RU2358777C1 - Light guides for interstitial laser hyperthermia of intraocular neoplasms and insertion technique - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: light guides are inserted into neoplasm transsclerally by an adjustable lanceolate needle and cannulas 23G or 25G perpendicularly to sclera on a line of the greatest diametre of the base and on a line perpendicular diametre at the distance 2.5-3.5 mm in both sides from the centre of tumour base. The depth of light guide insertion is specified from preliminary ultrasound: tumour height at the distance 2.5-3.5 mm on sclera from the centre of tumour basis minus 1.5-2 mm.

EFFECT: possibility for controlled depth hyperthermia, minimum injury of structures and eye tissues in light guide insertion and procedure, elimination of required additional surgeries following hyperthermia, necrosis limitation by tumour volume.

1 ex

Description

The invention relates to medicine and can be used in ophthalmology and ophthalmic oncology for interstitial laser hyperthermia of intraocular neoplasms of pre-equatorial and equatorial localization.

At the present stage of development of ophthalmic oncology, preference is given to organ-preserving methods of treating intraocular neoplasms, the main requirement for which is the principle of maximum radicalism with respect to the tumor with minimal damaging effects on surrounding healthy tissues.

According to the recommendations of A.F. Brovkina (2002), organ-preserving treatment is possible if the largest base diameter of the intraocular neoplasm with post-equatorial localization does not exceed 13-14 mm, and the proinence is 6.5 mm.

With large tumor sizes, enucleation is customary. However, back in 1978, L. Zimmerman and M. McLean showed that the frequency of metastases in patients who underwent enucleation is higher than in untreated patients. The survivability of the 5-year period after enucleation of the affected eye is from 50 to 75%, while when using brachytherapy this indicator is significantly higher - from 86 to 93% (E.S. Libman, A.F. Brovkina, 1989).

Based on the above data, the relevance of developing organ-preserving methods for the treatment of intraocular neoplasms, in relation to which enucleation is traditionally carried out, becomes obvious.

One of the promising methods of treatment of intraocular tumors, in particular, melanoma of the choroid (MX), is considered to be photodynamic therapy (PDT). Unfortunately, the effectiveness of PDT is limited by the height of the neoplasm, which is subject to experimental studies. Thirty-two New Zealand rabbits with pigmented choroid melanomas underwent PDT (Kim RY; Hu LK; Foster BS; Gragoudas ES; Young LH. Photodynamic therapy of pigmented choroidal melanomas of greater than 3 mm thickness. // Ophthalmology. 1996 Dec; 103 (12 ): 2029-36). The results of histomorphological studies confirmed the ability of PDT to destroy choroid melanomas with a thickness of not more than 4.6 mm. An earlier similar study (Gonzales VH, Hu LK, Theodossiadis PG, et al. Photodynamic therapy of pigmented choroidal melanoma. // Ophthalmol Vis Sci. 1995; 36: 871-878) showed the effectiveness of PDT against non-thick pigmented choroid melanomas more than 4.8 mm.

The effectiveness of MX brachytherapy is 70-73% with a five-year follow-up period [Brovkina AF, Zarubei GD On the effectiveness of brachytherapy for uveal melanomas. // Ophthalmol. journal - 1993. - No. 1. - S.1-4].

The main condition for successful brachytherapy of intraocular tumors is the calculation of the absorbed dose. However, in order to achieve the necessary doses at the “top” of the tumor in the treatment of large intraocular neoplasms, the surface dose of the ophthalmic applicator must be extremely high, which leads to serious complications associated with radiation exposure to the eye structures. These include:

- iridocyclitis - occurs in cases of irradiation of the eye with large doses, when the front edge of the ophthalmic applicator is located close to the ciliary body. Radiation iridocyclitis occurs with hypertension and requires intensive treatment (mydriatics, corticosteroids, antihypertensive drugs, etc.);

- reactive exudative retinal detachment occurs in 43% of patients with large tumors;

- radiation vasculitis, partial hemophalmus;

- retino- and neuroretinopathy, neovascular glaucoma are irreversible complications and make up 3, 1 and 1%, respectively.

The possibility of developing these complications correlates with the dose of radiation, its rigidity, size and location of the tumor:

- radiation cataract;

- radiation necrosis of the sclera [Ophthalmic oncology. / Ed. A.F. Brovkina. - M .: "Medicine", 2002. - S.132-133].

Interstitial laser hyperthermia does not have PDT-like efficacy limitations on tumor height and is not associated with the occurrence of complications inherent in brachytherapy.

Local hyperthermia involves the selective heating of tumor tissue to 43-44 ° C, in which thermal energy is supplied directly to the target tissues. Experimental studies have established that tumor tissue is heated to a greater extent than the surrounding normal tissue. The effect of hyperthermia on the tumor process is determined by the "heat dose" and the pH of the cells. Thermal exposure of 40-42 ° C improves blood flow in tissues, has anti-inflammatory and immunomodulating effects (Gelfond ML, Mizgirev IV, Barchuk AS et al. Selective laser hyperthermia of malignant neo-plasms: experimental and clinical research. // Proc. Of SPIE ( Laser use in Oncology II). - 2004. - Vol.4059. - P.13-24), reduces metastasis.

In the temperature range of 42.5-43 ° C, a cytotoxic effect develops due to the thermal inactivation of proteins and damage to the cytoplasmic membranes of cells of solid tumors (Konoplyannikov A.G. Electromagnetic hyperthermia (microwave and UHF ranges) in the treatment of tumor and non-tumor diseases. // Physical Medicine. - 1991 - T.1. - No. 1. - P.5-11). In addition, when the tumor is heated to 42 ° C (and above), the expression of heat shock proteins (HSP 70) is induced, accompanied by the development of local necrosis leading to the release of these polypeptides into the extracellular medium and the appearance of associative peptides (Osinsky S., Shidnia N. The 20th th anniversary of the International Clinical Hyperthermia Society (ICHS): experimental and clinical experience. // Exp.Oncology. - 2000. - Vol.22. - P.95-96). HSPs expressed on the surface of a tumor cell as antigen-presenting molecules participate in the activation of natural killer cells, T-lymphocytes, and act as chaperones for peptides. HSPs and their derivatives entering the extracellular space activate natural immune responses. Thus, at a temperature to which normal tissues are tolerant, irreversible damage to tumor cells occurs (Seegenschmiedt M.N., Erb J., Sauer R. Interstitial Hyperthermia combined with Radiotherapy: Rational Technology, Clinical Experiance. // Minimal invasive Medicine. - 1993 . - Vol.4. - No. 3. - P.22-34).

In modern oncology, interstitial hyperthermia is used to treat neoplasms of the soft tissues, head and neck, mammary glands, pelvic cavity and extremities. To carry out interstitial hyperthermia in these cases, there are various fibers, a procedure has been developed, including methods for introducing fibers.

The use of interstitial hyperthermia in ophthalmology is complicated by the inaccessibility and small size of neoplasms. Another problem is the lack of optical fibers modified for hyperthermia of intraocular tumors.

Therefore, it is urgent to develop a method for introducing optical fibers for interstitial laser hyperthermia of intraocular neoplasms, during the procedure, taking into account the lack of direct access and small size of the tumor, as well as modifying optical fibers to allow hyperthermia in the volume of the neoplasm at different depths.

Known optical fibers (400 and 600 μm) with diffusers for interstitial operations (http://www.laserstar.ru/pr_instr_acces.htm). However, when using these fibers, it is impossible to precisely control the depth of introduction of the fiber and, accordingly, the depth at which the hyperthermia is carried out.

The authors do not know the method of introducing optical fibers for interstitial laser hyperthermia of intraocular neoplasms.

The objective of the invention is the modification of optical fibers for interstitial laser hyperthermia and the development of a method for their administration in pre- and equatorial localization of intraocular neoplasms.

The technical result is the ability to conduct hyperthermia at a controlled depth, minimal damage to the structures and tissues of the eye with the introduction of optical fibers and the procedure, the absence of the need for additional surgical procedures after completion of hyperthermia, the limited necrosis of the tumor volume.

The technical result is achieved due to the fact that the fibers are calibrated with a division price of 1 mm and have a limiter; The fibers are inserted into the neoplasm transsclerally by means of spears of adjustable length and 23 G or 25 G cannulaes perpendicular to the sclera on the line of the largest base diameter and on the line perpendicular to its diameter at a distance of 2.5-3.5 mm on both sides from the center of the base of the tumor to a depth that determined according to preliminary ultrasound: the height of the tumor at a distance of 2.5-3.5 mm along the sclera from the center of the base of the tumor minus 1.5-2 mm.

An optical fiber (⌀400 μm, ⌀600 μm) with a diffuser is graduated with a division price of 1 mm, starting from the diffuser. A limiter is mounted on the light guide, for example, in the form of a rubber ring. Moving the limiter along the fiber, set the depth to which it is introduced into the structure of the tumor.

The optical fibers are introduced as follows.

Transsclerally diaphanoscopically clarify the location and size of the tumor, determine the boundaries of the projection of the base of the tumor onto the sclera, and select the largest diameter of the base of the tumor and the diameter perpendicular to it. The sclera points of introduction of optical fibers are marked: on the line of the largest diameter of the base and on the line of a diameter perpendicular to it at a distance of 2.5-3.5 mm on both sides of the center of the base of the tumor. Then, fibers are introduced into the structure of the intraocular neoplasm.

For the introduction of optical fibers, a spear with screw length control and cannulas for instruments 23 G (for optical fibers ⌀600 μm) or 25 G (for optical fibers ⌀400 μm) are used. Set the required length of the spear (the length of the extrascleral part of the cannula + scleral thickness + depth to which the fiber is inserted into the tumor). Then, using a spear installed in the cannula channel, a sclerotomy is performed and a full-length spear is introduced into the tumor structure perpendicular to the sclera. The spear is removed from the cannula channel and a light guide is inserted into it.

The maximum depth at which the fiber is inserted into the tumor is determined by preliminary ultrasound (seroscale B-scan): the height of the tumor at a distance of 2.5-3.5 mm along the sclera from the center of the base of the tumor minus 1.5-2 mm. To irradiate the entire tumor volume (at maximum depth, in the middle part, etc.), the depth of fiber insertion can be adjusted by introducing them into the channel to the maximum depth, 2/3 of the maximum depth, by 1/3. A limiter is used to control the depth of fiber insertion.

After the introduction of the optical fibers, interstitial laser hyperthermia of the tumor is performed, then the optical fibers and cannulas are removed, sclerotomy is not sutured.

To carry out hyperthermia with several optical fibers, several lasers or an optical splitter are used simultaneously. The invention is illustrated by the following data.

Clinical example. Patient N., 69 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 of the choroid OD. Tumor localization is temporally in the equatorial region. The size of the tumor according to ultrasound B-scan: base 10.0 × 14.0 mm, the size of the prominence of 7.5 mm During phage, a characteristic “spotted” fluorescence was detected.

The patient received informed consent for the treatment of choroid melanoma with interstitial laser hyperthermia.

Interstitial laser hyperthermia of the tumor was carried out using 600 μm fibers, which were introduced according to the proposed method using 23 G cannulas, the distance between the fibers was 5 mm. Hyperthermia was performed in the entire tumor volume, introducing fibers to the maximum depth, 2/3 of the maximum depth, and 1/3. The depth of introduction of the optical fibers was controlled using a limiter made in the form of a rubber ring.

Immediately after completion of hyperthermia and removal of optical fibers, sclerotomies are visible on the sclera without signs of damage to surrounding tissues. Sclerotomy was not sutured.

In a control study after 6 months, the chorioretinal lesion with heterogeneous pigmentation with a residual prominence of up to 1.4 mm was determined ophthalmoscopically at the site of the neoplasm. Ultrasound examination in the mode of energy Doppler mapping showed that the intratumoral blood flow in the projection of the focus was completely absent. The observation period of 1.5 years - without signs of continued growth.

Hyperthermia with the introduction of optical fibers according to the proposed method was carried out for 4 patients with intraocular neoplasms. Used fibers of 400 μm and 600 μm, which were introduced through cannulas 25 G and 23 G, respectively, the distance between the fibers was from 5 to 7 mm. In no case did additional surgical procedures be required after the completion of hyperthermia; there were no signs of damage to eye tissue outside the tumor.

Duration of observation - up to 18 months. In two cases, complete, in two, partial destruction of the tumor according to ultrasound data was achieved.

Thus, the inventive method provides the ability to conduct hyperthermia at a controlled depth, minimal damage to the structures and tissues of the eye with the introduction of optical fibers and the procedure, the absence of the need for additional surgical procedures after completion of hyperthermia, the limited necrosis of the tumor volume.

Claims (1)

A method for introducing optical fibers for interstitial laser hyperthermia of intraocular neoplasms, namely, that the optical fibers are introduced into the neoplasm transsclerally by means of a spear of adjustable length and 23G or 25G cannels perpendicular to the sclera on the line of the largest base diameter and on the line of a diameter perpendicular to it at a distance of 2.5-3, 5 mm in both directions from the center of the base of the tumor to a depth that is determined according to preliminary ultrasound: the height of the tumor at a distance of 2.5-3.5 mm along the sclera from the center of the base of the tumor minus 1.5-2 mm.