Barely 130 years after its first description, cholecystectomies are among the most commonly performed surgeries in the USA. The success of this operation with subsequent technical improvements, such as laparoscopic approaches, caused a paradigm shift in the management of gallstone disease. However, symptoms persist in 10-40 % of successfully operated patients. Reviewing monographs, textbooks, and articles published during the last 300 years, several important factors emerge as likely contributors to limited or poor treatment responses. Early on, clinicians recognized that cholelithiasis is quite common and thus often an incidental finding, especially if patients present with vague or atypical symptoms. Consistent with these observations, patients with such atypical symptoms are less likely to benefit from cholecystectomy. Similarly, lasting improvements are more reliably seen in patients with symptoms of presumed biliary origin and documented gallstones compared to individuals without stones, an important point in view of increasing rates of surgery for biliary dyskinesia. While cholelithiasis can cause serious complications, the overall incidence of clinically relevant problems is so low that prophylactic cholecystectomy cannot be justified. This conclusion corresponds to epidemiologic data showing that the rise in elective cholecystectomies decreased hospitalizations due to gallstone disease, but was associated with a higher volume of postoperative complications, ultimately resulting in stable combined mortality due to gallstone disease and its treatment. These trends highlight the tremendous gains in managing gallstone disease, while at the same time reminding us that the tightening rather than expanding indications for cholecystectomy may improve outcomes.

Cholesterol gallstone disease is a common clinical condition influenced by genetic factors, increasing age, female gender, and metabolic factors. Although laparoscopic cholecystectomy is currently considered the gold standard in treating patients with symptomatic gallstones, new perspectives regarding medical therapy of cholelithiasis are currently under discussion, also taking into account the pathogenesis of gallstones, the natural history of the disease and the analysis of the overall costs of therapy. A careful selection of patients may lead to successful non-surgical therapy in symptomatic subjects with a functioning gallbladder harboring small radiolucent stones. The classical oral litholysis by ursodeoxycholic acid has been recently paralleled by new experimental observations, suggesting that cholesterol-lowering agents which inhibit cholesterol synthesis (statins) or intestinal cholesterol absorption (ezetimibe), or drugs acting on specific nuclear receptors involved in cholesterol and bile acid homeostasis, might be proposed as additional approaches for treating cholesterol gallstones. In this review we discuss old, recent and future perspectives on medical treatment of cholesterol cholelithiasis.

Cholesterol gallstone formation is a complex process mediated by genetic and environmental factors. Until recently, the role of the immune system in the pathogenesis of cholesterol gallstones was not considered a valid topic of research interest. This review collates and interprets an extensive body of basic literature, some of which is not customarily considered to be related to cholelithogenesis, describing the multiple facets of the immune system that appear to be involved in cholesterol cholelithogenesis. A thorough understanding of the immune interactions with biliary lipids and cholecystocytes should modify current views of the pathogenesis of cholesterol gallstones, promote further research on the pathways involved, and lead to novel diagnostic tools, treatments, and preventive measures.

This paper reviews the published information assessing the kinetics and potential for adverse health effects related to exposure to the fuel oxygenate, methyl tert-butyl ether (MTBE). Data were obtained from previously published reports, using human data where possible. If human data were not available, animal studies were cited. The kinetic profile of MTBE in humans is similar for ingestion and inhalation. The concentrations of MTBE to which the general public is expected to be exposed are orders of magnitude below concentrations that have caused adverse health effects in animals. Controlled human studies have not replicated early epidemiology studies that suggested, but did not confirm, a possible association between MTBE exposure and nonspecific health complaints.

Cholecystectomy is currently advised only for patients with symptomatic gallstones. However, about 4% of patients with asymptomatic gallstones develop symptoms including cholecystitis, obstructive jaundice, pancreatitis, and gallbladder cancer.

To assess the benefits and harms of surgical removal of the gallbladder for patients with asymptomatic gallstones.

We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until 2006 for identifying the randomised trials using The Cochrane Hepato-Biliary Group search strategy.

Only randomised clinical trials (irrespective of language, blinding, or publication status) comparing cholecystectomy and no cholecystectomy were considered for the review.

We were unable to identify any randomised clinical trials comparing cholecystectomy versus no cholecystectomy.

We were unable to identify any randomised clinical trial comparing cholecystectomy versus no cholecystectomy.

There are no randomised trials comparing cholecystectomy versus no cholecystectomy in patients with silent gallstones. Further evaluation of observational studies, which measure outcomes such as obstructive jaundice, gallstone-associated pancreatitis, and/or gall-bladder cancer for sufficient duration of follow-up is necessary before randomised trials are designed in order to evaluate whether cholecystectomy or no cholecystectomy is better for asymptomatic gallstones.

Medical treatments that dissolve or remove gallbladder stones but leave the gallbladder in situ have the disadvantage of gallstone recurrence. Little is known about the composition of recurrent stones or whether they recur true to type. In 21 patients with recurrent stones detected 5-74 months (mean +/- SEM, 26 +/- 4 months) after being rendered stone-free with dissolution therapy (N = 15) or percutaneous cholecystolithotomy (N = 6), we compared pretreatment and postrecurrence gallstone number, maximum gallstone attenuation scores measured by computed tomography (CT) and, in 13, the dissolvability of the recurrent stones with oral bile acids +/- extracorporeal shock-wave lithotripsy. Before treatment, five patients had solitary and 16 had multiple stones but on recurrence, the gallstones differed in number from the primary stones in 10 of the 21 patients. As a result of patient selection, before dissolution, the primary stones were all radiolucent with maximum CT scores of < 100 Hounsfield units (HU) (mean 45, range 10-84 HU). On recurrence, the stones were again CT-lucent in 13 of the 15 patients but were CT-dense in the remaining two (118 and 176 HU). Initially, all six patients treated by percutaneous cholecystolithotomy had radio-opaque stones, with a mean CT score of 459 (range 100-969) HU. However, on recurrence, only one had calcified stones (HU 140); the remaining five had CT-lucent stones (16-98 HU, P < 0.05). Of the 13 patients whose recurrent, plain x-ray-lucent and CT-lucent stones were treated with oral bile acids +/- lithotripsy, 12 (92%) showed evidence of gallstone dissolution. We conclude that gallbladder stones do not recur true to type in up to two thirds of patients. However, irrespective of original gallstone composition, recurrent stones are usually radio- and CT-lucent, presumed cholesterol-rich, and therefore potentially dissolvable with oral bile acids.