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Biomedical subjects

J L Thistle

Publications and source records attributed to J L Thistle.

At least 19 recordsLinked to original sources

An assessment of the role of liver biopsies in asymptomatic patients with chronic liver test abnormalities.

OBJECTIVE: The role of liver biopsy in the management of patients with nonspecific chronic liver enzyme abnormalities is not well established. The aim of this study is to determine whether liver histology changes the clinical impression formed before liver biopsy and the preliminary management plan. METHODS: Consenting asymptomatic adult patients with persistent (> or = 6 months) liver test abnormalities were enrolled. Patients with a strong suspicion for a specific liver disease were excluded. A presumptive diagnosis and a preliminary management plan were documented before a liver biopsy. After the liver biopsy, the patients were reassessed to determine the effect of the biopsy on the diagnosis and management plan. RESULTS: A total of 36 patients were enrolled: 15 men and 21 women, with a median age of 51 yr. The prebiopsy diagnoses were nonalcoholic steatohepatitis (24), autoimmune hepatitis (3), primary biliary cirrhosis (2), primary sclerosing cholangitis (2), and miscellaneous (5 patients). The liver biopsy changed the diagnosis in 14% of cases. Lifestyle recommendations were not significantly altered by the biopsy. The liver biopsy affected the frequency of liver test monitoring in 13 patients (36%). Treatment recommendations were affected in 12 cases, 10 of whom were offered investigational therapy. CONCLUSIONS: Although a liver biopsy may help to definitively establish the final diagnosis in patients, the results alter the presumptive prebiopsy diagnosis infrequently, and no proven therapy exists for the vast majority of these patients. Therefore, the risks and benefits of a liver biopsy should be carefully weighed, especially in settings in which investigational therapies are unavailable.

Biopsy↗

Pathophysiology of bile duct stones.

Secondary duct stones are usually detected and easily removed at the time of cholecystectomy either during surgery or endoscopically before or after the operation. Primary duct stone diseases, although much less common, are often a greater therapeutic challenge. These stones may be huge, distributed throughout the biliary tree (including areas difficult to access), and unresponsive to pharmacologic measures. Recurrence of primary duct stones is the rule rather than the exception, and reliable methods for prevention remain to be established. Moreover, morbidity and mortality due to biliary obstruction, sepsis, and choliangiocarcinoma make primary bile duct stone disease a formidable adversary. A better understanding of their pathogenesis can facilitate more effective approaches to treatment and, most important, prevention.

Cholelithiasis↗

Direct contact dissolution therapy.

Direct contact dissolution using MTBE is a safe, effective treatment for many patients with cholesterol gallstones when performed by clinicians experienced with this technique. This may be the treatment of choice for many patients at high risk for general anaesthesia or surgery. Cholecystostomy using local anaesthesia with subsequent stone extraction is an alternative requiring prolonged catheter drainage, and is associated with some risk and discomfort (Hawkyard et al, 1990). Most experts concur that laparoscopic cholecystectomy cannot be performed safely and comfortably without general anaesthesia under most circumstances. A second small population of patients are inordinately apprehensive about general anaesthesia or surgical removal of their gallbladder and refuse standard therapy in spite of recurrent biliary symptoms. Although direct contact dissolution is generally well tolerated, it may require several days of paramedical attention with medical supervision. This procedure will be most efficiently, effectively and comfortably performed by an experienced team and is, therefore, probably best provided by referral centres with physicians sufficiently interested in the treatment of biliary tract stone disease to develop expertise with this method.

Catheterization↗

Dissolution of calcium bilirubinate and calcium carbonate debris remaining after methyl tert-butyl ether dissolution of cholesterol gallstones.

Methyl tert-butyl ether rapidly dissolves cholesterol gallstones, although insoluble debris may remain. Total gallstone dissolution could be achieved if safe solvents for these noncholesterol components can be developed. We evaluated the in vitro ability of ethylenediaminetetraacetic acid, citrate, dimethyl sulfoxide, and ionic or nonionic detergents to dissolve the predominantly calcium bilirubinate and calcium carbonate debris remaining after methyl tert-butyl ether gallstone dissolution. Ethylenediaminetetraacetic acid 1% or 2% at pH 9.5 was the most effective of the solvents studied for dissolving calcium and bile pigment. The addition of cholate (25-200 mM) or polysorbate (1%-10%) to ethylenediaminetetraacetic acid 1% at pH 9.5 enhanced pigment dissolution compared to ethylenediaminetetraacetic acid alone. Dissolution of pellets prepared from human gallstones and composed predominantly of either calcium bilirubinate or calcium carbonate was 80% and 85% at 4 h using ethylenediaminetetraacetic acid 1% plus polysorbate-20 1% at pH 9.5. We conclude that ethylenediaminetetraacetic acid, either alone or with a detergent, is an effective solvent for methyl tert-butyl ether-insoluble gallstone debris and deserves assessment in vivo.

Bilirubin↗

Gallstone dissolution in vitro using methyl tert-butyl ether: radiologic selection criteria.

Methyl tert-butyl ether dissolves cholesterol gallbladder stones when infused through a percutaneous transhepatic catheter. All gallstones, however, contain noncholesterol components that are insoluble in lipid solvents and may be too large to be aspirated through a small catheter or flushed from the gallbladder. To identify which patients have gallstones that are most likely to completely dissolve, we evaluated the ability of methyl tert-butyl ether to dissolve gallstones in vitro based on their radiodensity and size. Radiodensity influenced completeness of dissolution (p less than 0.01), but size did not (p greater than 0.5). Twenty-six of 32 radiolucent stones (81%) dissolved completely, leaving residual debris less than 2 mm in diameter. Only 2 of 32 radiopaque stones (6%) dissolved completely. Insoluble radiolucent and radiopaque stones less than 0.5 cm in diameter were black pigment stones. Four radiolucent and 19 of 22 radiopaque stones (86%) greater than 0.5 cm in diameter underwent partial dissolution leaving residual debris 2 mm or larger. By infrared spectroscopy, calcium bilirubinate and calcium carbonate were identified as the principal components of this methyl tert-butyl ether-insoluble debris. Until methods for dissolving or fragmenting noncholesterol components of gallstones are available, only patients with radiolucent gallstones should be treated with methyl tert-butyl ether.

Cholelithiasis↗

Safety of same-day sequential extracorporeal shock wave lithotripsy and dissolution of gallstones by methyl tert-butyl ether in dogs.

Passage of stone fragments after extracorporeal shock wave lithotripsy (ESWL) of gallstones has resulted in biliary colic, duct obstruction, and pancreatitis in some patients. Rapid dissolution of these fragments with methyl tert-butyl ether (MTBE) may prevent such side effects and achieve complete clearance of gallstones within hours rather than several months to a year or longer. This study examines the safety of same-day ESWL fragmentation and MTBE dissolution of surgically implanted human gallstones in 15 dogs. The animals were randomly assigned to one of four treatment groups to assess MTBE absorption from the gallbladder and to observe hematology and chemistry profiles after 0, 400, and 1,200 shock waves from a lithotriptor followed by MTBE dissolution therapy. They were sacrificed either immediately after treatment (12 dogs) or 2 weeks later (3 dogs). The results demonstrated that although ESWL causes moderate trauma to the gallbladder, this did not result in increased MTBE absorption or histologic evidence of mucosal disruption. Blood profiles demonstrated an increase in only the level of aspartate aminotransferase. The three dogs that were sacrificed 2 weeks after the combined treatment had no residual evidence of gallbladder injury or remaining stone material. In all animals, severe injury occurred where shock waves passed through lung or air-filled colon. This study suggests that same-day sequential fragmentation of gallstones by ESWL followed by dissolution of stone fragments with use of MTBE may be associated with only mild to moderate and reversible gallbladder trauma and can rapidly achieve clearance of gallstones.

Animals↗

The incidence of cholelithiasis and cholecystitis in Rochester, Minn, 1950 through 1969.

During the period 1950 through 1969, 2344 persons (755 men and 1589 women) in Rochester, Minn, met diagnostic and residency criteria for cholelithiasis. The age-adjusted average annual incidence rates per 100,000 population were 217 for men and 370 for women (adjusted rates were 255 and 276, respectively). Incidence rates increased with age in both sexes, but more rapidly so for men, so that by 70 years of age the rate for men was higher than that for women. For the decades covered in this study, no secular trend in incidence was detected for the two sexes combined or separately.

Age Factors↗

Dissolution of cholesterol gallbladder stones by methyl tert-butyl ether administered by percutaneous transhepatic catheter.

We treated 75 patients with symptomatic cholesterol gallstones by dissolving the stones with methyl tert-butyl ether (MTBE) instilled into the gallbladder through a percutaneous transhepatic catheter. The MTBE was continuously infused and aspirated manually four to six times a minute, for an average of five hours per day for one to three days; the treatment was monitored by fluoroscopy. The placement of the catheter and the administration of MTBE caused few side effects or complications, and treatment did not have to be stopped in any patient for this reason. In 72 patients there was complete dissolution of stones or more than 95 percent dissolution. Among 21 patients who were completely free of stones after treatment, 4 had recurrence of stone formation 6 to 16 months later. The other 51 patients had residual debris, which spontaneously cleared completely in 15 patients within 6 to 35 months; only 7 with persisting debris have had symptoms. Five of the initial 6 patients treated, but only 1 of the next 69 patients, have required surgery during follow-up periods of 6 to 42 months. We conclude that the dissolution of gallstones by MTBE delivered through a percutaneous transhepatic catheter is a useful alternative to surgery in selected patients with symptomatic cholesterol stones. Further study will be necessary to establish the long-term effectiveness of this treatment and its appropriate role in the management of the various types of gallstones.

Adult↗

Postdissolution gallstone recurrence. A clinical perspective.

The intuitive assumption that gallstones will rapidly recur in all patients is clearly incorrect. At least 50% of patients do not develop stones within three to five years of complete dissolution, and the risk may decrease after the first two or three years. This is not so surprising when one considers the complexity of the pathogenic process. Bile must be sufficiently supersaturated with cholesterol, an imbalance in nucleating and antinucleating factors must occur, at least transiently, and, for some patients, a defect in gallbladder emptying may be necessary. Occasionally, pathogenic mechanisms that had been present, eg, estrogens, obesity, or medications such as clofibrate, may no longer be active. The best method to reduce the risk of recurrence is to reverse one or more of the essential pathogenic mechanisms. Desaturating bile in cholesterol by oral therapy with a bile acid such as ursodiol should be effective. A search for other safe, effective, and cost-effective approaches persists, eg, for novel bile acids resistant to bacterial degradation and for various dietary regimens. Alteration of cholesterol nucleation with nonsteroidal antiinflammatory agents is also under investigation. In addition, enhancement of gallbladder emptying is an interesting approach that is worth studying. If stones do recur, the course of action is not always clear. Recurrent stones are usually "silent," and we do not usually treat asymptomatic stones. These small cholesterol stones are temptingly easy to dissolve, however. At least in those patients whose level of surgical risk would be high if symptoms developed, prophylactic dissolution therapy may be desirable.

Bile↗

Extracorporeal shock-wave lithotripsy and methyl tert-butyl ether for partially calcified gallstones.

To explore the possibility that gallbladder stone fragments might be able to be safely dissolved using methyl tert-butyl ether immediately after extracorporeal shock-wave lithotripsy (ESWL), a feasibility study in 8 patients with one to four partially calcified gallbladder stones was performed. The gallstones averaged 2.2 cm in diameter (range 1.3-3 cm) and contained layered or diffuse calcium detectable by computed tomography scan only (7 patients) or plain film (1 patient). After a 5F (1.7 mm) pigtail catheter was placed percutaneously into the gallbladder, ESWL fragmentation was performed using a renal stone lithotriptor. The patients were under general anesthesia and in the prone position on a support gantry designed for gallbladder stone ESWL. Following ESWL, methyl tert-butyl ether was infused and aspirated via the gallbladder catheter until no further stone material was radiologically detectable or could be dissolved. After 8-26 h (mean = 13 h) of methyl tert-butyl ether therapy, no radiologically detectable gallstones remained in 6 of 8 patients. Shell fragments of three peripherally calcified stones in 1 patient and the densely calcified, predominantly pigment stone in a second patient were refractory to combined therapy. Both ESWL and treatment with methyl tert-butyl ether were well tolerated in all patients, although bile leakage after catheter removal occurred in 3 patients, one of whom was treated by cholecystectomy. Additional measures to prevent bile leakage may be advisable if these two modalities are to be used in tandem. We found no evidence, however, that predissolution stone fragmentation with ESWL predisposed the gallbladder to either mucosal damage by methyl tert-butyl ether or increased absorption of it.

Aged↗

Gallstones: an update.

Gallstones are a major health problem in the United States. More than 20 million Americans have gallstones, and a million new cases are discovered each year. A resurgence of interest in this field has been stimulated by advances in understanding the pathogenesis of cholesterol gallstones and in nonsurgical treatments. The purpose of this symposium is to update these advances.

Cholelithiasis↗

Pros and cons of the nonsurgical treatments for gallbladder stones.

Dissolution of gallbladder stones is usually possible if the cholesterol content of the stones is high. Oral treatment with chenodiol or ursodiol is least invasive, but also least effective and slow. methyl tert-butyl ether requires delivery by percutaneous transhepatic catheter, but is rapidly effective. Extracorporeal shock wave lithotripsy enhances dissolution by oral bile acids, but is highly effective only for solitary stones less than or equal to 20 mm in diameter. Percutaneous cholecystostomy is most invasive, but effective regardless of stone composition. Stones will probably recur in 50 percent of patients with a patent cystic duct and intact gallbladder.

Cholecystostomy↗