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Original article
Clinical relevance of patency capsule combined with abdominal ultrasonography to detect small bowel strictures Akiko Shiotania, Jiro Hatab, Noriaki Manabeb, Hiroshi Imamurab, Manabu Ishiia, Minoru Fujitaa, Hiroshi Matsumotoa, Ken-ichi Tarumia, Keisuke Hondac and Ken Harumaa Background PillCam patency capsule (PC) is a novel and radiofrequency identification tag-free device that remains intact in the gastrointestinal tract for 30–33 h after ingestion and then disintegrates. The aim of this study was to determine the clinical relevance of PC combined with abdominal ultrasonography as a reliable indicator of functional patency. Patients and methods The study was prospective and PillCam PC was administered to consecutive patients with known or suspected small bowel strictures. PC was verified if it was excreted intact in 33 h after administration. Following excretion failure and radiograph detection in the pelvic cavity, ultrasonography was used to detect the PC in relation to the stricture. Results The participants were 52 patients with known or suspected small bowel strictures (58% women, mean age 51 years, including 32 with or suspected Crohn’s disease). Twenty-two patients (42.3%) retrieved PC in the stool within 33 h after ingestion. Radiograph identified the four PCs in the colon and eight were not observed. Ultrasonography precisely judged all 17 PCs retained including six PCs at the proximal side of small bowel stricture in the patients
Background Capsule retention is defined as failure of the excretion of capsule within 14 days of ingestion, and is the most serious complication, especially in patients with Crohn’s disease (CD) [1,2]. Reported retention rates range from 0.75% in healthy individuals to 21% in those with known small bowel strictures [3–7]. Small bowel radiography has a low diagnostic yield for the presence or absence of small bowel strictures unless there is significant proximal dilatation under double-contrast barium enteroclysis [4,5,8,9]. In addition, false-positive results similar to those seen with computed tomography (CT) enteroclysis may inappropriately exclude patients who could safely undergo the capsule endoscopy (CE) [10]. A direct approach to investigating whether the capsule will pass through the small intestine is to use a patency capsule (PC). PC is a self-disintegrating sham capsule and has the same size and shape as the video capsule. Original PC consisted of a single timer plug and a radiofrequency identification (RFID) tag [7]. The later developed PC, which contains two timer plugs, an internal RFID tag, and 0954-691X © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
considered ineligible for capsule endoscopy (CE). In all eligible patients, CE passed through the small intestine without incident. Conclusion PillCam PC combined with ultrasonography before CE appears to be a reliable indicator of functional patency to predict and minimize the risk of impaction in suspected or even known cases with small bowel stricture. Eur J Gastroenterol Hepatol 26:1434–1438 © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. European Journal of Gastroenterology & Hepatology 2014, 26:1434–1438 Keywords: capsule endoscopy, chronic nonspecific multiple ulcers of the small intestine, Crohn’s disease, patency capsule, small bowel strictures a Department of Internal Medicine, Division of Gastroenterology, bDepartment of Clinical Pathology and Laboratory Medicine and cDepartment of Comprehensive Medicine, Kawasaki Medical School, Okayama, Japan
Correspondence to Akiko Shiotani, MD, PhD, Department of Internal Medicine, Division of Gastroenterology, Kawasaki Medical School, 577 Matsushima Kurashiki City, Okayama Prefecture 701-0192, Japan Tel: + 81 86 462 1111; fax: + 81 86 462 1195; e-mail: [email protected] Received 5 August 2014 Accepted 11 September 2014
barium [6]. The RFID tag allowed the presence of the PC to be detected by the RFID scanner without radiation exposure to the patient, whereas the barium allowed detection by abdominal radiograph. PillCam PC is a novel RFID tag-free PC and is available in Japan. The presence or absence of PC is designed to be assessed by using abdominal radiograph 30–33 h after ingestion in patients who do not excrete [11]. The clinical usefulness of a novel RFID tag-free PC in patients at high risk of intestinal strictures has been reported recently. However, the precise location of PC by radiograph is often difficult to determine, especially when PC is detected in the pelvic cavity, and data on the PC are still limited [7,8,11–13]. We evaluated the novel PC and in addition the clinical relevance of the PC combined with ultrasonography to detect PCs and small bowel strictures.
Patients and methods The study was a prospective study carried out at the Hospital of Kawasaki Medical School in accordance with DOI: 10.1097/MEG.0000000000000225
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Patency capsule and abdominal ultrasonography Shiotani et al. 1435
the Declaration of Helsinki. Permission was granted by the Ethics Committee of Kawasaki Medical School (Okayama, Japan), and written informed consent to undergo CE was obtained from all the patients. Patients
Consecutive patients with CD or with known or suspected small bowel strictures in whom CE was planned and received PCs between September 2012 and February 2014 were included. Small bowel strictures were evaluated by abdominal ultrasonography in all patients and by additional small bowel follow through in patients with CD lesions in the small intestine or with suspected severe stenosis. Severe intestinal stenosis was defined as intestinal strictures with proximal small bowel dilation or intestinal occlusion detected by either abdominal ultrasonography or small bowel follow through. Patients with severe intestinal stenosis were excluded, and PC and CE were not performed.
to check passage of the capsule from the stomach [14,15]. Water and food were permitted 2 and 4 h, respectively, after CE reached the small intestine. During the PC and CE procedure, food was limited only in patients with known intestinal stricture because of CD treated by an elemental diet to avoid capsule impaction in the stricture; in these patients, only an elemental diet was permitted until confirmation of excretion of the capsule. In CD patients with known intestinal stricture, only an elemental diet was permitted until the excretion of the video capsule was verified. CE procedures were reviewed by recording them as thumb-nail photographs using RAPID Access 6.5 (Given Imaging Ltd) [13,14]. Analyses
Values are expressed as the mean ± SD. Mantel–Haenszel χ2 analysis and the unpaired t-test were used to measure differences in the CE findings.
Results Patency capsule
PillCam PC (Given Imaging Ltd, Tokyo, Japan) was administered to patients with known or suspected small bowel strictures. Patients were instructed to observe their stools carefully for the excreted PC and to return it to the hospital to verify its intact excretion within 33 h after administration. If patients failed to identify the capsule in their stools, passage of the PC was assessed by abdominal radiograph. Abdominal ultrasonography
Following excretion failure and radiograph detection of the PC in the pelvic cavity, abdominal ultrasonography was used and the location of the PC was evaluated by assessing its location in the stricture without special preparation such as administration of spasmolytic agents or instillation of water into the bowel. The sonographic instrument used was the SSA-390A system (Toshiba, Tokyo, Japan) with 3–6 MHz (main frequency, 3.5 MHz) transducers in a curved array and 6–9 MHz (main frequency, 7 MHz) transducers in a linear array. Linear strong echo showing the same size and shape of the PC, followed immediately by a clear acoustic shadow is the typical sonographic figure of the PC (Fig. 1). The small intestine was considered patent and safe for the CE if the PC was (a) excreted intact, (b) not detected by ultrasonography to be at the proximal side of a suspected small bowel stricture, or (c) detected in the colon within 33 h after ingestion. If PC was detected at the distal side of a suspected small bowel stricture or in the small intestine without stricture at 33 h after ingestion, PC was repeated. Capsule endoscopy
CE using PillCam SB 2 (Given Imaging Ltd) was performed as described previously using a real-time viewer
Fifty-two patients with known or suspected small bowel strictures (22 men and 30 women, mean age 51 years) received the PC test, including 26 patients with CD, six patients with suspected CD, 14 patients with suspected NSAID enteropathy, four patients with a history of ileus, and two patients with suspected small bowel tumor (Table 1). A 78-year-old woman with suspected NSAID enteropathy could not swallow PC and was excluded from the study. Ultrasonography was performed in all patients and small bowel follow through was performed in 24 patients with or suspected CD and one patient with ileus. Small bowel stricture was detected in 21 patients: 11 patients with CD, four patients with suspected CD, and six patients with suspected NSAID enteropathy. Twenty-two (42.3%) patients retrieved PC in their stool within 33 h after ingestion. In the remaining 29 patients without PC excretion, abdominal radiographs located three PCs in the ascending colon or cecum and one in the descending colon. With abdominal radiographs, PCs were confirmed to be absent in eight patients and were detected in the pelvic cavity of 17 patients (32.7%). Among these 17 patients, abdominal ultrasonography detected the patency at the oral side of small bowel stricture in six patients; five patients with CD and one patient with NSAID-induced diaphragm disease, and these were considered to be ineligible for CE. Among the remaining 11 patients, ultrasonography detected seven retained PCs in the colon and did not detect four retained PCs in the small intestine, which were thought to pass through the small intestine. In fact, two of the four PCs were excreted intact 2 h after ultrasonography and another PC was recognized in the colon by CT. Moreover, ultrasonography found two retained PCs in the small bowel, detecting no small bowel stricture on the anal side of retained PCs. They repeated PC tests, and ultrasonography detected their second PCs in the colon.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
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European Journal of Gastroenterology & Hepatology 2014, Vol 26 No 12
Fig. 1
(a)
(b) T
T
0
0
10C3 diffT6.0 49 fps
1
G:76 DR:65
2
1
2
3
∗
MI:1.5 20G 94 DR 55
12L5 3 diffT8.0 51 fps 4
4 5
Sonographic image of the retained patency capsule (PC) at the proximal site of the ileal stenosis (*) detected by ultrasonography. Linear strong echo, followed by a clear acoustic shadow is the typical sonographic figure of the PC. The arrows indicate the retained patency: (a) long axis view; (b) short axis view.
Demographic and clinical characteristics of the patients who received a patency capsule
Table 1
Number of patients Men [n (%)] Age [mean (SD)] Known/suspected small bowel strictures Clinical indication [n (%)] Crohn’s disease Suspected Crohn’s disease Suspected NSAID enteropathy Past history of ileus Suspected tumor
52 22 (42.3) 51 (20) 21/31 26 6 14 4 2
(50) (11.5) (26.9) (7.7) (3.8)
Including these patients, the 45 patients including 30 patients with PC excretion and 15 patients with retained PCs in the colon were allowed to undergo CE (Fig. 2). In all eligible patients, the video capsule passed through the small intestine without incident. The rates of entire small bowel observation and positive finding were 88.8 and 80%, respectively. There were no significant differences in the rates of entire small bowel observation and positive findings including the transit time between the group with PC excretion and the group with retained PC in the colon. The most frequent findings were erosions or ulcers; stricture was observed in 16 patients (eight patients with CD, five patients with chronic nonspecific multiple ulcers of the small intestine, and three patients with NSAID enteropathy) (Table 2). Nine patients (four patients with CD located in the colon, two patients with suspected CD, two patients with suspected NSAIDs enteropathy, and one with a history of ileus) had no significant findings. Among the 26 patients with CD, 21 patients were eligible to undergo CE. The ineligible patients were five patients with CD and one with a history of ileus. Among the 14 patients with suspected NSAIDs enteropathy, 12 patients had multiple erosions and ulcers including three patients with small bowel stricture.
Discussion In a previous study from Japan [16], the capsule retention rate in patients with known CD was 7.4%, and similar to that reported from western countries [2]. However, unlike in western countries, CD remained a contraindication for CE in Japan until after the PillCam PC was approved by the Japanese Ministry of Health, Labor and Welfare in July 2012. We prospectively evaluated the role of abdominal ultrasonography as an adjuvant to the PC test to better predict and minimize the risk of impaction in suspected or known cases with small bowel stricture. Use of an RFID scanner or fluoroscopy can aid detection of retained Agile PC, thus avoiding the need for radiography. However, even with abdominal radiograph or fluoroscopy, it may be difficult to identify the location of retained PC precisely because of overlapping of the large and the small intestine. Two cases with capsule retention despite successful small bowel passage of PC confirmed by abdominal radiographs have been reported [17]. CT can provide a more definitive method of localization, but is often precluded because of the cost and radiation dosage. Ultrasonography is a repeatable inexpensive and safe noninvasive diagnostic modality that is useful in the assessment of CD and its complications. Bowel-wall thickness and focal disappearance of the wall stratification sign can be used to assess disease activity and identify the presence of deep longitudinal ulcers [18–20]. The sensitivity and specificity of ultrasonography in the assessment of stricture of CD range from 74 to 100 and 91 to 93%, respectively [21–23]. A recent paper also indicated a high level of accuracy of small bowel contrast ultrasonography in the detection of lesions and complications in patients with CD compared with CT enteroclysis [24]. In our 17 patients with pelvic localization, ultrasonography identified that 11 patients (64.7%) were in fact eligible for CE. Ultrasonography precisely judged all 17 retained PCs, indicating the location of all retained
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Patency capsule and abdominal ultrasonography Shiotani et al. 1437
Fig. 2
Enrollment for patency capsule n=52 Swallowing disorders n=1
No excretion within 33 h n=29
Excretion within 33 h n=22
Abdominal radiograph out of body n=8
Abdominal radiograph in the colon n=4
Abdominal radiograph in the suspected SB n=17
Abdominal US In the colon n=7 (In the SB with no stricture, n=1∗) Out of the SB n=4
Eligible CE n=45
Abdominal US in the SB n=6
No eligible CE n=6
Summary of retrieved and retained patency capsules (PC). CE, capsule endoscopy; SB, small bowel; US, ultrasonography. *Ultrasonography detected a retained PC at the distal side of small bowel stricture or without small bowel stricture in two patients who repeated the PC test, and ultrasonography detected their second PC in the colon.
Table 2
Findings of capsule endoscopy
The number of capsule procedures Completion rate [n (%)] Gastric transit time [mean (SD)] (min) SB transit time [mean (SD)] (min) Capsule retention Positive finding rate [n (%)] Findings Erosions/ulcer Stenosis Tumor suspected Diagnosed disease Crohn’s disease NSAID enteropathy CNSU Malignant lymphoma Submucosal tumor suspected
Total
PC excretion
PC in the colon
45 40 (88.8) 63 (99)
30 28 (93.3) 73(116)
15 12 (80) 40 (42)
288(109) 0 36 (80)
283(118) 0 23 (76.7)
297 (86) 0 13 (86.7)
38 16 7
25 11 3
13 5 4
18 6 7 4 2
13a 3 4b 2 1
5a 3 3b 2 1
The number included one patient (a) with suspected Crohn’s disease and one patient with suspected CNSU (b). CNSU, chronic nonspecific multiple ulcers of the small intestine; PC, patency capsule; SB, small bowel.
PCs in the small intestine, passage through small intestine, or no small bowel stricture in the distal site of the retained PCs. Ultrasonography did not detect four retained PCs in the colon, including two PCs excreted intact 2 h after ultrasonography. The detection of a retained PC in the left side of colon seems to be difficult probably because of solid
stool. However, it is much easier to detect retained PCs in the ileum irrespective of the small bowel stricture. The PC was excreted intact in approximately half of our patients, and the result is similar to that reported in a previous multicenter clinical trial of PCs (56%) [8]. In one patient with suspected NSAID enteropathy, the retained patency was detected in the small intestine with no stricture, probably because of slow small bowel transit. She repeated PC using prokinetics, and ultrasonography detected her second PC in the colon. Prokinetics for PC examination in patients with slow transit may be required. Further study of effectiveness and safety using prokinetics is required. Among five ineligible patients for CE, ultrasonography indicated long segment stricture with bowel-wall thickness and anastomotic stricture in two CD patients each. Therefore, long segment bowel-wall thickness and anastomotic stricture in CD as well as diaphragm disease seem to be risk findings for capsule retention. The limitation of our study is the relatively small sample size. Further large prospective studies will be required to confirm that PillCam PC combined with abdominal ultrasonography before CE is a safe and reliable indicator of functional patency that predicts severe stenosis and minimizes the risk of impaction in known cases with intestinal stricture. In our study, three well-trained examiners with
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more than 10 years of experience performed ultrasonography, and the procedure time to detect the retained PC and observation of small intestine was a few minutes. We did not assess the exact procedure time and the reproducibility of abdominal ultrasonography. It is well known that the accuracy and utility of ultrasonography generally depend on the examiners’ skill as well as patient factors such as abdominal fat, gas, and stool in the lower gastrointestinal tract, etc. However, the previous assessment of ultrasonography reproducibility in patients with CD by Fraquelli et al. [25] indicated excellent agreement for intestinal stricture (k = 0.81–1). We excluded patients with severe intestinal stenosis with dilation at the proximal side to avoid obstruction induced by PC. The diagnosis of severe stenosis was subjective and this exclusion for the PC lacks evidence. Nonetheless, double-balloon endoscopy may be a better option for patients with severe stenosis, which is a good indication for endoscopic balloon dilatation before deciding on surgery [26,27]. In summary, PC was excreted intact in about 60% of patients and additional abdominal ultrasonography before CE was required in one-third of the patients. Ultrasonography diagnosed the location of all retained PCs in the small intestine and confirmed that there was no small bowel stricture in the distal site of the retained PCs. In all eligible patients, the video capsule passed through the small intestine without incident. The RFID tag-free PillCam PC combined with abdominal ultrasonography before CE appears to a reliable indicator of functional patency to predict and minimize the risk of impaction in suspected or even known cases with small bowel stricture. To confirm clinical relevance, a further study with a larger number of patients and a study of the reproducibility of abdominal ultrasonography are definitely required.
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Acknowledgements The authors thank Prof. David Y. Graham for helpful comments and English editions. Conflicts of interest
There are no conflicts of interest.
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References 1
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Dionisio PM, Gurudu SR, Leighton JA, Leontiadis GI, Fleischer DE, Hara AK, et al. Capsule endoscopy has a significantly higher diagnostic yield in patients with suspected and established small-bowel Crohn’s disease: a meta-analysis. Am J Gastroenterol 2010; 105:1240–1248, quiz 1249. Bourreille A, Ignjatovic A, Aabakken L, Loftus EV Jr, Eliakim R, Pennazio M, et al. World Organisation of Digestive Endoscopy (OMED) and the European Crohn’s and Colitis Organisation (ECCO). Role of small-bowel endoscopy in the management of patients with inflammatory bowel disease: an international OMED-ECCO consensus. Endoscopy 2009; 41:618–637. Cheon JH, Kim YS, Lee IS, Chang DK, Ryu JK, Lee KJ, et al. Korean Gut Image Study Group. Can we predict spontaneous capsule passage after retention? A nationwide study to evaluate the incidence and clinical outcomes of capsule retention. Endoscopy 2007; 39:1046–1052. Pennazio M, Santucci R, Rondonotti E, Abbiati C, Beccari G, Rossini FP, De Franchis R. Outcome of patients with obscure gastrointestinal bleeding after capsule endoscopy: report of 100 consecutive cases. Gastroenterology 2004; 126:643–653.
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Sears DM, Avots-Avotins A, Culp K, Gavin MW. Frequency and clinical outcome of capsule retention during capsule endoscopy for GI bleeding of obscure origin. Gastrointest Endosc 2004; 60:822–827. Caunedo-Alvarez A, Romero-Vazquez J, Herrerias-Gutierrez JM. Patency and Agile capsules. World J Gastroenterol 2008; 14:5269–5273. Spada C, Spera G, Riccioni M, Biancone L, Petruzziello L, Tringali A, et al. A novel diagnostic tool for detecting functional patency of the small bowel: the Given patency capsule. Endoscopy 2005; 37:793–800. Herrerias JM, Leighton JA, Costamagna G, Infantolino A, Eliakim R, Fischer D, et al. Agile patency system eliminates risk of capsule retention in patients with known intestinal strictures who undergo capsule endoscopy. Gastrointest Endosc 2008; 67:902–909. Matsumoto T, Esaki M, Kurahara K, Hirai F, Fuchigami T, Matsui T, Iida M. Double-contrast barium enteroclysis as a patency tool for nonsteroidal antiinflammatory drug-induced enteropathy. Dig Dis Sci 2011; 56:3247–3253. Voderholzer WA, Beinhoelzl J, Rogalla P, Murrer S, Schachschal G, Lochs H, Ortner MA. Small bowel involvement in Crohn’s disease: a prospective comparison of wireless capsule endoscopy and computed tomography enteroclysis. Gut 2005; 54:369–373. Nakamura M, Hirooka Y, Yamamura T, Miyahara R, Watanabe O, Ando T, et al. Clinical usefulness of novel tag-less Agile patency capsule prior to capsule endoscopy for patients with suspected small bowel stenosis. Dig Endosc 2014 [Epub ahead of print]. Postgate AJ, Burling D, Gupta A, Fitzpatrick A, Fraser C. Safety, reliability and limitations of the given patency capsule in patients at risk of capsule retention: a 3-year technical review. Dig Dis Sci 2008; 53:2732–2738. Delvaux M, Ben Soussan E, Laurent V, Lerebours E, Gay G. Clinical evaluation of the use of the M2A patency capsule system before a capsule endoscopy procedure, in patients with known or suspected intestinal stenosis. Endoscopy 2005; 37:801–807. Shiotani A, Honda K, Kawakami M, Nishi R, Murao T, Ishii M, et al. Use of an external real-time image viewer coupled with prespecified actions enhanced the complete examinations for capsule endoscopy. J Gastroenterol Hepatol 2011; 26:1270–1274. Shiotani A, Honda K, Kawakami M, Kimura Y, Yamanaka Y, Fujita M, et al. Analysis of small-bowel capsule endoscopy reading by using Quickview mode: training assistants for reading may produce a high diagnostic yield and save time for physicians. J Clin Gastroenterol 2012; 46:e92–e95. Esaki M, Matsumoto T, Watanabe K, Arakawa T, Naito Y, Matsuura M, et al. Use of capsule endoscopy in patients with Crohn’s disease in Japan: a multicenter survey. J Gastroenterol Hepatol 2014; 29:96–101. Koornstra JJ, Weersma RK. Agile patency system. Gastrointest Endosc 2009; 69:602–603, author reply 603–604. Hata J, Haruma K, Suenaga K, Yoshihara M, Yamamoto G, Tanaka S, et al. Ultrasonographic assessment of inflammatory bowel disease. Am J Gastroenterol 1992; 87:443–447. Futagami Y, Haruma K, Hata J, Fujimura J, Tani H, Okamoto E, Kajiyama G. Development and validation of an ultrasonographic activity index of Crohn’s disease. Eur J Gastroenterol Hepatol 1999; 11:1007–1012. Hata J, Haruma K, Yamanaka H, Fujimura J, Yoshihara M, Shimamoto T, et al. Ultrasonographic evaluation of the bowel wall in inflammatory bowel disease: comparison of in vivo and in vitro studies. Abdom Imaging 1994; 19:395–399. Gasche C, Moser G, Turetschek K, Schober E, Moeschl P, Oberhuber G. Transabdominal bowel sonography for the detection of intestinal complications in Crohn’s disease. Gut 1999; 44:112–117. Calabrese E, La Seta F, Buccellato A, Virdone R, Pallotta N, Corazziari E, Cottone M. Crohn’s disease: a comparative prospective study of transabdominal ultrasonography, small intestine contrast ultrasonography, and small bowel enema. Inflamm Bowel Dis 2005; 11:139–145. Maconi G, Bollani S, Bianchi Porro G. Ultrasonographic detection of intestinal complications in Crohn’s disease. Dig Dis Sci 1996; 41:1643–1648. Calabrese E, Zorzi F, Onali S, Stasi E, Fiori R, Prencipe S, et al. Accuracy of small-intestine contrast ultrasonography, compared with computed tomography enteroclysis, in characterizing lesions in patients with Crohn’s disease. Clin Gastroenterol Hepatol 2013; 11:950–955. Fraquelli M, Sarno A, Girelli C, Laudi C, Buscarini E, Villa C, et al. Reproducibility of bowel ultrasonography in the evaluation of Crohn’s disease. Dig Liver Dis 2008; 40:860–866. Hirai F, Beppu T, Sou S, Seki T, Yao K, Matsui T. Endoscopic balloon dilatation using double-balloon endoscopy is a useful and safe treatment for small intestinal strictures in Crohn’s disease. Dig Endosc 2010; 22:200–204. Sunada K, Yamamoto H, Yano T, Sugano K. Advances in the diagnosis and treatment of small bowel lesions with Crohn’s disease using double-balloon endoscopy. Therap Adv Gastroenterol 2009; 2:357–366.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Original article
Clinical relevance of patency capsule combined with abdominal ultrasonography to detect small bowel strictures Akiko Shiotania, Jiro Hatab, Noriaki Manabeb, Hiroshi Imamurab, Manabu Ishiia, Minoru Fujitaa, Hiroshi Matsumotoa, Ken-ichi Tarumia, Keisuke Hondac and Ken Harumaa Background PillCam patency capsule (PC) is a novel and radiofrequency identification tag-free device that remains intact in the gastrointestinal tract for 30–33 h after ingestion and then disintegrates. The aim of this study was to determine the clinical relevance of PC combined with abdominal ultrasonography as a reliable indicator of functional patency. Patients and methods The study was prospective and PillCam PC was administered to consecutive patients with known or suspected small bowel strictures. PC was verified if it was excreted intact in 33 h after administration. Following excretion failure and radiograph detection in the pelvic cavity, ultrasonography was used to detect the PC in relation to the stricture. Results The participants were 52 patients with known or suspected small bowel strictures (58% women, mean age 51 years, including 32 with or suspected Crohn’s disease). Twenty-two patients (42.3%) retrieved PC in the stool within 33 h after ingestion. Radiograph identified the four PCs in the colon and eight were not observed. Ultrasonography precisely judged all 17 PCs retained including six PCs at the proximal side of small bowel stricture in the patients
Background Capsule retention is defined as failure of the excretion of capsule within 14 days of ingestion, and is the most serious complication, especially in patients with Crohn’s disease (CD) [1,2]. Reported retention rates range from 0.75% in healthy individuals to 21% in those with known small bowel strictures [3–7]. Small bowel radiography has a low diagnostic yield for the presence or absence of small bowel strictures unless there is significant proximal dilatation under double-contrast barium enteroclysis [4,5,8,9]. In addition, false-positive results similar to those seen with computed tomography (CT) enteroclysis may inappropriately exclude patients who could safely undergo the capsule endoscopy (CE) [10]. A direct approach to investigating whether the capsule will pass through the small intestine is to use a patency capsule (PC). PC is a self-disintegrating sham capsule and has the same size and shape as the video capsule. Original PC consisted of a single timer plug and a radiofrequency identification (RFID) tag [7]. The later developed PC, which contains two timer plugs, an internal RFID tag, and 0954-691X © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
considered ineligible for capsule endoscopy (CE). In all eligible patients, CE passed through the small intestine without incident. Conclusion PillCam PC combined with ultrasonography before CE appears to be a reliable indicator of functional patency to predict and minimize the risk of impaction in suspected or even known cases with small bowel stricture. Eur J Gastroenterol Hepatol 26:1434–1438 © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. European Journal of Gastroenterology & Hepatology 2014, 26:1434–1438 Keywords: capsule endoscopy, chronic nonspecific multiple ulcers of the small intestine, Crohn’s disease, patency capsule, small bowel strictures a Department of Internal Medicine, Division of Gastroenterology, bDepartment of Clinical Pathology and Laboratory Medicine and cDepartment of Comprehensive Medicine, Kawasaki Medical School, Okayama, Japan
Correspondence to Akiko Shiotani, MD, PhD, Department of Internal Medicine, Division of Gastroenterology, Kawasaki Medical School, 577 Matsushima Kurashiki City, Okayama Prefecture 701-0192, Japan Tel: + 81 86 462 1111; fax: + 81 86 462 1195; e-mail: [email protected] Received 5 August 2014 Accepted 11 September 2014
barium [6]. The RFID tag allowed the presence of the PC to be detected by the RFID scanner without radiation exposure to the patient, whereas the barium allowed detection by abdominal radiograph. PillCam PC is a novel RFID tag-free PC and is available in Japan. The presence or absence of PC is designed to be assessed by using abdominal radiograph 30–33 h after ingestion in patients who do not excrete [11]. The clinical usefulness of a novel RFID tag-free PC in patients at high risk of intestinal strictures has been reported recently. However, the precise location of PC by radiograph is often difficult to determine, especially when PC is detected in the pelvic cavity, and data on the PC are still limited [7,8,11–13]. We evaluated the novel PC and in addition the clinical relevance of the PC combined with ultrasonography to detect PCs and small bowel strictures.
Patients and methods The study was a prospective study carried out at the Hospital of Kawasaki Medical School in accordance with DOI: 10.1097/MEG.0000000000000225
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Patency capsule and abdominal ultrasonography Shiotani et al. 1435
the Declaration of Helsinki. Permission was granted by the Ethics Committee of Kawasaki Medical School (Okayama, Japan), and written informed consent to undergo CE was obtained from all the patients. Patients
Consecutive patients with CD or with known or suspected small bowel strictures in whom CE was planned and received PCs between September 2012 and February 2014 were included. Small bowel strictures were evaluated by abdominal ultrasonography in all patients and by additional small bowel follow through in patients with CD lesions in the small intestine or with suspected severe stenosis. Severe intestinal stenosis was defined as intestinal strictures with proximal small bowel dilation or intestinal occlusion detected by either abdominal ultrasonography or small bowel follow through. Patients with severe intestinal stenosis were excluded, and PC and CE were not performed.
to check passage of the capsule from the stomach [14,15]. Water and food were permitted 2 and 4 h, respectively, after CE reached the small intestine. During the PC and CE procedure, food was limited only in patients with known intestinal stricture because of CD treated by an elemental diet to avoid capsule impaction in the stricture; in these patients, only an elemental diet was permitted until confirmation of excretion of the capsule. In CD patients with known intestinal stricture, only an elemental diet was permitted until the excretion of the video capsule was verified. CE procedures were reviewed by recording them as thumb-nail photographs using RAPID Access 6.5 (Given Imaging Ltd) [13,14]. Analyses
Values are expressed as the mean ± SD. Mantel–Haenszel χ2 analysis and the unpaired t-test were used to measure differences in the CE findings.
Results Patency capsule
PillCam PC (Given Imaging Ltd, Tokyo, Japan) was administered to patients with known or suspected small bowel strictures. Patients were instructed to observe their stools carefully for the excreted PC and to return it to the hospital to verify its intact excretion within 33 h after administration. If patients failed to identify the capsule in their stools, passage of the PC was assessed by abdominal radiograph. Abdominal ultrasonography
Following excretion failure and radiograph detection of the PC in the pelvic cavity, abdominal ultrasonography was used and the location of the PC was evaluated by assessing its location in the stricture without special preparation such as administration of spasmolytic agents or instillation of water into the bowel. The sonographic instrument used was the SSA-390A system (Toshiba, Tokyo, Japan) with 3–6 MHz (main frequency, 3.5 MHz) transducers in a curved array and 6–9 MHz (main frequency, 7 MHz) transducers in a linear array. Linear strong echo showing the same size and shape of the PC, followed immediately by a clear acoustic shadow is the typical sonographic figure of the PC (Fig. 1). The small intestine was considered patent and safe for the CE if the PC was (a) excreted intact, (b) not detected by ultrasonography to be at the proximal side of a suspected small bowel stricture, or (c) detected in the colon within 33 h after ingestion. If PC was detected at the distal side of a suspected small bowel stricture or in the small intestine without stricture at 33 h after ingestion, PC was repeated. Capsule endoscopy
CE using PillCam SB 2 (Given Imaging Ltd) was performed as described previously using a real-time viewer
Fifty-two patients with known or suspected small bowel strictures (22 men and 30 women, mean age 51 years) received the PC test, including 26 patients with CD, six patients with suspected CD, 14 patients with suspected NSAID enteropathy, four patients with a history of ileus, and two patients with suspected small bowel tumor (Table 1). A 78-year-old woman with suspected NSAID enteropathy could not swallow PC and was excluded from the study. Ultrasonography was performed in all patients and small bowel follow through was performed in 24 patients with or suspected CD and one patient with ileus. Small bowel stricture was detected in 21 patients: 11 patients with CD, four patients with suspected CD, and six patients with suspected NSAID enteropathy. Twenty-two (42.3%) patients retrieved PC in their stool within 33 h after ingestion. In the remaining 29 patients without PC excretion, abdominal radiographs located three PCs in the ascending colon or cecum and one in the descending colon. With abdominal radiographs, PCs were confirmed to be absent in eight patients and were detected in the pelvic cavity of 17 patients (32.7%). Among these 17 patients, abdominal ultrasonography detected the patency at the oral side of small bowel stricture in six patients; five patients with CD and one patient with NSAID-induced diaphragm disease, and these were considered to be ineligible for CE. Among the remaining 11 patients, ultrasonography detected seven retained PCs in the colon and did not detect four retained PCs in the small intestine, which were thought to pass through the small intestine. In fact, two of the four PCs were excreted intact 2 h after ultrasonography and another PC was recognized in the colon by CT. Moreover, ultrasonography found two retained PCs in the small bowel, detecting no small bowel stricture on the anal side of retained PCs. They repeated PC tests, and ultrasonography detected their second PCs in the colon.
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Fig. 1
(a)
(b) T
T
0
0
10C3 diffT6.0 49 fps
1
G:76 DR:65
2
1
2
3
∗
MI:1.5 20G 94 DR 55
12L5 3 diffT8.0 51 fps 4
4 5
Sonographic image of the retained patency capsule (PC) at the proximal site of the ileal stenosis (*) detected by ultrasonography. Linear strong echo, followed by a clear acoustic shadow is the typical sonographic figure of the PC. The arrows indicate the retained patency: (a) long axis view; (b) short axis view.
Demographic and clinical characteristics of the patients who received a patency capsule
Table 1
Number of patients Men [n (%)] Age [mean (SD)] Known/suspected small bowel strictures Clinical indication [n (%)] Crohn’s disease Suspected Crohn’s disease Suspected NSAID enteropathy Past history of ileus Suspected tumor
52 22 (42.3) 51 (20) 21/31 26 6 14 4 2
(50) (11.5) (26.9) (7.7) (3.8)
Including these patients, the 45 patients including 30 patients with PC excretion and 15 patients with retained PCs in the colon were allowed to undergo CE (Fig. 2). In all eligible patients, the video capsule passed through the small intestine without incident. The rates of entire small bowel observation and positive finding were 88.8 and 80%, respectively. There were no significant differences in the rates of entire small bowel observation and positive findings including the transit time between the group with PC excretion and the group with retained PC in the colon. The most frequent findings were erosions or ulcers; stricture was observed in 16 patients (eight patients with CD, five patients with chronic nonspecific multiple ulcers of the small intestine, and three patients with NSAID enteropathy) (Table 2). Nine patients (four patients with CD located in the colon, two patients with suspected CD, two patients with suspected NSAIDs enteropathy, and one with a history of ileus) had no significant findings. Among the 26 patients with CD, 21 patients were eligible to undergo CE. The ineligible patients were five patients with CD and one with a history of ileus. Among the 14 patients with suspected NSAIDs enteropathy, 12 patients had multiple erosions and ulcers including three patients with small bowel stricture.
Discussion In a previous study from Japan [16], the capsule retention rate in patients with known CD was 7.4%, and similar to that reported from western countries [2]. However, unlike in western countries, CD remained a contraindication for CE in Japan until after the PillCam PC was approved by the Japanese Ministry of Health, Labor and Welfare in July 2012. We prospectively evaluated the role of abdominal ultrasonography as an adjuvant to the PC test to better predict and minimize the risk of impaction in suspected or known cases with small bowel stricture. Use of an RFID scanner or fluoroscopy can aid detection of retained Agile PC, thus avoiding the need for radiography. However, even with abdominal radiograph or fluoroscopy, it may be difficult to identify the location of retained PC precisely because of overlapping of the large and the small intestine. Two cases with capsule retention despite successful small bowel passage of PC confirmed by abdominal radiographs have been reported [17]. CT can provide a more definitive method of localization, but is often precluded because of the cost and radiation dosage. Ultrasonography is a repeatable inexpensive and safe noninvasive diagnostic modality that is useful in the assessment of CD and its complications. Bowel-wall thickness and focal disappearance of the wall stratification sign can be used to assess disease activity and identify the presence of deep longitudinal ulcers [18–20]. The sensitivity and specificity of ultrasonography in the assessment of stricture of CD range from 74 to 100 and 91 to 93%, respectively [21–23]. A recent paper also indicated a high level of accuracy of small bowel contrast ultrasonography in the detection of lesions and complications in patients with CD compared with CT enteroclysis [24]. In our 17 patients with pelvic localization, ultrasonography identified that 11 patients (64.7%) were in fact eligible for CE. Ultrasonography precisely judged all 17 retained PCs, indicating the location of all retained
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Patency capsule and abdominal ultrasonography Shiotani et al. 1437
Fig. 2
Enrollment for patency capsule n=52 Swallowing disorders n=1
No excretion within 33 h n=29
Excretion within 33 h n=22
Abdominal radiograph out of body n=8
Abdominal radiograph in the colon n=4
Abdominal radiograph in the suspected SB n=17
Abdominal US In the colon n=7 (In the SB with no stricture, n=1∗) Out of the SB n=4
Eligible CE n=45
Abdominal US in the SB n=6
No eligible CE n=6
Summary of retrieved and retained patency capsules (PC). CE, capsule endoscopy; SB, small bowel; US, ultrasonography. *Ultrasonography detected a retained PC at the distal side of small bowel stricture or without small bowel stricture in two patients who repeated the PC test, and ultrasonography detected their second PC in the colon.
Table 2
Findings of capsule endoscopy
The number of capsule procedures Completion rate [n (%)] Gastric transit time [mean (SD)] (min) SB transit time [mean (SD)] (min) Capsule retention Positive finding rate [n (%)] Findings Erosions/ulcer Stenosis Tumor suspected Diagnosed disease Crohn’s disease NSAID enteropathy CNSU Malignant lymphoma Submucosal tumor suspected
Total
PC excretion
PC in the colon
45 40 (88.8) 63 (99)
30 28 (93.3) 73(116)
15 12 (80) 40 (42)
288(109) 0 36 (80)
283(118) 0 23 (76.7)
297 (86) 0 13 (86.7)
38 16 7
25 11 3
13 5 4
18 6 7 4 2
13a 3 4b 2 1
5a 3 3b 2 1
The number included one patient (a) with suspected Crohn’s disease and one patient with suspected CNSU (b). CNSU, chronic nonspecific multiple ulcers of the small intestine; PC, patency capsule; SB, small bowel.
PCs in the small intestine, passage through small intestine, or no small bowel stricture in the distal site of the retained PCs. Ultrasonography did not detect four retained PCs in the colon, including two PCs excreted intact 2 h after ultrasonography. The detection of a retained PC in the left side of colon seems to be difficult probably because of solid
stool. However, it is much easier to detect retained PCs in the ileum irrespective of the small bowel stricture. The PC was excreted intact in approximately half of our patients, and the result is similar to that reported in a previous multicenter clinical trial of PCs (56%) [8]. In one patient with suspected NSAID enteropathy, the retained patency was detected in the small intestine with no stricture, probably because of slow small bowel transit. She repeated PC using prokinetics, and ultrasonography detected her second PC in the colon. Prokinetics for PC examination in patients with slow transit may be required. Further study of effectiveness and safety using prokinetics is required. Among five ineligible patients for CE, ultrasonography indicated long segment stricture with bowel-wall thickness and anastomotic stricture in two CD patients each. Therefore, long segment bowel-wall thickness and anastomotic stricture in CD as well as diaphragm disease seem to be risk findings for capsule retention. The limitation of our study is the relatively small sample size. Further large prospective studies will be required to confirm that PillCam PC combined with abdominal ultrasonography before CE is a safe and reliable indicator of functional patency that predicts severe stenosis and minimizes the risk of impaction in known cases with intestinal stricture. In our study, three well-trained examiners with
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more than 10 years of experience performed ultrasonography, and the procedure time to detect the retained PC and observation of small intestine was a few minutes. We did not assess the exact procedure time and the reproducibility of abdominal ultrasonography. It is well known that the accuracy and utility of ultrasonography generally depend on the examiners’ skill as well as patient factors such as abdominal fat, gas, and stool in the lower gastrointestinal tract, etc. However, the previous assessment of ultrasonography reproducibility in patients with CD by Fraquelli et al. [25] indicated excellent agreement for intestinal stricture (k = 0.81–1). We excluded patients with severe intestinal stenosis with dilation at the proximal side to avoid obstruction induced by PC. The diagnosis of severe stenosis was subjective and this exclusion for the PC lacks evidence. Nonetheless, double-balloon endoscopy may be a better option for patients with severe stenosis, which is a good indication for endoscopic balloon dilatation before deciding on surgery [26,27]. In summary, PC was excreted intact in about 60% of patients and additional abdominal ultrasonography before CE was required in one-third of the patients. Ultrasonography diagnosed the location of all retained PCs in the small intestine and confirmed that there was no small bowel stricture in the distal site of the retained PCs. In all eligible patients, the video capsule passed through the small intestine without incident. The RFID tag-free PillCam PC combined with abdominal ultrasonography before CE appears to a reliable indicator of functional patency to predict and minimize the risk of impaction in suspected or even known cases with small bowel stricture. To confirm clinical relevance, a further study with a larger number of patients and a study of the reproducibility of abdominal ultrasonography are definitely required.
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Acknowledgements The authors thank Prof. David Y. Graham for helpful comments and English editions. Conflicts of interest
There are no conflicts of interest.
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