RU2449795C1 - Method of treating chronic pancreatitis - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine and aims at treating chronic pancreatitis. It involves superselective femoral catheterisation of branches of celiac axis, gastroduodenal or splenic arteries according to Seldinger's procedure. It is followed by continuous fractional infusion of a medicated mixture. Solutions No.1 and 2 are introduced alternately every 6 hour. The daily volume is 1.0 l. The solution No.1 contains hydrocortisone suspension 5-2.5 mg, contrical (aprotinin) 60000 Units and heparin 10000 Units in 0.25% novocaine 500 ml. The solution No. 2 contains Ringer's solution and heparin 10000 Units in 500 ml. Duration of the continuous fractional infusion is 4-6 days.

EFFECT: method allows more efficient drug-induced therapy of chronic pancreatitis by intensive local drug action.

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Description

The invention relates to medicine, namely to methods of endovascular treatment of inflammatory diseases, and can be used to treat chronic pancreatitis.

Chronic pancreatitis (CP), an incurable inflammatory and destructive disease of the pancreas of various etiologies and pathogenesis, which is based on primary or secondary, recurrent or sclerosing chronic inflammation of its connective tissue stroma. The pathogenetic mechanism of recurrent and continuous development of the disease is the interconnection and mutual activation of 3 processes:

a) inflammatory-sclerotic obstruction and destruction of the drainage structures of the gland parenchyma,

b) intraductal hypertension, self-activation of enzymes, tissue autolysis, recurrent parenchyma necrosis

c) secondary autoimmune inflammation

(Akzhigitov G.N. Pancreatitis / G.N. Akzhigitov, A.A. Grebenev, Yu.A. Nesterenko et al. / Pancreatitis. BME. T.18. Edition III. M.: Soviet Encyclopedia, 1982. P. 750-791.

Minushkin O.N. Chronic pancreatitis: some aspects of pathogenesis, diagnosis and treatment / O.N. Minushkin // Consilium-Medicum. T.4 (No. 1), 2002. Appendix: “Diseases of the pancreas”. Kucheryavy Yu.A. Extra-pancreatic changes in autoimmune pancreatitis / Yu.A. Kucheryavy // Gastroenterology. - T.9 (No. 1), 2007.)

General conservative and local endoscopic and surgical methods are used to treat chronic pancreatitis.

There is a method of treating autoimmune chronic pancreatitis with the administration of steroid drugs, starting with a dose of 30-40 mg per day (Ito T., Nishimozi I., Inuoe N., Kawabe K., Gibo J., Arita I., Okazaki K., Takayanagi R ., Otsuki M. “Treatment for autoimmune pancreatitis: consensus on the treatment for patients with autoimmune pancreatitis in Japan”, Journal of Gastroenterology, 2007, May; 42, Suppl. 18: 50-8). The same treatment is recommended by authors and patients with chronic pancreatitis without serological confirmation of its autoimmune origin. However, the general treatment of chronic pancreatitis with high doses of corticosteroids will cause undesirable consequences due to the steroid side effects on other organs and systems. In addition, steroids do not have a therapeutic effect, not the processes of enzymatic destruction of the gland parenchyma.

Closest to the claimed method (Prototype) is a method of treating acute pancreatitis by prolonged infusion into the celiac trunk and superior mesenteric artery of protease inhibitors and antibiotics described by a group of authors (Ishikava T., Imai m., Kamimura H., Ishiki T., Tsushiya A ., Togashi T., Watanabe K., Seki K., Ohta H., Ioshida T., Kamimnura T. “Therapeutic efficacy of continuous arterial infusion of the protease inhibitor and the antibiotics and via celiac and superior mesenteric artery for severe acute pancreatitis - pilot study ”Hepatogastroenterology, 2009, Mar-Apr; 56 (90); 524-8).

The prototype mismatch with the method proposed by the authors consists in treating another pancreatic disease (acute pancreatitis) with a different pathogenesis, using a different composition of infusate for local intensive drug therapy, as well as catheterizing the larger supply main arteries with a wider abdominal region of drug perfusion, including the stomach , liver and intestines.

The authors propose a method for the treatment of CP by superselective endovascular catheterization of the branches of the celiac trunk (gastroduodenal, splenic arteries) and prolonged infusion of the drug mixture, including suspended hydrocortisone and contracal (aprotinin), as well as heparin and novocaine.

The technical result of the proposed method is to increase the effectiveness of treatment of CP due to the use of pathogenetically targeted drugs (hydrocortisone and contracal), reducing their negative overall effect on the body by using minimum daily doses, enhancing the local effect of the drug mixture on the pancreas by catheterizing the branches of the celiac trunk and their drug (temporary) microembolism with hydrocortisone crystals.

The technical result is achieved by the fact that they produce a superselective femoral catheterization of one of the branches of the celiac trunk, gastroduodenal or splenic artery, depending on the location of the most affected segment of the pancreas and for 4-6 days perform continuous, fractional arterial infusion of the drug mixture with a daily volume of 1.0 l, by alternating, for 6 hours, an infusion of solution No. 1 containing in 500 ml of a 0.25% solution of novocaine 5-2.5 mg of hydrocortisone, 60,000 IU of contracal (aprotinin ) and 10000 PIECES of heparin, and solution No. 2 containing in 500 ml of Ringer's solution 10000 PIECES of heparin.

The proposed method is illustrated by figures 1-5.

Figure 1 In a blood smear mixed with a suspension of hydrocortisone, the sizes of red blood cells and hydrocortisone crystals are compared, which determine the mechanism of a temporary drug microembolism.

Figure 2 (A and B) The data of one of the methods for visualizing and monitoring the treatment of inflammatory and destructive changes in the pancreas - multispiral computed tomography.

Figure 3 (A and B) The superselective arteriography of the gastroduodenal artery, as well as contrasting the splenic artery, is performed immediately after catheterization (A) and before removal of the catheter at the end of the infusion (B), to control the intervention technique and its consequences.

Figure 4 (A, B, C, D) Reoarteriogastrography reflects arterial blood flow in the basin of the gastroduodenal artery (right gastro-omental artery). Its registration before the infusion, during its course and after the end allows you to control the dynamics of local blood supply in the infusion zone during treatment.

Figure 5 (A, B) An immunographic study of the intensity of the general and local inflammatory response, as well as the activity of humoral and cellular immunity reactions before and at different times after arterial infusion, which controls the leading pathogenetic mechanism of CP.

The method is as follows:

In X-ray surgery, under local anesthesia, femoral catheterization of the gastroduodenal or splenic branches of the celiac trunk is performed according to the main focus of the inflammatory-sclerotic lesion of the gland. An angiographic catheter of 3F or 4F caliber is used. Initial angiography of the organ arterial branch is performed. The catheter is fixed to the skin of the thigh, filled with a solution of heparin and its cannula is closed with a stopper.

In the intensive care unit, an infusomat is connected to the catheter and for 4-6 days a long intra-arterial organ infusion of solutions No. 1 is carried out - 0.5 l and solution No. 2 - 0.5 l alternately for 6 hours.

After the end of the infusion in the X-ray room, a final control organ arteriography is performed and the catheter is removed. A pressure bandage is applied to the site of the puncture of the femoral artery for 1 day, bed rest is prescribed in the ward at this time.

Subsequently, before discharge from the hospital, the treatment results are monitored by reoarteriogastrography, immunological blood tests. Ultrasound, MRI, MSCT, CT, biochemical blood tests, etc. It is advisable to monitor the patient on an outpatient or inpatient basis at different periods of treatment according to his condition.

Clinical observation:

Patient A., 46 years old, was admitted to the hospital on 05/19/10 (I / B 1-4283) with complaints of recurrent epigastric pain after eating, diarrhea. Has been ill since 2008. In 2009, he underwent surgery for corpus cystic adenoma of the pancreas tail - corpus caudal gland resection, splenectomy. Upon admission, a comprehensive examination was conducted. The diagnosis of chronic pancreatitis, the condition after corpus caudal resection of the pancreas. Hypertension 2 tbsp.

05/28/10 endovascular intervention - superselective catheterization of the gastroduodenal artery. An infusomat was connected in the ward and for 4 days a fractional arterial infusion of 500.0 ml per day of the drug mixture No. 1, containing 0.25% novocaine solution, a suspension of hydrocortisone 2.5 mg, contracal 60,000 units, heparin 10,000 units, and 500.0 ml / day of mixture No. 2, which included 0.25% Ringer, heparin 10,000 units.

The patient underwent intra-arterial infusion into the gastroduodenal artery quite satisfactorily, without signs of a violation of the main systems of homeostasis, without pain in the epigastrium. Disturbances and complications of medical intervention were not noted.

06/04/10 in satisfactory condition, without complaints of abdominal pain, was discharged home.

06/23/10 outpatient examination - does not feel pain in the abdomen, there are no other complaints either. Disability restored, returned to previous work.

The results of a specialized examination of patient A. before and after intra-arterial infusion at different times are given in comparison (Figure 2-5).

Figure 2. Abdominal CT scan

A. Before infusion, 05/15/10, the size of the head of the pancreas is within 45 × 38 mm (N = 22 × 29 mm), the contours are clear, uneven. The structure of the parenchyma is heterogeneous, there is a single petrificate. The body and tail of the pancreas are not visualized.

B. After infusion 06/22/10 head of the pancreas with dimensions 32 × 16, 5 × 36 mm. Its contours are quite clear, the structure is homogeneous, additional formations and pathological accumulation of contrast are not determined, the density in the arterial phase is 72 units of HU.

Figure 3 Superselective arteriography of the gastroduodenal artery (A) immediately after catheterization and before removal of the catheter (B). Angiograms indicate that during the infusion of the drug mixture, depletion of the organ arterial network did not occur.

Figure 4. Reoarteriogastrographic control of arterial blood flow in the stomach and indirectly in the gastro-duodenal artery during infusion.

A. RAGH immediately after catheterization of the gastroduodenal artery 25/05/10. A decrease in the pulse blood filling of the arteries of the stomach was noted, which may be associated with mechanical and reactive narrowing of the lumen of the arteries.

B. RAGH during infusion during the period of drug microembolism of microcirculatory vessels 05/29/10. A sharp narrowing of the small arteries of mechanical and functional origin is recorded.

B. RAGH after the termination of infusion and removal of the catheter on the 5th day (05/30/10), pulse blood flow indicators exceed the initial level.

G. RAGG in the following days (06/03/10) - normalization of arterial blood flow in the basin of the gastroduodenal artery.

Figure 5. Immunograms performed before (A) and after (B) organ intraarterial infusion.

A. Lack of effector functions PMNL 2 tbsp. An increase in the number of K, NK - cells.

B. Lack of effector functions PMNL 4 tbsp. T-lymphopenia 3 tbsp. Activation of cytotoxic lymphocytes. An increase in the production of immunoglobulin class A, a decrease in the production of immunoglobulin class G.

The inhibition of the inflammatory phagocytic reaction, as well as cellular and humoral immunity, which has occurred after infusion, is detected.

Thus, as a result of X-ray endovascular intervention according to a comprehensive examination in the near and early stages after it was noted:

a) The absence of adverse effects and complications associated with the application of the proposed method of treatment.

b) The disappearance of pain in the epigastrium.

c) Temporary reactive functional nature of arterial blood flow disturbances in the gastroduodenal artery basin. The absence of persistent arterial disorders due to drug arterial microembolism.

d) A marked decrease in the inflammatory phagocytic reaction, as well as cellular and humoral immunity reactions.

e) The reduction in size and the restoration of a homogeneous structure of the gland parenchyma as indicators of relief of chronic inflammation.

The claimed invention allows to increase the effectiveness of conservative minimally invasive drug treatment of chronic pancreatitis by:

a) the use of drugs (hydrocortisone and contracal (aprotinin), which have a pronounced pharmacological inhibitory effect on the leading pathogenetic mechanisms of the disease

b) reducing their overall adverse effect on the body through the use of minimum daily doses and enhancing their local effect on pancreatic tissue by significantly increasing the concentration in the organ microcirculatory blood flow, which is achieved by superselective catheterization of the branches of the celiac trunk and prolonged arterial infusion of the drug mixture containing these drugs .

c) reproducing a special method of pharmacokinetics — local arterial drug microembolism during the infusion of a suspension of hydrocortisone microcrystals.

The described method for the treatment of chronic pancreatitis can be used in patients without surgical complications of the disease as the main intervention or used at different times after surgical treatment of complications of pancreatitis.

Claims (1)

A method of treating chronic pancreatitis by prolonged arterial infusion of a drug mixture, including suspended hydrocortisone and aprotinin, characterized in that they produce super selective selective femoral catheterization of the branches of the celiac trunk, gastroduodenal or splenic arteries, according to Seldinger, and continuous fractional drug infusion is performed for 4-6 days daily volume of 1.0 l by alternating after 6 hours of introducing a solution of No. 1 containing in 500 ml of a 0.25% solution of novocaine 5-2.5 mg of suspension ii hydrocortisone ED 60000 kontrikala (aprotinin) and 10000 IU heparin and 500 ml №2 solution containing Ringer's solution, and 10,000 units of heparin.

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