2
Findings on colonoscopy revealed numerous large diverticula in 15 patients and occasional medium diverticula in 2 patients. The distribution was in the descending and sigmoid colon in 15 patients and only in the descending colon in 2 patients. We obtained mucosal biopsy specimens from the areas adjacent to the diverticula as well as from distant sites. Results: The diverticula were associated with adjacent erythema, patchy erosions, or petechiae in 4 of the 17 patients. Histopathology revealed mild chronic non – specific inflammation in 13 patients, collagenous colitis in 2 cases, lymphocytic colitis in 1 case and no inflammation in 1 patient. Two patients had ASCA positive serology and 1 patient had Omp c positive serology. Biopsies from areas distant to the diverticula were also studied. Conclusions: In this pilot study group there is a surprisingly high incidence (94 %) of inflammation in the mucosa adjacent to diverticula. This finding needs further controlled study to determine its significance in predicting and preventing acute or chronic diverticulitis. 343 TRENDS OF UTILIZATION OF VARIOUS TESTS USED FOR SCREENING FOR COLORECTAL CANCER (CRCA) IN THE MEDICARE POPULATION Mohamad A. Eloubeidi, M.D., M.H.S., Xinzhi Zhang, M.D., Maria Pisu, Ph.D., Norman Weissman, Ph.D. and Jeffrey Burkhardt, Ph.D.*. Division of Gastroenterology and Hepatology, University of Alabama at Brimigham, Birmingham, AL; Department of Health Services Administration, University of Alabama at Birmingham, Birmingham, AL and Center for Outcomes and Effectiveness Research and Education (COERE), University of Alabama at Birmingham, Birmingham, AL. Purpose: Effective July 2001, an enacted federal law entitles Medicare beneficiaries to receive a screening colonoscopy (cs) every 10 years. However, the use of various tests for screening for CRCA in the medicare population is not well defined prior to 2001.To determine trends of utili- zation of various tests to screen for CRCA in the Medicare population, and to analyze changes in practice of various specialists that utilize these tests. Methods: This study used data from Physician/Supplier Procedure Sum- mary (PSPS) File, which is a part of Part B Medicare Files including data on the utilization of physician services, covered by the Medicare Supple- mental Medical Insurance (SMI) plan. Each PSPS file contains frequency data, charge data, carrier number, physician specialty, and HCPCS proce- dure codes appearing on the Medicare claims. All Medicare physician and supplier services claims for CRCA screening from year 1997 to year 2000 were included in this study. CRCA screening procedures were divided into five categories and well designated CPT codes for screening were used: (1) Proctosigmoidoscopy (PS) (2) Flexible Sigmoidoscopy (FS) (3) Colonos- copy (4) Barium Enema (BE) (5) FOBT. Results: The variation in utilization from 1997 to 2000 shows that PS decreased by 35%, FS decreased by 11%, BE decreased by 33%, and FOBT decreased by 43%. Only CS increased during this period, by 39%. The increase was for both screening (% 32) and therapeutic polypectomy (40%). CS for high risk individuals increased by 89%. The use of CS increased across all specialties but mostly by physicians in ambulatory surgery centers (79%). The use of BE and PS decreased across all special- ties. While the use of FS decreased throughout specialties, it increased by 80% in ASC. Interestingly, the use of FOBT dropped strikingly by 43% and most significantly in general practice (–52%), internal medicine (–51%), and family practice (– 44%), respectively. Conclusions: Colonoscopy use for CRCA screening was rising while use of other tests was declining precipitously in the Medicare population. The decline in FOBT and FS use by primary care physicians is worrisome. Efforts are needed to address manpower needs in gastroenterology as well as increase education in PCP circles about CRCA screening. 344 THE ROLE OF POLYAMINES AND ORNITHINE DECARBOXYLASE IN SPORADIC ADENOMATOUS POLYPS OF THE COLON Giorgio Ricci, M.D., Gianluca Bersani, M.D., Monica De Mattei, M.D., Giordano Stabellini, M.D., Giovanni De Fabritiis, M.D., Angelo Rossi, M.D., Alessandra Suzzi, M.D., Francesco Santilli, M.D., Beatrice Gorini, M.D., Massimo Gandolfi, M.D. and Vittorio Alvisi, M.D.*. Clinical Experimental Medicine, Postgraduate School of Gastroenterology, University of Ferrara, Ferrara, Italy; Morphology & Embriology, Histology, University of Ferrara, Ferrara, Italy and Morphology, Human Anatomy, University of Milan, Milan, Italy. Purpose: The levels of Polyamines (PA) and Ornithine decarboxylase (ODC) in colonic mucosa are reported to be sensitive biochemical markers of potential cancer risk, especially when genetic factors occur. In sporadic adenomatous polyps of the colon the role of PA and ODC is less clear. Thus we have determined both PA – Putrescine (PUT), Spermidine (SPD), Spermine (SPM) – and ODC in the colonic mucosa of patients affected by sporadic polyps of the colon. The relation between histological type of the polyps and the PA–ODC mucosal levels was investigated. Methods: Thirty patients (32–79 yrs; 13 F) – after giving their informed consent – were admitted to the study, whenever polyps during colonoscopy were evidenced. Ten subjects with unconfirmed colon disease were con- trols. The removed polyps underwent histological examination. Mucosal biopsy specimens were obtained 2–3 cm distant from the polyp and from the control mucosa. The specimens were frozen with liquid nitrogen and stored at – 80°C. PA were determined with HPLC and ODC with radio- metric assay. PA values are expressed as nmol/g protein; ODC activity as pmol 14 CO 2 /hr/mg protein. Mann–Whitney’s test was used for the statis- tical analysis. Results: The values are expressed as medians and ranges in the table. In patients with Tubulovillous adenomas and moderate dysplasia SPD and ODC levels are significantly higher (p0.05) than controls. PUT SPD SPM ODC TubMild dys (10) 0.93 (0.24–1.43) 0.64 (0.23–1.76) 1.87 (0.46–3.92) 87 (21–223) TubVillMild dys (9) 0.79 (0.23–1.63) 1.29 (0.41–1.72) 2.29 (0.97–3.47) 98 (53–189) TubVillMod dys (11) 1.52 (0.25–2.87) 1.91 (0.47–3.28) 3.83 (0.69–4.94) 282 (104–598) Controls (10) 0.41 (0.29–0.61) 0.53 (0.31–0.84) 1.77 (0.21–2.77) 79 (21–157) Tubtubular; Villvillous; dysdysplasia; ModModerate Conclusions: Our results have evidenced the significant increase of SPD and ODC in sporadic polyps of the colon with enhanced dysplasia degree. This behavior would confirm the important role of such biomarkers on investigating the potential risk of colon cancer. 345 INCREASED EXPRESSION AND CO–LOCALIZATION OF COX–2, EGFR, ERBB2 AND HGF/MET RECEPTORS IN COLON CANCER. A KEY TO INCREASED GROWTH AND INVASIVENESS? Louis Hernandez, M.D., Woo S. Moon, M.D., Rama Pai, Ph.D., Jerald Jensen, M.D. and Andrzej S. Tarnawski, M.D.*. Gastroenterology, Department of Veterans Affairs Medical Center, Long Beach, CA. Purpose: Colorectal cancer is the second most frequent cancer in the Western world. Several lines of evidence indicate that in addition to growth factor receptors such as epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (HGF/Met–R), colon cancer growth and invasion may be promoted by prostaglandins, especially the E2 series (PGE2), generated by the cyclooxygenase–2 (Cox–2) enzyme. Our recent study demonstrated that PGE2 induces proliferation and growth of colon cancer cells by transactivating EGFR (Pai et al. Nature Med. 2002; 8:289 – S113 AJG – September, Suppl., 2002 Abstracts

Increased expression and co-localization of Cox-2, EGFR, ERBB2 and HGF/Met receptors in colon cancer. a key to increased growth and invasiveness?

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Page 1: Increased expression and co-localization of Cox-2, EGFR, ERBB2 and HGF/Met receptors in colon cancer. a key to increased growth and invasiveness?

Findings on colonoscopy revealed numerous large diverticula in 15patients and occasional medium diverticula in 2 patients. The distributionwas in the descending and sigmoid colon in 15 patients and only in thedescending colon in 2 patients. We obtained mucosal biopsy specimensfrom the areas adjacent to the diverticula as well as from distant sites.Results: The diverticula were associated with adjacent erythema, patchyerosions, or petechiae in 4 of the 17 patients. Histopathology revealed mildchronic non – specific inflammation in 13 patients, collagenous colitis in 2cases, lymphocytic colitis in 1 case and no inflammation in 1 patient. Twopatients had ASCA positive serology and 1 patient had � Omp c positiveserology. Biopsies from areas distant to the diverticula were also studied.Conclusions: In this pilot study group there is a surprisingly high incidence(94 %) of inflammation in the mucosa adjacent to diverticula. This findingneeds further controlled study to determine its significance in predictingand preventing acute or chronic diverticulitis.

343

TRENDS OF UTILIZATION OF VARIOUS TESTS USED FORSCREENING FOR COLORECTAL CANCER (CRCA) IN THEMEDICARE POPULATIONMohamad A. Eloubeidi, M.D., M.H.S., Xinzhi Zhang, M.D., Maria Pisu,Ph.D., Norman Weissman, Ph.D. and Jeffrey Burkhardt, Ph.D.*.Division of Gastroenterology and Hepatology, University of Alabama atBrimigham, Birmingham, AL; Department of Health ServicesAdministration, University of Alabama at Birmingham, Birmingham, ALand Center for Outcomes and Effectiveness Research and Education(COERE), University of Alabama at Birmingham, Birmingham, AL.

Purpose: Effective July 2001, an enacted federal law entitles Medicarebeneficiaries to receive a screening colonoscopy (cs) every 10 years.However, the use of various tests for screening for CRCA in the medicarepopulation is not well defined prior to 2001.To determine trends of utili-zation of various tests to screen for CRCA in the Medicare population, andto analyze changes in practice of various specialists that utilize these tests.Methods: This study used data from Physician/Supplier Procedure Sum-mary (PSPS) File, which is a part of Part B Medicare Files including dataon the utilization of physician services, covered by the Medicare Supple-mental Medical Insurance (SMI) plan. Each PSPS file contains frequencydata, charge data, carrier number, physician specialty, and HCPCS proce-dure codes appearing on the Medicare claims. All Medicare physician andsupplier services claims for CRCA screening from year 1997 to year 2000were included in this study. CRCA screening procedures were divided intofive categories and well designated CPT codes for screening were used: (1)Proctosigmoidoscopy (PS) (2) Flexible Sigmoidoscopy (FS) (3) Colonos-copy (4) Barium Enema (BE) (5) FOBT.Results: The variation in utilization from 1997 to 2000 shows that PSdecreased by 35%, FS decreased by 11%, BE decreased by 33%, and FOBTdecreased by 43%. Only CS increased during this period, by 39%.

The increase was for both screening (% 32) and therapeutic polypectomy(40%). CS for high risk individuals increased by 89%. The use of CSincreased across all specialties but mostly by physicians in ambulatorysurgery centers (79%). The use of BE and PS decreased across all special-ties. While the use of FS decreased throughout specialties, it increased by80% in ASC. Interestingly, the use of FOBT dropped strikingly by 43% andmost significantly in general practice (–52%), internal medicine (–51%),and family practice (–44%), respectively.Conclusions: Colonoscopy use for CRCA screening was rising while useof other tests was declining precipitously in the Medicare population. Thedecline in FOBT and FS use by primary care physicians is worrisome.Efforts are needed to address manpower needs in gastroenterology as wellas increase education in PCP circles about CRCA screening.

344

THE ROLE OF POLYAMINES AND ORNITHINEDECARBOXYLASE IN SPORADIC ADENOMATOUS POLYPSOF THE COLONGiorgio Ricci, M.D., Gianluca Bersani, M.D., Monica De Mattei, M.D.,Giordano Stabellini, M.D., Giovanni De Fabritiis, M.D., Angelo Rossi,M.D., Alessandra Suzzi, M.D., Francesco Santilli, M.D., BeatriceGorini, M.D., Massimo Gandolfi, M.D. and Vittorio Alvisi, M.D.*.Clinical Experimental Medicine, Postgraduate School ofGastroenterology, University of Ferrara, Ferrara, Italy; Morphology &Embriology, Histology, University of Ferrara, Ferrara, Italy andMorphology, Human Anatomy, University of Milan, Milan, Italy.

Purpose: The levels of Polyamines (PA) and Ornithine decarboxylase(ODC) in colonic mucosa are reported to be sensitive biochemical markersof potential cancer risk, especially when genetic factors occur. In sporadicadenomatous polyps of the colon the role of PA and ODC is less clear. Thuswe have determined both PA – Putrescine (PUT), Spermidine (SPD),Spermine (SPM) – and ODC in the colonic mucosa of patients affected bysporadic polyps of the colon. The relation between histological type of thepolyps and the PA–ODC mucosal levels was investigated.Methods: Thirty patients (32–79 yrs; 13 F) – after giving their informedconsent – were admitted to the study, whenever polyps during colonoscopywere evidenced. Ten subjects with unconfirmed colon disease were con-trols. The removed polyps underwent histological examination. Mucosalbiopsy specimens were obtained 2–3 cm distant from the polyp and fromthe control mucosa. The specimens were frozen with liquid nitrogen andstored at –80°C. PA were determined with HPLC and ODC with radio-metric assay. PA values are expressed as nmol/g protein; ODC activity aspmol 14CO2/hr/mg protein. Mann–Whitney’s test was used for the statis-tical analysis.Results: The values are expressed as medians and ranges in the table. Inpatients with Tubulovillous adenomas and moderate dysplasia SPD andODC levels are significantly higher (p�0.05) than controls.

PUT SPD SPM ODC

Tub�Mild dys(10)

0.93 (0.24–1.43) 0.64 (0.23–1.76) 1.87 (0.46–3.92) 87 (21–223)

TubVill�Milddys (9)

0.79 (0.23–1.63) 1.29 (0.41–1.72) 2.29 (0.97–3.47) 98 (53–189)

TubVill�Moddys (11)

1.52 (0.25–2.87) 1.91 (0.47–3.28) 3.83 (0.69–4.94) 282 (104–598)

Controls (10) 0.41 (0.29–0.61) 0.53 (0.31–0.84) 1.77 (0.21–2.77) 79 (21–157)

Tub�tubular; Vill�villous; dys�dysplasia; Mod�Moderate

Conclusions: Our results have evidenced the significant increase of SPDand ODC in sporadic polyps of the colon with enhanced dysplasia degree.This behavior would confirm the important role of such biomarkers oninvestigating the potential risk of colon cancer.

345

INCREASED EXPRESSION AND CO–LOCALIZATION OFCOX–2, EGFR, ERBB2 AND HGF/MET RECEPTORS IN COLONCANCER. A KEY TO INCREASED GROWTH ANDINVASIVENESS?Louis Hernandez, M.D., Woo S. Moon, M.D., Rama Pai, Ph.D., JeraldJensen, M.D. and Andrzej S. Tarnawski, M.D.*. Gastroenterology,Department of Veterans Affairs Medical Center, Long Beach, CA.

Purpose: Colorectal cancer is the second most frequent cancer in theWestern world. Several lines of evidence indicate that in addition to growthfactor receptors such as epidermal growth factor receptor (EGFR) andhepatocyte growth factor receptor (HGF/Met–R), colon cancer growth andinvasion may be promoted by prostaglandins, especially the E2 series(PGE2), generated by the cyclooxygenase–2 (Cox–2) enzyme. Our recentstudy demonstrated that PGE2 induces proliferation and growth of coloncancer cells by transactivating EGFR (Pai et al. Nature Med. 2002; 8:289–

S113AJG – September, Suppl., 2002 Abstracts

Page 2: Increased expression and co-localization of Cox-2, EGFR, ERBB2 and HGF/Met receptors in colon cancer. a key to increased growth and invasiveness?

293). However, the precise relationship between Cox–2 and growth factorreceptors remains unclear, forming the basis of this study.Methods: Human colon cancer specimens were obtained from patientsundergoing surgical resection. Tissue sections were immunostained withspecific antibodies against Cox–2, EGFR, ErbB2 and HGF/Met–R. Immu-nostaining was quantified by adding the intensity of the stain to the area ofstain using videoimage analysis system. Correlation between Cox–2 andEGFR, ErbB2 and HGF/Met receptors expression was determined.Results: Immunohistochemical staining of cancer tissues demonstratedincreased expression of Cox–2 (77.8% increase; p�0.05), EGFR (129.4%increase; p�0.002), ErbB2 expression (109% increase; p�0.0001) andHGF/Met–R (188.9% increase; p�0.04) vs. normal appearing colonicmucosa. Cox–2 overexpression correlated well with EGFR and ErbB2expression (both r � 0.668), especially at the invasive front of the cancers.Conclusions: (a) Colon cancer displays increased expression of Cox–2 anddistinct growth factor receptors. (b) Overexpression of Cox–2 showedcorrelation with increased ErbB2 and EGFR expression in colon cancer. (c)These findings indicate a spatial and temporal relationship between growthfactor receptors and Cox–2 expression in colon cancer growth and inva-sion.

346

THE USE OF COLONOSCOPY TO DETECT NEOPLASIA:GENDER AND AGE IMPLICATIONSTyler Stevens, M.D. and Carol A. Burke, M.D.*. The Department ofGastroenterology and Hepatology, The Cleveland Clinic Foundation,Cleveland, OH.

Purpose: A recent colonoscopy study in men found 52% of subjects withadvanced proximal neoplasia (APN) had no distal adenomas. The risk ofAPN in women and elderly subjects without distal adenomas is unknown.Our aim was to determine the effect of gender and age on prevalence ofadvanced adenomas and the risk of APN without distal neoplasia.Methods: All colonoscopy records between 1997–2000 were reviewed.Exams done for CRCA screening, change in bowel habit, or abdominalpain were included. Demographic information and location, size, andpathology of neoplasia was determined. “Distal” � rectum and sigmoid,“proximal” � remaining colonic segments. Advanced neoplasia (AN) �villous, tubulovillous or carcinoma in situ, size�1cm, or invasive cancer.Results: 981 subjects (49% female) were included. The mean age was 65(range 50–100). 194 (20%) subjects had neoplasia. 85/194 (44%) hadneoplasia distally and 109/194 (56%) had only proximal neoplasia. AN wasdetected in 43 (4.3%) subjects. (table 1) No difference was noted in theprevalence or location of AN between women vs men . Subjects �70 yrswere more likely to have advanced neoplasia distally. Of subjects withAPN 2/19 (13%) had distal neoplasia. Women with APN were more likelyto have distal adenomas 20% than men 0%. Distal neoplasia was morecommon in subjects with APN � 70 yrs (14%) than subjects �70 (8%).

Table 1. Prevalence and Location of Advanced Neoplasia

Advanced NeoplasiaAdvanced Neoplasia with

Distal Adenoma

Distal Proximal Total Proximal

Total 24/981 (2.4%) 19/981 (1.9%) 26/43 (60%) 2/19 (13%)Female 11/483 (2.3%) 10/483 (2.1%) 13/21 (62%) 2/10 (20%)Male 13/498 (2.6%) 9/498 (1.8%) 13/22 (59%) 0/9 (0%)� 70 yrs 12/630 (1.9%) 12/630 (1.9%) 13/24 (54%) 1/12 (8.3%)� 70 yrs 12/351 (3.4%) 7/351 (2.0%) 13/19 (68%) 1/7 (14%)

Conclusions:

1. More than half of subjects with proximal neoplasia and 75% withadvanced proximal neoplasia have no distal neoplasia.

2. The prevalence and location of advanced neoplasia is similar in womenand men.

3. Women and subjects � 70 yrs with advanced proximal neoplasia weremore likely to harbor distal neoplasia than men or younger subjects.

4. The use of flexible sigmoid for colorectal neoplasia screening wouldmiss more than 75% of subjects with advanced proximal neoplasia.

347

PREVALENCE OF COLORECTAL NEOPLASIA IN PATIENTSWITH A HISTORY OF BREAST CANCERJames Smith, M.D.* and J. Scott Manton, M.D. Gastroenterology,Ochsner Clinic Foundation, New Orleans, LA.

Purpose: To determine the prevalence of colorectal neoplasia in womenwith a history of breast cancer who underwent colonoscopy versus controlsin our patient population.Methods: Breast cancer patients and sex and age matched control patientsbetween the ages of 45–80 years were eligible for the study. Study grouppatients were taken from the breast cancer registry at our institution fromJanuary 1990 to December 2000. After review of the records of 1251 breastcancer patients, we found 180 who had colonoscopy. Breast cancer wasdiagnosed after colonoscopy in 36 patients and they were excluded fromthe study, leaving a study group of 144 patients who had colonoscopy afterthe diagnosis of breast cancer. The average interval between the diagnosisof breast cancer and colonoscopy in the study group was 3.1 years. Thecontrol group was taken from our endoscopy databank from January 2000to January 2001. The index colonoscopy was defined as the colonoscopynearest to the diagnosis of breast cancer for the study group.Results: Patient characteristics in the two groups including family history,smoking history, obesity, and NSAID use were similar. The indications forcolonoscopy in the study and control groups were similar: gastrointestinalbleeding (25.7% vs 16.7%), polyp on flexible sigmoidoscopy (27.1% vs31.7%), anemia (8.33% vs 10%), family history of colonic neoplasia(29.9% vs 22.8%), and change in bowel habits (13.9% vs 13.9%) respec-tively. Adenomatous polyps were found in 60/144(41.7%) and95/180(53%) patients in the study and control groups, respectively (byFisher’s Exact p �0.047). Colorectal cancer was found in 5/144 pa-tients(3.47%) in the study group and 1/180 (0.56%) in the control grou-p(RR�1.91[1.31,2.78], by Fisher Exact p�.06).Conclusions: Adenomatous polyps were significantly more prevalent inthe control group but only a trend existed for colorectal cancer to be moreprevalent in the breast cancer group. These results do not lend firm supportto the hypothesis that colon cancer is more common in patients with breastcancer. Properly designed prospective studies are needed to address thisissue further.

348

AN ONGOING STUDY TO ASSESS THE EFFICACY OF BOWELPREPARATION WITH THE USE OF A PRE–PACKAGED DIET/BOWEL PREPARATION KIT VERSUS CUSTOMARYPREPARATION FOR COLONOSCOPYMark H. Delegge, M.D.*. Division of Gastroenterology and HepatologyDigestive Disease Center, Medical University of South Carolina,Charleston, SC.

Purpose: The efficacy of standard bowel preparation for colonoscopy isoften limited by patient compliance. Patient compliance is often impactedby their tolerance of the prescribed cathartic and also by the discomfort ofmaintaining a clear liquid diet on the day of bowel preparation. Weoriginally reported on our results in 35 patients using a pre–packaged foodkit on the day of bowel preparation coupled with a magnesium citrate,bisacodyl tablet, bisacodyl suppository colon cleansing regimen as com-pared to a standard clear liquid diet and Fleet Phospha–Soda colon regimen.We now report on the results of 269 patients.Methods: 269 patients were prospectively randomized to one of two bowelpreparations on the day prior to colonoscopy. Active group 1 (A) receivedmagnesium citrate, oral bisacodyl tablets, a bisacodyl suppository and apre–packaged combination of a low residue solid and liquid food diet. Thecontrol group (C) received Fleet Phospha–Soda and a clear liquid diet,representing our standard bowel cleansing regimen. Patient tolerance of the

S114 Abstracts AJG – Vol. 97, No. 9, Suppl., 2002