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Cholelithiasis in sickle cell anemia: surgical considerations.

Gallstones are frequently found in patients with sickle cell anemia. The differentiation between acute calculous biliary tract disease and sickle cell crisis can be difficult and should be based on the clinical presentation, comparison with previous episodes of abdominal pain, and judicious use of hepatobiliary radionuclide scanning. Emergency cholecystectomy is associated with a high morbidity and should be avoided if possible. Elective cholecystectomy is associated with a lower but still significant risk of complications. We believe patients with sickle cell anemia and symptomatic cholelithiasis should have elective cholecystectomy. Careful management is essential to minimize the danger of postoperative complications.

Acute Disease↗

Rapid spontaneous resolution of cholelithiasis in a newborn.

We have described a newborn who had rapid resolution of cholelithiasis after a gallstone was incidentally discovered during sonographic evaluation of a renal mass. This case emphasizes the importance of conservative management and serial sonograms in infants with tumefacient sludge or gallstones without clinical or imaging evidence of biliary tract disease.

Cholelithiasis↗

Abdominal pain resulting from cerebrospinal fluid pseudocyst and cholelithiasis.

Patients treated with ventriculoperitoneal (VP) shunt procedures for hydrocephalus may have abdominal pain related to complications stemming from the shunt tubing itself or to other intra-abdominal disease. In patients with VP shunts, usually children, lack of absorption of cerebrospinal fluid (CSF) may produce a painful abdominal CSF pseudocyst. We have reported the rare occurrence of a CSF pseudocyst in an adult. The patient was also found to have cholelithiasis.

Abdominal Pain↗

Leaking gallbladder remnant with cholelithiasis complicating laparoscopic cholecystectomy.

Since its introduction in 1989, laparoscopic cholecystectomy has rapidly become the preferred alternative to open cholecystectomy for symptomatic cholelithiasis. Although possible complications of laparoscopic cholecystectomy are essentially the same as for open cholecystectomy, we report a case of an inadvertent subtotal cholecystectomy, a complication that we believe has not been previously reported.

Bile↗

Prevalence of asymptomatic cholelithiasis and risk of acute cholecystitis after kidney transplantation.

Prophylactic cholecystectomy for asymptomatic cholelithiasis is sometimes required before transplantation. However, there is little indication in the literature that transplant recipients are at any greater risk than individuals in the general population. Between January 1990 and December 1993, 211 renal transplant recipients underwent duplex sonography. All were asymptomatic. Twenty-one had positive findings: gallstones were found in 15 patients (7.11%) and sludge was found in 6 (2.84%). Of gallstone patients, seven (3%) were men and eight (4%) were women. One gallstone patient also had diabetes mellitus. The mean age by gender of the patients with calculi was 54 years for men and 38 years for women. Thirteen of the 15 patients with calculi (87%) have remained asymptomatic. Two patients (one diabetic) developed acute cholecystitis and underwent uncomplicated laparoscopic cholecystectomy. Patients with sludge were similar in gender and age to patients with gallstones; one patient had diabetes. No sludge patients became symptomatic. The incidence and morbidity of gallstones after kidney transplantation are low. Prophylactic cholecystectomy in asymptomatic patients before transplantation is not justified.

Acute Disease↗

Epidemiology of cholelithiasis in southern Italy. Part II: Risk factors.

OBJECTIVE: To determine behavioural, dietary and other common factors associated with new cases of gallstones, diagnosed by ultrasonography, in a prospective cohort study conducted in southern Italy. SUBJECTS AND METHODS: Between May 1985 and June 1986, systematic sampling from the electoral register of Castellana, a small town in southern Italy, yielded 2472 subjects who had had their gallbladder checked for gallstones by ultrasonography. Between May 1992 and June 1993, 1962 out of the 2235 (87.7%) subjects without gallstones at baseline agreed to a further ultrasound examination. At the first survey a standardized questionnaire was administered, inquiring about medical history, diet, cigarette smoking and other behavioural characteristics. Height and weight were also measured, and blood levels of glucose, cholesterol, HDL-cholesterol and triglycerides were determined by standard methods. The same variables were measured at the second survey. The diagnosis of gallstones was made with the same echograph by echographists working in the same department. Multiple logistic regression was used to determine which factors measured at the first survey were associated with the incident cases of gallstones. RESULTS: One hundred and four subjects had developed gallstones, an incidence of 9.7 per 1000 persons per year. Age, body mass index (BMI), weight change, a history of diabetes, constipation (shown by use of laxatives), cigarette smoking, years of schooling, consumption of fried foods and excessive oil, and pregnancy in females, were positively associated with the incidence of gallstones. Consumption of wine, coffee, fish and wholemeal bread was inversely associated. Sex, family history of cholelithiasis, use of oral contraceptives and serum lipids were not independent risk factors for gallstones. CONCLUSION: The results of this study confirm many gallstone-associated factors reported in previous cross-sectional and case-control studies, as well as in other cohort studies based on the clinical diagnosis of gallstones, such as BMI, ageing and wine consumption. Furthermore, use of laxatives, considered a proxy of constipation, appears to be another important independent risk factor for gallstones.

Adult↗

Influence of bilirubin uridine diphosphate-glucuronosyltransferase 1A promoter polymorphisms on serum bilirubin levels and cholelithiasis in children with sickle cell anemia.

PURPOSE: Genetic mutations in the uridine diphosphate (UDP)-glucuronosyltransferase 1A (UGT1A) enzyme promoter have been associated with unconjugated hyperbilirubinemia and Gilbert syndrome. The effects of UGT1A promoter polymorphisms on serum bilirubin levels and symptomatic gallstone formation were studied in a cohort of children with sickle cell anemia (SCA). METHODS: The UGT1A promoter genotype was deterrmined for 115 consecutive children with SCA. Steady-state laboratory parameters and previous cholecystectomy for symptomatic gallstones were recorded retrospectively, then analyzed according to UGT1A genotype. RESULTS: Children with SCA had a lower frequency of the normal (TA)6 UGT1A promoter allele (0.413) than the abnormal (TA)7 allele (0.461). A previously described shorter (TA)5 allele (frequency 0.074) and longer (TA)8 allele (frequency 0.052) were also observed. Children with the 7/7 UGT1A genotype had a significantly higher mean bilirubin level (5.8 +/- 3.1 mg/dL) than those with the 6/6 (2.4 +/- 0.8 mg/dL) or 6/7 genotype (3.0 +/- 1.1 mg/dL; P < 0.001 by analysis of variance). Patients with the 7/7 genotype were more likely to have previous cholecystectomy (87.5%) than those with the 6/6 (35.7%) or the 6/7 genotype (36.1%; P = 0.002 by chi2). CONCLUSIONS: Genetic variation in the UGT1A promoter significantly influences serum bilirubin levels and the development of symptomatic cholelithiasis in children with SCA. The UGT1A promoter polymorphisms represent an important nonglobin genetic modifier of clinical disease expression in SCA.

Adolescent↗

Cholelithiasis and choledocholithiasis after sequential cytarabine and asparaginase.

We report 2 children with acute leukemia who developed symptomatic cholelithiasis and choledocholithiasis shortly after receiving sequential high-dose cytarabine and asparaginase. Known risk factors for gallstone formation were not present in our patients. These children did not experience any unusual therapy-related hepatic toxicity after laparoscopic cholecystectomy.

Antimetabolites, Antineoplastic↗

Hepatic HMGCoA reductase in human cholelithiasis: effects of chenodeoxycholic and ursodeoxycholic acids.

To study further the role of hepatic cholesterol synthesis in patients with gallstones, the activity of the rate-limiting step in cholesterogenesis, hydroxymethyl glutaryl co-enzyme A reductase (HMGCoAR), was measured in operative wedge liver biopsies from ten patients with untreated cholesterol gallstones, six with pigment stones and ten controls. Hepatic HMGCoAR was also measured in six patients with cholesterol-rich gallstones treated for 1-24 months with 14.6-18.6 mg chenodeoxycholic acid (CDCA) kg-1 day-1, in two patients with radiolucent pigment stones treated with 17.3 and 17.7 mg CDCA kg-1 day-1 and in ten other patients with cholesterol-rich stones given 4.5-7.2 mg ursodeoxycholic acid kg-1 day-1 for 1-6 months. HMGCoAR activity was also related to the free and esterified cholesterol content of both hepatic homogenates and the microsomal fractions. Compared with the controls (HMGCoAR activity 14.6 +/- 1.6 (SEM) pmole mg microsomal protein-1 min-1), the mean activity in untreated cholesterol cholelithiasis was 32.2 +/- 2.0 (P < 0.001), but was near normal in patients with pigment stones (16.2 +/- 1.5). In cholesterol gallstone patients, chenodeoxycholic acid treatment reduced the mean enzyme activity by 51% compared with the untreated gallstone group (P < 0.001) and in smaller doses, ursodeoxycholic acid therapy lowered it by 40% (P < 0.001) but in the two patients with pigment stones, CDCA did not seem to affect HMGCoAR activity. Despite this four-fold variation in enzyme activity, there were no significant differences in mean free or esterified cholesterol concentrations in whole liver homogenates or in the microsomal fraction from any of the patient groups.

Adolescent↗

Gastric electrical activity in patients with cholelithiasis undergoing laparoscopic cholecystectomy: a prospective controlled study.

BACKGROUND: The aim of the present study was to evaluate the effect of gallstone disease (GD) and laparoscopic cholecystectomy on gastric electrical activity of slow waves, which was recorded via transcutaneous electrogastrography (EGG). METHODS: Twenty-one consecutive patients (M/F: 12/9, 52.7 +/- 15 years old) with GD and no previous history of abdominal operations or known disease affecting gastrointestinal motility were studied. The EGG was performed for 30 min prior to and 90 min after a standard meal, during a 4-6 month period prior to and after laparoscopic cholecystectomy. The percentile proportion of the three spectra of gastric slow waves frequency was studied, defined as follows: bradygastria, 1-2.1 cycles per min (c.p.m.); normogastria, 2.2-3.9 c.p.m.; and tachygastria, 4-9 c.p.m. The findings were compared to those of nine healthy subjects (M/F: 5/4, 49.5 +/- 14.8 years old). RESULTS: No statistically significant difference was found in percentile distribution of bradygastria, normogastria and tachygastria, pre- or post-prandially, neither before or after laparoscopic cholecystectomy, nor between patients and controls. CONCLUSIONS: Patients with GD do not exhibit differences in gastric electrical activity of slow waves in comparison to normal subjects and laparoscopic cholecystectomy does not alter gastric electrical activity. These findings suggest that cholelithiasis does not seem to cause dyspeptic symptoms due to gastric dysrythmias.

Adult↗

Ultrasonographic diagnosis of fetal cholelithiasis.

A case of opacity in the fetal gallbladder was diagnosed by ultrasound. The lesion resolved spontaneously in the postnatal period. Careful follow-up ultrasound examinations are necessary for fetal cholelithiasis in the pre- and postnatal periods, and conservative management is mandatory.

Adult↗

Drug-associated cholelithiasis: a case of sulindac stone formation and the incorporation of sulindac metabolites into the gallstones.

A case of drug-associated cholelithiasis (sulindac chlecystohepatolithiasis) in a 63-yr-old woman is reported. The patient was admitted to our hospital to undergo treatment for rheumatoid arthritis of 20 yr duration. She was treated with nonsteroidal anti-inflammatory drugs (NSAID: sulindac). Two months later, she presented with right upper quadrant pain. Diagnostic studies including ultrasonography (US), computed tomography (CT) and endoscopic retrograde cholangiography (ERC), led to the diagnosis of cholecystohepatolithiasis. She underwent cholecystectomy and choledochotomy with an extraction of intrahepatic stones. The intrahepatic stones were light yellow in color with a claylike appearance. Unexpectedly, an infrared spectroscopic analysis of the stone showed it to consist of sulindac metabolites. In addition, the dilated segment of the intrahepatic bile duct naturally returned to its normal size after the discontinuation of the drug administration. This is the first reported case of sulindac stone formation in the bile duct. No similar problems with other NSAIDs have been reported previously.

Anti-Inflammatory Agents, Non-Steroidal↗

Sucrose-positive Edwardsiella tarda mimicking a biogroup 1 strain isolated from a patient with cholelithiasis.

An unusual strain of Edwardsiella tarda mimicking a biogroup 1 isolate was recovered in a mixed infection from a woman suffering from cholelithiasis. Rare biochemical characteristics (e.g., H2S negativity) originally detected were related to an unusual biochemical property in this species, sucrose fermentation; other points of interest regarding this strain included the site of isolation (bile) and the failure of this isolate to produce many of the in vitro virulence markers associated with E. tarda.

Aged↗

Discriminant value of dyspeptic symptoms: a study of the clinical presentation of 221 patients with dyspepsia of unknown cause, peptic ulceration, and cholelithiasis.

This study aims to determine whether the features of dyspepsia can discriminate a subgroup of patients who present with non-ulcer dyspepsia from other diagnostic categories. The following groups were studied: One hundred and thirteen patients with endoscopically confirmed non-ulcer dyspepsia in the absence of clinical, biochemical or radiological evidence of other gastrointestinal diseases or disorders, termed essential dyspepsia; Fifty five patients with symptomatic and endoscopically proven peptic ulceration (32 duodenal ulcers, 23 gastric ulcers); Fifty three patients admitted to hospital with biliary pain and cholelithiasis without other lesion at laparotomy. All patients completed a structured history questionnaire at personal interview. Stepwise logistic regression analysis was done on 19 predefined variables to determine if one or more of these could discriminate between the diagnostic categories. The results suggest that certain groups of symptoms may be of diagnostic value, but many are not. Upper abdominal pain aggravated by food or milk, pain severity, night pain, vomiting, weight loss, and age significantly discriminated essential dyspepsia from the other diagnostic categories. A scoring system was established based on these discriminating symptoms. Using the weighted score, at a sensitivity of 57%, the specificity for a diagnosis of essential dyspepsia was 94%, but only prospective studies will determine if this scoring system is of actual clinical value.

Cholelithiasis↗

Cholesterol synthesis inhibition distal to squalene upregulates biliary phospholipid secretion and counteracts cholelithiasis in the genetically prone C57L/J mouse.

BACKGROUND AND AIMS: Newly synthesised cholesterol contributes poorly to biliary lipid secretion but may assume greater importance when the rate limiting enzyme 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) is upregulated. As this occurs in the gall stone susceptible C57L/J inbred mouse, we employed two cholesterol biosynthesis inhibitors, Tu 2208 and Ro 48-8071, potent inhibitors of squalene epoxidase and oxidosqualene-lanosterol cyclase, respectively, to assess their potential in preventing cholesterol cholelithiasis in the C57L/J mouse strain. Mice were fed a lithogenic diet comprising a balanced nutrient intake with 15% dairy fat, 1% cholesterol, and 0.5% cholic acid added. METHODS: We determined gall stone phenotype, HMGR activity, biliary lipid secretion rates, and counterregulatory events in male C57L/J mice and gall stone resistant AKR treated with Tu 2208 (30-60 mg/kg/day) or Ro 48-8071 (30-100 mg/kg/day), while ingesting chow or the lithogenic diet. RESULTS: Both agents reduced the gall stone prevalence rate from 73% to 17% in C57L/J mice, inhibited HMGR activity, and decreased hepatic cholesterol concentrations without appreciably influencing biliary cholesterol secretion. In C57L as well as AKR mice, both agents increased biliary phospholipid (which is mostly phosphatidylcholine) secretion rates and at the highest doses effectively reduced the biliary cholesterol saturation index. CONCLUSIONS: Cholesterol biosynthesis inhibitors acting distally to squalene do not reduce biliary cholesterol secretion rates despite reductions in cholesterol biosynthesis and hepatocellular levels. However, they effectively prevent gall stone formation through stimulation of pathways that lead to enhanced biliary phospholipid secretion.

Animals↗

Laparoscopic therapy of cholelithiasis.

Laparoscopic cholecystectomy has emerged as the treatment of choice for symptomatic cholecystolithiasis. Results will improve and complications rates decrease as surgeons gain experience in the method. New developments will permit a complete laparoscopic approach to cholelithiasis.

Cholecystectomy, Laparoscopic↗

Spontaneous resolution of cholelithiasis in infants.

Follow-up sonographic studies of five infants whose initial sonograms had displayed evidence for the diagnosis of cholelithiasis demonstrated spontaneous resolution of the gallbladder defects. These defects may have been caused by tumefactive sludge with acoustic shadowing. Whether sludge or gallstones are being imaged, in the absence of other clinical or imaging evidence of biliary tract disease, conservative (i.e., nonsurgical) management and serial sonograms are recommended.

Cholelithiasis↗

Cholelithiasis in the morbidly obese: diagnosis by US and oral cholecystography.

Forty-two morbidly obese patients underwent cholecystectomy at the time of gastroplasty, primarily for prophylactic reasons. Preoperatively, 37 patients underwent ultrasonography (US) of the gallbladder and oral cholecystography, four US only, and one oral cholecystography only. There was one indeterminate US study (2.4%) and one indeterminate oral cholecystogram (2.7%). At US study, gallstones were detected in six of the eight patients with gallstones (sensitivity = 75%), and the gallbladders of all 32 patients without gallstones were categorized as normal (specificity = 100%). The gallstones not identified measured 1-2 mm in diameter. Oral cholecystographic study enabled detection of gallstones in three of the seven patients with gallstones (sensitivity = 43%) and categorized as normal all 30 gallbladders without gallstones (specificity = 100%). The gallstones not seen were small and included those not detected by US. The results suggest that US is equal or superior to oral cholecystography for detection of cholelithiasis in obese patients.

Adult↗