RU2463027C1 - 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) of central and pre-equatorial localisation with prominence more than 4 mm. 2 hours after photosensibiliser 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 into tumour intravitreally, at distance of 4.0 mm from distal end of light conductor located is platinum insert-cathode; after that, electrochemical lysis of tumour with simultaneous ablation of tumour destruction products is performed, after which 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, tumour is ablated.

EFFECT: invention ensures reduction of trauma by electrochemical laser and photodynamic therapy of choroidal melanoma, preservation of sclera intactness in zone of tumour base, complete destruction and ablation of tumour, 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 central and preequatorial 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 trauma due to the need for intratumoral administration of several electrodes and a fiber, violation of the integrity of the eyeball in the area of the projection of the base of the tumor on the sclera, which can lead to the migration of tumor cells and, as a consequence, the germination of the tumor in the sclera.

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, preserve the integrity of the sclera in the area of the projection of the base of the tumor, complete destruction and removal of the tumor, 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 and corresponding in shape to ktsii bases tumor sclera, and size - less base Tumor 1 mm around the perimeter; a laser fiber is introduced intravitreal into the tumor with a diffuser made for the entire length of the intratumoral part of the fiber, while a platinum insert — a cathode — is located 4.0 mm from 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 with the simultaneous removal of the tumor decay products, after which the tumor is irradiated with a laser waveguide using a laser waveguide with a wavelength corresponding to the maximum absorption of FS light radiation, with a power of 20-30 mW for 5 minutes, then the tumor is removed.

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 4.0 mm from the distal end as an insert another electrode in the form of a ring, which reduces the invasiveness of the procedure and avoids the introduction of tumors of several instruments;

2) electrochemical lysis in the proposed form and the location of the electrodes causes the destruction of the tumor in its entire volume, and also helps to block the PS introduced and received into the tumor inside the tumor;

3) intrastromal laser irradiation of a 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);

5) intraocular removal of tumor decay products during ECL, as well as the removal of tumor residues after completion of intrastromal laser irradiation using a vitreotome, minimizes the risk of relapse and metastases in the long-term postoperative period.

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, in shape and size corresponds to the shape and size of the projection of the tumor base on the sclera. 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 4.0 mm from the distal end of the laser fiber with a diffuser, made for the entire length of the intratumoral part of the fiber. The diameter of the optical fiber is 0.8 mm. The length of the intratumoral part of the fiber is selected individually according to ultrasound scanning so that the fiber inserted into the tumor is located in the middle of the neoplasm: through the top of the tumor, perpendicular to the sclera.

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 covered with bioinert electrical insulation 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.

Then a 3-port 25 G vitrectomy is performed, after which a retinotomy, exposing the tumor, conducts a liquid-air exchange.

Next, a pars plana, 3.5 mm from the limb in the quadrant, which provides the most convenient access to the tumor, depending on its location, after the conjunctiva incision, sclerotomy is performed, through which a fiber with a cathode in the form of an insert of 4.0 mm from the distal end is intraocularly inserted into tumor: through the top of the tumor, perpendicular to the sclera.

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. During ECL, the decay products of the tumor by the vitreotome are intraocularly 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 optical fiber and one 25 G cannula are removed (for the vitreotome 25 G), the port for the 20 G vitreotome is expanded, with which the tumor remains are removed, the retina is put in place, endolasercoagulation of the retina is performed, the vitreous cavity is filled with silicone oil. Upon completion of ECL, the surface electrode is removed. When the muscles are cut off, they are hemmed into place.

The invention is illustrated by the following data.

Clinical example. Patient O., 62 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. The location of the tumor is central. 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. The integrity of the sclera in the area of the projection of the base of the tumor was preserved.

Photoditazine at a dose of 0.8 mg / kg was used for PDT. The electrochemical lysis of the tumor was carried out with a charge of 12 C; simultaneously with ECL, the decay products of the tumor were removed with a vitreotome. Laser irradiation inside the tumor was carried out with a power of 20 mW; upon completion, the remaining tumor was removed by a vitreotome.

In a control study after 6 months, the chorioretinal lesion with slight pigmentation along the edges of the retina was determined ophthalmoscopically at the site of the neoplasm. 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 inserted inside the tumor - a fiber with a platinum insert, which reduced the invasiveness of the intervention, the sclera integrity in the area of the projection of the tumor base was preserved.

Photolon, or radachlorin, or photoditazine in a dose of 0.8 to 1.0 mg / kg was used for PDT. The electrochemical lysis of the tumor was carried out with a charge of 12 to 18 C; at the same time with ECL, the decay products of the tumor were removed with a vitreotome. Laser irradiation inside the tumor was carried out with a power of 20 to 30 mW; upon completion, the remainder of the tumor was removed with a vitreotome.

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

Thus, the inventive method reduces the morbidity of electrochemical lysis and photodynamic therapy of choroid melanoma, preserves the integrity of the sclera in the area of the projection of the base of the tumor, the complete destruction and removal of the tumor, the prevention of metastasis.

Claims (2)

1. The method of electrochemical lysis and photodynamic therapy of choroid melanoma with a prominence of more than 4 mm, 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 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 and in shape corresponding to the shape of the projection of the base of the tumor and to the sclera, and in size - less than the base of the tumor by 1 mm around the entire perimeter; a laser fiber is introduced intravitreal into the tumor with a diffuser made for the entire length of the intratumoral part of the fiber, while a platinum insert — a cathode — is located 4.0 mm from the distal end of the fiber; then, electrochemical lysis of the tumor is carried out with simultaneous removal of the decay products of the tumor, 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, the tumor is removed. 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