Method for prevention of recurrent malignant pelvic tissues or non-organ retroperitoneal tumours following surgical management

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to oncology and may be used for the purpose of prevention of recurrent malignant pelvic tumours or non-organic retroperitoneal tumours following the surgical management. A photosensitiser having high tropism to pelvic and retroperitoneal tumour tissues is administered intravenously. A completely extracted tumour bed is exposed to a photodynamic effect within healthy tissues using a light source of wave length characteristic of the photosensitiser used. It is combined with simulating an exposure field by placing a moistened surgical drape in a surgical wound. The laser exposure is generated by using a macrolens from at least one position. An irradiation energy dose makes 840 J to 1710 J.

EFFECT: method enables improving the effectiveness of photodynamic therapy ensured by using the photosensitisers with high tropism to pelvic and retroperitoneal tumour tissues and a possibility to increase a dose of laser light through generating the exposure field and determining its clear limits.

3 cl, 2 ex

 

The invention relates to medicine, namely to methods of treatment of malignant tumors using laser radiation, and can be used for the treatment of malignant tumors of the pelvic organs, as well as with locally advanced tumors of the retroperitoneum or performing advanced combined surgical interventions.

There is a method of photodynamic therapy (PDT) of malignant brain tumors. This method is Loco-regional delivery of a photosensitizer (PS) in the spinal fluid space brain twice with an interval of 24 h After 2 h after re-introduction of the FS exercise 2 consecutive session of PDT bed of the removed tumor, using percutaneous installed fibers by exposure to a laser beam with a wavelength of 675 nm and a power of 0.15-0.20 W for 20 minutes While before PDT, evacuate 15-20 ml of liquor (2-4 ml remote liquor examined by a spectroscope and chromatographic to register FS in the liquor and determination of its concentration) for the prevention of intracranial hypertension. Sessions of PDT is carried out with an interval of 24 h ("Method of treatment of malignant brain tumors using photodynamic laser therapy" Ogienko A.P., Nikonov S.D., Stupak V., Denisov A.N., Penguin I.V. Application for invention No. 2001120426/14, publ. from 20.10.2003,).

The disadvantage of this method is the lack of shielding healthy tissue, leading to increased risk of complications associated with damage to the surrounding healthy tissues as the result of exposure to laser radiation. In addition, the well-known technique is an invasive compared with a single intraoperative photodynamic therapy, FS administered topically using invasive manipulation (through puncture endolyumbalno space), and not systemically by intravenous infusion. The consequence is an increase in the duration of treatment. Due to the invasiveness of the procedure used low dose laser irradiation, which reduces the efficiency of PDT.

Closest to the claimed invention by way of the same purposes on a set of attributes is a method of adjuvant photodynamic therapy of recurrent retroperitoneal sarcomas (Nambisan R.N., Karakousis C.P., Holyoke E.D., Dougherty, T.J. Intraoperative photodynamic therapy for retroperitoneal sarcomas. // Cancer. 1988 Mar 15; 61(6): P.1248-52). This work contains the modes and doses of PDT in intraoperative irradiation of the bed of the removed tumor retroperitoneal space. The range of total radiation power ranged from 18 to 288 j with a wavelength of 630 nm on the tumor bed. The area of irradiation was varied from 30 to 100 cm 2. As FS used Photofrin dose of 2.5 mg/kg of body weight of the patient. Taken as a prototype.

The disadvantages of the prototype method are: using FS, trapnest which retroperitoneal tumors has not been proven. The authors of this method was conducted extensive irradiation of the bed remote retroperitoneal tumors that could lead to falls in the area of laser irradiation loops intestine and colon, taking into account their ability to peristaltically and mobility, as well as other surrounding healthy organs, which does not allow to use optimally high-dose laser irradiation because of the risk of damage to healthy organs and tissues. Besides this fact may help to ensure that freely spaced loops of bowel, getting into the zone of radiation, can escape the tumor bed, which prevents the desired effect of laser radiation on the desired area.

The claimed invention is directed to solving the problem of prevention of local recurrence and increase the level of ablation surgical interventions in the treatment of malignant tumors of the pelvic organs or recurrence non-organ tumors of the retroperitoneal space.

Use in clinical practice, the proposed method allows to achieve several technical (medical) results:

in moznosti intraoperative exposure in the treatment of primary and recurrent tumors;

- improving the efficiency of PDT and through the use of FS with high trapnest to tumor tissues of the pelvic and retroperitoneal space;

the increasing radicalism of surgical interventions due to the suppression of possible subclinical elements: otkolovshikhsia during mobilization of tumor cells, additional rudiments of the tumor, multicentric forms of growth;

- the possibility of increasing the dose of laser radiation to 840-1710 j by simulating field exposure and shielding healthy tissue, loops and small intestine, and stomach, liver and arterial blood vessels, which, in turn, improves the efficiency of PDT and to reduce the number of relapses;

- uniform and complete delivery of the required dose of laser radiation in all the departments of the bed of the removed tumor at the expense of a clear definition of the boundaries of the bed of the removed tumor by modeling field exposure.

These therapeutic results by carrying out the invention are achieved due to the fact that, just as in the known method, perform intraoperative PDT by laser irradiation on the removed tumor bed or remote organ affected by the tumor.

The feature of the proposed method lies in the fact that the treatment of patients with primary or re what ideami malignant tumors of the pelvic organs or recurrence non-organ tumors of the retroperitoneum is performed with the use of FS, high trapnest to tumor tissues of the pelvic and retroperitoneal space (photoditazine, photosense)by laser irradiation to the tumor bed after its complete removal within healthy tissue using a light source with a wavelength characteristic of the used FS. At the same time carry out the modeling field exposure and screen loops of the small intestine, large intestine, stomach and great vessels using moistened surgical linen. Laser irradiation is performed using macroline from at least one position, the energy density of radiation is 20-30 j/cm2dose energy irradiation is 840-1710 J.

The invention consists in the following.

The inventors developed and tested in clinical practice methods of treatment of patients with bladder cancer with the presence of invasion paravesical fiber, which is planned to be implemented radical cystectomy, as well as the treatment of locally advanced tumors of the retroperitoneal space when expanded combined surgical interventions.

Tumors of this localization is characterized by the occurrence of local recurrence, the substrate of which is the presence of residual tumor tissue, determined microscopically after resection in the amount of R1 (prodolzheny the tumor growth), as well as the emergence of new beginnings tumor growth in the area of resection (actually a local recurrence).

An indication to perform intraoperative photodynamic therapy is the presence of morphologically confirmed resectable primary or recurrent tumor.

The authors found that FS photoditazine and photosense have high trapnest to tumor tissues of the pelvic and retroperitoneal space.

Developed by the authors, the method is based on the local irradiation of the bed of the removed tumor or organ with the tumor modeling required size and configuration of the field of exposure, as well as the shielding of the loops of the small intestine, colon, stomach and great vessels using moistened surgical linen, which allows to increase the dose of laser irradiation to 840-1710 j. This, in turn, increases the antitumor efficacy of PDT and to reduce the frequency of subsequent recurrence. Using the proposed method in clinical practice allows to solve the problem of prevention of local recurrence and the possible suppression of subclinical rudiments of the tumor.

The method is as follows.

At the first stage intravenous FS for a period of time, characteristic for each drug before performing laser irradiation on the bed of the removed tumor or organ with tumor

At the second stage, surgical access to the tumor, removal of the tumor or organ with the tumor depending on the tumor location.

The phase III perform field modeling of laser irradiation by placing moistened surgical linen in operating the wound so that the bed of the removed tumor was separated from the loops of intestine and colon, stomach and great vessels and maximum available for carrying out laser irradiation.

The fourth stage consists in carrying out laser irradiation on the removed tumor bed or remote organ (depending on tumor localization) using a light source with a wavelength characteristic of the used FS. For delivery of laser radiation in the area of the light exposure using a quartz fiber with a macrolens, focusing uniform radiation. Irradiation of one or more positions depending on the configuration and size of the bed of the removed tumor or organ with a tumor.

For this localization optimal choice is to use macroline due to the fact that in contrast to other optical fibers having end radiation, in particular optical fibers with end cleavage and others, only macroline gives the opportunity to shape the field of laser irradiation with a uniform dose of light in all its parts. For accounts who is performing the treatment with the strictly given dose of laser radiation.

The session is conducted with a dose of energy radiation from 840 j to 1710 j. The exposure time and the number of positions calculated depending on a given area of exposure.

The inventive method can be illustrated by the following clinical examples.

1. Patient A., 69, history 08-4458, was treated with clinical diagnosis of bladder cancer (MP) article III, pT3N0M0G3. Upon admission to the ward the patient according to the comprehensive examination (ultrasound, MRI, cystoscopy) identified invasive cancer MP, and therefore received surgical treatment in the amount of contractingstate, 2-sided ureterocutaneostomy, 2-way extended ilio-obturatorious lymphadenectomy, PDT bed remote MP with tumor. For the PDT used FS photosense, which was injected intravenously 2 hours before the operation. PDT was performed after resection of stage and modeling fields of laser irradiation using a moist surgical linen, the laser power of 2 W, a wavelength of 670 nm, the diameter of the light spot 8 cm, one field exposure (1 position), the exposure time of 8.5 minutes, the dose of energy 1710 j. Subsequently the patient was under strict observation period of 33 months, signs of recurrence and metastasis was not detected.

2. Patient U., 69. Diagnosis: recurrence non-organ retroperitoneal tumor. History: at the place of residence of the neck is Leno retroperitoneal tumor in the region of the upper edge of the body of the pancreas. Asked of Moscow.

According to the survey (ultrasound, CT), in the retroperitoneal space at the level of the celiac trunk is defined tumor mass of 3.74.7 cm, heterogeneous structure. The tumor is adjacent to the body of the stomach, shifts the body of the pancreas anteriorly and downwards. The celiac trunk and trunk vessels displaced, with no signs of involvement. According to immunohistochemical studies education - malignant paraganglioma.

The patient was operated in the amount of removal of retroperitoneal recurrence non-organ tumor photodynamic therapy on the tumor bed.

When the revision is to the left of the celiac trunk is defined tumor mass of 5.03.0 cm, photoelasticity consistency. The lower pole of education is the body of the pancreas, closely adapted to the splenic artery and vein, with no signs of germination. Partly sharp, partially blunt by the tumor is selected, removed in a single unit with the surrounding tissue. Conducted a session of PDT on the removed tumor bed after modeling field irradiation with FS photoditazine, which was injected intravenously for 2.5 h before surgery. Laser irradiation with a wavelength of 662 nm, three-irradiated (3 positions), the dose of laser irradiation - 1580 J.

The postoperative period was uneventful. During routine morphological examination - malignant paraganglioma. The observation period of 36 months without p is Isakov progression of the disease.

1. The way to prevent recurrence in the surgical treatment of malignant tumors of the pelvic organs or recurrence non-organ tumors of the retroperitoneum, including photodynamic effect on the removed tumor bed or remote organ, tumour, characterized in that the treatment is performed with the use of photosensitizers with high trapnest to tumor tissues of the pelvic and retroperitoneal space by laser irradiation to the tumor bed after its complete removal within healthy tissue using a light source with a wavelength characteristic of the used photosensitizer, at the same time carry out the modeling field exposure by placing moistened surgical linen in operating the wound, laser irradiation is performed using macroline from at least one position, the dose of energy irradiation ranges from 840 j to 1710 J.

2. The method according to claim 1, characterized in that the photosensitizer is used photoditazine, laser irradiation is performed with a wavelength of 662 nm.

3. The method according to claim 1, characterized in that the photosensitizer is used photosense, laser irradiation is performed with a wavelength of 670 nm.



 

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2 ex

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1 ex

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2 ex

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EFFECT: higher therapeutic and cosmetic effect.

1 ex

FIELD: medicine.

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EFFECT: reduced risk of metastasizing.

4 cl, 13 dwg

FIELD: medicine.

SUBSTANCE: method involves building tunnel to posterior eyeball pole in inferoexterior and superexterior quadrants. The tunnel is used for implanting flexible polymer magnetolaser implant to the place, the subretinal neovascular membrane is localized. The implant has a permanent magnet shaped as a cut ring and is provided with drug delivery system and a short focus scattering lens of laser radiator connected to light guide. The permanent implant magnet is axially magnetized and produces permanent magnetic field of 5-7 mTesla units intensity. It is arranged with its north pole turned towards sclera at the place of the subretinal neovascular membrane projection with extrascleral arrangement of laser radiator lens membrane being provided in the subretinal neovascular membrane projection area. The other implant end is sutured to sclera 5-6 mm far from the limb via holes made in advance. The implant is covered with conjunctiva and retention sutures are placed thereon. Light guide and drug supply system lead is attached to temple with any known method applied. Drugs are supplied via the implant drug supply system in retrobulbary way in any order. Triombrast is given in the amount of 0,4-0,6 ml and dexamethasone or dexone in the amount of 0,4-0,6 ml during 3-4 days every 12 h. 0.1-1% aqueous solution of khlorin is intravenously introduced at the third-fourth day after setting the implant as photosensitizer, selected from group containing photolon, radachlorine or photoditazine, at a bolus dose of 0.8-1.1 mg/kg. Visual control of subretinal neovascular membrane cells fluorescence is carried out by applying fluorescent diagnosis methods. After saturating the subretinal neovascular membrane with the photosensitizer to maximum saturation level, intravitreous, transretinal laser radiation of 661-666 nm large wavelength is applied at general dose of 30-120 J/cm2. The flexible polymer magnetolaser implant is removed and sutures are placed on conjunctiva. Permanent magnet of the flexible polymer magnetolaser implant is manufactured from samarium-cobalt, samarium-iron-nitrogen or neodymium-iron-boron system material. The photosensitizer is repeatedly intravenously introduced at the same dose in 2-3 days after the first laser radiation treatment. Visual intraocular neoplasm cells fluorescence control is carried out using fluorescent diagnosis techniques. Maximum level of saturation with the photosensitizer being achieved in the subretinal neovascular membrane via laser light guide and implant lens, repeated laser irradiation of the subretinal neovascular membrane is carried out with radiation dose of 30-60 J/cm2.

EFFECT: accelerated subretinal edema and hemorrhages resorption; regression and obliteration of the subretinal neovascular membrane; prolonged vision function stabilization.

6 cl

FIELD: medicine.

SUBSTANCE: method involves filling vitreous cavity with perfluororganic compound. Two electrodes manufactured from platinum group metal are intravitreally, transretinally introduced into intraocular neoplasm. Electrochemical destruction is carried out with current intensity of 10-100 mA during 1-10 min in changing electrodes polarity and their position in the intraocular neoplasm space, and the electrodes are removed. 0.1-1% aqueous solution of khlorin as photosensitizer, selected from group containing photolon, radachlorine or photoditazine, is intravenously introduced at a dose of 0.8-1.1 mg/kg. Visual control of intraocular neoplasm cells fluorescence is carried out by applying fluorescent diagnosis methods. After saturating the intraocular neoplasm with the photosensitizer to maximum saturation level, intravitreous, transretinal laser radiation of 661-666 nm large wavelength is applied at a dose of 30-120 J/cm2 in perfluororganic compound medium. The transformed retina and tumor destruction products are intravitreally removed with perfluororganic compound volume being compensated with its additional introduction. Boundary-making endolasercoagulation of retinotomy area is carried out. The perfluororganic compound is substituted with silicon oil. The operation is ended in placing sutures over sclerotmy areas and over conjunctiva. Perfluormetylcyclohexylperidin, perfluortributylamine or perfluorpolyester or like are used as the perfluororganic compound for filling vitreous cavity. Platinum, iridium or rhodium are used as the platinum group metals.

EFFECT: complete destruction of neoplasm; reduced dissemination risk.

6 cl, 12 dwg

FIELD: medicine, applicable for stopping of pains of various nature.

SUBSTANCE: the device has a quantum-mechanical oscillator located in a casing, magnet, vessel for medicinal agent and a hollow cylinder. The magnet is installed between the oscillator and the vessel. Positioned in the vessel is a hollow cylinder having through holes on its surface.

EFFECT: quick and absolute anestesia.

2 ex, 1 dwg

FIELD: medicine.

SUBSTANCE: method involves administering laser radiation therapy once a day using low intensity pulsating radiation of wavelength equal to 890nmand power density of 0.03 mW/cm2. Injured organ projection to frontal abdominal wall is exposed to radiation at the first laser therapy stage in two fields acting upon each field for 2 min with radiation pulse succession frequency equal to 80 Hz in applying stable contact-type method. Total treatment dose on two fields is equal to 0.008 J/cm2. The second laser therapy stage begins immediately after having finished the first one in applying radiation along the large intestine path using labile contact-type method in a way that radiation pulse succession frequency equal to 80 Hz is applied first during 1 min and then frequencies of 600, 150 and 300 Hz are applied also during 1 min, respectively. Total treatment dose is equal to 0.032 J/cm2 at the second stage. Total treatment dose is equal to 0.04 J/cm2 at both stages.

EFFECT: enhanced effectiveness in inhibiting dysbacteriosis; reduced frequency of postoperative complications.

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