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Sphincter of Oddi manometry before and after cholecystectomy
A548 AGA ABSTRACTS
• G2240 EFFECT OF L-ARGININE ON GALLBLADDER MOTILITY. A.S. van Petersen, H.A.J. Gielkens, J. Ringers, C.B.H.W. Lamers, A.A.M. Masclee. Dept. of Gastroenterology-Hepatology and Surgery, Leiden University Medical Center, The Netherlands. Nitric oxide (NO) derived from L-arginine by the enzyme nitric oxide synthase, exerts a myo-re!axive action on the gastrointestinal smooth muscle ceils. The NO-donor L-arginine, administered intravenously, induces relaxation of the fundus and delays gastric emptying. Little is known, however, on the effects of L-arginine and NO on gallbladder motility in man. Therefore, we have performed a placebo controlled study on the effect of L-arginine on gallbladder motility. Eight healthy volunteers (6 F, 2 M; age 25 _+4 yr) were investigated on 2 separate occasions after an overnight fast in random order during intravenous infusion of 1) L-arginine bolus + continuous infusion, 200 mg/kg/h in 270 min or 2) saline (control) for 270 min. Gallbladder motility was measured by ultrasonography. The effect of L-arginine on gallbladder motility was studied under basal conditions for 60 min, after neural cephalic-vagal stimulation with modified sham feeding (MSF) for 90 min, in response to hormonal stimulation with CCK (0.5 IDU*kg-loh -1) for 60 min and post CCK infusion (relaxation) for 60 min. Results: Fasting gallbladder volumes were not significantly different between the two experiments (18_+2 vs 17_+2cm3). During L-arginine basal gallbladder volume increased significantly (p<0.01) from 100% to 115 ± 5% (saline 100% to 95 _+4% n.s.). Gallbladder emptying in response to MSF was significantly (p<0.05) reduced during L-arginine (14 :t: 5% vs 25 _+6%). The gallbladder contraction in response to CCK was not different between L-arginine (80 _+4%) and saline (79 _+3%). One hour after the end of CCK infusion gallbladder relaxation was almost complete: 97 _+ 16% and 83 _+ 10% of original fasting volume (saline vs L-arginine). Plasma CCK did not increase during MSF; during CCK infusion plasma CCK levels increased significantly but were not different between the two experiments. Conclusions: The NO-donor L-arginine causes relaxation of the fasting gallbladder, impairs cephalic-stimulated gallbladder contraction but does not influence CCK stimulated gallbladder contraction. G2241 IS ENDOSCOPIC THERAPY A RATIONAL OPTION FOR TREATMENT OF C A R O L r S SYNDROME? W. Veltzke, A. Adler, H. Abou-Rebyeh, P. Neuhaus, R.E. Hintze. Central Interdisciplinary Endoscopy, Gastroenterology, Surgery, Charit6 Virchow-Klinikum, Humboldt-University of Berlin, Germany. Introduction: Inbom disorders of the biliary tract comprise biliary cysts leading to subsequent complications which are known as Caroli's syndrome. Large Caroli cysts give rise to development of many calculi which increase and lead to cholestasis and cholangitis. Due to regionary cholangitis and relapsing formation of calculi those patients frequently require endoscopic therapy and are exposed to a risk of 5% incidence to develop a cholangiocarcinoma. Methods: From November 1995 to November 1997 we treated endoscopically 11 patients with Caroli's syndrome (n---4 female, n=7 male, mean age: 39 years, range from 18 to 75 years). Endoscopic therapy was performed in all patients performing sphincterotomy and subsequent basket extraction of calculi. In addition, 1 patient required stenting of the CBD due to a benign stenosis and 4 patients received ESWL for fragmentation of intrahepatic calculi. Results: All biliary calculi were removed from 4 patients using ESWL as well as basket extraction, In spite of prophylaxis with ursodeoxycholic acid all patients had a relaps of concrement formation. 8 out of 11 (73%) patients received a combined therapy to remove all calculi. Initially, the less altered right or left hepatic duct system was endoscopically cleared from all calculi. This procedure required 5 endoscopic interventions per patient in average. Thereafter, hemihepatectomy of the other liver side was performed. Combined therapy successfully prevented these patients with Caroli's syndrome from relapsing complications. Another patient required surgical reconstruction of the hepatic confluence. A further patient sufferend from incurable destruction of both liver sides thus receiving liver transplantation. One patient with major destruction of the CBD while having a good liver function got a side-to-side choledocho-bulbostomy which facilitated endoscopic access to the bile duct system. Discussion: The importance of endoscopy consists of diagnosing Caroli's syndrome, to treat obstructive cholestasis leading to acute cholangitis by stone removal and to prepare the bile duct system for surgical reconstruction. Most patients with Caroli's syndrome can not be managed 0nly by endoscopy and need surgery at an appropriate time. Endoscopists should initially make up a therapeutical plan to prepare the bile duct system of affected patients for surgery. G2242 SPHINCTER OF ODDI MANOMETRY BEFORE AND AFTER CHOLECYSTECTOMY. H. Vester~,aard Middelfart, P. Matzen, L. Toft Jensen, P. Funch-Jensen. Departments of Medical and Surgical Gastroenterology Hvidovre Hospital, University of Copenhagen. DK-2650 Hvidovre, Denmark. A neuronal reflex exists between the gallbladder and the sphincter of Oddi (SO)r Disruption of this nerve pathway by cholecystectomy may influence SO-motility and the normal inhibitory response of cholecystokinin (CCK).
GASTROENTEROLOGY Vol. 114, No. 4 Aim - To investigate the effect of CCK on SO-motility before and after cholecystectomy. Methods- Eight women (median age 53 years, range 29-66 years) were investigated one day to 3 months before and 3-9 months after laparoscopic cholecystectomy which was undertaken for uncomplicated gallbladder stone disease. SO-motility was measured under basal conditions and during CCK infusion (5 nanogram/kg/min for 5 minutes). Results - Prior to cholecystectomy phasic contractions were inhibited by intravenous CCK in seven patients. In one patient CCK failed to suppress SOmotility. At the postoperative control CCK suppressed the phasic activity in all patients. Conclusion - Cholecystectomy did not influence the normal inhibitory effect of CCK on SO-motility. (An operative denervation of pericholedochal nerves responsible for SO-motility seems unlikely.) [1] Thune A, Saccone OTP, Scieehitano JP, Toouli J. Distension of the gallbladder inhibits sphincter of Oddi motility in humans. Gut 1991 ;32:690-3. G2243 THE EFFECTS OF OCTREOTIDE ON THE KINETICS OF DEOXYCHOLIC AND CHOLIC ACID. MJ Veysey, A Mallet 1, P Jenkins2, GM Besser2, GM Murphy and RH Dowling. Gastroenterology Unit and Mass Spectrometry Laboratory l, UMDS of Guy's & St Thomas' Hospitals and the Dept of Endocrinology St Bartholomew's Hospital 2, London, UK Background/Methods: Prolonged large bowel transit and an associated increase in the proportion of deoxycholic acid (DCA) in bile have been implicated in the pathogenesis of the cholesterol gallstones which develop in acromegalic patients treated with octreotide (OT). However, there are few data on the kinetics of DCA or cholic acid (CA) - that is, (i) the input/synthesis rates, (ii) the pool sizes and (iii) the conversion of CA to DCA - or on the relationship between these parameters and large bowel transit time (LBTT). Therefore, we used stable isotopes (2H4-DCA and 13C-CA), serum sampling and GC-mass spectrometry to measure DCA and CA kinetics and a marker shape technique to measure LBTF, in 8 acromegalic patients untreated with OT and 8 acromegalic patients on long-term (>3 months) OT, 5 of whom were studied before and during treatment. Results: Although the mean LB'I~ was significantly longer in the OT-treated than in the untreated acromegalic patients (48-+ (SEM)4.6 vs 33 -+4.0h, p<0.05), there were no significant differences in the mean DCA and CA. input/synthesis rates or pool sizes. However, in the paired before and during OT studies, there were significant increases in the DCA input rate (6.4 ± 1.3 vs 13 -+ 1.3pmol/kg/d, p<0.05) and pool size (18 -+ 5.3 vs 46 ± 10~amol/kg, p<0.05) and a significant decrease in the CA synthesis rate (16 ± 2.3 vs 7.4 ± 1.5; p<0.05). Furthermore, the mean conversion of t3C-CA to 13C-DCA was significantly greater on days 2, 3 and 4 (16 ± 8.4 vs 48 _+ 111amol, p<0.01; 13±3.1 vs 54±11, p<0.05 and 8.4±3.1 vs 32_+7.2, p<0.05, respectively). There were also positive linear relationships between LBTT and both DCA input rate (r=0.69; p<0.001) and pool size (r=0.76; p<0.001) and weak, but significant, negative linear relationships between LB'IT and CA synthesis rate (r=-0.48, p<0.01) and pool size (r=-0.35, p<0.05). Conclusinn: These data further support the hypothesis that by increasing DCA formation and absorption, prolongation of LBTf is a pathogenetic factor in the formation of gallstones in acromegalic patients treated with OT. G2244 URSODEOXYCHOLIC ACID REDUCES LIPID PEROXIDATION AND MUCIN SECRETAGOGUE ACTIVITY OF HUMAN BILE IN CHOLESTEROL GALLSTONE DISEASE. Christonh yon Ritter, Nair Sreejayan, Iris Mtiller, Gtinther Meyer*, Dieter Jiingst, Department of Medicine II and Surgery*, Klinikum Grosshadern, Ludwig-MaximiliansUniversity, 81366 Munich, Germany Background and Aim: Hypersecretion of gallbladder mucins has been implicated in the pathogenesis of cholesterol gallstone disease (CGD). We have shown that lipid peroxidation as assessed by malondialdehyde (MDA) is increased in lithogenic bile and that lithogenic bile causes mucin hypersecretion. Ursodeoxycholic acid (UDCA), an agent used in the therapy of CGD markedly reduces the lithogenicity of bile. The mechanism of this effect of UDCA is ill-defined. The aim of this study was to test whether UDCA acts via decreasing biliary lipid peroxidation and/or mucin secretagogue activity of bile. Method: In a double-blind, randomized, placebo controlled trial, patients (n=19) with symptomatic CGD were treated with UDCA (750 mg/day) or placebo for ten days prior to cholecystectomy when gallbladder bile samples were collected. MDA levels in bile samples were determined by measuring the MDA-thiobarbituric acid adduct fluorimetrically following HPLC separation. Bile samples were incubated with 3[H]N-acetly-D-ghicosamine labeled confluent monolayer of cultured dog gallbladder epithelial cells. Mucin secretagogue activity was assessed by measuring the release of 3[H]-glucosamine into the medium. Results: The mean MDA concentration in bile of the placebo treated group was significantly higher than that of the UDCA treated group (2.05 _+0.28 vs. 1.36 _+0,23 pM; p < 0.05). Similarly, the average increase in mucin secretion induced by bile samples of the placebo group was markedly higher than that
• G2240 EFFECT OF L-ARGININE ON GALLBLADDER MOTILITY. A.S. van Petersen, H.A.J. Gielkens, J. Ringers, C.B.H.W. Lamers, A.A.M. Masclee. Dept. of Gastroenterology-Hepatology and Surgery, Leiden University Medical Center, The Netherlands. Nitric oxide (NO) derived from L-arginine by the enzyme nitric oxide synthase, exerts a myo-re!axive action on the gastrointestinal smooth muscle ceils. The NO-donor L-arginine, administered intravenously, induces relaxation of the fundus and delays gastric emptying. Little is known, however, on the effects of L-arginine and NO on gallbladder motility in man. Therefore, we have performed a placebo controlled study on the effect of L-arginine on gallbladder motility. Eight healthy volunteers (6 F, 2 M; age 25 _+4 yr) were investigated on 2 separate occasions after an overnight fast in random order during intravenous infusion of 1) L-arginine bolus + continuous infusion, 200 mg/kg/h in 270 min or 2) saline (control) for 270 min. Gallbladder motility was measured by ultrasonography. The effect of L-arginine on gallbladder motility was studied under basal conditions for 60 min, after neural cephalic-vagal stimulation with modified sham feeding (MSF) for 90 min, in response to hormonal stimulation with CCK (0.5 IDU*kg-loh -1) for 60 min and post CCK infusion (relaxation) for 60 min. Results: Fasting gallbladder volumes were not significantly different between the two experiments (18_+2 vs 17_+2cm3). During L-arginine basal gallbladder volume increased significantly (p<0.01) from 100% to 115 ± 5% (saline 100% to 95 _+4% n.s.). Gallbladder emptying in response to MSF was significantly (p<0.05) reduced during L-arginine (14 :t: 5% vs 25 _+6%). The gallbladder contraction in response to CCK was not different between L-arginine (80 _+4%) and saline (79 _+3%). One hour after the end of CCK infusion gallbladder relaxation was almost complete: 97 _+ 16% and 83 _+ 10% of original fasting volume (saline vs L-arginine). Plasma CCK did not increase during MSF; during CCK infusion plasma CCK levels increased significantly but were not different between the two experiments. Conclusions: The NO-donor L-arginine causes relaxation of the fasting gallbladder, impairs cephalic-stimulated gallbladder contraction but does not influence CCK stimulated gallbladder contraction. G2241 IS ENDOSCOPIC THERAPY A RATIONAL OPTION FOR TREATMENT OF C A R O L r S SYNDROME? W. Veltzke, A. Adler, H. Abou-Rebyeh, P. Neuhaus, R.E. Hintze. Central Interdisciplinary Endoscopy, Gastroenterology, Surgery, Charit6 Virchow-Klinikum, Humboldt-University of Berlin, Germany. Introduction: Inbom disorders of the biliary tract comprise biliary cysts leading to subsequent complications which are known as Caroli's syndrome. Large Caroli cysts give rise to development of many calculi which increase and lead to cholestasis and cholangitis. Due to regionary cholangitis and relapsing formation of calculi those patients frequently require endoscopic therapy and are exposed to a risk of 5% incidence to develop a cholangiocarcinoma. Methods: From November 1995 to November 1997 we treated endoscopically 11 patients with Caroli's syndrome (n---4 female, n=7 male, mean age: 39 years, range from 18 to 75 years). Endoscopic therapy was performed in all patients performing sphincterotomy and subsequent basket extraction of calculi. In addition, 1 patient required stenting of the CBD due to a benign stenosis and 4 patients received ESWL for fragmentation of intrahepatic calculi. Results: All biliary calculi were removed from 4 patients using ESWL as well as basket extraction, In spite of prophylaxis with ursodeoxycholic acid all patients had a relaps of concrement formation. 8 out of 11 (73%) patients received a combined therapy to remove all calculi. Initially, the less altered right or left hepatic duct system was endoscopically cleared from all calculi. This procedure required 5 endoscopic interventions per patient in average. Thereafter, hemihepatectomy of the other liver side was performed. Combined therapy successfully prevented these patients with Caroli's syndrome from relapsing complications. Another patient required surgical reconstruction of the hepatic confluence. A further patient sufferend from incurable destruction of both liver sides thus receiving liver transplantation. One patient with major destruction of the CBD while having a good liver function got a side-to-side choledocho-bulbostomy which facilitated endoscopic access to the bile duct system. Discussion: The importance of endoscopy consists of diagnosing Caroli's syndrome, to treat obstructive cholestasis leading to acute cholangitis by stone removal and to prepare the bile duct system for surgical reconstruction. Most patients with Caroli's syndrome can not be managed 0nly by endoscopy and need surgery at an appropriate time. Endoscopists should initially make up a therapeutical plan to prepare the bile duct system of affected patients for surgery. G2242 SPHINCTER OF ODDI MANOMETRY BEFORE AND AFTER CHOLECYSTECTOMY. H. Vester~,aard Middelfart, P. Matzen, L. Toft Jensen, P. Funch-Jensen. Departments of Medical and Surgical Gastroenterology Hvidovre Hospital, University of Copenhagen. DK-2650 Hvidovre, Denmark. A neuronal reflex exists between the gallbladder and the sphincter of Oddi (SO)r Disruption of this nerve pathway by cholecystectomy may influence SO-motility and the normal inhibitory response of cholecystokinin (CCK).
GASTROENTEROLOGY Vol. 114, No. 4 Aim - To investigate the effect of CCK on SO-motility before and after cholecystectomy. Methods- Eight women (median age 53 years, range 29-66 years) were investigated one day to 3 months before and 3-9 months after laparoscopic cholecystectomy which was undertaken for uncomplicated gallbladder stone disease. SO-motility was measured under basal conditions and during CCK infusion (5 nanogram/kg/min for 5 minutes). Results - Prior to cholecystectomy phasic contractions were inhibited by intravenous CCK in seven patients. In one patient CCK failed to suppress SOmotility. At the postoperative control CCK suppressed the phasic activity in all patients. Conclusion - Cholecystectomy did not influence the normal inhibitory effect of CCK on SO-motility. (An operative denervation of pericholedochal nerves responsible for SO-motility seems unlikely.) [1] Thune A, Saccone OTP, Scieehitano JP, Toouli J. Distension of the gallbladder inhibits sphincter of Oddi motility in humans. Gut 1991 ;32:690-3. G2243 THE EFFECTS OF OCTREOTIDE ON THE KINETICS OF DEOXYCHOLIC AND CHOLIC ACID. MJ Veysey, A Mallet 1, P Jenkins2, GM Besser2, GM Murphy and RH Dowling. Gastroenterology Unit and Mass Spectrometry Laboratory l, UMDS of Guy's & St Thomas' Hospitals and the Dept of Endocrinology St Bartholomew's Hospital 2, London, UK Background/Methods: Prolonged large bowel transit and an associated increase in the proportion of deoxycholic acid (DCA) in bile have been implicated in the pathogenesis of the cholesterol gallstones which develop in acromegalic patients treated with octreotide (OT). However, there are few data on the kinetics of DCA or cholic acid (CA) - that is, (i) the input/synthesis rates, (ii) the pool sizes and (iii) the conversion of CA to DCA - or on the relationship between these parameters and large bowel transit time (LBTT). Therefore, we used stable isotopes (2H4-DCA and 13C-CA), serum sampling and GC-mass spectrometry to measure DCA and CA kinetics and a marker shape technique to measure LBTF, in 8 acromegalic patients untreated with OT and 8 acromegalic patients on long-term (>3 months) OT, 5 of whom were studied before and during treatment. Results: Although the mean LB'I~ was significantly longer in the OT-treated than in the untreated acromegalic patients (48-+ (SEM)4.6 vs 33 -+4.0h, p<0.05), there were no significant differences in the mean DCA and CA. input/synthesis rates or pool sizes. However, in the paired before and during OT studies, there were significant increases in the DCA input rate (6.4 ± 1.3 vs 13 -+ 1.3pmol/kg/d, p<0.05) and pool size (18 -+ 5.3 vs 46 ± 10~amol/kg, p<0.05) and a significant decrease in the CA synthesis rate (16 ± 2.3 vs 7.4 ± 1.5; p<0.05). Furthermore, the mean conversion of t3C-CA to 13C-DCA was significantly greater on days 2, 3 and 4 (16 ± 8.4 vs 48 _+ 111amol, p<0.01; 13±3.1 vs 54±11, p<0.05 and 8.4±3.1 vs 32_+7.2, p<0.05, respectively). There were also positive linear relationships between LBTT and both DCA input rate (r=0.69; p<0.001) and pool size (r=0.76; p<0.001) and weak, but significant, negative linear relationships between LB'IT and CA synthesis rate (r=-0.48, p<0.01) and pool size (r=-0.35, p<0.05). Conclusinn: These data further support the hypothesis that by increasing DCA formation and absorption, prolongation of LBTf is a pathogenetic factor in the formation of gallstones in acromegalic patients treated with OT. G2244 URSODEOXYCHOLIC ACID REDUCES LIPID PEROXIDATION AND MUCIN SECRETAGOGUE ACTIVITY OF HUMAN BILE IN CHOLESTEROL GALLSTONE DISEASE. Christonh yon Ritter, Nair Sreejayan, Iris Mtiller, Gtinther Meyer*, Dieter Jiingst, Department of Medicine II and Surgery*, Klinikum Grosshadern, Ludwig-MaximiliansUniversity, 81366 Munich, Germany Background and Aim: Hypersecretion of gallbladder mucins has been implicated in the pathogenesis of cholesterol gallstone disease (CGD). We have shown that lipid peroxidation as assessed by malondialdehyde (MDA) is increased in lithogenic bile and that lithogenic bile causes mucin hypersecretion. Ursodeoxycholic acid (UDCA), an agent used in the therapy of CGD markedly reduces the lithogenicity of bile. The mechanism of this effect of UDCA is ill-defined. The aim of this study was to test whether UDCA acts via decreasing biliary lipid peroxidation and/or mucin secretagogue activity of bile. Method: In a double-blind, randomized, placebo controlled trial, patients (n=19) with symptomatic CGD were treated with UDCA (750 mg/day) or placebo for ten days prior to cholecystectomy when gallbladder bile samples were collected. MDA levels in bile samples were determined by measuring the MDA-thiobarbituric acid adduct fluorimetrically following HPLC separation. Bile samples were incubated with 3[H]N-acetly-D-ghicosamine labeled confluent monolayer of cultured dog gallbladder epithelial cells. Mucin secretagogue activity was assessed by measuring the release of 3[H]-glucosamine into the medium. Results: The mean MDA concentration in bile of the placebo treated group was significantly higher than that of the UDCA treated group (2.05 _+0.28 vs. 1.36 _+0,23 pM; p < 0.05). Similarly, the average increase in mucin secretion induced by bile samples of the placebo group was markedly higher than that