Cholecystokinin and cholecystokinin-A receptor: An attractive treatment strategy for biliary dyskinesia?

Biliary dyskinesia is a relatively common gastrointestinal disease that is increasing in incidence as living standards improve. However, its underlying pathogenesis remains unclear, hindering the development of therapeutic drugs. Recently, "Expression and functional study of cholecystokinin-A receptors on the interstitial Cajal-like cells of the guinea pig common bile duct" demonstrated that cholecystokinin (CCK) regulates the contractile function of the common bile duct through interaction with the CCK-A receptor in interstitial Cajal-like cells, contributing to improving the academic understanding of biliary tract dynamics and providing emerging directions for the pathogenesis and clinical management of biliary dyskinesia. This letter provides a brief overview of the role of CCK and CCK-A receptors in biliary dyskinesia from the perspective of animal experiments and clinical studies, and discusses prospects and challenges for the clinical application of CCK and CCK-A receptors as potential therapeutic targets.

Biliary Dyskinesia: Fact or fiction?

Nearly 20,000 pediatric patients undergo cholecystectomy annually, and abnormal gallbladder emptying ("biliary dyskinesia") has replaced cholelithiasis as the leading indication for this operation in the USA. Nonetheless, patients with abnormal gallbladder emptying nuclear medicine scans do not uniformly benefit from cholecystectomy. This article reviews the available data on presentation, workup and treatment of patients with abnormally low and high rates of gallbladder emptying.

Diagnostic stringency and healthcare needs in patients with biliary dyskinesia.

AIM: We have recently shown an increase in cholecystectomies for biliary dyskinesia. Based on these results, we hypothesized that diagnostic criteria are less stringently applied which may contribute to ongoing resource utilization. METHODS: Using billing codes, patients seen for biliary dyskinesia were identified and data were extracted from the electronic medical record to confirm the diagnosis, obtain demographic and clinical data and assess resource utilization 1 year prior to and after cholecystectomy. RESULTS: A total of 972 patients were identified, with 894 undergoing cholecystectomy. In 259 patients, symptoms had started <3 months prior to evaluation. Functional gallbladder imaging revealed a mean gallbladder ejection fraction of 23.1 ± 0.7 %; of the patients undergoing surgery, 116 had a normal gallbladder ejection fraction. Sufficient up data for pre- and post-operative assessment of resource utilization was available for 368 patients. Emergency room (ER) visits decreased from 0.86 ± 0.07 to 0.69 ± 0.03 (P < 0.05), while hospitalization rates remained unchanged after surgery. Patients not meeting consensus criteria for the diagnosis of biliary dyskinesia were more likely to use opioids and have ER visits prior to and after cholecystectomy. Using multiple logistic regression benzodiazepine use, migraine history and prior ER visits independently predicted postoperative resource utilization. CONCLUSIONS: Our data demonstrate that a significant number of patients undergo cholecystectomy for biliary dyskinesia, even though they do not meet currently accepted diagnostic criteria. While healthcare resource utilization drops within the first year after surgery, ER visits and hospitalizations remain common, suggesting a more limited benefit of surgical approaches in these patients.

[Mebeverina drugs in the treatment of functional disorders of the digestive system].

Despite the identical content of mebeverine hydrochloride, Duspatalin and Niaspam, produced by different technological processes, can't be considered interchangeable as they are known to have different clinical effect in case of various functional diseases of alimentary organs. Duspatalin is effective in relieving biliary disfunction symptoms, Oddy's sphincter hypertonicity in particular, but has little effect on intestinal dyskinesia. Niaspam is known to have little effect on biliary dyskinesia, but has a prominent positive clinical effect on intestinal dyskinesia.

[Significance of biliary dysfunction in the pathogenesis of gallstone disease].

The paper shows the role of biliary dysfunction in the formation of biliary sludge. Found that among all motor dysfunction themost common is reduction of contractile function of the gallbladder (in 63.3% of cases), which is combined with 73.2% Oddi's sphincter hypertonus. T The combination of ursodeoxycholic acid (UDCA) with mebeverine has a better effect than monotherapy with UDCA, as increases the frequency of relief of biliary dyspepsia symptoms, normalizes the biliary tract functional status and 95% of cases leads to the elimination of biliary sludge.

The use of tenoten preparation in complex therapy of hypomotoric biliary dyskinesia.

A positive effect of tenoten on the course of biliary dyskinesia in patients with anxiety and depressive disorders was demonstrated. Tenoten can be recommended for the treatment of functional cholangio-pancreatoduodenal motility disturbances.

[Vegetotropic therapy and hypobaric hypoxic adaptation in gallbladder motor dysmotility].

The study of 67 chronic biliary patients (36 - gallbladder dysfunction, 25 acalculuous cholecystitis, 6 - cholelithiasis) was revealed their functional dysadaptation characterized by gallbladder dysmotility and autonomic dysfunction. Vegetotropic therapy (Propranolol, Metoclopramid, Atropine) according to the autonomic regulation activity has advantages in correction of the gallbladder dysmotility in comparison to the routine pharmacotherapy. Hypobaric hypoxic adaptation results in the increase of gallbladder emptying that opens perspectives for the non-pharmacological correction of the gallbladder hypokinetic dyskinesia.

[Use of grandaxin in hypermotor dysfunction of the biliary ducts in young people].

GOAL OF THE STUDY: Complex study of psychovegetative disorders at hypermotor dysfunction of biliary ducts in young people and correction of these disorders with the help of grandaxin. MATERIAL AND METHODS OF STUDY: Thirty-five patients with hypermotor dysfunction (biliary dyskinesia). The control group comprised 33 patients of the same sex and age. The mental status was assessed with the use of BMQP (brief multifactorial questionnaire for personality examination), Spielberger, Eysenck and Heck-Hess tests. The cardiac rate mathematical analysis method by R.M. Bayevsky and Wein-Solovyova tables were used to study the vegetative nervous system function. Vegetative disorders were corrected with the help of grandaxin. STUDY RESULTS: The mental status of patients with biliary dyskinesia differed reliably from that in the control group. When the vegetative system was examined in the biliary dyskinesia group in the state of rest, the parasympathetic reaction was greatly increased at the load, being greater than in the control group. CONCLUSION: When biliary dyskinesia is treated, it is recommended to correct psychovegetative disorders with the help of an original drug named grandaxin.

[Effect of etmosin on biliary motility disorders in patients with ischemic heart disease]. / Vplyv etmozynu na porushennia motoryky zhovchovyvidnykh shliakhiv u khvorykh na ishemichnu khvorobu sertsia.

We have studied the influence of Etmosin medication on severity of IHD clinical presentations and comprised biliary motility in 162 patients aged 26 to 60. Dynamic echocholecystography (DECG) has been applied. The obtained data suggest using Etmosin in patients with ischemic heart disease and comprised biliary motility makes for normalizing tonus of the Odi sphincter and decreasing the rate of episodes of angina pectoris, although was not found any influence of Etmosin on gall-bladder motility. The use of Etmosin enables in patients with IHD and comprised biliary motility to decrease reflex angina pectoris.

[Use of tykveol in the treatment of impaired biliary tract function in patients with chronic non-calculous cholecystitis]. / Primenenie tykveola v lechenii narushenii funktsional'nogo sostoianiia zhelchevyvodiashchikh putei u bol'nykh khronicheskim nekal'kuleznym kholetsistitom.

The therapeutic efficacy of tykveol was evaluated in 22 patients with chronic non-calculous cholecystitis and/or dyskinesia of the biliary tract (BT) concurrent with gallbladder deformity (GD). Supplementation of tykveol to the combined therapy in the patients with chronic non-calculous cholecystitis concurrent with GD was shown to exert a pronounced therapeutic effect. This caused positive changes in clinical symptoms and BT function, diminished the lithogenic propertes of bile. With the use of tykveol, recovery of neurohumoral regulation is an important factor that improves biliary tract function, as evidenced by decreased gastrin secretion.

[New approaches to diagnosing and treating hyperkinetic biliary dyskinesia associated with chronic acalculous cholecystitis]. / Novye podkhody k diagnostike i lecheniiu giperkineticheskikh diskinezii zhelchnogo puzyria v sochetanii s khronicheskim nakal'kuleznym kholetsistitom.

Ninety patients aged 21 to 56 years who had chronic non-calculous cholecystitis (CNCC) concurrent with hyperkinetic dyskinesia (HKD) detectable by a stepwise duodenal probing and sonography, by using a choleretic breakfast and by determining the relaxation coefficient (RC) that was equal to the ratio of the volume of the gallbladder (GB) after the use of a spasmolytic to the baseline GB volume. The patients were divided into 3 groups. The authors used as a spasmolytic agent pinaverium bromide (dicetel) in a dose of 50 mg (1 tablet) in Group 1), octylonium bromide (spasmomen) in a dose of 40 mg (1 dragee) in Group 2, and drotaverine (no-spa) in a dose of 40 mg (1 tablet). There was a more significant sonographic increase in the size of GB in Groups 1 and 2 as compared with Group 3. In the acute drug test and during long-term treatment as well, the highest spasmolytic effect was noted in patients receiving dicetel (Group 1) and spasmomen (Group 2) as compared with that in Group 3 patients taking drotaverine. With this, RC was 1.25 +/- 0.2, 1.6 +/- 0.15, and 1.08 +/- 0.1, respectively. No adverse reactions occurred in the patients having selective calcium blockers (SCBs) whereas the patients receiving no-spa were found to have the following side effects: dry mouth (n = 3), transient constipation (n = 1), and numb tongue (n = 1). Thus, the study has provided evidence for the fact that SCBs have some advantage over myotropic spasmolytic agents in the treatment of CNCC with the signs of HKD.

[Clinical efficacy of corinfar retard in the treatment of patients with biliary tract dyskinesia]. / Klinichna efektyvnist' korynfaru retardu u likuvanni khvorykh z dyskineziieiu zhovchnovyvidnykh shliakhiv.

Corinfar-Retard efficacy in patients with hypertonic-hyperkinetic type of biliary dyskinesia has been studied. 56 patients aged 26 to 30 had been prescribed Corinfar-Retard in 20 mg per day for 7 days. Dynamic echocholecystography has applied. Decrease in contraction of gall bladder and normalization of tonic contraction of sphincter Ody was found in the patients with previously diagnosed hypertonic-hyperkinetic type of biliary dyskinesia after having been treated with Corinfar-Retard.

[Using botulinum toxin type A in the gastrointestinal tract]. / Einsatz von Botulinumtoxin A im Gastrointestinaltrakt.

BACKGROUND: Botulinum toxin (BTX) is an extremely potent poison which interacts selectively with cholinergic neurons to inhibit the release of neurotransmitters. Local intrasphincteric injection of BTX has been suggested as possible therapy for several spastic disorders of the gastrointestinal tract. INDICATIONS: There is good evidence for the clinical benefit of BTX injection as an alternative treatment for achalasia and chronic anal fissures. Other possible indications for BTX injection such as sphincter of Oddi dyskinesia or cervical achalasia remain to be further established. BTX injection showed no severe side effects when compared to other interventional or operative treatment alternatives. However, the effect of BTX injection lasts only for several months and is fully reversible. The time-limited effect of BTX is a disadvantage in the treatment of achalasia. By contrast, the limited effect is advantageous in the treatment of chronic anal fissures as the normal function is restored after the lesion has healed and the BTX effect disappeared. The use of BTX has added a new therapeutic concept with few side effects to our interventional methods. When applied critically, this method can be used with benefit for the treatment of our patients.

[A choice of optimal vegetotropic pharmacotherapy in patients with chronic non-calculous cholecystitis in combination with dyskinesia of the gallbladder]. / Vybor optimal'noi vegetotropnoi farmakoterapii u bol'nykh khronicheskim nekal'kuleznym kholetsistitom.

The group of 117 patients (58 male and 57 female, age from 17 to 54) with chronic non-calculous cholecystitis was examined. The control group included 54 practically healthy persons. The motor-evacuation function of gallbladder was estimated on dynamic ultrasonographic findings of biliary system sorbet. The character of the autonomic regulation was determined on the basis of variability parameters of the heart rhythm. The results of the repeated dynamic ultrasonography of biliary system with sorbet on a background of vegetotropic medications (Atropine, Propranolol, Metoclopramide) have demonstrated that the variability parameters of heart rhythm can be used for an estimation of the autonomic regulation type and can become the basis of vegetotropic pharmacotherapy choice for the patients with chronic non-calculous cholecystitis and biliary dyskinesia.

The effect of cisapride on gallbladder contractility in type II diabetic patients.

BACKGROUND/AIMS: To investigate whether diabetics have altered gallbladder motility, and whether cisapride has any effect on gallbladder motility in these patients. The factors associated with abnormal gallbladder contractility, and with the effects of cisapride on gallbladder contractility in diabetics were also evaluated. METHODOLOGY: The gallbladder contractility parameters of 20 diabetics and 20 controls were assessed by real time ultrasonography. The same measurements were made after cisapride treatment in diabetics. RESULTS: Fasting gallbladder volume and residual gallbladder volume were statistically higher in the diabetic group than in the controls (P = 0.018 and P = 0.022, respectively). Multivariate analysis also showed a significant association between fasting gallbladder volume and existing diabetes (P = 0.0002). There was a significant positive correlation between level of hemoglobin A1c and fasting gallbladder volume (r = 0.48, P = 0.031). Responders to cisapride treatment had significantly higher hemoglobin A1c levels than nonresponders (6.6 +/- 1.3 vs. 9.1 +/- 1.8, respectively; P = 0.004). Logistic multiple regression analysis revealed that hemoglobin A1c level was the only independent factor that was predictive for efficacy of cisapride treatment. CONCLUSIONS: This study demonstrates that diabetics have impaired gallbladder contractility, and that control of diabetes is predictive for gallbladder contractility and response to cisapride therapy in these patients.

[Galstena efficacy in patients with biliary dyskinesia, chronic cholecystitis and cholelithiasis]. / "Galstena" u patsientov s diskineziei zhelchnovyvodiashchikh putei, khronicheskim kholetsistitom i zhelchno-kamennoi bolezn'iu.

The response of inflammation, bile secretion, lipid metabolism, LDL sensitivity to oxidation was studied in patients with bile duct dyskinesia (BDD), chronic cholecystitis (CC) and cholelithiasis (CL) before and after a course of therapy with galstena. The treatment improved general condition in 90% of the patients, dyspeptic symptoms relieved or stopped. Galstena relieved general or local inflammation, reduced mean levels of total cholesterol and LDL cholesterol, raised HDL cholesterol. In patients with BDD and cholelithiasis galstena did not change normal sensitivity of LDL to oxidation. A galstena course in BDD and CC patients significantly diminished bile lithogenicity and improved gall bladder contractility.