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Gallstones have a very high prevalence affecting 9.5 and 19.5% of men and women, respectively. The pathophysiology and risk factors for cholesterol gallstones are considered. Modern imaging techniques, in particular ultrasound, are very sensitive to detect cholecystolithiasis, while ERCP remains the gold standard to detect choledocholithiasis. ERCP could be supplanted soon by endosonography and MRCP. Biliary scintigraphy is useful to detect a 'vésicule exclue' and to document gallbladder/sphincter Oddi dysfunction. The different conservative management strategies including litholytic treatment with ursodeoxycholate and lithotripsy have been largely abandoned in favor of laparoscopic cholecystectomy. Litholytic treatment has still a role to play in the prevention of gallstone formation in patients with rapid weight loss and in the newly detected MDR3 defect associated with sludge formation. Biliary colic is treated with non-steroidal analgesic drugs, analgesics and/or spasmolytic agents.

Visceral pain is caused by either distension or contraction of the visceral muscular wall or obstruction of hollow gastrointestinal organs. Unlike the somatic pain due to peritonitis, visceral pain is diffuse, epigastric, periumbilical and is often accompanied by nausea, vomiting and restlessness. We demonstrate the significance of visceral pain in the differential diagnosis of the acute abdomen presenting five cases of appendicitis and cholecystitis. A correct early diagnosis of the acute abdomen while signs of local peritonitis are still absent (appendicitis in atypical location, recurrent acute appendicitis, spontaneous reopening of an occlusion) is facilitated by the awareness for the characteristics and symptoms of visceral pain, and therefore careful taking of the patient's history. A history lacking visceral pain on the other hand represents an important clue for the diagnosis of other conditions (gynecological, diverticulititis, etc.) with acute pelvic peritonitis.

Despite numerous experimental and clinical investigations there is no consensus on the evolution of chronic pancreatitis (CP). In the 1970s and 1980s, Sarles persistently emphasised the de novo evolution of CP due to pancreatolithiasis. In recent years, however, clinical and morphological studies have provided strong evidence for the initial proposal of acute pancreatitis progressing to chronic pancreatitis. The so-called necrosis-fibrosis-sequence theory is supported by immunohistochemical work suggesting that inflammatory mediators primarily contribute to tissue destruction and that infiltration of pancreatic nerves by immune cells is a pathogenetic factor for the generation of pain in CP. While Sarles postulates that acinar hypersecretion and an imbalance of pancreatic stone promoting and inhibiting factors trigger the evaluation of CP, the necrosis-fibrosis-sequence theory also involves other pathomechanisms (e.g. changes in ductal permeability, ischemia, oxidative stress) which have been shown to cause (acute) pancreatic injury. Despite this unifying template, which also lessens the need to identify independent mechanisms for the pathogenesis of acute and chronic alcoholic pancreatitis, there are still open questions, e.g. on genetic factors that (like in hereditary CP) may explain the different susceptibility of the pancreas to injury and the individual immunological response.

Cholelithiasis is a frequent disease in developed countries with significant economical implications. While the multifactorial pathogenesis of cholesterol gallstones has been widely accepted, the relative importance of the various contributing factors is not yet clear. One focus of research in recent years has been the identification and functional analysis of biliary proteins. Few proteins are synthesized in the biliary tract itself, the majority reflect the composition of serum proteins. Many biliary proteins modify cholesterol crystallization, the initial step of cholesterol gallstone formation. In cholelithiasis, biliary concentration of many pronucleating proteins are increased. However, this may be a consequence rather than the cause of the disease, because a majority of these proteins are acute-phase reactants. They may be secreted into bile at increased concentrations because of--often asymptomatic--cholecystitis due to gallstone disease. A number of protein-lipid interactions have been observed in search of a mechanism of action of biliary effector proteins. Only recently the potential modification of lipid removal from gallbladder bile by Apo A-I was described in addition to its direct antinucleating effect. In conclusion, biliary proteins directly modify cholesterol crystallization by protein-lipid interactions and may influence lipid absorption from the gallbladder.

Unlabelled: This study is to determine the role of nitric oxide (NO), as primary neurotransmitter of the non-adrenergic noncholinergic (NANC) innervation, of stone-diseased and stone-free human gallbladders. Human gallbladder muscle strips were mounted in modified Krebs-Henseleit-solution with atropine (1 microM), guanethidine sulf. (5 microM) and aerated with Carbogen. Electrical field stimulation (EFS, 70V, 0.5 ms, 100 pulses) was used at frequencies of 1, 3, 10 Hz to activate NANC nerves, L-omega-nitro-L-arginine (L-NNA, 100 microM), L-arginine (L-ARG, 120 microM) was used to manipulate the NO-synthase. Gallbladder slices of 3 microns were stained by means of APAAP-method (alkaline phosphatase anti alkaline phosphatase) for histological examination. In the control group (basal tone = 8.94 +/- 1.17 mN) EFS caused a frequency dependent reduction of basal tone (1 Hz = 5.73 +/- 0.81 mN; 3 Hz = 5.18 +/- 0.65 mN; 10 Hz = 4.63 +/- 0.49 mN). Incubation with L-NNA increased the tone (7.63 +/- 0.76 mN). Contractor group (basal tone = 7.79 +/- 0.93 mN) reacted like the control group but frequency independent and additionally with spontaneous phasic contractions. In the non-contractor group (basal tone 4.13 +/- 0.65 mN) EFS only decreased the frequency of spontaneous phasic contractions. L-NNA caused an increase in tone (5.97 +/- 0.84 mN) and frequency, L-Arginine significantly reversed this effect., Histology: Contractor group showed wrinkled mucosal membrane and mild grade of inflammation. Shallow mucosa, necrosis and high grade of inflammation were found in the non-contractor group., Conclusions: 1. In vitro, NANC-relaxation of human gallbladder is NO dependent. 2. Motility of stone-diseased gallbladders is modulated by NO and seems to depend on the degree of scarrification.

The main aim of our study was the investigation of gallbladder motility prior to gallstone formation in vivo in guinea pigs fed a lithogenic diet. In a first experiment guinea pigs were fed a lithogenic diet for 5, 15, 30 and 45 days. First gallstones (pigment calculi) appeared after 30 days diet application. The in vitro contractility after lithogenic diet remained unchanged. In a second experimental part the in vivo gallbladder contractility was measured in two experimental animal groups (control group and 21 days lithogenic fed guinea pigs). The isovolumetric pressure rise inside the gallbladder following the intravenous injection of 10(-9) mol/kg body weight ceruletid was the essential contractility parameter (intraluminal basal pressure 5 mm hg). Due to lithogenic feeding of 21 days--that means prior to gallstone formation--the isovolumetric pressure rise was significantly elevated (p < 0.01). Moreover we observed passive distensibility changes of gallbladder muscle due to muscular hyperplasia. The main result of this investigation is the fact that gallbladder muscle in guinea pigs fed a lithogenic diet response to ceruletid application with hypercontractility prior to provable pigment gallstone formation. However gallbladder hypomotility--believed to be a causal factor in cholelithogenesis--was not observed in our experimental conditions.

There is considerable debate whether or not the laparoscopic technique for cholecystectomy supersedes conventional procedures in patients with pre-existing cardiopulmonary disease. Hemodynamic stress and CO2 absorption from the peritoneum can have a negative effect on intraoperative safety. On the other hand, a more rapid recovery of lung function and a shorter stay in hospital are the obvious advantages. 74 patients were investigated in our study: 54 with a low cardiopulmonary risk (group 1, ASA classes I or II) and 20 high risk patients belonging to ASA class III (group 2). Series of blood-gas samples were drawn from an arterial catheter and the respiratory parameters and blood gas values measured before and at the end of the CO2-insufflation period were compared. No dangerous rise in paCO2 or decrease in pH occurred with the ventilation method used in this study (Ti:Te = 1:1, PEEP = 5 mbar, Rf = 10/min modification of the tidal-volume according to the measured paCO2 and ventilation with an O2/air mixture). No significant changes in arterial O2 saturation compared with baseline values occurred and values remained within the physiological range. We conclude that excessive intraoperative paCO2 increase can be avoided by modification of the ventilation procedure and that laparoscopic cholecystectomy is an advantageous technique in the patient with cardiopulmonary disease.

There are two types of gallstones: cholesterol and pigment stones. The pathogenesis is divided into three phases: supersaturation, nucleation and stone growth. Hypersecretion of biliary cholesterol, crystallization promoting and inhibiting factors, gallbladder hypomotility, arachidonyl lecithin, prostaglandins, mucin and calcium play an important role in the formation of gallstones. For the formation of pigment stones a decreased secretion of biliary acids, an increased secretion of unconjugated bilirubin into the bile and an infection of the biliary tract are the most important causative factors.

This study describes the influence of endogenous and exogenous prostaglandins upon CCK-induced motility patterns of human gallbladders with and without stones (indomethacin and nocloprost; an exogenous PGE2-analogon). From 48 gallbladders with- and 22 gallbladders without stones (control group) longitudinal muscle stripes were dissected and transferred to an organ bath and CCK, indomethacin and nocloprost dose response curves were established. In another experimental protocol, the effect of CCK after indomethacin or nocloprost preincubation is demonstrated. Moreover, specimens of gallbladders were taken for histology and gallstones for analyse. The results demonstrate that gallbladders with stones have a significant higher basic tonus and phasic activities compared to the stone-free controls. Because of these different responses to CCK, gallbladders of the stone-diseased group were divided in two groups: 64% of the gallbladders show a sensitivity and tonic response to CCK like the controls (contractors), 36% demonstrate a reduced sensitivity to CCK and only a slight tonic response (non-contractors). Indomethacin causes a fall in tonus in both stone-diseased groups. It stops spontaneous activity in the contractor and non-contractor group. With indomethacin preincubation all three groups response to CCK with a significant reduced sensitivity. CCK-induced activity is reduced in the control and contractor group. In the non-contractor group, muscle strips do not contract after indomethacin preincubation. Nocloprost induces significant contractions in the control and contractor group. In both groups, the response to CCK after nocloprost preincubation is stronger than the reaction without preincubation. In the non-contractor group, a change in tonus after nocloprost application cannot be demonstrated, there also is no response to CCK after nocloprost preincubation. These results corroborate the notion of a significant contribution of the endogenous prostaglandin system to the regulation of gallbladder motility by CCK.

In 50 diabetic patients without gallstones, including 26 patients with cardiovascular autonomic dysfunction, and 60 normal volunteers the fasting volume and volume reduction of the gallbladder after a liquid fatty meal were determined ultrasonically in intervals of ten minutes up to one hour. Simultaneously the gastric emptying of the liquid meal was followed by ultrasound imaging. Despite an association of other complications of diabetic disease (peripheral neuropathy, retinopathy) with autonomic cardiovascular dysfunction, an altered gallbladder resting volume or impaired fat-induced volume reduction was not evident in this group of patients when compared the diabetics without cardiovascular dysfunction or controls. The time to reach the minimal residual gallbladder volume was only tendentiously prolonged in diabetics with autonomic cardiovascular dysfunction. The residual volume of the stomach showed no significant difference between the three study groups using a liquid test meal. In conclusion neuropathic dysfunction of the gallbladder is unlikely to play a major pathogenetic role in the development of gallstones in diabetic patients.

Cholesterin is excreted into bile together with phospholipids and bile acids, which are essential for the formation of micelles. Cholesterin-supersaturation of the bile and a relative hyposecretion of bile acids, the presence resp. the lack of promotors and inhibitors of nucleation and a reduced gallbladder contractility are the most important factors in the formation of cholesterol stones. For the formation of pigment stones, however, an increase of bilirubin production and infection of the biliary tract are the causative factors.

The pathogenesis of acute pancreatitis is based on the following principles: 1. Biliary. In biliary pancreatitis there is a causal relationship between the induction of acute pancreatitis and the migration of gallstones. The basic pathomechanism seems to be a combination of an increase in permeability and pressure in the ductal system. 2. Intraacinar. Caerulein-pancreatitis is a well established experimental model which reflects the intracellular/interstitial type of activation. Basolateral secretion of pancreatic enzymes into the interstitial space represents the initial event. Intracellular activation of trypsin by the fusion of zymogen-granules and lysosomes has been advocated as an alternative mechanism. 3. Alcohol. The acute alcohol pancreatitis comprises a combined pathogenesis. Obstruction and reflux as well as the cytotoxic effect of alcohol seem to be the main principles. 4. Disturbance of pancreatic microcirculation. Ischemia of the pancreas seems to play a key role in the transition from pancreatic edema to necrosis. Improvement of capillary perfusion by isovolemic hemodilution with dextran 60 has been shown to be an efficient therapeutic tool.

Data about gallbladder motility in stone disease and stone free conditions are discussed controversially. This study is aimed at to evaluate in vitro the responses of human gallbladder muscle stripes to cholecystokinin, motilin and neurotensin. Following the results, a stratification of the "stone-disease-group" seems to be necessary: 41% of the gallbladders (stone disease) demonstrate a deep reduction in contractility to cholecystokinin ("non-contractors"), whereas 59% of the gallbladders contract in the same pattern like the controls ("contractors"). Interestingly, the majority of the gallbladders in the "contractor" group demonstrate a high spontaneous activity which is absent in stone free gallbladders. Motilin and neurotensin either do not induce any effect.

Incidence and clinical significance of cardiac side effects of extracorporeal shock-wave lithotripsy (ESWL) were prospectively analysed for 85 patients (26 men, 59 women; mean age 44 [17-81] years) with cholecystolithiasis (n = 70) or choledocholithiasis (n = 15). 24-hour ECG monitoring was undertaken on the day of treatment. Additionally, during ESWL cardiac rhythm and blood pressure were monitored. ESWL was performed with an electromagnetic lithotriptor under light anaesthesia with intravenous diazepam (10 mg) and pethidine (75-100 mg). There were no superventricular premature systoles in any of the patients during treatment. In 15 patients with occasional ventricular premature systoles (VPS) (6-81 per 23 hours) in the 24-hour ECG the number of VPS increased during the one-hour ESWL procedure significantly to 6-55 (P less than 0.05). 14 of these patients had an unremarkable cardiac history. Changing the lithotriptor coupling angle failed to suppress the VPS in only two patients. In these two it was necessary to trigger the shock wave with the ECG. Blood pressure rose markedly (up to 220 mm Hg systolic) during ESWL in only three patients, known hypertensives. But this rise was easily controlled with nifedipine, 10 mg sublingually. These data demonstrate that ESWL is a safe alternative to operative treatment, even in the presence of existing cardiac disease. Nonetheless, precautions should be taken in case there are complications.

In order to determine whether cholecystography and computed tomography (CT) are capable of better gallstone characterization than conventional radiography alone, 91 patients (76 females, 15 males; mean age 47 +/- 12 years) with symptomatic single gallstones were studied prospectively prior to extracorporeal shock-wave lithotripsy with concomitant oral stone dissolution therapy. In addition, the value of oral cholecystography in demonstrating patency of the cystic duct was compared with ultrasound assessment of gallbladder function. Despite "negative" plain gallbladder radiographs in all patients, oral cholecystography showed significant stone calcification in 8 of the 91 patients and CT showed stone calcifications in 52 of the 91 patients. In 12 patients the maximum stone density was between 50 and 90 Hounsfield units, and in 40 patients it was more than 90 Hounsfield units. CT revealed ring-like calcification in the majority (79%) of these stones. Oral cholecystography showed satisfactory concentration of contrast medium in all patients, while ultrasonography of the gallbladder following a chemically defined test meal demonstrated contractility of more than 50% of initial volume in 69 patients and of less than 30% in 9 patients. Although oral cholecystography is a simple, readily available complication-free method, ultrasound assessment of gallbladder contraction is better for selecting patients for extracorporeal shock-wave lithotripsy. CT allows significantly better characterization of gallstones than oral cholecystography and conventional plain gallbladder radiography.

The relationship between nucleation time (NT), total lipid concentration (TLC) and age was studied in a group of 45 gallstone patients (10 male, 35 female, age 50.1 +/- 14.5 yrs). Bile was obtained by direct fine needle puncture of the gallbladder under local anaesthesia and sonographic monitoring. There was a positive correlation between age and nucleation time (r = 0.626, p less than 0.001), in addition to a negative correlation between age and total bile lipid concentration (TLC) (r = -0.414, p = 0.005). The negative correlation between age and TLC indicates that gallbladder's ability to concentrate the bile decreases significantly with age. It is possible that the decreased concentration is a result of the chronic pathogenetic effects of gallbladder stones. Practically all patients showed a prolonged nucleation time after the 60th year (11.54 +/- 5.50 vs. 2.65 +/- 2.52 days). This would seem to indicate that these patients suffered primarily from bilirubin or calcified stones, currently unsuited for conservative therapy methods.

The results obtained by the examination of the post-operative bile viscosity behaviour sampled by T-drainages of 29 patients (investigations of the relative viscosity with the help of a modified horizontal capillary viscometer from the day of operation until the 9th postoperative day) confirm the importance of the biorheological classification of bile fluid as a Maxwell fluid (investigations of the absolute dynamic viscosity of 33 bile specimens with a Contraves-Low-Shear-Viscometer and representation of flow curves for rheological characterization). The Maxwell flow behaviour is characterized--among other things--by an exponential increase in the case of prestasis. This fact is important in all "low-flow-states" of different pathophysiological genesis and offers a concept with respect to a pathogenetically orientated cholelithiasis prophylaxis.

For many decades cholecystectomy has been the standard treatment for symptomatic cholecystolithiasis. In asymptomatic patients a waiting attitude can be taken. In recent years, non-surgical therapies have been developed for selected patients. Thus, in patients with mild or no symptoms medical dissolution of gallstones with ursodeoxycholic acid, chenodeoxycholic acid or a combination of these two bile acids can be tried if radiolucent stones with diameters below 15 mm are present in a functioning gallbladder (not more than half full of stones). Besides this therapy, cholelithotripsy with extracorporeal shock waves represents a new procedure, which, together with percutaneous or retrograde instillation of methyl tert-butyl ether, needs further evaluation. For elimination of stones from the common bile duct, endoscopic sphincterotomy and stone extraction have proved valuable non-surgical procedures. For choledochal stones not amenable to endoscopic extraction or dissolution by instillation of solvents, treatment by extracorporeal shock waves represents a valuable alternative to surgery. Thus, the past decades have not only brought progress in knowledge of gallstone disease but have also broadened the therapeutic armoury. Therefore, it is essential to select the most appropriate method for each situation.

In a controlled study of patients with cholelithiasis and patients with cholelithiasis and duodenal diverticula a significantly higher rate of bacteriocholia and miscolonization of the duodenum with intestinal bacteria as well as a significantly higher rate of interdigestive disorder of motility with missing of a wandering activity front was found in the group of patients with diverticula in 11 out of 25 patients. If a cyclic sober motility is found in patients with diverticula, the duration of cycle, the maximum pressure of the interdigestive complexes and its wandering speed are not significantly different from those of the control group. The studies allow the interpretation that retention of food in the diverticula is not the reason for the bacterial miscolonization of the duodenum and the biliary tract, but in patients with diverticula a disturbed self-cleaning mechanism is present. The pathogenesis of duodenal diverticula is not clear.

Intestinal perfusion methods with a nonabsorbable marker allow an exact quantitative determination of intestinal absorption and secretion provided that methodological pitfalls are avoided. A modified technique is applied to the simultaneous measurement of biliary and pancreatic secretion during and depending on emptying of a mixed test meal. A duodenal segment was perfused with an isotonic polyethyleneglycol solution (PEG). Reinjection of duodenal aspirates maintained a normal enterohepatic circulation of bile acids (interruption less than 10%). The perfusion was performed in healthy volonteers over a period of 12 to 24 hours, with three mixed formula meals containing 51CrCl3 as a marker ingested at conventional feeding hours. Influence of meal size was studied by means of a high caloric (40 Kcal/b. wt. per day) test meal. Patients with cholesterol gallstones and cirrhosis of the liver only received one formula test meal of 300 Kcal. Instead of concentrations output of trypsin, lipase, bile acids and cholesterol (the latter corrected for duodenal absorption) was calculated from the dilution of PEG in the duodenal juice and gastric emptying was determined by following quantitatively the flow of 51CrCl3. Gastric emptying can be expressed by a single exponential function over most of the time. Only the last 60-100 Kcals were expelled by the stomach at a faster rate. The daily biliary and pancreatic secretion depend indirectly on the amount of food ingested. But during the day light hours (with continuous meal flow), secretion was similar in high and low caloric subjects, while a significant difference became obvious during night hours corresponding to differences in gastric emptying time. Mean hourly output of bile acid, biliary cholesterol, trypsin and lipase is independent from meal size and secretion of pancreatic enzymes reaches the values close to those after maximal stimulation by i.v. CCK-PZ. Output of pancreatic enzymes does not differ in health and gallstone disease or cirrhosis of the liver respectively. Since during digestion in normals approximately one forth of the bile acid pool is secreted hourly into the gut, the number of daily enterohepatic cycles of bile acids can be calculated by 4-6. Patients with cholesterol gallstones maintain normal bile acid output by enhanced cycling of the small pool: An average of 50% of the pool passed the duodenum per hour. A decreased bile acid pool is also present in cases of advanced cirrhosis of the liver. However, hourly output of bile acids in these patients is significantly less than in mild cirrhosis (with normal bile acid pool) or normal controls. Therefore the hourly fraction of the pool secreted is similar to healthy subjects. These findings provide an important information to explain abnormalities in bile acid metabolism in cirrhosis.

This paper presents clinical data elucidating the natural history of gall stone disease, based on observations carried out on a secluded alpine population treated conservatively for generations. Special circumstances corroborating a statistical evaluation are outlined. Pertinent parameters supporting this study are anatomical findings at operation following the introduction of established surgical procedures into the region, with particular attention to age grouping within the collectives of patients. A total of 130 patients, operated on for gall stones for the first time in their lives, were evaluated, 18 patients undergoing incidental cholecystectomy for asymptomatic gall stones were excluded from this series. Of the remaining collective presenting with clinical symptoms of cholelithiasis, 54% were admitted for complications of the disease, i.e. 15% for acute cholecystitis and 39% for choledocholithiasis (including jaundice in 27%). We conclude that the natural history of gall stone disease in this region implicates the incidence of the above-mentioned inherent complications unless cured electively by early cholecystectomy.

Cholelithiasis is a civilization-related disease with multifactorial causation. The supersaturation of the bile with cholesterol is a deciding risk factor, which, however, does not lead to gallstone formation in each individual case. The connection between supersaturated bile and the formation of stone whose primary constituent is cholesterol, are the cholesterol-monohydrate crystals. Several risk factors lead to cholesterol supersaturation of the bile. Other risk factors induce or maintain the nucleation of the cholesterol crystals. In the following paper the nucleating and inhibiting factors and the pathophysiology of cholesterol gallstones will be discussed.

Regeneration of gallbladder epithelium of rodents is accelerated if a diet inducing cholelithiasis is given, as well as during starvation; both types of dietary regimens have something in common. The increased turnover of mucosal cells and the desquamation of these cells into the lumen of the gallbladder are causative factors for gallstone formation.

A number of disturbing factors may lead to total impairment of bile secretion by altering the physical chemical properties, enzyme activites of the number of available receptors of the hepatocyte plasma membrane or raise the permeability of the biliary tract. Other disturbing factors change the composition of the bile and may consequently favor the formation of gallstones. More recent information on the formation of gallstones has led in a relatively short time to a better recognition, prophylaxis and therapy of individual disorders of bile secretion. Thus the tendency to form cholesterol concrements can be detected by investigating the bile. Knowledge of risk factors makes prophylaxis possible and today the pharmacological control of biliary lipid secretion permits drug therapy of certain forms of gallstones disorders.

After introductory anatomical considerations a survey is given of the composition of bile and the physiology of bile secretion. According to the modern conception the bile acids give the osmotic power for the excretion of water and electrolytes. Apart from this, a bile fraction, which is also secreted by the liver cells into the canaliculi, is present, and in the biliary ducts a further volume fraction independent of bile acid is added, the secretion of which is determined by gastrointestinal hormones. Processes of reabsorption play a role particularly in the gallbladder. By formation of micelles the bile salts render the excretion of cholesterol possible. A normal bile secretion is necessary for the normal emulgation, digestion and absorption of the fats.

In the sparse literature dealing with the rheological characterization of bile You can find supporters of the Newtonian and the Maxwell flow behaviour theories. The submitted examinations of 33 bile specimens sampled postoperatively by T-drainages were carried out with the help of a Contraves-Low-Shear-Viscometer. They definitely show the bile fluid's exponential increase in absolute dynamic viscosity under low shear conditions. Consequently bile behaves like a Maxwell (= Non-Newtonian) fluid, especially considering the variously caused pathological retardation of bile flow. This fact may play a decisive role in fostering lithogenesis. The classification of bile as a fluid with Maxwell behaviour is probably a pathophysiologically important fact with respect to cholelithogenesis and offers a model for further discussion on the prevention of recurrent biliary tract concrements formation.