- Email: [email protected]
136
300
Journal of Gastrointestinal Surgery
Abstracts
feeding group (Table 1). Tube-related complications occurred in 6 out of 98 patients, and all were gastrojejunal tubes. Early postoperative jejunal tube feeding in patients undergoing pancreaticoduodenectomy is associated with a significantly lower rate of TPN use, hospital readmissions, and late complications. These data support routine use of a bridled nasojejunal feeding tube and early enteral nutrition.
TPN Readmit Early complications Late complications
Enteral feed (n98)
No enteral feed(n82)
p value
6 (6%) 12 (12%) 51 (52%) 12 (12%)
22 (27%) 22 (27%) 51 (62%) 25 (31%)
0.0003 0.015 NS 0.003
134 Neoadjuvant Gemcitabine (Gemzar), Paclitaxel (Taxol) and Radiation may Downstage Locally Advanced Pancreas Cancer Facilitating Resection David A Iannitti, Natalie Coburn, William Cioffi, John Tomicic, Harold I Wanebo, Thomas DiPetrillo, Howard Safran, Brown Medical School, Providence, RI; Roger Williams Medical Center, Providence, RI Introduction: Surgical resection for pancreatic cancer is the most effective treatment for this disease. Only 15% of patients at the time of diagnosis are candidates for resection. Forty percent of cases present with locally advanced, non-metatstatic disease, traditionally, not amenable to pancreatic resection. Neoadjuvant chemoradiation to downstage locally advanced pancreatic cancer for resection is evolving. The 5FU based chemoradiation only rarely achieves an adequate response to allow for resection. The Brown University Oncology Group (BRUOG) has evaluated paclitaxel (Taxol)/radiation and Gemcitabine (Gemzar)/paclitaxel/radiation treatment in a series of trials for medical effectiveness. We retrospectively reviewed our data to determine if these neoadjuvant modalities can downstage locally advanced pancreatic cancer to be resected. Results: 42 patients who initially had locally advanced disease were treated on a phase II trial of Taxol 50 mg/m2/wk with 50.4 Gy radiation. A significant number were downstaged, however were not medically cleared for surgery. Ultimately, 14 underwent surgical exploration. Four patients were resected, one had fibrosis with negative biopsy, and 9 had unsuspected liver metastases. Of the patients who were resected, 3 had partial responses and one had stable disease following chemoradiation. One patient, who initially had SMA encasement, is disease free at 6 years follow up. Gemcitabine was subsequently added to paclitaxel/radiation treatment in a phase I trial. Twenty patients were enrolled in the trial and 10 were treated at the maximally tolerated dose (MTD): gemcitabine 75 mg/m2/wk, paclitaxel 40 mg/m2/wk, and 50.4 Gy radiation. Of the 10 patients treated at the MTD, four patients had downstaging of disease such that they underwent exploration for resection. Prior to neoadjuvant treatment, one had portal vein thrombosis, the second had portal vein invasion, the third had superior mesenteric artery (SMA) encasement, and the fourth had both inferior vena cava and SMA involvement. A pancreaticoduodenectomy was performed on 3 of 4 patients with negative margins. A fifth patient was treated off protocol after the study was completed. This patient had post-chemoradiation resection with negative margins. Conclusion: The role for neoadjuvant chemoradiation for locally advanced pancreatic cancer is evolving. The BRUOG studies show that neoad-
juvant paclitaxel based chemoradiation regimens can downstage some patients with locally advanced disease, making their tumors amenable to resection. Paclitaxel/gemcitabine/radiation appears to be more effective in downstaging pancreatic cancer than 5FU based chemoradiation. The ultimate impact on survival remains uncertain.
BILIARY Gallstones 135 Outcome of Laparoscopic Cholecystectomy for Presumed Biliary Pancreatitis Bipan Chand, R M Walsh, The Cleveland Clinic Foundation, University Heights, OH; The Cleveland Clinic Foundation, Cleveland, OH Anatomic and clinical data have long supported the concept of gallstone migration as one cause of acute pancreatitis. Calculi should be excluded since cholecystectomy is potentially a curative treatment for this cause of pancreatitis. Similarly, cholecystectomy may also represent definitive treatment for idiopathic pancreatitis presumptively due to microlithiasis. A retrospective review of patients who underwent laparoscopic cholecystectomy for known calculus or idiopathic pancreatitis was conducted to assess outcome. A cholecystectomy database was queried for patients operated for pancreatitis between July 1995 and June 2000. A total of 94 patients underwent cholecystectomy, 72 of which were operated on for documented calculi by transcutaneous ultrasound. Twenty-two patients underwent surgery for presumed idiopathic pancreatitis based on a negative ultrasound and history. Patients with known calculi included 42 women and 30 men with a mean age of 62 (range 21-80) years. Common duct calculi were documented in 16 patients (17%). Pre-operative ERCPs were performed in 31 patients (43%) and was diagnostic of common duct stones in 8 (27%). Intraoperative cholangiography was successful in 68 of 72 patients (94%), and common duct stones were found in 10 (15%). Conversion to open was done in three (4%). At a mean follow-up of 57 months, pancreatic complications occurred postoperatively in 4 patients (7%): two with acute recurrent pancreatitis, one acute pancreatitis due to pancreatic divisum, and one ampullary stenosis. Patients with idiopathic pancreatitis presumed to have microlithiasis included 11 women and 11 men with a mean age of 45 (range 34-75) years. Preoperative evaluation included crystal analysis in two patients, ERCP in 9 (41%), and MRCP in two (9%). Open cholecystectomy was required in two (9%). Unsuspected calculi were discovered by pathology in six (23%), including two patients with common duct stones at operative cholangiography. At a mean followup of 47 months, subsequent biliary pancreatic disease occurred in six (27%); four with chronic idiopathic pancreatitis, one each with acute pancreatitis due to pancreatic divisum and sphincter of Oddi dysfunction by abnormal manometry. In summary, laparoscopic cholecystectomy confers long-term success in preventing pancreatic complications when calculi are diagnosed preoperatively. Patients with presumed idiopathic pancreatitis should be investigated for ductal abnormality with non-invasive testing. Empiric cholecystectomy is advised for patients with idiopathic pancreatitis and a normal pancreatic duct to achieve high clinical success by removing unsuspected calculi.
136 Cholesterol Crystal Nucleation in Heterozygous LeptinDeficient Lean Mice Khoi Q Tran, Matthew I Goldblatt, Deborah A Swartz-Basile, Attila Nakeeb, Henry A Pitt, Medical College of Wisconsin, Milwaukee, WI
Vol. 7, No. 2 2003
Abstracts
Background: Cholesterol gallstones result from cholesterol supersaturation of bile, biliary stasis and crystal nucleation. Obesity is a known risk factor, but a complete understanding of this phenomenon is lacking. Leptin, a hormone produced by adipocytes, has been implicated in the pathogenesis of both obesity and gallstone formation. We have demonstrated that lean heterozygous leptin-deficient mice have an intermediate gallbladder response to neurotransmitters and cholesterol saturation similar to both lean control and obese leptin-deficient mice. However, cholesterol crystal formation in heterozygous leptin-deficient mice has not been studied. Therefore, we hypothesized that bile from heterozygous mice would form cholesterol crystals at an intermediate rate between lean control and homozygous leptin-deficient obese mice. Methods: Seventy-five lean control (C57BL/6J), 54 lean heterozygous (C57BL/6J Lephet) and 36 obese (C57BL/6J Lepob) female mice underwent cholecystectomy at 12 weeks of age. Bile was collected, pooled, filtered and incubated at 37° C. Cholesterol monohydrate crystal formation was observed daily under polarized light microscopy for 17 days. Crystal observation time (COT) in days, crystal growth (slope) and crystal mass (total number) were measured and analyzed with the MannWhitney Rank Sum Test. Results: Crystal formation data are presented in the table. Conclusions: Lean heterozygous leptin deficient mice have crystal observation time, growth and mass similar to lean controls rather than homozygous leptin-deficient obese mice. Lean heterozygous leptin-deficient mice have serum leptin levels that are intermediate between lean control and leptin-deficient obese mice. We conclude, therefore, that serum leptin correlates with gallbladder response to neurotransmitters but not with cholesterol crystal formation.
301
cholesterol crystal formation under polarized light microscopy. Birefringent liquid and solid cholesterol monohydrate crystals were counted in ten high power fields. Crystal observation time (COT) in days, crystal growth rate (slope), and crystal mass (total number) were determined. Data were compared using the Mann-Whitney Rank Sum Test. Results: Liquid crystal results are presented in the table. Solid cholesterol crystals formed only in the lean control animals with a COT of 15.3 6.7, a slope of 1.8 1.5, and a crystal mass of 395 273 (p 0.03 for COT, slope, and mass vs leptin-resistant mice). Conclusions: These data suggest that leptin-resistant obese mice have delayed cholesterol crystal observation time, decreased crystal growth rate, and diminished crystal mass. These observations are consistent with the lower biliary cholesterol levels observed in leptin-resistant obese mice. Therefore, we conclude that a defect in gallbladder motility, as opposed to cholesterol metabolism, is primarily responsible for increased gallstone formation in leptin-resistant obesity.
Liquid Crystals in Lean and Leptin-Resistant Mice Study group
COT (days)
Crystal growth (slope)
Crystal mass (number)
Lean control Leptin-resistant
7.7 1.2 15.2 1.7*
210.7 98.2 1.8 1.5*
3204 1635 16 10*
*p0.05 vs lean controls.
138
Cholesterol monohydrate crystal formation Strain
Pools
COT
Crystal growth
Lean control Lean heterozygous Obese homozygous
9 8 6
7.0 0.3 7.1 0.3 5.7 0.6*
0.9 0.1 1.0 0.1 3.2 0.2†
Crystal mass 37 1.7 39 1.3 137 6.0†
*p 0.05, †p 0.001 vs. Lean control and heterozygous.
137 Reduced Biliary Cholesterol Crystal Formation in LeptinResistant Obese Mice Shannon J Graewin, Deborah A Swartz-Basile, Khoi Q Tran, Carol L Svatek, James M Kiely, Keun-Ho Lee, Attila Nakeeb, Henry A Pitt, Medical College of Wisconsin, Milwaukee, WI Background: Obesity is a major risk factor for cholesterol gallstone formation, but the pathogenesis of this phenomenon remains unclear. Previous studies from this laboratory have demonstrated that both leptin-deficient and leptin-resistant obese mice have diminished gallbladder motility. Leptin-deficient obese mice also have enhanced cholesterol crystal formation in-vitro despite normal biliary cholesterol. However, the majority of obese humans are leptin-resistant. Our lab has recently demonstrated that leptin-resistant obese mice have low biliary cholesterol levels. Therefore, we tested the hypothesis that leptin-resistant obese mice would have reduced cholesterol crystal formation. Methods: Eight week old lean control (C57BL/6J, n96) and leptin-resistant (Lep Db, n59) female mice were fed a non-lithogenic chow diet for four weeks. All animals then underwent cholecystectomy, and bile was collected, pooled, filtered, and maintained in a water bath at 37° C for 17 days. Bile was observed daily for
Leptin-Resistant Obese Mice Have Paradoxically Low Biliary Cholesterol Saturation Khoi Q Tran, Deborah A Swartz-Basile, Attila Nakeeb, Carol L Svatek, Henry A Pitt, Medical College of Wisconsin, Milwaukee, WI Background: Human obesity is associated with leptin resistance, elevated serum glucose and lipids, hepatic steatosis and cholesterol gallstone formation. These gallstones are thought to result from hypersecretion of biliary cholesterol as well as biliary stasis. We have previously demonstrated that leptin-deficient C57BL/6J Lepob obese mice have abnormal biliary motility and are prone to cholesterol crystal formation despite normal biliary lipids. However, leptin-resistant C57BL/6J Lepdb obese mice, which are know to have elevated serum leptin, glucose and lipids as well as hepatic steatosis, should be a more appropriate model for human gallstone formation. Therefore, we tested the hypothesis that leptinresistant mice would have increased gallbladder volume and biliary cholesterol saturation. Methods: C57BL/6J lean control mice (n60) and leptin-resistant Lepdb obese female mice (n60) were fed a non-lithogenic chow diet for four weeks. At 12 weeks of age, the mice were fasted overnight and then underwent cholecystectomy. Gallbladder volumes (GBV) were measured, and the bile was pooled for measurement of total bile acids (TBA), phospholipids (PPL) and cholesterol (XOL). Cholesterol saturation index (CSI) was calculated. Serum leptin and cholesterol levels were determined. Hepatic fat vacuoles were counted per high-power field (hpf). Data were analyzed by the Mann-Whitney Rank Sum Test. Results: Fasting GB volume in lean controls and Lepdb obese mice was 14.1 0.6 vs 39.0 1.6 L, p0.05. Serum leptin in lean control and Lepdb obese mice was 3.3 1.0 vs 191.9 14.8 ng/mL, p0.05. For Gallbladder bile lipids, serum cholesterol and hepatic fat vacuoles see table. Conclusions: These data suggest that leptin-resistant Lepdb obese mice have 1) increased gallbladder volume and 2) decreased biliary cholesterol saturation despite elevated serum cholesterol and hepatic steatosis. We conclude that the link between obesity and gallstone formation does not require hypersecretion of biliary cholesterol.
Journal of Gastrointestinal Surgery
Abstracts
feeding group (Table 1). Tube-related complications occurred in 6 out of 98 patients, and all were gastrojejunal tubes. Early postoperative jejunal tube feeding in patients undergoing pancreaticoduodenectomy is associated with a significantly lower rate of TPN use, hospital readmissions, and late complications. These data support routine use of a bridled nasojejunal feeding tube and early enteral nutrition.
TPN Readmit Early complications Late complications
Enteral feed (n98)
No enteral feed(n82)
p value
6 (6%) 12 (12%) 51 (52%) 12 (12%)
22 (27%) 22 (27%) 51 (62%) 25 (31%)
0.0003 0.015 NS 0.003
134 Neoadjuvant Gemcitabine (Gemzar), Paclitaxel (Taxol) and Radiation may Downstage Locally Advanced Pancreas Cancer Facilitating Resection David A Iannitti, Natalie Coburn, William Cioffi, John Tomicic, Harold I Wanebo, Thomas DiPetrillo, Howard Safran, Brown Medical School, Providence, RI; Roger Williams Medical Center, Providence, RI Introduction: Surgical resection for pancreatic cancer is the most effective treatment for this disease. Only 15% of patients at the time of diagnosis are candidates for resection. Forty percent of cases present with locally advanced, non-metatstatic disease, traditionally, not amenable to pancreatic resection. Neoadjuvant chemoradiation to downstage locally advanced pancreatic cancer for resection is evolving. The 5FU based chemoradiation only rarely achieves an adequate response to allow for resection. The Brown University Oncology Group (BRUOG) has evaluated paclitaxel (Taxol)/radiation and Gemcitabine (Gemzar)/paclitaxel/radiation treatment in a series of trials for medical effectiveness. We retrospectively reviewed our data to determine if these neoadjuvant modalities can downstage locally advanced pancreatic cancer to be resected. Results: 42 patients who initially had locally advanced disease were treated on a phase II trial of Taxol 50 mg/m2/wk with 50.4 Gy radiation. A significant number were downstaged, however were not medically cleared for surgery. Ultimately, 14 underwent surgical exploration. Four patients were resected, one had fibrosis with negative biopsy, and 9 had unsuspected liver metastases. Of the patients who were resected, 3 had partial responses and one had stable disease following chemoradiation. One patient, who initially had SMA encasement, is disease free at 6 years follow up. Gemcitabine was subsequently added to paclitaxel/radiation treatment in a phase I trial. Twenty patients were enrolled in the trial and 10 were treated at the maximally tolerated dose (MTD): gemcitabine 75 mg/m2/wk, paclitaxel 40 mg/m2/wk, and 50.4 Gy radiation. Of the 10 patients treated at the MTD, four patients had downstaging of disease such that they underwent exploration for resection. Prior to neoadjuvant treatment, one had portal vein thrombosis, the second had portal vein invasion, the third had superior mesenteric artery (SMA) encasement, and the fourth had both inferior vena cava and SMA involvement. A pancreaticoduodenectomy was performed on 3 of 4 patients with negative margins. A fifth patient was treated off protocol after the study was completed. This patient had post-chemoradiation resection with negative margins. Conclusion: The role for neoadjuvant chemoradiation for locally advanced pancreatic cancer is evolving. The BRUOG studies show that neoad-
juvant paclitaxel based chemoradiation regimens can downstage some patients with locally advanced disease, making their tumors amenable to resection. Paclitaxel/gemcitabine/radiation appears to be more effective in downstaging pancreatic cancer than 5FU based chemoradiation. The ultimate impact on survival remains uncertain.
BILIARY Gallstones 135 Outcome of Laparoscopic Cholecystectomy for Presumed Biliary Pancreatitis Bipan Chand, R M Walsh, The Cleveland Clinic Foundation, University Heights, OH; The Cleveland Clinic Foundation, Cleveland, OH Anatomic and clinical data have long supported the concept of gallstone migration as one cause of acute pancreatitis. Calculi should be excluded since cholecystectomy is potentially a curative treatment for this cause of pancreatitis. Similarly, cholecystectomy may also represent definitive treatment for idiopathic pancreatitis presumptively due to microlithiasis. A retrospective review of patients who underwent laparoscopic cholecystectomy for known calculus or idiopathic pancreatitis was conducted to assess outcome. A cholecystectomy database was queried for patients operated for pancreatitis between July 1995 and June 2000. A total of 94 patients underwent cholecystectomy, 72 of which were operated on for documented calculi by transcutaneous ultrasound. Twenty-two patients underwent surgery for presumed idiopathic pancreatitis based on a negative ultrasound and history. Patients with known calculi included 42 women and 30 men with a mean age of 62 (range 21-80) years. Common duct calculi were documented in 16 patients (17%). Pre-operative ERCPs were performed in 31 patients (43%) and was diagnostic of common duct stones in 8 (27%). Intraoperative cholangiography was successful in 68 of 72 patients (94%), and common duct stones were found in 10 (15%). Conversion to open was done in three (4%). At a mean follow-up of 57 months, pancreatic complications occurred postoperatively in 4 patients (7%): two with acute recurrent pancreatitis, one acute pancreatitis due to pancreatic divisum, and one ampullary stenosis. Patients with idiopathic pancreatitis presumed to have microlithiasis included 11 women and 11 men with a mean age of 45 (range 34-75) years. Preoperative evaluation included crystal analysis in two patients, ERCP in 9 (41%), and MRCP in two (9%). Open cholecystectomy was required in two (9%). Unsuspected calculi were discovered by pathology in six (23%), including two patients with common duct stones at operative cholangiography. At a mean followup of 47 months, subsequent biliary pancreatic disease occurred in six (27%); four with chronic idiopathic pancreatitis, one each with acute pancreatitis due to pancreatic divisum and sphincter of Oddi dysfunction by abnormal manometry. In summary, laparoscopic cholecystectomy confers long-term success in preventing pancreatic complications when calculi are diagnosed preoperatively. Patients with presumed idiopathic pancreatitis should be investigated for ductal abnormality with non-invasive testing. Empiric cholecystectomy is advised for patients with idiopathic pancreatitis and a normal pancreatic duct to achieve high clinical success by removing unsuspected calculi.
136 Cholesterol Crystal Nucleation in Heterozygous LeptinDeficient Lean Mice Khoi Q Tran, Matthew I Goldblatt, Deborah A Swartz-Basile, Attila Nakeeb, Henry A Pitt, Medical College of Wisconsin, Milwaukee, WI
Vol. 7, No. 2 2003
Abstracts
Background: Cholesterol gallstones result from cholesterol supersaturation of bile, biliary stasis and crystal nucleation. Obesity is a known risk factor, but a complete understanding of this phenomenon is lacking. Leptin, a hormone produced by adipocytes, has been implicated in the pathogenesis of both obesity and gallstone formation. We have demonstrated that lean heterozygous leptin-deficient mice have an intermediate gallbladder response to neurotransmitters and cholesterol saturation similar to both lean control and obese leptin-deficient mice. However, cholesterol crystal formation in heterozygous leptin-deficient mice has not been studied. Therefore, we hypothesized that bile from heterozygous mice would form cholesterol crystals at an intermediate rate between lean control and homozygous leptin-deficient obese mice. Methods: Seventy-five lean control (C57BL/6J), 54 lean heterozygous (C57BL/6J Lephet) and 36 obese (C57BL/6J Lepob) female mice underwent cholecystectomy at 12 weeks of age. Bile was collected, pooled, filtered and incubated at 37° C. Cholesterol monohydrate crystal formation was observed daily under polarized light microscopy for 17 days. Crystal observation time (COT) in days, crystal growth (slope) and crystal mass (total number) were measured and analyzed with the MannWhitney Rank Sum Test. Results: Crystal formation data are presented in the table. Conclusions: Lean heterozygous leptin deficient mice have crystal observation time, growth and mass similar to lean controls rather than homozygous leptin-deficient obese mice. Lean heterozygous leptin-deficient mice have serum leptin levels that are intermediate between lean control and leptin-deficient obese mice. We conclude, therefore, that serum leptin correlates with gallbladder response to neurotransmitters but not with cholesterol crystal formation.
301
cholesterol crystal formation under polarized light microscopy. Birefringent liquid and solid cholesterol monohydrate crystals were counted in ten high power fields. Crystal observation time (COT) in days, crystal growth rate (slope), and crystal mass (total number) were determined. Data were compared using the Mann-Whitney Rank Sum Test. Results: Liquid crystal results are presented in the table. Solid cholesterol crystals formed only in the lean control animals with a COT of 15.3 6.7, a slope of 1.8 1.5, and a crystal mass of 395 273 (p 0.03 for COT, slope, and mass vs leptin-resistant mice). Conclusions: These data suggest that leptin-resistant obese mice have delayed cholesterol crystal observation time, decreased crystal growth rate, and diminished crystal mass. These observations are consistent with the lower biliary cholesterol levels observed in leptin-resistant obese mice. Therefore, we conclude that a defect in gallbladder motility, as opposed to cholesterol metabolism, is primarily responsible for increased gallstone formation in leptin-resistant obesity.
Liquid Crystals in Lean and Leptin-Resistant Mice Study group
COT (days)
Crystal growth (slope)
Crystal mass (number)
Lean control Leptin-resistant
7.7 1.2 15.2 1.7*
210.7 98.2 1.8 1.5*
3204 1635 16 10*
*p0.05 vs lean controls.
138
Cholesterol monohydrate crystal formation Strain
Pools
COT
Crystal growth
Lean control Lean heterozygous Obese homozygous
9 8 6
7.0 0.3 7.1 0.3 5.7 0.6*
0.9 0.1 1.0 0.1 3.2 0.2†
Crystal mass 37 1.7 39 1.3 137 6.0†
*p 0.05, †p 0.001 vs. Lean control and heterozygous.
137 Reduced Biliary Cholesterol Crystal Formation in LeptinResistant Obese Mice Shannon J Graewin, Deborah A Swartz-Basile, Khoi Q Tran, Carol L Svatek, James M Kiely, Keun-Ho Lee, Attila Nakeeb, Henry A Pitt, Medical College of Wisconsin, Milwaukee, WI Background: Obesity is a major risk factor for cholesterol gallstone formation, but the pathogenesis of this phenomenon remains unclear. Previous studies from this laboratory have demonstrated that both leptin-deficient and leptin-resistant obese mice have diminished gallbladder motility. Leptin-deficient obese mice also have enhanced cholesterol crystal formation in-vitro despite normal biliary cholesterol. However, the majority of obese humans are leptin-resistant. Our lab has recently demonstrated that leptin-resistant obese mice have low biliary cholesterol levels. Therefore, we tested the hypothesis that leptin-resistant obese mice would have reduced cholesterol crystal formation. Methods: Eight week old lean control (C57BL/6J, n96) and leptin-resistant (Lep Db, n59) female mice were fed a non-lithogenic chow diet for four weeks. All animals then underwent cholecystectomy, and bile was collected, pooled, filtered, and maintained in a water bath at 37° C for 17 days. Bile was observed daily for
Leptin-Resistant Obese Mice Have Paradoxically Low Biliary Cholesterol Saturation Khoi Q Tran, Deborah A Swartz-Basile, Attila Nakeeb, Carol L Svatek, Henry A Pitt, Medical College of Wisconsin, Milwaukee, WI Background: Human obesity is associated with leptin resistance, elevated serum glucose and lipids, hepatic steatosis and cholesterol gallstone formation. These gallstones are thought to result from hypersecretion of biliary cholesterol as well as biliary stasis. We have previously demonstrated that leptin-deficient C57BL/6J Lepob obese mice have abnormal biliary motility and are prone to cholesterol crystal formation despite normal biliary lipids. However, leptin-resistant C57BL/6J Lepdb obese mice, which are know to have elevated serum leptin, glucose and lipids as well as hepatic steatosis, should be a more appropriate model for human gallstone formation. Therefore, we tested the hypothesis that leptinresistant mice would have increased gallbladder volume and biliary cholesterol saturation. Methods: C57BL/6J lean control mice (n60) and leptin-resistant Lepdb obese female mice (n60) were fed a non-lithogenic chow diet for four weeks. At 12 weeks of age, the mice were fasted overnight and then underwent cholecystectomy. Gallbladder volumes (GBV) were measured, and the bile was pooled for measurement of total bile acids (TBA), phospholipids (PPL) and cholesterol (XOL). Cholesterol saturation index (CSI) was calculated. Serum leptin and cholesterol levels were determined. Hepatic fat vacuoles were counted per high-power field (hpf). Data were analyzed by the Mann-Whitney Rank Sum Test. Results: Fasting GB volume in lean controls and Lepdb obese mice was 14.1 0.6 vs 39.0 1.6 L, p0.05. Serum leptin in lean control and Lepdb obese mice was 3.3 1.0 vs 191.9 14.8 ng/mL, p0.05. For Gallbladder bile lipids, serum cholesterol and hepatic fat vacuoles see table. Conclusions: These data suggest that leptin-resistant Lepdb obese mice have 1) increased gallbladder volume and 2) decreased biliary cholesterol saturation despite elevated serum cholesterol and hepatic steatosis. We conclude that the link between obesity and gallstone formation does not require hypersecretion of biliary cholesterol.