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Does dietary fish oil prevent cholesterol gallstone formation in inbred mice
April
Biliary Disorders A531
1998
• G2167 LONG-TERM ENDOBILIARY STENT PLACEMENT FOR CHOLANGITIS IN NONAGENARIANS: AN AGE APPROPRIATE APPROACH. D.E. McGuire, W.F. Zakko. Dept. of Gastroenterology, Cleveland Clinic Florida, Ft. Landerdale, FL. Introduction: Endoscopic sphincterotomy and stone extraction remains the
gold standard treatment for acute cholangitis. While endobiliary stent placement at the time of ERCP has been shown to be a highly effective, alternative treatment for cholangitis, data on this technique for patients in their tenth decade of life has been limited. The aim of this study was to prospectively evaluate the short and long term safety and outcome of endobiliary stent placement in nonagenarians presenting with bile duct infection who wished to defer repeat ERCP with sphincterotomy and stone removal. Methods: From July 1996 to October 1997, 3 patients aged 90 years or more (mean age = 91.3) were referred for evaluation of unstable cholangitis. All three patients had elevated serum transaminases, white blood cell counts, fever, and dilated bile ducts on ultrasonography. 2 of 3 patients had systolic blood pressure < 90 mm Hg at presentation. Only 1 patient had an intact gallbladder, and an additional patient had undergone choledochoduodenostomy previously. ERCP and endobiliary stent placement was performed in each patient because of either hemodynamic instability or large common bile duct stones prohibiting easy sphincterotomy and stone extraction. Moreover, after successful stent placement, patients were offered repeat ERCP with sphincterotomy and stone removal, surgery, and expectant follow-up as options. All 3 patients opted for conservative treatment. Results: ERCP with endobiliary stent placement was successful in all 3 patients. Common bile duct stones were found in all three. There were no complications. All 3 patients experienced complete resolution of cholangitis, and were discharged without difficulty. Mean follow-up was 9 months. 1 patient experienced recurrent cholangitis at 7 months, requiting repeat ERCP with sphincterotomy and stone extraction which was successful and without complications. The remaining patients have been stable at 15 months and 5 months respectively. Conclusions: ERCP with endobiliary stent placement for cholangitis in the nonagenarian is well-tolerated, and serves as a safe and efficacious alternative to sphincterotomy and stent removal in this age group. For the nonagenarian who is capable of follow-up and wishes no further intervention, long term stent placement is safe and may be appropriate in certain settings. • G2168 BALLOON SPHINCTEROPLASTY AND DELAYED CHOLECYSTECTOMY: WHAT IS THE RISK FOR RECURRENT BILIARY OBSTRUCTION? J Meenan; R Ede; PJ Ciclitira; RPH Thompson. Dept. Gastroenterology, St. Thomas' Hospital, London, United Kingdom. Balloon sphincteroplasty at ERCP permits the removal of biliary tree calculi with preservation of the sphincter of Oddi. This approach is attractive in younger patients, in whom the long-term sequelae of sphincteretomy remains uncertain. It is unknown however, whether preservation of sphincter function is associated with a risk of recurrent choledocholithiasis if cholecystectomy is delayed. METHODS: Forty-two patients (male: 18, female:24) of median age 62yrs. (19-87yrs.) underwent balloon sphincteroplasty for definite or suspected ductal stones seen at cholangiography. An 8mm or 10mm balloon (Microvasive) was inflated to 10atm. for 2 minutes. The biliary duct was subsequently trawled with a Dormia basket and extraction balloon. Following ERCP, patients were discharged and scheduled for cholecystectomy. RESULTS: Prior to ERCP, patient median liver blood results, expressed as a ratio of control values, were raised: bilirubin, 1.1; AIkP, 1.25 and GGT, 2.0. A median of i ductal stone (0-20), of median size 5mm (2-12mm) was removed. All ducts were cleared of calculi as determined by occlusion cholangiography. Gallbladder stones were present in 86% of patients. Twenty-five patients (60%) underwent cholecystectomy, median time 4wks. (1-58wks.). Six patients (14%) had previously undergone cholecystectomy (0.5-3yrs.). The remaining patients declined, or were considered unfit for surgery. The median follow-up period for all patients was 84wks. (12-168wks.). Biliary obstruction recurred in 4 cases (10%) by a median 20wks. (3-28wks.). All of these had remaining gallbladder stones. In 1 case, no ductal stones had been found at the index ERCP. DISCUSSION: Balloon sphincteroplasty for biliary tree stones is thought to preserve the normal physiology of the sphincter of Oddi. This study suggests that the risk of recurrent biliary obstruction in those patients awaiting, or have previously undergone, cholecystectomy is small. • G2169 DOES DIETARY FISH OIL PREVENT CHOLESTEROL GALLSTONE FORMATION IN INBRED MICE. N M6ndez-Sfinchez., G PoncianoRodrfguez, I Gracia, M Uribe. Deptartment of Gastroenterology, Medica Sur Clinical Foundation, and The Faculty of Chemistry, National University of Mexico, Mexico City. Back~,round: Recently, it has been reconsidered that the genetic factors play
an important role in the development of cholesterol gallstone disease. Also, the lith genes that determine susceptibility to cholesterol cholelithiasis in inbred mice have been proposed in two different strains (J Lipid Res 1997;38:1395-1411; Gastroenterology 1997;112:A1219). In addition, it has
been demonstrated that hypersecretion of biliary cholesterol is a characteristic of these inbred mice. On the other hand, some reports have proposed that dietary fish oil (FO) inhibits cholesterol nucleation and gallstone formation in the prairie dog (Gastroenterology 1989;96:A625). Aim: To investigate the effect of dietary FO on the prevention of cholesterol gallstone formation. Methods: Male NIH (control strain) and C57BL/6J (susceptible strain) mice, aged 12 weeks, were fed a chow diet (control) or lithogenic diet (LD) containing 15% dairy fat, 1% cholesterol and 0.5% cholic acid for 60 days. Control and LD were enriched with 5% FO for other groups (LD+FO and FO). The common bile duct was cannulated for measurement of biliary lipids and their analysis were determined by standard methodology. The animals were then sacrificed; gallbladders were observed for stone formation. Results:
Incidence of cholesterol gallstone Groups N Control LD LD + FO FO
NIH 6 (%) 0/6 (0) 2/6 (33) 0/6 (0) 0/6 (0)
Mice Strains C57BL/6J 6 (%) 0/6 (0) 6/6 (100) 6/6 (100) 0/6 (0)
p value
0.06 0.002
Biliary lipids in C57BL/6J mice: Cholesterol concentrations were higher in both groups LD (3.7 ± 0.2 and LD+EO (3.73 ± 0.2) compared with the control (1.87 ± 0.1) and FO (1.32 ± 0.2), p<0.05. Phospholipid concentrations were similar in all groups, and total bile salt concentration was increased in the LD group. In the NIH strain mice, LD and LD+FO groups had more cholesterol and phospholipids and bile salt (LD). Conclusions: FO do not prevent the cholesterol gallstone formation in susceptible C57BL/6J inbred mice. Contrariwise, FO prevents the cholesterol gallstone formation in NIH strain mice. Most likely because C57BL/6J mice probably exhibit higher cholesterol absorption from dietary and biliary sources compared with NIH mice at the intestinal level. G2170
REGULAR FOOD DIET (1200 KCAL/D) PREVENTS CHOLESTEROL GALLSTONE FORMATION IN OBESE PATIENTS DURING WEIGHT LOSS AND THIS EFFECT IS IMPROVED BY SUPLEMENTATION OF N-3 POLYNSATURATED FATTY ACIDS. N M~ndez-Sfinchez. V Gonzfilez. P Aeuavo. JM Sfinchez. MA Tanimoto. J Elizondo. M Utibe. Departments of Gastroenterology, Endoscopy and Radiology, The National Institute of Nutrition and M6dica Sur Clinical Foundation, Mexico City. Backeround: We have suggested that obesity is the major clinical factor
associated with gallstone formation, the risk for developing gallstones in obese persons is three to seven times higher than that in eutrophic persons, and the risk for gallstone formation in patients undergoing rapid weight reduction seems even greater (Ann Intern Med 1996;124:532-4). On the other hand, epidemiologic studies have suggested that populations consuming diets rich in n-3 polynsaturated fatty acids (n-3 PUFA) may be relatively protected from cholesterol gallstone disease, also clinical studies carried out in patients with radiolucent gallstones have reported that n-3 PUFA decreases biliary cholesterol saturation (Hepatology 1992;16:960-7). Aim: To investigate the effect of regular food diet (1200 Kcal/d) plus n-3 PUFA on biliary cholesterol saturation and nucleation time in obese patients during rapid loss of weight. Methods: Twelve female obese patients (mean age 38.5 ± 9 yr) were studied according to the following criteria: without a prior history of gallstones by ultrasound or cholecystectomy, no pregnancy, free of any medication. Patients then were assigned in a double-blind fashion to one of the two treatment groups for 6 weeks. Group A (n=7) received regular food diet supplemented with n-3 PUFA. These patients ingested 11.3 g/day MAxEPA oil (in three doses). Group B (n=5) received regular food diet and placebo. All patients received a 1,200 kcal diet. Body mass index (BMI) was recorded at the baseline and after treatment. Gallbladder bile was obtained by stimulating contraction and the analysis of biliary lipids and cholesterol nucleation time (NT) were determined by standard methodology. Results: There was a significant lost of body weight in patients of n-3 PUFA and placebo groups, p< 0.05 and p< 0.0009 respectively (see table). Absence of gallstones in patients of both groups was documented by ultrasound. Cholesterol saturation index (CSI) decreased significantly in patients treated with n-3 PUFA, p< 0.001, but not in the placebo group. Groups BMI CSI NT
A (n-3 PUFA) Be~re After 33.4±4.3 30.6±4.8 1.03±0.5 0.88±0.05 15.6±5.8 10.8±4.2
B (Placebo) Be~re A~er 33.2±1.4 30.7±1.1 1.02±0.05 1.0±0.3 14.5±5.7 10.8±2.1
Conclusions: Regular food diet (1200 Kcal/d) prevents cholesterol gallstone formation in obese patients during rapid loss of weight, and this effect is improved by supplementation with n-3 PUFA through the decrease of CSI.
Biliary Disorders A531
1998
• G2167 LONG-TERM ENDOBILIARY STENT PLACEMENT FOR CHOLANGITIS IN NONAGENARIANS: AN AGE APPROPRIATE APPROACH. D.E. McGuire, W.F. Zakko. Dept. of Gastroenterology, Cleveland Clinic Florida, Ft. Landerdale, FL. Introduction: Endoscopic sphincterotomy and stone extraction remains the
gold standard treatment for acute cholangitis. While endobiliary stent placement at the time of ERCP has been shown to be a highly effective, alternative treatment for cholangitis, data on this technique for patients in their tenth decade of life has been limited. The aim of this study was to prospectively evaluate the short and long term safety and outcome of endobiliary stent placement in nonagenarians presenting with bile duct infection who wished to defer repeat ERCP with sphincterotomy and stone removal. Methods: From July 1996 to October 1997, 3 patients aged 90 years or more (mean age = 91.3) were referred for evaluation of unstable cholangitis. All three patients had elevated serum transaminases, white blood cell counts, fever, and dilated bile ducts on ultrasonography. 2 of 3 patients had systolic blood pressure < 90 mm Hg at presentation. Only 1 patient had an intact gallbladder, and an additional patient had undergone choledochoduodenostomy previously. ERCP and endobiliary stent placement was performed in each patient because of either hemodynamic instability or large common bile duct stones prohibiting easy sphincterotomy and stone extraction. Moreover, after successful stent placement, patients were offered repeat ERCP with sphincterotomy and stone removal, surgery, and expectant follow-up as options. All 3 patients opted for conservative treatment. Results: ERCP with endobiliary stent placement was successful in all 3 patients. Common bile duct stones were found in all three. There were no complications. All 3 patients experienced complete resolution of cholangitis, and were discharged without difficulty. Mean follow-up was 9 months. 1 patient experienced recurrent cholangitis at 7 months, requiting repeat ERCP with sphincterotomy and stone extraction which was successful and without complications. The remaining patients have been stable at 15 months and 5 months respectively. Conclusions: ERCP with endobiliary stent placement for cholangitis in the nonagenarian is well-tolerated, and serves as a safe and efficacious alternative to sphincterotomy and stent removal in this age group. For the nonagenarian who is capable of follow-up and wishes no further intervention, long term stent placement is safe and may be appropriate in certain settings. • G2168 BALLOON SPHINCTEROPLASTY AND DELAYED CHOLECYSTECTOMY: WHAT IS THE RISK FOR RECURRENT BILIARY OBSTRUCTION? J Meenan; R Ede; PJ Ciclitira; RPH Thompson. Dept. Gastroenterology, St. Thomas' Hospital, London, United Kingdom. Balloon sphincteroplasty at ERCP permits the removal of biliary tree calculi with preservation of the sphincter of Oddi. This approach is attractive in younger patients, in whom the long-term sequelae of sphincteretomy remains uncertain. It is unknown however, whether preservation of sphincter function is associated with a risk of recurrent choledocholithiasis if cholecystectomy is delayed. METHODS: Forty-two patients (male: 18, female:24) of median age 62yrs. (19-87yrs.) underwent balloon sphincteroplasty for definite or suspected ductal stones seen at cholangiography. An 8mm or 10mm balloon (Microvasive) was inflated to 10atm. for 2 minutes. The biliary duct was subsequently trawled with a Dormia basket and extraction balloon. Following ERCP, patients were discharged and scheduled for cholecystectomy. RESULTS: Prior to ERCP, patient median liver blood results, expressed as a ratio of control values, were raised: bilirubin, 1.1; AIkP, 1.25 and GGT, 2.0. A median of i ductal stone (0-20), of median size 5mm (2-12mm) was removed. All ducts were cleared of calculi as determined by occlusion cholangiography. Gallbladder stones were present in 86% of patients. Twenty-five patients (60%) underwent cholecystectomy, median time 4wks. (1-58wks.). Six patients (14%) had previously undergone cholecystectomy (0.5-3yrs.). The remaining patients declined, or were considered unfit for surgery. The median follow-up period for all patients was 84wks. (12-168wks.). Biliary obstruction recurred in 4 cases (10%) by a median 20wks. (3-28wks.). All of these had remaining gallbladder stones. In 1 case, no ductal stones had been found at the index ERCP. DISCUSSION: Balloon sphincteroplasty for biliary tree stones is thought to preserve the normal physiology of the sphincter of Oddi. This study suggests that the risk of recurrent biliary obstruction in those patients awaiting, or have previously undergone, cholecystectomy is small. • G2169 DOES DIETARY FISH OIL PREVENT CHOLESTEROL GALLSTONE FORMATION IN INBRED MICE. N M6ndez-Sfinchez., G PoncianoRodrfguez, I Gracia, M Uribe. Deptartment of Gastroenterology, Medica Sur Clinical Foundation, and The Faculty of Chemistry, National University of Mexico, Mexico City. Back~,round: Recently, it has been reconsidered that the genetic factors play
an important role in the development of cholesterol gallstone disease. Also, the lith genes that determine susceptibility to cholesterol cholelithiasis in inbred mice have been proposed in two different strains (J Lipid Res 1997;38:1395-1411; Gastroenterology 1997;112:A1219). In addition, it has
been demonstrated that hypersecretion of biliary cholesterol is a characteristic of these inbred mice. On the other hand, some reports have proposed that dietary fish oil (FO) inhibits cholesterol nucleation and gallstone formation in the prairie dog (Gastroenterology 1989;96:A625). Aim: To investigate the effect of dietary FO on the prevention of cholesterol gallstone formation. Methods: Male NIH (control strain) and C57BL/6J (susceptible strain) mice, aged 12 weeks, were fed a chow diet (control) or lithogenic diet (LD) containing 15% dairy fat, 1% cholesterol and 0.5% cholic acid for 60 days. Control and LD were enriched with 5% FO for other groups (LD+FO and FO). The common bile duct was cannulated for measurement of biliary lipids and their analysis were determined by standard methodology. The animals were then sacrificed; gallbladders were observed for stone formation. Results:
Incidence of cholesterol gallstone Groups N Control LD LD + FO FO
NIH 6 (%) 0/6 (0) 2/6 (33) 0/6 (0) 0/6 (0)
Mice Strains C57BL/6J 6 (%) 0/6 (0) 6/6 (100) 6/6 (100) 0/6 (0)
p value
0.06 0.002
Biliary lipids in C57BL/6J mice: Cholesterol concentrations were higher in both groups LD (3.7 ± 0.2 and LD+EO (3.73 ± 0.2) compared with the control (1.87 ± 0.1) and FO (1.32 ± 0.2), p<0.05. Phospholipid concentrations were similar in all groups, and total bile salt concentration was increased in the LD group. In the NIH strain mice, LD and LD+FO groups had more cholesterol and phospholipids and bile salt (LD). Conclusions: FO do not prevent the cholesterol gallstone formation in susceptible C57BL/6J inbred mice. Contrariwise, FO prevents the cholesterol gallstone formation in NIH strain mice. Most likely because C57BL/6J mice probably exhibit higher cholesterol absorption from dietary and biliary sources compared with NIH mice at the intestinal level. G2170
REGULAR FOOD DIET (1200 KCAL/D) PREVENTS CHOLESTEROL GALLSTONE FORMATION IN OBESE PATIENTS DURING WEIGHT LOSS AND THIS EFFECT IS IMPROVED BY SUPLEMENTATION OF N-3 POLYNSATURATED FATTY ACIDS. N M~ndez-Sfinchez. V Gonzfilez. P Aeuavo. JM Sfinchez. MA Tanimoto. J Elizondo. M Utibe. Departments of Gastroenterology, Endoscopy and Radiology, The National Institute of Nutrition and M6dica Sur Clinical Foundation, Mexico City. Backeround: We have suggested that obesity is the major clinical factor
associated with gallstone formation, the risk for developing gallstones in obese persons is three to seven times higher than that in eutrophic persons, and the risk for gallstone formation in patients undergoing rapid weight reduction seems even greater (Ann Intern Med 1996;124:532-4). On the other hand, epidemiologic studies have suggested that populations consuming diets rich in n-3 polynsaturated fatty acids (n-3 PUFA) may be relatively protected from cholesterol gallstone disease, also clinical studies carried out in patients with radiolucent gallstones have reported that n-3 PUFA decreases biliary cholesterol saturation (Hepatology 1992;16:960-7). Aim: To investigate the effect of regular food diet (1200 Kcal/d) plus n-3 PUFA on biliary cholesterol saturation and nucleation time in obese patients during rapid loss of weight. Methods: Twelve female obese patients (mean age 38.5 ± 9 yr) were studied according to the following criteria: without a prior history of gallstones by ultrasound or cholecystectomy, no pregnancy, free of any medication. Patients then were assigned in a double-blind fashion to one of the two treatment groups for 6 weeks. Group A (n=7) received regular food diet supplemented with n-3 PUFA. These patients ingested 11.3 g/day MAxEPA oil (in three doses). Group B (n=5) received regular food diet and placebo. All patients received a 1,200 kcal diet. Body mass index (BMI) was recorded at the baseline and after treatment. Gallbladder bile was obtained by stimulating contraction and the analysis of biliary lipids and cholesterol nucleation time (NT) were determined by standard methodology. Results: There was a significant lost of body weight in patients of n-3 PUFA and placebo groups, p< 0.05 and p< 0.0009 respectively (see table). Absence of gallstones in patients of both groups was documented by ultrasound. Cholesterol saturation index (CSI) decreased significantly in patients treated with n-3 PUFA, p< 0.001, but not in the placebo group. Groups BMI CSI NT
A (n-3 PUFA) Be~re After 33.4±4.3 30.6±4.8 1.03±0.5 0.88±0.05 15.6±5.8 10.8±4.2
B (Placebo) Be~re A~er 33.2±1.4 30.7±1.1 1.02±0.05 1.0±0.3 14.5±5.7 10.8±2.1
Conclusions: Regular food diet (1200 Kcal/d) prevents cholesterol gallstone formation in obese patients during rapid loss of weight, and this effect is improved by supplementation with n-3 PUFA through the decrease of CSI.