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Hymecromone (4-MU) is a recognized agent currently used in clinical practice. Since 1960, hymecromone has been used in many countries as a choleretic and cholespasmolytic, a drug approved for use in humans with biliary tract disorders. The review presents both traditional European and Russian studies of the selective antispasmodic and choleretic properties of hymecromone, due to which hymecromone is the drug of choice for the treatment of biliary tract diseases, as well as new fundamental and clinical studies of numerous pleiotropic effects of 4-MU associated with inhibition of hyaluronic acid and many other properties of this exciting molecule. These include antibacterial, antiviral, and nonspecific anti-inflammatory effects. Positive results have been demonstrated in carbohydrate and lipid metabolism disorders, autoimmune diseases, as well as liver, heart, and kidney diseases. Numerous in vitro and in vivo studies have been presented in pancreatic, prostate, skin, esophagus, breast, liver, ovary, bone cancers, metastatic lesions, leukemia, autoimmune and inflammatory diseases. Hymecromone is indicated not only as a choleretic and cholespasmolytic but also as a choleseptic in cholangitis and chronic cholecystitis, including opisthorchiasis, which does not disagree with its label. Odecromone® (hymecromone, tablets 200 mg) is available on the Russian market; it replaced the originator drug and is its fully equivalent generic.

The term post-cholecystectomy syndrome (PCES) includes a heterogeneous group of symptoms and changes in patients who have previously undergone cholecystectomy. Patients with PCEC may have abdominal pain, jaundice, or dyspeptic symptoms. Many of these complaints can be related to complications, including bile duct damage, bile fistulas, and left stones in the bile ducts. Late complications include recurrent stones in the bile ducts and bile duct strictures. With the increasing number of cholecystectomies performed during the laparoscopy era, the number of patients with PCES is also increasing. The article details the clinical case of the formation of scar changes in choledochus, right and left hepatic ducts, which led to cholestasis and cholangitis, as well as the formation of liver cirrhosis two years after cholecystectomy.

This article provides an overview of the data on postcholecystectomy syndrome (PCES). The entire period of study of this frequent complication (up to 40%) can be divided into 2 periods: surgical and therapeutic. Surgical complications of cholecystectomy accounted for 10% and were studied by surgeons. This study led to the correction of surgical treatment, formulated the examination program and reduced and minimized surgical complications. The second part of the complications is made up of functional disorders of the sphincter of Oddi, which today are the leading ones and, apparently, remain so. The article gives an idea of PCES as a dynamic disorder of the sphincter of Oddi, gives the last definition of PCES given by the IV Roman Concensus, suggests an algorithm for diagnosis and treatment. As a clinical illustration, the authors present their own data on the diagnosis and treatment of 60 patients with PCES, which confirmed the point of view proposed by the international gastroenterological community. The authors separated two types of postcholecystectomy syndrome: one with a predominance of sphincter of Oddi (SO) spasm and another with a predominance of sphincter of Oddi hypotension. The drug of choice in the spastic type is the selective antispasmodic gimecromone, in which case a dose is of the essence. In case of a hypotonic type of postcholecystectomy syndrome, motor regulators to increase the SO tone should be used. The therapy should be stepwise with an assessment of the effect and correction of the next step of treatment. This treatment option for patients with postcholecystectomy syndrome we see today as the leading one. The features of treatment associated with the developing syndrome of bacterial overgrowth (SIBO) and chronic biliary insufficiency (CBI), which require constant monitoring (diagnosis) and permanent treatment, are considered.

Aim. Evaluation of the practice of using trimebutine (tablets, 300 mg, extended release), for the treatment of patients with functional gastrointestinal disorders (FGID) in primary health care. Materials and methods. A prospective observational multicenter non-interventional study was carried out, which included patients of both sexes aged 18 to 60 years with a verified diagnosis of functional gastrointestinal disorders (functional dyspepsia, irritable bowel syndrome, biliary tract dysfunction, sphincter of Oddi dysfunction, postcholecystectomy syndrome). Trimebutine was prescribed in accordance with the instructions for medical use: orally, 300 mg twice per day for 28 days. The severity of simptoms was evaluated by five-point rating scale. Results. The study included 4433 patients, the per protocol sample consisted of 3831 people. The proportion of patients with a significant decrease in the severity of abdominal pain after treatment was 74.73% (95% confidence interval CI 73.3276.11). At the and of the study a statistically significant decrease in the severity of FGID` simptoms was observed: epigastric pain/burning (mean score at the 1st visit was 1.21 [95% CI 1.181.25], at the 2nd visit 0.22 [95% CI 0.20.23]; p0.001), abdominal pain (1st visit 2.01 [95% CI 1.982.04), 2nd visit 0.33 [95% CI 0.310.35]; p0.001), biliary pain (1st visit 1.22 [95% CI 1.181.26], 2nd visit 0.2 [95% CI 0.190.22]; p0.001), postprandial fullness and early satiation (1st visit 1.29 [95% CI 1.251.32], 2nd visit 0.21 [95% CI 0.190.22]; p0.001), severity of heartburn (1st visit 0.92 [95% CI 0.880.95], 2nd visit 0.18 [95% CI 0.170.20]; p0.001), belching (1st visit 1.13 [95% CI 1.091.16], 2nd visit 0.22 [95% CI 0.210.24]; p0.001), as well as abdominal distention (1st visit 1.99 (95% CI 1, 96, 2.03), 2nd visit 0.43 [95% CI 0.410.45]; p0.001). Conclusion. The present prospective observational multicenter non-interventional study has demonstrated that trimebutine is an effective approach to treating FGID.

The occurrence of chronic diarrhea after cholecystectomy (CCY) has been described by many researchers. However, the main mechanisms of the development of this diarrhea are not fully understood. Supposed that dysregulation of the bile acids (ВA) absorption in the ileum is played a significant role in the development of diarrhea syndrome. Aim. To determine the role of the fibroblast growth factor 19 (FGF19) level in the serum and BA concentration in feces in pathogenesis of bile acid diarrhea (ВАD) in patients after CCY. Materials and methods. Sixty-one patients were examined at various times after CCY: 30 patients with chronic diarrhea that appeared after CCY (group 1) and 31 patients with normal stools (group 2). In all patients, the level of FGF19 in the blood serum, and the daily excretion of BA in the feces were studied. The control group consisted of 28 healthy individuals. Results. In the 1st group we found lower concentrations of FGF19 in the blood serum 86.2 ng/ml (67.8; 117.8) compared with concentrations in the 2nd group 259 ng/ml (170.6; 318.8), p0.001. The daily excretion of bile acids with feces in the 1st group was 657.4 mg/day (524.6; 830.1), which was twice more than in the 2nd group and the control group. It was established an inverse correlation between serum concentration of the FGF19 and the BA excretion in the feces in all examined patients. It indicates a possible relationship between the low concentration of FGF19 in blood serum and malabsorption of the BA. Conclusion. Low level of FGF19 in the blood serum and a high excretion of BA in the feces may be one of the causes of BAD in patients undergoing cholecystectomy. Our results indicate the important role of FGF19 in the development of chronic diarrhea, which can be considered as one of the variants of postcholecystectomy syndrome.

Aim. This study was designed to prove the connection between postcholecystectomy syndrome, chronic disorder of duodenal patency, adhesive disease of the abdominal cavity, and chronic colostasis and to develop the methods of its treatment.Materials and methods. During the period from 2004 to 2016 we monitored 140 patients with a clear picture of postcholecystectomy syndrome which was manifested after the surgeries on the extrahepatic biliary tract by clinic of passage disorders in the digestive tract.Results. The results of our study indicate that there are created a number of conditions that cause various pathologies in patients with colostasis who have unfavorable outcomes after cholecystectomy. Colostasis can cause functional changes in the biliary tract due to the overstretch of the colon areas by the accumulated contents. Functional disturbances can be a consequence of the tension of the mesocolon lowered by the transverse colon or duodenojejunal ligament narrowing the lumen of the duodenum. The hepatic angle of the large intestine in high position, deforming the bile duct and duodenum, can also cause postcholecystectomy syndrome.Conclusion. Long-term results of the surgical treatment of the pathological conditions after cholecystectomy depend not only on the condition of the organ which surgery was performed on but also on other physiologically related organs and body systems. The biliary and enteroenteric connections are very important in this case. Psychosomatic disorders of the patient are also crucial while assessing the long-term results of the surgical treatment of this type of patients. The results of the surgical treatment of the duodenal patency chronic disorders depend on the selected type of surgery. Thus, the exclusion of the duodenum from the food passage gives better results than the surgeries aimed at improving the passage of food through the duodenum. The choledochojejunostomy and duodenoenterostomy are not effective. In the most severe cases of duodenal patency chronic disorders two sided exclusion of the duodenum with duodenenterostomy can be the only effective method of its correction but the development of post-resection syndrome cannot be ruled out.

Aim. To estimate the incidence of abdominal pain syndrome (APS) and to assess quality of life (QOL) in patients within 10 years after cholecystectomy (CE). Subjects and methods. This investigation is part of a long-term prospective follow-up study of patients after CE for cholelithiasis (CL). It enrolled 145 people: 30 (21.5%) patients with baseline asymptomatic CL and 115 (80.7%) with its clinical manifestations. The time course of changes in APS and QOL were analyzed. Results. Over 10 years, all the patients showed a decrease in the incidence of APS from 84.1% (n=95) to 66.4% (n=75; p=0.004). In Group 1 (n=89), APS was at baseline detected in all the patients; 10 years later, its incidence declined to 67.4% (n=60; p < 0.001). Biliary pains were predominant; these had been identified significantly less frequently over the 10-year period in 47 (52.8%) patients; p

The article analyzes the causes of recurrent abdominal pain and dyspeptic phenomena in 657 patients after cholecystectomy. The authors found out that after gall bladder resection 48% of patients complain of pain and dyspepsia. Postcholecystectomy syndrome (dysfunction of Oddi’s sphincter) is diagnosed in 15.2% of the patients. The proportion of diseases of the esophagus and organs of the gastroduodenal zone is 36.4%, of the hepato-pancreato-biliary one is 38.3 per cent. Diagnostic errors at the preoperative stage and/or tactical ones during cholecystectomy amounted to 7.8%.

After cholecystectomy, elderly patients require special attention, due to the influence of involution processes in the body on the formation of complications. To identify prognostic criteria for the formation of fatty liver degeneration in the long-term period of minimally invasive cholecystectomy, 159 men were examined. Dysregulation of the biliary tract was determined using magnetic resonance cholangiopancreatography, elastography and magnetic resonance imaging of the liver. Microbial markers of the wall microbiome of the intestine were determined using chromatography-mass spectrometry. The relationship between an increase in body mass index and a decrease in the amount of obligate microbiome (r=-0,43, p<0,050), as well as with the formation of fatty liver degeneration in elderly patients, was revealed. The features of vegetative regulation in elderly people with fatty liver degeneration have been determined. It has been proven that in old age, a decrease in the number of obligate anaerobic association of microorganisms of the small intestine (on average from 15 659 to 7 630 in persons of the 2nd age subgroup and from 1 457 to 17 837 in the 3rd) is a predictor of fatty liver degeneration. The prognostic algorithm developed on the basis of the analysis of highly informative signs makes it possible to identify with an accuracy of at least 75% a high risk of fatty liver degeneration in the long-term period of cholecystectomy.

The article tells about the current concept of the postcholecystectomy syndrome according to the Rome Consensus II - III guidelines, and therapeutic approaches in the management of such patients.

A prospective clinical and instrumental study of 119 patients with cholelithiasis (CLT) and 71 patient with postcholecystectomy syndrome (PCES), who underwent cholecystectomy (CE) 2-45 years ago, was conducted. We established polymorphism of PCES clinical picture, which was presented by permanent pain syndrome (56.3%) and intermittent pain (43.7%) together with dyspepsia and motor vacuation disorders. Clinical symptoms occurred 1.2-3.7 times more often in a remote period (> 14 years after CE) regardless of the operation type. Various organic and functional GIT pathologies were found in 77.5 % of cases. Their prevalence one year after surgery is 15.1%, 2-14 years – 73.9%, 15-45 years – 84.0%ю. According to manometric data, PCES patients with prolonged pain syndrome are mostly susceptible to the functional disorders of sphincter of Oddi that are manifested through increased pressure and amplitude of contractions of sphinсter, choledochus and duodenum. It was established that the sphincter of Oddi dysfunction increases after the disappearance of reservoir and cumulative functions of the gall bladder, correlating with the development of GIT pathology in a distant period.

There are a lot of different views on the definition of postcholecystectomy syndrome. 4 major causes of complications after cholecystectomy are distinguished. Pathogenesis of digestive disorders associated with postcholecystectomy syndrome is proved to be a complex and multicomponent process, consisting of a number of interlinked and closely related pathogenic "rings". In case of absence of indications for surgical correction of the syndrome, prescription of combination of pancreatine in enterosoluble mini-microspheres and selective myotropic anti-spasmatic mebeverine is recommended as the optimal way of breaking the "vicious circle" described above.

Cholecystectomy is one of the most common surgical procedures done in Russia and worldwide. Complaints of pain and dyspepsia occur at least in half of patients who underwent the surgery. Postcholecystectomy syndrome (PCS) is a polyetiological syndrome with functional or organic causes. About half of pain and dyspepsia after cholecystectomy are associated with organic disease (distal common bile duct stricture, pancreatic and gastric cancer, acute pancreatitis, etc). Other cases are explained by functional causes, including sphincter of Oddi dysfunction and functional disorders of intestinal motility.

Aim. To define frequency of onset of small intestinal bacterial overgrowth syndrome (SIBOGS) in patients with postcholecystomy syndrome (PCS); to substantiate necessity of microflora correction and assess efficacy of rifaximine in the doses 800 and 1200 mg/day. Material and methods. A breath hydrogen test (BHT) was made in 82 PCS patients. Rifaximine was given to 40 SIBOGS patients: 20 of them received the drug in a dose 800 mg/day and 20 - in a dose 1200 mg/day for 7 days. The efficacy was estimated by attenuation of the clinical symptoms and parameters of BHT. Results. SIBOGS was detected in 73% of PCS patients. This was an indication for antibacterial treatment. Rifaximine in a dose 800 mg/day failed to attenuate pain and to eliminate dyspeptic syndromes in some patients, BHT in them was not normal. Administration of rifaximine in a dose 1200 mg/day normalized BHT in 90% patients and eliminated clinical symptoms in most of the patients. Conclusion. Rifaximine in a dose 1200 mg/day vs 800 mg/day in PCS patients with SIBOGS is more effective as it eliminates clinical symptoms and normalizes BHT.

Aim of investigation. To study the results of complex investigation of patients with postcholecystectomy syndrome for the sake of diagnostics of functional disorders of the sphincter of Oddi (SO) and targeted treatment.Material and methods. Overall 70 patients mainly with biliary colic after cholecystectomy were included in original study. The complex investigation, that included laboratory methods, ultrasound investigation, including that with test meal, endosonography, endoscopic cholangiopancreatography excluded organic changes of pancreatobiliary system. Successful SO manometry was executed in 27 of 32 patients.Results. Functional SO disorders (spasm of papilla of Vater, hyper- and hypokinetic dyskinesia, increased frequency of contractions, local stenosis of papilla of Vater in combination to sphincter dysfunction) were diagnosed in all patients, who underwent endoscopic SO manometry. Treatment was prescription was differential, spasmolytic and prokinetic drugs were applied.

Aim: Evaluation of the practice of using trimebutine (tablets, 300 mg, extended release), for the treatment of patients with functional gastrointestinal disorders (FGID) in primary health care., Materials and Methods: A prospective observational multicenter non-interventional study was carried out, which included patients of both sexes aged 18 to 60 years with a verified diagnosis of functional gastrointestinal disorders (functional dyspepsia, irritable bowel syndrome, biliary tract dysfunction, sphincter of Oddi dysfunction, postcholecystectomy syndrome). Trimebutine was prescribed in accordance with the instructions for medical use: orally, 300 mg twice per day for 28 days. The severity of simptoms was evaluated by five-point rating scale., Results: The study included 4433 patients, the per protocol sample consisted of 3831 people. The proportion of patients with a significant decrease in the severity of abdominal pain after treatment was 74.73% (95% confidence interval CI 73.3276.11). At the and of the study a statistically significant decrease in the severity of FGID` simptoms was observed: epigastric pain/burning (mean score at the 1st visit was 1.21 [95% CI 1.181.25], at the 2nd visit 0.22 [95% CI 0.20.23]; p0.001), abdominal pain (1st visit 2.01 [95% CI 1.982.04), 2nd visit 0.33 [95% CI 0.310.35]; p0.001), biliary pain (1st visit 1.22 [95% CI 1.181.26], 2nd visit 0.2 [95% CI 0.190.22]; p0.001), postprandial fullness and early satiation (1st visit 1.29 [95% CI 1.251.32], 2nd visit 0.21 [95% CI 0.190.22]; p0.001), severity of heartburn (1st visit 0.92 [95% CI 0.880.95], 2nd visit 0.18 [95% CI 0.170.20]; p0.001), belching (1st visit 1.13 [95% CI 1.091.16], 2nd visit 0.22 [95% CI 0.210.24]; p0.001), as well as abdominal distention (1st visit 1.99 (95% CI 1, 96, 2.03), 2nd visit 0.43 [95% CI 0.410.45]; p0.001)., Conclusion: The present prospective observational multicenter non-interventional study has demonstrated that trimebutine is an effective approach to treating FGID.

The occurrence of chronic diarrhea after cholecystectomy (CCY) has been described by many researchers. However, the main mechanisms of the development of this diarrhea are not fully understood. Supposed that dysregulation of the bile acids (ВA) absorption in the ileum is played a significant role in the development of diarrhea syndrome., Aim: To determine the role of the fibroblast growth factor 19 (FGF19) level in the serum and BA concentration in feces in pathogenesis of bile acid diarrhea (ВАD) in patients after CCY., Materials and Methods: Sixty-one patients were examined at various times after CCY: 30 patients with chronic diarrhea that appeared after CCY (group 1) and 31 patients with normal stools (group 2). In all patients, the level of FGF19 in the blood serum, and the daily excretion of BA in the feces were studied. The control group consisted of 28 healthy individuals., Results: In the 1st group we found lower concentrations of FGF19 in the blood serum 86.2 ng/ml (67.8; 117.8) compared with concentrations in the 2nd group 259 ng/ml (170.6; 318.8), p0.001. The daily excretion of bile acids with feces in the 1st group was 657.4 mg/day (524.6; 830.1), which was twice more than in the 2nd group and the control group. It was established an inverse correlation between serum concentration of the FGF19 and the BA excretion in the feces in all examined patients. It indicates a possible relationship between the low concentration of FGF19 in blood serum and malabsorption of the BA., Conclusion: Low level of FGF19 in the blood serum and a high excretion of BA in the feces may be one of the causes of BAD in patients undergoing cholecystectomy. Our results indicate the important role of FGF19 in the development of chronic diarrhea, which can be considered as one of the variants of postcholecystectomy syndrome.