monooctanoin and Cholelithiasis

Gallstones represent a major health problem in western society. For symptomatic gallstones, cholecystectomy is the gold standard. A considerable number of patients, however, cannot tolerate or are unwilling to undergo surgery and anaesthesia. For these patients, dissolution therapy, administered either systemically ('oral dissolution') or directly into the gallbladder ('contact dissolution'), might be preferable. In this review, the possibilities and limitations of dissolution therapy are discussed. It is concluded that dissolution is a good alternative in selected symptomatic patients and that it is useful as adjuvant therapy after lithotripsy (ESWL) of gall-bladder stones.

Topics: Caprylates; Chenodeoxycholic Acid; Cholelithiasis; Cyclohexenes; Edetic Acid; Ethers; Glycerides; Humans; Limonene; Methyl Ethers; Solvents; Terpenes; Ursodeoxycholic Acid

Endoscopic sphincterotomy and percutaneous approaches to the biliary tract have revolutionized the treatment of bile duct stones. Both the endoscopic and transhepatic approaches are less invasive than open surgery. This is an advantage for the mostly elderly and frail patients with common bile duct stones. Other patients with intrahepatic stones, e.g. young patients with oriental lithiasis, may also profit from the non-surgical approach. In this latter group it is often difficult for the surgeon to obtain access to the stone-bearing bile ducts. Due to the anatomical situation, size or impaction of stones the non-surgical approach, including mechanical disintegration, may primarily fail. Several techniques such as intracorporeal lithotripsy using electrohydraulic probes or laser light, extracorporeal shockwave lithotripsy or direct contact dissolution are now available and often allow complete clearance of the bile ducts. If a kidney lithotripter with radiographic devices is available, it should be used after an attempt at mechanical lithotripsy has failed (Figure 1). According to the literature, experience with this method is greater than with any other 'third-step approach'. The procedure is simple, relatively safe and successful in approximately 80% of patients. However, in at least one third of patients, several sessions have to be performed and further endoscopy is frequently required for extraction of fragments. Intracorporeal techniques may become the procedure of choice in the future, at least in patients with common bile duct stones. At the moment, however, the different devices are still not fully developed and too susceptible to damage. A further major drawback, especially with high-energy electrohydraulic intracorporeal lithotripsy, is the danger of bile duct injury or even perforation, so that most procedures must be performed under optical control. The use of contact dissolution cannot generally be recommended. Treatment with mono-octanoin or modified mono-octanoin solvents takes too long, is often not successful and has a high rate of side-effects. MTBE may shorten the procedure considerably, but is suitable only for cholesterol stones, and the danger of spill-over into the intestine with absorption and systemic side-effects has to be weighed against the probability of success.

Topics: Bile Acids and Salts; Bile Duct Diseases; Caprylates; Cholelithiasis; Cyclohexenes; Ethers; Glycerides; Humans; Laser Therapy; Limonene; Lithotripsy; Lithotripsy, Laser; Methyl Ethers; Solvents; Stents; Terpenes

It can be anticipated that most new therapies will generate considerable excitement and optimism when introduced. This is usually tempered with time as additional clinical experience is gained and therapeutic limitations and adverse effects are realized. All areas in the nonsurgical management of gallstones have experienced this course--some, such as ESWL, rather meteorically. Perspective, however, is important and may allow the appropriate use of each of these modalities in the correct clinical setting. For example, ursodiol when given in sufficient dose to nonobese patients with small radiolucent stones, could be expected to effect partial or complete dissolution in as many as 75% of patients, with minimal or no adverse effects and in a cost-effective manner. Contact dissolution using MTBE has been shown to be safe and generally effective but requires diligent characterization of stones to avoid those that are pigmented or heavily calcified. Similarly, ESWL combined with oral bile acids may be consistently effective if treatment is restricted to patients with acceptable cholesterol stone burdens and if treatment can be safely continued until fragments are substantially reduced. Continued experience with each of these treatment options, along with advances in research providing new solvents and technologies or in preventing recurrence, is likely to establish this field in an appropriately optimistic light.

Topics: Bile Acids and Salts; Caprylates; Cholelithiasis; Ethers; Glycerides; Humans; Methyl Ethers; Recurrence; Solvents

Contact dissolution of cholesterol gallstones with organic solvents is emerging as a rapid, safe, alternative treatment for symptomatic cholesterol gallbladder stones. Placement of a percutaneous transhepatic catheter into the gallbladder is a rapid and safe technique. The availability of safe, effective cholesterol solvents and solvent transfer devices means that cholesterol gallbladder stones can be eliminated rapidly and safely by CDOS, without the risk of general anesthesia or surgical dissection of the gallbladder bed. Patients with single gallstones are better candidates for CDOS than are patients with multiple gallstones because recurrence after dissolution is less common. Contact dissolution may well be judged the treatment of choice by the medical-surgical gallstone management team in some patients.

Topics: Caprylates; Cholelithiasis; Cholesterol; Ethers; Glycerides; Humans; Methyl Ethers; Solvents; Viscosity

Topics: Bile Acids and Salts; Caprylates; Cholelithiasis; Cholesterol; Ethers; Glycerides; Humans; Lithotripsy; Methyl Ethers; Ultrasonic Therapy

Mono-octanoin can be used either alone or as an adjunct to other techniques to dissolve cholesterol bile duct stones. This solvent can be administered through an existing T tube, through the nasobiliary route, or percutaneously through the liver. Unlike basket extraction, which requires a mature T-tube sinus tract, mono-octanoin can be used immediately postoperatively or for home dissolution therapy. The endoscopic extraction of bile duct stones has a 1 percent mortality rate and a 5 to 7 percent complication rate. Special mixtures of mono-octanoin, bile acids, and ethylene diaminetetraacetic acid (EDTA) are being evaluated to dissolve pigment stones. The use of methyl tert-butyl ether is still experimental but very effective. To be most successful, mono-octanoin treatment must be used in properly selected patients.

Topics: Bile Acids and Salts; Bile Duct Diseases; Caprylates; Catheters, Indwelling; Cholelithiasis; Ethers; Glycerides; Humans; Solvents

Monooctanoin is a cholesterol solvent indicated for dissolution of retained biliary stones. We summarize four reports--one from the U.S. Food and Drug Administration's Spontaneous Reporting System for Adverse Drug Reactions and three from published medical literature--of noncardiogenic pulmonary edema during intrabiliary monooctanoin in the United States. Based on these data, we show that pulmonary edema during intrabiliary monooctanoin infusion may occur in approximately one per 1000 patients treated.

Topics: Adult; Caprylates; Cholelithiasis; Glycerides; Humans; Pulmonary Edema; Solvents

Topics: Bile Duct Diseases; Caprylates; Chenodeoxycholic Acid; Cholelithiasis; Deoxycholic Acid; Ethers; Glycerides; Humans; Lithotripsy; Methyl Ethers; Solvents; Ursodeoxycholic Acid

Topics: Animals; Caprylates; Chenodeoxycholic Acid; Cholecystectomy; Cholelithiasis; Cystic Duct; Electrocoagulation; Ethers; Glycerides; Humans; Lithotripsy; Methyl Ethers; Radio Waves; Solvents; Ultrasonic Therapy

Topics: Caprylates; Cholelithiasis; Glycerides; Humans

Topics: Bile Acids and Salts; Bile Duct Diseases; Caprylates; Cholelithiasis; Cholesterol; Cyclohexenes; Edetic Acid; Ethers; Glycerides; Humans; Limonene; Methyl Ethers; Pigments, Biological; Recurrence; Solubility; Terpenes

Findings by several groups of investigators have provided a reliable data base that supports a nonoperative approach toward the management of so-called silent gallstones. Considerable progress has been made in the medical dissolution treatment of selected patients with cholesterol gallstones. Ursodeoxycholic acid, and, more recently, a combination of ursodeoxycholic and chenodeoxycholic acids have been shown to be both effective and safe in dissolving gallstones that are predominantly composed of cholesterol. A drawback of the bile acid dissolution therapy lies in a significant recurrence rate after treatment is discontinued. Currently, several new methods of gallstone treatment are under study, which involve either the injection of a cholelitholytic solution, such as methyl tert-butyl ether, into the gallbladder or the use of mechanical means, such as excorporeally induced shock waves, to disintegrate gallstones. These treatments, however, are effective only if the stones are composed mainly of cholesterol without significant admixtures of calcium salts, pigment, or mucus. Most of the treatment failures are probably related to the presence of calcifications that are not visible on conventional radiographs. Future improvements of gallstone dissolution therapy can be expected from the following possible developments: improvement in ability to predict gallstone composition; dissolution of calcium salt-, pigment-, and mucus-containing stones; early treatment, before calcifications occur; combination of chemical and mechanical methods of treatment; stimulation of gallbladder contraction; prevention of stone recurrence after dissolution; and synthesis of new cholelitholytic agents.

Topics: Bile Acids and Salts; Caprylates; Cholelithiasis; Ethers; Glycerides; Humans; Lithotripsy; Methyl Ethers

Monooctanoin (Capmul 8210), a digestion product of medium chain triglycerides, is a cholesterol solvent that has been used for the dissolution of retained cholesterol gallstones following cholecystectomy. Bile duct infusion of monooctanoin is associated with little toxicity, although potentially serious problems can result from absorption of the drug or tissue infiltration. Gastrointestinal side effects such as anorexia, nausea, vomiting, diarrhea, and abdominal pain have been reported most commonly. Complete gallstone dissolution has occurred in approximately 50-75 percent of patients receiving monooctanoin. Although mechanical stone removal is still considered to be the treatment of choice for retained gallstones, monooctanoin use appears promising for stone dissolution in patients in whom mechanical removal has been unsuccessful or is impossible.

Topics: Biological Availability; Biopharmaceutics; Caprylates; Cholelithiasis; Glycerides; Humans; Injections; Kinetics; Solvents

Topics: Adult; Aged; Animals; Calcium; Caprylates; Cattle; Chenodeoxycholic Acid; Cholelithiasis; Cholesterol; Clinical Trials as Topic; Common Bile Duct; Drug Evaluation, Preclinical; Female; Gallstones; Glycerides; Humans; In Vitro Techniques; Infusions, Parenteral; Male; Middle Aged; Particle Size; Solubility; Ursodeoxycholic Acid

Management of choledocholithiasis requires several strategies to solve the various clinical problems encountered. A maximal effort during cholecystectomy at discovery of the duct stones in almost one of every six patients should, of course, be continued. Cystic duct cholangiography should routinely be used in deciding whether to explore the common duct. Postexploratory choledochoscopy has demonstrated discovery value and will hopefully be increasingly used. More training and sharing of technical details is indicated. When a retained stone is discovered on T tube cholangiogram, several options are available with no one clearly superior. Waiting for the T tube tract to mature and attempting extraction via flexible endoscopes or Burhenne technique is probably most cost effective if appropriate skills are available, especially for small calculi. Calculi greater than 8 mm in diameter with some probability of having high cholesterol content may be best managed with monooctanoin infusion. Parenthetically, monooctanoin dissolution may reduce morbidity of ERS, since large stones that would require large, more risky sphincterotomies can in some instances be reduced to passable size by monooctanoin infusion via an endoscopically placed nasobiliary tube. Endoscopic sphincterotomy for retained stones is ordinarily reserved for patients in whom nonoperative retrieval has failed or the T tube has fallen out. When common duct obstruction due to stones occurs prior to or remote from cholecystectomy, ERS is the preferred method of management when available, under conditions previously noted. With improved discovery methods and less morbid therapeutic options, consequences of choledocholithiasis will be less formidable.

Topics: Age Factors; Aged; Caprylates; Cholangiography; Cholangiopancreatography, Endoscopic Retrograde; Cholangitis; Cholecystectomy; Cholelithiasis; Cholestasis, Extrahepatic; Endoscopy; Excipients; Gallstones; Glycerides; Humans; Middle Aged; Pancreatitis; Recurrence; Tomography, X-Ray Computed; Ultrasonography

Topics: Animals; Bile; Bile Acids and Salts; Caprylates; Chenodeoxycholic Acid; Cholelithiasis; Cholic Acid; Cholic Acids; Common Bile Duct; Cyclohexenes; Drug Therapy, Combination; Edetic Acid; Gallstones; Glycerides; Heparin; Humans; Intubation; Limonene; Lipid Metabolism; Recurrence; Solvents; Terpenes; Ursodeoxycholic Acid

Topics: Animals; Caprylates; Chenodeoxycholic Acid; Cholelithiasis; Cholesterol; Deoxycholic Acid; Glycerides; Humans; Ursodeoxycholic Acid

A method of individual selection of cholelitholytic agents was developed and tested in the clinic on the grounds of the findings of polarizing microscopy of bile and the results of study of gallstones by scanning electron microscopy. Its essence consists in visual appraisal of the effect of various solvents, used in the clinic, on the crystal structures of the patient's bile. The use of the developed method makes it possible to raise significantly the efficacy of contact solution of gallstones in combined treatment of cholelithiasis.

Topics: Aged; Caprylates; Cholelithiasis; Drug Therapy, Combination; Edetic Acid; Female; Glycerides; Humans; Microscopy, Electron, Scanning; Nitrates; Solvents

Topics: Caprylates; Cholecystectomy; Cholelithiasis; Clinical Trials as Topic; Glycerides; Humans

Topics: Adult; Aged; Animals; Calcium; Caprylates; Cattle; Chenodeoxycholic Acid; Cholelithiasis; Cholesterol; Clinical Trials as Topic; Common Bile Duct; Drug Evaluation, Preclinical; Female; Gallstones; Glycerides; Humans; In Vitro Techniques; Infusions, Parenteral; Male; Middle Aged; Particle Size; Solubility; Ursodeoxycholic Acid

This in vitro study compared the gallstone dissolution rates of mono-octanoin, mono-octanoin plus 10% distilled water, and mono-octanoin plus methyl tert-butyl ether 2:1. Sixteen stones were treated with each solvent at a slow perfusion rate of 3-4 ml/h and a rapid perfusion rate of 2.5 ml/30 min with 20-sec instillation/aspiration cycles, both with and without bile. The stones were weighed before, and 3, 6, 12 and 24 hrs after the start of treatment: the solvent was changed every 30 min. After 24 hrs of instillation/aspiration without bile, the mono-octanoin/methyl tert-butyl ether mixture reduced the weight of the stones by 93%, mono-octanoin plus water by 63%, and mono-octanoin alone by 52%; with bile, the figures were, respectively, 86%, 42% and 40%. The mono-octanoin/methyl tert-butyl ether mixture thus took approximately half the time needed by the other two preparations to dissolve the stones to the same extent, a finding which may be relevant for the clinical dissolution of bile duct stones.

Topics: Caprylates; Cholelithiasis; Drug Combinations; Glycerides; Humans; In Vitro Techniques; Methyl Ethers; Solvents; Time Factors

The dissolution rates and solubilities of cholesterol monohydrate, palmitic acid, and their mixtures in the cholelitholytic solvents monooctanoin (MO) and methyl tert-butyl ether (MTBE) and mixtures of these two solvents were determined. The dissolution rates obtained were consistent with the diffusion-controlled two-component noninteracting model. The addition of MTBE as cosolvent to MO resulted in an increase in the solubility of both cholesterol monohydrate and palmitic acid; in the case of the former, the solubility peaked at 80% MTBE. Neither solute exhibited a log-linear solubility relationship on addition of MTBE as cosolvent. Furthermore the increases in the dissolution rates of both components were much larger than could be explained by the solubility increases alone. Mass transfer coefficients increased dramatically with increasing MTBE content of the solvent, were consistently higher for palmitic acid, and reflected the decline in solvent viscosity. Incorporation of relationships among solubility, viscosity, and cosolvent composition into the two-component noninteracting model gave good correlation between predicted and observed rates over nearly 3 orders of magnitude.

Topics: Caprylates; Cholelithiasis; Cholesterol; Chromatography, Gas; Diffusion; Ethers; Glycerides; Kinetics; Methyl Ethers; Models, Biological; Palmitic Acids; Solubility; Solvents; Viscosity

During contact dissolution of gallstones, solvents may escape from the gallbladder and damage the intestinal mucosa. In order to compare the extent of this potential injury, we developed a method to objectively quantify the effects of two commonly used cholesterol solvents, methyl tert-butyl ether and mono-octanoin, on mucosal transport function in the rat intestine. Two intestinal segments in each of 184 anesthetized rats were cannulated. Three milliliters of either solvent were instilled in one segment and left for varying periods of time, while saline was instilled in the other as control. The segments were then washed and perfused for 45 min with an isotonic solution containing [3H]polyethylene glycol 4000 (a nonabsorbable reference marker) and either [14C]alpha-aminoisobutyric acid (a marker for active absorption) or [14C]mannitol (a marker for passive permeability). Methyl tert-butyl ether caused more inhibition of alpha-aminoisobutyric acid absorption (64%) than mono-octanoin (48%) and a greater reduction of dry weight per centimeter of the perfused segment (22%) compared with mono-octanoin (10%). Such effects appeared after only 1 min of solvent exposure and did not appreciably increase with longer exposures. Permeation of mannitol increased by 26% after 1 min of exposure to mono-octanoin and by 54% after a similar period of exposure to methyl tert-butyl ether. Longer exposures to both solvents did not seem to cause progressive increases in mannitol permeation. The results indicate that brief exposure of the rat jejunum to either of the two solvents causes a reduction in active transport ([14C]alpha-aminoisobutyric acid absorption), an increase in passive permeability (mannitol permeation), and a loss of mucosal constituents. We conclude that the intestinal mucosa is susceptible to solvent damage and may be used as a selectively sensitive model that can characterize the biological injury of gallstone solvents. The study also suggests that escape of the currently available solvents into the small intestine in patients undergoing contact dissolution of gallbladder stones may cause injury to the small intestine.

Topics: Animals; Biological Transport; Caprylates; Cholelithiasis; Ethers; Glycerides; Intestinal Absorption; Intestinal Mucosa; Male; Methyl Ethers; Rats; Rats, Sprague-Dawley; Solvents

A new litholytic mixture of mono-octanoin (MO) and methyl tert-butyl ether (MTBE) in a ratio of 2:1 (v/v) was employed in 42 patients with bile duct stones, 29 of them failures after papillotomy. Twenty-two of these patients had complicated stones. The new solvent mixture was given for 4-6 h/day and 2-3 ml were instilled every 30 min. Gentle aspiration and instillation were alternated so as to "stir" the preparation around the stones. Perfusion was given for up to six days. The mixture contributed to success in 37 cases (88%), 19 of them with complicated stones. Total dissolution was attained in 18 cases, and in the other 19 cases clearance was achieved after partial lysis followed by easy crushing with a basket. The mean volume of solvent perfused (+/- SD) was 84.9 +/- 39 ml (range 25-150), the mean duration of treatment was 16.5 +/- 7.4 h (range 5-30). Hospital stay averaged 4.6 +/- 1.6 days (range 2-7). There were five failures: in one patient eight large concretions were eliminated only after extracorporeal shock wave lithotripsy (ESWL). Two were re-operated and pigment stones were found. The last two refused alternative treatments. Side effects were minimal and easily managed by withdrawal of a few ml of bile. Treatment with the new solvent may be indicated as first-instance therapy in place of ESWL, laser endoscopy, electrohydraulic or mechanical lithotripsy for patients with complicated biliary stones, or in cases in which endoscopic papillotomy has failed.

Topics: Adult; Aged; Aged, 80 and over; Bile Duct Diseases; Caprylates; Cholelithiasis; Drug Combinations; Ethers; Female; Follow-Up Studies; Glycerides; Humans; Male; Methyl Ethers; Middle Aged; Solvents

Topics: Adult; Aged; Caprylates; Cholelithiasis; Combined Modality Therapy; Drug Combinations; Drug Evaluation; Female; Glycerides; Humans; Lithotripsy; Male; Middle Aged; Remission Induction; Solvents

The authors present a case report of a cholecystostomized high surgical-risk patient with gallstones in gallbladder and biliary duct treated with continuous monoctanoin infusion through a Pezzer's tube. They analyze the biological characters of such substance as solvent agent, its management and the results of treatment.

Topics: Aged; Caprylates; Catheterization; Cholelithiasis; Glycerides; Humans; Male

The techniques and results of contact dissolution of stones in the gallbladder of 27 patients subjected to laparoscopic cholecystostomy for acute cholecystitis were analysed. It was found that the main factors impeding effective dissolution were: the size of the stones over 1.5 cm and admixture of pigment in the concrements. The first Soviet produced litholytic preparation Oktalgin, synthesized by the authors jointly with the Zelinsky IOCh, AMS USSR, was used as the main solvent. The principal possibility of dissolving multiple stones of the gallbladder through laparoscopic cholecystostomy is proved.

Topics: Acute Disease; Caprylates; Cholecystitis; Cholelithiasis; Edetic Acid; Gallbladder; Glycerides; Humans; Laparoscopy; Nitrates; Solvents

Extracorporeal shockwave lithotripsy (ESWL) of gall bladder stones leaves residual fragments that need to be dissolved by chemical solvents. In this study we compared the in vitro dissolving capacity of methyl tert-butyl ether (MTBE), mono-octanoin, limonene, and limonene/mono-octanoin (70%/30%). From nine sets of five human gall stones obtained at cholecystectomy, four stones were used for dissolution and the fifth was used for chemical analysis of cholesterol, calcium, and bilirubin contents. Eight sets were cholesterol stones with a mean (SD) cholesterol content of 89.9 (5.6)%. These stones dissolved completely in either solvent, often leaving sand-like debris, with the exception of one stone. MTBE dissolved cholesterol gall stones 100 times faster than mono-octanoin and 10 times faster than limonene or the limonene/mono-octanoin mixture (p less than 0.001). The combination of limonene and mono-octanoin was as effective as limonene alone. Of the four solvents, MTBE is the best one to evaluate for dissolution of residual fragments after ESWL treatment of gall bladder stones.

Topics: Bilirubin; Calcium; Caprylates; Cholelithiasis; Cholesterol; Cyclohexenes; Ethers; Glycerides; Humans; Limonene; Methyl Ethers; Solvents; Terpenes

Topics: Bile Acids and Salts; Caprylates; Cholelithiasis; Education, Nursing, Continuing; Endoscopy; Ethers; Glycerides; Humans; Lithotripsy; Methyl Ethers; Sphincterotomy, Transduodenal

Despite advances in intraoperative choledochoscopy and cholangiography, it is still common for bile duct stones to remain after common bile duct (CBD) exploration. The incidence of bile duct calculi in those undergoing cholecystectomy ranges from 7-15%, and that of retained stones immediately after CBD exploration, from 10-13%. Re-exploration carries a postoperative mortality varying from 3-28%. Treatment by T-tube flushing with heparinized saline, cholate or mono-octanoin is of limited value. Flushing with methyltertiarybutyl ether via a nasobiliary drain was recently reported to be successful in 80%, but confirmation of its efficacy and lack of toxicity is still pending. Continuous infusion via a nasobiliary tube of modified mono-octanoin alternating with EDTA solution may dissolve calcium bilirubin stones. Endoscopic sphincterotomy is successful in 95%. Extraction of CBD stones by either basket or balloon catheter is possible in 85-90% of cases at the time of endoscopic sphincterotomy. Large stones remaining are treated by mechanical lithotripsy with a success rate of 82%, which raises the overall success rate of endoscopic CBD stone extraction after endoscopic sphincterotomy to 97%. However, when stones exceed 25 mm in diameter, the success rate is lower. Electrohydraulic lithotripsy (EHL) may damage the CBD wall because the exact site of spark discharge is under fluoroscopic, not direct endoscopic control. In the near future, applying EHL under direct vision via peroral cholangioscopy should decrease the hazards of this method.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Bile Duct Diseases; Caprylates; Cholecystectomy; Cholelithiasis; Endoscopy; Glycerides; Humans; Lithotripsy; Postoperative Complications; Solvents; Sphincterotomy, Transduodenal; Therapeutic Irrigation

The agent Octaglin was used for dissolving residual stones found in 5 patients in the early periods after operations on the biliary tract. It was administered through a drain left in the choledochus or cystic duct during the surgical intervention. The composition of the concrements was determined from examination of the biliary crystal structures by the method of polarizing light microscopy. The stones were dissolved completely in all cases so that 4 of the 5 patients did not need to be operated on for a second time.

Topics: Adult; Aged; Caprylates; Cholecystectomy; Cholelithiasis; Drainage; Female; Gallstones; Glycerides; Humans; Middle Aged; Solvents

A new three-phase therapeutical approach to retained biliary stones (RBS) is designed to shorten the long treatment times with Monooctanoin (Mo). In the first phase, the litholytic agent is infused to soften the stones. In the second one the calculi are crushed, and in the last complete elimination of the fragmentary stones into the duodenum is obtained after 1-2 flushings with ceruletide. In 6 patients a complete clearance of the stones was obtained (success 100%) together with a reduction in the litholytic agent dose (52%) and the infusion time (62%), in comparison with the results of using Mo. alone.

Topics: Adult; Aged; Caprylates; Ceruletide; Cholangiography; Cholelithiasis; Drug Evaluation; Female; Glycerides; Humans; Male; Middle Aged; Solvents

Groups of human cholesterol gallstones were subjected to monooctanoin with and without agitation, methyl-tert-butyl ether (MTBE) with and without agitation, and monooctanoin and MTBE used in succession with agitation. In this in vitro study, agitation greatly expedited the rate of dissolution with MTBE, by far the more potent of the two solvents. An additive effect was suggested when the solvents were used sequentially, monooctanoin followed by MTBE. Cholesterol-calcium stones were also dissolved by MTBE but at a slower rate, depending on the amount and distribution of calcium. Computed tomographic (CT) scans and mammographic images clearly delineated the amount and distribution of calcification, but plain radiographs did not. On the basis of these findings, the authors instituted two changes in their clinical protocol: All patients with gallstones are now examined by means of CT before chemical dissolution begins, and monooctanoin is instilled overnight before the MTBE procedure.

Topics: Caprylates; Cholelithiasis; Cholesterol; Ethers; Glycerides; Humans; In Vitro Techniques; Methyl Ethers; Tomography, X-Ray Computed

The influence of different solvents on cholesterol and pigment stones was investigated in vitro. Stone analysis was performed chemically, with infrared spectroscopy (IRS), scanning electron microscopy, energy-dispersive X-microanalysis (EDXA) and wave-length-dispersive X-microanalysis (WDXA). Each set of stones came from one source: eight human calcified cholesterol stones (CHS), eight fragments of bovine radiopaque Ca-bilirubinate stones (BBIL), and two complete BBIL. CHS and BBIL fragments were treated with (1) a buffered, alkaline 1% ethylenediamine tetraacetate solution (BA-EDTA; pH 9.5); (2) with BA-EDTA and monooctanoin preparation (GMOC) alternately; (3) with GMOC alone, and (4) with methyl-tert-butyl ether (MTBE). The complete BBIL were treated with BA-EDTA and MTBE. Furthermore, two human black pigment stones (BPS) were incubated in BA-EDTA. Calcified cholesterol stones are not dissolved by GMOC alone, nor by alternating treatment with BA-EDTA. They are dissolved by MTBE. MTBE is unsuitable for complete Ca-bilirubinate stones but MTBE, GMOC and GMOC/BA-EDTA alternately disaggregate stone fragments. This means that stone fragments behave differently from complete Ca-bilirubinate stones, which is important for further in vitro investigations. Ca-bilirubinate and black pigment stones are disaggregated in BA-EDTA. These results were confirmed with six CHS, 12 BBIL and 12 BPS from 5 further patients, incubated in the most eligible solvent for any individual stone type.

Topics: Animals; Bilirubin; Caprylates; Cattle; Cholelithiasis; Cholesterol; Edetic Acid; Ethers; Glycerides; Humans; Methyl Ethers; Microscopy, Electron, Scanning; Solvents

The authors describe percutaneous treatment of gallbladder or bile duct stones in 18 patients who were poor surgical candidates or in whom conventional therapy failed. Dissolution was performed in most cases with methyl tert-butyl ether (MTBE) because of its potent dissolution properties; other solvents used included monooctanoin or chelating solutions. Gallbladder stones were eliminated in 11 of 13 patients (six of seven with dissolution alone, four of four with dissolution and basket extraction, one with basket removal alone). In five patients with stones in the common bile duct (n = 3), cystic duct remnant (n = 1), and intrahepatic bile ducts (n = 1), stones were eliminated with dissolution alone in two and with dissolution plus basket extraction in one. In two patients percutaneous therapy failed due to complications (vagal hypotension with bile peritonitis and transient respiratory arrest) that occurred during catheter placement. Preliminary results suggest that MTBE is effective for dissolution of many gallbladder stones and some bile duct stones. Noncholesterol solvents and adjuvant mechanical maneuvers are valuable adjuncts to achieve complete stone elimination.

Topics: Bile Duct Diseases; Bile Ducts, Intrahepatic; Caprylates; Chelating Agents; Cholelithiasis; Ethers; Female; Gallstones; Glycerides; Humans; Male; Methyl Ethers; Solvents

Topics: Caprylates; Cholelithiasis; Cyclohexenes; Edetic Acid; Ethers; Glycerides; Humans; Limonene; Methyl Ethers; Terpenes

Cholecystostomy catheters and human cholesterol gallstones were implanted surgically in the gallbladders of eight pigs. Through the catheters, mono-octanoin or sterile water (H2O) was infused from two to seven days. The mono-octanoin dissolved pure cholesterol gallstones smaller than 200 g. There was no stone dissolution with infusion of sterile water and only one stone larger than 250 g was dissolved with mono-octanoin. Side effects included moderate-to-severe inflammation and ulceration of the gallbladder with mono-octanoin instillation, which precludes its widespread use with the present treatment regimen. Infusion of water caused little gallbladder irritation.

Topics: Animals; Caprylates; Catheters, Indwelling; Cholelithiasis; Gallbladder; Glycerides; Humans; Punctures; Solubility; Swine

The goal of this study was to identify the structural and compositional features of human gallstones that influence in vitro gallstone dissolution in the cholesterol solvent monooctanoin. Gallstones were obtained from 86 consecutive patients who had at least three morphologically similar stones. One stone from each patient was dissolved in ethanol/ether to determine cholesterol and matrix composition. The remaining two matched stones were dissolved in either monooctanoin plus ethanol (n = 86) or monooctanoin plus 2-mercaptoethanol (n = 86). The thiol reducing agent 2-mercaptoethanol has been previously shown to solubilize the isolated gallstone matrix and to accelerate the dissolution of intact, small cholesterol stones. Stone matrix content and initial diameter had the most significant predictive value for stone dissolution (p less than 0.0001 for each), whereas cholesterol content had no predictive value (p = 0.558). Stones incubated in monooctanoin containing 2-mercaptoethanol dissolved more rapidly than those incubated in monooctanoin plus ethanol (16.7% of initial weight per day vs. 13.8% of initial weight per day, p less than 0.0001). Matrix content correlated significantly with the difference in dissolution rate between stones dissolved in monooctanoin plus ethanol or monooctanoin plus 2-mercaptoethanol (p less than 0.0001). These data indicate that the matrix content of human cholesterol gallstones significantly inhibits in vitro stone dissolution in the cholesterol solvent monooctanoin. This finding may be relevant to the clinical dissolution of gallstones.

Topics: Caprylates; Cholelithiasis; Cholesterol; Ethanol; Glycerides; Mercaptoethanol; Regression Analysis; Solubility

Topics: Animals; Caprylates; Cholelithiasis; Dogs; Glycerides

Topics: Adult; Aged; Aged, 80 and over; Bile Duct Diseases; Caprylates; Cholelithiasis; Combined Modality Therapy; Endoscopy; Female; Glycerides; Humans; Male; Middle Aged; Reoperation

Topics: Caprylates; Carnitine; Chelating Agents; Cholelithiasis; Drug Industry; Glycerides; Hepatolenticular Degeneration; Humans; Orphan Drug Production; Trientine; United States; United States Food and Drug Administration

Mono-octanoin (glycerol-1-mono-octanoate) is a medium-chain diglyceride used to dissolve gallstones. We describe a patient in whom noncardiogenic pulmonary edema developed during intrabiliary infusion of monooctanoin. The temporal sequence suggests that the drug infusion initiated the lung injury.

Topics: Adult; Bile Duct Diseases; Caprylates; Cholelithiasis; Female; Glycerides; Humans; Pulmonary Edema; Radiography

Topics: Caprylates; Carnitine; Cholelithiasis; Citrates; Citric Acid; Drug Industry; Glycerides; Humans; Orphan Drug Production; United States; United States Food and Drug Administration; Urinary Calculi

Various gallstone solvents are compared to evaluate their efficacy. Cholesterol gallstones from 5 patients were weight matched and incubated in 5 different solutions at 37 degrees C. These solutions consisted of methyl-tertiary butyl ether (MTBE), 90% mono-octanoin (MO), absolute alcohol, normal saline, and water. Absolute alcohol and MTBE were found to induce faster stone dissolution than the mono-octanoin derivative. Concentrations of alcohol below 80%, normal saline, and water were not effective in dissolving stones. Newer agents such as MTBE may prove valuable in dissolution of stones in the human gallbladder or bile ducts.

Topics: Caprylates; Cholelithiasis; Ethanol; Ethers; Glycerides; Humans; Methyl Ethers; Sodium Chloride; Solvents; Water

Topics: Abscess; Acetylcysteine; Caprylates; Catheterization; Cholelithiasis; Drainage; Empyema; Glycerides; Humans; Infusions, Parenteral; Kidney Calculi; Solvents

We tested methyl tertiary butyl ether both in vitro and in vivo to evaluate its efficacy as a potential cholesterol gallstone solvent for direct instillation into the human gallbladder or bile duct. Like diethyl ether, methyl tertiary butyl ether is an aliphatic ether with an excellent cholesterol-solubilizing capacity. However, unlike diethyl ether which vaporizes at body temperature, methyl tertiary butyl ether remains a liquid having a boiling point of 55.2 degrees C. In vitro, methyl tertiary butyl ether dissolved human gallstones (40%-94% cholesterol) within 60-100 min. In contrast, monooctanoin, an established gallstone solvent, required greater than 50 h to dissolve similar stones. By direct catheter instillation in 6 dogs, methyl tertiary butyl ether required only 4-16 h to dissolve gallstones surgically implanted in the gallbladder. The dogs tolerated methyl tertiary butyl ether with only minor clinical, biochemical, or histologic effects. We conclude that further evaluation of methyl tertiary butyl ether for dissolution of human gallbladder and biliary duct cholesterol stones is warranted.

Topics: Animals; Caprylates; Cholelithiasis; Dogs; Drug Evaluation, Preclinical; Ethers; Female; Gallbladder; Glycerides; Humans; In Vitro Techniques; Methyl Ethers; Microscopy, Electron, Scanning; Solvents; Time Factors

Topics: Bile Acids and Salts; Caprylates; Cholelithiasis; Cholesterol; Cholic Acid; Cholic Acids; Glycerides; Heparin; Humans; In Vitro Techniques; Solubility; Solvents; Ursodeoxycholic Acid

Topics: Adult; Aged; Bile Duct Diseases; Caprylates; Cholecystectomy; Cholelithiasis; Female; Glycerides; Humans; Male; Middle Aged

Topics: Bile; Bile Duct Diseases; Bilirubin; Caprylates; Cholelithiasis; Cholesterol; Cholic Acid; Cholic Acids; Glycerides; Humans; Recurrence

Models of the common bile duct and gallbladder were constructed to study conditions that affect the rate of cholesterol gallstone dissolution by monooctanoin and other potential solvents. In the bile duct model, the rate of monooctanoin infusion was not an important factor in accelerating dissolution time. In contrast, the exclusion of bile from interfering with solvent-stone contact or the enhancement of solvent-stone contact by stirring significantly accelerated stone dissolution. The combination of both bile exclusion and stirring increased the dissolution rate of gallstones by monooctanoin 15-fold. When compared with two other ethers and with monooctanoin, methyl tert-butyl ether was found to be the most potent gallstone solvent. Methyl tert-butyl ether completely dissolved 219-mg cholesterol stones within 60 min. In the gallbladder model, in the absence of stirring both methyl tert-butyl ether and monooctanoin floated on bile, whereas the gallstones sank resulting in minimal stone-solvent contact. To increase the stone-solvent contact, we used a pump to create sufficient turbulence to mix the solvent with bile. Pump stirring of monooctanoin in the presence of bile achieved rates of stone dissolution approaching that of stirred monooctanoin without bile. Stirring of methyl tert-butyl ether and bile, however, did not achieve sufficient solvent-stone contact to appreciably accelerate dissolution in the presence of 50% bile. Stone-solvent contact was a critical factor in determining the rate of gallstone dissolution in both gallbladder and common bile duct models. Efforts to enhance contact include bile exclusion and intraluminal stirring--both of which are clinically applicable. Methyl tert-butyl ether is a potent new cholesterol gallstone solvent with excellent potential for use in humans. Even with this potent agent, however, rapid gallstone dissolution is likely to require removal of most of the bile from the dissolution medium.

Topics: Bile; Bile Ducts; Caprylates; Cholelithiasis; Cholesterol; Ethers; Gallbladder; Glycerides; Humans; In Vitro Techniques; Methyl Ethers; Models, Biological; Perfusion; Punctures; Solvents; Time Factors

A patient with a Billroth II resection and Crohn's disease subsequently developed obstructive jaundice and biliary sepsis. Three hepatic duct stones were demonstrated by ERC. After overcoming the obstruction by means of temporary retrograde internal drainage, perfusion of glyceryl-1-monooctanoate-carnosine and bile-acid-EDTA solution (2) was combined with sucralfate instillation into the blind loop via a duodenal tube. During successful treatment of the cholangiolithiasis, no deterioration of Crohn's disease was seen. Secondary effects such as abdominal pain or diarrhoea, were treated symptomatically.

Topics: Aged; Bile Acids and Salts; Caprylates; Carnosine; Cholelithiasis; Crohn Disease; Edetic Acid; Glycerides; Hepatic Duct, Common; Humans; Male; Mesocolon; Stomach

Seventeen patients who had intrahepatic calculi underwent perfusion with monooctanoin. While five patients responded with a decrease in size or number of calculi, only one had a complete response; 12 showed no response; and one died during the perfusion (however, the perfusion was not believed to have contributed to the death). Fifteen of the 17 patients required further treatment by a combination of basket extraction, oral administration of chenodeoxycholic acid, or surgery. The lack of response to monooctanoin perfusion was in part due to calculus composition. Because of the poor response to this treatment and the prolonged hospitalization generally required, monooctanoin is not recommended for dissolution of intrahepatic calculi.

Topics: Adult; Aged; Bile Ducts, Intrahepatic; Caprylates; Cholelithiasis; Glycerides; Humans; Middle Aged; Perfusion; Retrospective Studies

Monooctanoin, a cholesterol solvent, was infused into the biliary system of 11 patients. Twenty-eight (74%) of 38 total stones responded to monooctanoin: 16 (42%) decreased in size, and 12 (32%) dissolved completely. Ten stones (26%) did not change in size. We attribute this to inadequate drug-stone contact, which was corrected by placement of the infusion catheter contiguous to the stone(s). The use of a second catheter for biliary drainage avoided the side effect of biliary colic and increased patient compliance. An infusion rate greater than 5 ml per hour invariably produced pain and diarrhea. There were no significant side effects from monooctanoin in any of our patients when a two catheter system and an infusion rate of 5 ml per hour or less were used. A major drawback to use of this still experimental agent is the prolonged hospital stay. This may be ameliorated when at home use of monooctanoin is approved.

Topics: Adult; Aged; Bile Duct Diseases; Caprylates; Cholelithiasis; Glycerides; Humans; Middle Aged; Perfusion

Monooctanoin was infused through a cholecystostomy tube to dissolve multiple gallstones and re-establish cystic duct patency in a patient who was not a candidate for surgery.

Topics: Aged; Caprylates; Cholelithiasis; Glycerides; Humans; Intubation; Male

Monooctanoin (MO), when infused into the common bile duct (CBD), is an effective agent in dissolving retained CBD stones. If the stone migrates and obstructs the distal CBD, the solution could be infused under pressure resulting in intrahepatic reflux. The relationship between the infusion pressure and the safety of monooctanoin has not been evaluated. To study the effects of intrahepatic reflux of MO, a canine model was used and solutions were infused into an obstructed CBD under controlled pressure. Solutions of normal saline (NS), 150 mM sodium cholate (Ch), or MO were infused under pressures of 30, 40, and 50 cm. All of eight dogs died when infused with MO at 50 cm pressure with a mean administered dose of 1.4 +/- 0.4 cc/kg within a mean time of 87 +/- 38 min. Three of four dogs died at 40 cm pressure (1.7 +/- 0.4 cc/kg; 133 +/- 95 min) and only one of three dogs died at 30 cm pressure (2.5 cc/kg; 335 min). These dogs died from progressive hypoxia, acidosis, hemolysis, and hemorrhagic pneumonitis. Four dogs each were administered Ch at 50 and 40 cm pressure and all died with an average absorption of 19 cc/kg. Six dogs were tested with NS at 50 cm and all survived despite absorbing 180 cc/kg in 6 hr. MO at 50 cm pressure and Ch at both 40 and 50 cm pressure were significantly more toxic than saline. It is concluded that MO and Ch infused under pressure into CBD carry a significant risk of serious side effects. The infusion pressure must be monitored to prevent increased biliary pressure which might lead to intrahepatic reflux.

Topics: Animals; Bile Reflux; Biliary Tract Diseases; Caprylates; Cholelithiasis; Cholestasis; Cholic Acid; Cholic Acids; Common Bile Duct Diseases; Dogs; Glycerides; Models, Biological; Pressure; Solvents

Topics: Calculi; Caprylates; Cholelithiasis; Female; Glycerides; Humans; Liver Diseases; Middle Aged

Monooctanoin, a cholesterol solvent, was infused into the biliary tracts of six high risk patients, in an attempt to dissolve retained stones. The infusion rate was constant, 5-10 ml/h. The mean age of the patients was 76 years. Associated medical conditions were primarily cardiac in nature. Duration of infusion averaged 6 days. In two patients, the stones were completely dissolved. One patient was reoperated despite the stones appearing smaller after 6 days of infusion. At surgery, no stones were found. Two patients in whom dissolution was unsuccessful underwent reoperation. In both, retrieved stones were composed of less than 5% cholesterol. Five of the six patients experienced at least one episode of mild abdominal pain and vomiting. None developed cholangitis, pancreatitis, or significant biochemical abnormalities. Two of the three who underwent reoperation tolerated it without difficulty. While mechanical extraction, when feasible, is still the treatment of choice for retained biliary stones, chemical dissolution should be attempted before undertaking reoperation.

Topics: Abdomen; Aged; Caprylates; Cholelithiasis; Female; Glycerides; Humans; Infusions, Parenteral; Male; Pain; Risk; Solvents; Vomiting

Topics: Bile Duct Diseases; Caprylates; Cholelithiasis; Drainage; Glycerides; Humans; Solvents

Investigations of four bile duct stones demonstrated that the distribution of organic compounds, pigments, and crystalline calcium salts as well as the stone architecture can prevent dissolution with perfusion therapy. We describe perfusion media that will dissolve or disaggregate the substances mentioned in vitro. Isolated organic compounds, probably mucoproteins, could be disaggregated with a SH-activated enzyme-containing bile salt-EDTA-solution (BA-EDTA) at pH 6.5-8.2. After admixture of 5-10% glyceryl-1-monooctanoin-carnosine to the BA-EDTA solution a mucoprotein-rich pigment concrement (calcium-bilirubinate stone) was completely disaggregated and the calcium and pigment portion was dissolved within 36 h. Alternating administration of an enzyme-free BA-EDTA solution with glyceryl-1-monooctanoin-carnosine resulted in accelerated dissolution of a pigment containing cholesterol stone compared to CApmul 8210. These perfusion media have been successfully used in patients. Factors limiting stone dissolution remain stone architecture, crystalline carbonic occlusions in high concentration, and the topography of the biliary tree.

Topics: Bile Acids and Salts; Caprylates; Carnosine; Cholelithiasis; Dipeptides; Edetic Acid; Glycerides; Humans; In Vitro Techniques; Perfusion; Solubility; Solvents

A new gallstone solvent, monooctanoin, was tested in vitro on gallstones from 43 patients and compared with heparin, sodium dehydrocholate, and saline. Monooctanoin proved to be an excellent solvent, far superior to the other agents. It can completely dissolve or substantially reduce the size of most gallstones (except those composed of bilirubinate) in a relatively short time. Monooctanoin has been used on the bile duct stones in humans with favorable results. It can often eliminate the need for basket extraction of retained bile duct calculi. Potentially, it may be used to dissolve bile duct or gallbladder calculi in patients who are poor surgical risks.

Topics: Caprylates; Cholelithiasis; Dehydrocholic Acid; Glycerides; Humans; In Vitro Techniques; Sodium Chloride; Solvents

Topics: Administration, Oral; Caprylates; Chenodeoxycholic Acid; Cholelithiasis; Cholesterol; Cholic Acids; Endoscopy; Female; Gallstones; Glycerides; Humans; Intubation, Gastrointestinal; Liver

Monooctanoin, a cholesterol gallstone solvent, has been gaining wide acceptance as an effective safe agent for dissolving retained common bile duct stones when infused into the biliary tract. A woman with choledocholithiasis who received infusions of this agent into the biliary tract on three different occasions developed systemic side effects on each occasion. The severity of the side effects necessitated discontinuation of monooctanoin therapy.

Topics: Adult; Caprylates; Cholelithiasis; Female; Glycerides; Humans; Solvents

The ability of Capmul 8210, a commercial solvent that predominantly consists of glyceryl 1-mono-octanoate, to dissolve retained common duct stones by direct infusion into the T-tube was tested in 20 patients with a total of 43 stones. Of 19 patients who completed their infusion, stone disappearance was observed in 15, giving a success rate of 79%. The dissolution time for a single stone averaged four days. A slight rise in serum alkaline phosphatase and amylase levels occurred in some patients, and rapidly returned to normal when treatment was concluded. Other side effects, such as nausea and vomiting epigastric discomfort, or diarrhea, occurred occasionally but were easily controlled medically. We believe that this agent is a useful adjunct in the management of postoperative choledocholithiasis in the patient with an indwelling T-tube.

Topics: Alkaline Phosphatase; Amylases; Aspartate Aminotransferases; Bilirubin; Caprylates; Cholelithiasis; Glycerides; Humans

Retained bile duct stones in patients who have undergone prior cholecystectomy are removed by operation or endoscopic sphincterotomy. We achieved dissolution of cholesterol duct stones by perfusion with monooctanoin, a commercially available mixture of medium chain glycerides. Sixteen patients were treated in whom endoscopic sphincterotomy was impossible or unsuccessful. In 12 patients, 16 stones were dissolved within 6 to 25 days (mean, 15.6 days). In all successfully treated patients elevated serum liver enzymes became normal during therapy.

Topics: Aged; Caprylates; Catheterization; Cholangiography; Cholelithiasis; Endoscopy; Female; Glycerides; Humans; Male; Middle Aged

Topics: Bile Duct Diseases; Caprylates; Cholelithiasis; Glycerides; Humans

Topics: Caprylates; Cholelithiasis; Cholesterol; Cholic Acids; Glycerides; Heparin; Humans; In Vitro Techniques

Topics: Bile Ducts; Caprylates; Catheterization; Cholelithiasis; Endoscopy; Glycerides; Humans; Perfusion; Time Factors

Topics: Caprylates; Cholelithiasis; Cholesterol; Cholic Acids; Glycerides; Heparin; Humans; In Vitro Techniques; Solvents

Topics: Animals; Caprylates; Cholelithiasis; Drug Evaluation; Glycerides; Liver Function Tests; Macaca mulatta