A412 AGA ABSTRACTS GASTROENTEROLOGY, VOl. 108, NO. 4

THE NATURAL HISTORY OF GALLSTONES: A REAPPRAISAL. Cetta F Institute of Surgical Clinic~; University q/Siena ltaly. Recent epidemiologlc studies showed approximately two thirds of gallstones (GS) to be silent (i.e. asymptomatie). Therefore, according to common belief, they do not require surgery. We have previously suggested that GS are not a unique entity, but a heterogeneous disease, including many subtypes of GS with different composition, pathogenesis and also biological and clinical behaviour :1) During a 15y prospective study 1421 patients with GS (all symptomatic), underwent GS and bile analysis In the same period. 243 patients, who initially refused surgery, were followed~up (mean follow-up of 65 years, m~ximum 14 years). GS were single in 54, double in 2, multiple larger than 5 mm in 71, small GS in 33, multiple composite difficult to classify preoperatively in 85 cases. 51 of the 243 patients (21%) required operation, during the follow-up period. None of them had gallbladder carcinoma (GBC). 3 patients had black GS Only 4 of the 54 patients with single GS (74%) vs. 48 of 185 ~Jth multiple GS (26%) required operation (p=0,025). However, analyzing the entire series of 1421 subjects with GS, the following patients were observed: 43 patients who had GBC, I 1 bilio-bitiary fistulas (BBF), 27 bitiary-enteric fistulas (BEF), 9 biliary ileus (BI), 12 porcelain gallbladder (PGB) 81 of these I03 patients with severe GS related complications had at least one GS larger than 15 ram. 44 of these patients were unaware of having GS or wer " " ears.

GBC(43) BBF(II) [ BEF(27) BI(9) PGB(I2) Unaware 9 2 3 4

i Asymptomatie 1 t 3 [ 4 2 5 Total 20 (46.5%) 5 (45.4%) 9 (33.3%) 6 (66,6%) 5 (41.6%)

On the bas~s of the cumulative data, ~t is suggested that: (1) the natural history of GS is not unique, but differs according to age of patients or type. size and lapse of GS (2)'Patients used for long-term follow-up studies usually belong to a preselected group with a low rate of complications. In fact, they include only part of all patients with GS, who make up a surgical series, since patients requiring urgent operation, sometimes soon afl.er the initial GS formation, are not included. (3) The occurrence of symptoms is not due merely to chance. but mainly depends on the mutual relationships between the content (bile and GS) and the container (bile tract wall and flow). Therefore. there are some GS which are severely symptomatic from the beginning and then undergo early surgery and other GS which are asymptomatic for ever or become sympiomatic only after the formation of a second GS population, which determines obstruction of the cystic duct or of the ampulla of yatar. (4) Stone type is a major determinant of symptoms: "infectious'brown GS are associated with cholangitis in 60% of cases ('2). Stone size is also a basic determ/nant. In general, small GS (in pa{ticular black spicular microstones) are more frequently associated with jaundice or pancreatitis (2) On the contrary, large cholesterol GS usually remain asymptomatie for long time. However, some of the most severe complications, including GBC, occur in the latter ~oup, even if only a minor proportion of the entire group of large GS is symptomatic. Symptoms predicting GBC are usually lacking and early diagnosis is infrequent. On the basis of the present findings, a reappraisal of the natural history of GS is warranted. Cetta F: (1) C-astroenterology 1993; 104: A354; (2) Atilt, Sttrg. 1991; 213:315-326.

• I N H I B I T I O N O F S T E N T O C C L U S I O N BY A M P I C I L L I N - SULBACTAM IN AN I N - V I T R O MODEL. H.B. Chodash. T.K. Tsang, J.M. Pollack. Div. of Gastroenterology, Northwes!ern University, Evanston Hospital, Evanston, IL. An important first step in occlusion is bacterial biofilm formation, followed by deposition of granules (calcium bilirubinate, cholesterol, & calcium palmitate) to form occluding material. Previous in-vitro models to study biliary stent occlusion have used synthetic bile (contains no bilirubin) or pooled human bile (limited supply and uncertain handling) which may limit their usefulness. Our aim was to develop a new in-vi tro model of stent occlusion and use it to assess if ampicillin/sulbactam (amp/sul) can prevent occlusion. Methods: Porcine gallbladder bile is collected, cultured, and frozen at - 1 5 o c for 7 days pending final culture results. Sterile biles are pooled then E. colt and/or K. oxytoca are added. The bile is divided into 8 reservoirs, 4 of which amp/sul are added. The bile reservoirs are kept in the dark, at 37°C, and are connected to the study stents (10 Fr polyethylene) in a closed system. The air in the system is purged with a mixture of CO2 and N2. Bile is perfused through the stents at a rate of 0.5 cc/min using a peristaltic pump. Bile in the reservoirs are changed every 7 days, due to stability of bile pigments as we previously described. The stents were perfused for 8 weeks. The bile was cultured and analyzed at the beginning and end of one 7 day perfusion cycle to assess stability of pH, total bilirubin (TB), bile salts (BS), cholesterol (Xol), total ca lc ium (Ca) and phospholipids (PL). Results: In 4 stents treated with amp/sul, sterility was maintained for 8 weeks, and there was no significant loss in Ca, TB, BS, Xol or PL over the 7 day cycle. There was a slight rise in the pH from a mean of 7.1 to 7.3 (p<.05). There was no occlusion material seen in the stents by light microscopy (electron microscopy pending). In the 4 infected stents, the mean pH went from 7.1 to 7.5 (p<.05), mean Ca decreased from 10.0 mM to 7.8 mM (p<.05), mean Xol decreased 3.4 mM to 3.1 mM (!0<.05) and mean TB decreased 1201uM to 1100 uM (p<.05). A dark biofilm and occlusion material layer lined all 4 infected stents. Conclusions: In this in-vi tro model there is a loss o f TB, Ca, and Xol seen in the bile reservoirs of infected stents and not in treated/sterile stents due to a deposition of these materials in the biofilm matrix. Amp/sul appears to inhibit biofilm formation. The results of this study suggest that amp/sol prevents stent occlusion by inhibiting formation of infection-induced biofilm and deposition of calcium salts and Xol crystals. Antibiotics may be useful in prolonging stent patency if started prior to biofilm formation. This new model can be used to test the effects of other antibiotics or drugs on formation of occluding material in various stents.

ENDOSCOPIC STENT PLACEMENT IN THE TREATMENT OF BILE LEAKS OCCURRING AFTER ORTHOTOPIC LIVER TRANSPLANTATION (OLT). J Clark, M Uzer. Department of Medicine, Rush Presbyterian St. Luke's Medical Center, Chicago, IL. There has been a recent trend towards endoscopic management in the treatment of T-tube related bile leaks occurring after OLT. We report our experience with endoscopic stent placement in the management of this problem. METHODS: A retrospective review of the medical records of all patients undergoing OLT from February 1993 to February 1994. RESULTS: 62 patients underwent 69 OLTs during this time period. 56 of these were performed using a choledochocholedochostomy over a T- tube. 8 of these patients were referred for endoscopic therapy of a bile leak. One patient was referred twice for bile leaks on two separate occasions. All but one patient was symptomatic with either abdominal pain and/or fever, Bile leaks were associated with either a properly functioning indwelling T-Tube (n=l), inadver- tent T-tube migration (n=l), or intentional T-tube removal (n=7). ERCP was performed and a stent was placed across the T-tube insertion site ineach case. Stent diameter was either 7Fr (n=7) or 10Fr (n=2) with a length of 5cm (n=l), 7cm (n=2), or 9cm (n= 6). In no case was a distal obstruction noted. Endoscopic sphincterotomy was not required in any patient. TI.e leak healed in 8 of 9 (89%) patients. In all but one patient, ERCP with stent removal was performed at 26- 72 days (mean=39 days). Fever and abdominal pain resolved in all symptomatic patients within 48 hours. The only exception was a patient who developed a bile leak despite an indwelling T-tube. A 5cm 7Fr endoscopic stent was placed along side the T-tube. Initially he responded well but 5 days later he developed a recurrence of biliary peritonitis requiring surgical repair of the leak. The stent was removed endoscopic- ally and was found to be occluded. This stent occlusion was the only complication of endoscopic therapy in this series. CONCLUSION: ERCP with biliary stent placement is a safe and effective therapy in the management of bile leaks after OLT.

THE EFFICACY OF GLYCERYL TRINITRATE IN PATIENTS WITH SPHINCTER OF ODDI DYSFUNCTION. A PROSPECTIVE DOUBLE-BLIND STUDY. J.C, Cuer, A. Aoergel, M. Dap0igny, F. Lhopital, G. Bommelaer, R. Laugier*,Service d'Hfpato-gastroent~rologie, Hotel-Dieu, Clermont- Fen'and, *Hopital de la Conception, Marseille, France. Glyeeryl Trinitrate (GTN) has been shown to decrease basal pressure of sphincter of Oddi (SO) in humans, as we wondered whether a pharmacological relaxation of SO may have a beneficial effect on biliary type pain. (SO dysfunction is a recognised cause of pain and only endoscopic sphincterotomy has been shown to improve this condition). Aim of study: a) Evaluate the effects of GTN vs paeebo in deacreasing of

biliary pain. b) Effects of GTN regarding the SO manometry results. 23 patients (21 females, 2 males) suffering from biliary type pain (X age: 47) were included. All patients have undergone ERCP manometry with a triple lumen peffused catheter but the results of this examination were not used as a criterion for entry into the study. Each patient was randomly assigned to receive 0.40 mg of GTN (Natispray R Nativellc laboratory Paris Prance) sublingually (goup 1") or placebo (group II) in a prospective double-blind study, The patients were interviewed by an independent observer at 2, 4, and 6 months. Results: Improvement vs persistence of symptoms:

PLACEBO PLACEBO GTN OTN good no good no improvement improvement improvement improvement

normal SO 1 2 3 2 basal pressure elevated SO 0 2 12 1 basal pressure 1) Good improvement was observed in 83 % of patients trotted by GTN as compared with 20 % of those who received placebo, p<0. 01 .2) When dividing the patients in 2 groups according to their results of SO manometry a good improvement of patients trotted by GTN was observed in 92% of patients with elevated sphincter pressure as compared with 60% of patients with normal sphincter pressure p<0.001 and in the placebo, group a good improvement was observed in 0% of patients with elevated sphincter pressure as compared with 33% of patients with normal sphincter pressure p = 0.45. All patients (100%) of group I sloped the use of GTN because of side-effect s (headaches).Conlusion: Even with good eff icacy on symptoms GTN cannot be used in patients because of the side effects, but our study suggests that GTN could be a useful treatment before sphincterotomy on SO dysfunction.