Volume 21, Number 3
`
`October 1995
`
`Editor-in-Chief Howard M. Spiro, M.D.
`
`EDITORIAL
`The Diagnosis of Liver Diseases by
`Laboratory Tests
`
`CLINICAL STUDIES
`The Yale-Affiliated Gastroenterology
`Program: 1965-1995
`Sociodemographic Characteristics, Life
`Stressors, and Peptic Ulcer
`Chronic Gastritis
`Risk of Colonic Polyps in Patients with
`Gastric Polyps
`Clinicopathologic Characteristics of
`Helicobacter Pyloric Seropositive
`Gastric Adenocarcinomas
`Long-Term Survival After Resection for
`Advanced Gastric Carcinoma
`Effect of Some Abdominal Surgical
`Operations on Small Bowel Motility
`Six Patients Whose Perianal and Ileocolic
`Crohn's Disease Improved in the Dead
`Sea Environment
`Gastrointestinal Blood Loss Due to
`Cholesterol Crystal Embolization
`
`IN THIS ISSUE...
`
`Novel Colorectal Adenocarcinoma—
`Associated 40- and 47-kDa Protein
`Antigens Recognized By Anti-60-kDa
`Heat Shock Protein Antibody
`Torulopsis Giabrata—Infected Pancreatic
`Pseudocysts
`Genotypes of Hepatitis C Virus in Taiwan
`and the Progression of Liver Disease
`Spontaneous Rupture of Hepatocellular
`Carcinoma
`
`CASE STUDIES
`Recurrence of Acute Fatty Liver of
`Pregnancy
`Hyperthyroxinemia and Elevated Lipids
`Paraneoplastic Phenomena in
`Hepatocellular Carcinoma
`
`LESSONS IN CLINICAL RADIOLOGY
`Crohn's Disease: Comparing MRI of the
`Abdomen with Clinical Evaluation
`
`BRIEF REPORTS
`
`LETTER TO THE EDITOR
`
`Lippincott - Raven
`
`Ex. 1032 - Page 1
`
`

`

`___....,__vsteaitaaimuttmaaaaiata„
`
`Journal of Clinical Gastroenterology
`
`October 1995 Volume 21 Number 3
`
`Contents
`175 About This Issue
`Howard M. Spiro
`
`Editorial
`
`176 The Diagnosis of Liver Diseases by Laboratory Tests: An Alternative to Biopsy
`Julio Collazos
`
`Clinical Studies
`
`179 The Yale-Affiliated Gastroenterology Program: 1965-1995. A Community-University Model of
`Collaboration
`Vincent A. DeLuca and Howard M. Spiro
`
`185 Sociodemographic Characteristics, Life Stressors, and Peptic Ulcer: A Prospective Study
`Susan Levenstein, George A. Kaplan, and Margot Smith
`
`193 Chronic Gastritis: Its Clinical and Physiopathological Meaning
`Rodolfo Cheli, Gianni Testino, Attilio Giacosa, and Matteo Cornaggia
`
`198 A Multicenter, Multiyear, Case-Controlled Study of the Risk of Colonic Polyps in Patients with Gastric
`Polyps: Are Gastric Adenomas a New Indication for Surveillance Colonoscopy?
`Mitchell S. Cappell and Thomas C. Fiest
`
`203 Clinicopathologic Characteristics of Helicobacter Pyloric Seropositive Gastric Adenocarcinomas
`Wei-Jei Lee, Jaw-Town Lin, Wen Chung Lee, Chia-Tung Shun, Ruey-Long Hong, Ann-Lii Cheng,
`Po-Hung Lee, Ta-Cheng Wei, and Kai-Mo Chen
`
`208 Long-Term Survival After Resection for Advanced Gastric Carcinoma
`Y Adachi, M. Mori, Y. Maehara, and K. Sugimachi
`
`(continued)
`
`Listed in Index Medicus/MEDLINE, Current Contents/Clinical Medicine, SCISEARCH, Biomedical Database, Current
`Awareness in Biological Sciences, Current Advances in Cancer Research, and Excerpta Medico. Selected articles are abstracted
`in Modern Medicine.
`
`Journal of Clinical Gastroenterology (ISSN 0192-0790) is published eight times per year in January, March, April, June, July,
`September, October, and December by Lippincott-Raven Publishers at 12107 Insurance Way, Hagerstown, MD 21740. Business
`offices are located at 227 E. Washington Square, Philadelphia, PA 19106-3780. Second-class postage paid at Hagerstown, MD
`and at additional mailing offices.
`Copyright (1) 1995 by Lippincott-Raven Publishers. All rights reserved.
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`
`Ex. 1032 - Page 2
`
`

`

`Contents (continued)
`
`211 Effect of Some Abdominal Surgical Operations on Small Bowel Motility in Humans: Our Experience
`Gabrio Bassotti, Maria Luigina Chiarinelli, Ugo Germani, Giuseppe Chiarioni, and Antonio Morelli
`
`217 Six Patients Whose Perianal and Ileocolic Crohn's Disease Improved in the Dead Sea Environment
`Gerald M. Fraser and Yaron Niv
`
`220 Gastrointestinal Blood Loss Due to Cholesterol Crystal Embolization
`W Moolenaar and C.B.H.W Lamers
`
`224 Novel Colorectal Adenocarcinoma-Associated 40- and 47-kDa Protein Antigens Recognized By
`Anti-60-kDa Heat Shock Protein Antibody
`Michiro Otaka, Setsuya Otani, Hideaki Itoh, Toshiyuki Kuwabara, Akira Zeniya, Shusei Fujimori,
`Yohtalou Tashima, and Osamu Masamune
`
`230 Torulopsis Glabrata-Infected Pancreatic Pseudocysts: Diagnosis and Treatment
`Susana Escalante-Glorsky, Adel I. Youssef, and Yang K. Chen
`
`233 Genotypes of Hepatitis C Virus in Taiwan and the Progression of Liver Disease
`Jia-Horng Kao, Pei-Jer Chen, Ming-Yang Lai, Pei-Ming Yang, Jin-Chuan Sheu, Teh-Hong Wang, and
`* ,„ Ding-Shinn Chen
`
`238 Spontaneous Rupture of Hepatocellular Carcinoma: A Review of 141 Taiwanese Cases and Comparison
`with NonruptUre Cases
`Chiung-,YNChen, Xi-Zhang Lin, Jeng-Shiann Shin, Ching-Yih Lin, Tay-Chen Leow, Chi-Yi Chen, and
`Ting-Ts:ung Chang
`
`Case Studies
`
`243 Recurrence of Acute Fatty Liver of Pregnancy
`Mario Visconti, Giampiero Manes, Francesco Giannattasio, and Generoso Uomo
`
`246 Hyperthyroxinemia and Elevated Lipids as Paraneoplastic Phenomena in Hepatocellular Carcinoma:
`A Case Report
`Rayees Nizam and Fouzia Ahmed
`
`Lessons in Clinical Radiology
`
`249 Crohn's Disease: Pilot Study Comparing NIRI of the Abdomen with Clinical Evaluation
`Ute Kettritz, Kim Isaacs, David M. Warshauer, Richard C. Semelka
`
`Brief Reports
`
`254 More Evidence for the Increasing Prevalence of Adenocarcinoma of the Esophagus over an
`18-Year Period
`Michael Y.M. Chen, David J. Ott, and David W Gelfand
`
`255 Failure of Immunosuppressive Therapy To Prevent Relapse of Celiac Sprue
`Donald R. Duerksen, Mang M. Ma, and Laurence D. Jewell
`
`(continued)
`
`Lippincott-Raven Publishers cannot be held responsible for errors or for any consequences arising from the use of the information contained
`in this journal. The appearance of advertising in this journal does not constitute an endorsement or approval by Lippincott-Raven Publishers
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`+ .50.
`Manuscripts should be submitted to Howard M. Spiro, M.D., Editor, Yale University School of Medicine, 333 Cedar Street, Box 3333, New
`Haven, Connecticut 06520-8019. Telephone: (203) 785-5494.
`Advertising inquiries should be directed to Madelyn Lopez, Advertising Director, Lippincott-Raven Publishers, 1185 Avenue of the Americas,
`New York, NY 10036. Telephone: (212) 930-9666; Fax: (212) 575-1160.
`Printed in the United States of America.
`
`Ex. 1032 - Page 3
`
`

`

`Contents (continued)
`
`257 Sigmoidorectal Intussusception from a Sigmoid Lipoma
`Andrew W Thomas, Ricardo Mitre, and George J. Brodmerkel, Jr.
`
`258 Possible Association of Acute Pancreatitis with Naproxen
`Agustin Castiella, Pilar Lopez, Luis Bujanda, and Juan I. Arenas
`
`259 Large Cell Lymphoma of the Colon Presenting as a Second Malignancy in a Patient with Hairy Cell
`Leukemia
`Gustavo A. Lopera, Oscar A. Alvarez, and Makau Lee
`
`260 Portal Hypertension Due to Incomplete Membranous Obstruction of the Portal Vein
`Yusuf Bayraktar, Gurol Oksuzoglu, Ferhun Balkanci, Serap Arslan, David H. Van Thiel,
`Ahmet Gurakar, and Burhan Kayhan
`
`Letter to the Editor
`
`263 Spontaneous Peritonitis Caused by Streptococcus Bovis: Search for Colonic Neoplasia
`Zvi Ackerman, Rami Eliakim, and Ruth Stalnikowicz
`
`264 Announcement
`
`Ex. 1032 - Page 4
`
`

`

`Contents (continued)
`
`257 Sigmoidorectal Intussusception from a Sigmoid Lipoma
`Andrew W. Thomas, Ricardo Mitre, and George J. Brodmerkel, Jr.
`
`258 Possible Association of Acute Pancreatitis with Naproxen
`Agustin Castiella, Pilar Lopez, Luis Bujanda, and Juan I. Arenas
`
`259 Large Cell Lymphoma of the Colon Presenting as a Second Malignancy in a Patient with Hairy Cell
`Leukemia
`Gustavo A. Lopera, Oscar A. Alvarez, and Makau Lee
`
`260 Portal Hypertension Due to Incomplete Membranous Obstruction of the Portal Vein
`Yusuf Bayraktar, Gurol Oksuzoglu, Ferhun Balkanci, Serap Arslan, David H. Van Thiel,
`Ahmet Gurakar, and Burhan Kayhan
`
`Letter to the Editor
`
`263 Spontaneous Peritonitis Caused by Streptococcus Bovis: Search for Colonic Neoplasia
`Zvi Ackerman, Rami Eliakim, and Ruth Stalnikowicz
`
`264 Announcement
`
`Ex. 1032 - Page 5
`
`

`

`J Clin Gactmenterrd 1995;21(2):249-53.
`
`© 1995 i3rrincott Raven Publishers, Fhilade!rhia
`
`Lessons in Clinical Radiology
`
`•
`
`Robert K. Zeman, Editor
`
`Crohn's Disease
`Pilot Study Comparing. MRI of the Abdomen
`with Clinical Evaluation
`
`Ute Kettritz, M.D., Kim Isaacs, M.D., David M. Warshauer, M.D.,
`Richard C. Semelka,
`
`Fourteen patients underwent magnetic resonance imaging
`(MRI) examination (16 studies) and clinical evaluation con-
`currently. MRI studies included gadolinium enhancement
`and TI-weighted fat-suppressed spin echo. Separate investi-
`gators determined the severity of disease on MR images and
`on clinical evaluation in a blinded fashion. MRI studies were
`evaluated for percentage of mural contrast enhancement, wall
`thickness, and length of diseased bowel. An MR product was
`generated using these parameters. Clinical evaluation used
`the Crohn's Disease Activity Index (CDAI) and modified Index
`of the International Organization for the Study of Inflam-
`matory Bowel Disease (IOIBD). Linear correlation was found
`between the MR product and clinical indexes of disease ac-
`tivity. The correlation between MR product and the modified
`IOIBD index was statistically significant (R2 = 0.633, p
`0.0012). The correlation of MR product and CDAI was less
`close (R2 = 0.274, p = 0.0373). Among individual MR
`parameters, length of diseased bowel showed the greatest
`correlation with CDAI (R2 = 0.537, p = 0.0012). Percent-
`age contrast enhancement and bowel wall thickness showed
`significant correlation to the modified IOIBD index (R2 =
`0.739, p = 0.021) but not to the CDAI (R2 = 0.004, p =
`0.825). The results of this study show that the product of
`mural contrast enhancement, wall thickness, and length of
`diseased bowel correlated with clinical indexes of disease
`activity in Crohn's disease. Our findings suggest that MRI
`may be useful in evaluating the severity of Crohn's disease
`and may provide information complementary to clinical
`evaluation.
`Key Words: Magnetic resonance imaging—Crohn's disease —
`Crohn's Disease Activity Index—Intestines.
`
`Received December 6, 1994, Sent for revision March IS, 1995.
`Accepted April 15. 1995.
`From the Department of Radiology and Gastroenterology (U.K..
`D.M.W., R.C.S.), Internal Medicine (K.I.), University of North Caro-
`lina at Chapel Hill, Chapel Hill. North Carolina, U.S.A.
`Address correspondence and reprint requests to Dr. Richard C.
`Semelka at Department of Radiology, CB 7510. University of North
`Carolina at Chapel Hill, Chapel' Hill. NC 27599-7510, U.S.A.
`
`Crohn's disease is a chronic inflammatory disease
`of bowel that has a relapsing and remitting course. Dis-
`ease activity assessment is important in the evaluation
`of relapse and the response to therapy. Clinical evalua-
`tion of Crohn's disease activity is routinely performed
`as a measure of response to drug therapy. Diagnostic
`tests have limited value in the evaluation of disease se-
`verity, especially in patients with small-bowel Crohn's
`disease. Tests used to evaluate Crohn's disease activity
`include endoscopy, computed tomography (CT), and
`barium studies. Endoscopic assessment is dependent on
`visualizing the portion of the bowel that is inflamed.
`It is limited by the inability to visualize completely the
`small bowel and the lack of assessment of transmural
`inflammation (1-3). Barium studies are similarly lim-
`ited by the inability to assess transmural disease (4).
`Although CT can evaluate transmural disease, the lesser
`contrast resolution of CT makes evaluation of disease
`severity difficult. In patients who require multiple as-
`sessments of disease activity, the dose of ionizing radia-
`tion is a limiting factor for barium examinations and CT.
`Previous studies have shown good correlation between
`magnetic resonance imaging (MRI) using gadolinium
`enhancement and fat suppression and endoscopy for
`determining severity and type of inflammatory bowel
`disease (5.6). This pilot study was performed to com-
`pare abdominal MRI with clinical evaluation in the de-
`termination of disease severity in patients with Crohn's
`disease of the small bowel or small bowel and colon.
`
`METHODS
`
`Patients
`Fourteen patients (six men, ages 19-46 years with a mean
`age of 31.2 years) with known Crohn's disease, seen at Uni-
`
`249
`
`Ex. 1032 - Page 6
`
`

`

`F
`
`•
`
`250 (cid:9)
`
`U KETTRI7Z ET AL.
`
`versity of North Carolina hospitals, who were studied by MRI
`were included in this study. The MRI exam was clinically
`indicated in seven patients. The remaining seven patients were
`recruited for the study during a clinic visit. The duration
`of the disease ranged from 21 months to 18 years (average
`9.6 years). Ten patients had had surgery, and all patients were
`on medical therapy for Crohn's disease. Patients gave their
`informed consent to enter into this study in accordance with
`the requirement of our institutional review board. All patients
`underwent MRI examination within 3 days of the clinical
`evaluation of their disease activity; one patient underwent
`three studies combined with clinical evaluation. The patient
`who underwent three MRI exams had one done before initia-
`tion of drug therapy and 6 and 12 weeks after treatment
`was started.
`
`MRI
`MRI studies were performed on a 1.5-T imager (Magne-
`tom SP 4000; Siemens Medical Systems, Iselin, NJ, U.S.A.).
`Spoiled gradient echo (SGE) (TR = 140 ms, TE = 4.5 ms)
`images were taken in the transverse plane, acquiring 14 sec-
`tions of —1 cm thickness in a 20-s breath-hold period. Three
`SGE image acquisitions were obtained, to encompass the
`abdomen and pelvis. Tl-weighted fat-suppressed spin-echo
`(T1FS) (TR = 500-700 ms, TE = 15 ms) images were taken
`of the region of the terminal ileum. Image acquisition was
`performed in the transverse plane, and 12 sections were ac-
`quired in 5.4-6 min. Gadolinium chelate (Omniscan;
`Sanofi Winthrop Pharmaceuticals, New York, NY, or Mag-
`nevist; Berlex Laboratories Inc., Wayne, NJ, U.S.A.) was
`administered by rapid i.v. injection at a dose of 0.1 mmol/kg.
`SGE was performed immediately through the region of the
`terminal ileum. T1FS was initiated at 45 s postgadolinium
`through the terminal ileum and pelvis, and a second post-
`gadolinium TIFS acquisition was performed through the mid-
`and upper abdomen.
`
`Data analysis
`Measurements on MR images and clinical evaluation were
`determined by separate investigators in a prospective, blinded
`fashion. The clinical evaluations were done prospectively
`(before the MRI examination) in seven patients and retrospec-
`tively, but blinded as to MRI results, in seven patients.
`
`Image analysis
`Percentage of contrast enhancement (%CE) was deter-
`mined on a remote console using manually performed region
`of interest (ROI) measurements of signal intensity (SI) on
`pre- and postcontrast TIFS images. ROIs were measured of
`the bowel wall; inclusion of the bowel lumen was carefully
`avoided. Noise was measured anterior to the abdomen, and
`standard deviation (SD) of noise was used for calculations.
`The %CE was determined using the following formula:
`
`x 100 x
`
`% CE = SI bowel postcontrast — SI bowel precontrast
`SI bowel precontrast
`SD noise precontrast
`SD noise postcontrast
`The length of diseased bowel was determined on precon-
`trast SGE and postcontrast TIFS MR images. The most dis-
`eased segment of bowel was evaluated for %CE and wall
`thickness. Wall thickness was measured on the postcontrast
`T1FS images.
`
`J Clin Gastroenterol, Vol. 21, No. 3, 1995
`
`All MRI measurements were performed independently by
`two authors (R.C.S. and U.K.), and the average of the mea-
`surements was used for the calculations. The MRI product
`(MRP) was calculated using the following formula: MRP
`(%CE of diseased small bowel x length of diseased small
`bowel X wall thickness of diseased small bowel) + (%CE of
`diseased colon x length of diseased colon x wall thickness
`of diseased colon).
`
`Clinical evaluation
`The clinical indexes and laboratory measurements were
`made within 1 week of the MRI study. Disease activity was
`assessed using the Crohn's Disease Activity Index (CDAI)
`and the modified Oxford Index of the International Organi-
`zation for the Study of Inflammatory Bowel Disease (IOIBD)
`(7). For the patients who were prospectively enrolled into
`the study, a diary card was completed that rated daily ab-
`dominal pain, well-being, and number of bowel movements.
`The patient underwent physical examination and blood work
`before MRI examination. In patients who were studied after
`a clinically indicated MRI examination, the CDAI was cal-
`culated retrospectively through chart review and interview
`of the patients. Crohn's disease was considered active if the
`CDAI value was >150.
`The IOIBD was assessed using a 10-point rating system
`(8). The score was calculated prospectively in the seven pa-
`tients enrolled in the study from the clinic and retrospectively
`through chart review and interview of those who had a clin-
`ically indicated MRI examination.
`
`Statistical analysis
`Simple linear regressions were performed comparing the
`clinical tests with the MRI findings. This was done as an
`exploratory analysis. The statistical package used for analy-
`sis was Statview (Abacus Concepts Inc.) for the Macintosh.
`Statistical significance for correlation of data was determined
`using the simple linear regression models. The a priori hy-
`pothesis was that disease activity as measured by MRI is de-
`termined by bowel permeability (percentage enhancement),
`length of diseased bowel, and thickness of diseased bowel.
`In this pilot study, exploratory analyses were done looking
`at the MRP as well as the individual components measured
`on the MRI examination.
`
`RESULTS
`
`The CDAI ranged from 90 to 340 (mean 201.2). The
`modified IOIBD index ranged from 1 to 8 (mean 4.5),
`and the MRP ranged from 40.5 to 4,829.0 (mean 1,946.0).
`Significant correlation was present between the MRP
`and both the modified IOIBD index (Fig. 1) and the
`CDAI (Fig. 2). The greater correlation was found be-
`tween the MRP and the modified IOIBD index (Table 1).
`Among individual MR parameters, length of the dis-
`eased bowel, including small bowel and colon, demon-
`strated the closest correlation to the CDAI and the modi-
`fied IOIBD index. Contrast enhancement of the bowel
`wall and bowel wall thickness showed significant cor-
`relation to the modified IOIBD index but not to the CDAI
`(Table 1).
`
`Ex. 1032 - Page 7
`
`

`

`F
`
`• (cid:9)
`
`•
`
`ti
`
`MRI VERSUS CLINICAL EVALUATION OF CROHN'S DISEASE
`
`251
`
`0
`
`0
`
`O
`
`5000
`
`4500
`
`4000
`
`3500
`
`3000
`
`13 2500
`
`cc 2000
`
`1500
`
`1000
`
`500
`
`0
`
`-500
`
`2 (cid:9)
`
`3 (cid:9)
`
`4 (cid:9)
`
`5 (cid:9)
`IOIBD
`FIG. 2. Correlation between the modified index of the Inter-
`national Organization for the Study of Inflammatory Bowel
`Disease and %CE of the terminal ileum. R 2 = 0.739.
`
`6 (cid:9)
`
`7 (cid:9)
`
`8
`
`9
`
`inflammation than upon superficial lesions found by
`endoscopy (1,3). Radiographic findings in the National
`Cooperative Crohn's Disease Study of the U.S.A. did
`not correlate with clinical symptoms or response to drug
`therapy (4).
`MRI has been shown to be of value in the diagnosis
`of inflammatory bowel disease. Gadolinium-enhanced
`fat-suppressed MR images are sensitive for the detec-
`tion of Crohn's disease (5,6,9,10). MRI findings include
`full-thickness wall involvement (Fig. 3), circumferen-
`tial segment involvement interspersed with segments
`of asymmetric involvement, and inflammatory strand-
`ing in the mesentery due to dilated vasa recta and sinus
`tracts. Associated findings include presence of inflam-
`matory nodes, fistulas, and abscesses (5,6). Bowel wall
`thickness, length of diseased segments, and degree of
`contrast enhancement with gadolinium have been shown
`to correlate well with disease activity based on surgical
`and/or endoscopic findings (5,6). The individual param-
`eter that best correlated with endoscopic findings was
`the percentage of contrast enhancement. MRI criteria
`may also permit distinction of Crohn's disease from
`ulcerative colitis (5).
`In the current study, as in previous studies that have
`shown good correlation between MRI and findings at
`CT, endoscopy, and surgery, we have shown that MRI
`findings correlated to clinical evaluation in the assess-
`
`0 2 (cid:9)
`
`0
`
`2
`
`3
`
`4
`
`6
`
`7
`
`8
`
`9
`
`IOIBD
`FIG. 1. Correlation between the modified index of the Inter-
`national Organization for the Study of Inflammatory Bowel
`Disease (IOIBD) and the MR product. R 2 = 0.633.
`
`Serial examination
`In one patient identified through the clinic, an MRI
`examination was performed at the time of relapse di-
`agnosis of Crohn's disease. The patient was started on
`therapy, and repeated examinations were performed 6
`and 12 weeks after the initiation of therapy. Serial MRPs
`were 4,665, 965, and 1,779. (baseline, before treatment;
`6 weeks; and 12 weeks), corresponding to IOIBD scores
`of 8, 5, and 5 and to CDAI scores of 185, 116, 118, re-
`spectively, at each of the time points.
`
`DISCUSSION
`
`Treatment of Crohn's disease requires frequent as-
`sessment of disease activity. Different methods are used
`to determine disease severity. Previous studies have
`shown poor correlation between Crohn's disease clin-
`ical activity and the widely used diagnostic methods
`endoscopy and barium enema. This lack of correlation
`presumably reflects, in part, the limited ability of endos-
`copy to evaluate the terminal ileum, the limited ability
`of barium studies to assess acuity of disease, and the
`inability of both techniques to determine transmural
`involvement (1-4). In addition, it may represent the
`largely subjective nature of the clinical activity indexes
`and differences in patients' perception and reporting.
`Clinical activity may depend more upon transmural
`
`TABLE 1. Correlation coefficients (expressed as R2) between MR findings
`and CDAI and modified IOIBD (Oxford) Index
`
`MR product
`
`0.633
`(p = 0.0002)
`0.274
`(p = 0.0373)
`
`%CE
`
`0.739
`(p < 0.0001)
`0.004
`(p = 0.8252)
`
`Length of
`diseased bowel
`
`0.04
`(p = 0.4554)
`0.537
`(p = 0.0012)
`
`Bowel wall
`thickness
`
`0.393
`(p = 0.0093)
`0.156
`(p = 0.13)
`
`Modified IOIBD index
`
`CDAI
`
`p = P-value.
`
`J Clin Gastroenterol, Vol. 21, No. 3, 1995
`
`Ex. 1032 - Page 8
`
`(cid:9)
`(cid:9)
`(cid:9)
`(cid:9)
`

`

`252
`
`(A)
`
`(B)
`
`FIG. 3. A 43-year-old patient with severe ileal Crohn's dis-
`ease (CDAI, 185; modified IOIBD index, 8; MR product,
`4,664). Precontrast Ti-weighted fat-suppressed image
`(T1FS) (A) shows circumferential wall thickening of the il-
`eum. On the postcontrast T1FS image (B), the ileum shows
`substantial enhancement of the entire bowel wall.
`
`ment of Crohn's disease activity. To determine disease
`activity by MRI, we calculated an MRP that took into
`account %CE, wall thickness, and length of the dis-
`eased bowel segment. Disease activity was calculated
`as a sum for the small bowel and colon, which may
`more accurately reflect disease activity than evaluation
`of one segment of bowel. The MRP correlated (R2 =-
`0.633, p = 0.0002) to clinical activity as assessed by
`the IOIBD index. It did not correlate well with the more
`subjective Crohn's disease activity index (Fig. 1).
`Significant correlation was found between the %CE
`alone and the modified IOIBD index; %CE has been
`previously shown to correlate well with severity of dis-
`ease (5,6). The %CE reflects increased capillary leak-
`age and accumulation of fluid in the interstitial space,
`which corresponds to the degree of active inflammation.
`Of all the parameters examined, the %CE correlated
`to the greatest extent with the modified IOIBD.
`Length of diseased bowel reflects the extent of dis-
`ease distribution, which should influence a patient's
`symptomatology. We found significant correlation be-
`tween length of diseased small bowel and colon seg-
`ments and clinical disease activity looking at the more
`
`J Gun Gastroenterol, Vol. 21, No. 3, 1995
`
`U KETTRITZ ET AL.
`
`subjective CDAI index. Since abdominal pain and diar-
`rhea are weighted very heavily in this index, length
`of diseased bowel is likely to influence the score.
`The advantages of MRI include inherent objectivity
`of data and the safety of the technique. Objectivity is
`important under circumstances in which patients on
`medical therapy are monitored serially. The safety of
`the method is of value in Crohn's disease, since many
`patients are young and of childbearing potential and
`require serial examinations (10). The lack of ionizing
`radiation may be important in this context, and it is
`clearly an advantage over CT and barium studies. Other
`attractive features of MRI include direct sagittal imag-
`ing with a noninvasive procedure and limited bowel
`preparation.
`The difficulty in the analysis of this study is related
`to the limitation of the clinical activity indexes. The
`CDAI was developed in 1976 (7) by the National Co-
`operative Crohn's Disease Study and redefined in 1979
`(11). The widely used index is calculated from eight,
`mainly clinical variables. The CDAI is largely based
`on subjective symptoms and complaints and accordingly
`has been considered controversial since its introduction
`(2,12). Some of the symptoms, such as abdominal pain,
`diarrhea, and weight loss, could be related to structural
`changes (e.g., greater stool frequency and weight loss
`following ileostomy) more than to disease activity. The
`CDAI reflects the degree of illness more closely than
`the degree of disease activity (2,12). The patients in
`this study did not represent a uniform population—some
`had undergone large-bowel or small-bowel resection.
`Previous resection may lead to increased reporting of
`diarrhea.
`Comparisons between patients with respect to the
`CDAI may vary greatly depending on self-reporting.
`In this study, for 13 of 14 patients a single time point
`was examined. The difference in subjective data in de-
`termining the CDAI may be responsible for the relative
`lack of correlation of MRI parameters and CDAI score.
`On the other hand, in the patient who was studied before
`treatment and then treated and restudied, there was a
`marked improvement in clinical activity and MRI ac-
`tivity, as measured by the MRP. This preliminary evi-
`dence suggests a potential role for MRI in the serial
`assessment of patients. The MRI findings correlated
`better to the more objective assessment by the modified
`IOIBD index possibly because the parameters of the
`IOIBD index are not weighted and there is less subjec-
`tive variability.
`The relative expense of the technique may raise some
`concern in terms of routine use in activity assessment.
`However, the differences in procedural costs of MRI,
`colonoscopy, and CT are not substantial ($1,057, $1,200,
`and $776, respectively). A small-bowel follow-through
`is less expensive ($238) but is limited by the amount
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`Ex. 1032 - Page 9
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`MRI VERSUS CLINICAL EVALUATION OF CROHN'S DISEASE (cid:9)
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`253
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`of radiation exposure and the diminished ability to assess
`disease activity.
`Although this study is limited by using subjective
`clinical assessments to correlate with MRI for the de-
`termination of disease activity, we consider it an im-
`portant comparison because clinical evaluation is com-
`monly used in the assessment of disease severity. We
`have shown that MRI findings, particularly the MRP
`and %CE, correlate with clinical evaluation. Since cor-
`relation between endoscopy or barium studies and clin-
`ical evaluation has been less successful (1-4), this study
`suggests that MRI may compare better with clinical
`appearance than the other diagnostic tests.
`In conclusion, the MRP of %CE x wall thickness
`x length of diseased bowel correlated with clinical
`evaluation. More patients need to be studied using this
`comparison to confirm the results. Specifically, com-
`parison of MRI with serial clinical examination of pa-
`tients during the course of their disease may be bene-
`ficial, to show whether MRI data reflect response to
`disease therapy. This observation may increase the role
`of MRI in the evaluation of Crohn's disease, because
`data from MRI may be comparable to clinical evaluation.
`
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