Gastrointest Endoscopy Clin N Am 14 (2004) 115 – 127
Given capsule endoscopy in celiac disease Rima Petroniene, MD, PhDa, Elena Dubcenco, MDa, Jeffrey P. Baker, MD, FRCP(C)a, Ralph E. Warren, MD, FRCP(C)a, Cathy J. Streutker, MD, FRCP(C)b, Geoffrey W. Gardiner, MD, FRCP(C)b, Khursheed N. Jeejeebhoy, PhD, MBBS, FRCP(C)a,* a
Division of Gastroenterology, St. Michael’s Hospital and the University of Toronto, 30 Bond Street 3-035, Queen Wing, Toronto, Ontario M5B 1W8, Canada b Division of Pathology, St. Michael’s Hospital and the University of Toronto, 30 Bond Street 3-035, Queen Wing, Toronto, Ontario M5B 1W8, Canada
Celiac disease (CD) or gluten-sensitive enteropathy is an inflammatory disorder of the small intestine, caused by exposure to dietary gluten in genetically susceptible individuals. Dietary gluten provokes inflammation in the small intestine characterized by accumulation of the intraepithelial lymphocytes, development of crypt hyperplasia, and, ultimately, villous atrophy. In the majority of cases, the disease enters complete clinical and histologic remission when gluten is eliminated from the diet. Until fairly recently, CD was thought to be a relatively rare disorder with prevalence rates < 0.1% [1]. More recent studies showed that celiac sprue is a common disease affecting on average one in 200 white individuals [2,3]. This change in prevalence may be related to increasing physicians’ awareness of the silent nature of CD as well to improved diagnostic methods. The diagnosis of CD may be difficult because only a proportion of those with histologic abnormalities exhibit classical symptoms of CD. More than 50% of CD patients have no gastrointestinal (GI) symptoms or only nonspecific complaints, such as dyspepsia or anorexia [4– 6]. The analogy of an iceberg was suggested for CD, meaning that only a small portion of patients with classic symptoms are diagnosed, whereas the majority of asymptomatic individuals or subjects with mild, nonspecific symptoms remains undiagnosed and untreated
* Corresponding author. E-mail address:
[email protected] (K.N. Jeejeebhoy). 1052-5157/04/$ – see front matter D 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.giec.2003.10.005
116
R. Petroniene et al / Gastrointest Endoscopy Clin N Am 14 (2004) 115–127
[7]. On the other hand, growing body of evidence shows that early diagnosis and treatment can reduce the risk of malignant complications, such as lymphoma [8]. The gold standard for the diagnosis of CD is histopathology of the small bowel. Recently, serologic tests have been introduced as a screening tool. At present, four serologic tests are used to screen patients for CD. These include IgA anti-endomysial (AEA), IgA tissue-transglutaminase (tTG), IgA anti-gliadin (AGA), and IgG AGA antibodies. Although the sensitivity and specificity if these tests are high [9], false-negative results can occur in mild enteropathy [10] and in patients with IgA deficiency [9]. Genetic testing may facilitate the diagnosis. CD is associated with HLA-DQ2 in the majority of patients, and with HLA-DQ8 in a minority [11]. Although HLA-DQ typing has a high negative predictive value, the positive predictive value of the test is low because the above-mentioned HLA types are prevalent in a relatively large proportion of the general population [11]. Duodenal biopsies and demonstration of typical CD lesions (villous atrophy, crypt hyperplasia, increase in number of intraepithelial lymphocytes) remain a gold standard in diagnosis of CD. According to revised criteria of the European Society of Pediatric Gastroenterology and Nutrition, unequivocal diagnosis of CD requires characteristic histologic findings with clinical response to a glutenfree diet [12]. Yet, even biopsies may sometimes lead to false-negative conclusions because of the patchy nature of the mucosal damage [13]. Because of the relatively high prevalence of undiagnosed CD, any test or procedure that provides an indication for the presence of CD is of significant interest. Endoscopic markers may be useful in recognizing villous abnormalities. Awareness of endoscopic features of CD may alert endoscopists to the presence of CD and may be helpful in selecting patients for duodenal biopsies. Over the last 15 years there has been a series of publications reporting, analyzing, and discussing the data on the routine upper GI endoscopy in CD. Endoscopic evidence for villous atrophy was reported to be present in the majority of untreated celiac patients. The described endoscopic features include loss of Kerkring’s folds, visible vessels, mosaic appearance of the mucosa, and scalloping of the duodenal folds. In the literature, endoscopic visualization of at least one of the markers had a sensitivity of 87.5% to 100%, a specificity of 92% to 100%, a positive predictive value of 84% to 100%, and a negative predictive value of 96% to 99% [14 –18]. Among 36 patients who had histologically proven diagnosis of celiac disease, Maurino et al [15] found that 27 (75%) had a reduction or loss of Kerkring’s folds, 14 (39%) had a mosaic pattern, 12 (33%) had scalloped folds, and five (14%) had visible underlying blood vessels. Reduction in number, or loss, of Kerkring’s folds was the most sensitive and specific single endoscopic change indicating CD. Other studies seems to attribute optimal sensitivity for predicting villous atrophy to features of mosaic mucosa and scalloped folds [16,19,20]. Interobserver agreement is important in the studies involving subjective assessments, such as evaluation of endoscopic features. Niveloni et al [16] found an excellent interobserver agreement for the mosaic pattern (k = 0.76 for
R. Petroniene et al / Gastrointest Endoscopy Clin N Am 14 (2004) 115–127
117
both the videoendoscopic inspection alone and dye staining) and the scalloped folds (k = 0.83 and 0.76, respectively) but was only fair (k = 0.41 and 0.59, respectively) for the reduction in the number or loss of duodenal folds. The value of endoscopic markers in diagnosis of CD has been questioned recently, as some studies demonstrated low sensitivity of endoscopy in recognizing villous atrophy. In a large sample of more than 1200 patients with dyspeptic symptoms, the sensitivity of endoscopic markers for CD reached only 50% and positive predictive value was 60%, although both specificity and negative predictive values were very high (99%) [21]. Low diagnostic value of endoscopic methods was also detected in some pediatric populations [22,23]. The usefulness of endoscopic methods in CD has been discussed in the literature [24,25]. Discrepancies of the results across different studies to some extent can be explained by differences in the proportion of severe CD cases in comparison with milder ones. For example, prevalence of endoscopic marker was significantly lower for partial villous atrophy (58%) in comparison with subtotal villous atrophy (82%; P < 0.02) [26]. Studies of individuals presenting with typical CD symptoms might exhibit a much higher detection rate in comparison with unselected groups without clinical features suggestive of CD [25]. Other investigators, however, argued that the latter cannot be the main reason of low specificity [27]. Endoscopic markers perform relatively well in preselection of patients for duodenal biopsy, although they are unlikely to identify patients whose enteropathy is histologically only evident by increased intraepithelial lymphocytes without villous damage and may miss villous atrophy if it is patchy [17]. False-negative diagnoses also occur in treated celiac patients with mild atrophy [16]. The accuracy of endoscopic evaluation to some extent may depend on the experience of an endoscopist. More advanced endoscopic tools may provide additional advantages in recognizing abnormalities of the villi. Siegel et al [28] investigated the value of magnification endoscopy along with dye spraying in diagnosis of CD. Magnification endoscopy with dye spraying was both highly sensitive (94%) and specific (88%) in identifying patients with villous atrophy. This technique was more accurate (91%) in identifying patients with partial atrophy than standard endoscopy (9%, P < 0.01). It was also useful in identifying patients with patchy villous atrophy (five of five) to allow directed biopsies of abnormal tissue [28]. On the basis of the literature the visual appearance of the mucosa on conventional endoscopy can only accurately diagnose CD if magnification and dye spraying are used. These methods also are limited by the extent of the mucosa that can be examined. Recently, the Given Diagnostic Imaging System (Yoqneam, Israel) has been developed for visualization and detection of abnormalities in the small bowel. The unique advantages of the capsule endoscope, which may facilitate the diagnosis of CD, are the highly magnified and detailed view of the mucosa and the ability to scan the entire small bowel. Since capsule endoscopy (CE) has been introduced in clinical practice, studies assessing the value of this new technology in diagnosing small bowel disorders
118
R. Petroniene et al / Gastrointest Endoscopy Clin N Am 14 (2004) 115–127
have been performed. Results show that wireless CE provides excellent visualization of the small intestine, is painless, safe, and well tolerated by patients [29]. The method is now widely used in the setting of suspected small bowel bleeding as well as when small bowel disease is strongly suspected but conventional imaging techniques have failed to provide a diagnosis [30].
Given Diagnostic Imaging System Device description The Given Diagnostic Imaging System comprises three main components that include an ingestible M2A capsule, recorder, and workstation (http:// www.given imaging.com). The disposable Given capsule is 26.4 mm long and 11 mm in diameter (Fig. 1). After ingestion, the capsule moves through the digestive system propelled by peristalsis, acquiring the video images as it travels through the digestive tract. A complementary metal oxide semiconductor (CMOS) sensor and a microtransmitter inserted into the capsule allow the acquisition of high-quality video color images, which are transmitted via digital radio frequency communication channel to the Given data recorder unit located outside the body. The portable recorder consists of an antenna array carried near the body, a receiver, and memory for accumulation of the data during the examination. The total recording time is about 8 hours after which a physician transfers the accumulated data from the recorder to the RAPID workstation for interpretation. The data transmission is performed via high-capacity digital link. The workstation is a modified standard personal computer intended for off-line storage, interpretation, and analysis of the acquired data and for generating
Fig. 1. Given capsule endoscope. (Courtesy of Given Imaging.)
R. Petroniene et al / Gastrointest Endoscopy Clin N Am 14 (2004) 115–127
119
reports. The method of calculation allows a global image of the progression of the capsule and of the shape of the intestine. The outcome of the capsule test is a video film that presents the images acquired by the capsule while passing the gastrointestinal tract. Procedure The preparation for the test includes 10 to 12 hours of fasting. The use of laxatives or prokinetics before the test remains somewhat controversial. In our experience, the use of laxatives facilitates the quality of the Given images by clearing the contents of the small bowel, which occasionally may be cloudy. At our center, we prescribe patients with a dose of magnesium citrate to be taken the night before the test. Only a limited amount of clear fluids is allowed after administration of the laxative. No food or drinks are allowed for 10 to 12 hours before the test. We do not routinely use prokinetics. The procedure starts with the set-up of the system, which includes initiation of the recorder, attachment of the sensor arrays to the abdomen of a patient, and connection of the arrays to the recorder. The recorder is placed in the pocket of a special belt. The capsule is swallowed with a glass of water. After the capsule is ingested, patients are allowed to move around freely. They are asked to return to the facility 8 hours later for removal of the belt with the recorder and the sensor arrays. Before discharge, patients are asked to attempt to verify that the capsule exited the body. In our practice, abdominal radiographs are performed on patients who cannot confirm the capsule’s excretion 7 days after the test.
Differences in comparison to the conventional endoscopes CE exhibits some features that are different than those of conventional endoscopy. First, CE is painless and does not require sedation. The test is easy to perform, and no special facilities are required. Second, CE is done without air insufflation. This allows for the capsule ‘‘window’’ to slide close to the bowel wall, providing excellent visualization of the bowel mucosa. Due to magnification power of 8, the CE images of the small bowel mucosa may be comparable to those seen under the dissecting microscope. Third, CE provides an opportunity to explore the entire length of the small bowel. All these features make CE an attractive tool for assessment of patients with CD.
Given capsule endoscopy in celiac disease: case reports To our knowledge, apart from an abstract presented by our group at the Digestive Disease Week 2002, there have been no other published data on CE in CD. Our group has been performing a study dedicated to describe CE markers in CD and to establish the accuracy of the Given capsule in recognizing villous
120
R. Petroniene et al / Gastrointest Endoscopy Clin N Am 14 (2004) 115–127
atrophy as compared with histology. We hypothesize that villous atrophy can be easily recognized on the capsule images of the small bowel and that this noninvasive method could potentially be used in assessment of patients with CD. Later we present an illustrative series of CE findings on CD patients to highlight the spectrum of features seen in these patients. As mentioned previously, a significant advantage of CE is that it provides a close and magnified view of the mucosa allowing good visualization of the villi. This is well illustrated by the capsule image of the normal duodenal mucosa in Figs. 2A and B. On CE the healthy mucosa looks smooth and the finger-like villi are easily appreciated. Consistent with the imaging data, histology in this individual revealed normal mucosal architecture with tall villi, shallow crypts, and sparse infiltration of lymphocytes (Fig. 2C). When compared with normal small bowel, mucosa of patients affected with CD looks dramatically different on CE. In general, most endoscopic markers of CD as described in the literature are seen with greater clarity by CE. In our group of celiac patients we observed all of the following: scalloping of the folds, mosaicism, nodularity, visible vessels, and loss/reduction of folds (Fig. 3). In addition to general appearance of the mucosa, CE provides an opportunity to look at the details of the mucosa and assess the features of the villi. With
Fig. 2. Capsule endoscopy images of normal small bowel. (A) Proximal small bowel. (B) Distal small bowel. (C) Histology of normal small bowel. Normal mucosal architecture with normal villi-crypt ratio and absence of intraepithelial lymphocytes. (See also Color Plate 24).
R. Petroniene et al / Gastrointest Endoscopy Clin N Am 14 (2004) 115–127
121
Fig. 3. Capsule endoscopy images of celiac disease. (A) Scalloping of the small bowel folds. (B) Micronodularity. (C) Mosaicism. (D) Loss of folds. (E) Visible vessels. (See also Color Plate 25).
experience we are able to distinguish between normal/tall, shortened/broadened, or absent villi. CE also allows for approximate estimation of the length of the bowel involved with CD. Based on the CE recordings we identified two distinct groups of CD patients: those who had villous atrophy only in the proximal part of the small bowel and those who exhibited features of CD throughout the entire length of the intestine. We noticed differences in the clinical presentation between these two groups of patients. Individuals with atrophic-looking mucosa throughout the entire small bowel had typical symptoms of malabsorption (diarrhea, weight loss) as opposed to mild and nonspecific symptoms in patients with only proximal small bowel involvement. In addition, mucosa of patients with lengthy bowel involvement had distinct characteristics on the CE, such as significant atrophy with well-seen submucosal vessels and easily appreciated loss of folds. These features were not usually seen in patients in whom the disease was limited to the proximal small bowel. The following are a few examples of the CE findings in patients affected with CD. In all cases presented below, the diagnosis of CD was established based on clinical/serologic and histologic findings. Fig. 4A presents CE findings on a 17-year-old man, who presented with a 6-month history of postprandial nausea, bloating, and mild abdominal cramps. He had a positive family history of CD. Celiac serology, however, was negative
122
R. Petroniene et al / Gastrointest Endoscopy Clin N Am 14 (2004) 115–127
Fig. 4. Capsule endoscopy images. (A) Proximal small bowel. (B) Distal small bowel. (C) Histopathology. Partial villous atrophy, elongation of crypts, increased number of intraepithelial lymphocytes. (See also Color Plate 26).
(AEA and tTG). On upper endoscopy, his duodenum appeared normal. Duodenal biopsies were taken. He then underwent CE. The review of the capsule images revealed abnormally shortened villi in the proximal bowel. Mosaicism of the mucosa was also present. Histopathology showed present but blunted villi with elongation of crypts and increased number of intraepithelial lymphocytes (IELs). The findings represented partial villous atrophy consistent with CD (Fig. 4B). Review of the entire capsule video revealed that the endoscopic features of CD were present only in the small segment of the proximal small bowel, whereas the remaining bowel looked normal and had well preserved villi (Fig. 4C). Another CE image of CD is shown in Fig. 5A. This 54-year-old man was completely asymptomatic but had a ferritin of 14. On esophagogastroduodenoscopy (EGD), no endoscopic markers of CD were observed. Duodenal biopsies were taken to rule out CD. He underwent CE, which showed shortened villi along with scalloped folds. Histopathology revealed small stubby villi with an increased villous-crypt ratio and increased number of IELs. The pathologic diagnosis was that of subtotal villous atrophy consistent with CD (Fig. 5B). Again, CE showed that only the proximal small bowel was affected, whereas the distal small bowel had no features of CD (Fig. 5C).
R. Petroniene et al / Gastrointest Endoscopy Clin N Am 14 (2004) 115–127
123
Fig. 5. Capsule endoscopy images. (A) Proximal small bowel. (B) Distal small bowel. (C) Histopathology. Subtotal villous atrophy: small, stubby villi, increased number of intraepithelial lymphocytes. (See also Color Plate 27).
Fig. 6A shows an image from the proximal bowel of another celiac patient. This 57-year-old woman presented with iron deficiency anemia (Hgb 114, ferritin 14) but had no gastrointestinal complaints. EGD was performed, which showed scalloping of the valvulae conniventes, but no comments on villi could be provided. She underwent CE, which showed flat mucosa with no obvious villi. The mucosal folds looked scalloped and mosaic. Histologic assessment of the duodenal biopsies revealed total villous atrophy (Fig. 6B). According to CE, the features of the CD were present only in the proximal part of the small bowel. Villi in the distal parts of the small bowel looked absolutely normal (Fig. 6C). All three patients had different severity levels of mucosal damage—from partial to subtotal to total villous atrophy. Clinically, they all had minimal symptoms or were completely asymptomatic. In all three cases, CE revealed disease limited to the proximal small bowel. Although more cases need to be performed to draw any strong conclusions, it seems that the length of the bowel involvement rather than severity of the damage is responsible for patients’ clinical presentation. The following case report is in concordance with the latter statement.
124
R. Petroniene et al / Gastrointest Endoscopy Clin N Am 14 (2004) 115–127
Fig. 6. Capsule endoscopy images. (A) Proximal small bowel. (B) Distal small bowel. (C) Histopathology. Total villous atrophy. (See also Color Plate 28).
A 39-year-old woman was assessed for chronic severe diarrhea and weight loss. Her upper endoscopy was reported as normal, but duodenal biopsies showed total villous atrophy (Fig. 7A). CE (Fig. 7B) revealed atrophic-looking mucosa with patchy areas of paleness alternating with erythema. The underlying blood vessels were clearly visible, indicating a significant thinning of the mucosa. No villi were observed. The mucosa of the small bowel looked the same throughout the entire length up until the ileocecal valve was reached (see Fig. 7B). The patient was put on a strict gluten-free diet, but only minimal improvement in symptoms was achieved. A year later, she continues to have diarrhea and has not gained much weight. It seems that thin, atrophic, and featureless-looking mucosa on CE may signify more severe and possibly refractory disease. The extent of bowel involvement appears to correlate with the severity of symptoms. The data on the extent of small bowel involvement in CD is basically nonexistent. Cellier et al [31] looked at the value of enteroscopy in diagnosis of CD. The study showed that push-enteroscopy was useful only in patients with refractory CD, facilitating the diagnosis of ulcerative jejunitis. No correlation was found between symptoms and the extension of CD along the small bowel. Push-enteroscopy, of course, allows for an assessment of a longer segment of the
R. Petroniene et al / Gastrointest Endoscopy Clin N Am 14 (2004) 115–127
125
Fig. 7. Capsule endoscopy images. (A) Proximal small bowel. (B) Distal small bowel. (C) Histopathology. Total villous atrophy. (See also Color Plate 29).
small bowel as compared with EGD; however it is still limited to the evaluation of the proximal bowel. In this respect, CE may provide additional interesting data about the extent of the small bowel involvement in CD and the correlation between the length of the affected bowel and symptoms.
Summary Our experience suggests that CE provides good quality images of the small bowel mucosa, including well-defined villi. Dedicated CE studies on larger samples are necessary for description of typical CE markers in CD and for more accurate conclusions about the value of the method in recognizing villous atrophy. There is little doubt that the test may expand our knowledge of CD, especially with respect to the extent of small bowel involvement and the clinical consequences of the length affected. In addition, studies are warranted to evaluate the value of CE in diagnosing complications of CD, such as enteropathy-associated T-cell lymphoma, small bowel adenocarcinoma, and ulcerative enteritis. Furthermore, there may be a role for the CE in patients with other malabsorption conditions, and that also needs to be investigated.
126
R. Petroniene et al / Gastrointest Endoscopy Clin N Am 14 (2004) 115–127
References [1] Fasano A. Where have all the American celiacs gone? Acta Paediatr Suppl 1996;412:20 – 4. [2] Johnston SD, Watson RG, McMillan SA, Sloan J, Love AH. Coeliac disease detected by screening is not silent – simply unrecognized. QJM 1998;91(12):853 – 60. [3] Not T, Horvath K, Hill ID, Partanen J, Hammed A, Magazzu G, et al. Celiac disease risk in the USA: high prevalence of antiendomysium antibodies in healthy blood donors. Scand J Gastroenterol 1998;33(5):494 – 8. [4] Swinson CM, Levi AJ. Is coeliac disease underdiagnosed? BMJ 1980;281(6250):1258 – 60. [5] Bottaro G, Cataldo F, Rotolo N, Spina M, Corazza GR. The clinical pattern of subclinical/ silent celiac disease: an analysis on 1026 consecutive cases. Am J Gastroenterol 1999;94(3): 691 – 6. [6] Tursi A, Giorgetti G, Brandimarte G, Rubino E, Lombardi D, Gasbarrini G. Prevalence and clinical presentation of subclinical/silent celiac disease in adults: an analysis on a 12-year observation. Hepatogastroenterology 2001;48(38):462 – 4. [7] Feighery C. Fortnightly review: coeliac disease. BMJ 1999;319(7204):236 – 9. [8] Holmes GK, Prior P, Lane MR, Pope D, Allan RN. Malignancy in coeliac disease – effect of a gluten free diet. Gut 1989;30(3):333 – 8. [9] Farrell RJ, Kelly CP. Diagnosis of celiac sprue. Am J Gastroenterol 2001;96(12):3237 – 46. [10] Rostami K, Kerckhaert J, Tiemessen R, von Blomberg BM, Meijer JW, Mulder CJ. Sensitivity of antiendomysium and antigliadin antibodies in untreated celiac disease: disappointing in clinical practice. Am J Gastroenterol 1999;94(4):888 – 94. [11] Sollid LM. Coeliac disease: dissecting a complex inflammatory disorder. Nat Rev Immunol 2002;2(9):647 – 55. [12] Revised criteria for diagnosis of coeliac disease. Report of Working Group of European Society of Paediatric Gastroenterology and Nutrition. Arch Dis Child 1990;65(8):909 – 11. [13] Pearce CB, Duncan HD, Sinclair D, Poller DN. Small bowel biopsies in patients with iron deficiency anaemia. Gut 2001;49(4):595. [14] Magazzu G, Bottari M, Tuccari G, Arco A, Pallio S, Lucanto C, et al. Upper gastrointestinal endoscopy can be a reliable screening tool for celiac sprue in adults. J Clin Gastroenterol 1994;19(3):255 – 7 [discussion 257 – 8]. [15] Maurino E, Capizzano H, Niveloni S, Kogan Z, Valero J, Boerr L, et al. Value of endoscopic markers in celiac disease. Dig Dis Sci 1993;38(11):2028 – 33. [16] Niveloni S, Fiorini A, Dezi R, Pedreira S, Smecuol E, Vazquez H, et al. Usefulness of videoduodenoscopy and vital dye staining as indicators of mucosal atrophy of celiac disease: assessment of interobserver agreement. Gastrointest Endosc 1998;47(3):223 – 9. [17] Dickey W, Hughes D. Prevalence of celiac disease and its endoscopic markers among patients having routine upper gastrointestinal endoscopy. Am J Gastroenterol 1999;94(8):2182 – 6. [18] Brocchi E, Tomassetti P, Misitano B, Epifanio G, Corinaldesi R, Bonvicini F, et al. Endoscopic markers in adult coeliac disease. Dig Liver Dis 2002;34(3):177 – 82. [19] Ravelli AM, Tobanelli P, Minelli L, Villanacci V, Cestari R. Endoscopic features of celiac disease in children. Gastrointest Endosc 2001;54(6):736 – 42. [20] Brocchi E, Corazza GR, Caletti G, Treggiari EA, Barbara L, Gasbarrini G. Endoscopic demonstration of loss of duodenal folds in the diagnosis of celiac disease. N Engl J Med 1988;319(12): 741 – 4. [21] Bardella MT, Minoli G, Radaelli F, Quatrini M, Bianchi PA, Conte D. Reevaluation of duodenal endoscopic markers in the diagnosis of celiac disease. Gastrointest Endosc 2000;51(6):714 – 6. [22] Black DD, Haggitt RC, Whitington PF. Gastroduodenal endoscopic-histologic correlation in pediatric patients. J Pediatr Gastroenterol Nutr 1988;7(3):353 – 8. [23] Ozcay F, Demir H, Saltik IN. Low sensitivity of endoscopic markers in children with celiac disease. Gastrointest Endosc 2002;56(2):321 [author reply 321 – 3]. [24] Green PH, Shane E, Rotterdam H, Forde KA, Grossbard L. Significance of unsuspected celiac disease detected at endoscopy. Gastrointest Endosc 2000;51(1):60 – 5.
R. Petroniene et al / Gastrointest Endoscopy Clin N Am 14 (2004) 115–127
127
[25] Bardella MT, Minoli G, Ravizza D, Radaelli F, Velio P, Quatrini M, et al. Increased prevalence of celiac disease in patients with dyspepsia. Arch Intern Med 2000;160(10):1489 – 91. [26] Dickey W, Hughes D. Disappointing sensitivity of endoscopic markers for villous atrophy in a high-risk population: implications for celiac disease diagnosis during routine endoscopy. Am J Gastroenterol 2001;96(7):2126 – 8. [27] Brocchi E, Mangia L, Epifanio G, Misitano B, Corinaldesi R. Endoscopic markers in celiac disease: are they useful? Gastrointest Endosc 2001;54(2):281 – 2. [28] Siegel LM, Stevens PD, Lightdale CJ, Green PH, Goodman S, Garcia-Carrasquillo RJ, et al. Combined magnification endoscopy with chromoendoscopy in the evaluation of patients with suspected malabsorption. Gastrointest Endosc 1997;46(3):226 – 30. [29] Lewis BS, Swain P. Capsule endoscopy in the evaluation of patients with suspected small intestinal bleeding: results of a pilot study. Gastrointest Endosc 2002;56(3):349 – 53. [30] Scapa E, Jacob H, Lewkowicz S, Migdal M, Gat D, Gluckhovski A, et al. Initial experience of wireless-capsule endoscopy for evaluating occult gastrointestinal bleeding and suspected small bowel pathology. Am J Gastroenterol 2002;97(11):2776 – 9. [31] Cellier C, Cuillerier E, Patey-Mariaud de Serre N, Marteau P, Verkarre V, Briere J, et al. Push enteroscopy in celiac sprue and refractory sprue. Gastrointest Endosc 1999;50(5):613 – 7.
