PubMed Health⌕ Search

PubMed · 2247812

Gallstone dissolution.

Abstract

Many methods are available for gallstone dissolution, including oral bile salts; cholesterol solvents such as mono-octanoin or methyl tert-butyl either; and calcium or pigment solvents such as EDTA and polysorbate. Which of these approaches will be appropriate for an individual patient depends on the type of stones; whether they are in the gallbladder or the bile ducts; whether access to the biliary tree is available; the patient's age and general medical condition; and the availability of necessary expertise. In the US, both chenodeoxycholate and ursodeoxycholate are now available. Ursodeoxycholate is more expensive but appears to produce fewer side effects and may be more efficacious. These agents are most effective in thin women with small floating, radiolucent cholesterol stones in a functioning gallbladder. Only about half of the small subset of patients will experience partial or complete dissolution of stones within a year. Stone recurrence and the potential toxicity of long-term therapy are problems with this approach. Therefore, for most patients, cholecystectomy, either in the traditional fashion or using a laparoscopic approach (see article later in this issue by Gadacz et al), is the most cost-effective and perhaps the safest option. Intragallbladder instillation of methyl tert-butyl ether probably will be applicable only to a small subset of patients, and treatment is likely to be followed by a high recurrence rate. In patients with retained common duct cholesterol stones and access to the biliary tree, mono-octanoin therapy is advantageous in that it can be initiated as soon as cholangiography demonstrates no extravasation. In properly selected patients, a 90% success rate with this technique can be expected within 7 days.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

M A Talamini, T R Gadacz. 1990. Gallstone dissolution.. https://doi.org/10.1016/s0039-6109(16)45280-1

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Clostridium scindens: history and current outlook for a keystone species in the mammalian gut involved in bile acid and steroid metabolism.

Clostridium scindens is a keystone bacterial species in the mammalian gut that, while low in abundance, has a significant impact on bile acid and steroid metabolism. Numerous studies indicate that the two most studied strains of C. scindens (i.e. ATCC 35704 and VPI 12708) are important for a myriad of physiological processes in the host. We focus on both historical and current microbiological and molecular biology work on the Hylemon-Björkhem pathway and the steroid-17,20-desmolase pathway that were first discovered in C. scindens. Our most recent analysis now calls into question whether strains currently defined as C. scindens represent two separate taxonomic groups. Future directions include developing genetic tools to further explore the physiological role of bile acid and steroid metabolism by strains of C. scindens and the causal role of these pathways in host physiology and disease.

Bile Acids and Salts↗

Bile acid-mediated thrombospondin-1 induction in hepatocytes leads to transforming growth factor-beta-dependent hepatic stellate cell activation.

In cholestasis, bile acids induce hepatocyte apoptosis, while activation of hepatic stellate cells (HSCs) results in fibrosis. Since transforming growth factor-beta (TGF-beta) is a critical mediator in this process, we hypothesized that bile acids may participate in TGF-beta-mediated HSC activation in cholestasis. Bile acid treatment increased TGF-beta transcription in hepatocytes, while the total TGF-beta concentration in culture media rapidly decreased following bile acid treatment. Bile acid treatment promptly induced thrombospondin-1 expression in hepatocytes, which is a potent activator of latent TGF-beta, whereas this induction was not observed in bile acid-treated HSCs. HSCs co-cultured with hepatocytes showed a significantly higher level of Smad2 phosphorylation and collagen alpha1 synthesis following bile acid treatment than cells cultured without hepatocytes. Moreover, this enhanced collagen synthesis was significantly inhibited in the presence of TGF-beta receptor inhibitor. These observations imply that bile acids induce thrombospondin-1 expression in hepatocytes, which activates latent TGF-beta leading to HSC activation.

Bile Acids and Salts↗

Matrix metalloproteinase-7-catalyzed release of HB-EGF mediates deoxycholyltaurine-induced proliferation of a human colon cancer cell line.

Prior evidence indicates that bile acids stimulate colon cancer cell proliferation by muscarinic receptor-induced transactivation of epidermal growth factor receptors (EGFR). To explore further the mechanism underlying this action, we tested the hypothesis that bile acids activate a matrix metalloproteinase (MMP) that catalyzes release of an EGFR ligand. Initial studies showed that non-selective MMP inhibitors blocked the actions of deoxycholyltaurine (DCT), thereby indicating a role for MMP-catalyzed release of an EGFR ligand. DCT-induced cell proliferation was reduced by increasing concentrations of EGFR kinase inhibitors, by antibodies to the ligand binding domain of EGFR, by neutralizing antibodies to heparin binding-EGF-like growth factor (HB-EGF) and by CRM197, an inhibitor of HB-EGF release. These findings and our observations with more selective MMP inhibitors suggested that MMP-7, an enzyme known to release HB-EGF, plays a key role in mediating bile acid-induced H508 colon cancer cell proliferation. We observed that recombinant HB-EGF and MMP-7 mimicked both the signaling and proliferative actions of bile acids. Strikingly, reducing MMP-7 expression with either neutralizing antibody or small interfering RNA attenuated the actions of DCT. MMP-7 expression in H508 cells was confirmed using quantitative reverse transcription PCR. DCT stimulated a greater than 10-fold increase in MMP-7 gene transcription. Co-localization of pro-MMP-7 and pro-HB-EGF at the cell surface (immunofluorescence microscopy) was demonstrated, indicating proximity of the enzyme to its substrate. These findings provide strong evidence that in H508 human colon cancer cells, DCT-induced transactivation of EGFR is mediated by MMP-7-catalyzed release of the EGFR ligand HB-EGF.

Bile Acids and Salts↗