Inflammatory bowel disease unclassified

Inflammatory bowel disease unclassified first-author corresp ‡Corresponding Author ‡Corresponding Author †E-mail:zlym@zju.edu.cn †E-mail:zlym@zju.edu.cn zlym@zju.edu.cn Department of Gastroenterology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China Department of Gastroenterology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China Objective: 2 Inflammatory bowel diseases (IBDs) are idiopathic, chronic, and inflammatory intestinal disorders. The two main types, ulcerative colitis (UC) and Crohn’s disease (CD), sometimes mimic each other and are not readily distinguishable. The purpose of this study was to present a series of hospitalized cases, which could not initially be classified as a subtype of IBD, and to try to note roles of the terms indeterminate colitis (IC) and inflammatory bowel disease unclassified (IBDU) when such a dilemma arises. Methods: 2 Medical records of 477 patients hospitalized due to IBD, during the period of January 2002 to April 2009, were retrospectively studied in the present paper. All available previous biopsies from endoscopies of these patients were reanalyzed. Results: 2 Twenty-seven of 477 IBD patients (5.7%) had been initially diagnosed as having IBDU. Of them, 23 received colonoscopy and histological examinations in our hospital. A total of 90% (9/10) and 66.7% (4/6) of patients, respectively, had a positive finding via wireless capsule endoscopy (CE) and double-balloon enteroscopy (DBE). The barium-swallow or small bowel follow-through (SBFT) was performed on 11 patients. Positive changes were observed under computer tomographic (CT) scanning in 89.5% (17/19) of patients. Reasonable treatment strategies were employed for all patients. Conclusions: 2 Our data indicate that IBDU accounts for 5.7% of initial diagnoses of IBD. The definition of IBDU is valuable in clinical practice. For those who had no clear clinical, endoscopic, histological, or other features affording a diagnosis of either UC or CD, IBDU could be used parenthetically. Inflammatory bowel disease unclassified Ulcerative colitis Crohn’s disease Subtype Diagnosis Introduction 1 Disease classification is important, especially in the context of tailoring clinical therapy. Though many scanning procedures make the diagnosis of inflammatory bowel disease (IBD) earlier and easier, the variations and lack of endoscopic-histological correlation sometimes are difficult for decision-making. The terms indeterminate colitis (IC) and colonic inflammatory bowel disease unclassified (IBDU) were coined in an attempt to classify these entities more effectively (Guindi and Riddell, 2004 2004 ). Moreover, it provides benefits for both the decision-making of the correct treatment and the prognosis and understanding of disease course. To date, few reports have documented this specific kind of disease in Chinese patients; therefore, we herein retrospectively examined IBDU patient admitted to our hospital. Materials and methods 1 During the period of January 1, 2002 and April 15, 2009, 477 consecutive in-patients with clinically- and pathologically-confirmed IBD were studied. A diagnosis of IBDU was considered when the morphology included overlapping features of ulcerative colitis (UC) and Crohn’s disease (CD) regarded as inconsistent with either diagnosis (Branco et al., 2009 2009 ), and all such cases were confirmed after discussions by pathologists, endoscopists, and clinicians. In this series, 261 cases were classified as UC, 189 cases as CD, and 27 cases as IBDU. The notes of these 27 patients were carefully reviewed, with 22 as potential diagnosis of UC, and five favoring diagnosis of CD. Results 1 Clinical features 2 Eleven men and sixteen women with median age at onset of IBDU 40.22 years (range 13–75 years) were identified. Abdominal pain (21), diarrhea (11), fever (7), bloody stool (4), vomiting (4), abdominal distention (3), and constipation (1) were the main symptoms. During the course, three subjects also had extra-gastrointestinal manifestations (EIM), including arthralgia (3), erythema nodosun (3), mucocutaneous abscess (3), ulcer (2), and rectum-vagina fistula (1). Two subjects had a colonectomy performed and one underwent an appendectomy before diagnosis. Among the subjects with IBDU, seven involved both large bowel and small bowel at onset. Three (11.1%) had pancolonic involvement at the time of diagnosis. Four (14.8%) had primarily left-sided and right-sided diseases, respectively. Fourteen (51.8%) had small bowel involvement including seven in ileum and seven showing a distribution from the jejunum to ileum. The remaining two (7.4%) had extensive diseases. Modalities for diagnosis 2 Colonoscopy, upper gastrointestinal (GI) endoscopy, capsule endoscopy (CE), biopsies, serological findings, radiography, and other scanning procedures are the common modalities for separation of UC and CD. All 27 subjects underwent an endoscopy and surgical pathology study, including 23 cases conducted in our hospital. Segmental lesions of irregular or villous surface, pseudovillous appearance, backwash ileitis, and absence of lymphoid aggregates were observed in 22 potential UC subjects. Diffuse or pancolonic (rectal sparing) CD-like patchiness such as superficial fissuring ulceration or confluent linear ulcers, cobblestone sign, focal cryptitis, epithelioid granulomas, and crypt abscesses, with normal adjacent mucosa, was seen in five subjects. Only one specimen exhibited mild dysplasia. No crypt atrophy was microscopically observed. Nine of ten subjects who accepted CE examination had multiple erosions and ulcerations in the small intestine, with only one having a negative finding. Three subjects showed luminal narrowing of the small bowel on CE studies. Gastroscopy was conducted in ten subjects, and superficial gastritis was found in the biopsies from seven subjects. Scattered slit-like fissures in the small bowel were found in three out of six subjects who underwent double-balloon enteroscopy (DBE). The small bowel follow-through (SBFT) indicated the presence of aphthous ulcers or liner ulcers, stricture exacerbation, chronic shortening with tubular narrowing, and loss of haustration in 72.7% (8/11) subjects. Wall-thickening, pneumocolon, inflammatory mass, extraluminal findings, etc. were mainly observed in 89.5% (17/19) of the subjects under computer tomographic (CT) examination. In the full blood count, anemia was the common change which occurred in eighteen subjects. Seven subjects had high white blood count (WBC). Concentration of platelets was high in six subjects. The level of C-reactive protein (CRP) was elevated in ten subjects. Eight cases had hypoalbuminemia. Therapy and short-time outcome 2 A total of 21 subjects were treated with 5-aminosalicyclic acid (5-ASA). Eight subjects received steroids. All of the subjects’ symptoms went into remission and did well with conventional therapy. No subject experienced adverse events during 5-ASA treatment. Discussion 1 Since it was first proposed, the definition of IC/IBDU has changed over the years, and it has been universally accepted in pediatrics (Romano et al., 2008 2008 ). Children with IC/IBDU have an early age of disease onset, which rapidly progresses to pancolitis (Carvalho et al., 2006 2006 ). For adult patients, however, the debates around the term ‘IC/IBDU’ have been never-ending. Some experts observed that the great majority of IC/IBDU patients ( > 80%) had long-term functional results identical to those of patients with chronic UC (Tekkis et al., 2005 2005 ). A longitudinal study showed that 13% of subjects will remain unclassified after one year of follow-up (Notteghem et al., 1993 1993 ). In comparison, more experts consider that IC/IBDU is an interim or preliminary appellation rather than a distinctive clinical entity of IBD because less than 5% maintained that diagnosis over time (Burakoff, 2004 2004 ; Talbot, 2005 2005 ). The term IC/IBDU is widely used with a relatively lower threshold without uniformed criterion by pathologists, surgeons and clinicians. And the incidence of use of the term IC/IBDU is thought to be increasing despite the meaning indicated by the Montreal Working Party (Satsangi et al., 2006 2006 ), with referral bias being a possible reason. Some experts are afraid that construction of an ileoanal pouch in those patients who were initially misdiagnosed as IC/IBDU may result in significant morbidity and pouch failure when the ultimate diagnosis is CD (Marcello et al., 1997 1997 ). Thus, caution is warranted before using this term. Due to the poorly established histopathological criteria of IC/IBDU, more researches are required to sufficiently describe this sort of disease and to improve our recognition, while reducing the taxonomic dilemma and indiscriminate use in clinic practice. To date, few cases labeled with IC/IBDU in adults have been reported. The proportion of IC/IBDU cases among all IBD cases in our series, 5.7%, is equal to that reported by the previous studies (Yantiss and Odze, 2006 2006 ). In our clinical setting, patients should undergo a combined upper endoscopy, colonoscopy, and biopsy and/or imaging modalities as the initial diagnostic procedure. The diagnosis of IC/IBDU relies on the presence of the following (Geboes et al., 2008 2008 ): clear evidence of IBD but insufficient evidence to make a definite diagnosis of either UC or CD; clinical and macroscopic features of either CD or UC, without clear histology; inflammatory colitis containing features on macroscopic and microscopic evaluations of the colon that are consistent with both CD and UC; colitis without an identifiable cause and with clinical features of both UC and CD; mucosal ulcerative colitis with histological features of CD such as skip lesions, transmural inflammation, granulomata or mucin depletion, but no clinical or radiological evidence of CD; and colitis for which endoscopic, histologic, and radiologic criteria fail to discriminate between UC and CD of the colon. Colonoscopy with multiple biopsy specimens from different sites is the first-line procedure used to make a precise diagnosis. Pathologists play an important role in the diagnosis of IBD. Clinicians should offer detailed evidence for easier diagnosis. Upper gastroscopy, CE, CT, magnetic resonance imaging (MRI), and other ancillary tests are recommended. They sometimes provide important information in diagnostically-difficult cases. Technological advances, based on genetic markers and a better knowledge of immune responses, have allowed better characterization (Geboes et al., 2008 2008 ). Patients with IC/IBDU are often diagnosed as anti-neutrophil cytoplasmic antibody (ANCA)-negative and anti- Saccharomyces cerevisiae antibody (ASCA)-negative. Pseudomonas fluorescens -associated sequence I2 (anti-I2), the Bacteroides caccae TonB-linked outer membrane protein OmpW, ASCA, and fecal calprotectin, a new promising marker for intestinal inflammation, are non-invasive, sensitive, and specific tools used for early identification of IBD (Ashorn et al., 2009 2009 ). It has been reported that anti-synthetic mannoside antibodies (AΣMA) revealed the heterogeneity of the anti-oligomannose antibody response in CD subjects and increased the sensitivity of CD diagnosis when combined with ASCA (Vandewalle-El Khoury et al., 2008 2008 ). Suzuki et al. ( 2008 2008 ) found that anti-porcine pancreatic amylase (PPA) antibodies combined with ASCA/anti-I2 may be useful for differentiating CD from UC. There are also reports that infectious gastroenteritis was a close relative of IBD, but the value of serologic markers in distinguishing IBD remains controversial (Arai, 2010 2010 ; Dotan, 2010 2010 ; Dubinsky, 2010 2010 ). Serum C-reactive protein (CRP) correlates well with other measures of biological activity but not as well with clinical activity (Moscandrew and Loftus, 2009 2009 ). It was reported that CE is superior to IBD serological markers in identifying small bowel CD in IC subjects (Leighton et al., 2007 2007 ). In a large prospective study, only 50% of subjects with an initial diagnosis of IC and positive serology testing were ultimately reclassified as either UC or CD (Joossens et al., 2002 2002 ). To our knowledge, literature rarely refers to the management of IBDU alone. Treatment philosophies now attempt to alter the natural history of the disease and prevent long-term complications. Except for adequate food supplement, a broad range of therapies are available, including aminosalicylates, corticosteroids, immunomodulators, biologics, and surgery, though it is not entirely clear how well IBDU clinically responds to them. Whether it is a coined term or a real entity, to establish such a ‘grey zone’ is a philosophy of management. It is convenient and effective for doctors to pay more attention to the patients with overlapping histological features of CD and UC. For the sake of tailoring the pharmacological treatment especially prior to surgical intervention, CD- or UC-oriented IBDU is advised. This may be important when considering a subsequent restorative proctectomy (Wells et al., 1991 1991 ), but it can easily cause doctors to be less likely to explore the disease. IBDU-favoring CD may be treated according to the scheme of CD, while IBDU-favoring UC may be treated as similar to UC. Aminosalicylates are widely used as a basal medicine for treating mild to moderate IBDs in China. Sulfasalazine gradually trends to be substituted by 5-ASA products because of the side effects, while corticosteroids remain a conventional therapy. It is well-known that early corticosteroid administration improves the healing rate of peristomal pyoderma gangrenosum in IBD. We have less experience in using immunomodulators to treat IBD, but an Asian study showed that azathioprine is effective in corticosteroid-dependent Asian IBD subjects (Thia et al., 2011 2011 ). It was also reported that mycophenolate mofetil appeared safe, well tolerated, and efficacious for both short- and long-term therapies, without the need for dose escalation (Tan and Lawrance, 2009 2009 ). Bastida et al. ( 2010 2010 ) reported that thiopurine immunomodulators alone, or with other treatments, have a positive and long-lasting impact on the health-related quality of life (HRQoL) of IBD patients. Biological agents offer therapeutic options as rescue therapy after failing to respond to steroids. Though infliximab does not appear to increase rates of emergent surgery or multistep procedures in patients undergoing treatment for IC (Bordeianou et al., 2010 2010 ), it was shown to be effective in improving clinical symptoms (Gornet et al., 2003 2003 ). General opinion is that anti-tumour necrosis factor-alpha (TNF-α) medications, such as infliximab and adalimumab, are more efficacious in the treatment of CD than in the treatment of UC. Furthermore, the safety profile associated with infections and certain malignancies is under discussion (Ngo et al., 2010 2010 ). Pearce and Lawrance ( 2007 2007 ) proposed that careful patient selection may improve infliximab’s efficacy. Clinical remission appears greater after induction with three infliximab doses in CD subjects. Clinical efficacy is suggested for UC/IBDU. A prospective evaluation of the long-term outcome revealed that patients with IBDU and IC can undergo ileal pouch-anal anastomosis and expect a long-term outcome equivalent to patients with UC (Murrell et al., 2009 2009 ). Leukocytapheresis is a technology in development since 1999. Data show that granulocyte/monocyte adsorption (GMA; Adacolumn, JIMRO, Takasaki, Japan) in patients with steroid-dependent or steroid-refractory IBD is associated with striking efficacy and tapering or discontinuation of steroids, whereas in steroid-naive patients, GMA spared patients from steroids (Hanai, 2008 2008 ). It is an additional remission option for chronically active IBD patients (Lindberg et al., 2010 2010 ). With better use of standard therapies, approximately 50% of resection surgery was “potentially avoidable” (Gapasin et al., 2010 2010 ). Ileorectal anastomosis (IRA) in patients with UC gives an acceptable quality of life and functional outcome as compared to ileal pouch-anal anastomosis (IPAA) (da Luz Moreira et al., 2010 2010 ). Although the chance of an adverse outcome increases after IPAA on patients with UC/IC, such as risks of perineal complications and pouch loss, the operation continues to be performed on these patients (Pezim et al., 1989 1989 ; Dayton et al., 2002 2002 ). The reason that patients with IC should not be precluded from having IPAA surgery is that they are more likely to develop CD (Gramlich et al., 2003 2003 ). It was reported that ileoproctostomy is preferred over ileoanal pull-through in patients with IC (Bodzin et al., 1995 1995 ). The problem of too many IC/IBDU diagnoses in clinic practice is mainly due to the low threshold for this label, which then covers all cases of diagnostic uncertainty (Stange et al., 2006 2006 ). It is especially apposite in cases of acute fulminant disease of the colorectum (Martland and Shepherd, 2007 2007 ). To avoid the indiscriminate use of IC/IBDU, and to conquer the diagnostic obstacles, a combination of clinical presentation, endoscopic appearance, radiology, histology, surgical findings, and even serologic testing is advocated. The following points should be kept in mind: (1) Not all pathologically-ambiguous specimens are diagnosed as IC. Histological interpretation should not be relied upon too greatly. Although good pathologic materials make diagnosis much easier, it is quite difficult to obtain well-known histology especially during onset of the disease. We should think twice before making a diagnosis for those in a first attack because microscopic features and the features characteristic of disease activity vary with time and treatment. (2) Several circumstances, such as microscopic colitis, diverticulitis, and diversion colitis, may also show IBD-like changes (Yantiss and Odze, 2006 2006 ) on occasion. (3) Failure to recognize the morphologic variants of CD and UC and accept any of the “hardcore” features as definitive evidence of the two entities may lead to a potentially erroneous diagnosis of IC (Yantiss and Odze, 2006 2006 ). For instance, granulomas are not always CD-related. (4) Multiple deep biopsies may provide effective information that will assist in improving the accuracy of diagnoses. For CD diagnosis, specimen with submucosa or muscularis propria is beneficial for the judgment during diagnosis. (5) It is commonly believed that IC does not involve the upper gastrointestinal (GI) tract; therefore, for those with suspected IBD or new-onset IBDU, routine upper-endoscopy and CE at initial presentation facilitate the diagnosis. (6) To improve the compliance rate (especially in maintenance), medicine is required to be fast-acting, easily used, inexpensive, effective, and safe. (7) Surveillance and reassessment are necessary for benefit to the subjects, even for those who have a reasonable diagnosis of CD or UC. It might be of more benefit to reexamine the patients within one year initially, and then at follow-up intervals of a maximum 2.5 years. Because many cases presumed as IBDU are seen early in the disease course (Guindi and Riddell, 2004 2004 ; Talbot, 2005 2005 ), 50%–80% of them can be reclassified as definite UC or CD with time (Geboes and de Hertogh, 2003 2003 ). (8) Initial therapy has an influence on the further diagnostic testing and long-term prognosis (permanent ostomy vs. ileoanal pouch anastomosis). Inappropriateness of early management of newly diagnosed IBD may increase potential risk of adverse events. The presentation under endoscopy, radiology and pathology will change after treatment (medication or surgery). Therefore, one must be cautious during selection of therapy. Careful patient selection may improve response rates to medicine in IBD. Moreover, a series problem should be solved including phenotypes, epidemiology, location, behavior, severity, the nature history (remission or relapse), extraintestinal manifestations of the disease, a guideline for macroscopic and microscopic criteria, and management, as well as prognosis. Guidelines and diagnostic route charts for routine and special cases are expected. Further studies, such as the head-to-head comparison between patients with CD or UC and those clinical features inclining towards the diagnosis of CD or UC, would be very meaningful to improve our recognize of IBD. The drawback of our review is that the true nature history and outcome of IBDU are not known, as some of the long-term follow-up data are unavailable. It was reported that approximately 80% of IBDU cases were ultimately reclassified as either UC or CD within eight years of follow-up (Meucci et al., 1999 1999 ). There is now good evidence that the majority of IBDU diagnoses are likely to behave as unusual examples of UC, with only 10%–40% of them ultimately proving to be CD (Yantiss and Odze, 2006 2006 ). In conclusion, our clinical observations suggest that IC/IBDU is a clinicopathological entity. IC/IBDU should be diagnosed on the basis of a constellation of clinical, endoscopic, histological, radiological, and biochemical findings. Specimens in conjunction with appropriate techniques can avoid delays in diagnosis as time-dependent reappraisal of the lesions within weeks, and follow-up is needed to allow a more precise diagnosis. References R Arai . Serologic markers: impact on early diagnosis and disease stratification in inflammatory bowel disease . Postgrad Med , 2010 . 122 ( 4 ): 177 - 185 . 20675980 DOI: 10.3810/pgm.2010.07.2184 http://doi.org/10.3810/pgm.2010.07.2184 . Serologic markers: impact on early diagnosis and disease stratification in inflammatory bowel disease S Ashorn , T Honkanen , KL Kolho , M Ashorn , T Välineva , B Wei , J Braun , I Rantala , T Luukkaala , S Iltanen . Fecal calprotectin levels and serological responses to microbial antigens among children and adolescents with inflammatory bowel disease . Inflamm Bowel Dis , 2009 . 15 ( 2 ): 199 - 205 . 18618670 DOI: 10.1002/ibd.20535 http://doi.org/10.1002/ibd.20535 . Fecal calprotectin levels and serological responses to microbial antigens among children and adolescents with inflammatory bowel disease G Bastida , P Nos , M Aguas , B Beltrán , M Iborra , V Ortiz , V Garrigues , R Estevan , J Ponce . The effects of thiopurine therapy on health-related quality of life in inflammatory bowel disease patients . BMC Gastroenterol , 2010 . 10 ( 1 ): 26 20196836 DOI: 10.1186/1471-230X-10-26 http://doi.org/10.1186/1471-230X-10-26 . The effects of thiopurine therapy on health-related quality of life in inflammatory bowel disease patients JH Bodzin , SN Klein , SG Priest . Ileoproctostomy is preferred over ileoanal pull-through in patients with indeterminate colitis . Am Surg , 1995 . 61 ( 7 ): 590 - 593 . 7793739 . Ileoproctostomy is preferred over ileoanal pull-through in patients with indeterminate colitis L Bordeianou , H Kunitake , P Shellito , R Hodin . Preoperative infliximab treatment in patients with ulcerative and indeterminate colitis does not increase rate of conversion to emergent and multistep abdominal surgery . Int J Colorectal Dis , 2010 . 25 ( 3 ): 401 - 404 . 19798508 DOI: 10.1007/s00384-009-0800-5 http://doi.org/10.1007/s00384-009-0800-5 . Preoperative infliximab treatment in patients with ulcerative and indeterminate colitis does not increase rate of conversion to emergent and multistep abdominal surgery BC Branco , N Harpaz , DB Sachar , AJ Greenstein , P Tabrizian , JJ Bauer , AJ Greenstein . Colorectal carcinoma in indeterminate colitis . Inflamm Bowel Dis , 2009 . 15 ( 7 ): 1076 - 1081 . 19177428 DOI: 10.1002/ibd.20865 http://doi.org/10.1002/ibd.20865 . Colorectal carcinoma in indeterminate colitis R Burakoff . Indeterminate colitis: clinical spectrum of disease . J Clin Gastroenterol , 2004 . 38 ( Suppl. 1 ): S41 - S43 . 15115931 DOI: 10.1097/01.mcg.0000123991.13937.7e http://doi.org/10.1097/01.mcg.0000123991.13937.7e . Indeterminate colitis: clinical spectrum of disease RS Carvalho , V Abadom , HP Dilworth , R Thompson , M Oliva-Hemker , C Cuffari . Indeterminate colitis: a significant subgroup of pediatric IBD . Inflamm Bowel Dis , 2006 . 12 ( 4 ): 258 - 262 . 16633047 DOI: 10.1097/01.MIB.0000215093.62245.b9 http://doi.org/10.1097/01.MIB.0000215093.62245.b9 . Indeterminate colitis: a significant subgroup of pediatric IBD A da Luz Moreira , RP Kiran , I Lavery . Clinical outcomes of ileorectal anastomosis for ulcerative colitis . Br J Surg , 2010 . 97 ( 1 ): 65 - 69 . 20013930 DOI: 10.1002/bjs.6809 http://doi.org/10.1002/bjs.6809 . Clinical outcomes of ileorectal anastomosis for ulcerative colitis MT Dayton , KR Larsen , DD Christiansen . Similar functional results and complications after ileal pouch-anal anastomosis in patients with indeterminate vs. ulcerative colitis . Arch Surg , 2002 . 137 ( 6 ): 690 - 695 . 12049540 DOI: 10.1001/archsurg.137.6.690 http://doi.org/10.1001/archsurg.137.6.690 . Similar functional results and complications after ileal pouch-anal anastomosis in patients with indeterminate vs. ulcerative colitis I Dotan . New serologic markers for inflammatory bowel disease diagnosis . Dig Dis , 2010 . 28 ( 3 ): 418 - 423 . 20926866 DOI: 10.1159/000320396 http://doi.org/10.1159/000320396 . New serologic markers for inflammatory bowel disease diagnosis MC Dubinsky . Serologic and laboratory markers in prediction of the disease course in inflammatory bowel disease . World J Gastroenterol , 2010 . 16 ( 21 ): 2604 - 2608 . 20518081 DOI: 10.3748/wjg.v16.i21.2604 http://doi.org/10.3748/wjg.v16.i21.2604 . Serologic and laboratory markers in prediction of the disease course in inflammatory bowel disease J Gapasin , DR van Langenberg , G Holtmann , DJ Hetzel , JM Andrews . Potentially avoidable surgery in IBD: what proportion of patients come to resection without optimal preoperative therapy? A guidelines-based audit . Intern Med J , 2010 . Epub ahead of print DOI: 10.1111/j.1445-5994.2010.02328.x http://doi.org/10.1111/j.1445-5994.2010.02328.x . Potentially avoidable surgery in IBD: what proportion of patients come to resection without optimal preoperative therapy? A guidelines-based audit K Geboes , G de Hertogh . Indeterminate colitis . Inflamm Bowel Dis , 2003 . 9 ( 5 ): 324 - 331 . 14555917 DOI: 10.1097/00054725-200309000-00007 http://doi.org/10.1097/00054725-200309000-00007 . Indeterminate colitis K Geboes , JF Colombel , A Greenstein , DP Jewell , WJ Sandborn , MH Vatn , B Warren , RH Riddell . Indeterminate colitis: a review of the concept—what’s in a name? . Inflamm Bowel Dis , 2008 . 14 ( 6 ): 850 - 857 . 18213696 DOI: 10.1002/ibd.20361 http://doi.org/10.1002/ibd.20361 . Indeterminate colitis: a review of the concept—what’s in a name? JM Gornet , S Couve , Z Hassani , JC Delchier , P Marteau , J Cosnes , Y Bouhnik , JL Dupas , R Modigliani , F Taillard , 等 . Infliximab for refractory ulcerative colitis or indeterminate colitis: an open-label multicentre study . Aliment Pharmacol Ther , 2003 . 18 ( 2 ): 175 - 181 . 12869077 DOI: 10.1046/j.1365-2036.2003.01686.x http://doi.org/10.1046/j.1365-2036.2003.01686.x . Infliximab for refractory ulcerative colitis or indeterminate colitis: an open-label multicentre study T Gramlich , CP Delaney , AC Lynch , FH Remzi , VW Fazio . Pathological subgroups may predict complications but not late failure after ileal pouch-anal anastomosis for indeterminate colitis . Colorectal Dis , 2003 . 5 ( 4 ): 315 - 319 . 12814408 DOI: 10.1046/j.1463-1318.2003.00449.x http://doi.org/10.1046/j.1463-1318.2003.00449.x . Pathological subgroups may predict complications but not late failure after ileal pouch-anal anastomosis for indeterminate colitis M Guindi , RH Riddell . Indeterminate colitis . J Clin Pathol , 2004 . 57 ( 12 ): 1233 - 1244 . 15563659 DOI: 10.1136/jcp.2003.015214 http://doi.org/10.1136/jcp.2003.015214 . Indeterminate colitis H Hanai . Leucocytapheresis for inflammatory bowel disease in the era of biologic therapy . Eur J Gastroenterol Hepatol , 2008 . 20 ( 7 ): 596 - 600 . 18679059 DOI: 10.1097/MEG.0b013e3282f5e9f3 http://doi.org/10.1097/MEG.0b013e3282f5e9f3 . Leucocytapheresis for inflammatory bowel disease in the era of biologic therapy S Joossens , W Reinisch , S Vermiere , B Sendid , D Poulain , M Peeters , K Geboes , X Bossuyt , P Vandewalle , G Oberhuber , 等 . The value of ASCA and ANCA in IC: a prospective follow up study . Gastroenterology , 2002 . 122 ( 5 ): 1242 - 1247 . 11984510 DOI: 10.1053/gast.2002.32980 http://doi.org/10.1053/gast.2002.32980 . The value of ASCA and ANCA in IC: a prospective follow up study JA Leighton , P Legnani , EG Seidman . Role of capsule endoscopy in inflammatory bowel disease: where we are and where we are going . Inflamm Bowel Dis , 2007 . 13 ( 3 ): 331 - 337 . 17206673 DOI: 10.1002/ibd.20058 http://doi.org/10.1002/ibd.20058 . Role of capsule endoscopy in inflammatory bowel disease: where we are and where we are going A Lindberg , M Eberhardson , M Karlsson , P Karlén . Long-term follow-up with granulocyte and monocyte apheresis re-treatment in patients with chronically active inflammatory bowel disease . BMC Gastroenterol , 2010 . 10 ( 1 ): 73 20604939 DOI: 10.1186/1471-230X-10-73 http://doi.org/10.1186/1471-230X-10-73 . Long-term follow-up with granulocyte and monocyte apheresis re-treatment in patients with chronically active inflammatory bowel disease PW Marcello , DJJr Schoetz , PL Roberts , JJ Murray , JA Coller , LC Rusin , MC Veidenheimer . Evolutionary changes in the pathologic diagnosis after the ileoanal pouch procedure . Dis Colon Rectum , 1997 . 40 ( 3 ): 263 - 269 . 9118738 DOI: 10.1007/BF02050413 http://doi.org/10.1007/BF02050413 . Evolutionary changes in the pathologic diagnosis after the ileoanal pouch procedure GT Martland , NA Shepherd . Indeterminate colitis: definition, diagnosis, implications and a plea for nosological sanity . Histopathology , 2007 . 50 ( 1 ): 83 - 96 . 17204023 DOI: 10.1111/j.1365-2559.2006.02545.x http://doi.org/10.1111/j.1365-2559.2006.02545.x . Indeterminate colitis: definition, diagnosis, implications and a plea for nosological sanity G Meucci , A Bortoli , FA Riccioli , CM Girelli , F Radaelli , R Rivolta , M Tatarella . Frequency and clinical evolution of indeterminate colitis: a retrospective multi-centre study in northern Italy. GSMII (Gruppo di Studio per le Malattie Infiammatorie Intestinali) . Eur J Gastroenterol Hepatol , 1999 . 11 ( 8 ): 909 - 913 . 10514127 DOI: 10.1097/00042737-199908000-00018 http://doi.org/10.1097/00042737-199908000-00018 . Frequency and clinical evolution of indeterminate colitis: a retrospective multi-centre study in northern Italy. GSMII (Gruppo di Studio per le Malattie Infiammatorie Intestinali) ME Moscandrew , EVJr Loftus . Diagnostic advances in inflammatory bowel disease (imaging and laboratory) . Curr Gastroenterol Rep , 2009 . 11 ( 6 ): 488 - 495 . 19903425 DOI: 10.1007/s11894-009-0074-7 http://doi.org/10.1007/s11894-009-0074-7 . Diagnostic advances in inflammatory bowel disease (imaging and laboratory) ZA Murrell , GY Melmed , A Ippoliti , EA Vasiliauskas , M Dubinsky , SR Targan , PR Fleshner . A prospective evaluation of the long-term outcome of ileal pouch-anal anastomosis in patients with inflammatory bowel disease-unclassified and indeterminate colitis . Dis Colon Rectum , 2009 . 52 ( 5 ): 872 - 878 . 19502850 . A prospective evaluation of the long-term outcome of ileal pouch-anal anastomosis in patients with inflammatory bowel disease-unclassified and indeterminate colitis B Ngo , CP Farrell , M Barr , K Wolov , R Bailey , JM Mullin , JJ Thornton . Tumor necrosis factor blockade for treatment of inflammatory bowel disease: efficacy and safety . Curr Mol Pharmacol , 2010 . 3 ( 3 ): 145 - 152 . 20799925 . Tumor necrosis factor blockade for treatment of inflammatory bowel disease: efficacy and safety B Notteghem , JL Salomez , C Gower-Rousseau , R Marti , M Lemahieu , MC Nuttens , JL Dupas , JF Colombel , A Cortot . What is the prognosis in unclassified colitis? Results of a cohort study of 104 patients in the Northern-Pas-de-Calais region . Gastroenterol Clin Biol , 1993 . 17 ( 11 ): 811 - 815 . 8143946 . What is the prognosis in unclassified colitis? Results of a cohort study of 104 patients in the Northern-Pas-de-Calais region CB Pearce , IC Lawrance . Careful patient selection may improve response rates to infliximab in inflammatory bowel disease . J Gastroenterol Hepatol , 2007 . 22 ( 10 ): 1671 - 1677 . 17845695 DOI: 10.1111/j.1440-1746.2006.04739.x http://doi.org/10.1111/j.1440-1746.2006.04739.x . Careful patient selection may improve response rates to infliximab in inflammatory bowel disease ME Pezim , JH Pemberton , RWJr Beart , BG Wolff , RR Dozois , S Nivatvongs , R Devine , DM Ilstrup . Outcome of “indeterminant” colitis following ileal pouch-anal anastomosis . Dis Colon Rectum , 1989 . 32 ( 8 ): 653 - 658 . 2752851 DOI: 10.1007/BF02555768 http://doi.org/10.1007/BF02555768 . Outcome of “indeterminant” colitis following ileal pouch-anal anastomosis C Romano , A Famiani , R Gallizzi , D Comito , V Ferrau′ , P Rossi . Indeterminate colitis: a distinctive clinical pattern of inflammatory bowel disease in children . Pediatrics , 2008 . 122 ( 6 ): e1278 - e1281 . 19047226 DOI: 10.1542/peds.2008-2306 http://doi.org/10.1542/peds.2008-2306 . Indeterminate colitis: a distinctive clinical pattern of inflammatory bowel disease in children J Satsangi , MS Silverberg , S Vermeire , JF Colombel . The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications . Gut , 2006 . 55 ( 6 ): 749 - 753 . 16698746 DOI: 10.1136/gut.2005.082909 http://doi.org/10.1136/gut.2005.082909 . The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications EF Stange , SP Travis , S Vermeire , C Beglinger , L Kupcinkas , K Geboes , A Barakauskiene , V Villanacci , A von Herbay , BF Warren , 等 . European evidence based consensus on the diagnosis and management of Crohn’s disease: definitions and diagnosis . Gut , 2006 . 55 ( Suppl. 1 ): i1 - i15 . 16481628 DOI: 10.1136/gut.2005.081950a http://doi.org/10.1136/gut.2005.081950a . European evidence based consensus on the diagnosis and management of Crohn’s disease: definitions and diagnosis H Suzuki , Y Fukuda , H Koizuka , T Tomita , K Hori , M Suzuki , C O′Morain . Dietary antigens in Crohn’s disease: antibodies to porcine pancreatic amylase . Am J Gastroenterol , 2008 . 103 ( 3 ): 656 - 664 . 18028509 DOI: 10.1111/j.1572-0241.2007.01642.x http://doi.org/10.1111/j.1572-0241.2007.01642.x . Dietary antigens in Crohn’s disease: antibodies to porcine pancreatic amylase IC Talbot . Indeterminate colitis: a pathologist’s view . Dig Liver Dis , 2005 . 37 ( 9 ): 713 - 715 . 15919251 DOI: 10.1016/j.dld.2005.04.016 http://doi.org/10.1016/j.dld.2005.04.016 . Indeterminate colitis: a pathologist’s view T Tan , IC Lawrance . Use of mycophenolate mofetil in inflammatory bowel disease . World J Gastroenterol , 2009 . 15 ( 13 ): 1594 - 1599 . 19340901 DOI: 10.3748/wjg.15.1594 http://doi.org/10.3748/wjg.15.1594 . Use of mycophenolate mofetil in inflammatory bowel disease PP Tekkis , AG Heriot , O Smith , JJ Smith , AC Windsor , RJ Nicholls . Long-term outcomes of restorative proctocolectomy for Crohn’s disease and indeterminate colitis . Colorectal Dis , 2005 . 7 ( 3 ): 218 - 223 . 15859957 DOI: 10.1111/j.1463-1318.2005.00800.x http://doi.org/10.1111/j.1463-1318.2005.00800.x . Long-term outcomes of restorative proctocolectomy for Crohn’s disease and indeterminate colitis KT Thia , M Li , KL Ling , SC Kong , CJ Ooi . Azathioprine is effective in corticosteroid-dependent Asian inflammatory bowel disease patients . Inflamm Bowel Dis , 2011 . 17 ( 3 ): 809 - 815 . 20645318 DOI: 10.1002/ibd.21382 http://doi.org/10.1002/ibd.21382 . Azathioprine is effective in corticosteroid-dependent Asian inflammatory bowel disease patients P Vandewalle-El Khoury , JF Colombel , S Joossens , A Standaert-Vitse , M Collot , J Halfvarson , A Ayadi , CJ Landers , S Vermeire , P Rutgeerts , 等 . Detection of antisynthetic mannoside antibodies (AΣMA) reveals heterogeneity in the ASCA response of Crohn’s disease patients and contributes to differential diagnosis, stratification, and prediction . Am J Gastroenterol , 2008 . 103 ( 4 ): 949 - 957 . 18047546 DOI: 10.1111/j.1572-0241.2007.01648.x http://doi.org/10.1111/j.1572-0241.2007.01648.x . Detection of antisynthetic mannoside antibodies (AΣMA) reveals heterogeneity in the ASCA response of Crohn’s disease patients and contributes to differential diagnosis, stratification, and prediction AD Wells , I McMillan , AB Price , JK Ritchie , RJ Nicholls . Natural history of indeterminate colitis . Br J Surg , 1991 . 78 ( 2 ): 179 - 181 . 2015465 DOI: 10.1002/bjs.1800780214 http://doi.org/10.1002/bjs.1800780214 . Natural history of indeterminate colitis RK Yantiss , RD Odze . Diagnostic difficulties in inflammatory bowel disease pathology . Histopathology , 2006 . 48 ( 2 ): 116 - 132 . 16405661 DOI: 10.1111/j.1365-2559.2005.02248.x http://doi.org/10.1111/j.1365-2559.2005.02248.x . Diagnostic difficulties in inflammatory bowel disease pathology 10.1631/jzus.B1000172 2010-05-10 2011-01-25 2010-10-18 2022-01-05 Copyright © Zhejiang University and Springer-Verlag Berlin Heidelberg 2011 2011 Journal of Zhejiang University-SCIENCE B (Biomedicine and Biotechnology) 04 12