Method for regional polychemotherapy of metastatic hepatic disorder

FIELD: medicine, oncology.

SUBSTANCE: the present innovation deals with treating metastatic hepatic disorder in patients with malignant neoplasms. The method of regional polychemotherapy (RPCT) concentrates upon catheterization of proper hepatic artery (PHA) through gastro-omental artery to fulfill intra-arterial RPCT. Moreover, additionally after PHA catheterization it is necessary to catheterize an umbilical vein (UV) due to fulfilling arterio-venous shunting. For this purpose, one should connect catheters introduced into UV and PHA, with the help of a T-joint valve appliance (TVA); before carrying out RPCT it is important to conduct hepatic arterialization due to directing the blood from PHA through UV into the liver by setting TVA valves in position being open for PHA and UV; for carrying out RPCT one should locate TVA valves in position being open for introducing chemopreparations out of the system with a dosing tank of medicinal substances into PHA to carry out the infusion of chemopreparations. Seances for alternating hepatic arterialization and RPCT should be fulfilled daily once a day during the whole course of therapy. The innovation enables to simultaneously increase the concentration of chemopreparations in metastatic hepatic foci, detoxication hepatic function and sensitivity of tumor cells to chemopreparations as a result of additional preliminary oxygenation of hepatocytes.

EFFECT: higher efficiency of therapy.

1 cl, 6 dwg, 1 ex

 

The invention relates to medicine, namely to Oncology, and can be used in the treatment of metastatic liver disease in patients with malignant tumors.

In patients with malignant tumors with metastatic liver cancer is one of the promising methods of treatment is regional chemotherapy. To conduct regional chemotherapy in the localization of the pathological process in the liver using the introduction of drugs through its own hepatic artery, razbortovanny the umbilical vein, portal vein. Conducting regional chemotherapy via these vessels allows you to create a high concentration of anticancer drugs in the liver than systemic chemotherapy. A large concentration of anticancer drugs in the liver when conducting regional chemotherapy compared to the system increases the damaging effects of chemotherapeutic agents on tumor cells. However, introduced through these vessels in the liver anticancer drugs affect not only on tumor cells in metastatic lesions, but also in healthy hepatocytes. In cases where patients have concomitant liver disease (cirrhosis, hepatitis, liver failure of various etiologies) the advanced hepatocellular injury may increase the severity of liver failure, which in turn will necessitate the cessation of chemotherapy.

To improve liver function used technique, known in the literature as "arterialization" of the liver, implying not only the natural flow of arterial (oxygenated) blood through its own hepatic artery, but also additional, artificially created, introduction arterial (oxygenated) blood through the umbilical or the portal vein.

The known method arterialization of the liver, which form a continuous vascular anastomosis end-to-end between the splenic artery and umbilical vein. [Surgical Hepatology. / Edited by Petrovsky. - M.: Medicine. - 1972. - 352 S., S].

The disadvantage of this method is the difficulty of forming a vascular anastomosis between the splenic artery and umbilical vein. In many cases, in the presence of metastatic lesion of retroperitoneum catheterization of the splenic artery is impossible in General.

There is also known a method arterialization of the liver, which form a continuous vascular anastomosis between the umbilical vein and radial artery using extracorporeal shunt. This produces Bagirova umbilical vein, isolated radial artery, kanyoro it and using external shunt representing the silico the new tube, connect the catheter in the umbilical Vienna and the radial artery, and then hand the patient bandage to the body [Halperin AI, Semendyaeva M.I., Neklyudov E.A. liver Failure. - M.: Medicine, 1978. - 328 S. - P.205].

The disadvantage of this method is the difficulty of forming a vascular anastomosis between the radial artery and the umbilical vein, the need for fixing the arm to the torso, which significantly affects the quality of life of the patient.

To increase the concentration of the anticancer drug in the liver use different variants of regional chemotherapy.

There is a method of regional chemotherapy [Cytoreductive surgery for malignant liver tumors: intra-arterial regional and hyperthermic intraoperative intraperitoneally chemotherapy. / Malinowski N.N., Severtsev A.N., Brekhov H. and others // Kremlevskaya medicine. Clinical journal. - 2000. No. 2. - P.7-12], in which kateteriziruyut own the hepatic artery, followed by the introduction into it of chemotherapy.

The disadvantage of the above method is its high toxicity due to exposure to antineoplastic drugs not only on tumor cells, located in the metastatic foci in the liver, but also in healthy hepatocytes.

Also known the way re is inerney intraarterial chemotherapy Gasparyan, selected as a prototype, according to which for selective intra-arterial chemotherapy using directly the hepatic artery, entering the probe in its branches, preference is given to the gastro-epiploic artery [Gasparyan S.A., Ostroverkhov G., Trapeznikov NN. Regional long-term chemotherapy of malignant tumors. - "Medicine". - M - 1979. - 207 S., P.124-126].

The disadvantage of the above method is its relatively high toxicity due to exposure to antineoplastic drugs not only on tumor cells, located in the metastatic foci in the liver, but also in healthy hepatocytes. The disadvantage of this method often means the impossibility of its use in patients with concomitant chronic liver diseases, accompanied by the development of hepatic failure. Furthermore, the method-prototype does not enhance the sensitivity of tumor cells to the input of the drugs.

The invention solves the problem of strengthening the detoxification functions of the liver, with WATCHES, but also increase the sensitivity of tumor cells to the input of the drugs.

The problem is solved in that in patients with malignant tumors with metastatic liver cancer, suffering from various side the respective diseases, accompanied by the development of hepatic insufficiency, during catheterization own hepatic artery through gastroepiploic artery and holding intraarterial polychemotherapy additionally produce proactive arterialization of the liver, which additionally produce catheterization of the umbilical vein, connect the catheters introduced into the umbilical vein and own the hepatic artery using a tee valve device, and then within 2-3 hours produce the arterialization of the liver through the arterial blood to the liver via the umbilical vein by setting the branch valve device in the correct position, then changing the position of the tee valve device, is carried out for 4-6 hours regional polychemotherapy by the introduction of chemotherapy in private hepatic artery. In this session alternation arterialization of the liver and regional chemotherapy spend every day 1 time per day.

New in the invention is the alternation of arterialization of the liver and regional chemotherapy, and arterialization of the liver precedes the introduction of chemotherapy, which, on the one hand, allows to provide additional oxygenation of hepatocytes, and with the other hand to enhance the oxygenation of tumor cells, náchod is working in metastatic sites liver before the introduction of chemotherapy.

Increased oxygenation of hepatocytes improves the detoxification function and thus helps to reduce the toxicity of chemotherapy. In turn, the increased oxygenation of tumor cells prior to administration of chemotherapy increases their sensitivity to the effects of drugs.

Thus, the developed method allows to increase the concentration of anticancer drugs in metastatic foci in the liver by the regional sum of chemotherapy, to enhance the detoxification function of the liver due to additional oxygenation of hepatocytes, as well as to increase the sensitivity of tumor cells to chemotherapeutic drugs by their prior additional oxygenation.

The essence of the method is illustrated by drawings 1-6.

1 shows a diagram of the installation of the catheter in the umbilical vein and own the hepatic artery through gastroepiploic artery and the connection between them tee valve device, where:

1 - liver;

2 - the umbilical vein;

3 - native hepatic artery;

4 - gastro-duodenal artery;

5 - right gastroepiploic artery;

6 is a catheter inserted through the right gastroepiploic artery, the gastro-duodenal artery in its own hepatic artery;

7 is a catheter inserted in the PU is full-time vein;

8 - ground valve device.

Figure 2 shows the current arterial blood through the branch valve device in the umbilical vein during arterialization of the liver, where:

9 - cannula system for drug administration, coupled with the branch valve adaptation;

10 - body ground valve adaptation;

11 - valve tee valve adaptation;

12 - cannula catheter installed in the umbilical Vienna;

13. the cannula of the catheter is installed in its own hepatic artery;

14 - the direction of arterial blood from the native hepatic artery in the umbilical vein.

Figure 3 shows the introduction of anticancer drugs from the system in the native hepatic artery, where;

9 - cannula system for drug administration, coupled with the branch valve adaptation;

10 - body ground valve adaptation;

11 - valve tee valve adaptation;

12 - cannula catheter installed in the umbilical Vienna;

13. the cannula of the catheter is installed in its own hepatic artery;

15 - the direction of the current solution with anticancer drugs from the system in the native hepatic artery.

Figure 4 shows a flush solution heparin catheter, ustanovlennogo umbilical Vienna, where:

9 - cannula system for drug administration, coupled with the branch valve adaptation;

10 - body ground valve adaptation;

11 - valve tee valve adaptation;

12 - cannula catheter installed in the umbilical Vienna;

13. the cannula of the catheter is installed in its own hepatic artery;

16 - the direction of the current solution of heparin from the system into the umbilical vein.

Figure 5 shows the flush solution heparin catheter installed in its own hepatic artery, where:

9 - cannula system for drug administration, coupled with the branch valve adaptation;

10 - body ground valve adaptation;

11 - valve tee valve adaptation;

12 - cannula catheter installed in the umbilical Vienna;

13. the cannula of the catheter is installed in its own hepatic artery;

17 - the direction of the current solution of heparin from the system in the native hepatic artery.

Figure 6 shows the position of valve tee valve device in the period between sessions of chemotherapy

9 - cannula system for drug administration, coupled with the branch valve adaptation;

10 - body ground valve adaptation;

11 - valve tee valve lighting the mix;

12 - cannula catheter installed in the umbilical Vienna;

13. the cannula of the catheter is installed in its own hepatic artery;

The method is as follows. Produce upper median laparotomy with revision of the abdominal cavity. In the presence of metastases in the liver perform catheterization own hepatic artery. For this release of the right gastroepiploic artery 5 by Ecker et al. (1962), cut through the wall, enter the specified artery catheter 6. Hold the catheter from the right gastro-epiploic artery 5 through the gastro-duodenal artery 4 native hepatic artery 3. The presence of the catheter in its own hepatic artery is controlled by palpation. Usually the length of the introduced catheter is 12-14 see the Catheter is fixed in the right gastro-epiploic artery by ligatures. Bring on the anterior abdominal wall end mobilized the right gastro-epiploic artery entered into the catheter. The removal of the catheter in the anterior abdominal wall allows removal of the catheter in the subsequent (after completion of chemotherapy) without re-operation.

Access to the umbilical Vienna provide a cut length of 3-4 cm along the white line of the abdomen, at a distance of 3 cm above the navel. After dissection of the skin, aponeurosis and stratification transverse fascia of the abdomen in the wound l the GKO find the umbilical vein 2, lying on 1-2 cm to the right of the midline. Vienna, freed from the surrounding tissue, take in the wound and cut papersno before the arrival of the lumen. In the lumen of the vein is injected ureteric catheter or plastic tube with a diameter of 3-5 mm, If the lumen of the vein insufficient, make her Bagirova metal probe with levobrezni the end and only after that kateteriziruyut, the catheter 7 make it to the abdominal wall and fixed.

After installation and fixing of both catheters connected to the artery and vein tee valve device 8, thereby arterio-venous shunting. Remove catheters, United tee valve device, on the anterior abdominal wall, fixed to the skin, laparotomic wound is sutured in layers tightly. After the restoration of intestinal peristalsis, on average 2-4 days, start intraarterial polychemotherapy (APT) with pre-arterialization of the liver (figure 1).

The gates 11 tee valve device is switched to the position open for artery and vein (figure 2). In this position of the valves begin to produce the procedure nonauthoritative inflow of arterial blood in the umbilical vein 14. This procedure continued for 3-4 hours. The flow of arterial blood in the umbilical vein is independently due to the difference of ar is realnogo and venous pressure.

Then the gates 11 tee valve device is installed in position, open to drug administration in an artery, connecting through the system to the dispenser of drugs, whereby continuous prolonged infusions administered daily dose of anticancer drugs for 4-6 hours (figure 3).

After that, the valves 11 tee valve device is switched to the position in which access to the umbilical Vienna 2 (figure 4). Enter through the system in a catheter in the umbilical Vienna, heparin solution (16).

Then the gates 11 tee valve device is switched to the position in which access to private hepatic artery (figure 5). Enter through the system in the catheter in its own hepatic artery, a solution of heparin (17), after which the valves close access to the umbilical Vienna and native hepatic artery (6).

Procedure regional intraarterial polychemotherapy with the previous arterialization of the liver spend every day 1 time per day according to the scheme used WATCHES.

In the treatment process to provide dynamic, laboratory and biochemical control samples of blood obtained from the umbilical vein. To decrease toxicity and hepatotoxicity in umbilical ve is the injected hepatoprotectors, as well as drugs that enhance the reparative processes in the liver. Three weeks after the end of the course WEPT assess the effectiveness of therapy using ultrasound or CT, with courses WEPT repeat until achieving a complete or partial effect.

An example of clinical application of the developed method.

1. Patient W.,born in 1964 is being treated for 3 years about melanoma of the scalp.

In 2003-2004 a comprehensive treatment. At present, additional testing due to the deterioration of installed total metastatic liver damage. In the absence of other signs of metastasis decided to hold endovascular regional medication included in the planned volume phase arterialization of the portal system.

12.04.2005 performed laparotomy. Revision: confirmed metastatic lesion of both lobes of the liver, other pathological changes in the abdominal cavity is not revealed. In accordance with the agreed treatment plan the right gastroepiploic artery, it tied in the distal direction and a proximal - punctured special vascular dilator and catheterized. A catheter with a diameter of 1 mm retrograde conducted through the gastro-omental artery, through the gastro-12 duodenal art is Tory, and on reaching the mouth of the common hepatic artery conducted distal, bypassing the mouth of the right gastric artery. The catheter was recorded by the two covering the gastroepiploic artery ligatures in the area of the puncture and put through contraportada on the anterior abdominal wall.

In the round ligament of the liver allocated allitaliana umbilical vein, Bagirova along before reaching the portal system and receiving blood. It introduced a catheter with a diameter of 4 mm, a terminal whose Department is located in the portal vein. The catheter is fixed to the wound. The abdominal wall is sutured. The catheters are connected via the four-way shunt device.

Performed 1 cycle regional chemotherapy in the daily introduction of a fractional based achieve the total design cycle dose for 12 days. At 1 stage every day for 2 hours was carried out arterialization of the portal system so that the position of the shunt device ensured the flow of arterial blood in the portal system. Then there was isolated arterial infusion of chemotherapy drugs in the planned dose for 3 hours.

When control CT scan of the abdominal cavity through 1 month after treatment revealed a reduction of the metastatic foci in the liver from 3.5 cm to 0.5 cm On the proposed method treated 4 b is selected. Complications associated with toxicity of chemotherapy were observed.

The proposed sequence of actions during the execution of WATCHES allows you to simultaneously increase the concentration of anticancer drugs in metastatic foci in the liver by the regional sum of chemotherapy and enhance the detoxification function of the liver due to additional oxygenation of hepatocytes, in addition to increase the sensitivity of tumor cells to chemotherapeutic drugs by their prior additional oxygenation.

The method is tested on 18 patients with chronic concomitant diseases of the liver, accompanied by the development of hepatic failure. None were marked toxic effects after WATCHES, which would force to interrupt treatment.

1. The way of regional chemotherapy (CHT) metastatic lesions of the liver, including catheterization own hepatic artery (SPA) through the gastro-omental artery and conducting intra-arterial RPT, characterized in that it further after catheterization SPA kateteriziruyut umbilical vein (PV)by arteriovenous shunting, which connect the catheters introduced in PV and SPA, with the help of tee valve device, before RPT are arterialization of the liver through voltage is Alenia blood of the SPA through the RO to the liver through the establishment of valve tee valve device in position, open for SPA and PV, for RPT install valve tee valve device in position open for a drug administration system with dosing of drugs in the SPA, and spend infusion of chemotherapy.

2. The way of regional chemotherapy of metastatic lesions of the liver according to claim 1, characterized in that the sessions alternating arterialization of the liver and regional chemotherapy spend every day 1 time per day during the entire course.



 

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16 cl, 19 dwg

FIELD: medicine, abdominal surgery.

SUBSTANCE: one should drain biliary ducts and wash with 0.02%-sodium hypochlorite solution at the dosage of 150-200 ml, by drops, 3-4 times daily for 7-17 d. Moreover, also, during 7-17 d it is necessary to carry out infusion therapy through catheterized portal vein by applying conventional medicinal preparations and introduce 0.04%-sodium hypochlorite per 50-80 ml thrice daily. The innovation provides therapeutic efficiency at applying sodium hypochlorite in lower concentration against well known for sanitation of biliary tract that enables to decrease toxic effect of sodium hypochlorite during therapy conducted.

EFFECT: higher efficiency of therapy.

3 ex, 1 tbl

FIELD: medicine, oncology.

SUBSTANCE: method involves autoblood sample taking off in the amount 200-250 ml into a sterile flask with hemopreserving agent "Glugitsir" followed by centrifugation at 1500 rev/min for 30 min. Then supernatant plasma is placed into another sterile flask with a hemopreserving agent and cellular precipitate is reinfused. A single dose of a cytostatic agent is mixed with 10-100 ml of autoplasma, incubated at temperature 37°C for 1 h and administrated through catheter in abdominal cavity by puncture in lower quadrant of abdomen. Procedure is repeated if necessary. Method provides decreasing toxicity of chemotherapy, simple method and uniform distribution of volume of injected preparation for all abdomen cavity. Invention can be used in carrying out chemotherapy of abdomen cavity tumors with ascites.

EFFECT: improved method for treatment.

1 ex

FIELD: medical equipment.

SUBSTANCE: catheter has flexible catheter tube and device for controlled deviation of distal end part of catheter tube. Device for controlled deviation of distal end part of flexible catheter tube is made in form of wire conductor made of springing elastic material. Conductor is capable of free moving along catheter tube into neutral position or initial position. As a result, when conductor is more or less pulled in relatively its initial position, end part of flexible catheter tube does move. Conductor has twisted spiral-shaped end part which when being in neutral or initial position takes place directly in opposition to external end of catheter tube. As a result, when wire conductor is pulled in relatively its initial position inside flexible tube, the end part of tube deflects at adjusted angle under influence of compression power of twisted spiral-shaped end part, which straightens forcedly.

EFFECT: minimal invasive surgery; ability of controlling catheter tube outside patient's body.

5 cl, 2 dwg

FIELD: medicine.

SUBSTANCE: the present innovation deals with treating disorders chosen out of the group consisting of mitochondrial encephalomyopathy along with lactic academia and shock-like attacks (MELAS), neurogenic muscular fatigue, ataxia, retenitis pigmentosa/maternally inherited Li syndrome (NARP/MILS), syndrome of mitochondrial ataxia, relapsing infections, aphasia, hypouricemia/hypomyelination, attacks and aciduria of dicarbonic acids (MARIAHS), renal canalicular acidosis, Li syndrome, refractory epilepsy with deteriorations during infection, syndrome of multiple deletions mitochondrial DNA (mtDNA) and deficiency of cytochrome c-oxidase (COX, complex IV). Moreover, one should introduce efficient quantity of 2',3',5'-tri-O-acetyl-1-beta-D-uridine (triacetyluridine) for a patients who has such a disorder or with the risk for appearance of such a disorder. The innovation enables to either decrease or remove the symptoms of the diseases mentioned due to correcting the processes in synthetic pathway of pyrimidine.

EFFECT: higher efficiency of therapy.

19 cl, 5 ex, 1 tbl

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