RU2765846C1 - Method for isolated left-sided lobular umbilical-caval liver perfusion in an experiment - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to the field of medicine, in particular to surgery, oncology, transplantology. For isolated left-sided lobular umbilical-caval perfusion of the liver, isolation of the port-caval blood flow of the left lobe of the liver and its perfusion with a pharmaceutical are carried out in the experiment. For this purpose, the umbilical vein and inferior vena cava are cannulated in the experiment, vascular formations are sealed, a perfusion contour is formed and perfusion is performed with the exception of perfusate leakage into the right lobe of the liver.

EFFECT: method makes it possible to improve the previous and offer new methods for combined treatment of multiple mono- and bilobate liver lesions, as well as to create a basis for the development of new transplantation “ex vivo” technologies in abdominal surgery.

1 cl, 3 dwg, 2 ex

Description

SUBSTANCE: invention relates to medicine, in particular to surgery, oncology, transplantation, and can be used in carrying out techniques related to the need to isolate the porto-caval blood flow of the left lobe of the liver and its selective perfusion.

Currently, the problem of treating patients with metastatic lesions does not lose its relevance. Without specific treatment, the average life expectancy of patients with liver metastases is 6-18 months, and the median survival is 4.8-12 months (Yu.I. Patyutko et al. 2011; M.F. Cherkasov, 2015; S.V. Gorchakov , 2016; Yu.A. Shavrina, 2017).

Along with this, the methods of regional pharmacotherapy are of particular relevance (A.N. Belyaev, 2015). Currently, methods of isolated liver perfusion are widely used, however, they also have a number of disadvantages: complications caused by the leakage of a chemotherapy drug into the systemic circulation, the need to use equipment to create a roundabout artificial blood flow due to a forced block of the inferior vena cava (IVC) (F. Molly, 2013; T. Voron, 2013; T. J. Vogl, 2017). Currently, there is a need to improve these methods, which will make it possible to level their negative aspects, and to develop methods applicable in combination with staged liver resections.

A method for isolated liver perfusion is known (RF patent No. 2664631, publ. 21.09.2018). In this method, the liver is isolated from the systemic blood flow, a perfusion circuit is formed, and the liver affected by metastases is perfused with an antitumor drug. However, this method requires additional technical means to create a roundabout way of artificial blood supply due to the need to block blood flow in the IVC and does not provide for the possibility of perfusion of the liver lobes separately, and therefore, in some cases, the possibilities of its use are limited.

There is a known method of isolated lobar arterio-caval perfusion of the liver in the experiment (RF patent No. 2726591, published on 07/14/2020), where the perfusion of the isolated lobe is performed through the arterial bed, and the outflow occurs through the IVC, however, it does not provide for the ability to perform perfusion through the bed of the left branch portal vein (PV), which may be necessary under certain circumstances.

A known method of intraportal infusion in emergency surgery (Belyaev A.N. Methods of pharmacotherapy in emergency surgery / A.N. Belyaev // Remedium Privolzhye, 2015. - T. 133. - No. 3. - S. 36-38), in which intraoperatively, the umbilical vein is isolated, the lumen of which is opened and bougied, followed by the introduction of a catheter for infusion. Then the catheter is brought to the anterior abdominal wall, fixed to the skin. After that, ozonized saline is injected intraportally. However, this method does not provide for the isolation of the lobar vascular bed of the liver, and therefore the risk of leakage of the pharmaceutical into the systemic circulation is inevitable. Thus, this method cannot be used in the treatment of malignant tumors as a method of high-dose regional chemotherapy.

A method for isolated left-sided lobar umbilical-caval perfusion of the liver in an experiment is proposed, the purpose of which is to perform sequential surgical techniques that allow isolating the porto-caval blood flow of the left lobe of the liver and conducting its selective perfusion with the necessary pharmaceutical preparation. This method is proposed to be used in oncology for high-dose regional chemotherapy or in combination with the methods of staged liver resections, ex vivo operations, as well as in transplantology.

The problem is solved by the fact that in the method of isolated left-sided lobar umbilical-caval perfusion of the liver in the experiment, after explantation of the cadaveric liver, EV, its left branch and IVC are mobilized, and short hepatic veins that flow into the IVC are ligated and crossed; further, the umbilical vein is mobilized in the round ligament of the liver, and its recanalization is performed; after that, a venous cannula with an outer diameter of 6 to 12 mm is installed and fixed in the umbilical vein; then install a venous cannula with an outer diameter of 12 to 35 mm in the IVC; The IVC and the left branch of the explosive are sealed to prevent leakage of the perfusate; after that, a perfusion circuit is formed by connecting the inflow system (from the reservoir with the perfusate to the liver) to the cannula in the umbilical vein, the outflow system (from the liver to the reservoir) - to the cannula in the IVC, the circuit also includes reservoirs with a solution for perfusion and for its circuit outlet collection, perfusion pump, thermostatic bath and connectors; then, to determine the interlobar border of the liver, a solution of a water-soluble dye is injected into the venous cannula in a volume of 20 to 150 ml; further, the identified interlobar border is marked with X-ray-positive objects; after that, an isolated left-sided lobar umbilical-caval perfusion of the liver is performed in the following mode: perfusate flow rate - 110-650 ml/min, duration - 20-60 min, perfusate temperature - 4-43°C; further, during perfusion, in order to control the spread of perfusate in the parenchyma and possible leakage, a water-soluble X-ray contrast solution is injected with a total volume of 100-150 ml/min, and fluoroscopy is performed.

The technical characteristics of cannulas, the composition of the contour and solution, perfusion parameters, as well as the need for X-ray contrast studies are determined depending on the actual requirements and the optimal ones are selected.

The use of this method clearly demonstrates the possibility of isolating the porto-caval blood flow of the left lobe of the liver in order to conduct its selective perfusion with a solution of the necessary pharmaceutical preparation. In addition, the method of isolated left-sided lobar umbilico-caval perfusion of the liver is indicated in cases where there is no possibility of prompt access and cannulation of the IV, and can also be an alternative to isolated lobar arterio-caval perfusion. The introduction of the presented method into clinical practice will improve the previous and propose new methods of combined treatment of multiple mono- and bilobar lesions of the liver, as well as create the basis for the development of new transplantation ("ex vivo") technologies in abdominal surgery.

These ranges were selected empirically during the experiment. The presented values of the diameter of the vascular cannulas are determined by the need to maintain proper speed indicators, and cannot be larger than the diameter of the vessels used. Since it is difficult to create adequate hydrodynamic conditions on cadaveric tissue, since the higher the diameter of the return venous cannula, the more efficient the outflow of perfusate from the liver and, consequently, the less resistance to the flow of perfusate in the vascular bed of the perfused lobe. In this regard, the diameter of the cannula in the IVC (12-32 mm) is always larger than that of the cannula installed in the umbilical vein (6-12 mm). When using cannulas of a smaller diameter, it is difficult to carry out perfusion on a liver preparation using the presented method and will not correspond to physiological ones.

With the minimum and maximum morphometric characteristics of the explanted preparation, from 20 ml to 150 ml of a water-soluble dye, respectively, was injected to determine the topography of the interlobar border. When the volume of the injected solution is reduced to less than 20 ml, conditions arise under which it is impossible or difficult to determine the interlobar boundary, which leads to experimental errors. Also, we have experimentally determined that 150 ml is sufficient for effective mapping of the portal channel, and the introduction of a larger volume of dye, from the point of view of economic justification, is not advisable.

The speed parameters of perfusion were as close as possible to physiological ones. However, they were corrected taking into account work on cadaveric tissue. Thus, at a rate of less than 110 ml/min, the efficiency of perfusion decreased, as evidenced by the nature of the distribution of the perfusate along the vascular bed. An increase in the perfusate flow rate above 650 ml/min led to damage to the cadaveric liver parenchyma, which affected the quality of the study. The duration of perfusion in the experiment was determined in accordance with the requirements of clinical practice.

The volume of injected water-soluble X-ray contrast solution from 100 to 150 ml/min was determined by the rate of perfusion. However, the introduction of a smaller volume reduced the information content of fluoroscopic data, and a larger one was inappropriate.

The invention is illustrated in FIG. 1, which shows a diagram of a perfusion circuit for performing isolated left-sided lobar umbilico-caval perfusion of the liver in an experiment, and experimental examples are given, which are explained in FIG. 1, fig. 2, fig. 3. In FIG. 2 and 3 show x-ray images obtained during fluoroscopy of an isolated left-sided lobar umbilical-caval perfusion of the liver using an x-ray contrast agent.

As shown in FIG. 1, the first stage is preparation for perfusion of the liver preparation 5. Next, an open perfusion circuit is formed by connecting the inflow system to the cannula installed in the umbilical vein and the outflow system to the cannula in the IVC - dotted lines. The circuit also includes tanks with perfusate 1 and for collecting spent perfusate 6. A thermostatic bath is installed on the path of the solution inflow to the perfused lobe 2. The movement of perfusate in the circuit creates a perfusion pump 3, the flow direction is indicated by arrows. If necessary, drugs are injected and additional devices are connected using connectors 4.

Example No. 1 - umbilico-caval perfusion of the left lobe of the liver, illustrated in Fig. 1, fig. 2.

The liver preparation was explanted from the unembalmed corpse of patient V., who died from a disease not directly related to the organ under study.

At the first stage, after preliminary preparation of the preparation, the necessary vascular formations were mobilized (IVC, VV, and its left branch), ligated, and the short hepatic veins were crossed. Next, the umbilical vein was mobilized in the round ligament of the liver and recanalized using a vascular bougie. After that, a cannula was installed and fixed in the umbilical vein (venous straight reinforced cannula 18 Fr, Maquet, Germany) 9 in Fig. 2 for the inflow of perfusate and for the outflow of perfusate, the cannula into the IVC (venous straight reinforced cannula 36 Fr, Maquet, Germany). In order to divert the perfusate into the circuit, the ends of the IVC were sealed with a twisted suture, and a vascular tourniquet was placed on the left branch of the EV.

In the second step, an open perfusion circuit was formed as shown in Fig. 1, which included the perfusate reservoir 1 in FIG. 1, thermostatic bath 2 in FIG. 1, peristaltic pump "LOIP ls-301" (manufactured by JSC "LOiP", Russia) 3 in Fig. 1, purchased with the support of the government of St. Petersburg (PSP diploma No. 18787) and injection connectors 4 in FIG. 1. To collect the spent perfusate, a container made of polymeric material 6 in FIG. 1. Then, in order to determine the interlobar border of the liver, 20 ml of 0.05% brilliant green was bolused into the cannula installed in the umbilical vein, which led to the staining of the left lobe of the liver in the color of the dye. As a result of the dye injection, the portal sign determined the interlobar border of the liver - the dotted line and triangles in Fig. 2, which was located in the projection of the line drawn between the groove of the IVC and the fossa of the gallbladder. Further, in order to compare the external topographic data with the X-ray picture, the identified interlobar border - the dotted line and triangles in Fig. 2 - marked with X-ray positive objects, indicated by circles in FIG. 2.

The third stage was the perfusion of the left lobe of the liver 8 in Fig. 2 in mode: flow rate - 110 ml/min, duration - 20 min, perfusate temperature - 4°C. During perfusion, in order to control perfusate leakage, into the venous cannula 9 in FIG. 2 introduced X-ray contrast solution "Omnipak" diluted with physiological in a ratio of 1: 1 with a total volume of 100 ml and, using the installation of X-ray diagnostic surgical mobile "RTS-612" (CJSC "NIPK" Elektron ", Russia) performed fluoroscopy, the results of which are shown in Fig. 2. The results of fluoroscopy made it possible to compare the external topographic data of the interlobar border of the liver - the dotted line with triangles in FIG. 2, and prove the possibility of determining the intrahepatic interlobar border of the liver by external signs in cases of normal anatomy. So on the radiograph, the distribution of contrast is determined within the boundaries of the perfused left lobe of the liver 8 in Fig. 2, while in the right lobe 7 in FIG. 2 contrast was not determined.

Example No. 2 - umbilico-caval perfusion of the left lobe of the liver, illustrated in Fig. 1, fig. 3.

The liver preparation was explanted from the unembalmed corpse of patient K., who died from a disease not directly related to the organ under study.

At the first stage, after preliminary preparation of the preparation, the necessary vascular formations were mobilized (IVC, VV, and its left branch), ligated, and the short hepatic veins were crossed. Next, the umbilical vein was mobilized in the round ligament of the liver and recanalization was performed using a Billroth forceps. After that, a cannula was installed and fixed in the umbilical vein (venous straight reinforced cannula 28 Fr, Maquet, Germany) 9 in Fig. 3 for the inflow of perfusate and for the outflow of perfusate, the cannula into the IVC (straight venous reinforced cannula 40 Fr, Maquet, Germany). In order to divert the perfusate into the circuit, the ends of the IVC were sealed with a twisted suture, and a vascular tourniquet was placed on the left branch of the EV.

In the second step, an open perfusion circuit was formed as shown in Fig. 1, which included the perfusate reservoir 1 in FIG. 1, thermostatic bath 2 in FIG. 1, peristaltic pump "LOIP ls-301" (manufactured by JSC "LOiP", Russia) 3 in Fig. 1, purchased with the support of the government of St. Petersburg (PSP diploma No. 18787) and injection connectors 4 in FIG. 1. To collect the spent perfusate, a container made of polymeric material 6 in FIG. 1. Then, in order to determine the interlobar border of the liver, 80 ml of 0.4% basic fuchsin was bolused into the cannula installed in the umbilical vein, which led to the staining of the left lobe of the liver in the color of the dye. As a result of the dye injection, the portal sign determined the interlobar border of the liver - the dotted line and triangles in Fig. 3, which was located in the projection of the line drawn between the groove of the IVC and the fossa of the gallbladder. Further, in order to compare the external topographic data with the X-ray picture, the identified interlobar border - the dotted line and triangles in Fig. 3-marked with X-ray positive objects indicated by circles in FIG. 3.

The third stage was the perfusion of the left lobe of the liver 8 in Fig. 3 in mode: flow rate - 510 ml/min, duration - 40 min, perfusate temperature - 21°C. During perfusion, in order to control perfusate leakage, into the venous cannula 9 in FIG. 3 introduced X-ray contrast solution "Omnipak" diluted with physiological in a ratio of 1: 1 with a total volume of 120 ml and, using the installation of X-ray diagnostic surgical mobile "RTS-612" (CJSC "NIPK" Elektron ", Russia) performed fluoroscopy, the results of which are shown in Fig. 3. The results of fluoroscopy made it possible to compare the external topographic data of the interlobar border of the liver - the dotted line with triangles in FIG. 3, and to prove the possibility of determining the intrahepatic interlobar border of the liver by external signs in conditions of normal anatomy. So on the radiograph, the distribution of contrast is determined within the boundaries of the perfused left lobe of the liver 8 in Fig. 3, while in the right lobe 7 in FIG. 3 contrast was not detected.

Thus, the possibility of vascular isolation of the porto-caval blood flow of the left lobe of the liver for its selective perfusion has been demonstrated.

Claims (1)

The method of isolated left-sided lobar umbilical-caval perfusion of the liver in the experiment, characterized in that after the explantation of the cadaveric liver, the portal vein, its left branch and the inferior vena cava are mobilized, and short, small, hepatic veins that flow into the inferior vena cava are ligated and crossed ; further, in the round ligament of the liver, the umbilical vein is mobilized, and its recanalization is performed in a blunt way; after that, a venous cannula with an outer diameter of 6 to 12 mm is installed and fixed in the umbilical vein; then install a cannula with an outer diameter of 12 to 35 mm into the inferior vena cava; the inferior vena cava and the left branch of the portal vein are sealed to prevent leakage of perfusate; after that, a perfusion circuit is formed by connecting the inflow system from the perfusate reservoir to the preparation, to the cannula in the umbilical vein and the outflow system, from the preparation to the reservoir, to the cannula in the inferior vena cava, the circuit also includes reservoirs with perfusion solution and for its circuit outlet collection, perfusion pump, thermostatic bath and connectors; then, to determine the interlobar border of the liver, a solution of a water-soluble dye is injected into the arterial cannula in a volume of 20-150 ml; further, the identified interlobar border is marked with X-ray-positive objects; after that, an isolated left-sided lobar umbilical-caval perfusion of the liver is performed in the following mode: perfusate flow rate - 110-650 ml/min, duration - 20-60 min, perfusate temperature - 4-43°C; further, during perfusion, in order to control the spread of perfusate in the parenchyma and possible leakage, a water-soluble X-ray contrast solution is injected with a total volume of 100-150 ml/min, and fluoroscopy is performed.

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