1
A384 AGA ABSTRACTS GASTROENTEROLOGY, VoI. IO8, No. 4 ENDOSCOPIC SPHINCTEROTOMY FOR THE PREVENTION OF FURTHER ATTACKS OF ACUTE PANCREATITIS IN PATIENTS WITH GALLBLADDER IN SITU. R. Pczzilli, N. D'Impcrio, P. Billi, D. Baroncini, B. Barakat, A. Piemontese, P.R. Dal Monte, M. Miglioli. Emergency Department, St. Orsola Hospital, and Digestive Endoscopy Departmcnt, Bcllaria Hospital, Bologna, Italy. Acute pancreatitis tAP) is a complication which al'lccts 6%-8% of all patients with symptomatic gallstones; although, this percentage may be higher than 21)% in thosc with microlithiasis (Hepato-Gastroenterol 1993:40:550-555). Butch et al. (Arch Surg 1991);125:853-860) rcportcd a risk of 44% of further attacks of AP in the absence of cholccystcctomy. The aim of this study was to cvaluatc the thsefulness of endoscopic sphincterotomy (ES) to prevent rccurrenccs of AP in patients with biliary stones and gallbladdcr in situ. Twenty-two acute biliary pancreatitis patients (5 M, 17 F, mean age 72 years, range 40-86) were studied. The diagnosis was based on typical abdominal pain associated with a two-fold increasc o1 serum lipase and was lmthcr confirmed by imaging techniques. On the basis of Atlanta criteria (Arch Surg 1993;128:586-590), 18 patients had mild acute pancreatitis and 4 a scvctc discasc. Ultrasonography showed biliary lithiasis in 20 of the 22 paticnt.s studicd ERCP, pcrtormcd within 72 hours from hospitalization, showed lithiasis or microlithiasis of the common bile duct in 20 patients and of the gallbladder in 18; papillary stcnosis was lound in 9 patients; all thc subjccts under,vent urgent ES. Mean follow-up pcriod of the 22 patients was 14 montbs (range 1-39 months). Two paticnts complained early complications rclatcd to endoscopic procedures: one had intestinal perforation resolved with nasobiliary drainage and medical treatment; the other patient had moderate blecding which required two units blood transfusion. Wc did not rcporl any latal complication. The mcan length of hospitalization was 12 days (range 7-48 days). During the lollow-up period, 3 patients underwent to urgent cholccystcctomy lot gallbladder cmpyema (one patient on thc 15th day, the 2nd, on thc 40th day and the 3rd, 1,5 months after ES). One patient complained relapse of upper abdolninal pare and lurther examination rcvcalcd chronic pancrcatitis. During the follow-up period, relapse of acute pancreatitis was nil. In conclusion, rcsuhs o1 our study suggest that ES is useful to prevent further attacks of acute pancrcatitis in patients with gallbladder in situ in which cholecystectomy is inadvisable. SERUM B2 MICROGLOBUL1N IN THE EARLY ASSESSMENT OF THE SEVERITY OF ACUTE PANCREATITIS. A COMPARATIVE STUDY WITH INTERLEUKIN 6, INTERLEUKIN 8 AND C-REACTIVE PROTEIN. R Pezzilli, P. Billi, R. Minieru, M. Fiocchi, O. Cappelletti, G. Spruvien, M. Mlgliuli. Emcrgcncy Department and Central Laboratory. St. Orsola Hospital, Bologna, Italy B2-micruglobulin (B2-M) has been lound on the sur/ace of all human nucleated cells; it is the invariant light chain o[ class 1 major histocompatibility antigens (HLA-A, B, (2). It has been reported that serum levels of B2-M increase in patients with inflammatory disorders: however, nu studies have been carried out to evaluate its behavior in patients with acute pancreatitis. It has also been reported that serum intcrleukin 6 (1L-6) and intcrleukin 8 (IL-8) arc useful markers for assessing the severity of acute pancreatitis, although, most of the pertinent studics were tamed out using homcmade assays. Commercial immunoassavs fur serum determination of these cvtokines have recently been developed. The aim ol this study was to compare the sensitivity, specificlty and diagnostic accuracy of serum 1?,2-M, IE-6, IL-8, and C-reactive protein (CRP) in the assessment of the severity of acute pancreatiris using commercial kits t~.)r their respective assays (B2-M, Du Pont de Nemours, USA; Predicta IL-6 ELISA kit, Genzyme Co., USA: Quantikine human IL-8 Immunoassay, R&D System, USA; CRP, Beckman, USA). Thirty-eight patients with acute pancreatitis (25 M, 13 F, mean age 59 years, range 16-97) were studied; the diagnosis was based on characteristic abdominal pain associated with a two-fold increase of serum lipase, and it was confirmed by imaging techniques. According lu the Atlanta criteria, 15 patients had severe illness and 23 had mild disease. The tour serum markers were determined in all paticnts on admission, as well as daily [or the lollowing 5 days. The sensitivity (calculatcd on patients with severe pancrcatitis) and specificity (calculated on paticnts wilh mild pancreatitis), of these scrum markers lor establishing the severity of acute pancreatiUs arc reported in the Table. Days 1 2 3 4 5 6 Sensitivity (%) 132-M 585 51) 43 50° 46§ 455 IL-6 100' 1(S)$ 86 79 46§ 365 IL-8 100" 100$ 93 86 77 64 CRP 8 57 lt)O 100 85 91 Specificity (%) I.~2-M 81 77 '58 74 78 74 1L-6 86 68 8'5 I(X) ° (Xi I(X) 1L-8 81 91 955 96§ ~ 100 CRP 90 73 (',4 70 78 87 " P<t).tX)l; ° P<0.005: $ P<0.OI; § P<0.05 with respect to CRP (chi-square test) The results of our study indicate that, when assayed during thc first 24 huurs of disease onset, tl2-M, I1~-6, and IL-8 are better markers than CRP fur evaluating the severity of acute pancreatitis. PANCREATITIS ASSOCIATED WITH ACUTE GASTROENTERITIS. A_, Pfeiffer, T. lbrahim, M. Fuchs, J. Fischer, T. Sehmidt, H. Kacss, Dept. of Gastroenterology, Hospital Bogenhausert, Munich, Germany. The incidence of pancreatitis associated with acute gastroenteritis is disputed. Data on the frequency of raised serum amylase and lipase activities range between 2 and 62 % (Lancet 1991; 338; 571; Arch Intern Med 1983; 143: 215-19; Lancet 1991; 337:1611). Although cases of severe pancreatitis have been reported (Br Med J 1989;298: 1004), the clinical relevance of an increase in serum amylase or lipase is questioned in the majority of the patients (Lancet 1991; 338: 571). The aim of the study was to evaluate in acute gastroentedtis i) the frequency of raised serum lipase and its relationship with various causative pathogens and ii) the association of a raised serum lipa.se with clinical and sonographic signs of acute pancrcatitis. Method: Review of microbiological stool exarmnations, of serum lipase activities (normal value < 190 U/L) and of the reports of the clinical course and the abdomi- nal ultrasound performed routinely in 248 patients (41, 17-93 years, 137 women) hospitalized for acute gamoenteritis. Results: Pathogen patients patients with a raised serum lipase n n % Salmonella 74 33 44.6 Staph. aureus 21 1 4.8 Ca.mpylohacter jejunl 19 4 21.1 Miscellaneous 14 4 28.6 None isolated 97 l 1 11.3 None investigated 23 2 8.7 None of all the 55 patients with a raised semm lipasc had a dimcally apparent pan- creatitis and none of them presented any sonographic sign of acute pancreatitis. Conclusion: In acute gastroentcritis, a raised serum lipase can be associated with various causative pathogens, but most frequently with salmonella. The lack of clinical and sonographic signs of acute pancreatitis suggests that hyperlipasaemia in acute gnstroenteritis is only of minor clinical relevance in the investigated pa- tients. ISOFORM-SPECIFICITY OF RA.B3B/D EFFECTOR DOMAIN PEPTIDE STIMULATED AMYLASE RELEASE IN PANCREATICACINI AND INHIBITION BY RAB3B/DANTIBODIES. A. Piiper, D. Stryjek-Kaminska, W.F. Caspa-y, S. Zeuzem. Department of Medicine, Universityof Frankfurt a M, Germany. Small molecular weight GTP-binding proteins of the Rab family regulate vesicular Iransport within the cell. Rab3 proteins appear to be involved in regulated exocytosis We have previously shown that a modi~ed peplide corresponding to ~e elfecter domain of the small molecular weight GTP-~eding protein Rab3A, Rab3A AL, stimulates inositol 1,4,5-1risphosphate (1,4,5-1P3)- production and amylase release in digitonin-permeabilized pancreatic adni. Experiments using monodonal anti~dles reveal that the Rab34ike protein present in panoreaCdc adni is not the Rab3Aisoforrn.However,~nce the puta~e elfector domains of the four yet known Rab3 proteins (A, B, C, D) differ only in the C-terrninal four amino acid residues, Rab3A effector domain paptido could mimick the action of the pancreas-specific Rab3 isoform.Methg~ls:Pano'ea~c adni were isolated from rat pancreas by collagenase digestion. Amylaserelease and 1,4,SqP3-pmduction were measured by a coforimetric assay and radioimmuno assay, raspec'dvely. Results: The data show that peptides corresponding to different Rab3 isoforms stimulate both 1,4,5-1P3-.production and amylase secretion with an order of potency Rab3B/D>Rab3AAL>Rab3A=Rab3C. For Rab3A,B/D and C effector domain pe~des the concen'aalionscausing half- maximal responc.e (ECso) were 0.3, 0.02 and 0.3 nM for amylase release and 3.0, 02 and 3.0 nM ~ 1,4,5-1P 3 accurnula~on, re~. A RablA effector domainpeptide,RablAAL, and a scrambled peptido of Rab3A N- were by several orders of magnitude less potent in eliciting these responses compared to the naf, ve Rab3 eflector domain peptidos. An antiserum directed against Rab3B/D peptide abolished Rab3B/D peptide-, but not CCK-ieduced amylase release. None of the pel~das in~uenced 1A,5-1P3-produclionand amylase release in intact adni. Conclusion: These data suggest that the puta~ve target for Rab3 effector domain peptides prefere~ally interacts with Rab3B/D pe~de, and that phosphotipase C and exocy~is might be regulatedby Rab3B- or Rab3D-like proteins in pano"ea~cadnar cells. Suppocted by theD e ~ Forschung~mchafl (Ze237/4-1)

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Page 1: Pancreatitis associated with acute gastroenteritis

A 3 8 4 AGA ABSTRACTS GASTROENTEROLOGY, VoI. IO8, No. 4

ENDOSCOPIC SPHINCTEROTOMY FOR THE PREVENTION OF FURTHER ATTACKS OF ACUTE PANCREATITIS IN PATIENTS WITH GALLBLADDER IN SITU. R. Pczzilli, N. D'Impcrio, P. Billi, D. Baroncini, B. Barakat, A. Piemontese, P.R. Dal Monte, M. Miglioli. Emergency Department, St. Orsola Hospital, and Digestive Endoscopy Departmcnt, Bcllaria Hospital, Bologna, Italy.

Acute pancreatitis tAP) is a complication which al'lccts 6%-8% of all patients with symptomatic gallstones; although, this percentage may be higher than 21)% in thosc with microlithiasis (Hepato-Gastroenterol 1993:40:550-555). Butch et al. (Arch Surg 1991);125:853-860) rcportcd a risk of 44% of further attacks of AP in the absence of cholccystcctomy. The aim of this study was to cvaluatc the thsefulness of endoscopic sphincterotomy (ES) to prevent rccurrenccs of AP in patients with biliary stones and gallbladdcr in situ. Twenty-two acute biliary pancreatitis patients (5 M, 17 F, mean age 72 years, range 40-86) were studied. The diagnosis was based on typical abdominal pain associated with a two-fold increasc o1 serum lipase and was lmthcr confirmed by imaging techniques. On the basis of Atlanta criteria (Arch Surg 1993;128:586-590), 18 patients had mild acute pancreatitis and 4 a scvctc discasc. Ultrasonography showed biliary lithiasis in 20 of the 22 paticnt.s s tudicd ERCP, pcrtormcd within 72 hours from hospitalization, showed lithiasis or microlithiasis of the common bile duct in 20 patients and of the gallbladder in 18; papillary stcnosis was lound in 9 patients; all thc subjccts under,vent urgent ES. Mean follow-up pcriod of the 22 patients was 14 montbs (range 1-39 months). Two paticnts complained early complications rclatcd to endoscopic procedures: one had intestinal perforation resolved with nasobiliary drainage and medical treatment; the other patient had moderate blecding which required two units blood transfusion. Wc did not rcporl any latal complication. The mcan length of hospitalization was 12 days (range 7-48 days). During the lollow-up period, 3 patients underwent to urgent cholccystcctomy lot gallbladder cmpyema (one patient on thc 15th day, the 2nd, on thc 40th day and the 3rd, 1,5 months after ES). One patient complained relapse of upper abdolninal pare and lurther examination rcvcalcd chronic pancrcatitis. During the follow-up period, relapse of acute pancreatitis was nil. In conclusion, rcsuhs o1 our study suggest that ES is useful to prevent further attacks of acute pancrcatitis in patients with gallbladder in situ in which cholecystectomy is inadvisable.

SERUM B2 MICROGLOBUL1N IN THE EARLY ASSESSMENT OF THE SEVERITY OF ACUTE PANCREATITIS. A COMPARATIVE STUDY WITH INTERLEUKIN 6, INTERLEUKIN 8 AND C-REACTIVE PROTEIN. R Pezzilli, P. Billi, R. Minieru, M. Fiocchi, O. Cappelletti, G. Spruvien, M. Mlgliuli. Emcrgcncy Department and Central Laboratory. St. Orsola Hospital, Bologna, Italy

B2-micruglobulin (B2-M) has been lound on the sur/ace of all human nucleated cells; it is the invariant light chain o[ class 1 major histocompatibility antigens (HLA-A, B, (2). It has been reported that serum levels of B2-M increase in patients with inflammatory disorders: however, nu studies have been carried out to evaluate its behavior in patients with acute pancreatitis. It has also been reported that serum intcrleukin 6 (1L-6) and intcrleukin 8 (IL-8) arc useful markers for assessing the severity of acute pancreatitis, although, most of the pertinent studics were tamed out using homcmade assays. Commercial immunoassavs fur serum determination of these cvtokines have recently been developed. The aim ol this study was to compare the sensitivity, specificlty and diagnostic accuracy of serum 1?,2-M, IE-6, IL-8, and C-reactive protein (CRP) in the assessment of the severity of acute pancreatiris using commercial kits t~.)r their respective assays (B2-M, Du Pont de Nemours, USA; Predicta IL-6 ELISA kit, Genzyme Co., USA: Quantikine human IL-8 Immunoassay, R&D System, USA; CRP, Beckman, USA). Thirty-eight patients with acute pancreatitis (25 M, 13 F, mean age 59 years, range 16-97) were studied; the diagnosis was based on characteristic abdominal pain associated with a two-fold increase of serum lipase, and it was confirmed by imaging techniques. According lu the Atlanta criteria, 15 patients had severe illness and 23 had mild disease. The tour serum markers were determined in all paticnts on admission, as well as daily [or the lollowing 5 days. The sensitivity (calculatcd on patients with severe pancrcatitis) and specificity (calculated on paticnts wilh mild pancreatitis), of these scrum markers lor establishing the severity of acute pancreatiUs arc reported in the Table.

Days 1 2 3 4 5 6

Sensitivity (%) 132-M 585 51) 43 50 ° 46§ 455 IL-6 100' 1(S)$ 86 79 46§ 365 IL-8 100" 100$ 93 86 77 64 CRP 8 57 lt)O 100 85 91

Specificity (%) I.~2-M 81 77 '58 74 78 74 1L-6 86 68 8'5 I(X) ° (Xi I(X) 1L-8 81 91 955 96§ ~ 100 CRP 90 73 (',4 70 78 87

" P<t).tX)l; ° P<0.005: $ P<0.OI; § P<0.05 with respect to CRP (chi-square test)

The results of our study indicate that, when assayed during thc first 24 huurs of disease onset, tl2-M, I1~-6, and IL-8 are better markers than CRP fur evaluating the severity of acute pancreatitis.

• P A N C R E A T I T I S A S S O C I A T E D W I T H A C U T E G A S T R O E N T E R I T I S . A_, Pfeiffer, T. lbrahim, M. Fuchs, J. Fischer, T. Sehmidt, H. Kacss, Dept. of Gastroenterology, Hospital Bogenhausert, Munich, Germany.

The incidence of pancreatitis associated with acute gastroenteritis is disputed. Data on the frequency of raised serum amylase and lipase activities range between 2 and 62 % (Lancet 1991; 338; 571; Arch Intern Med 1983; 143: 215-19; Lancet 1991; 337:1611). Although cases of severe pancreatitis have been reported (Br Med J 1989;298: 1004), the clinical relevance of an increase in serum amylase or lipase is questioned in the majority of the patients (Lancet 1991; 338: 571). The

a im of the study was to evaluate in acute gastroentedtis i) the frequency of raised serum lipase and its relationship with various causative pathogens and ii) the association of a raised serum lipa.se with clinical and sonographic signs of acute pancrcatitis.

Method: Review of microbiological stool exarmnations, of serum lipase activities (normal value < 190 U/L) and of the reports of the clinical course and the abdomi- nal ultrasound performed routinely in 248 patients (41, 17-93 years, 137 women) hospitalized for acute gamoenteritis.

Results: Pathogen patients patients with a raised

serum lipase n n %

Salmonella 74 33 44.6 Staph. aureus 21 1 4.8 Ca.mpylohacter jejunl 19 4 21.1 Miscellaneous 14 4 28.6 None isolated 97 l 1 11.3 None investigated 23 2 8.7

None of all the 55 patients with a raised semm lipasc had a dimcally apparent pan- creatitis and none of them presented any sonographic sign of acute pancreatitis.

Conclusion: In acute gastroentcritis, a raised serum lipase can be associated with various causative pathogens, but most frequently with salmonella. The lack of clinical and sonographic signs of acute pancreatitis suggests that hyperlipasaemia in acute gnstroenteritis is only of minor clinical relevance in the investigated pa- tients.

ISOFORM-SPECIFICITY OF RA.B3B/D EFFECTOR DOMAIN PEPTIDE STIMULATED AMYLASE RELEASE IN PANCREATIC ACINI AND INHIBITION BY RAB3B/D ANTIBODIES. A. Piiper, D. Stryjek-Kaminska, W.F. Caspa-y, S. Zeuzem. Department of Medicine, Universityof Frankfurt a M, Germany.

Small molecular weight GTP-binding proteins of the Rab family regulate vesicular Iransport within the cell. Rab3 proteins appear to be involved in regulated exocytosis We have previously shown that a modi~ed peplide corresponding to ~e elfecter domain of the small molecular weight GTP-~eding protein Rab3A, Rab3A AL, stimulates inositol 1,4,5-1risphosphate (1,4,5-1P3)- production and amylase release in digitonin-permeabilized pancreatic adni. Experiments using monodonal anti~dles reveal that the Rab34ike protein present in panoreaCdc adni is not the Rab3A isoforrn. However, ~nce the puta~e elfector domains of the four yet known Rab3 proteins (A, B, C, D) differ only in the C-terrninal four amino acid residues, Rab3A effector domain paptido could mimick the action of the pancreas-specific Rab3 isoform. Methg~ls: Pano'ea~c adni were isolated from rat pancreas by collagenase digestion. Amylase release and 1,4,SqP3-pmduction were measured by a coforimetric assay and radioimmuno assay, raspec'dvely. Results: The data show that peptides corresponding to different Rab3 isoforms stimulate both 1,4,5-1P3-.production and amylase secretion with an order of potency Rab3B/D>Rab3AAL>Rab3A=Rab3C. For Rab3A, B/D and C effector domain pe~des the concen'aalions causing half- maximal responc.e (ECso) were 0.3, 0.02 and 0.3 nM for amylase release and 3.0, 02 and 3.0 nM ~ 1,4,5-1P 3 accurnula~on, r e ~ . A RablA effector domain peptide, RablA AL, and a scrambled peptido of Rab3A N- were by several orders of magnitude less potent in eliciting these responses compared to the naf, ve Rab3 eflector domain peptidos. An antiserum directed against Rab3B/D peptide abolished Rab3B/D peptide-, but not CCK-ieduced amylase release. None of the pel~das in~uenced 1A,5-1P3-produclion and amylase release in intact adni. Conclusion: These data suggest that the puta~ve target for Rab3 effector domain peptides prefere~ally interacts with Rab3B/D pe~de, and that phosphotipase C and exocy~is might be regulated by Rab3B- or Rab3D-like proteins in pano"ea~c adnar cells.

Suppocted by the D e ~ Forschung~mchafl (Ze 237/4-1)