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Postprandial refilling and turnover of bile: Role in pathogenesis of gallstone recurrence
April 1995
P o s t p r a n d i a l Refilling A n d T u r n o v e r O f Bile: Role I n P a t h o g e n e s i s O f G a l l s t o n e R e c u r r e n c e RP Jazrawi. P Pazzi, ML Petroni, TC Northfield Dept. of Medicine, St. George's Hospital Medical School London UK. Impaired gallbladder (GB) motility is implicated in gallstone disease. We have used simultaneous measurements by ultrasound and scintigraphy to determine new parameters of gallbladder motor function like postprandial refilling and turnover index which were both markedly impaired in gallstone patients (1). Our aim was to assess these parameters in patients with and without gallstone recurrence following complete dissolution by bile acids. We studied 22 gallstone patients, 11 with (R) and 11 without (NR) recurrence at least 24 months after stopping treatment, and 11 healthy controls (C), GB counts for 99mTcHIDA and GB volumes were measured fasting and postprandially at 10 rain intervals for 90 min. We calculated % postprandial refilling, turnover of bile and turnover index. Patients with recurrence (R, 28+4 mls) had a markedly larger fasting GB volume than NR (19+3) and C (16:t:1). They also had reduced GB emptying (p< 0.05) by scintigraphy (at 30-90 min) but not by ultrasound, reduced postprandial refilling (7090 rain) and reduced turnover (50-90 rain). All these differences were more marked by comparison with healthy controls. The NR group had less marked differences compared to C. One NR patient with very low turnover at the time of study developed recurrence 6 months later. We conclude that gallbladder motility abnormalities persist after gallstone dissolution and that they play an important role in the pathogenesis of gallstone recurrence. (1) Gastroenterology 1994; 106: A 341.
@CANCER RISK AND RELATIVE SURVIVAL FOLLOWING SPHINCTERECTOMY FOR STONES IN THE COMMON BILE DUCTS - A POPI~TION-BASED COHOR'I STUDY. B.M. Kar!son,1'2 A. Ekbon~z3 D. Arvidsson) Depts. of SurgeryI and Cancer Epidemiology2, University Hospital, Uppsala, Sweden; Dept. of Epidemiology3, Harvard School of Public Health, Boston, MA, USA Endoscopic sphincterectomy of the sphincter Oddi in order to remove stones in the common bile duct was introduced in 1977 in Sweden. This procedure was initially confined mainly to older patients due to concerns that the absence of a functional sphincter would lead to a long-term increased risk for primary liver cancer, cancer of the bile ducts, and pancreatic cancer as well as severe cholangitis. Since the introduction of laparascopic cholecystectomy in the beginning of the 1990'ies this procedure has been more common and used in all age-groups. However, very little is known aboui the long-term effects after sphincterectomy. The aim of this study was therefore to analyse the long-term effects with regards to the risk of cancer and relative survival in a population-based cohort of patients subjected to sphincterectomy due to stones in the common bile duct with sufficient follow-up time. Methods: We identified all 992 patients subjected to endoscopic sphincterectomy due to stones in the common bile duct between 1977-1985 in six hospitals in central Sweden. The mean age at the procedure was 70.4 years with an even sex distribution. The patients were followed up through 1992 through linkage with the Swedish Death Registry and through 1991 through linkage to the Swedish Cancer Registry. The median follow-up time was I 1 and 10 years respectively. Results: During the first two years after sphincterectomy there was a high incidence of both cancers of the bile ducts and the pancreas, probably due to overlooked cancers at the time of the sphincterectomy. Five years or more after the sphincterectomy there were only 3 cancers diagnosed in the pancreas, the bile ducts, and the liver combined. The expected number of cancers in those sites were derived from the background population and was very close to that observed, 3.04, (standardized incidence ratio/SIR/= 0.99, 95% confidence interval/CI/0~2-2.9). Analysis of relative survival showed a slightlydecreased survivalthe first year after sphincterectomy but thereafier the survival did not differ from that of the normal population. Conclusion: Endoscopic sphincterect0my for stones in the common bile duct does not seem to affect the risk of cancer the pancreas, liver or common bile ducts and do not affect the long-time survival.
Biliary Disorders
A419
• LONG-TERM OUTCOME OF ENDOSCOPIC SPHINCTEROTOMY 1N PATIENTS WITH GROUP I1 SPHINCTER OF ODDI DYSFUNCTION. R.M. Kaikaus, L. Jacob, J.E. Geenen, M.F. Catalano, M.J. Schmalz, G.K. Johnson, D.J Geenen, W. J. Hogan. St. Luke's Hospital, Racine, and St. Luke's Medical Center, Milwaukee, WI. Endoscopic sphincterotomy (ES) has been described as an effective treatment of patients with Group I1 sphincter of Oddi dysfunction (SOD), i.e. those with severe abdominal pain, and one or two of the following features: i. common bile duct (CBD) diameter >12 mm; ik delayed (> 45 min) emptying of the CBD during ERCP; and iii. elevated (> 2x normal) liver enzymes. However, the patients' long-term outcome following this treatment is not known. We report here the 12-year follow-up of a group of 47 patients first described in 1989 (Geenen et al., N Engl J Med, 320: 82). METHODS: All patients were interviewed over the telephone, and the same questionnaire was used as in the original study. Details of repeat ERCP, operations, and subsequent illnesses were obtained. Symptoms (upper abdominal pain suggestive of SOD) were graded on an analog scale of 0-10, (6-10: poor; 3-5 fair; and <2 good). Of the 47 patients in the initial study, 23 had elevated SO pressures and 24 had normal pressures. Both groups had been randomiy assigned to ES or sham ES. Of the high pressure group, 11 had undergone ES, and 12 received sham treatment only. Similarly, 12 patients in the normal pressure group had undergone ES and 12 had sham ES. Seven of the 12 patients with elevated SO pressures who had undergone sham ES were subsequently crossed over to receive ES. RESULTS: Of the original study patients, 22 were successfully contacted. Two patients had died, one of congestive heart failure, and another of carcinoma of the pancreas (occurring eight years after entry into the study)~ Seven of the 11 patients with elevated SO pressures who had undergone ES could be contacted. Of these, four still reported good results, while two had fair, and one reported a poor response. Six of the seven cross-over patients were contacted; of these, four reported continuing good response, while one each reported fair and poor results. Of the five remaining control patients with elevated SO pressures, only one could be contacted, and was symptom free. In the normal SO pressure group, eight of the 24 patients could be contacted. In the ES group, one patient continued to rate his response good, while one each had symptom scores of fair and poor. Of the four patients who were in the control group, three are symptom-free, while one still has significant pain. CONCLUSIONS: Patients with Group 11 SOD with elevated basal SO pressures who had ES continue to report long-term improvement. The course of untreated patients, and of those with normal SO pressures, appears more varied, possibly because of the small number of patients who could still be contacted.
EFFECT OF FENTANYL ON CANINE SPHINCTER OF ODDI TONE. M.N. Katz, C.E. Sievert, B.K. Abeyta, S.E. $ilvis, J. A. Vennes. Divisions of Oasw~nntcrology, University of Minnesota and VA Medical Center, Minneapolis, Minnesota. The appropriate choice of sedative agents for clinical manometric assessment of sphincter of Oddi tone remains conlroversial, because of concerns regarding their effects on smooth muscle. To investigate possible effects of a commonly used synthetic narcotic, fentanyl, on biliary rnanomelry, we utilized an in vlvo canine duodenostomy.p~..,tion which
pmv/des access to the sphincter of Oddi under direct visualization in the awake animal. A standard 3 channel Arndorfer bili~/manomeu'y catheter was used to cannulate the sphincter of Oddi and obtain manometric tracings, Doses of fentanyl administered were selected to approximate clinically relevant concenmltions in humans (range: 1.98-3.30 nwg/kg). Nine dogs were used i n this study, with multiple manometric measurements performed in each dog. Results: Fontanyl consistently elicited a dramatic "re[~ularization"of the biliary manome~x tracing within 30 seconds of bolus mtravenons adminislration. This phenomenon was characterized by marked uniformity of the tracing: high amplitude waves occurring with a frequency between 17-19 per minute. Despite the regularization of the tracin~g, no significant change was observed in baseline tone, as compared wgh pre-fentanyl measurements. This fentanyl effect is conu'asted with the effect of morphine administration in this model, which results in a low amplitude, slower frequency (10 waves/rain.) manometric pattern, with rise in baseline tone in several subjects. This fentanyl response was inhibited by pre-treatmnnt with naloxone,suggesting that changes induced by fentanyl may be mediated via opiate receptor-linked pathways.
Conclusions: Therapeutic fentanyl administration does not affect baseline sphincterof Oddi tone in the dog, although "regularizadon"of the manometric pattern is observed. Given current clinicaldefinitions for sphincterof Oddi dysfunction/biliarydyskinesia, fentanyl may prove a useful agent in conscious sedation during biliarymanometry by facilitating easier and readier assessment without affecting basal tone. Further studies are needed to elucidate the mechanism of the fentsnyl regularization effect and to characterize the manometric effects of other potentially useful sedative agents.
P o s t p r a n d i a l Refilling A n d T u r n o v e r O f Bile: Role I n P a t h o g e n e s i s O f G a l l s t o n e R e c u r r e n c e RP Jazrawi. P Pazzi, ML Petroni, TC Northfield Dept. of Medicine, St. George's Hospital Medical School London UK. Impaired gallbladder (GB) motility is implicated in gallstone disease. We have used simultaneous measurements by ultrasound and scintigraphy to determine new parameters of gallbladder motor function like postprandial refilling and turnover index which were both markedly impaired in gallstone patients (1). Our aim was to assess these parameters in patients with and without gallstone recurrence following complete dissolution by bile acids. We studied 22 gallstone patients, 11 with (R) and 11 without (NR) recurrence at least 24 months after stopping treatment, and 11 healthy controls (C), GB counts for 99mTcHIDA and GB volumes were measured fasting and postprandially at 10 rain intervals for 90 min. We calculated % postprandial refilling, turnover of bile and turnover index. Patients with recurrence (R, 28+4 mls) had a markedly larger fasting GB volume than NR (19+3) and C (16:t:1). They also had reduced GB emptying (p< 0.05) by scintigraphy (at 30-90 min) but not by ultrasound, reduced postprandial refilling (7090 rain) and reduced turnover (50-90 rain). All these differences were more marked by comparison with healthy controls. The NR group had less marked differences compared to C. One NR patient with very low turnover at the time of study developed recurrence 6 months later. We conclude that gallbladder motility abnormalities persist after gallstone dissolution and that they play an important role in the pathogenesis of gallstone recurrence. (1) Gastroenterology 1994; 106: A 341.
@CANCER RISK AND RELATIVE SURVIVAL FOLLOWING SPHINCTERECTOMY FOR STONES IN THE COMMON BILE DUCTS - A POPI~TION-BASED COHOR'I STUDY. B.M. Kar!son,1'2 A. Ekbon~z3 D. Arvidsson) Depts. of SurgeryI and Cancer Epidemiology2, University Hospital, Uppsala, Sweden; Dept. of Epidemiology3, Harvard School of Public Health, Boston, MA, USA Endoscopic sphincterectomy of the sphincter Oddi in order to remove stones in the common bile duct was introduced in 1977 in Sweden. This procedure was initially confined mainly to older patients due to concerns that the absence of a functional sphincter would lead to a long-term increased risk for primary liver cancer, cancer of the bile ducts, and pancreatic cancer as well as severe cholangitis. Since the introduction of laparascopic cholecystectomy in the beginning of the 1990'ies this procedure has been more common and used in all age-groups. However, very little is known aboui the long-term effects after sphincterectomy. The aim of this study was therefore to analyse the long-term effects with regards to the risk of cancer and relative survival in a population-based cohort of patients subjected to sphincterectomy due to stones in the common bile duct with sufficient follow-up time. Methods: We identified all 992 patients subjected to endoscopic sphincterectomy due to stones in the common bile duct between 1977-1985 in six hospitals in central Sweden. The mean age at the procedure was 70.4 years with an even sex distribution. The patients were followed up through 1992 through linkage with the Swedish Death Registry and through 1991 through linkage to the Swedish Cancer Registry. The median follow-up time was I 1 and 10 years respectively. Results: During the first two years after sphincterectomy there was a high incidence of both cancers of the bile ducts and the pancreas, probably due to overlooked cancers at the time of the sphincterectomy. Five years or more after the sphincterectomy there were only 3 cancers diagnosed in the pancreas, the bile ducts, and the liver combined. The expected number of cancers in those sites were derived from the background population and was very close to that observed, 3.04, (standardized incidence ratio/SIR/= 0.99, 95% confidence interval/CI/0~2-2.9). Analysis of relative survival showed a slightlydecreased survivalthe first year after sphincterectomy but thereafier the survival did not differ from that of the normal population. Conclusion: Endoscopic sphincterect0my for stones in the common bile duct does not seem to affect the risk of cancer the pancreas, liver or common bile ducts and do not affect the long-time survival.
Biliary Disorders
A419
• LONG-TERM OUTCOME OF ENDOSCOPIC SPHINCTEROTOMY 1N PATIENTS WITH GROUP I1 SPHINCTER OF ODDI DYSFUNCTION. R.M. Kaikaus, L. Jacob, J.E. Geenen, M.F. Catalano, M.J. Schmalz, G.K. Johnson, D.J Geenen, W. J. Hogan. St. Luke's Hospital, Racine, and St. Luke's Medical Center, Milwaukee, WI. Endoscopic sphincterotomy (ES) has been described as an effective treatment of patients with Group I1 sphincter of Oddi dysfunction (SOD), i.e. those with severe abdominal pain, and one or two of the following features: i. common bile duct (CBD) diameter >12 mm; ik delayed (> 45 min) emptying of the CBD during ERCP; and iii. elevated (> 2x normal) liver enzymes. However, the patients' long-term outcome following this treatment is not known. We report here the 12-year follow-up of a group of 47 patients first described in 1989 (Geenen et al., N Engl J Med, 320: 82). METHODS: All patients were interviewed over the telephone, and the same questionnaire was used as in the original study. Details of repeat ERCP, operations, and subsequent illnesses were obtained. Symptoms (upper abdominal pain suggestive of SOD) were graded on an analog scale of 0-10, (6-10: poor; 3-5 fair; and <2 good). Of the 47 patients in the initial study, 23 had elevated SO pressures and 24 had normal pressures. Both groups had been randomiy assigned to ES or sham ES. Of the high pressure group, 11 had undergone ES, and 12 received sham treatment only. Similarly, 12 patients in the normal pressure group had undergone ES and 12 had sham ES. Seven of the 12 patients with elevated SO pressures who had undergone sham ES were subsequently crossed over to receive ES. RESULTS: Of the original study patients, 22 were successfully contacted. Two patients had died, one of congestive heart failure, and another of carcinoma of the pancreas (occurring eight years after entry into the study)~ Seven of the 11 patients with elevated SO pressures who had undergone ES could be contacted. Of these, four still reported good results, while two had fair, and one reported a poor response. Six of the seven cross-over patients were contacted; of these, four reported continuing good response, while one each reported fair and poor results. Of the five remaining control patients with elevated SO pressures, only one could be contacted, and was symptom free. In the normal SO pressure group, eight of the 24 patients could be contacted. In the ES group, one patient continued to rate his response good, while one each had symptom scores of fair and poor. Of the four patients who were in the control group, three are symptom-free, while one still has significant pain. CONCLUSIONS: Patients with Group 11 SOD with elevated basal SO pressures who had ES continue to report long-term improvement. The course of untreated patients, and of those with normal SO pressures, appears more varied, possibly because of the small number of patients who could still be contacted.
EFFECT OF FENTANYL ON CANINE SPHINCTER OF ODDI TONE. M.N. Katz, C.E. Sievert, B.K. Abeyta, S.E. $ilvis, J. A. Vennes. Divisions of Oasw~nntcrology, University of Minnesota and VA Medical Center, Minneapolis, Minnesota. The appropriate choice of sedative agents for clinical manometric assessment of sphincter of Oddi tone remains conlroversial, because of concerns regarding their effects on smooth muscle. To investigate possible effects of a commonly used synthetic narcotic, fentanyl, on biliary rnanomelry, we utilized an in vlvo canine duodenostomy.p~..,tion which
pmv/des access to the sphincter of Oddi under direct visualization in the awake animal. A standard 3 channel Arndorfer bili~/manomeu'y catheter was used to cannulate the sphincter of Oddi and obtain manometric tracings, Doses of fentanyl administered were selected to approximate clinically relevant concenmltions in humans (range: 1.98-3.30 nwg/kg). Nine dogs were used i n this study, with multiple manometric measurements performed in each dog. Results: Fontanyl consistently elicited a dramatic "re[~ularization"of the biliary manome~x tracing within 30 seconds of bolus mtravenons adminislration. This phenomenon was characterized by marked uniformity of the tracing: high amplitude waves occurring with a frequency between 17-19 per minute. Despite the regularization of the tracin~g, no significant change was observed in baseline tone, as compared wgh pre-fentanyl measurements. This fentanyl effect is conu'asted with the effect of morphine administration in this model, which results in a low amplitude, slower frequency (10 waves/rain.) manometric pattern, with rise in baseline tone in several subjects. This fentanyl response was inhibited by pre-treatmnnt with naloxone,suggesting that changes induced by fentanyl may be mediated via opiate receptor-linked pathways.
Conclusions: Therapeutic fentanyl administration does not affect baseline sphincterof Oddi tone in the dog, although "regularizadon"of the manometric pattern is observed. Given current clinicaldefinitions for sphincterof Oddi dysfunction/biliarydyskinesia, fentanyl may prove a useful agent in conscious sedation during biliarymanometry by facilitating easier and readier assessment without affecting basal tone. Further studies are needed to elucidate the mechanism of the fentsnyl regularization effect and to characterize the manometric effects of other potentially useful sedative agents.