Characteristics of amino acid profiles and incretin hormones in patients with gallstone disease: a pilot study.

INTRODUCTION: Gallstone disease is associated with insulin resistance, type 2 diabetes mellitus, and increased risk of incident ischemic heart disease. It is known that the profile of branched­chain amino acids (BCAAs) is altered in cardiac diseases as well as metabolic diseases, such as diabetes and obesity. The role of BCAAs in gallstone disease is still not known. OBJECTIVES: The aim of this study was to evaluate the concentration of essential amino acids and incretin hormones in patients with cholecystolithiasis. PATIENTS AND METHODS: The study included 31 patients with cholecystolithiasis and 25 gallstone­free controls. The levels of free exogenous and endogenous amino acids, bile acids, glucagon­like peptide 1, glucose­dependent insulinotropic polypeptide, ghrelin, C-peptide, and insulin were measured in the fasting state and 1 hour after consumption of a 300­kcal mixed meal. RESULTS: The mean fasting and postprandial levels of valine, isoleucine, leucine, and lysine were higher in the study group than in controls (all P.

Transvaginal Hybrid NOTES Cholecystectomy: A Single-Centre Long-Term Experience on Sexual Function.

INTRODUCTION: Transvaginal hybrid NOTES cholecystectomy is an alternative approach to the traditional laparoscopic technique. Despite increasing data regarding clinical outcomes following transvaginal hybrid NOTES cholecystectomy, there is still a lack of long-term results, particularly with regard to sexual function. Therefore, the aim of this study was to evaluate long-term outcome of a series of transvaginal hybrid cholecystectomy. PATIENTS AND METHODS: Female patients with symptomatic cholecystolithiasis who underwent transvaginal hybrid NOTES cholecystectomy were retrospectively analysed regarding clinical and surgical outcome parameters. Furthermore, all patients received a 17-question survey postoperative with questions about sexual intercourse, the domains satisfaction and pain of the German Female Sexual Function Index. RESULTS: Overall, 47 of 80 patients were included in the study with a completed survey responses (return rate 58.6%), with a mean age of 48 years, mean body mass index of 29 and mean operative time of 47 min. The median follow-up was 40 months. There were no intra- or postoperative complications and no conversion to a laparoscopic or open approach. No significant differences were found for postoperative sexual function (painful intercourse, inability to achieve orgasm), although sexual intercourse was less frequent postoperatively (p = 0.022). Forty-four patients (93.7%) were satisfied with the aesthetic and the overall postoperative result, and 40 patients (85.1%) would recommend the applied surgical technique to friends and family. CONCLUSION: The findings show that transvaginal hybrid NOTES cholecystectomy is a safe procedure for female patients, particularly with regard to sexual function.

Is there an association between type 1 diabetes in children and gallbladder stones formation?

BACKGROUND AND AIMS: A number of studies in adults have evaluated the prevalence of gallstones in the diabetic population and showed a significant association with type 1 diabetes (T1D) and type 2 diabetes. The pediatric literature is limited to a single small case series. We conducted a cross-sectional study to evaluate for the presence of association between T1D in children and gallstones formation. PATIENTS AND METHODS: Children diagnosed with T1D in a diabetic clinic have been examined for existence of gall bladder stone formation from November 2008 through November 2009. All have been subjected to the following: History, physical examination, blood tests (liver function tests, lipid profile, glycosylated hemoglobin [HbA1C]), and an ultrasound (US) of the gall bladder. RESULTS: One hundred and five children with T1D have been enrolled consecutively over a 1-year period: age ranged between 8 months and 15.5 years, 62 patients were females. The mean age at diagnosis was 6.3 ± 2.9 years (range 0.85-11 years), mean duration of T1D was 2.2 ± 2.1 years (range 0.2-8 years), mean body mass index was 16.5 ± 3.4, mean HbA1c was 10.7 ± 2.4%, and 61.3% of patients had a HbA1c level >10%. The mean serum cholesterol was 4.16 ± 0.75 mmol/L (normal 3.65-5.15 mmol/L) and mean serum triglyceride 1.02 ± 1.3 mmol/L (normal 0-1.7 mmol/L). Two patients had hyperlipidemia. US of the gallbladder did not show any case of gallstones or sludge formation. CONCLUSION: Data from our study do not show any association between T1D in children and gallstones formation, with diabetes duration of less than 8 years. The relatively short duration of diabetes and possibility that our study was underpowered might have been reasons for the absence of any association.

[Ultrasonography in the diagnosis of cholelithiasis and its complications].

The author presents the results of ultrasound investigation (USI) of 419 patients with cholecystocholedocholithiasis. The diagnostic accuracy of USI methods in patients with calculous cholecystitis was 98.8%. Direct signs of visualization of concrements in the common bile duct (CBD) were found but in 68.5% of patients. On the basis of USI results the common bile stones were found in 287 (68.5%) patients. The concrements omitted in transabdominal USI were diagnosed using endoscopic retrograde cholangiopancreaticography, magnetic resonance cholangio-pancreaticography, endoscopic ultrasonography as well as in operative intervention.

[Regulation of blood circulation in the surgical correction of portal hypertension].

56 patients with portal hypertension were examined who underwent decompressive shunt surgery. Cardiorhytmography and integral rheography body were performed in different stages. In the late postoperative period, there were positive changes in the autonomic regulation of functions: reduced tension index and sympathetic influence on heart rhythm, increases the value of other indicators of heart rate variability. Due to an increase in heart rate and peripheral vascular resistance normalizes blood pressure while reducing the values of cardiac output. There is a further normalization of the reactivity of blood circulation: arterial pressure and vascular resistance during the functional test remained at a constant level of magnitude of shock and cardiac index significantly increased and then decreased to the level of the original values, which corresponds to the reaction apparently healthy. Disorders of regulation, state and reactivity of blood flow in portal hypertension, manifested: 1. Reduction of heart rate variability with a significant increase in sympathetic activity of autonomic nervous system. 2. Reduction of cardiac output and vascular resistance, heart rate, changes in physiological determination of hemodynamic parameters: Blood pressure is determined only by the vessel resistance. 3. Reduction of blood pressure in response to breath holding test.

[Low-flow xenon anesthesia in surgical patients with hypertension].

A comparative study of central hemodynamics in 60 patients with essential hypertension during low flow anesthesia with xenon and nitrous oxide is carried out. The main group consisted of 30 patients, 22 male and 8 female, in the median age of 45.9 +/- 23 years. 22 patients out of those had 2nd stage essential hypertension, while the other 8 had 3rd stage. The control group consisted of 30 patients, 20 male and 10 female, in the median age of 45.1 + 1.3 years. 4 patients had 3rd stage essential hypertension, 26 patients had 2nd stage. The both groups were clinically comparable by the character and severity of the main disease, the carried out surgery (open cholecystectomy) and the qualification of surgeons. Results of the research showed, that low flow monoanesthesia with xenon abruptly eradicated the unfavourable consequences of induction of anesthesia (3-5 mg/kg of sodium thiopental or 2-2.5 mg/kg of propofol) and had a positive effect on the parameters of central hemodynamics of patients with essential hypertension. Xenon anesthesia, compared to nitrous oxide, rapidly stabilized the parameters of blood pressure and heart rate and can be recommended as a method of choice in patients with essential hypertension and compromised myocarium. Nitrous oxide with bolus of regular fentanyl doses doesn't reliable anesthesiological protection during open cholecystectomy and shows signs of toxicity.

Hereditary liver disease: gallstones.

Gallstones are common in Western countries and due to pain and complications pose a substantial burden on health care systems. In general, cholesterol gallstones are distinguished from bilirubin gallstones. Bilirubin gallstones form if the ion product of unconjugated bilirubin and calcium in gallbladder bile exceeds the solubilisation capacities of mixed micelles and vesicles. Cholesterol gallstones develop if the amount of cholesterol in gallbladder bile exceeds the maximum concentration that is soluble at the given concentration of bile salts and phospholipids. In addition, cholesterol gallstone formation requires hypomotility of the gallbladder and a mucin gel as nucleation matrix for monohydrate crystals. The individual risk of gallstone formation is determined by interactions of lithogenic alleles of gallstone susceptibility genes and multiple environmental factors. For asymptomatic gallstones, expectant management is recommended, whereas an episode of gallstone-associated pain substantially increases the risk of complications such as cholecystitis, cholangitis and pancreatitis and therefore necessitates cholecystectomy.

An immunohistochemical study of osteopontin in pigment gallstone formation.

Mucin glycoproteins from the gallbladder epithelium are thought to contribute to the matrix or nucleus of gallstones and other biomineralization systems. The involved acidic glycoproteins have been reported in bile and gallstones. In addition, osteopontin (Opn) is a noncollagenous acidic bone matrix glycoprotein that possesses calcium-binding properties. To investigate the role of Opn in pigment gallstone formation, the involvement of Opn in pigment gallstone formation was studied immunohistochemically in the gallbladder wall and in the stones. Staining for Opn was strongly positive in the epithelium of stone-laden gallbladders and in their stones. The stone-laden gallbladders were infiltrated by macrophages, which intensely stained for Opn. Sections of the pigment stones, under low magnification, showed a lamellar pattern of Opn immunolabeling and showed a reticular pattern under high magnification. Our results indicate that Opn, an acidic glycoprotein from the gallbladder epithelium, seems to be involved in lithiasis. Opn from macrophages and/or the epithelium seems to help form the matrix protein.

¿Cuál es la prevalencia de litiasis de la vía biliar principal en pacientes con colecistolitiasis sintomática? / Frequency of choledocholithiasis among patients with cholelithiasis and a clinical suspicion of common bile duct obstruction

INTRODUCCIÓN: La litiasis de la vía biliar principal (LVBP) es la complicación más frecuente de la colecistolitiasis sintomática. Existe controversia acerca de su prevalencia. El objetivo de este estudio es determinar la prevalencia de LVBP en colecistolitiasis sintomática. Material y Método: Estudio de corte transversal. Se estudiaron mediante colangiografía retrógrada endoscópica (CRE), pacientes con colecistolitiasis sintomática y con sospecha de LVBP atendidos en el Hospital Obrero N 1 de la Caja Nacional de Salud La Paz, Bolivia en el período 2005-2006. El tamaño de la muestra se calculó con base en un nivel de confianza de 95%, poder de 80%, frecuencia esperada de LVBP de 59%, y peor escenario de 54%; escenario que da una muestra de 313 pacientes. Se utilizó estadística descriptiva, se calculó prevalencia de LVBP y se aplicó estadística analítica para estudiar asociaciones. Resultados: De los 2001 pacientes internados por colecistolitiasis sintomática, se solicitaron 435 CRE, identificándose en 175 pacientes LVBP, lo que representa una prevalencia de 40,2%. El promedio de edad de los pacientes estudiados fue de 63,1 años y el 51,9% eran de género femenino. Clínicamente, el dolor abdominal, se presentó en 409 pacientes (94,0%), ictericia en 262 casos (60,2%) y alza térmica en 68 pacientes (15,6%). La CRE no identificó lesiones en 68 pacientes (15,6%) y LVBP en 175 casos (40.2%). La morbilidad asociada a la papilotomía endoscópica fue de 4,4%, y no se registró mortalidad. Se verificó asociación entre LVBP y niveles de fosfatasa alcalina (p=0,04), bilirrubina total (p=0,001) y bilirrubina directa (p=0,01). Conclusión: En pacientes portadores de colecistolitiasis sintomática con sospecha de LVBP, la realización de una CRE preoperatoria es una alternativa a considerar.

Background: Choledocholithiasis is the most common complication of symptomatic cholelithiasis. Aim: To evaluate the prevalence of choledocholithiasis among patients with symptomatic cholelithiasis. Patients and Methods: Patients admitted to the hospital with a symptomatic cholelithiasis confirmed by ultrasonography, were subjected to a endoscopic retrograde cholangiography if there was a clinical suspicion of choledocholithiasis. Results: Two thousand and one patients with symptomatic cholelithiasis were admitted and an endoscopic retrograde cholangiography was requested to 435 (age range 14 to 95 years, 226 females). Of these, 409 (94%) had abdominal pain, 263 (60%) had jaundice and 68 (16%) had fever. In 175 (40%) a choledocholithiasis was diagnosed. Sixteen patients (4%) had bleeding after the endoscopic papillotomy, that was self limited in 14, two had an acute pancreatitits and one had a duodenal perforation. There was an association between the presence of choledocholithiasis and serum alkaline phosphatases and bilirubin. Conclusions: Choledocholithiasis is common in patients with cholelithiasis and a clinical suspicion of common bile duct obstruction.

Acute cholecystitis complicating cardiac surgery: case series involving more than 16,000 patients.

BACKGROUND: Acute cholecystitis after cardiac surgery is rare but carries a high mortality. Its management remains controversial. METHODS: We reviewed all cases of calculous cholecystitis (CC) and acalculous cholecystitis (ACC) encountered at our institution over the past 11 years. Data collection included preoperative variables, details of performed procedures, postoperative course, and outcome. RESULTS: The overall incidence was 0.03% for CC and 0.08% for ACC (5 and 13 of 16,576 patients, respectively). Patients in the ACC group appeared to be sicker patients whereas most patients in the CC group had an uncomplicated recovery from cardiac surgery. The diagnosis was straightforward with typical presentation and ultrasonographic findings in the CC group. In the ACC group, the presentation was less specific, and although useful as diagnostic tool, ultrasonography findings were not as consistent as in the CC group. In the CC group, 3 patients underwent surgery, and 2 patients were treated conservatively. One patient died of cardiac causes after uncomplicated cholecystectomy. In the ACC group, 7 patients were treated medically and 6 patients underwent surgery. The overall mortality was 23% (3 patients). All deaths occurred in patients treated surgically. CONCLUSIONS: Given the low incidence of CC, we do not recommend preoperative screening or intervention for cholelithiasis. Treatment should be according to established guidelines. Patients with ACC, without overt peritonitis, should initially be treated conservatively with appropriate antibiotics. However, failure of significant improvement within 48 hours or a worsening clinical picture should lead to surgical intervention.

Role of caveolae in the pathogenesis of cholesterol-induced gallbladder muscle hypomotility.

Muscle cells from human gallbladders (GB) with cholesterol stones (ChS) exhibit a defective contraction, excess cholesterol (Ch) in the plasma membrane, and lower binding of CCK-1 receptors. These abnormalities improved after muscle cells were incubated with Ch-free liposomes that remove the excess Ch from the plasma membrane. The present studies were designed to investigate the role of caveolin-3 proteins (Cav-3) in the pathogenesis of these abnormalities. Muscle cells from GB with ChS exhibit higher Ch levels in the plasma membrane that were mostly localized in caveolae and associated with parallel increases in the expression of Cav-3 in the caveolae compared with that in GB with pigment stones (PS). The overall number of CCK-1 receptors in the plasma membrane was not different between muscle cells from GB with ChS and PS, but they were increased in the caveolae in muscle cells from GB with ChS. Treatment of muscle cells from GB with ChS with a Galpha(i3) protein fragment increased the total binding of CCK-1 receptors (from 8.3 to 11.2%) and muscle contraction induced by CCK-8 (from 11.2 to 17.3% shortening). However, Galpha(q/11) protein fragment had no such effect. Moreover, neither fragment had any effect on muscle cells from GB with PS. We conclude that the defective contraction of muscle cells with excessive Ch levels in the plasma membrane is due to an increased expression of Cav-3 that results in the sequestration of CCK-1 receptors in the caveolae, probably by inhibiting the functions of Galpha(i3) proteins.

The influence of gallbladder function on the symptomatology in gallstone patients, and the outcome after cholecystectomy or expectancy.

The purpose of this study was to examine whether gallbladder function as assessed by a hepatobiliary scintigraphy was related to the symptomatology in gallstone patients and to the outcome 1 year after either cholecystectomy or watchful waiting. The study included 100 patients with uncomplicated gallstone disease. Fifty-six patients had a functioning gallbladder and 44 had a nonfunctioning gallbladder. Patients with a nonfunctioning gallbladder had significantly more vomiting and received more pain-killing injections during pain attacks. Otherwise, there were no differences in pain patterns or characteristics of dyspeptic symptoms in relation to gallbladder function. In patients with a functioning gallbladder, there were no significant differences between the group of patients with impaired and normal gallbladder function. Cholecystectomy was performed in 69 patients and at the 1-year follow-up; 22% continued to have pain attacks, but this was not related to the gallbladder function preoperatively. In 31 patients without cholecystectomy, 14 patients became asymptomatic within a 1-year follow-up. However, this was not related to gallbladder function. In conclusion, gallbladder function evaluated by a hepatobiliary scintigraphy was not related to the symptoms in gallstone patients, and was not related to the occurrence of symptoms after cholecystectomy or watchful waiting.

Relation of gallbladder function and Helicobacter pylori infection to gastric mucosa inflammation in patients with symptomatic cholecystolithiasis.

BACKGROUND: Inflammatory alterations of the gastric mucosa are commonly caused by Helicobacter pylori (Hp) infection in patients with symptomatic gallstone disease. However, the additional pathogenetic role of an impaired gallbladder function leading to an increased alkaline duodenogastric reflux is controversially discussed. AIM: To investigate the relation of gallbladder function and Hp infection to gastric mucosa inflammation in patients with symptomatic gallstones prior to cholecystectomy. PATIENTS: Seventy-three patients with symptomatic gallstones were studied by endoscopy and Hp testing. METHODS: Gastritis classification was performed according to the updated Sydney System and gallbladder function was determined by total lipid concentration of gallbladder bile collected during mainly laparoscopic cholecystectomy. RESULTS: Fifteen patients revealed no, 39 patients mild, and 19 moderate to marked gastritis. No significant differences for bile salts, phospholipids, cholesterol, or total lipids in gallbladder bile were found between these three groups of patients. However, while only 1 out of 54 (<2%) patients with mild or no gastritis was found histologically positive for Hp, this infection could be detected in 14 (74%) out of 19 patients with moderate to marked gastritis. CONCLUSION: Moderate to marked gastric mucosa inflammation in gallstone patients is mainly caused by Hp infection, whereas gallbladder function is not related to the degree of gastritis. Thus, an increased alkaline duodenogastric reflux in gallstone patients seems to be of limited pathophysiological relevance.

Mechanisms of disease: the genetic epidemiology of gallbladder stones.

Cholelithiasis is one of the most prevalent and most expensive gastroenterologic diseases. It belongs to the group of complex metabolic disorders that affect humans, and its critical pathogenic mechanisms are not well defined. As a result, primary or secondary prevention strategies are sparse, and the only effective treatment is cholecystectomy. Here we provide an update on the molecular pathogenesis of gallbladder stones, evidence supporting the hypothesis that genetic factors are key elements predisposing to gallstones, and progress in human genetic studies of cholesterol stones. Data from recent identical twin, family and linkage studies provide conclusive evidence for a strong genetic component to gallstone disease. Furthermore, epidemiologic studies in at-risk populations indicate that gallstone formation is caused by multiple environmental influences and common genetic factors and their interactions. By contrast, monogenic subtypes of cholelithiasis, such as ATP-binding-cassette transporter deficiencies, appear to be rare. The summary of human association studies illustrates that distinct common gene variants might contribute to gallstone formation in different ethnic groups. The characterization of lithogenic genes in knockout and transgenic mice and the identification of many gallstone-susceptibility loci in inbred mice provide the basis for studies of the corresponding genes in patients with gallstones. The transfer of findings from mouse genetics to the bedside might lead to new strategies for individual risk assessment and reveal novel molecular targets for prevention and medical therapies.