- Email: [email protected]
Correlation between predicted and actual consequences of capsule endoscopy on patient management
Available online at www.sciencedirect.com
Digestive and Liver Disease 40 (2008) 761–766
Digestive Endoscopy
Correlation between predicted and actual consequences of capsule endoscopy on patient management A.P. de Graaf, J. Westerhof, R.K. Weersma, W.J. Thijs, A.J. Limburg, J.J. Koornstra ∗ Department of Gastroenterology and Hepatology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands Received 10 January 2008; accepted 19 February 2008 Available online 3 April 2008
Abstract Background. Capsule endoscopy (CE) is a relatively new diagnostic modality in the evaluation of patients with suspected small bowel pathology. It is unclear to what extent physicians are able to predict the clinical consequences of CE on patient management. Methods. In this prospective study, 180 consecutive CE examinations were analysed. Prior to CE, referring physicians were asked to indicate the consequences of CE according to potential different CE outcomes. The influence of CE on patient management was determined with at least 1 year follow-up. Management consequences were defined as major (surgical or endoscopic intervention, or medical therapy) or minor (nonspecific therapy, including iron supplementation, or no further diagnostic tests). Results. CE led to major management consequences in 32% of cases. Of patients with obscure gastrointestinal bleeding and normal CE findings, 91% were independent of blood transfusions and experienced no further bleeding episodes during a mean follow-up of 33 months. In 78% of 118 cases that were evaluated, the actual consequences of CE matched the consequences predicted by the referring physicians. Conclusion. CE had a major impact on patient management in about one third of investigations. In the majority of cases, physicians adequately predicted the clinical consequences of CE. © 2008 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. Keywords: Capsule endoscopy; Obscure gastrointestinal bleeding
1. Introduction Capsule endoscopy (CE) is a relatively new diagnostic technique to explore the small bowel. Capsule endoscopy has proven to be a valuable tool in the evaluation of obscure gastro-intestinal (GI) bleeding [1,2], suspected Crohn’s disease [3–5], celiac disease [6,7] and polyposis syndromes such as Peutz–Jeghers syndrome [8,9]. It has shown to have a higher diagnostic yield for most of these indications compared to conventional diagnostic methods such as push-enteroscopy (PE), enteroclysis, small-bowel-followthrough and CT angiography or conventional angiography [2,4,10–14]. ∗ Corresponding author at: Department of Gastroenterology and Hepatology, University Medical Centre Groningen, University of Groningen, P.O. Box 30001, 9700 RB Groningen, The Netherlands. Tel.: +31 503613354; fax: +31 503619306. E-mail address: [email protected] (J.J. Koornstra).
A feature of CE that has been studied less often is the influence of findings of CE on the further management and outcome of patients. In most studies published on this issue, follow-up is usually limited and patient series are relatively small. Another aspect of CE that has not been studied in detail is whether physicians ordering CE procedures are able to predict the clinical consequences of CE for the management of their individual patients. Since CE is usually not available in every hospital, patients are often referred from regional hospitals to a central referral centre. With a relatively new diagnostic modality like CE, one could imagine that it may be difficult for referring physicians, who probably see only a few patients with an indication for CE per year, to predict the clinical consequences of this modality for patient management. It is therefore important to know which possible consequences the referring physician has in mind, when deciding that a CE procedure is indicated. By comparing the actual consequences of CE for patient management
1590-8658/$30 © 2008 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.dld.2008.02.025
762
A.P. de Graaf et al. / Digestive and Liver Disease 40 (2008) 761–766
2. Materials and methods
medical therapy (for example for Crohn’s disease); (c) other changes in medical therapy (for example discontinuation of NSAIDs); (d) additional diagnostic procedures (push-enteroscopy, intra-operative enteroscopy or double balloon enteroscopy) and (e) surgery. For example, if a patient was referred for obscure-occult GI bleeding, the referring physician had to indicate prior to CE which consequence the finding of ‘no abnormalities’ would have on further patient management, which consequence the finding of ‘angiectasias’ would have on further patient management and so on for every possible finding. For analysis of the correlation between the actual and predicted consequences of CE on patient management, the first step was retrieving the findings of CE for each case. Next, the actual consequence of those findings for patient management, as assessed during the follow-up period, was determined. Finally, the actual consequence on patient management was compared with the consequence predicted by the referring physician.
2.1. Patients and methods
2.2. Capsule endoscopy procedure
Data from all consecutive CE studies performed in the University Medical Centre Groningen between September 2003 and December 2005 were analysed. Our hospital is a tertiary care centre with a referral base drawing from the northern part of the Netherlands. This is reflected by the fact that 52.2% of patients included in this study were referred from hospitals in the area just for CE. Prior to each CE, data were collected regarding patient age, gender, medication use, in particular oral anticoagulation and non-steroidal anti-inflammatory drugs (NSAIDs), need for blood transfusions, previously performed diagnostic investigations (gastroduodenoscopy, colonoscopy, push-enteroscopy, SBFT, angiography, computed tomography) and the reason for performing the CE procedure. The reasons for performing a CE procedure were classified in six different categories: (1) obscure-occult GI bleeding; (2) obscure-overt GI bleeding; (3) suspected Crohn’s disease; (4) polyposis syndromes; (5) suspected small bowel carcinoid and (6) other indications. Obscure-occult GI bleeding was defined as chronic iron-deficiency anemia without any clinically evident bleeding episode with negative upper and lower endoscopy. Obscure-overt GI bleeding included a history of bleeding episodes marked by melena, hematemesis and/or hematochezia. Referring physicians were asked in a questionnaire prior to each CE to predict the consequences of CE according to different potential findings. The following potential findings were given: (a) no abnormalities; (b) angiectasias; (c) ulcers/erosions; (d) mass lesion. For each potential finding, physicians were asked to indicate which consequence they would draw from this finding. The following possible consequences were given: (a) conservative therapy (iron supplementation/occasional blood transfusion or wait-and see/no further investigations); (b) introduction of specific
Patients were given standard instructions for the procedure and informed consent was obtained. Patients started fasting from midnight before the procedure. Bowel preparation consisted of 4 l of polyethylene glycol (PEG). The capsule (Given Imaging Ltd., Yoqneam, Israel) was swallowed in the morning and patients were allowed to drink fluids after 3 h and to consume a light meal after 5 h. The CE results were reviewed by at least two of four gastroenterologists (RKW, WJT, AJL or JJK). Any controversial finding was extensively discussed, and findings were classified as relevant or irrelevant. The most relevant findings obtained from CE were documented and categorized as angiectasia(s), ulcer(s)/erosion(s), polyp(s)/tumour(s), or incidental abnormality of esophagus, stomach or colon. CE was considered complete when the cecum was reached. The clinical outcomes and consequences for patient management of CE were determined at least 12 months after the CE had been performed. Referring physicians were asked to provide patient reports or computerized medical charts. In addition, information was obtained on the occurrence of (re)bleeding episodes and the need for blood transfusions. The consequences of CE on patient management were classified as major or minor in accordance with an earlier publication by Neu et al. [15]. As major consequences were regarded: surgery, endoscopic intervention (e.g. double balloon enteroscopy, push enteroscopy or colonoscopy with argon plasma coagulation-APC), or medical therapy based on positive findings at CE (e.g. introducing Crohn’s disease medication, discontinuating NSAIDs). Consequences were considered as minor following CE when no specific therapy was started (e.g. iron supplementation therapy) or when no further diagnostic tests had been performed due to either negative findings of CE or positive findings of CE considered to be irrelevant.
with the predicted consequences, one could estimate whether the expectations of referring physicians are appropriate. If referring physicians would perform poorly on predicting the consequences of CE on patient management, efforts should be made to better define the indications for CE to avoid unnecessary CE procedures. It must be realised that several factors influence physicians’ expectations, including the results and extent of previous clinical investigations, patient characteristics, availability of possible treatment modalities, incidence of expected diseases and the level of experience of the physician with the procedure. In this study we evaluated the consequences of CE on patient management with a follow-up after the procedure of at least 1 year. In addition, we studied to what extent the consequences of CE on patient management actually matched the referring physicians’ predicted consequences of CE.
A.P. de Graaf et al. / Digestive and Liver Disease 40 (2008) 761–766
763
Table 1 Findings of CE and in relation to the reasons for performing the procedure Findings
All cases
Obscure occult GIB
Obscure overt GIB
Suspected Crohn’s
Polyposis syndromes
Other
n
%
n
%
n
%
n
%
n
%
n
%
Angiectasia(s) Ulcer(s)/erosion(s) Polyp/tumour Abnormality in stomach or colon No abnormalities
38 25 9 6 102
21 14 5 3 57
24 11 1 5 59
10 1 2 2 12
37 4 7 7 45
1 12 0 0 22
3 34 0 0 63
0 0 5 0 2
0 0 71 0 29
1 1 1 0 6
11 11 11 0 67
Total
180
26 11 1 4 60 102
27
35
7
9
in patients undergoing CE for obscure-overt GI bleeding (55%) and polyposis syndromes (71%).
3. Results 3.1. Patients and findings
3.2. Clinical outcome and consequences 180 CE studies were reviewed in 179 patients (mean age 55 years, range 16–90, 42% male). One patient with Peutz–Jeghers syndrome underwent two procedures during the study period because of regular surveillance of the small bowel. The indications for performing CE were obscureoccult GI bleeding (57% of cases), obscure-overt GI bleeding (15%), suspected Crohn’s disease (19%), suspected polyps (4%; Lynch syndrome n = 2, familial adenomatous polyposis n = 2, Peutz–Jeghers syndrome n = 1), suspected small bowel carcinoid (2%) and other indications (3%). Most patients (n = 141), including all patients with obscure-occult or obscure-overt GI bleeding, had undergone upper and lower gastrointestinal endoscopy prior to CE. All patients with suspected Crohn’s disease had undergone ileocolonoscopy prior to CE. CE was performed without complications in 179/180 cases. One patient experienced capsule retention at an unexpected small bowel stenosis and underwent elective surgery [16]. The cecum was reached during recording time in 146 (80.7%) cases. Findings of CE for all referral indications are summarized in Table 1. The most frequent finding was angiectasia(s), detected in 38 patients (21%). Active bleeding or oozing of angiectasias was seen in 8 of these patients. The overall diagnostic yield was 43%, i.e. in 102 cases (57%) no abnormalities were found on CE. The diagnostic yield was highest
Information on the clinical outcome and consequences of the CE with at least 12 months follow-up was obtained for 165/179 patients. In 53 patients (32%), CE had resulted in major-, in the remaining 112 cases in minor changes in patient management (68%). Table 2 summarizes the outcome of CE depending on the initial indication for the procedure. Major management changes were mainly seen in patients undergoing CE for obscure-overt GI bleeding, polyposis syndromes and suspected Crohn’s disease. For patients undergoing CE for obscure-occult GI gastrointestinal bleeding, mostly minor management changes were observed. Six patients underwent surgery, consisting of partial small bowel resection. Two patients had anastomotic ulcers after previous small bowel surgery, 1 patient had ulcerative stenotic Crohn’s disease, 1 had a Dieulafoy lesion in the ileum [17], 1 patient had a large duodenal adenoma and 1 patient had massively bleeding angiectasias for which surgery was performed. Therapeutic endoscopic procedures were carried out in 31 patients (16 PE, 8 double balloon enteroscopy, 3 intraoperative enteroscopy, 4 colonoscopy), in the majority of cases to treat angiectasias with APC. Major management changes consisting of medical therapy had occurred in 16 patients. This concerned 1 patient with known Crohn’s dis-
Table 2 Management changes following CE in relation to the reason for the procedure Consequence
All cases n
Obscure GI bleeding n
Overt GI bleeding n
Suspected Crohn’s n
Polyposis syndromes n
Other n
Major Surgery Therapeutic endoscopy Medical therapy
6 31 16
1 14 4
2 10 2
2 2 10
1 4 0
0 1 0
Minor Iron supplementation Wait-and-see
67 45
59 16
6 4
1 17
0 2
1 6
165
94
24
32
7
8
Total
764
A.P. de Graaf et al. / Digestive and Liver Disease 40 (2008) 761–766
Table 3 Correlation between predicted and actual consequences of CE Predicted consequence
Actual consequences
ultimate consequences matched in 77% (not significantly different). Total
Major
Minor
Major Minor
27 10
16 65
43 75
Total
37
81
118
ease, 9 patients with newly diagnosed Crohn’s disease and 6 patients in whom NSAIDs were discontinued. Overall, 112 patients were managed with a minor intervention, consisting of iron supplementation therapy in the majority of cases (Table 2). CE had shown no abnormalities in 100 patients from whom follow-up data were available. This mostly concerned patients with obscure-overt or obscure-occult gastrointestinal bleeding (70%). These patients were initially managed with iron supplementation (64%), occasional blood transfusion (3%) or a wait-and-see policy (33%). Follow-up of these 70 patients during a mean period of 33 months (range 12–50 months) revealed no clinically evident bleeding episodes in all but 3 patients. The three patients experiencing bleeding episodes proved to suffer from gastric Dieulafoy lesions (in two) and one patient with an ulcerative colonic anastomosis. Taken together, 67 of 70 patients (96%) who underwent CE for obscure GI bleeding with normal CE findings were well managed with conservative therapy on long-term follow-up. 3.3. Correlation between actual and predicted consequences of CE From 118 cases, questionnaires with the predicted consequences and actual consequences of CE during the follow-up period were available. In the remaining 62 cases, the questionnaires had not been returned or data had been provided insufficiently. Results are summarized in Table 3. For 43 cases, CE had a finding for which a major consequence on patient management had been predicted by the referring physicians. In 27 of these cases (63%), the actual clinical consequence of the procedure on patient management indeed concerned a major consequence. For 75 cases with findings for which a minor consequence had been predicted by the referring physician, the actual consequences on patient management had indeed been minor in 87% of the cases. So, the consequences of CE on patient management were more often over-estimated than under-estimated. Overall, predicted and actual consequences matched in 78% of the investigated cases (Kendall’s coefficient of concordance 0.52, p < 0.001). The consequences were best predicted if the findings were angiectasias or active bleeding (data not shown). If the CE revealed ulcers and/or erosions, physicians’ predictions were relatively poor. In case of positive findings on CE, the predicted and actual consequences matched in 79% of cases. When CE had revealed no abnormalities, the predicted and
4. Discussion Although the higher diagnostic yield of CE compared with other diagnostic techniques for small bowel pathology has been firmly established, the impact of this relatively new modality on patient management is less clear. In this prospective study we determined the clinical outcome after CE and the correlation with the expectations from the referring physicians. We found that CE had major management consequences in about one-third of cases, and that in most cases, the consequences were adequately predicted by the referring physicians. With any new technology comes the question of whether physicians are able to correctly estimate patient outcomes. In order for a physician to appreciate the value of a new procedure, he or she needs to understand the risks, benefits and consequences of the procedure. The success of a novel procedure, in terms of its diagnostic and clinical yield, partly relies upon the physicians’ beliefs and intentions with respect to this procedure [18]. Our study is the second report in which this aspect of capsule endoscopy was studied. Physicians proved to perform well in estimating the consequences of CE on patient management, reflected by an overall match in 78% of the investigated cases between the anticipated and ultimate consequences. The match results were similar in CE procedures with positive and negative findings, suggesting that physicians estimate the consequences of the procedure well, irrespective of whether the procedure yielded positive or negative findings. Subgroup analysis showed that if CE revealed angiectasias or active bleeding, physicians had best predicted the management consequences. This finding was expected, as it is relatively clear that in these cases additional therapeutic endoscopic or surgical interventions are needed. Physicians were less precise in predicting the clinical consequences if erosions or ulcers were found on CE. This is also not surprising, as it has become clear that this finding is an unspecific, not uncommon, finding of CE, with a large differential diagnosis. Up to 10% of healthy subjects demonstrate mucosal breaks and erosions on CE [19]. Such erosions and ulcers may also be the result of NSAID use [20] and need not necessarily implicate the presence of Crohn’s disease. Given the lack of standardization in the description of such lesions, it is important that a simple scoring system for this purpose is being developed. Recently, such a scoring index to quantify mucosal changes associated with inflammatory diseases was reported [21]. Our findings are markedly in accordance with those of Gubler et al. [22]. In their recent study in 128 patients, with a similar design, findings of capsule endoscopy and further management were consistent with the clinical predictions in 73% of cases, as compared to 78% in our study.
A.P. de Graaf et al. / Digestive and Liver Disease 40 (2008) 761–766
An important clinical question is how to manage patients with normal findings on capsule endoscopy, especially those with obscure-occult gastrointestinal bleeding. These patients are usually managed conservatively. We found that the majority of these patients did not experience recurrent bleeding and did not require blood transfusions during follow-up. This has also been demonstrated in several other studies [23–25]. Evidence accumulates that patients with obscure-occult GI bleeding and a negative CE are probably best managed conservatively without embarking on further investigations [14]. Iron supplementation should be given to those with symptomatic anemia. The overall diagnostic yield of CE in our study was 43%. Many studies are available that have focused on the diagnostic yield of CE, which ranges from 45 to 70%, depending on the indication for the procedure [14]. For obscure GI bleeding, the diagnostic yield has been reported to vary between 47 and 63% [2]. In our study, the diagnostic yield was higher for obscure-overt GI bleeding than for obscure-occult GI bleeding, which is in accordance with other studies [2]. For suspected small bowel Crohn’s disease, it was 39% which is somewhat lower than in other reports [4]. The diagnostic yield for polyposis syndromes such as Peutz–Jeghers syndrome and familial adenomatous polyposis was high, as in other studies [8,9]. We found that CE had major management consequences in 32% of cases. In a similar study in 56 patients with 6 months follow-up, in which major and minor consequences were identically defined as in our study, major management changes were seen in 38% [15]. Several other studies are available on outcomes of CE in which changes in patient management have been described [23–28]. In a study of 43 patients with a mean follow-up of 6.7 months, 28% had changes in management than can be considered as major [26]. In a large series of 300 patients with a mean followup of 17 months, management was altered in 26% of patients [27]. Several studies have determined the outcome of CE in patients with obscure GI bleeding. Estevez studied 95 patients with obscure GI bleeding with a mean follow-up of 11 months and found that 23% of patients were managed with endoscopic or surgical therapy following CE [28]. In a large series of 260 patients with obscure GI bleeding and a mean followup of 9.6 months, a similar outcome of 24% was reported [23]. Our results in patients with obscure GI bleeding, in whom CE led to endoscopic or surgical therapy in 23% of cases, are in line with these studies. Taken together, the influence of CE on patient management is remarkably constant in the available studies, including the present report, being around 25%. In conclusion, this study with a mean follow-up of almost 3 years confirms previous data that CE has a considerable diagnostic yield and a major influence on patient management in about one third of cases. Our results indicate that the physicians’ awareness of the potential consequences of CE is generally appropriate when ordering the investigation.
765
Practice points • In about one third of patients, capsule endoscopy has major consequences on patient management, defined as surgical, endoscopic or pharmacological intervention. • In patients with obscure gastrointestinal bleeding and normal findings at capsule endoscopy, it is safe to manage these patients conservatively without further investigations. • The diagnostic yield of capsule endoscopy is higher in patients with obscure-overt than in those with obscure-occult gastrointestinal bleeding. • Referring physicians are generally able to estimate the consequences of capsule endoscopy on patient management when ordering the procedure.
Research agenda • Studies with longer follow-up are needed to establish patient outcomes after capsule endoscopy, especially in those with normal findings. • Efforts should be made to define criteria for optimal patient selection, to increase the diagnostic and therapeutic yield of capsule endoscopy.
Conflict of interest statement None declared.
Acknowledgements We thank, in addition to the referring specialists in our hospital, the following specialists for patient referral and for providing data on the follow-up of patients: Dr. Bergmann, Dr. van der Waaij, Dr. van Tol, Dr. van der Heide (Martini Hospital Groningen), Dr. Capelle, Dr. Jebbink, Dr. Spoelstra, Dr. Meerman, Dr. van der Linde (Medical Center Leeuwarden), Dr. Wouters, Dr. Vosmaer, Dr. Haanstra (Scheper Hospital Emmen), Dr. Laterveer, Dr. Jager, Dr. Gerretsen, Dr. Korte, Dr. Riemens, Dr. Borst (Diakonessen Hospital Meppel), Dr. Tel, Dr. Voskuil, Dr. Daling, Dr. Adriaanse, Dr. Vermeer, Dr. Wesche, (Tjongerschans Hospital Heerenveen), Dr. Klompmaker (Wilhelmina Hospital Assen).
766
A.P. de Graaf et al. / Digestive and Liver Disease 40 (2008) 761–766
We thank Prof. J.H. Kleibeuker for critical reading of the manuscript. [15]
References [16] [1] Pennazio M. Capsule endoscopy: where are we after 6 years of clinical use? Dig Liver Dis 2006;38:867–78. [2] Triester SL, Leighton JA, Leontiadis GI, Fleischer DE, Hara AK, Heigh RI, et al. A meta-analysis of the yield of capsule endoscopy compared to other diagnostic modalities in patients with obscure gastrointestinal bleeding. Am J Gastroenterol 2005;100:2407–18. [3] Mow WS, Lo SK, Targan SR, Dubinsky MC, Treyzon L, Abreu-Martin MT, et al. Initial experience with wireless capsule enteroscopy in the diagnosis and management of inflammatory bowel disease. Clin Gastroenterol Hepatol 2004;2:31–40. [4] Triester SL, Leighton JA, Leontiadis GI, Gurudu SR, Fleischer DE, Hara AK, et al. A meta-analysis of the yield of capsule endoscopy compared to other diagnostic modalities in patients with non-stricturing small bowel Crohn’s disease. Am J Gastroenterol 2006;101:954–64. [5] Girelli CM, Porta P, Malacrida V, Barzaghi F, Rocca F. Clinical outcome of patients examined by capsule endoscopy for suspected small bowel Crohn’s disease. Dig Liver Dis 2007;39:148–54. [6] Rondonotti E, Spada C, Cave D, Pennazio M, Riccioni ME, De Vitis I, et al. Video capsule enteroscopy in the diagnosis of celiac disease: a multicenter study. Am J Gastroenterol 2007;102:1624–31. [7] Hopper AD, Sidhu R, Hurlstone DP, McAlindon ME, Sanders DS. Capsule endoscopy: an alternative to duodenal biopsy for the recognition of villous atrophy in coeliac disease? Dig Liver Dis 2007;39:140–5. [8] Burke CA, Santisi J, Church J, Levinthal G. The utility of capsule endoscopy small bowel surveillance in patients with polyposis. Am J Gastroenterol 2005;100:1498–502. [9] Schulmann K, Hollerbach S, Kraus K, Willert J, Vogel T, Moslein G, et al. Feasibility and diagnostic utility of video capsule endoscopy for the detection of small bowel polyps in patients with hereditary polyposis syndromes. Am J Gastroenterol 2005;100:27–37. [10] Marmo R, Rotondano G, Piscopo R, Bianco MA, Cipolletta L. Metaanalysis: capsule enteroscopy vs. conventional modalities in diagnosis of small bowel diseases. Aliment Pharmacol Ther 2005;22:595–604. [11] de Leusse A, Vahedi K, Edery J, Tiah D, Fery-Lemonnier E, Cellier C, et al. Capsule endoscopy or push enteroscopy for first-line exploration of obscure gastrointestinal bleeding? Gastroenterology 2007;132:855–62. [12] Chong AK, Taylor A, Miller A, Hennessy O, Connell W, Desmond P. Capsule endoscopy vs. push enteroscopy and enteroclysis in suspected small-bowel Crohn’s disease. Gastrointest Endosc 2005;61:255–61. [13] Saperas E, Dot J, Videla S, Alvarez-Castells A, Perez-Lafuente M, Armengol JR, et al. Capsule endoscopy versus computed tomographic or standard angiography for the diagnosis of obscure gastrointestinal bleeding. Am J Gastroenterol 2007;102:731–7. [14] Mergener K, Ponchon T, Gralnek I, Pennazio M, Gay G, Selby W, et al. Literature review and recommendations for clinical application of small-bowel capsule endoscopy, based on a panel discussion by
[17]
[18]
[19]
[20]
[21]
[22]
[23]
[24]
[25]
[26] [27]
[28]
international experts. Consensus statements for small-bowel capsule endoscopy, 2006/2007. Endoscopy 2007;39:895–909. Neu B, Ell C, May A, Schmid E, Riemann JF, Hagenmuller F, et al. Capsule endoscopy versus standard tests in influencing management of obscure digestive bleeding: results from a German multicenter trial. Am J Gastroenterol 2005;100:1736–42. Weersma RK, Limburg AJ, Karrenbeld A, Koornstra JJ. Iron deficiency anaemia 10 years after small bowel resection in infancy. Gut 2007;56:488. Wegdam JA, Hofker HS, Dijkstra G, Stolk MF, Jacobs MA, Suurmeijer AJ. Occult gastrointestinal bleeding due to a Dieulafoy lesion in the terminal ileum. Ned Tijdschr Geneeskd 2006;150:1776–9. Myers RE, Hyslop T, Gerrity M, Schlackman N, Hanchak N, Grana J, et al. Physician intention to recommend complete diagnostic evaluation in colorectal cancer screening. Cancer Epidemiol Biomarkers Prev 1999;8:587–93. Bar-Meir S. Review article: capsule endoscopy—are all small intestinal lesions Crohn’s disease? Aliment Pharmacol Ther 2006;24(Suppl 3):19–21. Maiden L, Thjodleifsson B, Seigal A, Bjarnason II, Scott D, Birgisson S, et al. Long-term effects of nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 selective agents on the small bowel: a cross-sectional capsule enteroscopy study. Clin Gastroenterol Hepatol 2007;5:1040–5. Gralnek IM, Defranchis R, Seidman E, Leighton JA, Legnani P, Lewis BS. Development of a capsule endoscopy scoring index for small bowel mucosal inflammatory change. Aliment Pharmacol Ther 2008;27:146–54. Gubler C, Fox M, Hengstler P, Abraham D, Eigenmann F, Bauerfeind P. Capsule endoscopy: impact on clinical decision making in patients with suspected small bowel bleeding. Endoscopy 2007;39:1031–6. Carey EJ, Leighton JA, Heigh RI, Shiff AD, Sharma VK, Post JK, et al. A single-center experience of 260 consecutive patients undergoing capsule endoscopy for obscure gastrointestinal bleeding. Am J Gastroenterol 2007;102:89–95. Lai LH, Wong GL, Chow DK, Lau JY, Sung JJ, Leung WK. Longterm follow-up of patients with obscure gastrointestinal bleeding after negative capsule endoscopy. Am J Gastroenterol 2006;101: 1224–8. Delvaux M, Fassler I, Gay G. Clinical usefulness of the endoscopic video capsule as the initial intestinal investigation in patients with obscure digestive bleeding: validation of a diagnostic strategy based on the patient outcome after 12 months. Endoscopy 2004;36: 1067–73. Rastogi A, Schoen RE, Slivka A. Diagnostic yield and clinical outcomes of capsule endoscopy. Gastrointest Endosc 2004;60:959–64. Sidhu R, Sanders DS, Kapur K, Hurlstone DP, McAlindon ME. Capsule endoscopy changes patient management in routine clinical practice. Dig Dis Sci 2007;52:1382–6. Estevez E, Gonzalez-Conde B, Vazquez-Iglesias JL, de Los Angeles Vazquez-Millan M, Pertega S, Alonso PA, et al. Diagnostic yield and clinical outcomes after capsule endoscopy in 100 consecutive patients with obscure gastrointestinal bleeding. Eur J Gastroenterol Hepatol 2006;18:881–8.
Digestive and Liver Disease 40 (2008) 761–766
Digestive Endoscopy
Correlation between predicted and actual consequences of capsule endoscopy on patient management A.P. de Graaf, J. Westerhof, R.K. Weersma, W.J. Thijs, A.J. Limburg, J.J. Koornstra ∗ Department of Gastroenterology and Hepatology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands Received 10 January 2008; accepted 19 February 2008 Available online 3 April 2008
Abstract Background. Capsule endoscopy (CE) is a relatively new diagnostic modality in the evaluation of patients with suspected small bowel pathology. It is unclear to what extent physicians are able to predict the clinical consequences of CE on patient management. Methods. In this prospective study, 180 consecutive CE examinations were analysed. Prior to CE, referring physicians were asked to indicate the consequences of CE according to potential different CE outcomes. The influence of CE on patient management was determined with at least 1 year follow-up. Management consequences were defined as major (surgical or endoscopic intervention, or medical therapy) or minor (nonspecific therapy, including iron supplementation, or no further diagnostic tests). Results. CE led to major management consequences in 32% of cases. Of patients with obscure gastrointestinal bleeding and normal CE findings, 91% were independent of blood transfusions and experienced no further bleeding episodes during a mean follow-up of 33 months. In 78% of 118 cases that were evaluated, the actual consequences of CE matched the consequences predicted by the referring physicians. Conclusion. CE had a major impact on patient management in about one third of investigations. In the majority of cases, physicians adequately predicted the clinical consequences of CE. © 2008 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. Keywords: Capsule endoscopy; Obscure gastrointestinal bleeding
1. Introduction Capsule endoscopy (CE) is a relatively new diagnostic technique to explore the small bowel. Capsule endoscopy has proven to be a valuable tool in the evaluation of obscure gastro-intestinal (GI) bleeding [1,2], suspected Crohn’s disease [3–5], celiac disease [6,7] and polyposis syndromes such as Peutz–Jeghers syndrome [8,9]. It has shown to have a higher diagnostic yield for most of these indications compared to conventional diagnostic methods such as push-enteroscopy (PE), enteroclysis, small-bowel-followthrough and CT angiography or conventional angiography [2,4,10–14]. ∗ Corresponding author at: Department of Gastroenterology and Hepatology, University Medical Centre Groningen, University of Groningen, P.O. Box 30001, 9700 RB Groningen, The Netherlands. Tel.: +31 503613354; fax: +31 503619306. E-mail address: [email protected] (J.J. Koornstra).
A feature of CE that has been studied less often is the influence of findings of CE on the further management and outcome of patients. In most studies published on this issue, follow-up is usually limited and patient series are relatively small. Another aspect of CE that has not been studied in detail is whether physicians ordering CE procedures are able to predict the clinical consequences of CE for the management of their individual patients. Since CE is usually not available in every hospital, patients are often referred from regional hospitals to a central referral centre. With a relatively new diagnostic modality like CE, one could imagine that it may be difficult for referring physicians, who probably see only a few patients with an indication for CE per year, to predict the clinical consequences of this modality for patient management. It is therefore important to know which possible consequences the referring physician has in mind, when deciding that a CE procedure is indicated. By comparing the actual consequences of CE for patient management
1590-8658/$30 © 2008 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.dld.2008.02.025
762
A.P. de Graaf et al. / Digestive and Liver Disease 40 (2008) 761–766
2. Materials and methods
medical therapy (for example for Crohn’s disease); (c) other changes in medical therapy (for example discontinuation of NSAIDs); (d) additional diagnostic procedures (push-enteroscopy, intra-operative enteroscopy or double balloon enteroscopy) and (e) surgery. For example, if a patient was referred for obscure-occult GI bleeding, the referring physician had to indicate prior to CE which consequence the finding of ‘no abnormalities’ would have on further patient management, which consequence the finding of ‘angiectasias’ would have on further patient management and so on for every possible finding. For analysis of the correlation between the actual and predicted consequences of CE on patient management, the first step was retrieving the findings of CE for each case. Next, the actual consequence of those findings for patient management, as assessed during the follow-up period, was determined. Finally, the actual consequence on patient management was compared with the consequence predicted by the referring physician.
2.1. Patients and methods
2.2. Capsule endoscopy procedure
Data from all consecutive CE studies performed in the University Medical Centre Groningen between September 2003 and December 2005 were analysed. Our hospital is a tertiary care centre with a referral base drawing from the northern part of the Netherlands. This is reflected by the fact that 52.2% of patients included in this study were referred from hospitals in the area just for CE. Prior to each CE, data were collected regarding patient age, gender, medication use, in particular oral anticoagulation and non-steroidal anti-inflammatory drugs (NSAIDs), need for blood transfusions, previously performed diagnostic investigations (gastroduodenoscopy, colonoscopy, push-enteroscopy, SBFT, angiography, computed tomography) and the reason for performing the CE procedure. The reasons for performing a CE procedure were classified in six different categories: (1) obscure-occult GI bleeding; (2) obscure-overt GI bleeding; (3) suspected Crohn’s disease; (4) polyposis syndromes; (5) suspected small bowel carcinoid and (6) other indications. Obscure-occult GI bleeding was defined as chronic iron-deficiency anemia without any clinically evident bleeding episode with negative upper and lower endoscopy. Obscure-overt GI bleeding included a history of bleeding episodes marked by melena, hematemesis and/or hematochezia. Referring physicians were asked in a questionnaire prior to each CE to predict the consequences of CE according to different potential findings. The following potential findings were given: (a) no abnormalities; (b) angiectasias; (c) ulcers/erosions; (d) mass lesion. For each potential finding, physicians were asked to indicate which consequence they would draw from this finding. The following possible consequences were given: (a) conservative therapy (iron supplementation/occasional blood transfusion or wait-and see/no further investigations); (b) introduction of specific
Patients were given standard instructions for the procedure and informed consent was obtained. Patients started fasting from midnight before the procedure. Bowel preparation consisted of 4 l of polyethylene glycol (PEG). The capsule (Given Imaging Ltd., Yoqneam, Israel) was swallowed in the morning and patients were allowed to drink fluids after 3 h and to consume a light meal after 5 h. The CE results were reviewed by at least two of four gastroenterologists (RKW, WJT, AJL or JJK). Any controversial finding was extensively discussed, and findings were classified as relevant or irrelevant. The most relevant findings obtained from CE were documented and categorized as angiectasia(s), ulcer(s)/erosion(s), polyp(s)/tumour(s), or incidental abnormality of esophagus, stomach or colon. CE was considered complete when the cecum was reached. The clinical outcomes and consequences for patient management of CE were determined at least 12 months after the CE had been performed. Referring physicians were asked to provide patient reports or computerized medical charts. In addition, information was obtained on the occurrence of (re)bleeding episodes and the need for blood transfusions. The consequences of CE on patient management were classified as major or minor in accordance with an earlier publication by Neu et al. [15]. As major consequences were regarded: surgery, endoscopic intervention (e.g. double balloon enteroscopy, push enteroscopy or colonoscopy with argon plasma coagulation-APC), or medical therapy based on positive findings at CE (e.g. introducing Crohn’s disease medication, discontinuating NSAIDs). Consequences were considered as minor following CE when no specific therapy was started (e.g. iron supplementation therapy) or when no further diagnostic tests had been performed due to either negative findings of CE or positive findings of CE considered to be irrelevant.
with the predicted consequences, one could estimate whether the expectations of referring physicians are appropriate. If referring physicians would perform poorly on predicting the consequences of CE on patient management, efforts should be made to better define the indications for CE to avoid unnecessary CE procedures. It must be realised that several factors influence physicians’ expectations, including the results and extent of previous clinical investigations, patient characteristics, availability of possible treatment modalities, incidence of expected diseases and the level of experience of the physician with the procedure. In this study we evaluated the consequences of CE on patient management with a follow-up after the procedure of at least 1 year. In addition, we studied to what extent the consequences of CE on patient management actually matched the referring physicians’ predicted consequences of CE.
A.P. de Graaf et al. / Digestive and Liver Disease 40 (2008) 761–766
763
Table 1 Findings of CE and in relation to the reasons for performing the procedure Findings
All cases
Obscure occult GIB
Obscure overt GIB
Suspected Crohn’s
Polyposis syndromes
Other
n
%
n
%
n
%
n
%
n
%
n
%
Angiectasia(s) Ulcer(s)/erosion(s) Polyp/tumour Abnormality in stomach or colon No abnormalities
38 25 9 6 102
21 14 5 3 57
24 11 1 5 59
10 1 2 2 12
37 4 7 7 45
1 12 0 0 22
3 34 0 0 63
0 0 5 0 2
0 0 71 0 29
1 1 1 0 6
11 11 11 0 67
Total
180
26 11 1 4 60 102
27
35
7
9
in patients undergoing CE for obscure-overt GI bleeding (55%) and polyposis syndromes (71%).
3. Results 3.1. Patients and findings
3.2. Clinical outcome and consequences 180 CE studies were reviewed in 179 patients (mean age 55 years, range 16–90, 42% male). One patient with Peutz–Jeghers syndrome underwent two procedures during the study period because of regular surveillance of the small bowel. The indications for performing CE were obscureoccult GI bleeding (57% of cases), obscure-overt GI bleeding (15%), suspected Crohn’s disease (19%), suspected polyps (4%; Lynch syndrome n = 2, familial adenomatous polyposis n = 2, Peutz–Jeghers syndrome n = 1), suspected small bowel carcinoid (2%) and other indications (3%). Most patients (n = 141), including all patients with obscure-occult or obscure-overt GI bleeding, had undergone upper and lower gastrointestinal endoscopy prior to CE. All patients with suspected Crohn’s disease had undergone ileocolonoscopy prior to CE. CE was performed without complications in 179/180 cases. One patient experienced capsule retention at an unexpected small bowel stenosis and underwent elective surgery [16]. The cecum was reached during recording time in 146 (80.7%) cases. Findings of CE for all referral indications are summarized in Table 1. The most frequent finding was angiectasia(s), detected in 38 patients (21%). Active bleeding or oozing of angiectasias was seen in 8 of these patients. The overall diagnostic yield was 43%, i.e. in 102 cases (57%) no abnormalities were found on CE. The diagnostic yield was highest
Information on the clinical outcome and consequences of the CE with at least 12 months follow-up was obtained for 165/179 patients. In 53 patients (32%), CE had resulted in major-, in the remaining 112 cases in minor changes in patient management (68%). Table 2 summarizes the outcome of CE depending on the initial indication for the procedure. Major management changes were mainly seen in patients undergoing CE for obscure-overt GI bleeding, polyposis syndromes and suspected Crohn’s disease. For patients undergoing CE for obscure-occult GI gastrointestinal bleeding, mostly minor management changes were observed. Six patients underwent surgery, consisting of partial small bowel resection. Two patients had anastomotic ulcers after previous small bowel surgery, 1 patient had ulcerative stenotic Crohn’s disease, 1 had a Dieulafoy lesion in the ileum [17], 1 patient had a large duodenal adenoma and 1 patient had massively bleeding angiectasias for which surgery was performed. Therapeutic endoscopic procedures were carried out in 31 patients (16 PE, 8 double balloon enteroscopy, 3 intraoperative enteroscopy, 4 colonoscopy), in the majority of cases to treat angiectasias with APC. Major management changes consisting of medical therapy had occurred in 16 patients. This concerned 1 patient with known Crohn’s dis-
Table 2 Management changes following CE in relation to the reason for the procedure Consequence
All cases n
Obscure GI bleeding n
Overt GI bleeding n
Suspected Crohn’s n
Polyposis syndromes n
Other n
Major Surgery Therapeutic endoscopy Medical therapy
6 31 16
1 14 4
2 10 2
2 2 10
1 4 0
0 1 0
Minor Iron supplementation Wait-and-see
67 45
59 16
6 4
1 17
0 2
1 6
165
94
24
32
7
8
Total
764
A.P. de Graaf et al. / Digestive and Liver Disease 40 (2008) 761–766
Table 3 Correlation between predicted and actual consequences of CE Predicted consequence
Actual consequences
ultimate consequences matched in 77% (not significantly different). Total
Major
Minor
Major Minor
27 10
16 65
43 75
Total
37
81
118
ease, 9 patients with newly diagnosed Crohn’s disease and 6 patients in whom NSAIDs were discontinued. Overall, 112 patients were managed with a minor intervention, consisting of iron supplementation therapy in the majority of cases (Table 2). CE had shown no abnormalities in 100 patients from whom follow-up data were available. This mostly concerned patients with obscure-overt or obscure-occult gastrointestinal bleeding (70%). These patients were initially managed with iron supplementation (64%), occasional blood transfusion (3%) or a wait-and-see policy (33%). Follow-up of these 70 patients during a mean period of 33 months (range 12–50 months) revealed no clinically evident bleeding episodes in all but 3 patients. The three patients experiencing bleeding episodes proved to suffer from gastric Dieulafoy lesions (in two) and one patient with an ulcerative colonic anastomosis. Taken together, 67 of 70 patients (96%) who underwent CE for obscure GI bleeding with normal CE findings were well managed with conservative therapy on long-term follow-up. 3.3. Correlation between actual and predicted consequences of CE From 118 cases, questionnaires with the predicted consequences and actual consequences of CE during the follow-up period were available. In the remaining 62 cases, the questionnaires had not been returned or data had been provided insufficiently. Results are summarized in Table 3. For 43 cases, CE had a finding for which a major consequence on patient management had been predicted by the referring physicians. In 27 of these cases (63%), the actual clinical consequence of the procedure on patient management indeed concerned a major consequence. For 75 cases with findings for which a minor consequence had been predicted by the referring physician, the actual consequences on patient management had indeed been minor in 87% of the cases. So, the consequences of CE on patient management were more often over-estimated than under-estimated. Overall, predicted and actual consequences matched in 78% of the investigated cases (Kendall’s coefficient of concordance 0.52, p < 0.001). The consequences were best predicted if the findings were angiectasias or active bleeding (data not shown). If the CE revealed ulcers and/or erosions, physicians’ predictions were relatively poor. In case of positive findings on CE, the predicted and actual consequences matched in 79% of cases. When CE had revealed no abnormalities, the predicted and
4. Discussion Although the higher diagnostic yield of CE compared with other diagnostic techniques for small bowel pathology has been firmly established, the impact of this relatively new modality on patient management is less clear. In this prospective study we determined the clinical outcome after CE and the correlation with the expectations from the referring physicians. We found that CE had major management consequences in about one-third of cases, and that in most cases, the consequences were adequately predicted by the referring physicians. With any new technology comes the question of whether physicians are able to correctly estimate patient outcomes. In order for a physician to appreciate the value of a new procedure, he or she needs to understand the risks, benefits and consequences of the procedure. The success of a novel procedure, in terms of its diagnostic and clinical yield, partly relies upon the physicians’ beliefs and intentions with respect to this procedure [18]. Our study is the second report in which this aspect of capsule endoscopy was studied. Physicians proved to perform well in estimating the consequences of CE on patient management, reflected by an overall match in 78% of the investigated cases between the anticipated and ultimate consequences. The match results were similar in CE procedures with positive and negative findings, suggesting that physicians estimate the consequences of the procedure well, irrespective of whether the procedure yielded positive or negative findings. Subgroup analysis showed that if CE revealed angiectasias or active bleeding, physicians had best predicted the management consequences. This finding was expected, as it is relatively clear that in these cases additional therapeutic endoscopic or surgical interventions are needed. Physicians were less precise in predicting the clinical consequences if erosions or ulcers were found on CE. This is also not surprising, as it has become clear that this finding is an unspecific, not uncommon, finding of CE, with a large differential diagnosis. Up to 10% of healthy subjects demonstrate mucosal breaks and erosions on CE [19]. Such erosions and ulcers may also be the result of NSAID use [20] and need not necessarily implicate the presence of Crohn’s disease. Given the lack of standardization in the description of such lesions, it is important that a simple scoring system for this purpose is being developed. Recently, such a scoring index to quantify mucosal changes associated with inflammatory diseases was reported [21]. Our findings are markedly in accordance with those of Gubler et al. [22]. In their recent study in 128 patients, with a similar design, findings of capsule endoscopy and further management were consistent with the clinical predictions in 73% of cases, as compared to 78% in our study.
A.P. de Graaf et al. / Digestive and Liver Disease 40 (2008) 761–766
An important clinical question is how to manage patients with normal findings on capsule endoscopy, especially those with obscure-occult gastrointestinal bleeding. These patients are usually managed conservatively. We found that the majority of these patients did not experience recurrent bleeding and did not require blood transfusions during follow-up. This has also been demonstrated in several other studies [23–25]. Evidence accumulates that patients with obscure-occult GI bleeding and a negative CE are probably best managed conservatively without embarking on further investigations [14]. Iron supplementation should be given to those with symptomatic anemia. The overall diagnostic yield of CE in our study was 43%. Many studies are available that have focused on the diagnostic yield of CE, which ranges from 45 to 70%, depending on the indication for the procedure [14]. For obscure GI bleeding, the diagnostic yield has been reported to vary between 47 and 63% [2]. In our study, the diagnostic yield was higher for obscure-overt GI bleeding than for obscure-occult GI bleeding, which is in accordance with other studies [2]. For suspected small bowel Crohn’s disease, it was 39% which is somewhat lower than in other reports [4]. The diagnostic yield for polyposis syndromes such as Peutz–Jeghers syndrome and familial adenomatous polyposis was high, as in other studies [8,9]. We found that CE had major management consequences in 32% of cases. In a similar study in 56 patients with 6 months follow-up, in which major and minor consequences were identically defined as in our study, major management changes were seen in 38% [15]. Several other studies are available on outcomes of CE in which changes in patient management have been described [23–28]. In a study of 43 patients with a mean follow-up of 6.7 months, 28% had changes in management than can be considered as major [26]. In a large series of 300 patients with a mean followup of 17 months, management was altered in 26% of patients [27]. Several studies have determined the outcome of CE in patients with obscure GI bleeding. Estevez studied 95 patients with obscure GI bleeding with a mean follow-up of 11 months and found that 23% of patients were managed with endoscopic or surgical therapy following CE [28]. In a large series of 260 patients with obscure GI bleeding and a mean followup of 9.6 months, a similar outcome of 24% was reported [23]. Our results in patients with obscure GI bleeding, in whom CE led to endoscopic or surgical therapy in 23% of cases, are in line with these studies. Taken together, the influence of CE on patient management is remarkably constant in the available studies, including the present report, being around 25%. In conclusion, this study with a mean follow-up of almost 3 years confirms previous data that CE has a considerable diagnostic yield and a major influence on patient management in about one third of cases. Our results indicate that the physicians’ awareness of the potential consequences of CE is generally appropriate when ordering the investigation.
765
Practice points • In about one third of patients, capsule endoscopy has major consequences on patient management, defined as surgical, endoscopic or pharmacological intervention. • In patients with obscure gastrointestinal bleeding and normal findings at capsule endoscopy, it is safe to manage these patients conservatively without further investigations. • The diagnostic yield of capsule endoscopy is higher in patients with obscure-overt than in those with obscure-occult gastrointestinal bleeding. • Referring physicians are generally able to estimate the consequences of capsule endoscopy on patient management when ordering the procedure.
Research agenda • Studies with longer follow-up are needed to establish patient outcomes after capsule endoscopy, especially in those with normal findings. • Efforts should be made to define criteria for optimal patient selection, to increase the diagnostic and therapeutic yield of capsule endoscopy.
Conflict of interest statement None declared.
Acknowledgements We thank, in addition to the referring specialists in our hospital, the following specialists for patient referral and for providing data on the follow-up of patients: Dr. Bergmann, Dr. van der Waaij, Dr. van Tol, Dr. van der Heide (Martini Hospital Groningen), Dr. Capelle, Dr. Jebbink, Dr. Spoelstra, Dr. Meerman, Dr. van der Linde (Medical Center Leeuwarden), Dr. Wouters, Dr. Vosmaer, Dr. Haanstra (Scheper Hospital Emmen), Dr. Laterveer, Dr. Jager, Dr. Gerretsen, Dr. Korte, Dr. Riemens, Dr. Borst (Diakonessen Hospital Meppel), Dr. Tel, Dr. Voskuil, Dr. Daling, Dr. Adriaanse, Dr. Vermeer, Dr. Wesche, (Tjongerschans Hospital Heerenveen), Dr. Klompmaker (Wilhelmina Hospital Assen).
766
A.P. de Graaf et al. / Digestive and Liver Disease 40 (2008) 761–766
We thank Prof. J.H. Kleibeuker for critical reading of the manuscript. [15]
References [16] [1] Pennazio M. Capsule endoscopy: where are we after 6 years of clinical use? Dig Liver Dis 2006;38:867–78. [2] Triester SL, Leighton JA, Leontiadis GI, Fleischer DE, Hara AK, Heigh RI, et al. A meta-analysis of the yield of capsule endoscopy compared to other diagnostic modalities in patients with obscure gastrointestinal bleeding. Am J Gastroenterol 2005;100:2407–18. [3] Mow WS, Lo SK, Targan SR, Dubinsky MC, Treyzon L, Abreu-Martin MT, et al. Initial experience with wireless capsule enteroscopy in the diagnosis and management of inflammatory bowel disease. Clin Gastroenterol Hepatol 2004;2:31–40. [4] Triester SL, Leighton JA, Leontiadis GI, Gurudu SR, Fleischer DE, Hara AK, et al. A meta-analysis of the yield of capsule endoscopy compared to other diagnostic modalities in patients with non-stricturing small bowel Crohn’s disease. Am J Gastroenterol 2006;101:954–64. [5] Girelli CM, Porta P, Malacrida V, Barzaghi F, Rocca F. Clinical outcome of patients examined by capsule endoscopy for suspected small bowel Crohn’s disease. Dig Liver Dis 2007;39:148–54. [6] Rondonotti E, Spada C, Cave D, Pennazio M, Riccioni ME, De Vitis I, et al. Video capsule enteroscopy in the diagnosis of celiac disease: a multicenter study. Am J Gastroenterol 2007;102:1624–31. [7] Hopper AD, Sidhu R, Hurlstone DP, McAlindon ME, Sanders DS. Capsule endoscopy: an alternative to duodenal biopsy for the recognition of villous atrophy in coeliac disease? Dig Liver Dis 2007;39:140–5. [8] Burke CA, Santisi J, Church J, Levinthal G. The utility of capsule endoscopy small bowel surveillance in patients with polyposis. Am J Gastroenterol 2005;100:1498–502. [9] Schulmann K, Hollerbach S, Kraus K, Willert J, Vogel T, Moslein G, et al. Feasibility and diagnostic utility of video capsule endoscopy for the detection of small bowel polyps in patients with hereditary polyposis syndromes. Am J Gastroenterol 2005;100:27–37. [10] Marmo R, Rotondano G, Piscopo R, Bianco MA, Cipolletta L. Metaanalysis: capsule enteroscopy vs. conventional modalities in diagnosis of small bowel diseases. Aliment Pharmacol Ther 2005;22:595–604. [11] de Leusse A, Vahedi K, Edery J, Tiah D, Fery-Lemonnier E, Cellier C, et al. Capsule endoscopy or push enteroscopy for first-line exploration of obscure gastrointestinal bleeding? Gastroenterology 2007;132:855–62. [12] Chong AK, Taylor A, Miller A, Hennessy O, Connell W, Desmond P. Capsule endoscopy vs. push enteroscopy and enteroclysis in suspected small-bowel Crohn’s disease. Gastrointest Endosc 2005;61:255–61. [13] Saperas E, Dot J, Videla S, Alvarez-Castells A, Perez-Lafuente M, Armengol JR, et al. Capsule endoscopy versus computed tomographic or standard angiography for the diagnosis of obscure gastrointestinal bleeding. Am J Gastroenterol 2007;102:731–7. [14] Mergener K, Ponchon T, Gralnek I, Pennazio M, Gay G, Selby W, et al. Literature review and recommendations for clinical application of small-bowel capsule endoscopy, based on a panel discussion by
[17]
[18]
[19]
[20]
[21]
[22]
[23]
[24]
[25]
[26] [27]
[28]
international experts. Consensus statements for small-bowel capsule endoscopy, 2006/2007. Endoscopy 2007;39:895–909. Neu B, Ell C, May A, Schmid E, Riemann JF, Hagenmuller F, et al. Capsule endoscopy versus standard tests in influencing management of obscure digestive bleeding: results from a German multicenter trial. Am J Gastroenterol 2005;100:1736–42. Weersma RK, Limburg AJ, Karrenbeld A, Koornstra JJ. Iron deficiency anaemia 10 years after small bowel resection in infancy. Gut 2007;56:488. Wegdam JA, Hofker HS, Dijkstra G, Stolk MF, Jacobs MA, Suurmeijer AJ. Occult gastrointestinal bleeding due to a Dieulafoy lesion in the terminal ileum. Ned Tijdschr Geneeskd 2006;150:1776–9. Myers RE, Hyslop T, Gerrity M, Schlackman N, Hanchak N, Grana J, et al. Physician intention to recommend complete diagnostic evaluation in colorectal cancer screening. Cancer Epidemiol Biomarkers Prev 1999;8:587–93. Bar-Meir S. Review article: capsule endoscopy—are all small intestinal lesions Crohn’s disease? Aliment Pharmacol Ther 2006;24(Suppl 3):19–21. Maiden L, Thjodleifsson B, Seigal A, Bjarnason II, Scott D, Birgisson S, et al. Long-term effects of nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 selective agents on the small bowel: a cross-sectional capsule enteroscopy study. Clin Gastroenterol Hepatol 2007;5:1040–5. Gralnek IM, Defranchis R, Seidman E, Leighton JA, Legnani P, Lewis BS. Development of a capsule endoscopy scoring index for small bowel mucosal inflammatory change. Aliment Pharmacol Ther 2008;27:146–54. Gubler C, Fox M, Hengstler P, Abraham D, Eigenmann F, Bauerfeind P. Capsule endoscopy: impact on clinical decision making in patients with suspected small bowel bleeding. Endoscopy 2007;39:1031–6. Carey EJ, Leighton JA, Heigh RI, Shiff AD, Sharma VK, Post JK, et al. A single-center experience of 260 consecutive patients undergoing capsule endoscopy for obscure gastrointestinal bleeding. Am J Gastroenterol 2007;102:89–95. Lai LH, Wong GL, Chow DK, Lau JY, Sung JJ, Leung WK. Longterm follow-up of patients with obscure gastrointestinal bleeding after negative capsule endoscopy. Am J Gastroenterol 2006;101: 1224–8. Delvaux M, Fassler I, Gay G. Clinical usefulness of the endoscopic video capsule as the initial intestinal investigation in patients with obscure digestive bleeding: validation of a diagnostic strategy based on the patient outcome after 12 months. Endoscopy 2004;36: 1067–73. Rastogi A, Schoen RE, Slivka A. Diagnostic yield and clinical outcomes of capsule endoscopy. Gastrointest Endosc 2004;60:959–64. Sidhu R, Sanders DS, Kapur K, Hurlstone DP, McAlindon ME. Capsule endoscopy changes patient management in routine clinical practice. Dig Dis Sci 2007;52:1382–6. Estevez E, Gonzalez-Conde B, Vazquez-Iglesias JL, de Los Angeles Vazquez-Millan M, Pertega S, Alonso PA, et al. Diagnostic yield and clinical outcomes after capsule endoscopy in 100 consecutive patients with obscure gastrointestinal bleeding. Eur J Gastroenterol Hepatol 2006;18:881–8.