Русский | English    

 
 
One more opinion on biliary diseases           
  
  
Main         About author        
 
 
 
 

 
 

Biliary Diseases
Laparoscopic Cholecystectomy. Postcholecystectomy Syndrome.
Treatment: Celecoxib and Ursodeoxycholic acid

Share this:  

Read this article in PDF format

Biliary diseases (gallbladder dysfunction, chronic acalculous cholecystitis, chronic calculous cholecystitis, gallstone disease, postcholecystectomy syndrome) are very widespread diseases of the digestive apparatus [1-8].

Currently in the U.S. there are approximately 30 million patients with cholelithiasis, and about 15 million patients recovering from surgery, which is 14.3% of the total population, in Canada – 25.0% (8.7 million), in Chile – 21.6-35.2% ( 4.8 million), in Peru – 14.3% (4.2 million), in South Africa – 10.0% (4.9 million), in Italy – 13.8% (8.3 million), in Sweden – 15.0-50.5% (2.4 million), in Denmark – 8.8-24.0% (about 1.0 million), in Norway – 21.9% (about 1.0 million), in the Great Britain – 7.5-21.7% (9.1 million), in Austria – 25.5% (2.1 million), in Germany – 19.7% (16.1 million), in Poland – 19.5% (7.4 million), in Romania – 10.9% (2.3 million), in France – 15.7% (10.3 million), in Russia – 5.0- 25.0% (20.1 million), in India – 6.1% (74.0 million), in China – 3.5% (47.1 million), in Japan – 3.2% (4.1 million), etc. [10-14]. Cholesterol cholelithiasis is 70-80% of the total number of gallstone disease [10-14].

Early diagnosis and treatment of pathology of biliary system is of great clinical importance because of the transformation of functional disorders of the biliary system in organic pathology - the gallbladder dysfunction → chronic cholecystitis acalculous without biliary sludge → chronic acalculous cholecystitis with biliary sludge → chronic calculous cholecystitis, which occurs as a result violation of colloidal stability of bile and join the inflammatory process [1-9].

Chronic calculous cholecystitis and cholesterol gallstone disease as diseases requiring surgical treatment, considered one of the main problems in gastroenterology. Laparoscopic cholecystectomy is considered the "gold" standard in the treatment of chronic calculous cholecystitis [15-23]. Annually in the U.S. operated by 750,000 patients [10-14], in Germany - 190,000 [10-14], Russia - 160.000 [4].

The absence of the gallbladder leads to functional biliary hypertension and increased hepatic and common bile duct [8, 24-31]. 3-5 years after cholecystectomy increases right and left hepatic ducts equity [8, 24-31].

Functional hypertension in the common bile duct contributes to the appearance of functional and hypertension in Wirsung's pancreatic duct with the development of the phenomena of chronic pancreatitis [8, 24-31]. At the same time period in some patients this is accompanied by the progression of chronic pancreatitis, sphincter of Oddi dysfunction and duodenogastric reflux [8, 24-45].

Duodenogastric reflux of mixture of bile with pancreatic juice promotes atrophic gastritis in the antral part of stomach [8, 24-45].

From 40% to 60% of patients after cholecystectomy dyspeptic suffering from various disorders, from 20% to 40% of pains of different localization [32-45].

Up to 70% of patients after cholecystectomy have chronic effects of "bland" cholestasis, chronic cholestatic hepatitis and chronic compensatory bile acid-dependent apoptosis of hepatocytes [31-36].

Patients undergoing cholecystectomy had an increased prevalence of metabolic risk factors for cardiovascular disease, including type 2 diabetes mellitus, high blood pressure, and high cholesterol levels [46-50].

Part of patients after cholecystectomy with increased concentration of hydrophobic hepatotoxic co-carcinogenic deoxicholic bile acid in serum and/or feces with increased risk of colon cancer [51-60].

For the treatment of biliary sludge and dissolution of cholesterol gallstones is used ursodeoxycholic bile acid [61-64]. When using the ursodeoxycholic bile acid the dissolution efficiency varies from 20% to 70%, the dissolution time is from 6 to 24 months, and the recurrence of cholelithiasis is 10% per annum or 50% within 5 years [61-64].

Absorption and concentration and evacuation function of the gall bladder plays an important role in the physiology of the formation of gallbladder bile. The mechanism of formation of lithogenic gallbladder bile was due to lower absorption and concentration functions of the gallbladder. Reducing the concentration of bile acids in gallbladder bile associated with lower water absorption of the gallbladder mucosa. Increasing the concentration of cholesterol in phospholipid vesicles - a decrease in absorbance phospholipid vesicles [9, 65-70].

Pathogenesis of cholesterol gall stones include the presence of:

  1. chronic "bland" intragallbladder cholestasis (reduced absorption, concentration and evacuation function of the gall bladder), contributing to the formation of lithogenic gallbladder bile, and
  2. chronic "bland" intrahepatic cholestasis (reduced excretory function of the liver), may influence the formation of lithogenic hepatic bile. These factors contribute to the formation of cholesterol gallstones in the gall bladder [9, 65-70].

Absorption, concentration and evacuation function of the gall bladder plays an important role in the regulation of gallbladder-dependent and gallbladder-independent enterohepatic circulation of bile acids. The gallbladder in humans, accumulating bile acids and excluding them from the enterohepatic circulation, helps reduce the formation of secondary hydrophobic hepatotoxic bile acids (lithocholic and deoxycholic bile acids) and thus protects the liver, gastric mucosa, gallbladder, and colon cancer from exposure to them.

Absorption and concentration and evacuation function of the gallbladder, the functional state of the sphincter of Oddi and anatomical features of the sphincter of Oddi hepatopancreatic ampulla determine development and dominance of a certain type of pathology in each individual patient with biliary tract disease [9, 65-96].

Celecoxib, effectively blocking the inflammation in the gallbladder wall, significantly reduces the risk of cholesterol gallstones [97].

Ursodeoxycholic acid during chronic administration, blocking the inflammation in the gallbladder wall [98-101], dissolving the crystals of monohydrate cholesterol [102-103], reducing the gallbladder bile lithogenicity [104-108], restoring the evacuation function of the gallbladder [109-114], improving accumulative-excretory function of the liver [115-119], increasing blood flow to the liver [120-128] and reducing lithogenicity hepatic bile [115, 117], significantly reduces the risk of biliary sludge in the transformation of cholesterol gallstones [129], the risk of acute calculous cholecystitis and biliary colic [130-131], the risk of acute biliary pancreatitis and recurrent pancreatitis [130-135] in patients with cholelithiasis.

And also, ursodeoxycholic acid during chronic administration, restoring the "passage" of hepatic bile in the gall bladder and reducing the "passage" of hepatic bile into the duodenum, eliminates the mechanism of duodenal-gastric reflux of bile, reduces the risk of bile-reflux gastritis (atrophic antral gastritis) and the appearance of intestinal metaplasia in gastric antral [136-143].

References

  1. Heuman DM, Moore EW, Vlahcevic ZR. Pathogenesis and dissolution of gallstones. In: Zakim D, Boyer ND, editors. Hepatology, a Textbook of Liver Disease. 2nd ed. Philadelphia: Saunders, 1990: 1480-1516.
  2. Sherlock S, Dooley J. Diseases of the liver and biliary system. 9th ed. Oxford: Blackweel Scientific Publications, 1993: 562-591.
  3. Carey MC. Formation and growth of cholesterol gallstones: the new synthesis. In: Fromm H, Leuschner U, editors. Bile Acids-Cholestasis-Gallstones. Advances in Basic and Clinical Bile Acid Research. Dordrecht: Kluwer, 1996: 147-175.
  4. Carey MC. Pathogenesis of cholesterol and pigment gallstones: some radical new concepts. In: Gerok W, Loginov AS, Pokrowskij VI, editors. New Trends in Hepatology 1996. Dordrecht: Kluwer, 1996: 64-83.
  5. Paumgartner G. Nonsurgical management of gallstone disease. In: Feldman M, Scharschmidt BF, Sleisenger MH, editors. Sleisenger and Fordtran’s Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, Management. 6th ed. Philadelphia: WB Saunders Company, 1998: 984-993.
  6. Lammert F, Sauerbruch T. Mechanisms of disease: the genetic epidemiology of gallbladder stones. Nat Clin Pract Gastroenterol Hepatol 2005; 2: 423-433.
  7. Marschall HU, Einarsson C. Gallstone disease. J Intern Med 2007; 261(6): 529-542.
  8. Zubovski GA. Radio and Ultrasonic Diagnosis of Biliary Tract Diseases. Moscow: Medicine, 1987: 36-174.
  9. Turumin JL. Mechanisms of development of morpho-functional disturbances in the gallbladder and liver in the pathogenesis of cholesterol cholecystolithiasis: Thesis … DMSci. Irkutsk, 2000: 1-258.
  10. Nakeeb A, Comuzzie AG, Martin L, Sonnenberg GE, Swartz-Basile D, Kissebah AH, Pitt HA. Gallstones: genetics versus environment. Ann Surg 2002; 235(6): 842-849.
  11. Russo MW, Wei JT, Thiny MT, Gangarosa LM, Brown A, Ringel Y, Shaheen NJ, Sandler RS. Digestive and liver diseases statistics, 2004. Gastroenterology 2004, 126(5):1448-1453.
  12. Shaffer EA. Epidemiology and risk factors for gallstone disease: has the paradigm changed in the 21st century? Curr Gastroenterol Rep 2005; 7(2):132-140.
  13. Portincasa P, Moschetta A, Palasciano G. Cholesterol gallstone disease. Lancet 2006; 368(9531): 230-239.
  14. Lammert F, Miquel JF. Gallstone disease: from genes to evidence-based therapy. J Hepatol 2008; 48 (Suppl 1): S124-135.
  15. Soper NJ, Stockmann PT, Dunnegan DL, Ashley SW. Laparoscopic cholecystectomy. The new “gold standard”? Arch Surg 1992; 127(8): 917-921.
  16. Begos DG, Modlin IM. Laparoscopic cholecystectomy: from gimmick to gold standard. J Clin Gastroenterol 1994; 19(4): 325-330.
  17. Moss G. Laparoscopic cholecystectomy and the gold standard. J Laparoendosc Surg 1995; 5(1): 63-64.
  18. Ido K, Kimura K. Endoscopic treatment of digestive system diseases. 5. Laparoscopic cholecystectomy has become the gold standard of cholecystectomy. Nihon Naika Gakkai Zasshi 1996; 85(9): 1450-1453.
  19. Sain AH. Laparoscopic cholecystectomy is the current "gold standard" for the treatment of gallstone disease. Ann Surg 1996; 224(5): 689-690.
  20. Bingener-Casey J, Richards ML, Strodel WE, Schwesinger WH, Sirinek KR. Reasons for conversion from laparoscopic to open cholecystectomy: a 10-year review. J Gastrointest Surg 2002; 6(6): 800-805.
  21. Bingener J, Richards ML, Schwesinger WH, Strodel WE, Sirinek KR. Laparoscopic cholecystectomy for elderly patients: gold standard for golden years? Arch Surg 2003; 138(5): 531-535.
  22. Bueno Lledó J, Planells Roig M, Arnau Bertomeu C, Sanahuja Santafé A, Oviedo Bravo M, García Espinosa R, Martí Obiol R, Espí Salinas A. Outpatient laparoscopic cholecystectomy: a new gold standard for cholecystectomy. Rev Esp Enferm Dig 2006; 98(1): 14-24.
  23. Nilsson E, Fored CM, Granath F, Blomqvist P. Cholecystectomy in Sweden 1987-99: a nationwide study of mortality and preoperative admissions. Scand. J. Gastroenterol 2005; 40(12): 1478-1485.
  24. Barthet M, Affriat C, Bernard JP, Berthezene P, Dagorn JC, Sahel J. Is biliary lithiasis associated with pancreatographic changes? Gut 1995; 36(5): 761-765.
  25. Barthet M, Spinoza S, Affriat C, Berthezene P, Sahel J. Influence of age and biliary lithiasis on the diameter of the common bile duct. Gastroenterol Сlin Biol 1995; 19(2): 156-160.
  26. Potter GD. Bile acid diarrhea. Dig Dis Sci 1998; 16(2): 118-124.
  27. Arlow FL, Dekovich AA, Priest RJ, Beher WT. Bile acid-mediated postcholecystectomy diarrhea. Arch Intern Med 1987; 147(7): 1327-1329.
  28. Portincasa P, van de Meeberg P, van Erpecum KJ, Palasciano G, VanBerge-Henegouwen GP. An update on the pathogenesis and treatment of cholesterol gallstones. Scand J Gastroenterol 1997; 223: 60-69.
  29. Portincasa P, Di Ciaula A, Palmieri V, Velardi A, VanBerge-Henegouwen GP, Palasciano G. Impaired gallbladder and gastric motility and pathological gastroesophagal reflux in gallstone patients. Europ J Clin Invest 1997; 27(8): 653-661.
  30. Fort JM, Azpiroz F, Casellas F, Andreu J, Malagelada JR. Bowel habit after cholecystectomy: physiological changes and clinical implications. Gastroenterology 1996; 111(3): 617-622.
  31. Isogai M, Yamaguchi A, Hori A, Nakano S. Hepatic histopathological changes in biliary pancreatitis. Amer J Gastroenterol 1995; 90(3): 449-454.
  32. Mulvihill SJ. Surgical management of gallstone disease and postoperative complications. In: Feldman M, Scharschmidt BF, Sleisenger MH, editors. Sleisenger and Fordtran’s Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, Management. 6th ed. Philadelphia: WB Saunders Company, 1998: 973-984.
  33. Honda A, Yoshida T, Tanaka N, Matsuzaki Y, He B, Shoda J, Osuga T. Increased bile acid concentration in liver tissue with cholesterol gallstone disease. J Gastroenterol 1995; 30(1): 61-66.
  34. Geraghty JM, Goldin RD. Liver changes associated with cholecystitis. J Clin Pathol 1994; 47(5): 457-460.
  35. Carey MC, Duane WC. Enterohepatic circulation. In: Arias IM, Boyer JL, Fausto N, Jakoby WB, Schachter DA, Shafritz DA, editors. The Liver, Biology and Pathobiology. 3rd ed. New York: Raven Press, 1994: 719-767.
  36. Hofmann AF. Bile secretion and the enterohepatic circulation of bile acids. In: Feldman M, Scharschmidt BF, Sleisenger MH, editors. Sleisenger and Fordtran’s Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, Management. 6th ed. Philadelphia: WB Saunders Company, 1998: 937-948.
  37. Ros E, Zambon D. Postcholecystectomy symptoms. A prospective study of gallstone patients before and two years after surgery. Gut 1987; 28(11): 1500-1504.
  38. Middelfart HV, Kristensen JU, Laursen CN, Qvist N, Højgaard L, Funch-Jensen P, Kehlet H. Pain and dyspepsia after elective and acute cholecystectomy. Scand J Gastroenterol 1998; 33(1): 10-14.
  39. Bisgaard T, Rosenberg J, Kehlet H. From acute to chronic pain after laparoscopic cholecystectomy: a prospective follow-up analysis. Scand J Gastroenterol 2005; 40(11): 1358-1364.
  40. Berhane T, Vetrhus M, Hausken T, Olafsson S, Søndenaa K. Pain attacks in non-complicated and complicated gallstone disease have a characteristic pattern and are accompanied by dyspepsia in most patients: the results of a prospective study. Scand J Gastroenterol 2006; 41(1): 93-101.
  41. Vetrhus M, Berhane T, Søreide O, Søndenaa K. Pain persists in many patients five years after removal of the gallbladder: observations from two randomized controlled trials of symptomatic, non-complicated gallstone disease and acute cholecystitis. J Gastrointest Surg 2005; 9(6): 826-831.
  42. Bilhartz LE, Horton JD. Gallstone disease and its complications. In: Feldman M, Scharschmidt BF, Sleisenger MH, editors. Sleisenger and Fordtran’s Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, Management. 6th ed. Philadelphia: WB Saunders Company, 1998: 948-972.
  43. Saraswat VA, Sharma BC, Agarwal DK, Kumar R, Negi TS, Tandon RK. Biliary microlithiasis in patients with idiopathic acute pancreatitis and un-explained biliary pain: response to therapy. J Gastroenterol Hepatol 2004; 19(10): 1206-1211.
  44. Liu CL, Fan ST, Lo CM, Tso WK, Wong Y, Poon RT, Lam CM, Wong BC, Wong J. Clinico-biochemical prediction of biliary cause of acute pancreatitis in the era of endoscopic ultrasonography. Aliment Pharmacol Ther 2005; 22(5): 423-431.
  45. Venneman NG, Buskens E, Besselink MG, Stads S, Go PM, Bosscha K, van Berge-Henegouwen GP, van Erpecum KJ. Small gallstones are associated with increased risk of acute pancreatitis: potential benefits of prophylactic cholecystectomy? Am J Gastroenterol 2005; 100(11): 2540-2550.
  46. Méndez-Sánchez N, Bahena-Aponte J, Chávez-Tapia NC, Motola-Kuba D, Sánchez-Lara K, Ponciano-Radríguez G, Ramos MH, Uribe M. Strong association between gallstones and cardiovascular disease. Am J Gastroenterol 2005; 100(4): 827-830.
  47. Gonzalez-Perez A, Garcia Rodriguez LA. Gallbladder disease in the general population: association with cardiovascular morbidity and therapy. Pharmacoepidemiol Drug Saf  2007; 16(5): 524-531.
  48. Méndez-Sánchez N, Zamora-Valdés D, Flores-Rangel JA, Pérez-Sosa JA, Vásquez-Fernández F, Lezama-Mora JI, Vázquez-Elizondo G, Ponciano-Rodríguez G, Ramos MH, Uribe M. Gallstones are associated with carotid atherosclerosis. Liver Int 2008; 28(3): 402-406.
  49. Ruhl CE, Everhart JE. Gallstone disease is associated with increased mortality in the United States. Gastroenterology 2011; 140(2): 508-516.
  50. Chavez-Tapia NC, Kinney-Novelo IM, Sifuentes-Rentería SE, Torres-Zavala M, Castro-Gastelum G, Sánchez-Lara K, Paulin-Saucedo C, Uribe M, Méndez-Sánchez N. Association between cholecystectomy for gallstone disease and risk factors for cardiovascular disease. Ann Hepatol 2012; 11(1): 85-89.
  51. Ochsenkuhn T, Bayerderffer E, Meining A, Schinkel M, Thiede C, Nussler V, Sackmann M, Hatz R, Neubauer A, Paumgartner G. Colonic mucosal proliferation is related to serum deoxycholic acid levels. Cancer 1999; 85(8): 1664-1669.
  52. Shekels LL, Beste JE, Ho SB. Tauroursodeoxycholic acid protects in vitro models of human colonic cancer cells from cytotoxic effects of hydrophobic bile acids. Lab Clin Med 1996; 127(1): 57-66.
  53. Ekbom A, Yuen J, Adami HO, McLaughlin JK, Chow WH, Persson I, Fraumeni JF. Cholecystectomy and colorectal cancer. Gastroenterology 1993; 105(1): 142-147.
  54. Goldbohm RA, van den Brandt PA, van Veer P, Dorant E, Sturmans F, Hermus RJ. Cholecystectomy and colorectal cancer: evidence from a cohort study on diet and cancer. Int J Cancer 1993; 53(5): 735-739.
  55. Bayerderffer E, Mannes GA, Richter WO, Ochsenkuhn T, Wiebecke B, Kepcke W, Paumgartner G. Increased serum deoxycholic acid levels in men with colorectal adenomas. Gastroenterology 1993; 104(1): 145-151.
  56. Bayerderffer E, Mannes GA, Ochsenkuhn T, Dirschedl P, Paumgartner G. Variation of serum bile acids in patients with colorectal adenomas during a one-year follow-up. Digestion 1994; 55(2): 121-129.
  57. Bayerderffer E, Mannes GA, Ochsenkuhn T, Dirschedl P, Wiebecke B, Paumgartner G. Unconjugated secondary bile acids in the serum of patients with colorectal adenomas. Gut 1995; 36(2): 268-273.
  58. Kamano T, Mikami Y, Kurasawa T, Tsurumaru M, Matsumoto M, Kano M, Motegi K. Ratio of primary and secondary bile acids in feces. Possible marker for colorectal cancer? Dis Colon Rectum 1999; 42(5): 668-672.
  59. Johansen C, Chow WH, Jorgensen T, Mellemkjaer L, Engholm G, Olsen JH. Risk of colorectal cancer and other cancers in patients with gallstones. Gut 1996; 39(3): 439-443.
  60. Chow WH, Johansen C, Gridley G, Mellemkjair L, Olsen JH, Fraumeni JF. Gallstones, cholecystectomy and risk of cancers of the liver, biliary tract and pancreas. Br J Cancer 1999; 79(3-4): 640-644.
  61. Bilhartz LE. Cholesterol gallstone disease: the current status of nonsurgical therapy. Amer J Med Sci 1988; 296(1): 45-56.
  62. Fromm H, Malavolti M. Bile acid dissolution therapy of gallbladder stones. Baillieres Clin Gastroenterol 1992; 6(4): 689-95.
  63. Nilsell K. Biliary lipid metabolism in gallstone disease and during gallstone dissolution treatment. Stockholm: Repro-Print AB, 1985: 1-105.
  64. Paumgartner G. Nonsurgical management of gallstone disease. In: Feldman M, Scharschmidt BF, Sleisenger MH, editors. Sleisenger and Fordtran’s Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, Management. 6th ed. Philadelphia: WB Saunders Company, 1998: 984-993.
  65. Pazzi P, Petroni ML, Prandini N, Adam JA, Gullini S, Northfield TC, Jazrawi RP. Postprandial refilling and turnover: specific gallbladder motor function defects in patients with gallstone recurrence. Eur J Gastroenterol Hepatol 2000; 12(7): 787-794.
  66. Jazrawi RP, Pazzi P, Petroni ML, Prandini N, Paul C, Adam JA, Gullini S, Northfield TC. Postprandial gallbladder motor function: refilling and turnover of bile in health and in cholelithiasis. Gastroenterology 1995; 109(2): 582-591.
  67. Ginanni Corradini S, Ripani C, Della Guardia P, Giovannelli L, Elisei W, Cantafora A, Codacci Pisanelli M, Tebala GD, Nuzzo G, Corsi A, Attili AF, Capocaccia L, Ziparo V. The human gallbladder increases cholesterol solubility in bile by differential lipid absorption: a study using a new in vitro model of isolated intra-arterially perfused gallbladder. Hepatology 1998; 28(2): 314-322.
  68. Ginanni Corradini S, Yamashita G, Nuutinen H, Chernosky A, Williams C, Hays L, Shiffman ML, Walsh RM, Svanvik J, Della Guardia P, Capocaccia L, Holzbach RT. Human gallbladder mucosal function: effects on intraluminal fluid and lipid composition in health and disease. Dig Dis Sci 1998; 43(2): 335-343.
  69. Corradini SG, Elisei W, Giovannelli L, Ripani C, Della Guardia P, Corsi A, Cantafora A, Capocaccia L, Ziparo V, Stipa V, Chirletti P, Caronna R, Lomanto D, Attili AF. Impaired human gallbladder lipid absorption in cholesterol gallstone disease and its effect on cholesterol solubility in bile. Gastroenterology 2000; 118(5): 912-920.
  70. Corradini SG, Liguori F. Recent studies on the pathogenesis of cholelithiasis: the role of the gallbladder epithelium. Recenti Prog Med 2001; 92(7-8): 471-476.
  71. Ko CW, Beresford SA, Schulte SJ, Matsumoto AM, Lee SP. Incidence, natural history, and risk factors for biliary sludge and stones during pregnancy. Hepatology 2005; 41(2): 359-365.
  72. Shoda J, Ueda T, Ikegami T, Matsuzaki Y, Satoh S, Kano M, Matsuura K, Tanaka N. Increased biliary group II phospholipase A2 and altered gallbladder bile in patients with multiple cholesterol stones. Gastroenterology 1997; 112(6): 2036-2047.
  73. Shoda J, Kano M, Asano T, Irimura T, Ueda T, Iwasaki R, Furukawa M, Kamiya J, Nimura Y, Todoroki T, Matsuzaki Y, Tanaka N. Secretory low-molecular-weight phospholipases A2 and their specific receptor in bile ducts of patients with intrahepatic calculi: factors of chronic proliferative cholangitis. Hepatology 1999; 29(4): 1026-1036.
  74. Shoda J, Ueda T, Kawamoto T, Todoroki T, Asano T, Sugimoto Y, Ichikawa A, Maruyama T, Nimura Y, Tanaka N. Prostaglandin E receptors in bile ducts of hepatolithiasis patients and the pathobiological significance for cholangitis. Clin Gastroenterol Hepatol 2003; 1(4): 285-296.
  75. Myers SI, Inman LR, Kalley-Taylor B, Riva A, Bartula L. Increased intragallbladder pressure stimulates gallbladder eicosanoid release. Prostaglandins 1994; 48(1): 53-66.
  76. LaMorte WW, Booker ML, Scott TE, Williams LF Jr. Increases in gallbladder prostaglandin synthesis before the formation of cholesterol gallstones. Surgery 1985; 98(3): 445-451.
  77. Sasaki H, Tazuma S, Kajiyama G. Effects of 16,16-dimethyl prostaglandin E2 on biliary mucous glycoprotein and gallstone formation in guinea pigs. Scand J Gastroenterol 1993; 28(6): 495-499.
  78. von Ritter C, Niemeyer A, Lange V, Möhrle W, Richter WO, von Meyer L, Brandl H, del Pozo R, Jüngst D. Indomethacin decreases viscosity of gallbladder bile in patients with cholesterol gallstone disease. Clin Invest 1993; 71(11): 928-932.
  79. Longo WE, Panesar N, Mazuski JE, Kaminski D. Synthetic pathways of gallbladder mucosal prostanoids: the role of cyclooxygenase-1 and 2. Prostaglandins Leukot Essent Fatty Acids 1999; 60(2): 77-85.
  80. Grossmann EM, Longo WE, Mazuski JE, Panesar N, Kaminski DL. Role of cytosolic phospholipase A2 in cytokine-stimulated prostaglandin release by human gallbladder cells. J Gastrointest Surg 2000; 4(2): 193-200.
  81. Inoue K, Fuchigami A, Higashide S, Sumi S, Kogire M, Suzuki T, Tobe T. Gallbladder sludge and stone formation in relation to contractile function after gastrectomy. Ann Surg 1992; 215(1): 19-26.
  82. Das JB, Cosentino CM, Levy MF, Ansari GG, Raffensperger JG. Early hepatobiliary dysfunction during total parenteral nutrition: an experimental study. J Pediatr Surg 1993; 28(1): 14-18.
  83. Spier BJ, Pfau PR, Lorenze KR, Knechtle SJ, Said A. Risk factors and outcomes in post-liver transplantation bile duct stones and casts: A case-control study. Liver Transpl 2008; 14(10): 1461-1465.
  84. Inoue T, Mashima Y. The pathophysiological characteristics of bile from patients with gallstones: the role of prostaglandins and mucin in gallstone formation. Jap J Surg 1990; 20(1): 10-18.
  85. Sunami Y, Tazuma S, Kajiyama G. Gallbladder dysfunction enhances physical density but not biochemical metastability of biliary vesicles. Dig Dis Sci 2000; 45(12): 2382-2391.
  86. Xiao ZL, Rho AK, Biancani P, Behar J. Effects of bile acids on the muscle functions of guinea pig gallbladder. Am J Physiol Gastrointest Liver Physiol 2002; 283(1): G87-G94.
  87. Kano M, Shoda J, Satoh S, Kobayashi M, Matsuzaki Y, Abei M, Tanaka N. Increased expression of gallbladder cholecystokinin: a receptor in prairie dogs fed a high-cholesterol diet and its dissociation with decreased contractility in response to cholecystokinin. J Lab Clin Med 2002; 139(5): 285-294.
  88. Nishioka T, Tazuma S, Yamashita G, Kajiyama G. Partial replacement of bile salts causes marked changes of cholesterol crystallization in supersaturated model bile systems. Biochem J 1999; 340 (Pt 2): 445-451.
  89. Jüngst C, Sreejayan N, Eder MI, von Stillfried N, Zündt B, Spelsberg FW, Kullak-Ublick GA, Jüngst D, von Ritter C. Lipid peroxidation and mucin secretagogue activity in bile of gallstone patients. Eur J Clin Invest 2007; 37(9): 731-736.
  90. Rege RV, Prystowsky JB. Inflammation and a thickened mucus layer in mice with cholesterol gallstones. J Surg Res 1998; 74(1): 81-85.
  91. Myers SI, Bartula LL, Colvin MP, Parkman HP, Braverman AA, Ruggieri MR. Bile duct ligation induced acute inflammation up regulates cyclooxygenase-2 content and PGE2 release in guinea pig gallbladder smooth muscle cell cultures. Prostaglandins Leukot Essent Fatty Acids 2005; 72(5): 327-333.
  92. Ghosh M, Kawamoto T, Koike N, Fukao K, Yoshida S, Kashiwagi H, Kapoor VK, Agarwal S, Krishnani N, Uchida K, Miwa M, Todoroki T. Cyclooxygenase expression in the gallbladder. Int J Mol Med 2000; 6(5): 527-532.
  93. Kamisawa T, Okamoto A. Biliopancreatic and pancreatobiliary refluxes in cases with and without pancreaticobiliary maljunction: diagnosis and clinical implications. Digestion 2006; 73(4): 228-236.
  94. Beltrán MA, Contreras MA, Cruces KS. Pancreaticobiliary reflux in patients with and without cholelithiasis: is it a normal phenomenon? World J Surg 2010; 34(12): 2915-2921.
  95. Liang TB, Liu Y, Bai XL, Yu J, Chen W. Sphincter of Oddi laxity: An important factor in hepatolithiasis. World J Gastroenterol 2010; 16(8): 1014-1018.
  96. Zhang ZH, Wu SD, Wang B, Su Y, Jin JZ, Kong J, Wang HL. Sphincter of Oddi hypomotility and its relationship with duodenal-biliary reflux, plasma motilin and serum gastrin. World J Gastroenterol 2008; 14(25): 4077-4081.
  97. Chen XW, Cai JT. The impact of selective cycloxygenase-2 inhibitor celexibo on the formation of cholesterol gallstone. Zhonghua Nei Ke Za Zhi 2003; 42(11): 797-799.
  98. Ikegami T, Matsuzaki Y, Fukushima S, Shoda J, Olivier JL, Bouscarel B, Tanaka N. Suppressive effect of ursodeoxycholic acid on type IIA phospholipase A2 expression in HepG2 cells. Hepatology 2005; 41(4): 896-905.
  99. Kano M, Shoda J, Irimura T, Ueda T, Iwasaki R, Urasaki T, Kawauchi Y, Asano T, Matsuzaki Y, Tanaka N. Effects of long-term ursodeoxycholate administration on expression levels of secretory low-molecular-weight phospholipases A2 and mucin genes in gallbladders and biliary composition in patients with multiple cholesterol stones. Hepatology 1998; 28(2): 302-313.
  100. Guarino MP, Carotti S, Morini S, Perrone G, Behar J, Altomare A, Alloni R, Caviglia R, Emerenziani S, Rabitti C, Cicala M. Decreased number of activated macrophages in gallbladder muscle layer of cholesterol gallstone patients following ursodeoxycholic acid. Gut 2008; 57(12): 1740-1741.
  101. Carotti S, Guarino MP, Cicala M, Perrone G, Alloni R, Segreto F, Rabitti C, Morini S. Effect of ursodeoxycholic acid on inflammatory infiltrate in gallbladder muscle of cholesterol gallstone patients. Neurogastroenterol Motil 2010; 22(8): 866-873.
  102. Mizuno S, Tazuma S, Kajiyama G. Stabilization of biliary lipid particles by ursodeoxycholic acid. Prolonged nucleation time in human gallbladder bile. Dig Dis Sci 1993; 38(4): 684-693.
  103. Tazuma S, Sasaki H, Mizuno S, Sagawa H, Hashiba S, Horiuchi I, Kajiyama G. Effect of ursodeoxycholic acid administration on nucleation time in human gallbladder bile. Gastroenterology 1989; 97(1): 173-178.
  104. Jüngst C, Sreejayan N, Zündt B, Müller I, Spelsberg FW, Hüttl TP, Kullak-Ublick GA, del Pozo R, Jüngst D, von Ritter C. Ursodeoxycholic acid reduces lipid peroxidation and mucin secretagogue activity in gallbladder bile of patients with cholesterol gallstones. Eur J Clin Invest 2008; 38(9): 634-639.
  105. Fischer S, Müller I, Zündt BZ, Jüngst C, Meyer G, Jüngst D. Ursodeoxycholic acid decreases viscosity and sedimentable fractions of gallbladder bile in patients with cholesterol gallstones. Eur J Gastroen-terol Hepatol 2004; 16(3): 305-311.
  106. Sauter GH, Thiessen K, Parhofer KG, Jüngst C, Fischer S, Jüngst D. Effects of ursodeoxycholic acid on synthesis of cholesterol and bile acids in healthy subjects. Digestion 2004; 70(2): 79-83.
  107. Fahey DA, Carey MC, Donovan JM. Bile acid/phosphatidylcholine interactions in mixed monomolecular layers: differences in condensation effects but not interfacial orientation between hydrophobic and hydrophilic bile acid species. Biochemistry 1995; 34(34): 10886-10897.
  108. Guarino MP, Carotti S, Sarzano M, Alloni R, Vanni M, Grosso M, Sironi G, Maffettone PL, Cicala M. Short-term ursodeoxycholic acid treatment improves gallbladder bile turnover in gallstone patients: a randomized trial. Neurogastroenterol Motil 2005; 17(5): 680-686.
  109. Guarino MP, Cong P, Cicala M, Alloni R, Carotti S, Behar J. Ursodeoxycholic acid improves muscle contractility and inflammation in symptomatic gallbladders with cholesterol gallstones. Gut 2007; 56(6): 815-820.
  110. Mas MR, Comert B, Mas N, Yamanel L, Ozotuk H, Tasci I, Jazrawi RP. Effects of long term hydrophilic bile acid therapy on in vitro contraction of gallbladder muscle strips in patients with cholesterol gallstones. World J Gastroenterol 2007; 13(32): 4336-4339.
  111. Colecchia A, Mazzella G, Sandri L, Azzaroli F, Magliuolo M, Simoni P, Bacchi-Reggiani ML, Roda E, Festi D. Ursodeoxycholic acid improves gastrointestinal motility defects in gallstone patients. World J Gastroenterol 2006; 12(33): 5336-5343.
  112. Xiao ZL, Biancani P, Carey MC, Behar J. Hydrophilic but not hydrophobic bile acids prevent gallbladder muscle dysfunction in acute cholecystitis. Hepatology 2003; 37(6): 1442-1450.
  113. van de Heijning BJ, van de Meeberg PC, Portincasa P, Doornewaard H, Hoebers FJ, van Erpecum KJ, Vanberge-Henegouwen GP. Effects of ursodeoxycholic acid therapy on in vitro gallbladder contractility in patients with cholesterol gallstones. Dig Dis Sci 1999; 44(1): 190-196.
  114. Mendez-Sanchez N, Brink MA, Paigen B, Carey MC. Ursodeoxycholic acid and cholesterol induce enterohepatic cycling of bilirubin in rodents. Gastroenterology 1998; 115(3): 722-732.
  115. Beuers U. Drug insight: Mechanisms and sites of action of ursodeoxycholic acid in cholestasis. Nat Clin Pract Gastroenterol Hepatol 2006; 3(6): 318-328.
  116. Pemberton PW, Aboutwerat A, Smith A, Warnes TW. Ursodeoxycholic acid in primary biliary cirrhosis improves glutathione status but fails to reduce lipid peroxidation. Redox Rep 2006; 11(3): 117-123.
  117. Jeong HJ, Kim CG. Pretreatment with ursodeoxycholic acid (UDCA) as a novel pharmacological intervention in hepatobiliary scintigraphy. Yonsei Med J 2005; 46(3): 394-398.
  118. Lukivskaya OY, Maskevich AA, Buko VU. Effect of ursodeoxycholic acid on prostaglandin metabolism and microsomal membranes in alcoholic fatty liver. Alcohol 2001; 25(2): 99-105.
  119. Bouscarel B, Ceryak S, Robins SJ, Fromm H. Studies on the mechanism of the ursodeoxycholic acid-induced increase in hepatic low-density lipoprotein binding. Lipids 1995; 30(7): 607-617.
  120. Bomzon A, Ljubuncic P. Ursodeoxycholic acid and in vitro vasoactivity of hydrophobic bile acids. Dig Dis Sci 2001; 46(9): 2017-2024.
  121. Ljubuncic P, Said O, Ehrlich Y, Meddings JB, Shaffer EA, Bomzon A. On the in vitro vasoactivity of bile acids. Br J Pharmacol 2000; 131(3): 387-398.
  122. Sinisalo J, Vanhanen H, Pajunen P, Vapaatalo H, Nieminen MS. Ursodeoxycholic acid and endothelial-dependent, nitric oxide-independent vasodilatation of forearm resistance arteries in patients with coronary heart disease. Br J Clin Pharmacol 1999; 47(6): 661-665.
  123. Pak JM, Adeagbo AS, Triggle CR, Shaffer EA, Lee SS. Mechanism of bile salt vasoactivity: dependence on calcium channels in vascular smooth muscle. Br J Pharmacol 1994; 112(4): 1209-1215.
  124. Ohtake M, Sandoh N, Sakaguchi T, Tsukada K, Hatakeyama K. Enhancement of portal blood flow by ursodeoxycholic acid in partially hepatectomized rats. Surg Today 1996; 26(2): 142-144.
  125. Bomzon A, Ljubuncic P. Bile acids as endogenous vasodilators? Biochem Pharmacol 1995; 49(5): 581-589.
  126. Pak JM, Lee SS. Vasoactive effects of bile salts in cirrhotic rats: in vivo and in vitro studies. Hepatology 1993; 18(5): 1175-1181.
  127. Benedetti A, Alvaro D, Bassotti C, Gigliozzi A, Ferretti G, La Rosa T, Di Sario A, Baiocchi L, Jezequel AM. Cytotoxicity of bile salts against biliary epithelium: a study in isolated bile ductule fragments and isolated perfused rat liver. Hepatology 1997; 26(1): 9-21.
  128. Itoh S, Kono M, Akimoto T. Psoriasis treated with ursodeoxycholic acid: three case reports. Clin Exp Dermatol 2007; 32(4): 398-400.
  129. Günsar C, Melek M, Karaca I, Sencan A, Mir E, Ortaç R, Canan O. The biochemical and histopathological effects of ursodeoxycholic acid and metronidazole on total parenteral nutrition-associated hepatic dysfunction: an experimental study. Hepatogastroenterology 2002; 49(44): 497-500.
  130. Tomida S, Abei M, Yamaguchi T, Matsuzaki Y, Shoda J, Tanaka N, Osuga T. Long-term ursodeoxycholic acid therapy is associated with reduced risk of biliary pain and acute cholecystitis in patients with gallbladder stones: a cohort analysis. Hepatology 1999; 30(1): 6-13.
  131. Venneman NG, van Berge-Henegouwen GP, van Erpecum KJ. Pharmacological manipulation of biliary water and lipids: potential consequences for prevention of acute biliary pancreatitis. Curr Drug Targets Immune Endocr Metabol Disord 2005; 5(2): 193-198.
  132. Venneman NG, van Erpecum KJ. Gallstone disease: Primary and secondary prevention. Best Pract Res Clin Gastroenterol 2006; 20(6): 1063-1073.
  133. Testoni PA, Caporuscio S, Bagnolo F, Lella F. Idiopathic recurrent pancreatitis: long-term results after ERCP, endoscopic sphincterotomy, or ursodeoxycholic acid treatment. Am J Gastroenterol 2000; 95(7): 1702-1707.
  134. Saraswat VA, Sharma BC, Agarwal DK, Kumar R, Negi TS, Tandon RK. Biliary microlithiasis in patients with idiopathic acute pancreatitis and unexplained biliary pain: response to therapy. J Gastroenterol Hepatol 2004; 19(10): 1206-1211.
  135. Tsubakio K, Kiriyama K, Matsushima N, Taniguchi M, Shizusawa T, Katoh T, Manabe N, Yabu M, Kanayama Y, Himeno S. Autoimmune pancreatitis successfully treated with ursodeoxycholic acid. Intern Med 2002; 41(12): 1142-1146.
  136. Scarpa PJ, Cappell MS. Treatment with ursodeoxycholic acid of bile reflux gastritis after cholecystectomy. J Clin Gastroenterol 1991; 13(5): 601-603.
  137. Stefaniwsky AB, Tint GS, Speck J, Shefer S, Salen G. Ursodoxycholic acid treatment of bile reflux gastritis. Gastroenterology 1985; 89(5): 1000-1004.
  138. Realini S, Reiner M, Frigerio G. Treatment of dyspeptic disorders, lithiasis and biliary dyskinesia with ursodeoxycholic acid. Analysis of a controlled multicenter study. Schweiz Med Wochenschr 1980; 110(22): 879-880.
  139. Rosman AS. Efficacy of ursodeoxycholic acid (UDCA) in treating bile reflux gastritis. Gastro-enterology 1987; 92(1): 269-272.
  140. Pazzi P, Scalia S, Stabellini G. Bile reflux gastritis in patients without prior gastric surgery: Therapeutic effects of ursodeoxycholic acid. Cur Ther Res 1989; 45: 476-680.
  141. Piepoli AL, Caroppo R, Armentano R, Caruso ML, Guerra V, Maselli MA. Tauroursodeoxycholic acid reduces damaging effects of taurodeoxycholic acid on fundus gastric mucosa. Arch Physiol Biochem 2002; 110(3): 197-202.
  142. Ozkaya M, Erten A, Sahin I, Engin B, Ciftci A, Cakal E, Caydere M, Demirbas B, Ustün H. The effect of ursodeoxycholic acid treatment on epidermal growth factor in patients with bile reflux gastritis. Turk J Gastroenterol 2002; 13(4): 198-202.
  143. Thao TD, Ryu HC, Yoo SH, Rhee DK. Antibacterial and anti-atrophic effects of a highly soluble, acid stable ursodeoxycholic acid (UDCA) formula in Helicobacter pylori-induced gastritis. Biochem Pharmacol 2008; 75(11): 2135-2146.
  144. Kumar A, Deed JS, Bhasin B, Kumar A, Thomas S. Comparison of the effect of diclofenac with hyoscine-N-butylbromide in the symptomatic treatment of acute biliary colic. ANZ J Surg 2004; 74(7): 573-576.
  145. Henderson SO, Swadron S, Newton E. Comparison of intravenous ketorolac and meperidine in the treatment of biliary colic. J Emerg Med 2002; 23(3): 237-241.
  146. Dula DJ, Anderson R, Wood GC. A prospective study comparing i.m. ketorolac with i.m. meperidine in the treatment of acute biliary colic. J Emerg Med 2001; 20(2): 121-124.
  147. Chaudhary A, Gupta RL. Double blind, randomised, parallel, prospective, comparative, clinical evaluation of a combination of antispasmodic analgesic Diclofenac + Pitofenone + Fenpiverinium (Manyana vs Analgin + Pitofenone + Fenpiverinium (Baralgan) in biliary, ureteric and intestinal colic. J Indian Med Assoc 1999; 97(6): 244-245.
  148. Golhar KB, Gupta RL. Open labelled evaluation of injection Manyana (a combination of diclofenac + pitofenone + fenpiverinium) in ureteric, biliary and intestinal spasm – a preliminary report. J Indian Med Assoc 1999; 97(9): 398-400.
  149. Al-Waili N, Saloom KY. The analgesic effect of intravenous tenoxicam in symptomatic treatment of biliary colic: a comparison with hyoscine N-butylbromide. Eur J Med Res 1998; 3(10): 475-479.
  150. Smucny JJ. IM diclofenac for biliary colic. J Fam Pract 1997; 45(4): 287-288.
  151. Akriviadis EA, Hatzigavriel M, Kapnias D, Kirimlidis J, Markantas A, Garyfallos A. Treatment of biliary colic with diclofenac: a randomized, double-blind, placebo-controlled study. Gastroenterology 1997; 113(1): 225-231.
  152. Schmieder G, Stankov G, Zerle G, Schinzel S, Brune K. Observer-blind study with metamizole versus tramadol and butylscopolamine in acute biliary colic pain. Arzneimittelforschung 1993; 43(11): 1216-1221.
  153. von Ritter C, Niemeyer A, Lange V, Möhrle W, Richter WO, von Meyer L, Brandl H, del Pozo R, Jüngst D. Indomethacin decreases viscosity of gallbladder bile in patients with cholesterol gallstone disease. Clin Invest 1993; 71(11): 928-932.
  154. Camp Herrero J, Artigas Raventós V, Millá Santos J, Allende Honorato L, Domínguez Granados R, Moreno Carretero E. The efficacy of injectable flurbiprofen in the symptomatic treatment of biliary colic. Med Clin (Barc) 1992; 98(6): 212-214.
  155. Anez MS, Martínez D, Pacheco JL, González H, Rivera J, Pelaschier E, Uzcátegui L, Romero MD, Molina Z, Roditti de Montilla M. Indomethacin in the treatment of acute cholecystitis and biliary colic. G E N 1991; 45(1): 32-37.
  156. Inoue T, Mishima Y. The pathophysiological characteristics of bile from patients with gallstones: the role of prostaglandins and mucin in gallstone formation. Jap J Surg 1990; 20(1): 10-18.
  157. Svanvik J, Thornell E, Jivegard L. Treatment of biliary colic and acute cholecystitis with prostaglandin synthetase inhibitors. Dig Dis Sci 1990; 35(2): 284.
  158. Goldman G, Kahn PJ, Alon R, Wiznitzer T. Biliary colic treatment and acute cholecystitis prevention by prostaglandin inhibitor. Dig Dis Sci 1989; 34(6): 809-811.
  159. Rossi PC, Giudicelli N, Parenti G, Pacetti E. Sodium diclofenac in the treatment of biliary pain: a controlled study using hyoscine N-butylbromide. Clin Ter 1988; 126(6): 405-410.
  160. Karachalios GN, Tsimiklic S, Asimakis G, Helas G. Treatment of biliary colic with prostaglandin-synthetase inhibition: diclofenac sodium. Singapore Med J 1986; 27(3): 207-209.
  161. Marsala F, Cavrini P, Bufalino L, Gardini F. Treatment of acute pain of ureteral and biliary colic with naproxen sodium administered by the parenteral route. Int J Clin Pharmacol Res 1986; 6(6): 495-500.
  162. Kaminski DL, Deshpande Y, Thomas L, Qualy J, Blank W. Effect of oral ibuprofen on formation of prostaglandins E and F by human gallbladder muscle and mucosa. Dig Dis Sci 1985; 30(10): 933-940.
  163. Magrini M, Rivolta G, Movilia PG, Moretti MP, Liverta C, Bruni G. Successful treatment of biliary colic with intravenous ketoprofen or lysine acetylsalicylate. Curr Med Res Opin 1985; 9(7): 454-460.
  164. Jönsson PE, Erichsen C, Holmin T, Petersson BA. Double-blind evaluation of intravenous indomethacin and oxycone-papaverine in the treatment of acute biliary pain. Acta Chir Scand 1985; 151(6): 561-564.
  165. Niinikoski J, Nelimarkka O, Pekkola P. Intravenous indomethacin in biliary pain. A clinical investigation with metamizole as the control. Ann Chir Gynaecol 1984; 73(2): 69-72.
  166. Broggini M, Corbetta E, Grossi E, Borghi C. Diclofenac sodium in biliary colic: a double blind trial. Br Med J (Clin Res Ed). 1984; 288(6423): 1042.
  167. Turumin JL, Kozlova NM. The clinical aspects of the pathogenetic treatment of the patients with chronic acalculous cholecystitis. Acta Gastroenterologica Belgica 2007; 70 (Fasc. 1): A34.
  168. Turumin JL, Kozlova NM. Clinical effects of the pathogenetic treatment of patients with chronic acalculous cholecystitis. Gut 2007; 56(Suppl. 3): 280 (G-449).
  169. Turumin JL, Kozlova NM. The restoration of the functional and metabolic state of hepatobiliary system in the patients with chronic acalculous cholecystitis before and after pathogenetic treatment. Acta Gastroenterologica Belgica 2007; 70(Fasc. 1): A32.
  170. Ilchenko IA, Deliukina OV. Significance of biliary dysfunction in the pathogenesis of gallstone disease. Eksp Klin Gastroenterol 2011; (7): 70-8.

 

Patents (Russia)

  1. Agent for prophylaxis of stone formation in gallbladder (Salsola collina Pall.): Patent RU 2020947 C1 // Publication Date: 1994.10.15 / Semenov AA, Kuznetsov IG, Syrchina AI, Tjurjumin JaL, Nikiforov SB, Lokheh EV.
  2. Medical-prophylaxis agent of cholesterol-regulating action and a method of disease treatment caused cholesterol metabolism damage in organism (Salsola collina Pall.): Patent RU 2043111 C1 // Publication Date: 1995.09.10 / Chupin SP.
  3. Method for treating the cases of hypomotor hypokinetic dyskinesia of biliary tract: Patent RU 2105577 C1 // Publication Date: 1998.02.27 / Paltsev AI.
  4. Method of treatment of patients with calculous cholecystitis (MTBE): Patent RU 2129026 C1 // Publication Date: 1999.04.20 / Shanturov VA, Tjurjumin JaL, Maltsev AB.
  5. Method for rehabilitating patients after cholecystectomy: Patent RU 2221576 C1 // Publication Date: 2004.01.20 / Sidorov VV, Korjukina IP, Tuev AV, Guseva TP, Zavrazhnykh LA, Popova TN, Ovchinnikova SM, Bukina NM, Smirnov VV.
  6. Method for setting differential diagnosis of Oddi sphincter dysfunction: Patent RU 2245102 C1 // Publication Date:  2005.01.27 Bull. №3 / Deripaskina AV, Jakovlev AA, Nelasov NJu.
  7. Method for predicting functional disorders of Oddi’s sphincter by applying dynamic sonography: Patent RU 2247535 C2 // Publication Date: 2005.03.10 Bull. №7 / Akhmedov VA, Zhukov NA.
  8. Method for diagnosis biliary dyskinesia cases: Patent RU 2269292 C2 // Publication Date: 2006.02.10 Bull. №4 / Butov MA, Kuznetsov PS, Shelukhina SV, Eremina JO, Ardatova VB.
  9. Method for evaluating functional state of biliary system in patients after cholecystectomy: Patent RU 2283032 C1 // Publication Date: 2006.09.10 Bull. № 25 / Gibadulina IO, Gibadulin NV, Bogoutdinov MS, Grjaznov SV, Tupitsyna TJ.
  10. Drug possessing hepatoprotective activity (Salsola collina Pall.): Patent RU 2277925 C2 // Publication Date: 2006.12.20 Bull. № 17 / Semenov A.A., Syrchina A.I., Azhunova T.A., Tolstikhina V.V.
  11. Method for treatment of diseases caused and accompanying disturbance in metabolism of bile acids and cholesterol: Patent RU 2294207 C2 // Publication Date: 2007.02.27 Bull. №6 / Ardatskaja MD, Minushkin ON, Maksimov VA, Sazonova II, Maslovskij LV.
  12. Differential diagnosis method for distinguishing chronic pancreatitis cases of alcoholic and biliary etiology:   Patent RU 2302003 C1 // Publication Date: 2007.06.27 Bull. №18 / Lazebnik LB, Tsaregorodtseva TM, Vasilev JV, Zhivaeva NS, Vinokurova LV, Serova TI, Lychkova AE.
  13. Method for diagnosing chronic pancreatitis of alcoholic etiology:  Patent RU 2320997 C2 // Publication Date: 2008.03.27 Bull. № 9 / Lazebnik LB, Vinokurova LV, Trubitsyna IE, Lychkova AE, Gubina AV.
  14. Method of treatment of chronic pancreatitis with stenosis of main Wirsung’s duct: Patent RU 2341203 C1 // Publication Date: 2008.12.20 Bull. № 35 / Pogrebnjakov VJ, Ivanov PA, Likhanov ID, Berditskij AA, Goncharov SA.
  15. Method of treatment of chronic cholecystitis exacerbation: Patent RU 2348405 C2 // Publication Date: 2009.03.10 Bull. №7 / Kozlova NM, Tjurjumin JL.
  16. Method of determining dyskinesis of gallbladder and Oddi’s sphincter: Patent RU 2369333 C2 // Publication Date: 2009.10.10 Bull. №28 / Il'chenko AA, Maksimov VA, Chernyshev AL, Tarasov KM, Deljukina OV, Orlova JN, Lychkova AE.
  17. Method of treating patients with chronic noncalculous cholecystitis and biliary dyskinesia: Patent RU 2387444 C2 // Publication Date: 2010.04.27 Bull. №12 / Safonova SL, Emeljanova EA, Platonova AA.
  18. Method of correcting psychovegetative disorders in patients with cholelithiasis after cholecystectomy: Patent RU 2401659 C2 // Publication Date: 2010.10.20 Bull. № 29 / Plotnikova EJ.
  19. Method for prediction of developing function-type Oddi’s sphincter dyssynergia following cholecystectomy: Patent RU 2414712 C1 // Publication Date: 2011.03.20 Bull. № 8 / Serova EV, Vinnik JS, Tepljakova OV, Kovaleva OA, Kotlovskij JV.
  20. Diagnostic technique for function-type Oddi’s sphincter dyssynergia following cholecystectomy: Patent RU 2416802 C1 // Publication Date: 2011.04.20 Bull. №11 / Serova EV, Vinnik JS, Tepljakova OV.
  21. Method of medical rehabilitation of patients after cholecystectomy: Patent RU 2429888 C2 // Publication Date: 2011.09.27 Bull. №27 / Kulikov AG, Sarapulova NJ, Eremeev AV, Ivanova IZ.
  22. Method of treating cholelithiasis (MTBE): Patent RU 2437654 C1 // Publication Date: 2011.12.27 Bull. №36 / Sajfutdinov RG.
  23. Method of treating and improving quality of life in patients with chronic pancreatitis: Patent RU 2448675 C1 // Publication Date: 2012.04.27 Bull. № 12 / Romanova MM, Babkin AP, Shirjaev OJ, Kharkina DN.

 

Patents (USA)

  1. Method for the treatment of gallstones: PatentUS 4205086 // Publication Date: 1980.05.27 / Babayan V.K.
  2. Method for therapeutic use of methyl tertiary-butyl ether (MTBE): Patent US 4758596 // Publication Date: 1988.06.19 / Thistle JL, Allen MJ.
  3. Apparatus and method for removing obstructions in bodily organs or cavities: Patent US 4902276 // Publication Date: 1990.02.20 / Zakko S.F.
  4. Low viscosity solvent mixture for dissolution of cholesterol gallstones (MTBE): Patent US 4910223 // Publication Date: 1990.05.20 / Hofmann AF.
  5. Therapeutic gallstone dissolution method (MTBE): Patent US 5212202 // Publication Date: 1993.05.18 / Hofmann AF, Schteingart CD.
  6. Compositions and methods for treating gastrointestinal hypomotility and associated disorders: Patent US 20070010543 A1 // Publication Date: 2007.01.11 / Ashburn TT.
  7. FXR agonists for the treatment of nonalcoholic fatty liver and cholesterol gallstone diseases: Patent US 20090163474 A1 // Publication Date: 2009.06.25 / Zhang S, Harnish D, Evans MJ, Wang J.
  8. Method for the treatment of gallstones: Patent US 20090248033 A1 // Publication Date: 2009.10.01 / Forsell P.
  9. Use of Ezetimibe in the prevention and treatment of cholesterol gallstones: Patent US 20100016273 A1 // Publication Date: 2010.01.21 / Miquel Poblete JF, Nervi Oddone F, Gigotti Rivera AG, Zanlungo Matsuhiro S.
  10. Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases: Patent US 20100152118 A1 // Publication Date: 2010.06.17 / Shailubhai K.
  11. Farnesoid X receptor agonists: Patent US 8158665 // Publication Date: 2012.04.17 / Caldwell R, Deaton  DN, Mcfadyen RB, Navas III F, Spearing PK.
 
 

 
Dr. Jacob L. Turumin

About author, main scientific results and acknowledgments

Dr. Jacob L. Turumin (Iakov L. Tyuryumin), MD, PhD, DMSci, 04.23.1960, Doctor of Medical Sciences is engaged by elaboration of the effective pathogenetic proved methods of treatment of the biliary diseases and the pancreatic diseases, directed on decrease of morbidity, on prolongation of complete clinical remission period, on improvement of quality of life of patients after cholecystectomy, on increase of vital activity and life span (Russia).

In 1989-1990 he took an active part in elaboration of the theme “Remedy for prevention of gallstone formation in the gallbladder” and the hepato-protective agent “Siberian Tea” (Salsola Collina) - Patent No. 2020947 RU.

In 1991 Turumin J.L. successfully defended his Ph.D. thesis: "Role of cholestanol in the pathogenesis of cholesterol cholelithiasis" - Patent No.: RU 1691750.

In 1996 the new model of the pathogenesis of cholesterol cholelithiasis was first presented at the XIV International Bile Acid Meeting "Bile Acids in Hepatobiliary Diseases - Basic Research and Clinical Application" (Freiburg, Germany, 1996).

In 1997 the new conception of the "Role of the Gallbladder in a Human" was first presented at the XIX Congress of the Latin American Federation of the International College of Surgeons (La Paz, Bolivia, 1997).

In 2000 he defended his Doctor's degree thesis: "Mechanism of development of morphological-functional disturbances in the gallbladder and liver in the pathogenesis of cholesterol cholelithiasis".

In 2006, for the first time in the world, Dr. Turumin JL (MD, PhD, DMSci) removed a large (25*22 mm), thick (4-5 mm) primary melanoma without surgical treatment, without radiation therapy, without chemotherapy and without immunotherapy on the left cheek in a 42 year-old woman. The tumour was removed by means of local treatment with use of drops of disulfiram solution and drops of CuSO4 solution. Local, transit, regional and distant metastasis аrе absent since 2006, i.e. duration of disease-free period is 7 years.

In 2007 a new algorithm of pathogenetic treatment of the biliary diseases was first presented at Falk Symposium No.161 "Future Perspectives in Gastroenterology (Dresden, Germany, 2007).

In 2010 he accepted an active participation in elaboration of the theme "Model of formation of functional disturbances in the sphincter of Oddi in patients with biliary diseases".

In 2010 - 2011 he took an active part in in elaboration of the theme "The algorithm of the pathogenetic treatment of primary and metastatic melanoma".

In 2010-2011 he took an active part in elaboration and in completion of the theme “The Algorithm of the Pathogenetic Treatment of Symptomatic (with biliary pain) Biliary Diseases with Concomitant Functional Disorders in Sphincter of Oddi”.

In 2012-2013 he took an active part in elaboration and in completion of the theme "Functional disorders in the sphincter of Oddi and possibly reflux associated diseases in the hepato-biliary-cholecysto-pancreatico-duodeno-gastro-esophageal region".

In 2013 the article "Turumin JL, Shanturov VA, Turumina HE. The role of the gallbladder in humans. Revista de Gastroenterología de México. 2013; 78(3): 177-187" was published.

At present the algorithm of pathogenetic treatment of the biliary diseases is used in 105 countries of the North America, Central America and South America, Europe and Asia Pacific, Africa and Middle East (Russia, Canada, USA, Barbados (West Indies), Mexico, Panama, Puerto Rico, Venezuela, Peru, Bolivia, Colombia, Costa Rica, Dominican Republic, Ecuador, El Salvador, Guatemala, Nicaragua, Paraguay, Uruguay, Brazil, Argentina, Chile, Norway, Sweden, Finland, Great Britain, Ireland, Island, Denmark, Belgium, Netherlands, Austria, Germany, Switzerland, France, Spain, Portugal, Luxemburg, Italy, Israel, Bosnia and Herzegovina, Croatia, Macedonia, Serbia, Slovenia, Greece, European Countries, Bulgaria, Czech Republic, Slovakia, Hungary, Romania, Poland, Estonia, Latvia, Lithuania, Belarus, Ukraine, Moldova, Armenia, Georgia, Azerbaijan, Kazakhstan, Uzbekistan, Tajikistan, Kyrgyzstan, Turkey, Iraq, Iran, Pakistan, India, Bangladesh, Sri Lanka, Nepal, Philippines, Singapore, Thailand, Bangladesh, Indonesia, Malaysia, Vietnam, Hong Kong, Taiwan, China, Mongolia, South Korea, Japan, Australia, New Zealand, Madagascar, Egypt, Algeria, Ghana, Nigeria, Morocco, Tunisia, Lebanon, Tanzania, Qatar, Bahrain, United Arab Emirates, Oman, Saudi Arabia, Palestinian Territories, Yemen, Libya, Syria, and South Africa, Botswana).

In general, as a result of the scientific activity, 193 scientific works have been published, 6 patents, 2 monographs, 64 abstracts were presented on 23 international congresses and symposiums.Read more

 

Contact me:

drjacobturumin@yahoo.com

 

 


 
 
 
      ©   Я.Л. Тюрюмин,   2010