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Aim: to provide data on the pathogenesis of functional biliary pain and provide rationale for the use of trimebutine for this indication.Key points. Biliary pain is one of the most frequent reasons for patients to see a doctor. The diagnosis of functional disorder of the gallbladder and Oddi's sphincter is legitimate only after the exclusion of organic causes from both the gastrointestinal tract and other organs and systems. The initial appeal to surgeons with a complaint of pain in the epigastrium or right hypochondrium may lead to unjustified surgical intervention that does not bring relief to the patient's suffering. The consequences of cholecystectomy also have an anatomical and physiological justification for the occurrence or preservation of biliary pain. Currently, two main hypotheses are being considered to explain its cause: increased intraluminal pressure due to morphological and functional obstacles to bile outflow and visceral hypersensitivity. In the multilevel system of regulation of the gallbladder and sphincter apparatus, the opioid system occupies a special place. The agonist of peripheral receptors of the enkephalinergic system, trimebutine, in clinical studies led to the relief of biliary pain in more than 80 % of patients with functional biliary disorders, while a significant decrease in the severity of diarrhea, dyspeptic, and constipation syndromes was revealed.Conclusion. The prescription of the peripheral receptor agonist of the enkephalinergic system, trimebutine, is pathogenetically justified for functional biliary pain.

A 30-year-old female patient presented with monthly episodes of severe intermittent upper abdominal pain, especially after consuming fatty meals. Over a period of 5 years, she visited the emergency department 21 times due to the intensity of the pain. Although the pain appeared consistent with biliary pain, both blood and imaging tests showed no abnormalities. Despite not meeting the Rome IV criteria, we suspected sphincter of Oddi dysfunction (SOD). To further investigate, we conducted hepatobiliary scintigraphy (HBS), which revealed a clear delay in bile excretion. With the patient's informed consent, we performed endoscopic sphincterotomy (EST) and as of 10 months later, there have been no recurrences. This case demonstrates an instance of SOD that could not be diagnosed using the Rome IV criteria alone but was successfully identified through HBS. It underscores the possibility of hidden cases of SOD among patients who regularly experience severe epigastric pain, where routine blood or imaging tests may not provide a diagnosis. HBS may be a useful non-invasive test in confirming the presence of previously undiagnosed SOD. As SOD can be easily treated with EST, updating the current diagnostic criteria to include such types of SOD should be considered in the future. [ABSTRACT FROM AUTHOR]

Low phospholipid-associated cholelithiasis (LPAC) is a rare, still poorly understood genetic disorder characterized by the association of an ABCB4 mutation and low biliary phospholipid concentration with recurrent cholelithiasis, responsible for the development of intrahepatic lithiasis in adults. The mutation of the ABCB4 gene, which codes for the ABCB4/MDR3 ductal protein, a biliary transporter, leads to precipitation of cholesterol crystals in the bile ducts leading to the formation of intrahepatic stones. The diagnosis should be suspected when at least 2 of the following criteria are present: onset of symptoms before age 40; recurrence of biliary symptoms (biliary colic, jaundice, cholangitis, acute pancreatitis) after cholecystectomy; presence of echogenic foci in the liver indicative of intrahepatic stones or biliary sludge; previous episode(s) of intrahepatic cholestasis during pregnancy; and a family history of gallstones in first degree relatives. Imaging techniques, especially ultrasound, play an important role in the detection of intrahepatic stones. The majority of clinical situations are simple and not serious, often managed by medical treatment with ursodeoxycholic acid, but certain complicated forms may require more invasive endoscopic or surgical treatment. We report a case of a 43-year-old woman, cholecystectomized 5 years ago, who presented with liver colic-like pain with cytolysis and biological cholestasis. Ultrasound and MRI showed the presence of intrahepatic calculi disseminated along the bile duct pathway creating a comet tail appearance and generating a posterior shadow cone. The interrogation of the patient showed that her sister was being followed for LPAC syndrome. The diagnosis of LPAC syndrome was retained and the patient was put under medical treatment with ursodeoxycholic acid with regular clinical, biological and radiological follow-up.

Introduction. This multicentre prospective non-interventional observational study was conducted to obtain additional data about Odeston efficacy and safety in routine clinical practice. The objectives of the study included collection of clinical characteristics of patients, evaluation of Odeston effects in treatment of biliary pain and changes in the gallbladder emptying, evaluation of compliance to therapy, and treatment effect satisfaction.Materials and methods. The study was conducted from July 2020 to April 2021 at the premises of 60 study sites in 4 cities of the Republic of Kazakhstan. Patients having indications for Odeston administration according to the patient leaflet were enrolled. The study included 2 patient visits and an intermediate telephone contact. A visual analogue scale and RAPID questionnaire were used to characterise biliary pain; severity of associated symptoms, bowel habit and a quality of life according the SF-12 were also assessed. A rate of a ≥50 % reduction in symptom severity was used as a primary efficacy criterion; a rate of a ≥10 improvement in the SF-12 quality of life score was used as a secondary efficacy criterion. Compliance to treatment was evaluated using a number of days on Odeston. Treatment satisfaction was assessed using 5 grades.Results. 877 patients, 68.2 % of females and 31.8 % of males, were included in the study; the mean age was 46.0 ± 14.9 years. Primary functional biliary disorder was diagnosed in 65.3 % of patients, chronic non-calculous cholecystitis — 51.4 %, uncomplicated gallbladder disease — in 8.9 %, biliary sludge — 38.4 %, sphincter of Oddi functional disorder — 5.3 % of patients. A dose of Odeston was prescribed at the discretion of the physician. Group A patients received 600 mg (n = 89), group B received 1200 mg of Odeston a day (n = 788). In group B, an incidence of pronounced pain interference with daily living activities was higher. In both groups, the mean VAS scores were reduced to 1 point on treatment, a primary efficacy criterion was achieved in 77.3 % of patients in group A and in 79.8 % of patients in group B, р < 0.05. In both groups, a reduction in the incidence of constipation and diarrhea (р < 0,001) and an increase in the mean scores of physical and mental functioning were noted (р < 0.001, though a secondary efficacy criterion was not achieved (a ≥10 change in the SF-12 score). A prevalence of ultrasonographic sings of biliary sludge was reduced, and an increased gallbladder emptying was observed (p < 0.001). 77.4 % of patients in a total group of patients reported about drug administration for 21 days. A number of patients who were completely satisfied with treatment was higher in group B (p = 0.027).Conclusions. It was found that biliary pain interfered with daily living activities and commonly accompanied by other symptoms of gastrointestinal dysmotility. Odeston effectively reduces the severity of biliary pain, corrects dyspeptic disorders and normalizes stool pattern in patients with functional and organic diseases of the biliary system. Treatment satisfaction was higher with a dose of 1200 mg a day, particularly in more pronounced interference of pain with daily living activities.

Background. Biliary sludge (BS) refers to the pre-stone stage of gallstone disease. Timely treatment of this condition with ursodeoxycholic acid (UDCA) drugs helps prevent the progression of the disease. However, not all drugs used in practice are equally effective in relieving clinical manifestations, resolving sludge according to ultrasound results and tolerance. Aim. To evaluate the therapeutic efficacy of the drug Ursofalk in comparison with other UDCA drugs used for the treatment of BS. Materials and methods. We examined 105 people with different types of BS identified during ultrasound examination (US); they were divided into 2 groups depending on the UDCA drug taken. In patients, the dynamics of clinical manifestations was assessed using a questionnaire, as well as the dynamics of the ultrasound picture while taking UDCA. Results. Statistical analysis showed that Ursofalk significantly better relieves biliary pain (p=0.025) and biliary dyspepsia (p=0.039), pain regression occurs faster (p=0.01) in 21 days. It also has a better tolerance in 94.34% of cases compared to other drugs 67.31% (p=0.017). Ursofalk has a greater effect on the regression of BS according to ultrasound results after 3 months (p=0.022) and 6 months (p=0.016). Conclusion. The drug studied by us demonstrated high efficiency in relation to patients with BS, while there were minimal side effects, which led to a better tolerability of therapy.

Abstract Multiseptated gallbladder (MSG) (also known as “Honeycomb gallbladder”) is a rare condition that was first described by Knetsch in 1952, and there are around 150 cases described over the world. MSG has been described as a congenital anomaly in most of the cases and as acquired in a few. Moreover, the phenomenon was described with a variety of different symptoms and management. The aim of this article is to have better understanding of this condition and management approach. We are reporting a 4‐year‐old girl, who presented to Sidra Medicine, Qatar with MSG. We have also included 97 cases for review and analysis. The median age of presentation of the condition was 27 years but may present in neonates and in the elderly, while gender was not a risk factor. Abdominal pain is the most common presenting symptom, but it can present without symptoms. Certain congenital anomalies were detected in the pancreaticobiliary system in few patients with MSG. Medical treatment was reported in eight symptomatic patients, four of whom failed therapy. Cholecystectomy was performed in 40 patients, which resulted in resolutions of symptoms in 13 of them. Based on the available literature, congenital MSG is probably due to in‐pouching of gallbladder wall to its own cavity forming septa containing muscular fibers. MSG can be diagnosed solely via imaging, and ultrasound appears to be an effective and feasible mode of diagnosis. Medical treatment efficacy is not well‐known, but cholecystectomy has resulted in complete resolution in symptomatic patients.

Introduction. The prevalence of functional biliary disorders continues to increase with insufficient effectiveness of existing treatment approaches. Among them, functional biliary disorders of sphincter of Oddi account for at least 50%.Objective. To study efficacy, safety and tolerability of a fixed combination of glycyrrhizic acid and ursodeoxycholic acid (Fosfogliv Urso) in capsule form in patients with functional biliary disorders of sphincter of Oddi.Materials and Methods. The study included 32 patients diagnosed with functional biliary sphincter of Oddi disorders established according to the Rome Criteria IV revision (2016). Patients received Fosfogliv Urso (250 mg ursodeoxycholic acid and 35 mg glycyrrhizic acid) 1 capsule 3 times a day for 8 weeks. Prior to treatment, all study participants underwent a standard set of laboratory and instrumental examinations.Results. Against the background of Fosfogliv Urso treatment, statistically significant decrease of biliary pain prevalence up to 48.3% (p < 0.001); intense biliary pain up to 11.4% (p < 0.0001); intensity of pain syndrome on visual analogue scale down to 1.7 ± 0.9 cm was registered (p < 0.0001). Alanine aminotransferase activity significantly decreased to 34.0 ± 4.0 U/L (p < 0.001). There was a tendency of choledochal diameter decrease to 0.57 ± 0.01 cm. Treatment efficacy was rated by patients as very good and good in 83.4% of cases. The safety profile was assessed as favorable and tolerability as satisfactory.Discussion. The results obtained were superior to those previously obtained for ursodeoxycholic acid monotherapy and confirmed the data of the previously conducted phase III study. The rationality of the combination is due to the mutual complementation and possible synergism of the pharmacological effects of glycyrrhizinic and ursodeoxycholic acids.Conclusion. The results obtained allow to recommend the prescription of Fosfogliv Urso in the complex scheme of treatment and prophylaxis of functional biliary disorders of sphincter of Oddi.

Sphincter of Oddi dysfunction (SOD) is a benign non-tumoral disorder of the major papilla. It occurs mainly after cholecystectomy but can also occur before surgery. Biliary pain and biliary colic are the most frequent symptoms although recurrent pancreatic pain or pancreatitis can also be presenting symptoms. In about half of the cases, there is a fibrotic stricture of the sphincter of Oddi, probably secondary to the passage of biliary stones, while in the remaining half, the syndrome is due to ampullary motility disorders. The diagnosis of SOD first requires exclusion of choledocholithiasis or ampullary tumor, by means of ERCP, endoscopic ultrasound or magnetic resonance imaging. Findings on biliary manometry will establish the diagnosis, but this technique is performed less and less often because its high risk of inducing pancreatitis discourages its use as a diagnostic procedure. Biliary scintigraphy offers a risk-free alternative albeit with lower sensitivity. Medical treatment relies on the administration of trimebutine and nitroglycerine when pain occurs. Their efficacy is moderate. Sometimes patients are referred for endoscopic sphincterotomy. Endoscopic treatment should be performed only for patients with biliary pain associated with hepatic function disorders and/or bile duct dilatation. Practicians and patients should be aware that endoscopic sphincterotomy in this clinical setting is associated with a high risk of pancreatitis and its efficacy is limited in patients with pain but without laboratory anomalies or dilatation of the biliary duct (type III Milwaukee classification). Patients with Milwaukee classification type III disorders have mostly functional complaints or psychosocial disabilities and require only medical management. [ABSTRACT FROM AUTHOR]

The review article presents current data on functional disorders of the biliary system, taking into account the latest recommendations of experts of the Rome Foundation (Rome Criteria IV, 2016) and the Russian Gastroenterological Association (specialized clinical recommendations, 2018). According to modern concepts, biliary dysfunction is a group of functional disorders of the biliary system caused by motor disorders and increased visceral sensitivity. According to the literature data, the prevalence of functional disorders of GB and OS is 10-15%, and violation of OS function is revealed in 30-40% of patients who underwent cholecystectomy (CE). The presence of biliary pain is an obligatory condition in the diagnosis of functional disorders of GB and OS. Bilirubin and serum transaminases (AST, ALT) levels may increase in biochemical blood analysis in patients with functional OS disorder of biliary type, and pancreatic amylase and lipase in case of functional OS disorder of pancreatic type. Ultrasound examination of abdominal organs is considered to be the priority among instrumental methods. This technique allows to exclude organic lesions of both the GB and visualized ducts, and adjacent organs (GSD, biliary tract, liver and pancreas neoplasms). Magnetic resonance cholangiopancreatography (MRCP) is used as a clarifying method, which allows to visualize the state of biliary ducts throughout. Ultrasonic cholecystography is used to assess the contractile activity of the GB. When duct dilation is detected and/or when liver/pancreatic enzyme levels are elevated in the absence of changes according to MRCP data, it is reasonable to perform an endoscopic ultrasound examination. According to the latest recommendations of the Russian Gastroenterological Association (2018), the foundation of pharmacotherapy for this group of diseases are antispasmodics and ursodeoxycholic acid (UDCA).

Gallstone disease is revealed in 10–20% of the population with a clear tendency to affect the younger population. In a clinically manifested course, cholecystectomy remains the treatment of choice. Symptoms and signs persist or even become more severe after gallbladder surgery in 10-15% of cases (“postcholecystectomy syndrome”). Postcholecystectomy syndrome includes heterogeneous disorders of liver, pancreas, duodenum, sphincter of Oddi, etc. that can be associated with errors or negative consequences of surgical intervention. Often, symptoms may persist because of previously unrecognized chronic diseases of neighboring organs. The spectrum of effective conservative measures is rather limited. The Advisory Board was held on May 4, 2019, in Almaty (Kazakhstan) to re-estimate the definitions and categories related to the issue of the postcholecystectomy syndrome and to develop the diagnostic and treatment algorithm for patients with the postcholecystectomy dysfunction of the sphincter of Oddi. The statements discussed by the interdisciplinary team of gastroenterologists and surgeons were addressed to general practitioners, therapists, gastroenterologists, and surgeons. The Advisory Board emphasized that organic and functional biliary diseases manifest mainly by biliary pain, main characteristics of which were defined in the Rome IV consensus based on the statistical analysis of a large pool of clinical data. For a more accurate bile duct system assessment and the exclusion of cholelithiasis, the examination algorithm was proposed, which included abdominal ultrasound investigation, endoscopic ultrasound investigation of the pancreatobiliary area, and magnetic resonance cholangiopancreatography. Diagnostic algorithm for differentiation of functional biliary disorders from organic gastrointestinal pathology was developed. Sphincter of Oddi dysfunction may be considered as a postcholecystectomy syndrome manifestation in 1.5-3% of cases. Apart from rational nutrition, conservative management of functional gastrointestinal diseases implies pharmacological therapy. The efficacy of non-steroidal anti-inflammatory drugs, prokinetics, nitrates, antispasmodics, calcium channel antagonists, botulinum toxin, and hymecromone was demonstrated in previous studies. Papillosphincterotomy is not effective in relieving biliary pain in cases of the sphincter of Oddi dysfunction. The proposed algorithm for the management of patients with the postcholecystectomy syndrome was presented.

Multiseptated gallbladder (MSG) (also known as "Honeycomb gallbladder") is a rare condition that was first described by Knetsch in 1952, and there are around 150 cases described over the world. MSG has been described as a congenital anomaly in most of the cases and as acquired in a few. Moreover, the phenomenon was described with a variety of different symptoms and management. The aim of this article is to have better understanding of this condition and management approach. We are reporting a 4‐year‐old girl, who presented to Sidra Medicine, Qatar with MSG. We have also included 97 cases for review and analysis. The median age of presentation of the condition was 27 years but may present in neonates and in the elderly, while gender was not a risk factor. Abdominal pain is the most common presenting symptom, but it can present without symptoms. Certain congenital anomalies were detected in the pancreaticobiliary system in few patients with MSG. Medical treatment was reported in eight symptomatic patients, four of whom failed therapy. Cholecystectomy was performed in 40 patients, which resulted in resolutions of symptoms in 13 of them. Based on the available literature, congenital MSG is probably due to in‐pouching of gallbladder wall to its own cavity forming septa containing muscular fibers. MSG can be diagnosed solely via imaging, and ultrasound appears to be an effective and feasible mode of diagnosis. Medical treatment efficacy is not well‐known, but cholecystectomy has resulted in complete resolution in symptomatic patients. [ABSTRACT FROM AUTHOR]

Introduction. The term «functional disorders of the biliary tract and bile ducts» defines the conditions, which produce typical patterns of biliary pains in the absence of obvious signs of organic lesions of the gallbladder and bile ducts. The materials of the Rome IV consensus present the diagnostic criteria of their main types – functional disorders of the gall bladder and sphincter of Oddi. Vasilenko Clinic of Internal Diseases Propedeutics, Gastroenterology and Hepatology of the University Clinical Hospital No. 2 of Sechenov University carried out a noninterventional observational program to study the experience in using Trimedat® (trimebutine maleate) in the routine outpatient and inpatient practice in the treatment of patients with functional diseases of the biliary tract. Information partners of the program are the Russian Gastroenterological Association (RGA) and the Russian Society for the Study of the Liver (RSSL).Materials and methods. The program included patients of both sexes aged 18 to 65 years with ICD-10 diagnoses «spasm of the sphincter of Oddi» (K 83.4), «postcholecystectomy syndrome» (K 91.5), «other specified diseases of the gallbladder» (K 82.8) , «other specified diseases of the bile ducts» (K 83.8), «disorders of gallbladder and biliary tract in diseases classified elsewhere» (K 87.0), if the clinical picture was consistent with functional biliary disorders according to the Rome IV criteria and in cases when the doctor decided to prescribe Trimedat® therapy. Patients were observed for 28 ± 1 days. The dynamics of biliary pain and discomfort, as well as other symptoms (in particular, nausea, flatulence) were evaluated on the background of the therapy, using the Gastrointestinal Symptom Score Scale, in which the severity of each symptom is estimated by 7 grades (Alekseev N.Yu., 2006) with adding a section to evaluate the biliary disorders. In the presence of criteria for functional disorders of the gallbladder, an ultrasound control of the fraction of its discharge was carried out before and after the therapy.Results. 100 patients (33 (33%) men and 67 (67%) women, the average age 42.2 ± 13.2 years (18–65 years)) were enrolled in the program. In accordance with the Rome IV Consensus, the majority of patients (83 (83%)) had the functional disorders of GB; in 16 (16%) patients with the removed GB, the picture corresponded to the functional disorder of SO, one patient with kept GB was diagnosed with SO dysfunction. The treatment with Trimedate® at a standard dosage resulted in a decrease in the proportion of pain in the epigastric region (in the Scale section evaluating the biliary tract symptoms), the degree of nausea and bloating. Differences between the visits were estimated by the Friedman’s test, p

Background: Studies have shown that patients with abdominal pain and biliary dyskinesia (low ejection fraction <35 ​%) have significant improvement of symptoms following laparoscopic cholecystectomy, but there is lack of evidence that demonstrates whether patients with biliary symptoms and a normal ejection fraction (>35 ​%) will have similar results., Methods: Retrospective, single center study of patients with biliary pain and negative workup, including HIDA with EF>35 ​%, who were treated with laparoscopic cholecystectomy from 2017 to 2022., Results: There were 117 total patients. The mean age was 45.49 ​± ​15.5 years and 101 (86 ​%) were female. 101 (86 ​%) of patients underwent a right upper quadrant ultrasound, 91 had normal findings, 9 difficult to visualize anatomy and 1 had adenomyomatosis. All patients had a normal HIDA scan and ejection fraction 104 (89 ​%) of patients followed up in clinic within 30 days of surgical intervention. 87 (84 ​%) reported resolution of pre-operative symptomatology after surgical intervention. There was no statistically significant correlation between pain with CCK administration during HIDA (p ​= ​0.803) scan or ejection fraction (p ​= ​0.0977) with resolution of symptoms., Conclusions: Laparoscopic cholecystectomy appears to be a beneficial intervention for patients with abdominal pain and normokinetic biliary disease. Offering surgical intervention early on can potentially save patients from exhaustive diagnostic investigations and possibly misdiagnosis., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Delayed cholecystectomy in patients with symptomatic gallstone disease is associated with recurrence. Limited data on the recurrence patterns and the factors that determine them are available., Objective: We aimed to determine the pattern of relapse in each symptomatic gallstone disease (acute pancreatitis, cholecystitis, cholangitis, symptomatic choledocholithiasis, and biliary colic) and determine the associated factors., Methods: RELAPSTONE was an international multicenter retrospective cohort study. Patients (n = 3016) from 18 tertiary centers who suffered a first episode of symptomatic gallstone disease from 2018 to 2020 and had not undergone cholecystectomy during admission were included. The main outcome was relapse-free survival. Kaplan-Meier curves were used in the bivariate analysis. Multivariable Cox regression models were used to identify prognostic factors associated with relapses., Results: Mean age was 76.6 [IQR: 59.7-84.1], and 51% were male. The median follow-up was 5.3 months [IQR 2.1-12.4]. Relapse-free survival was 0.79 (95% CI: 0.77-0.80) at 3 months, 0.71 (95% CI: 0.69-0.73) at 6 months, and 0.63 (95% CI: 0.61-0.65) at 12 months. In multivariable analysis, older age (HR = 0.57; 95% CI: 0.49-0.66), sphincterotomy (HR = 0.58, 95% CI: 0.49-0.68) and higher leukocyte count (HR = 0.79; 95% CI: 0.70-0.90) were independently associated with lower risk of relapse, whereas higher levels of alanine aminotransferase (HR = 1.22; 95% CI: 1.02-1.46) and multiple cholelithiasis (HR = 1.19, 95% CI: 1.05-1.34) were associated with higher relapse rates., Conclusion: The relapse rate is high and different in each symptomatic gallstone disease. Our independent predictors could be useful for prioritizing patients on the waiting list for cholecystectomies., (© 2024 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background: Acute biliary pain is the most common presentation of gallstone disease. Untreated patients risk recurrent pain, cholecystitis, obstructive jaundice, pancreatitis and multiple hospital presentations. We examine the outcome of implementing a policy to offer laparoscopic cholecystectomy on index presentation to patients with biliary colic in a tertiary hospital in Australia. Methods: This is a retrospective cohort study of adult patients presenting to the emergency department (ED) with biliary pain during three 12‐month periods. Outcomes in Group A, 3 years prior to policy implementation, were compared with groups 2 and 7 years post implementation (Groups B and C). Primary outcomes were representations to ED, admission rate and time to cholecystectomy. Results: A total of 584 patients presented with biliary colic during the three study periods. Of these, 391 underwent cholecystectomy with three Strasberg Type A bile leaks and no bile duct injuries. The policy increased admission rates (A = 15.8%, B = 62.9%, C = 29.5%, P < 0.001) and surgery on index presentation (A = 12.0%, B = 60.7%, C = 27.4%, P < 0.001). There was a decline in time to cholecystectomy (days) (A = 143, B = 15, C = 31, P < 0.001), post‐operative length of stay (days) (A = 3.6, B = 3.2, C = 2.0, P < 0.05) and representation rates to ED (A = 42.1%, B = 7.1%, C = 19.9%, P < 0.001). There was a decline in policy adherence in the later cohort. Conclusion: Index hospital admission and cholecystectomy for biliary colic decrease patient representations, time to surgery, post‐operative stay and complications of gallstone disease. This study demonstrates the impact of the policy with initial improvement, the dangers of policy attrition and the need for continued reinforcement. [ABSTRACT FROM AUTHOR]

Purpose of Review: Portal cavernoma cholangiopathy is a rare condition, a proper recognition of which is critical. Solid data on this condition are scarce. This review aims at updating current knowledge on its definition, manifestations, diagnosis, and management.Recent Findings: A consensus has been reached to prefer the denomination portal cavernoma cholangiopathy for the bile duct irregularities associated with portal cavernoma. Such irregularities are characterized by stenosis with or without dilatation and are mostly related to the impinging on bile duct lumen by portoportal collaterals. While bile duct irregularities are found in over 80% of patients with portal cavernoma, clinical manifestations, and complications (cholecystitis and biliary stones, but rarely cholestasis) occur in only 5-35% of them. Diagnosis can be and should be based on findings at magnetic resonance cholangiography and portography. Differential diagnosis includes primary and secondary sclerosing cholangitis, and cholangiocarcinoma. Asymptomatic patients may be managed expectantly. Endoscopic procedures are to be used in the first line for complications. Combined endoscopic and surgical approaches including portosystemic shunting can be considered in refractory or recurrent cases.Summary: Portal cavernoma cholangiopathy mostly is a morphologic entity which is present in a majority of patients with portal cavernoma. The minority of patients with acute biliary complications should be treated as conservatively as possible. Late consequences of chronic cholestasis appear to be rare. [ABSTRACT FROM AUTHOR]

Background: Cholecystectomy is a common operation, increasingly performed, in the USA, for "functional gall bladder disorder" (FGBD). Outcomes of these surgeries are uncertain. In planning a study of FGBD, we needed to define the best outcome measures.Methods: We sought the opinions of patients (52 with FGBD and 100 with stones for comparison) coming to cholecystectomy. They were asked to respond in four ways about the minimum benefit they would count as "success."Results: We found that most patients do not expect cholecystectomy to relieve their pain-related disability completely, regardless of the presence or absence of stones.Conclusions: Future studies of the success of surgery should use patient-centered outcome assessments, such as PGIC (patient's global impression of change), in addition to objective measures of the impact of treatment on key symptoms, such as pain. [ABSTRACT FROM AUTHOR]

Introduction:Post-cholecystectomy syndrome and the concept of a causal relationship to sphincter of Oddi dysfunction, despite the controversy, has presented a clinically relevant conflict for decades. Historically surgeons, and now gastroenterologists have expended tremendous efforts towards trying to better understand the dilemma that is confounded by unique patient phenotypes. Areas covered:This review encompasses the literature from a century of experience on the topic of post-cholecystectomy syndrome. Relevant historical and anecdotal experiences are examined in the setting of insights from evaluation of recently available controlled data. Expert commentary:Historical observations and recent data suggest that patients with post-cholecystectomy syndrome can be categorized as follows. Patients with sphincter of Oddi stenosis will most often benefit from treatment with sphincterotomy. Patients with classic biliary pain and some objective evidence of biliary obstruction may have a sphincter of Oddi disorder and should be considered for endoscopic evaluation and therapy. Patients with atypical post-cholecystectomy pain, without any evidence consistent with biliary obstruction, and/or with evidence for another diagnosis or dysfunction should not undergo ERCP. [ABSTRACT FROM PUBLISHER]

Background: Approximately 10–15% of the adult population suffer from gallstone disease, cholelithiasis, with more women than men being affected. Cholecystectomy is the treatment of choice for people who present with biliary pain or acute cholecystitis and evidence of gallstones. However, some people do not experience a recurrence after an initial episode of biliary pain or cholecystitis. As most of the current research focuses on the surgical management of the disease, less attention has been dedicated to the consequences of conservative management. Objectives: To determine the clinical effectiveness and cost-effectiveness of cholecystectomy compared with observation/conservative management in people presenting with uncomplicated symptomatic gallstones (biliary pain) or cholecystitis. Data sources: We searched all major electronic databases (e.g. MEDLINE, EMBASE, Science Citation Index, Bioscience Information Service, Cochrane Central Register of Controlled Trials) from 1980 to September 2012 and we contacted experts in the field. Review methods: Evidence was considered from randomised controlled trials (RCTs) and non-randomised comparative studies that enrolled people with symptomatic gallstone disease (pain attacks only and/or acute cholecystitis). Two reviewers independently extracted data and assessed the risk of bias of included studies. Standard meta-analysis techniques were used to combine results from included studies. A de novo Markov model was developed to assess the cost-effectiveness of the interventions. Results: Two Norwegian RCTs involving 201 participants were included. Eighty-eight per cent of people randomised to surgery and 45% of people randomised to observation underwent cholecystectomy during the 14-year follow-up period. Participants randomised to observation were significantly more likely to experience gallstone-related complications [risk ratio = 6.69; 95% confidence interval (CI) 1.57 to 28.51; p = 0.01], in particular acute cholecystitis (risk ratio = 9.55; 95% CI 1.25 to 73.27; p = 0.03), and less likely to undergo surgery (risk ratio = 0.50; 95% CI 0.34 to 0.73; p = 0.0004), experience surgery-related complications (risk ratio = 0.36; 95% CI 0.16 to 0.81; p = 0.01) or, more specifically, minor surgery-related complications (risk ratio = 0.11; 95% CI 0.02 to 0.56; p = 0.008) than those randomised to surgery. Fifty-five per cent of people randomised to observation did not require an operation during the 14-year follow-up period and 12% of people randomised to cholecystectomy did not undergo the scheduled operation. The results of the economic evaluation suggest that, on average, the surgery strategy costs £1236 more per patient than the conservative management strategy but was, on average, more effective. An increase in the number of people requiring surgery while treated conservatively corresponded to a reduction in the cost-effectiveness of the conservative strategy. There was uncertainty around some of the parameters used in the economic model. Conclusions: The results of this assessment indicate that cholecystectomy is still the treatment of choice for many symptomatic people. However, approximately half of the people in the observation group did not require surgery or suffer complications in the long term indicating that a conservative therapeutic approach may represent a valid alternative to surgery in this group of people. Owing to the dearth of current evidence in the UK setting a large, well-designed, multicentre trial is needed. Study registration: The study was registered as PROSPERO CRD42012002817 Funding: The National Institute for Health Research Health Technology Assessment programme.

BACKGROUND: This study assesses the safety and effectiveness of endoscopic biliary sphincterotomy (ES) in the treatment of papillary stenosis (PS) with and without biliary stones. METHODS: The records of all patients who had endoscopic retrograde cholangiopancreatography (2,689 patients) from January 1, 1991, to August 1, 2010, were reviewed. There were 117 patients with PS who had ES. RESULTS: All patients had biliary pain, a dilated common bile duct (CBD) with a maximum diameter of 10 to 25 mm, and elevated liver function tests. There were 46 patients who had prior cholecystectomy of whom 20 patients had CBD stones. The remaining 71 patients had no prior biliary surgery; there were no biliary stones in 14 patients. All patients were symptom free after ES with or without CBD stone retrieval. CONCLUSIONS: ES is the optimal treatment for PS in patients with or without biliary stones. ES eliminates pain, corrects CBD dilation, and restores LFTs to normal. [ABSTRACT FROM AUTHOR]

The most common functional disorder of the biliary tract and pancreas relates to the activity of the Sphincter of Oddi. The Sphincter of Oddi is a small smooth muscle sphincter strategically placed at the junction of the bile duct, pancreatic duct, and duodenum. The sphincter controls flow of bile and pancreatic juices into the duodenum and prevents reflux of duodenal content into the ducts. Disorder in its motility is called Sphincter of Oddi dysfunction. Clinically this presents either with recurrent abdominal biliary type pain or episodes of recurrent pancreatitis. Manometry may identify the motility abnormalities, the most clinically significant being an abnormally elevated basal pressure. The most effective treatment once an abnormal basal pressure is identified is division of the sphincter. This is associated with good long-term results. [ABSTRACT FROM AUTHOR]

Objective. To assess the outcome of laparoscopic cholecystectomy on the basis of an abnormal provocative 99mtechnetium-labelled hepato imino diacetic acid (HIDA) scan for patients with typical biliary pain and normal trans-abdominal ultrasound (TUS) scan. Patients and methods. Prospective data were collected for 1201 consecutive patients with typical biliary symptoms. Patients who were found to have a normal TUS and upper GI endoscopy subsequently underwent cholescintigraphy (HIDA scan). Patients with an abnormal HIDA scan, i.e.<40% ejection fraction with Sincalide® (cholecystokinin octapeptide) - were offered cholecystectomy. Symptoms and histology were reviewed postoperatively. Results. In all, 48/1201 (4%) patients with typical biliary symptoms had a normal ultrasound and endoscopy; 35/48 patients had an abnormal provocative HIDA scan and all underwent laparoscopic cholecystectomy. Histology in all cases revealed chronic cholecystitis and 18 patients had sludge or microlithiasis within the gallbladder. At 6-week follow-up, 31 of the 35 patients were completely asymptomatic or improved. Furthermore, 79% of patients remained symptom-free or improved at a median follow-up of 28.5 months (range 4-70). Conclusions. HIDA scan is a useful clinical tool as an adjunct to the diagnosis and management of patients who present with typical biliary pain and a normal TUS scan. [ABSTRACT FROM AUTHOR]

Acalculous biliary pain has been related to gallbladder dysfunction that produces a gallbladder emptying defect—a condition which favours the development of lithiasis. It is therefore probable that microlithiasis is present in patients with gallbladder dysfunction. The aims of this study were to measure gallbladder emptying and investigate bile abnormalities in patients with acalculous biliary pain. In 92 consecutive patients, gallbladder emptying was assessed by quantitative cholescintigraphy (abnormal ejection fraction ≤40%). In 64 patients, a microscopic study was performed on duodenal bile, defining abnormality as the presence of cholesterol crystals in any amount and/or calcium bilirubinate granules and/or microspheroliths at a rate of >10 per slide. The ejection fraction was abnormal in 45 patients (49%) (median 25.1%, range 6.8–39.3%) and normal in the remaining 47 cases (median 71.3%, range 41.0–96.1%). Bile was abnormal in 32 of 64 patients (50%), the most frequent finding being calcium bilirubinate granules. In the patients with bile abnormalities, abnormal ejection fraction was more frequent (20 of 32) and the median ejection fraction was lower (30.9%, range 12.0–94.1%) than in the patients with normal bile (16 of 32 with an abnormal ejection fraction; median ejection fraction 50.7%, range 6.8–96.1%). Abnormal bile was frequent (55.5%) in patients with reduced ejection fraction, but was not uncommon in patients with normal ejection fraction (33.3%). Fewer patients showed no alteration (25%). It is concluded that in most patients, acalculous biliary pain coexists with gallbladder dysfunction or abnormal bile, the combination of both alterations being common. [ABSTRACT FROM AUTHOR]

Background: Pain following cholecystectomy can pose a diagnostic and therapeutic dilemma. We reviewed our experience with calculi retained in gallbladder and cystic duct remnants that present with recurrent biliary symptoms.Methods: Over the last 6 years, seven patients were referred to us for the evaluation of recurrent biliary colic or jaundice. There were four men and three women ranging in age from 35 to 70 years. All seven had biliary pain similar to the symptoms that precede cholecystectomy; two of them also had also associated jaundice and one had pancreatitis. The time from cholecystectomy to onset of symptoms ranged from 14 months to 20 years (median, 8.5 Years). Four had undergone laparoscopic cholecystectomy and three had had an open cholecystectomy; none had an operative cholangiogram.Results: Five of seven underwent diagnostic endoscopic retrograde cholangiography (ERC), which revealed obvious filling defects in the cystic duct or gallbladder remnant. The final patient was diagnosed by laparoscopic ultrasound after eight negative radiographic studies. Four patients underwent laparotomy and resection of a retained gallbladder and/or cystic duct. Two patients were treated with extracorporeal shock-wave lithotripsy (ESWL); one of them also required endoscopic biliary holmium laser lithotripsy. One patient underwent successful repeat laparoscopic cholecystectomy. There were no treatment-related complications. At a median follow-up of 11.5 months, all have achieved complete stone clearance and are asymptomatic.Conclusion: Retained gallbladder and cystic duct calculi can be a source of recurrent biliary pain, and a heightened suspicion may be required to make the diagnosis. This entity can be prevented by accurate identification of the gallbladder-cystic duct junction at cholecystectomy and by routine use of cholangiography. A variety of therapeutic options can be employed to obtain a successful outcome. [ABSTRACT FROM AUTHOR]

Background: Diagnosis and identification of patients with acalculous biliary pain, who would benefit from surgery, remains a significant clinical problem. The cholecystokinin (CCK) provocation test helps diagnosis, but lack of consistency limits its usefulness. Aim: To characterize the response of gallbladder muscle strips, from patients with acalculous biliary pain, to hormonal and muscarinic stimulation and to compare these with strips from gallstone patients and normal controls. Patients: Eleven patients with acalculous biliary pain were studied, 5 had a positive CCK test. Eight gallbladders from gallstone patients and 6 from partial hepatectomies were used for comparison. Methods: Muscle strips from the body and neck of the gallbladder were suspended in organ baths and dose-response curves were constructed for CCK-8 and carbachol. Results: In the acalculous group the strips from the body were less sensitive to carbachol than those of the neck. Conclusion: Since we found no differences in the CCK responses for the groups, it casts doubt over the effectiveness of the CCK test to diagnose acalculous biliary pain. Since carbachol sensitivity was different, it might be that a similar test using muscarinic stimulation would help in the diagnosis of this difficult group of patients.Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Biliary sludge (BS) refers to the pre-stone stage of gallstone disease. Timely treatment of this condition with ursodeoxycholic acid (UDCA) drugs helps prevent the progression of the disease. However, not all drugs used in practice are equally effective in relieving clinical manifestations, resolving sludge according to ultrasound results and tolerance., Aim: To evaluate the therapeutic efficacy of the drug Ursofalk in comparison with other UDCA drugs used for the treatment of BS., Materials and Methods: We examined 105 people with different types of BS identified during ultrasound examination (US); they were divided into 2 groups depending on the UDCA drug taken. In patients, the dynamics of clinical manifestations was assessed using a questionnaire, as well as the dynamics of the ultrasound picture while taking UDCA., Results: Statistical analysis showed that Ursofalk significantly better relieves biliary pain (p=0.025) and biliary dyspepsia (p=0.039), pain regression occurs faster (p=0.01) in 21 days. It also has a better tolerance in 94.34% of cases compared to other drugs 67.31% (p=0.017). Ursofalk has a greater effect on the regression of BS according to ultrasound results after 3 months (p=0.022) and 6 months (p=0.016)., Conclusion: The drug studied by us demonstrated high efficiency in relation to patients with BS, while there were minimal side effects, which led to a better tolerability of therapy.

In an open, randomized prospective clinical trial the analgesic effect of indomethacin and ketobemidon was compared in 67 patients with acute cholecystitis (28 received 5 mg ketobemidon and 39 received 50 mg indomethacin). Both drugs showed a good and significant pain relief, exhibiting no significant difference in the analgesic effect and no serious adverse reactions. It was concluded that indomethacin administered intravenously is an alternative to ketobemidon intravenously in the treatment of pain resulting from acute cholecystitis and may offer some advantages. [ABSTRACT FROM AUTHOR]