Chronic Crohn's Disease Research Articles

Adenocarcinoma Arising in a Rectovaginal Fistula in Crohn Disease

Adenocarcinomas occurring in the vagina are rare. Their correct classification may be very challenging to both the gynecologist and the pathologist, but it is essential for appropriate therapy. Although most adenocarcinomas in the vagina arise from other sites in the female genital tract, a significant minority reflects metastasis from a colorectal site. We report a very unusual occurrence of an adenocarcinoma that presented as a mass in the vagina protruding through the introitus. It arose in a rectovaginal fistula consequent to chronic Crohn disease, but it did not extend to involve the colonic mucosa. Neither the initial clinical examination nor the pathologic examination suggested the correct diagnosis. We report this case to remind the gynecologists of the potential complications of Crohn disease, and to highlight for the pathologists the difficulty that is often encountered in the correct identification of the source of carcinomas that are found in the vagina.

Over-expression of paneth cell-derived anti-microbial peptides in the gut of patients with ankylosing spondylitis and subclinical intestinal inflammation

Subclinical gut inflammation has been demonstrated in patients with AS. Altered expression of paneth cell (PC) anti-microbial peptides have been reported in the inflamed ileum of patients with Crohn's disease (CD). Here, we investigated the expression of PC-derived peptides in subclinical gut inflammation in AS. Multiple adjacent mucosal biopsies from terminal ileum were obtained from 25 patients with AS, 30 CD and 15 healthy controls (HCs). Expression of human α-defensin 5 (HD-5), phospholipase A2 (PLA2), lysozyme and SOX-9 molecules was assessed by quantitative Taqman RT-PCR on mucosal samples. Immunohistochemistry with anti-human HD-5 antibody and genotyping of relevant NOD2 mutations was also performed. HD-5, PLA2 and lysozyme transcript levels were strongly increased in AS and CD with similar degrees of intestinal inflammation when compared with normal controls. Immunohistochemical evaluation showed a normal number of PCs in both AS patients with chronic gut inflammation and CD patients with less-inflamed ileal samples. Conversely, CD patients with higher degree of gut inflammation had a reduced number of PCs and low expression levels of HD-5. In this study, we provide evidence that over-expression of PC-derived anti-microbial peptides occurs in the ileum of AS patients with subclinical gut inflammation, likely representing an important early alteration of the mucosal innate immune component and intestinal host defence in AS.

Methotrexate for maintenance of remission in chronic active Crohnʼs disease

According to current guidelines methotrexate (MTX) should be considered as a second-line immunomodulator in patients with chronic active Crohn's disease (CD) if purine analogs are not tolerated or there is a lack of efficacy. However, its therapeutic role remains controversial to the present day. Medical records of all eligible patients treated in the outpatient clinic of the Johann Wolfgang Goethe-University Hospital between December 2000 and January 2009 were reviewed. Sixty-three patients were identified. The mean duration of treatment was 100 weeks (range, 2-364 weeks) with a mean cumulative dose of MTX of 2130 mg (range, 40-9005 mg). In 50 (79%) patients started on MTX clinical remission could be achieved within 3 months of treatment. The cumulative probability of these patients to maintain remission was 95.3%, 89.5%, 70.6%, and 62.8% at 6 months, 1, 2, and 3 years of treatment, respectively. The respective figures of the meta-analysis were 94%, 86%, 75%, 53%, and 43. Drug-related side effects were reported in 50 patients (79%), leading to withdrawal of MTX in 21 cases (33%). Along with previous observations our data demonstrate the efficacy of MTX as a second-line immunomodulator in chronic active CD. However, its use is limited due to intolerable side effects in a large proportion of patients. The results should encourage further research in order to establish the definite significance of MTX in chronic active CD.

S1221 A Case Control Comparison of Chronic Stenosing Enteritis and Crohn's Disease

S1221 A Case Control Comparison of Chronic Stenosing Enteritis and Crohn's Disease

Development of mutinous adenocarcinoma in chronic Crohn's disease fistulae without luminal involvement

Summary: A patient with Crohn’s disease who developed mucinous adenocarcinoma in chronic fistulae is reported. Malignancy may complicate chronic nonhealing Crohn’s sinus tracts and fistulae, even with no mucosal involvement by carcinoma. Persistent non-remitting perianal induration and pain should alert the physician to the possibility of underlying malignancy. Prompt examination under anesthesia and biopsy or fine-needle aspiration may facilitate diagnosis and therapy of the carcinoma at an early stage. Key Words: Carcinoma-Crohn’s diseaseFistulae. Crohn’s disease is associated with an increased incidence of colorectal cancer (1-13). Anorectal cancer may arise in chronic nonhealing perianal Crohn’s disease. However, to our knowledge, no prior report has documented cancer in fistulae in the absence of mucosal involvement. We present a case of a mucinous adenocarcinoma complicating chronic perianal Crohn’s disease, which did not involve the bowel lumen, suggesting that cancer may arise de novo in Crohn’s disease fistulae or sinus tracts.

Das Kompetenznetz chronisch entzündliche Darmerkrankungen (KN-CED)—Vernetzte Forschung führt zur Identifikation von Krankheitsursachen und zur Verbesserung der Patientenversorgung

The competence network chronic inflammatory bowel disease (KN-CED) is one of 17 networks of competence initiated by the German Federal Ministry of Education and Research (BMBF). These networks are concerned with disease patterns which are characterized by their high frequency, high mortality rate or which present a large expense factor. The project-executing organization is the German Center for Air and Space Travel (DLR e. V.). The central structure of organization is the Telematic Platform for medical Networks (TMF e. V.). Aim of the KN-CED is to investigate, in their complexity, the incurable chronic diseases ulcerative colitis and Crohn's disease, particularly with regard to the causes of disease, the establishment of new therapy standards as well as patient care. To achieve this goal, the competence network is integrated into both national and international research associations and is also backed by the national self-help group DCCV and the pharmaceutical industry. Principal items of the competence network are the core facilities and their main focus on molecular genetics, animal and cell models and serum markers. Having stored the data of more than 4,000 patients so far, the central database of the competence network is one of the largest databases worldwide with regard to inflammatory bowel disease (IBD). The successful cooperation within the network is reflected in numerous publications. Thus, two of the three known genes of Crohn's disease were identified. Also with the participation of the competence network national guidelines for the diagnosis and therapy of IBD were generated.Furthermore, the competence network operates study centers where significant therapeutic developments in the field of biotechnological drugs are taking place. The analysis of existing structures of care as well as the development of standards of organization for patients with IBD top the research within the competence network and emphasize the claim to find comprehensive answers to the questions connected with IBD.

Mesenteric Pulsatility Index Analysis Predicts Response to Azathioprine in Patients with Crohnʼs Disease

Mesenteric blood flow measurement has been found to predict relapse after steroid-induced remission in patients with Crohn's disease (CD) and ulcerative colitis (UC). Therefore, we assessed prospectively the possible relationship between changes in mesenteric blood flow and prognosis in chronically active patients with need of immunosuppressive therapy with azathioprine (AZA) or 6-mercaptopurine (6-MP). Doppler ultrasound (DUS) measurements of the pulsatility index (PI) of the superior mesenteric artery (SMA) and inferior mesenteric artery (IMA) were performed in 52 patients with chronically active inflammatory bowel disease (CD 31 patients; UC 21 patients) before beginning therapy with AZA/6-MP (US1) and during clinical remission (CD activity index <150, Truelove index score I) (US2). Patients were weaned from concomitant therapy with corticosteroids as soon as possible and were followed up for 12 months. After 1 year, 16 patients with CD (51.6%) and 13 patients with UC (61.9%) were in remission, whereas 23 patients had recurrent disease or had undergone surgery. A decreased SMA PI at US2 predicted clinical relapse in all patients with CD [100%; P < 0.001; mean (+/-SD) 77 +/- 67 d after US1], but only 4 of 8 patients (50%; difference not significant; mean 84 +/- 75 d after US1) with UC. Conversely, an increase of SMA PI was associated with sustained remission in the majority of CD patients (12/16 patients; 75%; P < 0.002), but in only 7 of 13 patients (54%) with UC. Flow measurements in the IMA and postprandial values for both arteries were less reliable. Repeated DUS measurements of the SMA PI predict response to AZA/6-MP in patients with chronic active CD.

Chronic Sinonasal Disease in Patients with Inflammatory Bowel Disease

The objective of this study was to explore the possible relationship between inflammatory bowel disease (IBD) and chronic sinonasal disease. A cross-sectional study was undertaken of 241 patients with Crohn's disease (CD) or ulcerative colitis from a tertiary medical center IBD clinic. Patient demographic data and information regarding IBD diagnosis and management, sinonasal disease diagnosis and management, and complications related to these diagnoses were gathered by retrospective chart review and a standardized patient survey. One hundred sixty surveys (67%) were returned and analyzed. Overall 48% of patients with IBD reported chronic sinonasal disease symptoms. Patients with CD had a higher prevalence of sinonasal disease than patients with ulcerative colitis (53% versus 32%; p < 0.02). The subgroup of CD patients with obstructive bowel complications had the highest prevalence of sinonasal disease (68% versus 27%; p = < 0.001), with 23% reporting chronic rhinosinusitis, 13% reporting chronic rhinitis, and an additional 32% reporting chronic nasal or sinus symptoms. The prevalence of chronic sinonasal disease is elevated in patients with IBD, occurring in approximately one-half of patients followed at a tertiary IBD center. Patients with CD experiencing obstructive complications had significantly increased rates of sinonasal disease. The relationship between chronic sinonasal disease and obstructive CD is not defined, but several hypotheses are generated.

The Value of Routinely Performed Ultrasonography in Patients with Crohn Disease

Background: In active Crohn disease (CD), abdominal ultrasound can demonstrate morphological changes in the bowel wall. By contrast, the role of ultrasonography in periods with no disease activity has never been evaluated. In this prospective study we investigated the outcome of routinely performed abdominal ultrasonography in CD patients irrespective of symptoms and disease activity. Methods: 255 consecutive patients with chronic CD (117 M, 138 F, mean age ( ± s ) 38 ± 14) were evaluated by high-resolution ultrasonography of the bowel wall and abdomen. The findings were graded with respect to further diagnostic and/or therapeutic implications. In addition, the CD activity index (CDAI) was determined. In patients with pathological sonographic findings, complementary procedures (e.g. endoscopy, computed tomography, biopsy or operation) were performed to validate the suspected diagnosis. Results: In 46/255 (18%) patients with CD, the diagnosis of a transmural inflammatory reaction (TMR) with or without fistula was made by ultrasonography. In respect of CDAI, 29/46 (63%) of these patients were graded as active disease (CDAI >150) and 17/46 (37%) as inactive disease (CDAI h 150). Of the 17 patients with a TMR and CDAI h 150, 4 patients revealed interenteric fistula, 7 patients mesenteric or perirectal fistula, whereas 6 patients presented with a transmural mesenteric inflammatory reaction without fistula. All fistulae were confirmed by radiography. Ultrasonography of the remaining abdominal organs revealed pathological findings with further diagnostic implications in 25/255 (10%) patients and with therapeutic implications in 9/255 (4%) patients. Conclusion: Routinely performed ultrasonography of the abdomen reveals pathological findings with therapeutic implications not only in symptomatic but also in asymptomatic patients with CD. It can therefore be recommended as a screening tool for this group of patients.

Infliximab induces apoptosis in monocytes from patients with chronic active Crohn's disease by using a caspase-dependent pathway

Background & Aims: Treatment with a chimeric anti–tumor necrosis factor (TNF) antibody (infliximab) has been shown to be highly efficient for patients with steroid-refractory Crohn's disease (CD). However, the mechanism of action remains largely unknown. As monocytopenia is commonly observed after treatment with infliximab, we investigated the role of infliximab–induced monocyte apoptosis. Methods: Peripheral blood monocytes from healthy volunteers and patients with chronic active CD (CDAI > 250) were isolated by density gradient centrifugation methods. Apoptosis was determined by annexin V staining DNA-laddering, and transmission electron microscopy. Activation of caspases and mitochondrial release of cytochrome C was determined by immunoblotting. Transcriptional activation of members of the Bcl-2 family have been analyzed by ribonuclease protection assay. Results: Treatment with infliximab at therapeutic concentrations resulted in monocyte apoptosis in patients with chronic active CD in a dose-dependent manner. Infliximab–induced monocyte-apoptosis required the activation of members of the caspase-family since activation of caspase-8, -9, and -3 could be determined. Caspase activation was induced by a CD95/CD95L independent signaling pathway with mitochondrial release of cytochrome C. Cytochrome C release seemed to be triggered by transcriptional activation of Bax and Bak. Monocyte apoptosis in vivo as determined by annexin-V binding and caspase-3 activation could be shown in patients with chronic active CD as soon as 4 hours after treatment with infliximab. Conclusions: Monocyte apoptosis induced by infliximab may be an important mechanism that could explain the powerful anti-inflammatory properties of infliximab in patients with chronic active CD.GASTROENTEROLOGY 2001;121:1145-1157

Genetically related Escherichia colistrains associated with Crohn's disease

Escherichia colistrains isolated from patients with Crohn's disease (CD) with chronic ileal lesions (n=14), early endoscopic recurrent lesions (n=20), without endoscopic recurrence (n=7), and controls (n=21) were compared by ribotyping....

New insights into the pathogenesis of anemia of chronic diseases: Induction of ferritin synthesis and development of anemia during recombinant human interleukin-10 (rHuIL-10) treatment of chronic active Crohn's disease (CACD)

• G4499 NEW INSIGHTS INTO THE PATHOGENESIS OF ANEMIA OF CHRONIC DISEASES: INDUCTION OF FERRITIN SYNTHESIS AND DEVELOPMENT OF ANEMIA DURING RECOMBINANT HUMAN INTERLEUKIN-10 (rHuIL-10) TREATMENT OF CHRONIC ACTIVE CROHN'S DISEASE (CACD). H. Tilg, A. Kaser, Innsbruck, Austria; S. Schreiber, Berlin, Germany; M. Gregor, Ttibingen, Germany; P. Rutgeerts, Leuven, Belgium; S. van Deventer, Amsterdam, The Netherlands; C. Gasche, Vienna, Austria; J.C. Koningsberger, Utrecht, The Netherlands; L. Abreu, Madrid, Spain; B. Duclos, Strasbourg, France; R.A. van Hogezand, Leiden, The Netherlands; M. Cohard, P. Grint, Kenilworth, NJ, USA; G. Weiss, Innsbruck, Austria.

Methotrexate improved symptoms and reduced the need for prednisone in chronic active Crohn disease

Source Citation Feagan BG, Rochon J, Fedorak RN, et al. Methotrexate for the treatment of Crohn's disease. N Engl J Med. 1995 Feb 2;332:292-7.

Lack of association between smoking and inflammatory bowel disease in Jewish patients in Israel

Background/Aims: An excess of smokers in patients with Crohn's disease (CD) and a paucity of smokers in patients with ulcerative colitis (UC) were reported in many studies. The aim of this study was to examine the association between smoking and inflammatory bowel disease (IBD) in Israel. Methods: Two independent studies were performed. Patients with recent IBD in comparison with matched population and outpatient controls and patients with chronic UC and CD were studied. Altogether, 475 subjects were investigated. Results: In both studies, the presence of current smokers was lower in CD (9% and 18%) than in UC (24% and 26%). The proportions of nonsmokers in both studies were similar (UC, 61% and 65%; CD, 67% and 70%) and comparable to those found in their two control groups (57% and 61%; 63% and 68%, respectively) and to the general population of Israel. All differences in smoking habits between patient groups and their controls were not statistically significant, except for the paucity of current smokers in the small group of patients with newly diagnosed CD ( P < 0.05). A matched analysis produced similar results. Conclusions: The expected associations between smoking and IBD could not be confirmed. Two hypotheses are considered: (1) the association between smoking and IBD may not be universal, and (2) our findings may be related to the higher genetic predisposition to IBD in Jewish people.

Cyclosporine was effective for corticosteroid-resistant ulcerative colitis

TherapeuticsNovember 1, 1994Cyclosporine was effective for corticosteroid-resistant ulcerative colitisJoseph J. Nidiry, MDJoseph J. Nidiry, MDHarvard University College of Medicine, Washington, D.C., USA (J.J.N.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-1994-121-3-068 SectionsAboutFull Text ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookTwitterLinkedInRedditEmail Source CitationLichtiger S, Present DH, Kornbluth A, et al. Cyclosporine in severe ulcerative colitis refractory to steroid therapy. N Engl J Med. 1994 Jun 30;330:1841-5.References1 Sartor RB. Cyclosporine therapy for inflammatory bowel disease. N Engl J Med. 1994;330:1897-8. Google Scholar2 Brynskov J, Freund L, Rasmussen SN, et al. A placebo-controlled, double-blind, randomized trial of cyclosporine therapy in active chronic Crohn's disease. N Engl J Med. 1989;321:845-50. Google Scholar Author, Article, and Disclosure InformationAffiliations: Harvard University College of Medicine, Washington, D.C., USA (J.J.N.) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoOral mesalamine prevented relapse in patients with Crohn disease who were in remission for < 3 months Arvey I. Rogers November 1, 1994Volume 121, Issue 3Page: 68KeywordsAttentionBacterial pathogensBloodCholesterolClostridium difficileColonCrohn's diseaseDiarrheaDrugsEnzymesHypertensionImmunosuppressivesInflammatory bowel diseaseSafetySepsisSteroid therapyToxinsTransplantationUlcerative colitis ePublished: 9 March 2020 Issue Published: November 1, 1994 Copyright & PermissionsCopyright © 1994 by American College of Physicians. All Rights Reserved.Loading ...

Drug therapy for inflammatory bowel disease: Part II

Part II of this two-part article (See The American Journal of Surgery 1992; 164: 85-9) reviews the current definition of the role of immunosuppressive therapy in inflammatory bowel disease (IBD) and the use of antibiotics in IBD, as well as summarizes the uses of the new agents on the horizon for the treatment of IBD. Azathioprine and 6-mercaptopurine have steroid-sparing effects in patients with refractory Crohn's disease and ulcerative colitis, treat Crohn's disease-associated fistulas, and are the first agents to demonstrate efficacy in the prophylaxis of Crohn's disease. Their low risk for the development of lymphoreticular malignancy remains a factor in decisions regarding their long-term use. Cyclosporine is steroid sparing in active chronic Crohn's disease and, given intravenously, may help treat severe, refractory ulcerative colitis. Antibiotics have expanding roles: metronidazole is effective for the primary treatment of Crohn's disease, fistulas, abscess, bacterial overgrowth, and pouchitis (after ileoanal anastomosis). Other potential agents show promise in pilot studies but await controlled trials.

Final Report on a Placebo-Controlled, Double-Blind, Randomized, Multicentre Trial of Cyclosporin Treatment in Active Chronic Crohn's Disease

In a previous report we published the immediate results of a 3-month placebo-controlled trial (n = 34) showing that cyclosporin (n = 37) has a beneficial therapeutic effect in active chronic Crohn's disease. Here we report on the final outcome of the patients. During the 3-month tapering-off period eight initially improved patients (36%) in the cyclosporin group worsened, as did six (55%) in the placebo group. The therapeutic gain of cyclosporin treatment was consistently significant during this period. It ranged from 22% to 25% (95% confidence limits, 2-46%). An outcome ranking showed that 7 patients of the cyclosporin group (19%) were substantially improved, 7 (19%) moderately improved, and 23 (62%) not improved after the tapering off. In contrast, no significant differences were seen during the 6-month follow-up period. Four patients of the cyclosporin group (11%) were substantially improved, 3 (8%) moderately improved, and 30 (81%) not improved at final follow-up. Significant interactions between cyclosporin and prednisolone treatment were demonstrated both at the end of the initial treatment period and at the end of the tapering-off period. We conclude that a short course of cyclosporin treatment does not result in long-term improvement in active chronic Crohn's disease.

Is the assay of disaccharidase activity in small bowel mucosal biopsy relevant for clinical gastroenterologists?

In a retrospective study, jejunal mucosal disaccharidase and alkaline phosphatase activities have been investigated in 40 controls and patients with proven celiac sprue (n = 26), lactase deficiency (n = 26), osteoporosis or osteomalacia (n = 16), chronic pancreatitis (n = 12), giardiasis (n = 7), or Crohn's disease (n = 7). Apart from a nonselective reduction of mucosal enzyme activities in the sprue syndrome and a selective reduction of lactase activity in the patients with primary lactase deficiency, assays of mucosal disaccharidases revealed only inconstant or slight deviations from the control group and were not of diagnostic significance for any of the above-mentioned disorders. Isolated forms of enzyme deficiencies other than lactase deficiency, such as sucrase-isomaltase or trehalase deficiency were not present among 168 investigations carried out from 1972-1982. It is concluded that assay of small intestinal disaccharidase or alkaline phosphatase activities does not expand the diagnostic impact of morphological examination of small bowel biopsy specimens and modern noninvasive methods for the detection of carbohydrate malabsorption. Thus, the method does not appear a necessary or relevant investigation in routine clinical practice.

Editorial

After establishing criteria of patient selection, disease activity and, remission we performed lymphoplasmapheresis in seven patients with severely active chronic Crohn's disease. Five of the seven responded, but the results were unpredictable, not cost-effective, and had 100% morbidity. We then changed the protocol to selectively remove T-cells by differential ultracentrifugation. The initial goal was to remove 40 times 10(9) T-cells, but it was changed to 80 times 10(9) in order to increase the length of remission. We found that all patients with steroid-dependent chronically active Crohn's disease show evidence of protein calorie malnutrition. We used total parenteral nutrition with T-lymphocyte apheresis in the last 21 of 25 patients so treated. We have now completed a series of 54 patients, achieving a statistically valid remission, lasting an average of more than 18 months, in 48 of them. Criteria of remission included absolute zero steroid dosage. There has been no mortality or evidence of immunocompromise. The only morbidity (four patients) was the need for intravenous catheters during the apheresis procedure. This work has been confirmed elsewhere. Immune studies in active, untreated disease show low serum values of interleukin-2, as well as abnormalities of T-cell responsiveness to interleukin-2. The mechanism of how T-lymphocyte apheresis works is not clear, but it represents a promising new approach to the treatment of Crohn's disease.

Is the ascending colon dispensable in resection for Crohn's disease?

Resection for chronic ileocaecal Crohn's disease may be conservative with ileo-ascending-colon anastomosis, or be extended to standard right hemicolectomy. The two operations have been compared to determine whether preservation of the ascending colon is advantageous. Stool frequency, consistency and weight were similar after the two operations. A slower stool transit time was the only clinical difference associated with preservation of the ascending colon. An adaptable and patient-acceptable technique for domicillary collection of stools is described.