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Physical Activity and Reduced Risk of Symptomatic Gallstones - a ProspectiveCohort StudyPaul R. Banim, Kay-Tee Khaw, Nick Wareham, Sheila Bingham, Robert Luben, AndrewHart

Background. Physical activity may protect against gallstone formation by reducing bile stasisand plasma triglycerides and by raising HDL levels. No prospective studies have previouslyinvestigated this hypothesis in both genders using a physical activity questionnaire validatedagainst physiological measurements. The aim of this study was to investigate this relationshipusing a questionnaire to provide a simple global index of physical activity and to determineif physical activity predicts disease independently of known risk factors for gallstones.Methods. A total of 25 639 men and women, aged 45-74, years were recruited into EPIC-Norfolk (European Prospective Investigation into Cancer) and completed a questionnairewhich recorded both occupational and recreational physical activity. Participants were thenranked into four groups of physical activity, ranging from active to inactive. This questionnairehad been validated against both energy expenditure, as assessed by 4-day heart rate mon-itoring, and cardio-respiratory fitness, assessed by sub-maximal oxygen uptake. The cohortwas monitored for the development of symptomatic gallstones and each case matched withfour controls for age and sex. Odds ratios were calculated using unconditional logisticregression, adjusted for body mass index (BMI), alcohol intake, hormone replacement therapy(HRT) & parity. Results. In the cohort, 219 participants (67.6% women) developed sympto-matic gallstones at a mean age of 61.3 years (SD = 9.0 years). Increased physical activitydecreased the risk of symptomatic gallstones stones in a linear manner across the fourcategories of physical activity (odds ratio for trend = 0.85, 95% CI=0.72-1.0, p<0.05). Anactive vs inactive level of physical activity gave an odds ratio of 0.48 (95% CI =0.26-0.89p=0.02). Physical activity was independently associated with a reduced risk of gallstonesafter multivariate adjustment for known risk factors (p<0.05). Conclusions. Increased physicalactivity was associated with decreased risk of symptomatic gallstones, a consistent findingin epidemiological studies, and now reported for the first time using a physical activityquestionnaire validated against physiological measurements. If the level of physical activityin the population could be raised, then 42% of symptomatic gallstones could be prevented.

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Gallstone Disease in Swedish Twins Is Linked to ABCG8 D19H RiskGenotypeDespina Katsika, Marcin Krawczyk, Stephanie Schwartz, Paul Lichtenstein, Curt A.Einarsson, Frank Lammert, Hanns-Ulrich Marschall

Background: Recently, the D19H variant of the hepatocanalicular cholesterol transporterABCG8 was found to be strongly linked to gallstone disease (GD) in Caucasians. We nowinvestigated this polymorphism in Swedish Twins. Material and Methods: The SwedishTwin Registry was merged with the Outpatient Discharge registry for gallstone related ICDdiagnoses and screened for monozygotic (MZ) twins born between 1915 and 1956 withGD living in the Stockholm area. Abdominal ultrasound was performed in the MZ twinswith undefined GD, and three concordant dizygotic (DZ) twin pairs were included; 88%of twins were females. ABCG8 D19H genotyping was performed using PCR-based assayswith 5'-nuclease and fluorescence detection (TaqMan). For statistics, non-parametric linkage(NPL) score analysis was employed. Results: Overall prevalence of D19H among affectedtwins was 30.4%. Of 25 MZ twin pairs, 20 were concordant and 5 were discordant for GD.Hetero- or homozygous 19H carriers were observed in 8 twin pairs; 7 of these were concordantfor GD. With a 19H allele frequency of 10.3% in healthy Swedish controls, an NPL score of3.95 (p<0.0001) was estimated, indicating significant linkage of ABCG8 D19H to gallstones.Conclusion: These data from twins as perfectly matched affected pairs confirm the D19Hvariant of the cholesterol transporter ABCG8 as risk factor for GD.

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Decreased Postprandial Gallbladder Emptying in Patients with Black PigmentStones: A Comparative Study in Patients with Cholesterol Stones and NormalSubjectsKenichi Hakamada, Shunji Narumi, Yoshikazu Toyoki, Masaki Nara, Keinosuke Ishido,Takuya Miura

BACKGROUND AND AIM: The incidence of black pigment stones (BPS) and cholesterolstones (CS) is increasing in Japan. However, the mechanism of BPS formation is still notcompletely understood. We hypothesize that a reduced motor function of gallbladder anda functional discordance of bile evacuation is associated with BPS formation. METHODS:The pattern of bile evacuation from the gallbladder was quantified by computer cholescintig-raphy in 28 normal subjects, 22 patients with CS, and 14 with BPS. The parameters of thegallbladder contractility including ejection period (EP), ejection fraction (EF), and ejectionrate (ER) of each individual were measured. RESULTS: A significantly shorter EP was observedin patients with BPS in comparison to those with CS (p<0.05). EFs in BPS patients significantlydecreased in comparison to those in CS and normal subjects (p<0.0001, p<0.05). EFs inCS patients also significantly decreased in comparison to those in normal subjects (p<0.005).Consequently, ERs in patients with BPS and CS were significantly smaller than those innormal subjects (p<0.005, p<0.001). Moreover, in cases where postprandial reflux of aradioisotope into the common hepatic duct from the gallbladder was observed, EFs andERs of either CS or BPS showed a significant reduction. CONCLUSIONS: Bile evacuationfrom the gallbladder is reduced in patients with BPS, in comparison to those with CS andto healthy volunteers. Bile stagnation due to impaired gallbladder kinetics seems one of thepredisposing factors for the development of BPS.

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Extrahepatic Cholestasis Increases Liver Stiffness (Fibroscan ®) Irrespectiveof FibrosisSebastian Mueller, Gunda Millonig, Stefanie Friedrich, Andreas Welker, Peter Becker,Frank Reimann, Helmut Karl Seitz

Introduction: Transient elastography is a non-invasive and rapid novel tool to assess fibrosisin chronic liver disease. Liver stiffness is indirectly measured by the propagation velocityof ultrasound waves within the liver. However, it remains to be determined if other liverdiseases such as cholestasis interfere with fibrosis assessment. Aim: The aim of the presentstudy was to prospectively evaluate the role of mechanical cholestasis with liver stiffnessmeasured by Fibroscan® (Echosens, Paris). Study design: 10 consecutive patients withmechanical cholestasis due to benign or malign bile duct obstruction were assessed for liverstiffness before and after drainage via ERCP. Liver stiffness was measured immediately beforeERCP, 1 and 3 days after recanalisation of the bile ducts. Cholestasis parameters (alkalinephosphatase, gammaGT and bilirubin) were correlated to liver stiffness. Results: In all 10patients liver stiffness was elevated to a degree that suggested advanced liver fibrosis or livercirrhosis (mean 12.5 kPa, range 8.0 to 18.2 kPa) at the time of cholestasis. After establishingbiliary drainage stiffness decreased in those that were successfully treated to mean valuesof 7.5 kPa at day 1 and 5.2 kPa at day 3 after intervention. Only one patient who couldnot be drained sufficiently due to multiple liver biliary stenoses remained above 14 kPadespite ERCP. The decrease in liver stiffness correlated statistically significantly with decreasedbile duct dilation detected by ultrasound and with decreasing AP, gammaGT and bilirubin.Conclusion: Extrahepatic cholestasis increases liver stiffness irrespective of fibrosis. Onceextrahepatic cholestasis is excluded e.g. by ultrasound and laboratory parameters, transientelastography is a valulable tool to assess liver fibrosis in chronic liver diseases. This projectwas supported by the Dietmar Hopp Foundation.

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The Clinical and Radiologic Characteristics of Focal Mass-FormingAutoimmune PancreatitisBeom Jin Kim, Jong Kyun Lee, Woo Ik Chang, Won-Seok Choi, Su Rin Shin, Kyu TaekLee, Jong Chul Rhee, Kee Taek Jang, SeongHo H. Choi

Objectives Autoimmune pancreatitis (AIP) is unique form of chronic pancreatitis (CP) easilydiagnosed by characteristics of diffuse swelling of parenchyma and irregular narrowing ofthe main pancreatic duct (MPD), relatively. However, focal mass-forming (FMF) AIP ishard to distinguish from pancreatic cancer, almost of them has been diagnosed in patientsundergoing pancreatectomy for presumed pancreatic cancer, until recently. So we investigatethe clinical and radiologic features of focal mass-forming AIP to avoid unnecessary surgery.Methods We enrolled 23 chronic inflammatory pancreatic mass patients who receivedpancreatectomy for presumed pancreatic cancer from April 1995 to December 2005. Thesepatients were devided into FMF AIP and CP through the histologic criteria of HISORt.And curatively resected 26 pancreatic cancer patients were enrolled for control. Then weinvestigated the clinical and radiologic features of each groups. Results Eight of 23 patients(35%) were diagnosed as FMF AIP. Abdominal pain was not present in AIP, but 11 CP(73.3%, p=0.005) and 15 pancreatic cancer presented abdominal pain (57.7%, p=0.025).In the delayed phase of CT, seven of 8 FMF AIP showed homogenous enhancement (87.5%),whereas only 3 CP (25%) showed. In pancreatic cancer, no patients showed homogenousenhancement. Peripancreatic strands was not seen in FMF AIP, whereas 7 in CP (58.3%,p=0.011) and 10 in pancreatic cancer (66.7%, p=0.003). None of FMF AIP showed theupstream MPD dilatation more than 5mm, whereas 5 in CP (50%, p=0.037) and 8 inpancreatic cancer (80%, 0.002). Proximal pancreatic atrophy was observed in none of FMFAIP, whereas 6 of 10 in pancreatic cancer (p=0.016). In the pancreatogram, FMF AIP showedMDP stenosis predominantly (68.7%), rather than obstruction (16.7%), while pancreaticcancer showed MPD obstruction predominantly (71.4%). Conclusions Features at CT thatcan help distinguish FMF AIP from pancreatic cancer include delayed homogenous enhance-ment of the pancreatic mass lesion, absence of peripancreatic strands and significanctupstream MDP dilatation, and absence of proximal pancreatic atrophy. Moreover, the stenosisof MPD in pancreatogram also raises the probability of diagnosis of FMF AIP.

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A Comparative Study of Outcomes Between Endoscopic Naso-CholecysticDrainage (ENGBD) and Percutaneous Transhepatic Cholecystic Drainage(PTGBD) in Patients with Acute CholecystitisByungmoo Yoo, Min Cheul Kim, Jin Hong Kim

Background and Aim : The standard treatment for acute cholecystitis is early laparoscopiccholecystectomy. In cases of increased operative risk surgery, could be postponed or rejected,and instead alternative methods, such as percutaneous or endoscopic drainage, may beattempted. We compared the outcomes between ENGBD and PTGBD as alternative methodsfor the treatment of acute cholecystitis. Patients and Methods : We have retrospectivelyevaluated the clinical data of 130 patients treated with PTGBD or ENGBD for acute cholecys-titis. 47 patients were treated with ENGBD and 83 patients were performed by PTGBD.After successful ERC, the insertion of the guide wire via cystic duct into the gallbladder wasattempted. Following gallbladder cannulation, nasocholecystic drainage catheter(5 Fr or 7Fr) was negotiated into position under fluoroscopic control. A USG guided transhepaticapproach was used to access the gallbladder in all patients. After puncture of the gallbladder,a guide wire was inserted into the gallbladder. Then an 8.5 Fr catheter was inserted intothe gallbladder via guide wire. We compared the outcomes between the two groups in patientswho had been successful performed. Results : There were no statistical significances(p<0.05,statistically significance) in mean age (p=0.097), gender(p=0.581), DM(p=0.629), Hyperten-sion(p=0.698) between the two groups. The success rates(p=0.005) of the ENGBD andPTGBD were 87.7%(41/47), 98.8%(82/83) respectively. 39 patients were calculous cholecys-titis, 2 patients were acalculous cholecystitis in ENGBD, 78 patients and 4 patients inPTGBD respectively. Patients who were conservatively treated or who underwent laparoscopic

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