MD1882Z - Method for minimally invasive combined treatment of esophagogastric varices in patients with decompensated liver cirrhosis - Google Patents

Abstract

The invention relates to medicine, in particular to hepatology and surgery, and can be used for minimally invasive combined treatment of varicose veins of the esophagus and stomach in patients with decompensated liver cirrhosis. The essence of the invention is that under general anesthesia, approaches to laparoscopic intervention are prepared, ascitic fluid is evacuated, abdominal organs are examined with the removal of fibrin adhesions, then ligation of vessels is performed along the greater curvature of the stomach and the fundus of the stomach to the esophagus for azygoportal disconnection using technology using high-frequency alternating current of 470 kHz, with a maximum voltage of 120 V, a current of 4 A and a maximum power of 150 W, after which, using an endoscope at the level of the esophagogastric junction in varicose veins of the esophagus and the fundus of the stomach, fibrin glue is introduced in retrograde and anterograde directions, including two components that are introduced separately by mixing them into the lumen of the vessel, namely the first component includes a fibrinogen solution, and the second component includes a mixture of thrombin solutions with a 10% solution of albumin, aprotinin and Ca+2 chloride, with the following ratio of components, per 1 ml: fibrinogen solution (mg) 15...45 thrombin solution (U) 25...100 10% albumin solution (ml) 10...20 aprotinin solution (AKE) 250...1000 Ca+2 chloride solution (μmol) 15...30.

Description

[0001] The invention relates to medicine, in particular to hepatology and surgery, and can be used for combined minimally invasive treatment of esophageal-gastric varices in patients with decompensated liver cirrhosis.

[0002] Hemorrhage from esophageal and gastric varices is one of the most serious complications of portal hypertension and is the main cause of death in patients with cirrhosis. In the case of compensated cirrhosis, namely in 40% of these patients, esophageal varices are present (D'Amigo G. et al. Pharmacological treatment of portal hypertension an evidence-based approach. Seminaries Liver Disease, 1999, vol. 19, p. 475-505). This rate increases to 60% if the patient presents ascites, i.e. in the case of decompensated cirrhosis (Schepis F. et al. Which patient with cirrhosis should undergo endoscopic screening for esophageal varices detection. Hepatology, 2001, vol.33, p. 333-338). 20...25 years ago, the mortality rate for the first bleeding episode was 50%, and for subsequent bleeding episodes the percentage reaches 80% (De Franchis R. et al. Natural history of portal hypertension in patients with cirrhosis. Clin. Liver Dis. 2001, vol. 5, p. 645-663). Current data indicate a 3-fold decrease in mortality in the case of bleeding from esophagogastric varices (Bosh J. et al. Prevention of variceal rebleeding. Lancet, 2003, vol. 361, p. 952-954).

[0003] In the case of esophageal-gastric variceal bleeding, the optimal therapeutic modality for each patient differs. The analysis of recent data from the specialized literature has highlighted the tendency of clinics, which are active in the field of portal hypertension (PH) syndrome treatment, to develop and perfect azygo-portal disconnection (AAD) operations (Dagenais M., Langer B., Taylor B.R., Greig P.D. Experience with radical esophago-gastric devascularization procedures (Sugiura) for variceal bleeding outside Japan. World J. Surg., 1994, vol. 18(2), p. 222-228; Idezuki Y., Kokudo N., Sanjo K., Bandai Y. Sugiura procedure for management of variceal bleeding in Japan. World J. Surg., 1994, vol. 18(2), p. 216-221; Selzner M., Tuttle-Newhall J.E., Dahm F., Suhocki, P., Clavien P.A. Current indication of a modified Sugiura procedure in the management of variceal bleeding. J. Am. Coll. Surg., 2001, vol. 193(2), pp. 166-173; Ma Y.G., Li X.S., Zhao J., Chen H., Wu M.C. Modified Sugiura procedure for the management of 160 cirrhotic patients with portal hypertension. Hepatobiliary Pancreat. Dis. Int., 2004, vol. 3(3), pp. 399-401; Mathur S.K., Shah S.R., Nagral S.S., Soonawala Z.F. Transabdominal extensive esophagogastric devascularization with gastroesophageal stapling for management of noncirrhotic portal hypertension: long-term results. World J. Surg, 1999, vol. 23(11), pp. 1168-1174; Qazi S.A., Khalid K., Hameed A.M., Al-Wahabi K., Galul R., Al-Salamah S.M. Transabdominal gastro-esophageal devascularization and esophageal transection for bleeding esophageal varices after failed injection sclerotherapy: long-term follow-up report. World J. Surg., 2006, vol. 30(7), p.1329-1337).

But the danger of incomplete obliteration of esophageal vessels (VE) persists (Hosking S.W., Johnson A.G. What happens to esophageal varices after transection and devascularization? Surgery, 1987, vol. 101(5), p. 531-534; Johnson M., Rajendran S., Balachandar T.G., Kannan D., Jeswanth S., Ravichandran, P., Surendran R. Transabdominal modified devascularization procedure with or without esophageal stapler transection an operation adequate for effective control of a variceal bleed. Is esophageal stapler transection necessary? World J. Surg., 2006, vol. 30(8), p.150718). At present, the effect of DAP interventions on VE remains questionable, as well as the justification for their use in the surgical treatment of portal hypertension, which is why minimally invasive methods are needed for azygo-portal disconnection, namely their combination with other methods, which lead to endoscopic sealing of varices with adhesives for the purpose of prophylaxis of profuse esophageal-gastric bleeding.

[0005] The method of treatment of esophageal-gastric varices in patients with decompensated liver cirrhosis is known, which consists in performing splenectomy with azygo-portal disconnection, which constituted a surgical way of resolving cirrhogenic splenopathy and correcting the denatured portal hemocirculation in liver cirrhosis [1].

[0006] The disadvantages of the method are that it is a traumatic method, especially for patients with decompensated liver cirrhosis, with a high rate of complications, such as hepatorenal failure, DIC syndrome, postoperative asplenic sepsis, total portal thrombosis.

[0007] The method of treatment of esophago-gastric varices in patients with decompensated liver cirrhosis is known, namely the Sugiura procedure, which includes esophago-gastric devascularization, splenectomy and esophageal transection [2].

[0008] The disadvantages of the mentioned method are that it is an invasive treatment method, which is sometimes difficult to tolerate by patients with decompensated liver cirrhosis, postoperative complications were up to 46% of patients treated by the mentioned method, and after 2 months postoperatively in 32% relapses of esophageal-gastric varices occurred.

[0009] Also known is the method of treatment of esophageal-gastric varices in patients with decompensated liver cirrhosis, namely by the modified Sugiura surgical intervention, namely by performing transabdominal esophageal-gastric devascularization, stapled esophageal transection and splenectomy. The average age was 46 years (18...56 years). The etiology of portal hypertension was liver cirrhosis in 60% and portal vein thrombosis in 40%. Previously, variceal hemorrhages were confirmed endoscopically in all patients on the background of treatment with beta-blockers or endoscopic sclerotherapy +/- band ligation [3].

[0010] The disadvantages of the mentioned method are that it is an invasive treatment method, which is sometimes difficult to tolerate by patients with decompensated liver cirrhosis, recurrences of bleeding from esophageal-gastric varices have been reported, and the method has been shown to be effective and with good results only in non-cirrhotic patients and in cirrhotic patients with compensated liver function.

[0011] The combined method of treatment of esophageal-gastric varices in patients with liver cirrhosis is known, which includes performing gastro-esophageal decongestion and GEDS splenectomy (Hassab), and consists in performing perhiatal devascularization of the lower part of the esophagus, complete separation of the stomach, ligation of the left gastric artery on the lesser curvature of the stomach, peritonization of the greater curvature, splenectomy with drainage and aspiration of the contents from the splenic bed and combined with sclerotherapy of esophageal-gastric varices [4].

[0012] The disadvantages of the mentioned method are that it is an invasive treatment method, which is sometimes hardly tolerated by patients with decompensated liver cirrhosis, variceal rebleeding has varied from 5.5% in 3 years to 7% in 10 years, when done correctly, up to 17% and 18.8% when done incompletely; higher rates include minor bleeding due to gastritis, while sclerosing can cause severe pain and in some cases local necrosis with severe complications, namely perforations of the esophagus, mediastinitis, frequent relapses of repeated hemorrhages, and at a distance it can be complicated with esophageal stenosis as a result of atrophic processes after repeated manipulations.

[0013] The problem solved by the invention consists in developing a method for combined minimally invasive treatment of esophageal-gastric varices, which would be bearable for patients with decompensated liver cirrhosis, which would prevent the occurrence of profuse hemorrhages from esophageal-gastric varices, which can be fatal, and hepatic encephalopathy, the method would also lead to a reduction in blood loss during the intervention and at the same time to a reduction in the procedure time, which in turn reduces the duration of sedation for patients.

[0014] The essence of the invention is that under general anesthesia, the approaches are prepared for a laparoscopic intervention, the ascitic fluid is evacuated, the abdominal organs are inspected with the removal of fibrin adhesions, then the vascular sealing of the veins on the greater curvature of the stomach and the gastric fundus up to the esophagus is performed for azygo-portal disconnection using a technology using high-frequency alternating current of 470 kHz, with a maximum voltage of 120 V, current intensity of 4 A and maximum current power of 150 W, after which, with the help of an endoscope at the level of the esophageal-gastric junction, a fibrin adhesive is injected into the esophageal and gastric fundus varices in the retrograde and anterograde direction, which includes two components, which are introduced separately with their mixing into the lumen of the vessel, namely the first component includes a fibrinogen solution, and the second component includes a mixture of thrombin solutions with albumin solution of 10%, aprotinin and Ca+2 chloride, in the following ratio of components, per 1 ml:

Fibrinogen (mg) 15...45

[0016] thrombin (IU) 25...100

[0017] 10% albumin solution (ml) 10...20

[0018] aprotinin (KIU) 250...1000

[0019] Ca+2 chloride (µmol) 15...30.

[0020] The result of the invention is that it allows for effective hemostasis due to minimally invasive azygo-potal disconnection procedures, which reduce the procedure time and the duration of sedation, while effective hemostasis is due to effective filling of the varices with the formation of a clot of a hard consistency and a long retraction capacity, which facilitates the formation of paraesophageal extraluminal collaterals, which lead to the prophylaxis of repeated variceal hemorrhages.

[0021] The advantages of the method are that:

[0022] - it is a minimally invasive method;

[0023] - it is tolerated by patients with decompensated liver cirrhosis;

[0024] - prevents the occurrence of profuse bleeding from esophageal-gastric varices;

[0025] - prevents hepatic encephalopathy;

[0026] - reduces blood loss compared to sutures and clips;

[0027] - reduces procedure time;

[0028] - reduces the duration of sedation of patients;

[0029] - obtaining a fibrin clot of a hard consistency;

[0030] - secure fixation of the fibrin clot to the inner walls of the varicose vein;

[0031] - due to the hard consistency, the biological degradation period of the curd is long;

[0032] - formation of extraluminal paraesophageal collaterals;

[0033] - avoiding hemorrhagic relapses.

The method is carried out in the following manner.

[0035] The patient examined and diagnosed with the presence of esophageal-gastric varices under general anesthesia, the approaches are prepared for a laparoscopic intervention, the ascitic fluid is evacuated, the abdominal organs are inspected with the removal of fibrin adhesions, then the vascular sealing of the veins on the greater curvature of the stomach and the gastric fundus up to the esophagus is performed for azygo-portal disconnection using a technology using high-frequency alternating current of 470 kHz, with a maximum voltage of 120 V, current intensity of 4 A and maximum current power of 150 W, (LigaSure technology), after which with the help of the endoscope at the level of the esophageal-gastric junction, a fibrin adhesive is injected into the esophageal and gastric fundus varices in the retrograde and anterograde direction, which includes two components, which are introduced separately with their mixing into the lumen of the vessel, namely the first component includes a fibrinogen solution, and the second component includes a mixture of thrombin solutions with 10% albumin solution, aprotinin and Ca+2 chloride, in the following ratio of components, per 1 ml:

Fibrinogen (mg) 15...45

[0037] thrombin (IU) 25...100

[0038] 10% albumin solution (ml) 10...20

[0039] aprotinin (KIU) 250...1000

[0040] Ca+2 chloride (µmol) 15...30.

[0041] LigaSure technology provides a unique combination of pressure and energy to create a perfect vascular seal with every application. It ensures the fusion of vessels up to 7 mm in diameter without prior dissection or isolation. The average sealing cycle is from 2 to 4 seconds. The seals withstand a systolic blood pressure pressure three times higher than the normal value. The mentioned technology consists in the use of high-frequency alternating current of 470 kHz, with a maximum voltage of 120 V, a current intensity of 4 A and a maximum current power of 150 W.

[0042] The results of the combined minimally invasive treatment of esophageal-gastric varices in patients with decompensated liver cirrhosis with the performance of azygo-portal disconnection with the concomitant use of fibrin glue in 196 patients with surgical portal hypertension, treated in the period 2011...2024, distributed according to the Child grading in: A/B/C-48/1124/24. The surgical indications were determined by the history of variceal hemorrhages with an increased risk of relapse and erosive-ulcerative gastropathies. The improvement of hepatic functional reserves in the postoperative period was noted in the absolute majority of patients by improving the Child score and ensuring adequate porto-hepatic perfusion confirmed by ultrasonographic Doppler flowmetry. The general early postoperative mortality was 7.4%, being correlated with the functional liver reserves: Child A/B/C- 1/10/8, or 2.08/5.38/33.3 percent of cases. The general rate of long-term survival at 1, 3 and 5 years was 86.5%, 75.6% and 68.7%, respectively. Depending on the Child category, the 5-year and 10-year survival is: “A”- 86.2%,- 65.4% “B”- 73.5% - 42.7% and -“C”- 7.8%- 0.4%. Long-term deaths were caused by the progression of cirrhosis with hepatorenal insufficiency, evolution into cirrhosis-liver cancer.

[0043] Embodiments of the invention.

Example 1

[0045] Patient D., 64 years old, hospitalized in the surgery department with the diagnosis: Decompensated liver cirrhosis Child C (10) of viral etiology HVB and HVC. Portal hypertension. Gastroesophageal varices gr. III-IV. At fibroesophagogastroscopy the presence of esophageal varices gr. III-IV in the lower 1/3 of the esophagus and the presence of varices of degree III-IV in the fundal region of the stomach without hemorrhage were determined. The claimed treatment method was used, namely under general anesthesia, the approaches were prepared for a laparoscopic intervention, ascitic fluid was evacuated, the abdominal organs were inspected with the removal of fibrin adhesions, then vascular sealing of the veins on the greater curvature of the stomach and the gastric fundus up to the esophagus was performed for azygo-portal disconnection using a technology using high-frequency alternating current of 470 kHz, with a maximum voltage of 120 V, current intensity of 4 A and maximum current power of 150 W (LigaSure technology), after which, with the help of an endoscope at the level of the esophageal-gastric junction, a fibrin adhesive was injected into the esophageal and gastric fundus varices in the retrograde and anterograde directions, which includes two components, which were introduced separately with their mixing into the lumen of the vessel, namely the first component includes a fibrinogen solution, and the second component includes a mixture of thrombin solutions with 10% albumin solution, aprotinin and Ca+2 chloride in the claimed quantitative ratio. After injection, the formation of a hard and stable fibrin clot was obtained and well fixed in the variceal lumen with complete filling of the variceal lumen and hemostasis by ligation of the esophageal varices. Discharged after 7 days in satisfactory condition. At repeated control after 1, 3, 6 months, the presence of single varices at the level of the lower 1/3 of the esophagus and without risk of hemorrhage were determined.

Example 2

[0047] Patient A., 32 years old, hospitalized in the surgery department with the diagnosis: Decompensated liver cirrhosis Child C (10) of HCV viral etiology. At fibroesophagogastroscopy, the presence of esophageal varices of grade III-IV in the lower 1/3 of the esophagus and the presence of varices of grade III-IV in the fundal region of the stomach without hemorrhage were determined. The claimed treatment method was performed, namely under general anesthesia, the approaches were prepared for a laparoscopic intervention, ascitic fluid was evacuated, the abdominal organs were inspected with the removal of fibrin adhesions, then vascular sealing of the veins on the greater curvature of the stomach and the gastric fundus up to the esophagus was performed for azygo-portal disconnection using a technology using high-frequency alternating current of 470 kHz, with a maximum voltage of 120 V, current intensity of 4 A and maximum current power of 150 W (LigaSure technology), after which, with the help of an endoscope at the level of the esophageal-gastric junction, a fibrin adhesive was injected into the esophageal and gastric fundus varices in the retrograde and anterograde directions, which includes two components, which were introduced separately with their mixing into the lumen of the vessel, namely the first component includes a fibrinogen solution, and the second component includes a mixture of thrombin solutions with 10% albumin solution, aprotinin and Ca+2 chloride in the claimed quantitative ratio. After injection, the formation of a hard and stable fibrin clot was obtained and well fixed in the variceal lumen with complete filling of the variceal lumen and hemostasis by ligation of the esophageal varices. Discharged after 7 days in satisfactory condition. At repeated control after 1, 3, 6 months, the presence of single varices at the level of the lower 1/3 of the esophagus and without risk of hemorrhage were determined.

[0048] 1. Ţîbîrnă C., Anghelici G., Moraru V., Crudu O., Pisarenco S., Danu M., Pavliuc G., Splenectomy with azygo-portal disconnection in the treatment of cirrhogenic portal hypertension, Arta medica No. 3 (46), 2011, Found on the Internet < https://ibn.idsi.md/en/vizualizare_articol/150304>

[0049] 2. D. Mariette, C. Smadja, G Borgonovo, D. Grange, D. Franco, The sugiura procedure: a prospective experience, Surgery, PubMed, 1994, vol. 115, p. 282-289, Found on the Internet < https://pubmed.ncbi.nlm.nih.gov/8128352/>

[0050] 3. Mehmet Haciyanli, Hudai Gene, Hakan Halici, yusuf Kumkumoglu, Ozlem S. Gur, Tuncay Ozturk, Results of modified Sugiura operation in variceal bleeding in cirrhotic and noncirrhotic patients. Hepatogastroenterology, PubMed, vol 50, 2003, pp 784-788, Found on the Internet < https://pubmed.ncbi.nlm.nih.gov/12828085/>

[0051] 4. Hassab M.A., Gastro-esophageal decongestion and splenectomy CEDS (Hassab), in the management of bleeding varices, Review of literature, International Surgery, PubMed, 1998, p. 38-41, Found on the Internet < https://pubmed.ncbi.nlm.nih.gov/9706516/>

Claims (1)

1. Method of combined minimally invasive treatment of esophageal-gastric varices in patients with decompensated liver cirrhosis, which consists in preparing the approaches for a laparoscopic intervention under general anesthesia, evacuating ascitic fluid, inspecting the abdominal organs with removing fibrin adhesions, then performing vascular sealing of the veins on the greater curvature of the stomach and the gastric fundus up to the esophagus for azygo-portal disconnection using a technology using high-frequency alternating current of 470 kHz, with a maximum voltage of 120 V, current intensity of 4 A and maximum current power of 150 W, after which, using an endoscope at the level of the esophageal-gastric junction, a fibrin adhesive is injected into the esophageal and gastric fundus varices in the retrograde and anterograde directions, which includes two components, which are introduced separately with their mixing into the lumen of the vessel, namely the first component includes a solution of fibrinogen, and the second component includes a mixture of thrombin solutions with 10% albumin solution, aprotinin and Ca+2 chloride, in the following ratio of components, per 1 ml: fibrinogen (mg) 15...45 thrombin (IU) 25...100 10% albumin solution (ml) 10...20 aprotinin (KIU) 250...1000 Ca+2 chloride (µmol) 15...30.