RU2462266C2 - Method for regional infusion chemotherapy of hepatic metastases - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely oncology, and may be used in conducting the regional infusion chemotherapy of hepatic metastases. That is ensured by introducing a chemopreparation into an artery feeding a metastatic centre that is followed by occlusion of arterial branches. Before introducing the chemopreparation in areas of the hepatic parenchyma adjoining the metastatic centres, 15% sodium fumarate 200-300 ml is introduced at 0.5-1.0 ml/sec.

EFFECT: use of the given method enables reducing or eliminating side reactions of the chemotherapy.

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Description

The inventive method relates to medicine, in particular to the management of patients with metastatic liver damage caused by malignant lesions of the intestine and other abdominal organs.

With morphological confirmation of malignant liver damage, there may be cases when surgical intervention (tumor resection) is undesirable. So, in the presence of unresectable metastases, with a very high risk of extensive resections, and in case the patient refuses surgical intervention, the only method of treatment is regional infusion chemotherapy.

Regional infusion chemotherapy includes the introduction into the artery that feeds the metastatic lesion, a chemo preparation in the form of an oil suspension and subsequent mechanical occlusion of the arterial branches, for example with pieces of a hemostatic sponge. [Ed. A.I.Granova and M.I. Davydova. Interventional radiology in oncology. St. Petersburg: Tome, 2007, p. 154-156.]

Regional infusion chemotherapy leads to hypoxic and cytostatic damage to tumor foci (metastases) by reducing their arterial blood supply and introducing cytostatic drugs into them.

However, the introduction of chemicals and embolizing agents is inevitably accompanied by lysis and destruction of not only tumor cells, but also liver cells, namely hepatocytes. Because of this, patients soon after the administration of chemotherapy develop liver failure of varying severity, which manifests itself in a decrease in the protein-synthetic, detoxifying functions of the liver, hyperbilirubinemia, jaundice, hepatomegaly, which is accompanied by disorders of the central nervous and cardiovascular and excretory systems, sometimes the phenomena of hemorrhagic diathesis. All this additionally weakens the patient who has already undergone a serious operation, and can lead to the refusal of further treatment.

The result, the achievement of which the claimed invention is directed, is to reduce or eliminate adverse reactions during regional infusion chemotherapy.

This result is achieved by the fact that in the method of regional infusion chemotherapy of liver metastases, including the introduction into the artery that feeds the metastatic lesion, the chemotherapy drug and subsequent mechanical occlusion of the arterial branches, before administering the chemotherapy drug to the areas of the hepatic parenchyma adjacent to the metastatic lesions, 200-300 ml are administered % of an initial solution of sodium fumaric acid at a rate of 0.5-1.0 ml / sec.

A 15% aqueous solution of fumarate sodium, known under the brand name "Confumin" [RU No. 2189813, 2002] is approved for clinical investigation (permission of the Ministry of Health and Social Development of the Russian Federation No. 304 of 07.25.07).

As a chemotherapeutic drug, doxorubicin, oxaloplatin, epirubicin, mitomycin were used. C, gemcitabine; chemotherapy drugs were administered alone (chemoembolization) or together with an oil solution (oil chemoembolization) depending on the state of metastases.

To perform regional infusion chemotherapy, patients underwent diagnostic angiography of the liver vessels, and a catheter was inserted into the artery feeding the metastatic nodes. Before catheter chemoembolization of the hepatic artery (HEPA), 200 ml of confumin was injected through the catheter, and before oil chemoembolization of the hepatic artery (MCEPA) 300 ml of confumin. Then, immediately after the same catheter, chemoembolizate (chemotherapy, hemostatic sponge, with CEPA) or oil chemoembolizate (chemotherapy, hemostatic sponge, Lipiodol oil solution, with MHEPA) was administered.

Further, the claimed invention is illustrated by examples, but not limited to.

Example 1

A 64-year-old patient F. (and / or No. 89764) was admitted to the oncological and proctology department of the city clinical oncology dispensary in St. Petersburg on 10.01.08 with a diagnosis of sigmoid colon cancer T4N1M1 (liver) (histology - moderately differentiated adenocarcinoma) with subcompensated stenosis. The diagnosis is made clinically, endoscopically and radiologically. Concomitant diseases: coronary heart disease (CHD), grade 2 hypertension (GB 2), atherosclerotic cardiosclerosis.

After preoperative preparation, January 18, 2008, an intra-abdominal resection of the sigmoid colon was performed. The operation lasted 1 hour 10 minutes. Ultrasound examination and intraoperative revision of the abdominal cavity revealed 3 metastatic nodes in the 5th segment of the right lobe of the liver.

02/15/08 was transferred to the Department of X-ray surgical treatment and diagnosis (ORHMDiL) city cancer dispensary.

After diagnostic angiography, selective catheterization of the branches of the own hepatic artery was performed. Then, the catheter tip was inserted into the artery supplying the metastatic node with the introduction of 200 ml of confumin before HEPA. The administration of confumin was carried out in healthy areas of the hepatic parenchyma adjacent to the metastatic nodes. The rate of administration of confumin was 1 ml / sec. Then, chemoembolizate was introduced into the right hepatic artery.

After the introduction of chemoembolizate, a decrease in pain in the liver was noted; from 2 days there was an increase in the protein-synthetic function of the liver, normalization of aminotransferases, bilirubin, fibrinogen, prothrombin index, normalization of electrolyte balance, buffered blood bases and an increase in blood pH.

Example 2

A 70-year-old patient G. (w / w No. 89957) was admitted to the oncological and proctology department of the city clinical oncology dispensary in St. Petersburg on March 20, 2008 with a diagnosis of rectal cancer T4N0M1 (liver) (histology - highly differentiated adenocarcinoma) with subcompensated stenosis. The diagnosis is made clinically, endoscopically and radiologically. Concomitant diseases: coronary heart disease, GB 3, atherosclerotic cardiosclerosis.

After preoperative preparation, 03/28/08, peritoneal-perineal rectification of the rectum was performed. The operation lasted 2 hours 40 minutes. Ultrasound examination and intraoperative revision of the abdominal cavity revealed 2 metastatic nodes in 3 segments of the left lobe of the liver.

04/20/08 was transferred to the Department of X-ray surgical treatment and diagnosis (ORHMDiL) city cancer dispensary.

After diagnostic angiography, selective catheterization of the branches of the own hepatic artery was performed. Then, the catheter tip was inserted into the artery supplying the metastatic node with the introduction of 300 ml of confumin before MHEPA. The administration of confumin was carried out in healthy areas of the hepatic parenchyma adjacent to the metastatic nodes. The rate of confumin was 1 ml / sec. Then, the oil chemoembolizate of super-liquid lipiodol (Lipiodol ultra fluid, Bik Gulden GmbH, Germany) was injected with the chemotherapy into the left hepatic artery. As a chemotherapeutic drug, 50 mg of oxaloplatin was used. Then, the arterial blood flow was reduced with pieces of a hemostatic sponge.

After the introduction of chemoembolizate, a decrease in pain in the liver was noted; from 2 days there was an increase in the protein-synthetic function of the liver, normalization of aminotransferases, bilirubin, fibrinogen, prothrombin index, normalization of electrolyte balance, buffered blood bases and increased blood pH.

Example 3. (Control)

Patient D., 57 years old (and b / w No. 90641), was admitted to the oncology and coloproctology department of the city clinical oncology dispensary in St. Petersburg on 12.09.08 with a diagnosis of transverse colon cancer T4N2M1 (liver) (histology - moderately differentiated adenocarcinoma) with subcompensated stenosis. The diagnosis is made clinically, endoscopically and radiologically. Concomitant diseases: coronary heart disease (CHD), grade 2 hypertension (GB 2), exertional angina 2 fc, atherosclerotic cardiosclerosis, non-insulin-dependent diabetes mellitus.

After preoperative preparation, 01/18/08, an intra-abdominal resection of the transverse colon was performed. The operation lasted 1 hour 10 minutes. Ultrasound examination and intraoperative revision of the abdominal cavity revealed 3 metastatic nodes in the right lobe of the liver.

10/06/08 was transferred to the Department of X-ray surgical treatment and diagnosis (ORHMDiL) city cancer dispensary.

After diagnostic angiography, selective catheterization of the branches of the own hepatic artery was performed. Then, chemoembolizate and a hemostatic sponge were introduced into the right hepatic artery.

Immediately after HEPA, the patient developed severe pain in the right hypochondrium, nausea, vomiting, which is associated with ischemia of healthy areas of the liver. Biochemically, an increase in aminotransferase activity of 6-8 times, a decrease in the fibrinogen of the prothrombin index, an increase in bilirubin, a blood pH, a decrease in the buffer base of the blood, and a violation of the electrolyte composition of the blood were noted biochemically.

To reduce the negative effects of regional chemotherapy in the general well-being of the patient, complex therapy was used, consisting of the introduction of antiemetics, to reduce the pain syndrome - the introduction of narcotic painkillers, infusion therapy in the oncology and coloproctology department.

As can be seen from the above examples, administration of confumin before regional chemotherapy helps to reduce hypoxic and cytostatic damage to the liver and, as a result, helps to reduce the incidence of liver failure in this category of patients.

Claims (1)

A method of regional infusion chemotherapy of liver metastases, including the introduction of a chemotherapy drug and subsequent occlusion of the arterial branches into the artery that feeds the metastatic lesion, characterized in that 200-300 ml of a 15% solution is introduced into the areas of the hepatic parenchyma adjacent to the metastatic lesions. sodium fumaric acid at a rate of 0.5-1.0 ml / s.