumor, containing at the distal end another electrode in the form of a ring as an insert, it allows reducing the invasiveness of the procedure and avoiding the introduction of several instruments into the tumor;

2. Carrying out electrochemical lysis with the proposed shape and location of the electrodes causes destruction of the tumor in its entire volume, and also helps to block the PS that was introduced and entered into the tumor inside the tumor;

3. Laser irradiation inside the tumor with a wavelength corresponding to the maximum absorption of PS light radiation (photodynamic therapy (PDT)), leads to the death of the remaining viable tumor cells, prevents the dissemination of tumor cells and metastasis;

4. The combined effects of ECL and PDT can reduce the parameters of ECL (electric charge - up to 12-18 C compared with the standard 25-30 C).

The claimed technical result can be obtained only by using the totality of the techniques proposed by us method.

The method is as follows.

Chlorine-type PS, for example photolon or radachlorin, or photoditazine, is administered intravenously to the patient at a dose of 0.8-1.0 mg / kg for 10 minutes.

2 hours after the administration of FS, ECL is performed.

To conduct ECL, 2 electrodes are required: anode and cathode.

An electrode made in the form of a grid is used as an anode. To conduct ECL, it is applied to the surface of the sclera in the area of the projection of the base of the tumor, so the inventive electrode can be called surface.

The surface electrode is made in the form of a grid of platinum wire with a diameter of 0.05 mm with a cell size in the light of 0.2 mm, the shape corresponds to the projection of the base of the tumor onto the sclera, and its size is less than the base of the tumor by 1 mm around the entire perimeter. This choice of electrode size is due to the feature of the ECL procedure, after which further destruction of the tumor tissue occurs - delayed lysis, as a result of which the necrosis zone increases compared to the original lesion. A hole with a diameter of 1 mm is made in the center of the grid for introducing a fiber through it. At any point on the grid, a flexible electrical wire is rigidly attached, the free end of which is designed to be connected to an ECL apparatus.

The second electrode - the cathode - is made in the form of a ring of platinum with a thickness of 0.3 mm, the width of the ring is 2 mm. The cathode is located in the form of an insert at the distal end of the laser fiber with a diffuser made over the entire length of the intratumoral part of the fiber. The diameter of the optical fiber is 0.8 mm.

An electric wire is rigidly attached to the cathode, located in a groove made in the optical fiber of the fiber. The free end of the wire is intended for connection to an ECL apparatus. The electric wire is coated with bioinert electrical insulating material, for example fluoroplast-4.

At the preparatory stage for ECL, if necessary, rectus muscles are cut off to provide access. Transsclerally diaphanoscopically clarify the location and size of the tumor, determine the boundaries of the projection of the base of the tumor on the sclera and outline them with a coloring substance, for example, 1% aqueous-alcoholic solution of brilliant green. A surface electrode is applied to the sclera in the area of projection of the base of the tumor and hemmed with 2 interrupted sutures to the sclera. A laser fiber with a platinum cathode insert located at its distal end is inserted transsclerally through the anode opening into the tumor structure.

Then carry out the electrochemical lysis (destruction) of the tumor with a charge of 12-18 C (the charge passed through the conductor during the lysis) for 20 minutes. Upon completion of ECL, the surface electrode is removed.

After that, an intrastromal irradiation of the tumor with laser radiation with a wavelength of 662 nm, with a power of 20-30 mW for 5 minutes is carried out by means of a laser fiber. At the end of the irradiation, the light guide is removed.

The invention is illustrated by the following data.

Clinical example. Patient K., 53 years old. He entered the Kaluga branch of Eye Microsurgery with suspicion of neoplasm of the choroid of the right eye. According to the results of a comprehensive examination, the diagnosis was made: Melanoma choroid OD. Tumor localization is temporally in the equatorial region. The size of the tumor according to the data of ultrasonic B-scan: base - 11 × 13 mm, the size of the prominence - 6 mm. During phage, a characteristic “spotted” fluorescence was detected.

The patient received informed consent for the treatment of choroid melanoma according to the proposed method with the inventive system of electrodes and fiber. A single instrument was introduced inside the tumor - a fiber with a platinum insert, which reduced the invasiveness of the intervention.

Photoditazine at a dose of 0.8 mg / kg was used for PDT. Electrochemical lysis of the tumor was performed with a charge of 12 CL. Laser irradiation inside the tumor was performed with a power of 20 mW.

In a control study after 6 months, a chorioretinal lesion with a residual prominence of up to 1.0 mm was determined ophthalmoscopically at the site of the neoplasm. Ultrasound examination in the mode of energy Doppler mapping of intratumoral blood flow in the projection of the focus was completely absent. The observation period of 2 years - without relapse and metastases.

The proposed method with the inventive electrode and fiber system was used in 3 patients with MX with a glimpse of more than 4 mm. In all cases, the only instrument was injected into the tumor - a fiber with a platinum insert, which reduced the invasiveness of the intervention.

Photolon or radachlorin, or photoditazine at a dose of 0.8 to 1.0 mg / kg, were used to conduct PDT. Electrochemical lysis of the tumor was performed with a charge of 12 to 18 C. Laser irradiation inside the tumor was performed with a power of 20 to 30 mW.

In all cases, in the remote postoperative period, a flat chorioretinal lesion was determined at the site of the neoplasm. Duration of observation - from 10 to 24 months - without relapse and metastases.

Thus, the claimed method provides a reduction in the morbidity of electrochemical lysis and photodynamic therapy of choroid melanoma, the complete destruction of the tumor, the prevention of metastasis.

Claims (2)

1. The method of electrochemical lysis and photodynamic therapy of choroid melanoma, including intravenous administration of a chlorine-type photosensitizer (PS) at a dose of 0.8-1.0 mg / kg for 10 min, electrochemical lysis and photodynamic therapy of intraocular neoplasm, characterized in that through 2 hours after the introduction of the FS on the area of the projection of the tumor on the sclera, an electrode-anode is applied and hemmed to it, made in the form of a grid of platinum wire with a hole in the center and corresponding in shape to the projection of the base of the tumor onto the sc Yeru and size - less base Tumor 1 mm around the perimeter; through the hole of the anode, a laser fiber with a diffuser, made for the entire length of the intratumoral part of the fiber, is transsclerally inserted into the tumor structure, while a platinum cathode insert is located at the distal end of the fiber; then, electrochemical lysis of the tumor is carried out, after which an intrastromal irradiation of the tumor with laser radiation with a wavelength corresponding to the maximum absorption of PS light radiation is carried out by means of a laser fiber. 2. The method according to claim 1, characterized in that the electrochemical lysis of the tumor is carried out with a charge of 12-18 C for 20 minutes, and intrastromal irradiation of the tumor is performed with a power of 20-30 mW for 5 minutes