~ - f~

Wl105

No Association Between Pancreatic and Liver Status in 132 Japanese Male Alcoholics Yuji Nakamura, Yasunori Kobayashi, kkiko Ishikawa, Shintaro Sekiguchi, Susumu Higuchl, Katsuya Maruyama

Background: Alcohohc chronic pancreatitis (ACP) and alcoholic lwer cirrhosis (ALO are major alcohoMnduced diseases in most countries. In Japan, 55.5% of some 32,000 patients treated fbr chronic pancreatitis in 1994 had ACP (Linet al., J Gastroenterol 35:136-141, 2000) and 11.7% of about 17,000 deaths annually' from lwer failure in recent years were due to ALC alone, excluding deaths from hepatitis B and C (Zeniya and Nakajima, Nippon Rinsho 60 Suppl 1:233-241, 2002). Aim: This study was designed to help elucidate the mechanisms and possible association of ACP and ALC. Method: Consenting participants (n = 132) from all patients consecutively admitted to Kurihama National Hospital from July 2000 to Augnst 2002 were interviewed face to face about quantity and duration of drinking, usual alcoholic drinks, smoking, education, and marital status. All were analyzed for signs of pancreatitis by endoscoDc retrograde choLangiopancreatography (ERCP) and for hepam- celkdar function by Child-Pugh classification, and also examined sonographically for gall- stones; 77 were genotyped for the alcohol-metabolizing enzymes alcohol dehydrogenase-2 (ADH2) and aldehyde dehydmgenase-2 (ALDH2). Resnhs: Grouping the patients by ERCP pancreatography (normal to mild pancreatitis, 77; moderate, 28; marked, 27) and bepatocel- fular function (normaL/Child A, 117; Child B, 12; Child C, 3) revealed no associations between ACP and ALC. Nor were ACP and ALC associated with regard to total ethanol consumed or duration of drinking. ADH2 and ALDH2 genotypmg showed no risk for either ACP or ALC. Spirits drinkers were at higher risk fur ACP (odds ratio 2.2, p<0.05) but not for ALC Conversely, unmarried men were at higher risk for ALC (odds ratio 3.6, p<O.05) but not for ACE Gallstones occurred more frequently in the Child B and Child C groups thau ni the nonual/Child A group (odds ratio 4.0, p<0.05), hut the frequency of gallstones did not differ significantly- across ERCP groups. Conclusion: Pancreatography findings and Cl~il&Pugh scores for this group of alcoholic patmnts suggest that ACP and ALC are unrelated.

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Accuracy of the Optimized 13c-Mixed Triglyceride Breath Test for the Diagnosis of S[eatorrhea in Clinical Practice Julio lglesias-Garcia Maria Vilarinoqnsua, Marta Iglesi~ts~Rey, Victoria Lourido, Enrique Domingrmz-Munoz

Breath test with 13C-labded mixed triglym:eride (13C -MTG) was recently optimized by our group tot the diagnosis of steatorrhea in patients with exocrine pancreatic insufficiency. Aim of our study was to evaluate the accuracy of this optimized 13C-MTG breath test fur the diagnosis of steatorrhea in clinical practice. MethtKls: 43 consecutive patients with clinical suspicion of steatorrbea were included prospectively in this study. Out of them, 31 suffered from chronic pancreatitis and 12 underwent previous gastrointestinal resection. Fecal fat excretion was aualyzed in all patients by near-infrared analysis. Steatorrhea was defined as the excretion of > 7 5gr/day of fat in feces). The optimized 13C-MTG breath test was performed by, gi~ang a ~l id test meal containing 16 gr of fat and 250 mg of substrate. Breath samples were collected betore and in 15 rain intervals tbr 6 hours after the meal. The global cumulative 13CO2 recovery (%) was considered as the result of the test. Data were analyzed by polynomic regression and the sensibility and specificity of the test were calculated by drawing the corresponding ROC curve. Results are expressed as mean and standard deviation and compared by the Wilcoxon test tbr unpaired data. Results (see table). The correlation coefficient obtained between faecal fat quantification and 13C-MTG breath test was 0.7 (p<0.0001). The sensitivity and specificity" of the 13C-MTG breath test for the diagnosis of steatorrbea were 90.5% and 91%, respectively, for an optimal cut-off point of 57.4% of i3CO2 recovered. Conclusion: The optinrized 13C-MTG breath test is a simple and very accurate tool for the diagnosis of steatorrhea in clinical practice.

Daily fecal fat ~ (sr/day) 13C.IdTG breath test (%t3CO2)

NO ~mteatorthea (n=21) 4.05~ 1,41 73.821.93 Esteatotthea (n=22) 20,1 10,33 27,5 ~ 26.73

p<o,o01 p<O,O01

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Exocrine Pancreatic Involvement in Primitive Syndrome of Sjogren Marcello Candelli, Chiara Manganelli, Enrico C. Celestino, Simona Turco, Giulia Pignataro, Maria A. Zocco, Alessandro Armuazi, Luigi Scullica, Giovanni Gasbarrini, Antonio Gasbarrini

Background. Primitive Syndrome of Sjogren(pSS) has been related to exocrine pancreatic involvement. Several diagnostic tests are available to investigate pancreatic function but most of them show low sensitivity. Aims of our stud), was to assess the prevalence of pancreatic involvement in pSS using non invasive test: Fecal Chymotb~psin (FC), [eeal efastaseq (El) and 13C Mixed Triglyceride Breath Test (MBT) and to investigate a relation between exocrine function and Schirmer Test (ST). Methods: we enrolled 24 patients (18 f , 6 m; mean age 43 +A 7 years) affected by pSS and 24 heakhy sex and age matched controls. Each subject underwent (MBT). Four mg/kg of 13C Mixed Triglyceride were administred. Breath samples were collected every 30 minutes for 6 hours just before and after labeled meal ingestion 13C enrichment was evaluated by isotope ratio mass spectrometer (BreathMat, FinneganMat, Bremen, Germany,). Results were espressed as cumulatwe percentage dose of 13C recovered at 6 hours (CPDR 6). Serum amylase, lipase, FC and El, were also evaluated. Lacrimal function was studied by' ST expressed as m m Results: tour patients and 1 control showed kiw levels of FC (<6.8 UUg~, 5 patients and no controls showed low levels of E1 (<200 UI/g) and CPDR6 low values were found in 4 patients and in no controls (< 27.8%). Patients showed lower levels of E1 (285 +/- 124 vs 391 +,/- 103; p<0.01) and FLC (34.8 +/- 21.1 vs 57.6 22.3 p <0.01) than controls. No differences on serum amylase an fipase were found between groups. Patients with at least two pancreatic function test positive were considered affected by pancreatic impairement. Pancreatic impairement was more prevalent in pSS than in controls (6/24, 25% vs 0/24; p<0.001). Interestingly, patients with pancreatic impairment showed a lower values of ST than other pSS patients (1,6 +/- 0,58 vs 5.0 +/- 1.2; p < 0,01) Conclusion: exocrine pancreatic involvement is frequent in pSS and should be suspected in case of severe lacrimal dysfunctions (ST < 2mm). Not invasive pancreatic function test could be useful to investigate pancreatic function in pSS.

W1108

Clinico-Pathological Features of Extrapancreatic Bile Duct Abnormalities Observed in Autoimmune Pancreatitis Kenji Hirano, Yutaka Komatsu, Natsuyo Yamamoto, Yonsuke Nakai, Hiroyuki lsayama, Minoru Tada, Takao Kawabe, Masao Omata, Nobuo Toda, Kazumi Tagawa, Naoki Sasahira, Tetsuro Katamoto, Takeshi Tsujino, Ryo Nakata, Tateo Kawase

AIM: We aimed to clarify the dinico-pathological features of extrapancreauc bile duct abnormalities associated with autoimmune pancreatitis, PATIENTS AND METHODS: Seven- teen patients (15 men and 2 women) with autoimmune pancreatins were included in this study'. The characteristics of autoimmune pancreatitis were studied by laboratory data, and by imaging modalities including ERCP, MRCP, EUS and CT. Patbolological features were evaluated by percutaneons needle biopsy of pancreas in 14 and of liver in 15 of 17 patients respectively. RESULTS: 1) Nine patients (53%) showed extrapancreatic bile duct abnormalit- ies like primary sclerosing cholangitis. In 6 patients among them, these changes appeared months after the diagnosis. In 5 patients who received intradnctal ultrasonography on the first ERCP, thickening of the bile duct wall was observed not only in stenotic areas but also in non-stenotic areas. 2) In 14 (93%) of 15 patients undergoing liver biopsy, lyTnphocytes infiltration with fibrosis in the portal area was observed. 3)Retroperitoneal fibrosis was recognized in 5 patients (29%). 4) Interstitial pneumonia was recognized in 4 patients (24%). 5) An increased level of IgG4 was observed in all 17 patients. 6) Prednisolone (30-40mg) was administered in 15 patients. All of them showed the improvement of narrowing of the main pancreatic duct, pancreatic swelling, and bile duct abnormalities. Retroperitoneal fibrosis and interstitial pneumonia were also improved by prednisolone therapy. CONCLU- SION: Autoimmune pancreatitis is thought to be a kind of systemic disease in which bile duct abnormalities, retroperitoneal fibrosis and interstitial pneumonia are often observed besides pancreatic changes, therefore, steroid therapy should be performed in this disease.

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A Comparison of the Pancreolauryl Ratio with Faecal Pancreatic Elastase-1 for Assessing Pancreatic Exocrine Function David Elphick, David Bullmiore, Kapi[ Kapur

Introduction: An ELISA kit for measurement of Faecal Pancreatic Elastase-1 (FED has recently been introduced for the investigation of pancreatic insufficiency We compared this test with the urine pancreolauryl ratio (PLR), The clinical response to pancreatic enzyme supplements is used as the standard against which they are compared. Methods: 45 patients under investigation for chronic diarrhoea were included in the study. All had urinary PLR measured as an outpatient. In keeping with many centres in the U.K., the urinary PLR has been the standard investigation tot pancreatic insufficiency in our hospital to date. All patterns also had a FE1 level measured on a single stool sample. 33 patients (with either a high clinical suspicion of pancreatic insufficiency, a PLR < 20 or a FE1 < 200 microgram/ gram faeces) were given a trial of pancreatic enzyme supplemems at standard dose, and their clinical response assessed. A subjective improvement in diarrhoea and objective evidence of weight gain (at least 5 % gum over 6 months) was required to record a positive response. Results: We found a strong correlation between FE1 level and clinical response to pancreatic supplements. (pwafue of 0.013 by Chi-Square analysis). See table. However, a similar analysis

A-631 AGA Abstracts

yielded no significant correlation between PLR and clinical response to Creon. (p-value O. 15). Conclusion: FE 1 more accurately' predicts response to pancreatic enzyn'te supplements than PLK This may be due to the inaccuracy inherent in performing the unne PLR as an outpatient. 1"he urinary" PLR requires two separate ten hour urine collections and a strict dietary intake, which many patients may find diffivuh to adhere to. W e have now adopted the FE1 for ~essment ot pancreatic excvrine function ni our hospital.

Response to enzyme supplements against FEI I ~ .

FEt < 200 FEI > 200 P ~ response ; 9 8 24 No Response 3 6 9

22 11 33

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FDG-PET As A Clinical Tool In Differentiation Between Pancreatic Carcinoma and Chronic Panereatitis Mariette Van Kouwen, Wire Oyen, Harry Van Goor, Jan Jansen, Joost Drenth

Background: 2-(18F)-fluow-2-deoxy-D-glucose positron emission tomography (FDG-PET) is a novel imaging technique, which enables detection of malignancies. FDG-PET has been established as an important clinical tool for diagnosis of pancreatic carcinoma. Early detection is mandatory as cure can only be achieved in non-advanced disease. This is, however, very difficult with cons, entional radiological techniques. Patients with chronic pancreatitis (CP) are at risk to develop a pancreatic carcinoma and a simple and reliable screenings method for malignant degeneration is highly desirable. We set out to investigate whetber FDG-PET scan is able to ditlerentiate between chronic pancreatitis and pancreatic carcinoma. Methods: We peribrmed FDG-PET scanning in 56 patients with chronic pancreatitis and in 16 patients with (histology proven) pancreas carcinoma. A positive scan was defined as an FDG accumula- tion in the pancreas region. Resuhs: In 50 of the 56 chronic pancreatitis (89%) patients, pancreatic FDG accumulation was absent. Minor FDG accumulation was seen in 3 patients, whereas 3 patients had significant accumulation. In patients with pancreatic carcinoma, all patients had a positive PET scan. Conclusion: FDG-PET scanning was positive in all patients with pana'eatie carcinoma, but was negative in the large majority (89%) of chronic pancreatitis patients. In CP patients with a positive PET scan maligrtancy should be excluded. FDG- PET has a potential rola as a diagnostic tool for detecting pancreatic carcinoma in longstanding chronic pancreatitis

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Prospective Evaluation of the Diagnostic Accuracy of the lntraductal Secretin Stimulation Test (IDST) and the Standard Secretin Stimulation Test (SST) in the Diagnosis of Chronic Pancreatitis (CP) Peter Draganov Anand Patel, Phillip Toskes, Chris Forsmark

SST is the gold standard tbr thnctiorul assessment of the pancreas with the I HCO3] being the most accurate parameter compared to pancreatic histology" obtained at surgery (Am J Gastroentcrol 1992; 87:1170). We evaluated 633 SST and found the peak [ HCO3] of the first 15-rain collection to be a poor predictor for CP, suggesting the short collection time in the IDST may be an inaccurate indicator of pancreatic function (Gastroim Endoscopy 1996: 43:408), IDST has also been suggested as an accurate test of pancreatic function. In this study we prospectively evaluated the diagnostic accuracy of 1DST using SST as a gold standard in patients with abdominal pain suspected to be due to CP, Methods: 19 patients were enrolled (9 M, 10 F). All patients underwent SST first and then 1DST. 9 patients received biologic porcine secretin (1 U/kg~ and 10, equivalent dose of synthetic human (02 mcg/kg). SST was performed by" collecting duodenal secretions via oroduodenaI tube in 15- man aliquots for one hour. IDST was pedormed by cannulatnig the pancreatic duct at the time of ERCP and then collecting pancreatic juice in 5-rain aliquots for 15 rain. All samples were analyzed by, back titration for [ HCO3L Peak [ HCO3I values of <80 mEq/1 for SST and < 105 mEq/1 for IDST were considered abnormal. Results: 10 patients had an abnormal SJT Sensitivity of IDST was 80% specificity 22% and overall accuracy of 52%. In our population the positive predictive value was 53% and negative predictive v'alue 50%. Because the large number of false positive test and some prior studies validating the peak [ HCO3] < 95 mEq to be diagnostic of CP, led us to reevaluate IDST performance with peak [ HCO31 < 95 mEq considered abnormal Sensitivity decreased (70%), specit]city increased (44%) but the accuracy remained poor (57%) Subgroup analysis showed that in patients with abnormal SST in = 10) the two tests (SST and IDST) correlated in 80%. In patients with normal SST (n=9) the two test correlated in only 22%. None of the 19 patients achieved maximal [ HCO3] concentration during the first 15 mni of the SST. Conclusion: The diagnostic accuracy of IDST in patients with suspected CP is poor. The talse positive rate is high, and may be due to short duration (15 rain) of pancreatic juice collection. IDST performance is particularly poor in patients with normal SST which could lead to over diagnosis of CP

Wl112

Abdominal Pain (AP) from Gastroparesis is indistinguishable from AP from Chronic Pancreatitis (CP) Virmeet Singh, G. Nicholas Verne, Pamela Snyder, Philfip Toskes

AP is ofien the primary and presenting symptom of CP. In this study we present 41 patients suspected of having AP caused by CP who turned out to have gastroparesis as a major cause of their AP. In addition to AP, 81% reported early satiety and 44% bloating but the severity of AP was out of proportion compared to the dysmotility symptoms. METHODS: We perkmned a 4-year retrospective review of 41 patients (32F, 9MY referred tbr evaluation of chronic, intractable AP of such severity requiring frequent ER visits and hospitalizations. RESULTS: Of tbe 41 patients, 9 had establisbed big duct CP and 32 were presumed m have small duct CP. All patients with a presumptive diagnosis of CP underwent further testing

(ERCP, EUS, MRCP and/or secretin stimulation) with the result that 56% (181:32) did not have CP. All 41 patients had gastnc emptying scintigraphy (GES) off narcotics and were found to have delayed gastric emptying (GE) defined as a GE half-time (TI/2) >90 mm (normal 45-90 rain). Patients received a scrambled egg meal radiolabeled with 99m-Techne- tium. In the two sets of patients, GE > o r < 4 hrs, a dose of 200mg IV EES was given and the new T1/2 measured. 19 of 41 patients had a GE>4 hrs, Two did not get EES secondary to EES allergy'. 3/17 did not respond to IV EES during GES. 82% (14/17) were EES responders. All 14 responders received long term PO EES therapy (lOOmg PO QID) with 6/14 (43%) reporting symptom relief The 6 treatment failures were given 1V EES via PICC line with a 66.7% (4/6) response rate. 22 of 41 patients had a GE < 4 hrs. 1 patient refused IV EES, 19/21 (91%) responded to IV EES during GES 18/19 responders received long term PO EES with a 13/18 (72%) response rate. Only 2/32 discontinued PO EES therapy secondary to intolerable G1 symptoms. Mean T1/2 post IV EES for both groups was 13.5 min (range 5-44 man), Mean follow-up period in the study was 118 months (range 2-45 months). CONCLUSION: 1) Abdominal pain secondary to gastroparesis was very" difficult to distinguish from abdominal pain of chronic pancreatitis. 2) Gastroparesis and chronic pancreatitis treqnently co-exist and proper management requires recognition and treatment of both. Patients with suspected gastroparesis should undergo gastric emptying scintigraphy. 3) If gastroparesis is present, in those with a T1/2 < 4 hrs, a good clinical response can be expected with long-term PO EES. If T1/2 > 4 hrs response rates with PO EES are poor but IV EES is an effective and well-tolerated akemative treatment.

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Oral Pancreatic Enzyme Supplementation in Patients with Exocrine Pancreatic Insufficiency: Is It Enough to Evaluate Clinical Response? Julio Iglesias-Garcia, Maria Iglesias-Garcia, Maria Iglesias-Rey, Enrique Dominguez-Munoz

Malnutrition related to exocrine pancreatic insufficiency is an important prognostic factor in chronic pancreatitis. Because of the absence of objective methods to establish the optimal dose of oral pancreatic enzymes, supplementation treatment is usually individualized based on clinieal parameters such as absence of diarrhoea, weight gain or absence of weight loss. Aim of our study was to evaluate the utility of the clinical response ibr the control of the efficacy of pancreatic enzyme supplementation in patients with exocrine pancreatic insufficiency due to chronic pancreatins~ Methods: 31 patients diagnosed of severe chronic pancreatitis by imaging techniques and exocrine pancreatic insufficiency by optimized breath test with 13C-mLxed triglyceride and faecal fat quantification (NIRA) were included. All patients were on a good clinical status under treatment with oral pancreatic enzymes (Kreon. Solvay-Pharma) at a stable dose over the last 12 months. In all of them, different nutritional parameters were evaluated, among them biochemical (retinol binding protein (RBP), pre- albumin and transferrin) and anthropometrical (body mass index (BMI) data. Resnhs are expressed as mean +_ standard deviation. Results: Required dose of pancreatic enzyanes ranged from 60000 to 180000 U lipase daily. Serum RBP levels were 2.7_+0.7 mg/dL (normal 3-6 mg/dL), pre-albumin 22.3 _+4.9 mg/dL (normal 21-41 mg/dL) and transfemn 257.3 _+ 51.2 mg/dL (normal 205-365 mg/dL) Values of BMI were 24A _+ 4,7 (normal>20). 21 patients (67%) had RBP levels below the lower hmit of normal, 6 of them (19%) also had abnormally low values of pre-albumin, 2 (6%) decreased levels of transferrin and 8 (26%) low BMI. All nutritional parameters were within normal range in patients with normal serum RBP levels. Conclusion: Oral pancreatic enz)nne supplementation in patients with exocrine pancreatic insufficiency due to chronic pancreatitis cannot be correctly optimized based on clinical evaluation (symptoms and signs). Serum levels of liposoluble vitamins remain frequently' abnormally low despite a theoretically- adequate oral enzyme substitution. This study confirms the need for objective methods to optimize the oral pancreatic enzyme supplementation in patients with exocrine pancreatic insufficiency.

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A Comperatives Study of Diabetic Complications in Patients with 1-Type and Pancreatic Diabetes Mellitus and in Patients with Chronic Pancreatitis Eszter Schafer, Roland Gasparics, Adam Fekete, Ist'~an Filiczky, Akos Pap

INTRODUCTION: Pancreatic disease can induce diabetes mellitus: in chronic pancreatitis about 2/3 of patients are reported to have diabetes, 1/3 to be insulin-dependent. It has been claimed that long-term diabetic complications occur rarely and in a less severe form in PDM AIMS: To study and compare the prevalences of exocrine end endocrine pancreatic insufficiency and the late complications of diabetes mellitus in patients with 1-Type-, pancre- atic diabetes mellitus (PDM) and in chronic pancraetins (CP). PATIENTS & METHODS: This study was performed on 70 patients with Type-1 diabetes meUitns and 69 patients with diabetes meUitus secondary to alcoholic chronic pancreatitis and 25 patients with CP served as a control group~ Patients were mathched for the degree of exocrin pancreatic insufficiency according to the Lundh test. During the study ophtalmoscopy, cardiovascular reflextests according to Ewing criteria, graduated tuning fork test, neurometer, mini-doppler and biochemical laboratory techniques were used. RESULTS: Diabetic background retinopa- thy was significantly, more common in patients with 1-Type DM (28/70 in 1-Type DM vs. 11/69 in PDM and 3/25 in CP). Peripheric sensory- neuropathy (3/70 vs. 28/69 and 9/25) and parasympathetic neuropathy (1/70 vs. 19/69 and 5/25) occur more frequently in case of exocrine pancreatic insufficiency. No significant difterences were found between the gomps in autonomic sympathetic neuropathy, nephropathy and rnacroangiopathy. CONCLUSION: Both chronic alcoholism and diabetes meUitus play important role in these findings, but poor glycaemic status may responsible for the higher prevalence of diabetic complications in patients with PDM.

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