33 remaining patients only 2 did not achieve complete clinical remission. One had CC and another had LC both of which were persistent histologically on follow-up biopsy. An additional 18 patients were available for follow-up biopsy all of whom were in clinical remission. 17 patients had histological remission while 1 with CC did not. This patient has remained in clinical remission without therapy. 2 patients relapsed. One had CC and relapsed 12 months post-therapy. The other had LC and relapsed 16 months post-therapy. Follow- up biopsies confirmed histological recurrence. Both patients achieved remission within 1 month after resuming mesalamine. Mean follow-up time for all patients post-therapy was 18 months. Conclusions: 1.Mesalamine is effective in producing both clinical and histological remission in microscopic colitis. 2.Maintenance therapy is not indicated for the majority of patients with microscopic colitis. 3.The relapse rate is low but patients who do relapse can expect to garner remission upon resuming mesafamine. 4.One case showed that histological remission was not needed to induce clinical remission.

482

Evaluation of a New Genetic Test Compared to Lactose Hydrogen Breath Test for the Diagnosis of Acquired Primary Lactase Deficiency Christoph Hoegenauer, Heinz F. Hammer, Karin Mellitzer, Wilfried Renner, Hermann Toplak

Background & Aims: Recent publications have demonstrated that the DNA variant -13910 T/C upstream of the LCT gene is associated with acquired primary factase deficiency (APLD). We therefore compared the value of genetic testing for the -13910 T/C variant (gene-test) to lactose hydrogen breath (H2 test) test, which is currently the clinically most widely used test for the diagnosis of acquired primary lactase deficiency. Methods: 60 consecutive patients referred for the work-up of suspected lactose intolerance were tested for the presence of the -13910 T/C variant by polymerase chain reaction restriction fragment length polymor- phism (PCR-RFLP) analysis. In these patients also a H2- test after ingestion of 50g lactose was performed for 240 minutes. Symptoms after lactose ingestion were recorded using a graduated questionnaire. Patients with discrepancy of results between H2 and gene-test were further evaluated for causes of secondary lactose malabsorption or H2 nonexcretion. Results: 21 patients had a positive test result of the hydrogen breath test for lactose malabsorption, whereas 39 patients tested negative. 14 of the 21 patients with the positive H2 test and 2 of the 39 patients with the negative H2 test reported symptoms. The results of the H2 test compared to the gene-test are shown in the table. Three patients had a negative gene-test result but a positive H2 test; all of these patients reported symptoms after lactose ingestion, and none had evidence of small bowel disease as determined by normal small bowel biopsies. Two patients had a positive gene-test result and a negative H2 test and reported no symptoms after lactose ingestion. One of these patients had a normal increase of breath hydrogen after 25g of lactulose which excluded H2 nonexcretion and a normal increase in serum glucose after an oral lactose load, which confirmed the result of the lactose hydrogen breath test. The second patient did not return for follow up studies. Sensitivity, specificity, positive predictive value, and negative predictive value of the gene-test as compared to the lactose hydrogen breath test were 86%, 94%, 90%, and 93% respectively. Conclusions: Analysis of -13910 T/C variant has a high sensitivity and specificity for detecting APLD in the clinical setting. False positive and false negative results compared to the lactose hydrogen breath test Occur.

Results of hydrogen breath test ~ test) and -13~10 TIC variant analysis (Germ test)

6onel~d pos. 6 e n e ~ neg. H2 tnt POe. 18 3 l ~ t u t nell. 2 37

483

Oral Vitamin A for the Treatment of Chronic Radiation Proctopathy: A Randomized, Controlled Trial Josh Levitsky, Eli D. Ehrenpreis, Ashesh B. Jani, Joseph Ahn, John J. Hong

BACKGROUND: Chronic radiation proctopathy commonly occurs > 6 months after pelvic irradiation of prostate and pelvic malignancies. We have recently reported success in treating a patient with oral vitamin A for a radiation-induced anal ulcer. AIM: To perform a randomized, double-blinded, placebo-controlled trial invesugating the efficacy of oral vitamin A for chronic radiation proctopathy. METHODS: Inclusion criteria: 1) > 6 months after pelvic irradiation 2) endoscopic confirmation of radiation proctopathy 3) ->2 symptoms (diarrhea, urgency, rectal pain, rectal bleeding, fecal incontinence, tenesmns) occurring at least once weekly with a severity score of --3 on a 5-point Likert scale. Patients were randomized to either vitamin A 8,000 IU BID or placebo for 3 months. The combined (frequency and severity) scores were recorded at baseline and monthly. Patients were considered responders if there was a ->4 point reduction in the combined score from baseline to 3 months. Non- responders to placebo were offered vitamin A 8,000 IU BID for 3 months. RESULTS: 16 patients were enrolled: 14 males, 2 females; median age- 71 (range 45-87); cancers- 13 prostate, 2 cervical, 1 rectal. 8 were randomized to vitamin A and 8 to placebo. At baseline, the median combined score for the vitamin A group was 25 and for the placebo group was 32 (ns, ANOVA). 7/8 patients (88%) responded to vitamin A, while only 2/8 patients (25%) responded to placebo (p<O.05, Fisher's Exact Test). After 3 months, the vitamin A group had a statistically significant reduction in the median combined score from baseline (25 to 12, p<O.05, ANOVA), while the placebo-treated group had no change in the score from baseline (32 to 26.5, ns). Five non-responders to placebo were given vitamin A open label; all five were responders. CONCLUSIONS: This is the first randomized, controlled trial for functional symptoms due to chronic radiation proctopathy. Our patients had a significant reduction in the frequency and severity of symptoms when treated with vitamin A compared to placebo. The wound healing and repair properties of vitamin A result in improved rectal function and decreased bleeding in patients with chronic radiation proctopathy.

484

Defective Bile Acid Metabolism: A New and Common Finding in Children with Constipation Alan F. Hofmann, Lee R. Hagey, Rachel E Mower, Joel E. Lavine, Vera Loening-Bancke

The two natural C24 dibydroxy bile acids, chenodeoxycholic acid (a primary bile acid) and deoxycholic acid (a secondary bile acid formed by bacterial 7-dehydroxylation of cholic acid) appear to act as endogenous cathartics in man. An increased concentration of these bile acids in the colon causes secretion and increased propulsive motility manifest clinically as diarrhea; a decreased concentration causes constipation. Trihydroxy bile acids are not cathartic. We reasoned that some cases of childhood constipation are caused by defective bile acid metabolism that in turn results in a decreased colonic concentration of these two cathartic dihydroxy bile acids. To test this hypothesis, fecal bile acids were analyzed in stool samples from children referred for constipation (N = 25) or from children with normal bowel habits (N =9). Children in the constipated group ranged in age from 0.2 to 10.8 years, and in the control group from 1.0 to 8.5 years. The bile acid composition of an isopropanol extract was determined by electrospray mass spectrometry. This powerful analytical technique separates bile acids, bile acid precursors, and bile alcohols by molecular weight and gives the relative proportions of the 20 different metabofttes of cholesterol that predominate in fecal samples of children. Abnormal fecal bile acid composition was found in 13 of 25 constipated children, but in only 1 of 9 healthy controls (p<0.05). Three types of defects were present: 1) an increased proportion of C27 bile acids (20-71%, N=5) , indicating defective oxidation of the cholesterol side chain by peroxisomal enzymes; 2) increased sulfation of dihydroxy bile acids (50-88%, N = 7), a biotransformation that is known to abolish the cathartic activity of these bile acids; and 3) a predominance of cholic acid synthesis (86%) in a 2 year old child in whom a dehydroxyfating bacterial flora had not yet developed. We conclude that abnormal hepatic bile acid metabolism causing a decreased proportion of the cathartic, dihydroxy bile acids is frequent in constipated children. Furthar studies are required to determine whether this astonishing finding is an incidental association or, as seems likely, a tree cause and effect relationship.

485

Growth Hormone (GH) Therapy In Children With Short Bowel Syndrome (SBS): A Randomized, Placebo Controlled Trial Carlos Lifschitz, Christopher Duggan, Claire Langston, Jon Vanderboof, Robert J. Shulman

Background: There are few effective therapies to assist children with SBS to decrease depen- dence on parenteral nutrition (PN). GH has been used in adults but the results have been inconclusive. Methods: To determine the efficacy of GH in decreasing dependence 6n PN, 13 PN-dependent children with SBS received either GH (0.14 mg.kg t.d ~) or placebo (P) subcutaneously daily for 3 too. after which they were svatcbed to the other treatment in a randomized, double blind tnal. Children had studies at: baseline (B), after 3 mo. of GH or P and after the second 3 too. of GH or P. Measurements included: Feeding tolerance, dual energy x-ray absorptiometry, small bowel biopsy, and anthropometrics. After the GH/P thai, children received enteral glutamine for 3 too. (0.6 g.kgkd~). Results: The mean (_+ SD) age of the children was 6.3 + 4.5 yr of age. Eleven subjects completed the study. One child was weaned from PN, 1 tolerated bolus feeding as opposed to continuous infusion EN, and 2 who had had growth hilure for several too. on EN demonstrated accelerated growth. There was a difference in lean body mass between P (13.3 _+ 6.8 kg) and GH (14.3 _+ 5.9) treatments that depended on the baseline value (12.1 _+ 6.0). The greater the baseline lean body mass, the greater was the response to GN (p = 0.054). There was a difference in fat mass between P (4.2 _+ 3.2 kg) and GH (3.2 -+ 2.1) treatments that depended on the baseline value (3.2 + 2.2). The greater the baseline fat mass, the less was the response to GH (p = 0.026). The difference in mucosal surface length to muscularis mucosa length differed between P (2.8 - 1.2) and GH (3.1 + 0.8) treatments and depended on the baseline value (3.0 -+ 1.0). The smaller the mucosal surface length to musculafis mucosa length the greater was the response to GH (p = 0.011). There were no differences between treatments in bone mineral content, weight, or height response. There were no further changes in tolerance to EN after ghitamine. Summary: These preliminary results suggest that in children with SBS 1) GH treatment may be beneficial in individual children in terms of decreasing the need for PN and 2) has modest positive effects on body composition and mucosal histology; 3) there was no apparent benefit from glutamine treatment. The improvement in EN tolerance observed in 4/11 children may be due to a GH effect on anabolism and/or improved energy utilization.

527

Anorectal Ultrasound Staging Based on Depth of Invasion for Carcinoma of the Anal Canal Charles Heise, Enrique Hernandez de Anda, Robert Madoff, Charles O. Finne, Julio Garcia-Agnilar

Purpose: Staging of squamous cell carcinoma of the anal canal (SCCAC) is based upon tumor size, though accurate measurements vathin the anal canal are difficult. Both depth of penetration and lymph node status can now be evaluated using anorectal ultrasound (ARUS). In this study we compare the clinical and ARUS staging of patients with SCCAC Methods: 43 patients with SCCAC underwent pre-treatment staging by clinical exam and by anorectal ultrasound between 1990 and 2000. Clinical T (cT) stage was defined by tumor size according to AJCC criteria (TI: < 2cm; T2 :>2 <5 cm; T3 :>5 cm; T4: other organs). Clinical nodal status was assessed by palpation of inguinal lymph nodes. Clinical TNM staging was based on AJCC criteria. Ultrasound T (uT) stage was based on depth of tumor penetration (uTl: invasion into submucosa; uT2: into internal sphincter; uT3a: into external sphincter; uT3b: through external sphincter; uT4: other organs). Ultrasound nodal status also assessed perirectal lymph nodes. Ultrasound based TNM stages are: h T1N0,T2N0; II: T3N0,T4N0; llI: any T,N1 and IV: metastatic disease. Clinical and ultrasound TNM stages are compared. Disease free survival was analyzed by ultrasound stages. Results: The cT

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