RU2644934C1 - Method for endoscopic treatment of gastroduodenal ulcers - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: endoscopic treatment of gastroduodenal ulcers is carried out after stable hemostasis is achieved. Injections of autoplasma enriched with platelet growth factors are made by an endoscopic injector into the paravasal zone submucally into the submucosal and partially muscular layer. The autoplasma is injected 1.0-3.0 ml per 1 injection under the bottom of the ulcerative defect along its perimeter at 4-5 points. On the surface of the defect, 1-5 ml of Hemocompact glue is applied.

EFFECT: method allows to shorten epithelization and healing time of an ulcerous surface and to reduce the time of surgical treatment, to reduce the risk of relapses.

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Description

The invention relates to endoscopic methods of treating gastroduodenal ulcers. In recent years, methods of local treatment of this complex disease by introducing various drugs through the endoscope are becoming more widespread.

The prevalence of peptic ulcer of the stomach and duodenum in Russia does not decrease and now, according to various authors, amounts to about 1.5-10% of the adult population, mainly under the age of 50 (Amelchugova O.S., Tretyakova O.V. et al. , 2014, Sorokina E.A., 2015).

Depending on the localization, ulcers of the stomach (cardiac and subcardial sections, the body of the stomach, antrum, pyloric canal), duodenum (bulb, post-bulbar section), as well as combined stomach and duodenal ulcers (Kuzin M.N., Subbotin AM with et al., 2014).

More recently, antibiotics began to be used against peptic ulcer to get rid of its main cause - Helicobacter pylori bacteria. The Second Maastricht Agreement puts in the first place among the indications for anti-helicobacter therapy gastric ulcer and duodenal ulcer, regardless of the phase of the disease (exacerbation or remission), including their complicated forms (Malfertheiner P., Megraud E, Morain C. O 'et al., 2002). However, drug treatment of peptic ulcer has a limitation associated with the systemic effect of drugs on the body, which is accompanied by the appearance of side effects, so the priority is the use of methods and means that act locally on the ulcerative process of the gastric mucosa. In this direction, the most appropriate and promising is the use of endoscopic methods in combination with local drug exposure, i.e. drug delivery to the focus of the disease.

The use of endoscopic methods in the complex treatment allows optimizing the results of treatment, reducing the healing time of chronic ulcers by 10-15 days. For endoscopic ulcer therapy, drugs such as solcoseryl, methyluracil, which improve tissue regeneration, silver nitrate solutions that form a biological active film, solutions of calendula, sea buckthorn oil, autofibronectin, etc. are used. (Kerin V.V., Glazov A.V. et al.).

The prototype of the invention is an endoscopic method for the treatment of peptic ulcer RU 2141830 C1 “A method for the treatment of duodenal ulcer” (Patent holder “State Scientific and Clinical Center for Miners' Health”), in which, during endoscopy, 15-20 ml of autoplasmic heparin cryoprecipitate is applied to the area of the ulcer defect, heated to room temperature, in a dosage of 2-3 ml, for 10-15 minutes. In this case, therapeutic endoscopy is performed 2-5 times.

The disadvantage of this method is the complexity of the non-standardized manufacture of the introduced type of autoplasma and the absence of a clinical test of effectiveness in gastric ulcer. Also, our claimed method allows to achieve flattening of the bottom, raised bottom of the ulcer, the appearance of regional epithelialization already on the 4th day, and not “scarring” on the 7th day, as described in the prototype. In addition, we use Hemocompact glue as an applicant for synergy of the hemostatic effect, which has the protective properties of aggressive hydrochloric acid. Therefore, the duration and number of therapeutic endoscopies of our invention, sufficient to level the symptoms and scarring, is 1 time, and not 2-5, as in the prototype.

Also known is the “Method of treating ulcerative pyloroduodenal stenosis”, RU 2527336 C2 (Patent holder “State budgetary institution of higher education of the Chita State Medical Academy of the Ministry of Health of the Russian Federation”), which also injects the patient’s platelet-rich blood plasma into the gastric mucosa. The introduction of autoplasma is carried out along the edge of the scar-altered tissues of the pyloric canal, along the entire perimeter evenly in 6 points of 0.2 ml. Then, daily for 5-8 days, they act on the stenosed area of ionized argon plasma in the mode of monopolar spray coagulation with a power of 30 W, with an argon feed rate of 1.5 liters per minute for 5-6 seconds, the number of exposures per session is from 3 to 5.

The disadvantage of this method is the use of an endoscopic argon plasma coagulation method, which is additional to injections of platelet-rich autoplasma, which significantly complicates and increases the cost of this surgical treatment. Despite the significant similarities between the pathology and therapeutic mechanism of action, the effectiveness of this method, in addition, has not been proven precisely with gastroduodenal ulcers.

An endoscopic method for treating gastroduodenal ulcers RU 2097048 C1 “A method for treating gastroduodenal ulcers” (Patent holder Sataev Valery Uralovich) is also known in patients under 14 years of age, in which the ulcer surface is previously cleaned from fibrinous plaque using a 3% solution, hydrogen peroxide, washed with water, rinsed air, sightly apply a preparation heated to body temperature of the patient containing autofibronectin, the concentration of which is 2-2.5 mg / ml of solution.

The disadvantage of this method is the lack of clinical efficacy testing in patients after 14 years, because the pathogenesis of the disease in this age period is very different, as well as the complexity of the endoscopic procedure and preparation of the type of autoplasma used.

The aim of the invention is to reduce the time of epithelialization and healing of ulcers and reduce the time for surgical treatment.

A method of treating gastroduodenal ulcers is as follows: autoplasma is injected submucosally into the paravasal zone, departing 1-2 mm from the source of hemorrhage, from 4-5 points, 1.0-3.0 ml per 1 injection. The injection is carried out perpendicularly, the plasma is introduced into the submucosal and partially muscle layer of the organ, where the necessary tension is infiltrated. For one endoscopic procedure, from 5 to 15 ml of the drug is administered in total. The exact amount of autoplasma is determined by the size of the ulcer. The procedure is carried out once and after it continues only standard therapy. After a single procedure, there was a decrease in fibrinous plaque on the ulcer, relief of the inflammatory process and a decrease in the size of the ulcer surface by 1.5-2 times. At the end of the full course of treatment (4-7 days), patients are undergoing conservative therapy and follow-up with follow-up FEGDS after 1, 3 and 6 months.

In order to improve the terms of ulcer epithelization and prevent the recurrence of bleeding before using Hemocompact glue, we used autoplasma enriched with platelet factors (OTPA).

The method of obtaining our type of OTPA was as follows. Through a specialized intravenous catheter (butterfly for blood extraction PE, Plazmolifting company), with minimal trauma to the vein in the elbow bend, the patient's blood was taken in special sterile tubes with a volume of 8 ml, in compliance with aseptic rules. OTPA was obtained by collecting blood in specialized PlasmoliftingTM tubes (8 ml). The mode of centrifugation is 4000 rpm for 5 minutes, on a PE-6910 centrifuge Plazmolifting (Russia).

The OTPA thus obtained is a plasma in which the platelet concentration in it is 3-3.5 times higher than normal. Normal platelet concentration averages 220,000 cells per 1 μl. A platelet concentration in OTPA of approximately 400% of their level in peripheral blood is considered clinically effective. it should contain ≥1 million platelets in 1 μl (Marx R.E., 2004). However, a greater variability in the concentration of platelet-derived growth factors (Creaney L. et al., 2008) has been reported in the literature, their clinical efficacy has been demonstrated even at a lower concentration (Creaney L. et al., 2008; Sanchez M. et al., 2008) . OTPA contains seven major growth factors: PDGF, pDEGF, TGF (α and β), VEGF, EGF, FGF and IGF (Aminova Z.M. et al., 2012; Floryan K. et al., 2004; Sanchez M. et al., 2008).

To improve the effectiveness of endoscopic therapy, a multicomponent Hemocompact hemostatic adhesive, registered in the Russian Federation and entered into the state register of medical devices and medical equipment (registration certificate No. FS 01032005.2045), was applied to the ulcer surface after autoplasma injections. The certificate of conformity is issued according to the certification system of Gosstandart of Russia No. ROSS 1Sh IM09. VO 1332.

The glue is intended mainly for stopping and preventing acute gastroduodenal bleeding and preventing their relapses, other endosurgical and surgical interventions in gynecology, traumatology as a hemobtatic sealing material to prevent bleeding at surgical sites and to prevent relapse.

The glue is made of the following substances:

- an aqueous solution of feracryl 1%, manufactured by the Chemical farm of the city of Usolye - Sibirsky, FSP - 2-11, registration certificate No.000 / 55 of 01.01.2001;

- sodium alginate, produced by the Arkhangelsk algae plant, registration certificate No. 000/01 of 01/01/2001;

- acetic acid (dry cleaning) for pharmacology, the content is not lower than 99.85% according to GOST 61-75, GOST 2654-86. Manufacturer "Nitrogen";

- distilled water for pharmacology, according to GOST 6709-72, produced on Akvadistillyator brand DE4 firm "Analit - Service."

For a clinical study of the method, 29 patients with bleeding who were endoscopically injected with autoplasma enriched with platelet factors were selected, and then 1-5 ml of Hemocompact glue was applied to the ulcer surface, depending on the size of the defect.

The depth of ulcers in patients ranged from 0.2 cm and more than 1 cm, while more often deep ulcers were localized in the body of the stomach, in the duodenum, the average depth of ulcers ranged from 0.3 cm to 0.5 cm, and more often on the back wall of the intestine. Conservative therapy and stopping bleeding by various methods of endoscopic hemostasis in an isolated and combined form were performed for all patients with UHD.

After stable hemostasis was achieved by isolated or combined methods, with the Forrest IIc endoscopic picture, in order to prevent recurrence of bleeding and accelerate the process of ulcer epithelization, endoscopic injections of autoplasma enriched with platelets into the submucosal layer along the perimeter of the ulcer were performed in 4-5 places.

All 29 patients were previously taken through a specialized intravenous catheter for blood sampling according to the method described above. Plasma was obtained by centrifuging the blood of patients, from which a solution of autoplasma enriched in platelet factor was prepared.

Control endoscopy was performed every 2 days. During control examinations, it was found that as a result of treatment, including endoscopic injections of OTPA and the use of Hemocompact glue, it was possible to accelerate the process of epithelialization of gastric and duodenal ulcers (duodenal ulcer) expressed in the appearance of granulations in the ulcer area on 4.1 ± 1.3 days of treatment. Ulcer healing occurred on 9.4 ± 1.9 days. During the hospital stay, all patients had no recurrence of bleeding. Patients were discharged in satisfactory condition for outpatient treatment, where they received antiulcer therapy. Patients were discharged on 14.1 ± 1.5 days.

Positive endoscopic and clinical effects were obtained in all 29 patients, i.e. in 100% of cases. Follow-up observations over 1.5 years showed that in 27 patients the healing effect was persistent, 2 patients required a second course of endoscopic autoplasma treatment after 1.5 years, which is associated with the refusal of maintenance therapy, violation of diet and diet.

Thus, the advantages of our method of endoscopic treatment include its increased effectiveness, shortening the duration of the procedure, safety, affordability and low cost. The use of endoscopic injections of autoplasma with OTPA along the perimeter of the ulcer accelerates the process of epithelialization of gastric ulcers and duodenum by 2 times, reducing the likelihood of recurrence of bleeding. After two or three treatment procedures, the disappearance of pain and other symptoms accompanying the disease are noted. We give clinical examples:

Example 1. Patient Z., 58 years old, was admitted to the admission department on 05/11/16 with a clinic of the completed YAGDK. The first symptoms of bleeding appeared 20 hours ago. A peptic ulcer history for 12 years, when a stomach ulcer was first detected with endoscopy. True bleeding arose for the first time. Previously, with exacerbations of peptic ulcer, he received drug treatment 1-2 times a year. Last exacerbation 2 years ago.

During examination of the patient by the arriving team: the condition is serious, lethargic, adynamic, the skin is pale. Pulse 102 in 1 minute, blood pressure 110/85 mm Hg General blood test: Нb-85 g / l, erythrocytes - 2.5 × 1012 / l. The patient underwent emergency endoscopy: found a stomach ulcer measuring 1.5 × 2.0 cm, depth to 0.4 cm, oval. The ulcer is located along the lesser curvature and is covered with a blood clot, from the blood clot continued bleeding is noted. Around the ulcer, point hemorrhagic foci were found.

Conclusion: Gastric ulcer, lesser curvature, gastric bleeding Forrest Ib.

The patient performed combined endogemostasis. After endohemostasis, given the serious condition, but in the absence of bleeding, the patient was transferred to the intensive care unit.

In the intensive care unit, intensive therapy of posthemorrhagic anemia and antiulcer therapy have been started. After the condition improved, after 2 days a control endoscopy was performed, a gastric ulcer was found with undercut, friable edges measuring 1.5 × 2.0 cm, with a black scab at the bottom, and no signs of bleeding were found. Endoscopic injections of the patient’s autoplasm enriched with platelet factors into the submucosa in 4 places along the lower semicircle of the edges of the ulcer defect and the use of Gemocompact glue were performed. The next day he was transferred to the surgical department, where the course of conservative anti-ulcer treatment was continued. On the 6th day after admission to the clinic (05.17.2016), a control endoscopy was performed. The gastric ulcer is flat and clean along the lesser curvature, the size is 1.3 × 1.8 along the lower semicircle of the edges of the ulcer defect, pronounced epithelization occurs, the edges are not undercut, which cannot be said about the opposite semicircle, where autoplasma injections were not performed.

May 31, 2016, in satisfactory condition, was discharged home. A follow-up examination in June 20, 2016, recurrence of peptic ulcer and relapses of the HCC was not noted.

Example 2. Patient G., 46 years old, was admitted to the emergency department with a diagnosis of Peptic ulcer in the acute stage, concomitant chronic duodenitis.

From the anamnesis, exacerbation of peptic ulcer a third time during the year. Prior to this, he received conservative therapy for 6 weeks.

Suffers from peptic ulcer for 6 years. Twice a year exacerbation of an ulcer. He was treated on an outpatient and inpatient basis with temporary success. Last aggravation from 10/15/2015. He was treated on an outpatient basis, received oral proton pump inhibitors and anti-Helicobacter pylori drugs. Due to the lack of effect, 10/30/2015 was hospitalized in the therapeutic department, where he received a complex of antiulcer drugs (proton pump blockers, antibiotics, antacids, vitamins). Against the background of the treatment, the pain syndrome decreased, but there was no endoscopically positive dynamics. FEGDS-control from 10.11.2015 an ulcer on the lesser curvature of the stomach 2 cm in diameter, moderate perifocal inflammation.

A course of endoscopic treatment with the use of OTPA and Hemocompact was carried out, with a reduction in drug therapy, only ranitidine 150 mg was taken at night.

During endoscopy, 15 ml of OTPA were injected into the area of the ulcer defect, 3 ml in a dose, 5 times over 15 minutes, followed by the application of Hemocompact glue. After the procedure, the patient did not eat for 3 hours. On the fifth day after the start of treatment with control FEGDS at the site of the ulcer defect, restoration of the glandular epithelium, the absence of dystrophic changes, the defect decreased to 1 cm, the bottom is filled with granulation tissue.

Subsequently, the patient received conservative antiulcer therapy, including oral proton pump inhibitors and anti-Helicobacter pylori. FEGDS control 10 days after endoscopic use of autoplasma and Hemocompact: the defect healed.

Claims (1)

A method for endoscopic treatment of gastroduodenal ulcers, including the use of autoplasma, characterized in that injections of autoplasma enriched with platelet-derived growth factors are carried out by an endoscopic injector in the submucosal layer under the bottom of the ulcer defect at 4-5 points, followed by the application of Gemocompact glue on top of the ulcer surface.