Cholecystectomy protects against extrahepatic bile duct cancer: is this a result of the removal of gallstones?
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Bile Duct Neoplasms↗
Biomedical subjects
R D Soloway
Publications and source records attributed to R D Soloway.
Primary cholesterol hepatolithiasis: a disease with a different pathogenesis.
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Apolipoprotein A-I↗
Differences in antigen expression between neoplastic and nonneoplastic gallbladder epithelium. An immunohistochemical study.
Immunoreactivity for a panel of 15 monoclonal antibodies (MAbs), which are known to react with different gastrointestinal tumor antigens, was assessed in formalin-fixed paraffin-embedded sections that were prepared from cholecystectomy specimens obtained from Mexican patients. Each case was classified histologically into one of the following groups: (1) invasive adenocarcinoma (N = 21), (2) high-grade dysplasia (carcinoma in situ) (N = 2), (3) low-grade dysplasia (N = 4), hyperplasia (4) (N = 15), and (5) chronic cholecystitis (N = 10). Significant differences (P < 0.05) were identified among the five histopathologic groups in the proportion of epithelial cells demonstrating immunoreactivity with MAbs to Lewisb; Lewis(a); sialylated Lewis(a); sialylated Lewis(a) and Lewis(a); Y antigen; H antigen; X antigen; X-like antigen; 200-kDa protein of CEA; 180-, 160-, 50-, 40-kDa proteins of CEA; 30- to 37-kDa protein; and an undefined antigen identified by MAb 99-57, with invasive carcinoma more frequently being positive as compared to nonneoplastic (hyperplasia, chronic cholecystitis) epithelium. Significant differences were also observed among the five histopathologic groups (P < or = 0.0005) in the proportion of epithelial cells demonstrating immunoreactivity with MAbs to Y antigen and the 20- to 50-kDa glycoprotein. However, with these two antibodies immunoreactivity was more frequently found in nonneoplastic epithelium rather than in invasive carcinomas. No significant differences in immunoreactivity were detected among the different histologic groups with MAb to blood group B antigen, types 1 and 2. This study demonstrates that cellular antigens are both developed and lost during the process of neoplastic transformation in the gallbladder.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenocarcinoma↗
Primary malignant fibrous histiocytoma of the liver MRI findings.
Primary malignant fibrous histiocytoma (MFH) is an unusual tumor which involves the deep fascia or skeletal muscles of the extremities or retroperitoneum. It rarely arises in the liver and, to our knowledge, the MRI appearance of primary MFH of the liver has never been reported. We present a patient with primary MFH of the liver and discuss the findings on MRI, CT, and angiography.
Histiocytoma, Benign Fibrous↗
Clostridium difficile diarrhea in patients with AIDS versus non-AIDS controls. Methods of treatment and clinical response to treatment.
We reviewed the hospital charts of 17 patients with AIDS and Clostridium difficile diarrhea to determine antibiotic use before C. difficile infection, methods of treatment for C. difficile diarrhea, and response of diarrhea to treatment. Left shift and total white blood cell count before and after treatment for C. difficile were also determined. Non-HIV-infected patients with C. difficile diarrhea served as controls. In the patients with AIDS, resolution of diarrhea was noted in 15 (88%) patients. In 25 (76%) control patients, diarrhea resolved with treatment. The patients with AIDS also had a significant decrease (p < 0.05) in left shift in white blood cell count with treatment; the controls did not. Our study therefore suggests that C. difficile diarrhea is at least as likely to resolve with antibiotic therapy in patients with AIDS as it is in those with the non-AIDS-related disorder. We also found that patients with AIDS and C. difficile diarrhea are more likely than patients without AIDS to have a decreased left shift in white blood cell count after antibiotic therapy.
AIDS-Related Opportunistic Infections↗
Inhibition of calcium hydroxyapatite formation by polyamines.
The lithogenic potential of bile depends not only on supersaturation of solutes but also on the presence of pro- and anti-nucleating factors. For example, glycine-conjugated dihydroxy bile salt dimers are potent inhibitors of calcium hydroxyapatite precipitation that function by "poisoning" the nascent crystal. Although most inhibitors of apatite formation are anions, theoretically polycations should also be effective, and because significant concentrations of polyamines are present in bile, we have investigated the ability of these molecules to inhibit apatite formation. In vitro, each polyamine (2-10 mmol/l) was able to inhibit apatite formation, and the inhibiting power was correlated with ionic charge. Thus putrescine (2+) was the weakest inhibitor and spermine (4+) was the strongest. Mixtures of polyamines were less effective than were the individual polyamines, except at higher concentrations. Although polyamines were effective over short periods of time (270 min), over longer times (3 days) spermine was unable to prevent apatite formation. Using infrared spectroscopy, we found no evidence for interaction between phosphate ions and spermine in solution. Taken together, these results suggest that polyamines are modest inhibitors of apatite formation that likely function by retarding the dissolution of the intermediate amorphous calcium phosphate phase.
Bile↗
Interaction of bile salts with calcium hydroxyapatite: inhibitors of apatite formation exhibit high-affinity premicellar binding.
Of the major human bile salts, only the glycine-conjugated dihydroxy species prevent the transformation of amorphous calcium phosphate to calcium hydroxyapatite, a component of gallstones; we have proposed that this inhibition occurs by competition between the bile salt and HPO4(2-) anions for binding site on the apatite crystal embryo. Now we show that the binding affinity of bile salts to fully mature hydroxyapatite has the following order: glycine-conjugated dihydroxy salts > taurine-conjugated dihydroxy salts > glycocholate approximately taurocholate. Glycine-conjugated dihydroxy bile salts bound with high affinity as "premicellar" aggregates, but the remaining species appeared to bind as a wider range of aggregate sizes. Glycochenodeoxycholate binding was decreased as the pH increased from 6.6 to 9.8 and the apatite surface charge reversed from net positive to net negative. Binding was competitively inhibited by HPO4(2-), but not by H2PO4-. Ca2+ promoted the binding of glycochenodeoxycholate, taurochenodeoxycholate and glycocholate, and for the latter two bile salts the increase was associated with enhanced "premicellar" binding. The binding of taurocholate was not influenced by Ca2+. When either glycocholate or taurocholate was mixed with glycochenodeoxycholate, mixed aggregates were formed that had a lower affinity for apatite than had pure glycochenodeoxycholate aggregates. Because only glycine-conjugated dihydroxy bile salts inhibit apatite formation, these results suggest that inhibition depends on high-affinity "premicellar" bile salt-apatite binding.
Anions↗
Glycochenodeoxycholic acid inhibits calcium phosphate precipitation in vitro by preventing the transformation of amorphous calcium phosphate to calcium hydroxyapatite.
Calcium hydroxyapatite can be a significant component of black pigment gallstones. Diverse molecules that bind calcium phosphate inhibit hydroxyapatite precipitation. Because glycine-conjugated bile acids, but not their taurine counterparts, bind calcium phosphate, we studied whether glycochenodeoxycholic acid inhibits calcium hydroxyapatite formation. Glycochenodeoxycholic acid (2 mM) totally inhibited transformation of amorphous calcium phosphate microprecipitates to macroscopic crystalline calcium hydroxyapatite. This inhibition was not mediated by decreased Ca2+ activity. Taurocholic acid (2-12 mM) did not affect hydroxyapatite formation, but antagonized glycochenodeoxycholic acid. Both amorphous and crystalline precipitates contained a surface fraction relatively rich in phosphate. The surface phosphate content was diminish by increasing glycochenodeoxycholic acid concentrations, and this relationship was interpreted as competition between bile acid and HPO4(-4) for binding sites on the calcium phosphate surface. A phosphate-rich crystal surface was associated with rapid transition from amorphous to crystalline states. These results indicate that glycochenodeoxycholic acid prevents transformation of amorphous calcium phosphate to crystalline hydroxyapatite by competitively inhibiting the accumulation of phosphate on the crystal embryo surface.
Calcium↗
Gallstone fragmentation during biliary lithotripsy: effect of stone composition and structure.
In vitro lithotripsy with the Siemens Lithostar was conducted on 36 radiolucent or minimally calcified gallstones housed in an anthropomorphic phantom. The ease and pattern of fragmentation were correlated with global composition for the entire stone, regional or microcomposition (determined by Fourier-transform infrared spectroscopy), and microstructure (determined by scanning electron microscopy). Stones made up of more than 62% cholesterol required 50% more shock waves to pulverize all fragments to 0.3 cm or less than did stones of less than 62% cholesterol (p less than .01). An inverse relationship was found between the number of shock waves needed for fragmentation and the cholesterol content (r = .77). Although a broad range of fragmentation responses occurred, little variation was seen in the ease of fragmentation within stone families. The majority of stones fractured along radially oriented cholesterol plates, but one third of stones treated showed initial chipping or flaking at the periphery before radial fracture. This type of peripheral erosion most often occurred in stones with peripheral pigment rims. These stones required more shock waves and lagged in pulverization compared with more homogeneous cholesterol stones. The efficiency of fragmentation during biliary lithotripsy correlates with the stones' global cholesterol content. A stone's architecture, as reflected by its regional composition and microstructure, partially predicts the mechanism of fragmentation. These in vitro data may be useful in further refining criteria for selecting patients and understanding the fragmentation process.
Bile Pigments↗
Serum CEA and CA 19-9: potential future diagnostic or screening tests for gallbladder cancer?
The poor prognosis of gallbladder cancer and the presence of high-risk populations make the identification of a screening test for this disease very desirable. As part of an ongoing case-control study of gallbladder cancer being conducted in Mexico City, Mexico, and in La Paz, Bolivia, blood specimens were sought from all patients with cancer of the gallbladder and on controls of similar age and sex undergoing upper abdominal surgery. Each sample was analyzed for carcino-embryonic antigen (CEA) and CA 19-9. Using the specimens from Bolivia, a serum CEA cutoff of 4.0 ng/ml yielded a sensitivity of 50.0% and a specificity of 92.7%, while a serum CA 19-9 cutoff of 20.0 units/ml yielded a sensitivity of 79.4% and a specificity of 79.2%. Using ROC curve analysis, the latter was a much better test than the former (p less than 0.05). Using the tests in series or in parallel did not substantively improve the results. The specimens from Mexico were used for validation purposes, and yielded very similar results. In conclusion, serum CA 19-9 and CEA are fairly good tests for discriminating patients with gallbladder cancer from patients with gallstones and no cancer, the former being a better test than the latter. These tests may be useful in identifying disease recurrences. In addition, if a sufficiently high-risk population could be identified, this could potentially become a useful screening test for this serious disease, allowing early intervention. However, additional data are needed prior to recommending this clinically.
Antigens, Tumor-Associated, Carbohydrate↗
Pigment gallstone pathogenesis: from man to molecules.
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Animals↗
Gallstone composition in relation to buoyancy at oral cholecystography.
Although it is recognized that some gallstones float at oral cholecystography, the reasons for this are not known. To determine how stone type and composition are related to stone buoyancy, the authors analyzed gallstones from 90 patients in the National Cooperative Gallstone Study. Seventeen patients had floating and 73 had nonfloating radiolucent stones at oral cholecystography. Stone analysis showed that all 17 floating stones were cholesterol stones; 64 of the nonfloating stones were cholesterol stones, while nine were pigment stones. The cholesterol contents of floating and nonfloating cholesterol stones were similar, 90.4% +/- 1.7 and 87.0% +/- 1.2 of stone weight, respectively. The calcium salt content of the nonfloating cholesterol stones was 3.2% +/- 0.6, while that of the floating cholesterol stones was only 1.1% +/- 0.4 (P = .02). The results indicate that floating gallstones are cholesterol stones with a significantly lower calcium salt content than that of nonfloating cholesterol stones.
Cholecystography↗
Protective action of luminal bile salts in necrotizing acute pancreatitis in mice.
Bile salts in the intestinal lumen act to inhibit the release of cholecystokinin (CCK). Recent studies have shown that CCK may play a permissive role in the development of acute pancreatitis. In this study, the amount of luminal bile salts in female Swiss Webster mice was either decreased by feeding 4% (wt/wt) cholestyramine or increased by feeding 0.5% sodium taurocholate for 1 wk. Plasma levels of CCK were stimulated by cholestyramine and inhibited by taurocholate. Then, acute pancreatitis was induced either by caerulein injections, or by feeding a choline-deficient, ethionine-supplemented (CDE) diet. Feeding of cholestyramine significantly decreased survival from 25% to 0% in the CDE pancreatitis, and increased the magnitude of elevation of serum amylase levels and the extent of pancreatic necrosis in both models of pancreatitis; CCK-receptor blockade with CR-1409 completely abolished the adverse effects of cholestyramine. In contrast, feeding of taurocholate significantly increased survival to 100% and decreased the elevation of serum amylase and pancreatic necrosis; CCK-8 antagonized these actions of taurocholate. Luminal bile salts appear to provide a physiologic protection against necrotizing pancreatitis, at least in part, both by inhibiting the release of CCK and by promoting resistance of the pancreas to CCK excessive stimulation in vivo.
Acute Disease↗
Current therapy of chronic liver disease.
The study of chronic liver disease has been hampered by insufficient information relative to the pathogenesis of the many forms of hepatitis. Consequently, well-designed treatment strategies are frequently lacking. Wilson's disease is characterised by excessive copper accumulation in the liver and other organs. While d-penicillamine is clearly effective, many patients may not tolerate its many adverse effects. Trientine, oral zinc and unithiol have all shown promise as therapeutic alternatives. Autoimmune chronic active hepatitis responds well to prednisone and azathioprine. Cyclosporin has also produced clinical improvement in several case reports but no comparison has yet been made with the current standard therapy. Recombinant interferon-alpha (IFN alpha) has demonstrated the ability to inhibit hepatitis B viral replication, and the combination of oral corticosteroids followed by IFN alpha is more effective than either agent alone in eliminating viral replication in patients with chronic active hepatitis B. Currently, primary sclerosing cholangitis (PSC) has no standard medical management, but corticosteroids and methotrexate may each have a future role in its treatment. Drug treatment for primary biliary cirrhosis (PBC) has been disappointing, and early reports of success with d-penicillamine were not confirmed in large well-controlled trials. While some reports of improvement with several agents have been described, larger studies are still needed. Alcoholic liver disease continues to be associated with significant morbidity and mortality and numerous investigators have researched several different medical avenues of treatment. Success reported with androgens and the antithyroid agent propylthiouracil in alcoholic liver disease will need confirmation by other research before these agents can be recommended for routine use. Finally, colchicine may prove to be effective in slowing the rate of fibrosis in cirrhosis, but this has yet to be conclusively proven.
Animals↗
The "buried bumper syndrome": a complication of percutaneous endoscopic gastrostomy.
Percutaneous endoscopic gastrostomy is used for long-term nutritional support and can be performed with relatively few complications. We describe a patient in whom the internal bumper eroded into the stomach wall and was completely covered by gastric epithelium 11 months after gastrostomy tube placement. The gastrostomy tube itself was patent, and the end still protruded into the lumen of the stomach so that tube feeding was not impaired. Endoscopy, in combination with passage of Savary dilators over a guidewire, was safely used to remove the gastrostomy tube and buried bumper. We recommend this approach in patients with the "buried bumper" syndrome to prevent continued tube migration into the gastric and abdominal walls.
Aged↗
Gastric bezoar complicating gastric stapling.
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Bezoars↗
Gallbladder mucin and cholesterol and pigment gallstone formation in hamsters.
We measured gallbladder mucin production by hamsters fed diets lithogenic for either cholesterol or pigment gallstones. In hamsters on the cholesterol stone diet, gallbladder production of 3H-glucosamine-labeled mucin was elevated two- and seven-fold after 1 and 3 weeks, respectively. After 1 week cholesterol crystals were seen in a mucus gel on the gallbladder surface. In hamsters on the pigment stone diet, gallbladder mucin production was significantly elevated after 1 and 3 weeks. The first precipitation of pigment crystals was in mucus in bile or on the gallbladder surface. Black pigment stones grew by agglomeration of pigment crystals enmeshed in mucus. In conclusion, gallbladder mucin production is increased before cholesterol or pigment stone formation, and the earliest deposition of crystals is in mucus in bile or on the gallbladder surface.
Animals↗
Quantitative infrared spectroscopy of common bile duct gallstones.
The aim of this study was to determine the composition of gallstones from the common bile duct of patients from the United States and the relationship of stone type to the time interval after cholecystectomy. We analyzed 56 sets of common bile duct gallstones collected over a 10-yr period using infrared and atomic absorption spectroscopy and chemical methods. Twenty-four sets (43%) of stones were cholesterol stones containing 85.3% cholesterol, 3.2% pigment, 0.6% phosphate, and 1.3% total calcium. Ten sets (18%) were black pigment stones containing 36.5% pigment, 11.4% cholesterol, 7.6% carbonate, 3.0% phosphate, and 6.2% total calcium. Twenty-two sets (39%) were brown pigment stones containing 52.7% pigment, 16.5% calcium palmitate, 10.1% cholesterol, 0.4% phosphate, and 3.4% total calcium. Most of the 26 stones found at the same time as or within several months after cholecystectomy were either cholesterol (69%) or black pigment (19%). In contrast, the majority (59%) of the 22 common duct stones that were diagnosed greater than or equal to 21 mo after cholecystectomy were brown pigment stones. In conclusion, brown pigment stones are a distinct type of pigment stone characterized by their content of substantial amounts of calcium palmitate. They comprise a significant proportion of common duct stones in this series of United States patients, particularly of those found greater than or equal to 21 mo after cholecystectomy.
Calcium Carbonate↗