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from a norvegian population-based cohort. Gastroenterology 2007;133:412–22. 4. Louis E, Vernier-Massouille G, Grimaud JC et al. Infliximab discontinuation in Crohn’s disease in stable remission on combined therapy with immunosuppressors: a prospective ongoing cohort study. Gastroenterology 2009;136:A146. 5. Ng SC, Plamondon S, Gupta A et al. Prospective evaluation of anti-tumor necrosis factor therapy guided by magnetic resonance imaging for Crohn’s disease perineal fistulas. Am J Gastroenterol 2009;104:2973–86. 6. Present DH, Rutgeerts P, Targan S et al. Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med 1999;340:1398–405. 7. Schwartz DA. Imaging and treatment of Crohn’s perianal fistulas: to see is to believe. Am J Gastroenterol 2009;104:2987–9. 8. Migaleddu V, Scanu AM, Quaia E et al. Contrast-enhanced ultrasonography evaluation of inflammation activity in Crohn’s disease. Gastroenterology 2009;137:43–61. 9. Rimola J, Rodriguez S, Garcia-Bosch O et al. Magnetic resonance for assessment of disease activity and severity in ileocolonic Crohn’s disease. Gut 2009;58:113–20. 10. Van Assche G, Vanbeckevoort D, Bielen D et al. Magnetic resonance imaging of the effects of infliximab on perianal fistulizing Crohn’s disease. Am J Gastroenterol 2003;98:332–9. 11. Horsthuis K, Lavini C, Bipat S et al. Perianal Crohn disease: evaluation of dynamic contrast-enhanced MR imaging as an indicator of disease activity. Radiology 2009;251:380–7. 1
Department of Hepatogastroenterology, ADEN EA 3234 Rouen University Hospital, Rouen Cedex, France; 2Department of Radiology, LITIS EA Rouen University Hospital, Rouen Cedex, France. Correspondence: Guillaume Savoye, MD, PhD, Department of Hepatogastroenterology, Rouen University Hospital C. Nicolle, 1 Rue de Germont, Rouen Cedex 76031, France. E-mail:
[email protected]
Response to Savoye and Savoye-Collet Siew C. Ng, PhD1, Arun Gupta, MD2, David Burling, MD2 and Michael A. Kamm, MD3 doi:10.1038/ajg.2010.36
To the Editor: We are grateful to Savoye and Savote-Collet for their interest in our article (1). Their letter raises the issue of the potential value of dynamic contrast-enhanced magnetic resonance imaging (CEMRI) in assessing the degree of inflammation associated with perianal fistulas in Crohn’s disease. In a study from Amsterdam (2), investigators selected a single image on MRI, felt to represent the site of maximum inflammation, The American Journal of GASTROENTEROLOGY
determined by subjective “eye balling.” They found for the group that the levels of both Creactive protein and perianal disease activity index correlated with the area of maximum fistula enhancement on MRI. Although of potential interest, this method may be less comprehensive and less clinically useful than an overall subjective assessment of all the images obtained in a scan. In their study (2) only one radiologist made the assessment, in contrast to our own study (1) in which two experienced radiologists made independent assessments, followed by a comparison of these assessments, producing a high degree of concordance. To the best of our knowledge the reproducibility of observer reading of enhancement characteristics on CEMRI has not been assessed. In addition, CEMRI may vary between and within individuals, for the same degree of inflammation. Finally to the authors’ knowledge there are no published data that show a clear benefit of CEMRI vs. non-enhanced MRI in determining the management of perianal fistulas. We agree that these techniques should be compared in the future, and patient outcomes related to these two techniques, to determine which offers the best clinical and predictive value. It may well be that subjective assessment by an experienced radiologist is as good, or better than, other techniques in determining the nature or timing of therapeutic intervention or cessation. Our study evaluated the clinical utility of MRI in determining when anti-TNF antibody therapy could be stopped; we do not have equivalent data for CEMRI. In our study, a small number of patients had not relapsed, at least in the medium term, following the cessation of biological therapy, after an MRI diagnosis of deep tissue healing. As Schwartz pointed out in his editorial (3), our study showed that MRI is an effective tool in providing an alternative, and more “detailed” complementary assessment, to clinical assessment. This has great relevance in the era of biological drugs and the goal of achieving mucosal healing or “deep fistula healing.” Now that MRI data are beginning to show the importance of imaging in the monitoring and management of these patients, we can start addressing the issue of which MRI technique is better. There is also a need for an adequate definition of healing on imaging. Non-enhanced MRI is probably adequate,
and cost- and time-efficient, for the anatomical assessment of large-volume perianal disease. CEMRI may provide additional benefit in the assessment of smaller volumes of sepsis or when trying to distinguish between residual inflammation, granulation tissue, and healing. Both techniques will have strengths and weaknesses; the challenge remains to compare the techniques and define in which type of patient each techniques offers the optimal clinically relevant assessment in a cost-effective manner. CONFLICT OF INTEREST
The authors declare no conflict of interest. REFERENCES 1. Ng SC, Plamondon S, Gupta A et al. Prospective evaluation of anti-tumor necrosis factor therapy guided by magnetic resonance imaging for Crohn’s perineal fistulas. Am J Gastroenterol 2009;104:2973–86. 2. Horsthuis K, Lavini C, Bipat S et al. Perianal Crohn disease: evaluation of dynamic contrastenhanced MR imaging as an indicator of disease activity. Radiology 2009;251:380–7. 3. Schwartz D. Editorial: imaging and the treatment of Crohn’s perianal fistulas: to see is to believe. Am J Gastroenterol 2009;104:2987–9. 1
Department of Gastroenterology, St Mark’s Hospital, London, UK; 2Department of Radiology, St Mark’s Hospital, London, UK; 3St Vincent’s Hospital, University of Melbourne, Melbourne, Victoria, Australia. Correspondence: Siew C. Ng, PhD, Department of Gastroenterology, St Mark’s Hospital, Watford Road, Harrow, London HA1 3UJ, UK. E-mail:
[email protected]
Toward a Definition of a Global PsychoPhysiological Criterion of Vulnerability to Relapse in Inflammatory Bowel Diseases Sonia Pellissier, PhD1, Cécile Dantzer, PhD2, Frédéric Canini, MD, PhD1,3, Nicolas Mathieu, MD4 and Bruno Bonaz, MD, PhD1,4 doi:10.1038/ajg.2009.763
To the Editor: We read with great interest the article by Graff et al. (1). The authors described, in the population-based Manitoba inflammatory bowel disease (IBD) cohort compared with matched controls, VOLUME 105 | JUNE 2010 www.amjgastro.com
Letters to the Editor
that IBD patients reported more negative perception of their health status than controls and used more often avoidant than active coping strategies during active disease. They found differences in psychological adjustment between active and non-active disease. The authors concluded that particular attention should be paid to the psychological needs in the active period. These findings are very interesting but we should go further into the comments. Indeed, one wonders who among inactive IBD patients are the more vulnerable to relapse, especially because IBDs are associated with autonomic disturbances. The autonomic nervous system, as a bidirectional interface, mediates several types of modulating information (emotions, pain, inflammation, etc.) between the brain and the gut. In this context, we have recently performed a study in IBD patients compared with matched controls (2). Patients were separated according to their affective adjustment (a global psychological factor including anxiety trait and state, depressive symptomatology, negative mood, and perceived stress, which explains 74% of the variance). A state of vulnerability was revealed in half of the patients, even in remission. In Crohn’s disease, as in ulcerative colitis, negative affects were associated with emotion-focused coping (less beneficial for good health), whereas only patients with positive affects presented similar coping strategies with controls, i.e., often more problem-focused coping. Moreover, inadequate heart rate variability was observed only in IBD patients with negative psychological adjustment. We think that considering the three main following criteria: (i) a stress-like dysautonomia, (ii) a global psychological distress, and (iii) preferential emotion-focused coping strategies, should help the physician detect patients who are more likely to relapse (under a stressful life event, for instance). This hypothesis is supported by several studies that have revealed that, in Crohn’s disease, the time course of the disease is negatively influenced by low avoidant coping strategies (3) and that an inadequate heart rate variability is known to represent an important risk factor of morbidity in several chronic clinical disorders (4). In conclusion, as IBDs are multifactorial diseases, it seems relevant that future research aims at identifying those © 2010 by the American College of Gastroenterology
IBD patients who are more vulnerable to stress. This psycho-physiological vulnerability should also be a flag to consider the psychological needs in the follow-up of IBD patients in the remission period. CONFLICT OF INTEREST
The authors declare no conflict of interest. REFERENCES 1. Graff LA, Walker JR, Clara I et al. Stress coping, distress, and health perceptions in inflammatory bowel disease and community controls. Am J Gastroenterol 2009;104:2959–69. 2. Pellissier S, Dantzer C, Canini F et al. Psychological adjustment and autonomic disturbances in inflammatory bowel diseases and irritable bowel syndrome. Psychoneuroendocrinol; e-pub ahead of print 11 November 2009. 3. Bitton A, Dobkin PL, Edwardes MD et al. Predicting relapse in Crohn’s disease: a biopsychosocial model. Gut 2008;57:1386–92. 4. Almoznino-Sarafian D, Sarafian G, Zyssman I et al. Application of HRV-CD for estimation of life expectancy in various clinical disorders. European Journal of Internal Medicine 2009;20:779–83. 1
Stress et Interactions Neuro-Digestives (SIND), Grenoble Institut des Neurosciences (GIN), Centre de Recherche INSERM U836 UJF-CEA-CHU, Grenoble, France; 2Laboratoire Inter-Universitaire de Psychologie: Personnalité, Cognition, Changement Social (LIP/PC2S), Université de Savoie, Chambéry, France; 3Département des Facteurs Humains, Pôle de Neurophysiologie du Stress, Centre de Recherches du Service de Santé des Armées Emile Pardé, La Tronche, France; 4Clinique Universitaire d’HépatoGastroentérologie, CHU de Grenoble, Grenoble, France. Correspondence: Bruno Bonaz, MD, PhD, Hépato-Gastroentérologie, Clinique Universitaire, CHU de Grenoble, Grenoble Cedex 09, F-38043, France. E-mail:
[email protected]
Successful Endoscopic Closure of Anastomotic Leakage Following Anterior Resection of the Rectum by Endoclip Application Mehmet Ibis, MD1, Yavuz Beyazit, MD1, Ibrahim Koral Onal, MD1, Mevlut Kurt, MD1 and Erkan Parlak, MD1 doi:10.1038/ajg.2009.761
To the Editor: A 50-year-old woman who had undergone low anterior resection for
rectal cancer was referred to our clinic 2 weeks after the procedure for colonoscopic evaluation due to persistent and excessive drainage from a surgical drain. The patient was generally well, with no signs of peritonitis or sepsis. A computerized tomography confirmed the absence of a perianal abscess. Anastomotic dehiscence over almost half of the entire circumference of the anastomosis was observed by flexible rectosigmoidoscopy 8 cm from the anal verge. Complete repair was successfully achieved using a total of 10 endoclips carefully applied along the line of anastomosis (Figure 1a–c). On 3-month follow-up the patient was symptom-free, and treatment with chemoradiotherapy was commenced. A control rectosigmoidoscopy showed an intact anastomosis with no signs of leakage. Two of the hemoclips were retained (Figure 1d–f). Anastomotic leakage is a common postoperative complication of rectal cancer surgery with a reported frequency of 8–16% (1), resulting in increased morbidity and mortality, prolonged hospitalization, and added cost (2). Low rectal cancer, surgeon inexperience, and the presence of diabetes mellitus were found to be risk factors for anastomotic leakage after anterior resection for rectal cancer (3). Conventional management of clinical anastomotic leaks with local or diffuse peritonitis calls for taking down the anastomosis with exteriorization of the proximal bowel end. Minimally invasive laparoscopic techniques have also been used in select cases (4). Data on endoscopic management of anastomotic leakage are lacking, although some reports on the successful use of fibrin adhesives and endoscopic vacuum-assisted closure may be encountered in the literature (5,6). Endoclip application, on the other hand, has been successfully utilized in the management of leaks of the upper gastrointestinal tract (7,8). Based on these reports, we attempted to repair the anastomotic dehiscence in our patient by endoclip application, which proved successful. This procedure offers a feasible alternative to conventional methods reserved for the management of post-surgical anastomic leakage, especially in the absence of infection (peritonitis, abscess, etc.). Further trials need to be conducted before any judgment can be made on the efficacy of endoclip application in this setting. The American Journal of GASTROENTEROLOGY
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