RU2477625C1 - Method for cryodestruction of adrenal tumours - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, oncology, and may be used for cryodestruction of adrenal tumours. For this purpose, pathological areas are exposed to liquid nitrogen at temperature -196°C covering the same local area of epinephros. The same temperature density is maintained within the contact exposure area for three cryocycles. The cryocycle length is 1 minute. The cycle pause is 1 minute.

EFFECT: method enables providing effective local destruction of the tumour ensured by the preserved morphological structure and functional activity of intact adrenal tissue.

5 dwg, 1 tbl

Description

The invention relates to medicine, specifically to surgery, and can be used for cryosurgical treatment of adrenal tumors in an experiment.

Modern adrenal surgery is represented by traditional interventions, endovideoscopic operations (1), operations from small accesses and gentle methods, which include radiofrequency ablation (5), cryoablation (4). At the same time, there is no consensus among surgeons regarding the choice of a particular method of surgery for various pathologies of the adrenal glands; indications and contraindications to the use of minimally invasive sparing surgical procedures are not substantiated. Surgical interventions for adrenal tumors are classified as high risk, due to complex anatomical relationships with surrounding organs, the risk of damage to large vessels. Currently used methods are limited mainly by adrenalectomy (3) or other organ-bearing types of operations and are fraught with the development of serious complications. Until now, there are no options for local organ-preserving effects on the pathological process.

Tumors of the adrenal gland less than 2 cm in diameter, the so-called incidentalomas, accidentally detected during imaging studies of the abdominal cavity and retroperitoneal space or during surgical interventions in these areas due to the complexity and trauma of conventional methods of surgery, it is recommended to observe and only with an increase in size of more than 3 see adrenalectomy is proposed, which in some cases leads to the progression of the process, malignancy of tumors and other complications (1).

A known method of cryodestruction based on freezing the adrenal glands with a sprayed stream of liquid nitrogen to a temperature of -135-145 ° C followed by spontaneous slow thawing and repeated similar freezing (6).

This method is the closest to the claimed technical essence and is selected as a prototype.

The disadvantage of this method is the lack of organ-preserving effect, since the method involves cooling the entire adrenal gland. The disadvantages include unstable and uneven in size and depth cooling of the adrenal gland caused by unregulated atomization of the refrigerant from the device onto the adrenal gland tissue. The amount of refrigerant sprayed on the fabric decreases from the center to the periphery, which reduces the uniformity of the speed and depth of cooling from the center to the periphery.

A new technical task is to increase the efficiency of the method by maintaining the functional activity of the unaffected adrenal tissue.

To solve the problem in the method of cryodestruction of adrenal tumors, which consists in exposure to pathological zones with liquid nitrogen, they act at a temperature of -196 ° C on the same local area of the adrenal gland for three cryocycles, one minute each, with a break between cycles of 1 min while maintaining the same temperature density in the contact zone.

The methods of cryodestruction used in the treatment of various neoplasms have advantages over traditional surgical operations, namely, they can locally destroy the pathological area of the tissue without damaging the surrounding healthy tissue, and prevent the dissemination of tumor cells.

In addition, the cryosurgical method has a hemostatic and anesthetic effect, which ensures a favorable course of the wound process after cryodestruction, causes a minimal inflammatory reaction, allows for surgery with less trauma and to reduce its duration. These positive aspects of the cryotherapy method are very relevant and can be used in adrenal surgery.

The effectiveness of the proposed method is explained by the action of ultra-low temperatures on biological tissues. The impact of ultra-low temperatures on biological tissues leads to a slowdown and termination of blood flow, respiration, and nerve conduction in them. The main pathogenetic factor in the destruction of cells is the process of freezing water both extracellularly and intracellularly. Damage to the cell membranes by ice crystals, inhibition of intracellular metabolism, which causes cell death. Of great importance is the local cessation of blood circulation with thrombosis of small vessels, while the large vessels maintain their integrity due to the high resistance of collagen and elastic fibers to cold. The absence of a damaging effect on the walls of large vessels allows cryodestruction in the immediate vicinity of them, which is especially important for the adrenal gland in view of the increased vascularization of this organ.

Using the proposed method for local cryodestruction of pathological foci of the adrenal gland allows to increase the efficiency of local destruction of the tumor and to preserve the morphological structure and functional activity of unaffected adrenal tissue.

The method allows locally destroying a given volume of pathological tissue and preserving the viability and functional activity of the surrounding healthy tissue.

Distinctive features showed in the claimed combination of new properties that are not obvious to a specialist and do not follow explicitly from the prior art.

An identical set of essential features was not found in the study of medical, scientific and patent literature.

The proposed method can be used in practical health care to increase the effectiveness of the treatment of patients with limited adrenal tumors.

Thus, the present invention meets the conditions of patentability "Novelty", "Inventive step" and "Industrial applicability".

The invention will be clear from the following description and the attached Figures 1-5 and table No. 1.

Figure 1 shows a diagram of the operation, where 1A is a cryoapplicator, 1B is a crater, 1B is an ice sphere, and 1G is an adrenal gland.

Figure 2 shows the data of histological examination (term 1 day).

Figure 3 shows the data of histological examination (term 7 days).

Figure 4 shows the data of histological examination (term 14 days).

Figure 5 shows the data of histological examination (term 1 month).

The method is as follows.

At the first stage, adrenal gland access and excision are performed. Under general anesthesia, the upper-median laparotomy operative access is performed. After opening the abdominal cavity, an approach and the allocation of the corresponding adrenal gland are carried out. When the right adrenal gland is isolated, the colon is withdrawn medially, and the liver and gall bladder are up. The parietal leaf of the posterior wall of the abdominal cavity is cut laterally to the ascending colon, the exposed fascia of Gerota is opened and the right kidney is pulled down. In case of isolation of the left adrenal gland, the splenic bend of the colon is removed medially, the parietal peritoneum is vertically cut laterally from it, and the splenic-colon ligament is crossed. Gerota's fascia is opened vertically, the left kidney is pulled down. In this case, retroperitoneal fatty tissue is exposed at the level of the gate and the upper pole of the corresponding kidney. Above the upper pole of the kidney is the adrenal gland, which is covered with gauze napkins. At this point, the first stage is considered complete.

At the second stage, the adrenal surface area is marked with three single single sutures using an atraumatic needle with colored non-absorbable monofilament at three points around the cryodestruction zone. Cryotherapy is performed on this site. For the implementation of cryotherapy, for example, porous-permeable cryoapplicators made of titanium nickelide with a smoothed working part and a volumetric porous part of different tip diameters from 2 to 20 mm are used (7). The applicator porosity is 20-30%, pore sizes are 10-200 microns, pores are open, interconnected. The alloy material is based on titanium nickelide. The proposed design provides localized exposure and a constant density of the temperature regime in the selected tissue section for cryodestruction (up to 2 cm).

Porous-permeable nickel-titanium applicators can clearly localize the process of cryotherapy without damaging the surrounding tissue, to create the necessary degree of tissue cooling. The amount of nitrogen used to fill the applicator corresponds to the amount of free space containing air (on average 10-50 ml), which contributes to a minimum flow of liquid nitrogen. In the process of filling the applicator, liquid nitrogen displaces the air contained in the pores, and the effect of swirling steam is determined. The porous structure of the applicators retains liquid nitrogen without leaking it until complete evaporation. Instruments made of liquid titanium nickelide filled with liquid nitrogen maintain a temperature close to the boiling point of nitrogen for 1.5-2 minutes, during which time the effect of cryosurgical manipulations is highest. As the amount of nitrogen is consumed, the applicator is covered with hoarfrost. Visually, by changing the color of its surface, the end of its work is clearly defined. The tip of the cryoapplicator is immersed in liquid nitrogen for several minutes, thereby cooling the tip to a temperature of -196 ° C, after which the adrenal tissue is actually frozen, consisting of several cryocycles. One cryocycle is continued for 1 minute, the time between cryocycles, when the adrenal tissue has time to thaw visually, is 1 minute. Perform 3 cryocycles on the same local area of the adrenal gland. One minute of exposure to liquid nitrogen freezes the tissue to a depth of 0.5-0.8 cm. The thickness of the adrenal gland section of the dog is 0.5-0.6 cm, these 0.5-0.6 cm are frozen, including the crater and the ice sphere 1 minute followed by thawing for 1 minute. Visually, the impact zone is represented by a crater with a depth of 0.2-0.3 cm and a bottom represented by a through ice sphere of 2-3 mm thickness, as well as side walls of a crater 2 mm wide similar to an ice sphere.

The aftereffect is a towering shaft (tissue site) above the surface of the adrenal tissue, which corresponds to the crater area and the adjacent ice sphere. The site rises above the surface of the adrenal gland and is represented by an edematous cyanotic-crimson shaft of adrenal gland tissue with dilated, stasized small vessels and small petechial hemorrhages.

The second stage of the operation is considered complete.

After the operation, hemostasis is monitored, suturing of the posterior peritoneal sheet, suturing of the abdominal wall in layers.

Example 1. The implementation of the method in the experiment.

For the experiment we used a mongrel dog, a cable, weighing 15 kg, age 2.5 years.

Operation - May 20, 2010. Local cryodestruction of pathological sections of the adrenal gland by exposure to a cryoapplicator of porous permeable titanium nickelide filled with a refrigerant.

At stage I, prompt access and adrenal gland isolation are performed. After preliminary removal of the scalp from the anterolateral abdominal wall, treatment of the skin twice with 5% alcohol solution of iodine, twice with 70% ethyl alcohol in the operating room, surgery is performed under intravenous anesthesia with xylazine solution (0.25-0.5 ml / 10 kg) by median laparotomy.

With laparotomic access, a midline incision of soft tissues is carried out for 10-15 cm. Along the incision line, the skin with subcutaneous tissue is layered in layers, the abdominal cavity is opened along the white line of the abdomen.

. Правая надпочечниковая железа на короткой правой центральной надпочечниковой вене прилежит к задней поверхности нижней полой вены на уровне отхождения от нее правой почечной вены. Путем отведения петель тонкой и толстой кишок кнутри, почек книзу, селезенки и желудка слева, а печени справа кверху обнажается жировая клетчатка с лежащим в ней надпочечником. Надпочечник обкладывают марлевыми салфетками от окружающих органов и тканей. Первый этап считают оконченным.After opening the peritoneum, the approach and the allocation of the corresponding adrenal gland are carried out. The left adrenal gland is located lateral to the inferior vena cava above the left kidney. In this case, the central adrenal vein crosses the gland in the center, departing at a right angle from the inferior vena cava, and then plunges into the thickness

. The right adrenal gland on the short right central adrenal vein is adjacent to the posterior surface of the inferior vena cava at the level of discharge of the right renal vein from it. By removing the loops of the small and large intestines inside, the kidneys down, the spleen and stomach to the left, and the liver, fatty tissue with the adrenal gland lying in it is exposed upward. The adrenal gland is covered with gauze napkins from surrounding organs and tissues. The first stage is considered completed.

At the second stage, the surface area of the gland is marked with three single single sutures using an atraumatic needle with non-absorbable colored monofilament at three points around the cryodestruction zone. Cryotherapy is performed on this site. For this, cryoapplicators of porous-permeable titanium nickelide of different tip diameters with a static working element are used, filled with refrigerant (liquid nitrogen) from 2 to 10 mm. The cryoapplicator is immersed in liquid nitrogen, while the porous-permeable structure of titanium nickelide absorbs the refrigerant, filling up completely after 1-2 minutes. Achieving cooling of the working part of the applicator to a temperature of -196 ° C, after which the adrenal tissue is actually frozen, consisting of several cryocycles. The readiness of the applicator for operation is determined by the termination of evaporation from the Dewar vessel, into which the working part of the applicator is immersed. A cryoapplicator saturated with liquid nitrogen is placed on the marked area of the adrenal gland until its working surface is in firm contact with the tissue surface. One cryocycle of exposure to liquid nitrogen lasts for a duration of 1 minute. When visually observing the process of cryotherapy under the applicator and 1-2 mm around it, the formation of an ice sphere is noted, which thaws out for 1 minute. 3 cryocycles are carried out on the same local area of the adrenal gland. During the experiment, freezing of the adrenal gland tissue of the dog to the entire thickness (0.5-0.6 cm) is achieved. Visual inspection of the cryoapplication process reveals that the surface of the ice sphere did not exceed the diameter of the nozzle by more than 2 mm. The second stage is considered completed.

After the operation, control on hemostasis. The wound of the abdominal wall is sutured in layers continuous and interrupted sutures. The operation is considered completed.

After the operation, animals are monitored dynamically.

Laboratory research

A dog takes blood from a vein to control serum cortisol and norepinephrine levels. The results of the study at different periods of the experiment will be clear from table No. 1.

Table number 1 Criteria
Fence Dates Cortisol, nmol / L Norepinephrine, pg / ml Before surgery 220.0 ± 0.2 370.2 ± 0.2 1 day after cryodestruction 280.4 ± 0.1 450.6 ± 0.1 7 days after cryodestruction 246.2 ± 0.2 396.2 ± 0.2 14 days after cryodestruction 226.8 ± 0.2 372.4 ± 0.2 1 month after cryodestruction 218.1 ± 0.1 354.6 ± 0.1

From table No. 1 it can be seen that already 1 day after cryodestruction, a surge in the increase in the level of hormones in the cortex and adrenal medulla (cortisol, norepinephrine) is observed. In the future, there is a tendency to a decrease in the level of hormones by 14 days, and normalization of the level 1 month after cryodestruction of the adrenal gland, which proves the viability and functional activity of the unaffected areas of adrenal tissue.

Data histological examination of the material (1 day, 7 days, 14 days, 1 month). (Fig. 2, 3, 4, 5).

Figure 2 illustrates vascular disorders manifested in venous plethora, marginal standing of leukocytes, severe swelling and edema. Infiltrate is represented mainly by lymphocytes and macrophages. The glomerular and bundle zones are completely destroyed due to infiltrates and hemorrhages. In the mesh zone, areas with multiple dystrophic disturbances, an increase in cell size, multiple vacuolization of the cytoplasm, a small pyknotic nucleus, and a coarsely dispersed chromatin structure were determined.

In Fig.3, vascular disorders over inflammatory and degenerative prevail. Cortical and medulla are completely destroyed, pronounced venous congestion in the capsule. Focal lymphohistiocytic infiltrate.

Figure 4 revealed and clearly differentiated the cortical and medulla. In the cortical substance, the glomerular, bundle, and mesh zones with small focal infiltrates differentiated. In the medulla, small-cell infiltrates. In some sections of histological preparations, practically intact adrenal tissue with correctly oriented “layers” was determined.

In Fig. 5, single focal round cell infiltrates with single small hemorrhages. Small glomerular edema with small infiltrates. Edema and degeneration of the glomerular zone, small foci of fibrosis. In some areas, almost healthy adrenal tissue was detected.

The proposed method was tested in an experiment on 10 outbred dogs of both sexes and showed the effectiveness of the technique and the ability to maintain the functional activity of unaffected adrenal tissue, which is confirmed by histological and hormonal studies.

Sources of information taken into account when compiling the description

1. Adrenal neoplasms. Egiev V.N., Maistrenko N.A., Schetinin V.V. St. Petersburg, Nauka, 2007 .-- p. 146.

2. Mini-access in adrenal surgery: Opportunities and prospects. Materials XX Congress of Surgeons. Ukraine, 2002 .-- from 524.

3. Adrenal gland surgery. Kalinin A.P., Maistrenko N.A. - M.: Medicine, 2000 .-- p. 118.

4. Ablation of adrenal neoplasms. Michel D. Beland, William W. Mayo-Smith. Abdominal Imaging, USA (2009) 34: 588-592.

5. Radiofrequency ablation: other abdominal organs. Lees W.R., Gillams A. Abdominal Imaging, London (2005) 34: 451-455.

6. Adrenal hyperfunction: principles and methods of correction. Kogan A.S., Gonchar A.M., Kulikov L.K. Novosibirsk, Nauka, 1988 .-- from 204.

7. Medical materials and shape memory implants. Porous-permeable cryoapplicators of titanium nickelide, edited by V.E. Gunter, Volume 9. Tomsk, MITS Publishing House, 2010. - p. 306.

8. Anatomy of a dog and cat (Coll. Authors) / Per. with him. E. Boldyreva, I. Kravets. - M .: "AQUARIUM BEECH", 2003. - from 556.

Claims (1)

The method of cryodestruction of adrenal tumors, consisting in exposure to pathological zones with liquid nitrogen, characterized in that they act at a temperature of -196 ° C on the same local area of the adrenal gland while maintaining the same temperature density in the contact zone for three cryocycles, duration 1 min each, with a break between cycles of 1 min.

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