Leading article
Capsule endoscopy as a panenteric diagnostic tool M. Hale and M. E. McAlindon Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Trust, Glossop Road, Sheffield S10 2JF, UK (e-mail: [email protected])
Published online 19 November 2013 in Wiley Online Library (www.bjs.co.uk). DOI: 10.1002/bjs.9321
Capsule endoscopy (CE), first described in 20001 , may be one of the most important advances in gastrointestinal (GI) diagnostics since the introduction of endoscopy. A swallowed pill camera acquires images (subsequently converted to video format on a computer) as peristalsis propagates it through the GI tract. The first model, designed to examine the small bowel and overcome the technical difficulty of flexible enteroscopy, has been adopted widely by many Western gastroenterologists, and in some countries is seen as the first-choice modality for small-bowel imaging2 . The wider application of this technology, however, and its role in disorders of interest to surgeons seem unappreciated. The commonest indication for small-bowel CE is GI bleeding (occult or overt), conventionally after nondiagnostic upper and lower GI endoscopic and radiological investigation3 . CE identifies pathology in 46–60 per cent of these patients3 , and is more sensitive than small-bowel barium contrast radiology, computed tomography (CT), magnetic resonance imaging (MRI), push enteroscopy and angiography4 . Flat vascular lesions (angioectasias) and inflammatory disease are the commonest diagnoses, and may be apparent on direct mucosal visualization before becoming evident on radiological imaging. Thermal ablation of angioectasia or a need for biopsy requires flexible enteroscopy, which has therefore become the interventional counterpart of CE in much the same way that endoscopic retrograde cholangiopancreatography is now the therapeutic counterpart 2013 BJS Society Ltd Published by John Wiley & Sons Ltd
of magnetic resonance cholangiopancreatography. The double-balloon enteroscope5 has inflatable balloons both on the tip of the enteroscope and on a fine overtube that glides over the scope. Passage of the enteroscope (through oral or anal routes) deep into the small bowel is achieved by sequential inflation and deflation of balloons to provide anchorage while incrementally advancing the enteroscope tip. Examinations take up to an hour, and usually require more sedation than other modes of endoscopy or general anaesthesia. Small-bowel tumours are reported in up to 9.6 per cent of CE examinations performed to investigate obscure GI bleeding3 . These include malignant or potentially malignant (GI stromal tumours, adenocarcinoma, carcinoid, lymphoma), benign (haemangioma, adenoma, lipoma) and metastatic (particularly from melanoma, lung, renal or breast primaries) lesions. CE is more accurate than small-bowel barium radiology at detecting small-bowel tumours, and can also detect smaller lesions than MRI4 . CE is not without limitations in the small bowel. It can miss some lesions that are largely submucosal. If there is a high index of suspicion, crosssectional imaging such as contrastenhanced CT is recommended. The sensitivity of CE in identifying inflammation has also presented some challenges: suspected Crohn’s disease may be difficult to confirm histologically; the use of non-steroidal anti-inflammatory drugs (including low-dose aspirin) is widespread and
these drugs cause erosions in up to two-thirds of patients. Minor mucosal breaks occur in 10–15 per cent of healthy volunteers6 . The main risk of CE is capsule retention, occurring in 1 per cent of patients with suspected bleeding, but in as many as 5–13 per cent of those known to have Crohn’s disease4 . Radiological investigation, particularly small-bowel MRI, is seen as the mainstay of investigation for those with established penetrating or stenosing disease as transmural involvement can be defined in crosssection, but CE may still be used to assess mucosal activity. To confirm functional patency of the GI tract, a dissolving patency capsule (the same size and shape as the capsule endoscope) containing a radiofrequency tag has been developed (Agile patency capsule; Given Imaging, Yoqneam, Israel). Absence of the radiofrequency signal 30 h postingestion predicts safe GI transit of the capsule endoscope4 . Further advances led to oesophageal CE. PillCam ESO (Given Imaging) has cameras at both ends, acquiring simultaneous bidirectional images at a higher rate (14 versus 2 per second) than the small-bowel capsule, and has sensitivities of 80, 100 and 83 per cent in diagnosing reflux oesophagitis, Barrett’s oesophagus and varices respectively, compared with upper GI endoscopy4 . Although better tolerated by patients than conventional endoscopy, uptake in clinical practice has been limited. The development of the doubleheaded capsule overcame one of the obstacles to the use of a colon capsule: BJS 2014; 101: 148–149
Capsule endoscopy as a panenteric diagnostic tool
the ability to see both sides of haustral folds. The problem of variable, and sometimes rapid, transit noted with the initial version of the colon capsule has been addressed in an updated model, the PillCam Colon 2 (PCC2; Given Imaging), which adjusts the frame acquisition rate according to the speed of transit (to between 4 and 35 frames per second) and in which each lens has a 172◦ angle of view7 . Bowel preparation seems critical, and currently most regimens include an oral prokinetic agent and two additional ‘booster’ doses of Phosphosoda (C. B. Fleet, Lynchburg, Virginia, USA) on top of a conventional polyethylene glycol–electrolyte solution. Compared with the earlier colon capsules, recent multicentre trials suggest a much improved sensitivity of PCC2 in detecting polyps greater than 6 mm in size of between 84 and 89 per cent8 . Bowel cleanliness scores were ‘good’ or ‘excellent’ in 78–81 per cent of patients. Where PCC2 stands in relation to other colonic imaging modalities has yet to be established, but early data compare favourably with those for virtual colonoscopy, and even with conventional colonoscopy when performed in ‘tandem’ or ‘back to back’ colonoscopy trials9 . A possible role for PCC2 in colorectal cancer screening is intriguing. Hassan and colleagues10 calculated that, if a colon capsule-based programme were associated with a 30 per cent better compliance rate, it would be as cost-effective as faecal occult blood screening, using the data from trials of the original colon capsule model, which was much less sensitive (64 per cent) in detecting polyps larger than 6 mm8 .
2013 BJS Society Ltd Published by John Wiley & Sons Ltd
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It is thus now possible to visualize the whole GI tract using CE with a single capsule. Preliminary data suggest that adequate gastric examination can be achieved using a magnet to control capsule movement11 . Perhaps we are about to witness a change in practice, with remote imaging devices such as CE becoming the primary diagnostic tool, directing conventional (intubational) endoscopy to lesions for biopsy or therapy. The addition of tissue sampling and therapeutic CE is not yet a realistic clinical tool, but may not be many years behind7 .
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6
7
Disclosure
The authors declare no conflict of interest. 8
References 1 Iddan G, Meron G, Glukhovsky A, Swain P. Wireless capsule endoscopy. Nature 2000; 405: 417. 2 McAlindon ME, Parker CE, Hendy P, Mosea H, Panter S, Davison C et al. Provision of service and training for small bowel endoscopy in the UK. Frontline Gastroenterol 2012; 3: 98–103. 3 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: 2407–2418. 4 Ladas SD, Triantafyllou K, Spada C, Riccioni ME, Rey JF, Niv Y et al; ESGE Clinical Guidelines Committee. European Society of Gastrointestinal Endoscopy (ESGE): recommendations (2009) on clinical
www.bjs.co.uk
9
10
11
use of video capsule endoscopy to investigate small-bowel, esophageal and colonic diseases. Endoscopy 2010; 42: 220–227. Yamamoto H, Sekine Y, Sato Y, Higashizawa T, Miyata T, Iino S et al. Total enteroscopy with a nonsurgical steerable double-balloon method. Gastrointest Endosc 2001; 53: 216–220. Sidhu R, Brunt LK, Morley SR, Sanders DS, McAlindon ME. Undisclosed use of nonsteroidal anti-inflammatory drugs may underlie small-bowel injury observed by capsule endoscopy. Clin Gastroenterol Hepatol 2010; 8: 992–995. Neumann H, Fry LC, Neurath MF. Review article on current applications and future concepts of capsule endoscopy. Digestion 2013; 87: 91–99. Spada C, De Vincentis F, Cesaro P, Hassan C, Riccioni ME, Minelli Grazioli L et al. Accuracy and safety of second-generation PillCam COLON capsule for colorectal polyp detection. Therap Adv Gastroenterol 2012; 5: 173–178. Heresbach D, Barrioz T, Lapalus MG, Coumaros D, Bauret P, Potier P et al. Miss rate for colorectal neoplastic polyps: a prospective multicenter study of back-to-back video colonoscopies. Endoscopy 2008; 40: 284–290. Hassan C, Zullo A, Winn S, Morini S. Cost-effectiveness of capsule endoscopy in screening for colorectal cancer. Endoscopy 2008; 40: 414–421. Keller J, Fibbe C, Volke F, Gerber J, Mosse AC, Reimann-Zawadzki M et al. Inspection of the human stomach using remote-controlled capsule endoscopy: a feasibility study in healthy volunteers (with videos). Gastrointest Endosc 2011; 73: 22–28.
BJS 2014; 101: 148–149
Capsule endoscopy as a panenteric diagnostic tool M. Hale and M. E. McAlindon Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Trust, Glossop Road, Sheffield S10 2JF, UK (e-mail: [email protected])
Published online 19 November 2013 in Wiley Online Library (www.bjs.co.uk). DOI: 10.1002/bjs.9321
Capsule endoscopy (CE), first described in 20001 , may be one of the most important advances in gastrointestinal (GI) diagnostics since the introduction of endoscopy. A swallowed pill camera acquires images (subsequently converted to video format on a computer) as peristalsis propagates it through the GI tract. The first model, designed to examine the small bowel and overcome the technical difficulty of flexible enteroscopy, has been adopted widely by many Western gastroenterologists, and in some countries is seen as the first-choice modality for small-bowel imaging2 . The wider application of this technology, however, and its role in disorders of interest to surgeons seem unappreciated. The commonest indication for small-bowel CE is GI bleeding (occult or overt), conventionally after nondiagnostic upper and lower GI endoscopic and radiological investigation3 . CE identifies pathology in 46–60 per cent of these patients3 , and is more sensitive than small-bowel barium contrast radiology, computed tomography (CT), magnetic resonance imaging (MRI), push enteroscopy and angiography4 . Flat vascular lesions (angioectasias) and inflammatory disease are the commonest diagnoses, and may be apparent on direct mucosal visualization before becoming evident on radiological imaging. Thermal ablation of angioectasia or a need for biopsy requires flexible enteroscopy, which has therefore become the interventional counterpart of CE in much the same way that endoscopic retrograde cholangiopancreatography is now the therapeutic counterpart 2013 BJS Society Ltd Published by John Wiley & Sons Ltd
of magnetic resonance cholangiopancreatography. The double-balloon enteroscope5 has inflatable balloons both on the tip of the enteroscope and on a fine overtube that glides over the scope. Passage of the enteroscope (through oral or anal routes) deep into the small bowel is achieved by sequential inflation and deflation of balloons to provide anchorage while incrementally advancing the enteroscope tip. Examinations take up to an hour, and usually require more sedation than other modes of endoscopy or general anaesthesia. Small-bowel tumours are reported in up to 9.6 per cent of CE examinations performed to investigate obscure GI bleeding3 . These include malignant or potentially malignant (GI stromal tumours, adenocarcinoma, carcinoid, lymphoma), benign (haemangioma, adenoma, lipoma) and metastatic (particularly from melanoma, lung, renal or breast primaries) lesions. CE is more accurate than small-bowel barium radiology at detecting small-bowel tumours, and can also detect smaller lesions than MRI4 . CE is not without limitations in the small bowel. It can miss some lesions that are largely submucosal. If there is a high index of suspicion, crosssectional imaging such as contrastenhanced CT is recommended. The sensitivity of CE in identifying inflammation has also presented some challenges: suspected Crohn’s disease may be difficult to confirm histologically; the use of non-steroidal anti-inflammatory drugs (including low-dose aspirin) is widespread and
these drugs cause erosions in up to two-thirds of patients. Minor mucosal breaks occur in 10–15 per cent of healthy volunteers6 . The main risk of CE is capsule retention, occurring in 1 per cent of patients with suspected bleeding, but in as many as 5–13 per cent of those known to have Crohn’s disease4 . Radiological investigation, particularly small-bowel MRI, is seen as the mainstay of investigation for those with established penetrating or stenosing disease as transmural involvement can be defined in crosssection, but CE may still be used to assess mucosal activity. To confirm functional patency of the GI tract, a dissolving patency capsule (the same size and shape as the capsule endoscope) containing a radiofrequency tag has been developed (Agile patency capsule; Given Imaging, Yoqneam, Israel). Absence of the radiofrequency signal 30 h postingestion predicts safe GI transit of the capsule endoscope4 . Further advances led to oesophageal CE. PillCam ESO (Given Imaging) has cameras at both ends, acquiring simultaneous bidirectional images at a higher rate (14 versus 2 per second) than the small-bowel capsule, and has sensitivities of 80, 100 and 83 per cent in diagnosing reflux oesophagitis, Barrett’s oesophagus and varices respectively, compared with upper GI endoscopy4 . Although better tolerated by patients than conventional endoscopy, uptake in clinical practice has been limited. The development of the doubleheaded capsule overcame one of the obstacles to the use of a colon capsule: BJS 2014; 101: 148–149
Capsule endoscopy as a panenteric diagnostic tool
the ability to see both sides of haustral folds. The problem of variable, and sometimes rapid, transit noted with the initial version of the colon capsule has been addressed in an updated model, the PillCam Colon 2 (PCC2; Given Imaging), which adjusts the frame acquisition rate according to the speed of transit (to between 4 and 35 frames per second) and in which each lens has a 172◦ angle of view7 . Bowel preparation seems critical, and currently most regimens include an oral prokinetic agent and two additional ‘booster’ doses of Phosphosoda (C. B. Fleet, Lynchburg, Virginia, USA) on top of a conventional polyethylene glycol–electrolyte solution. Compared with the earlier colon capsules, recent multicentre trials suggest a much improved sensitivity of PCC2 in detecting polyps greater than 6 mm in size of between 84 and 89 per cent8 . Bowel cleanliness scores were ‘good’ or ‘excellent’ in 78–81 per cent of patients. Where PCC2 stands in relation to other colonic imaging modalities has yet to be established, but early data compare favourably with those for virtual colonoscopy, and even with conventional colonoscopy when performed in ‘tandem’ or ‘back to back’ colonoscopy trials9 . A possible role for PCC2 in colorectal cancer screening is intriguing. Hassan and colleagues10 calculated that, if a colon capsule-based programme were associated with a 30 per cent better compliance rate, it would be as cost-effective as faecal occult blood screening, using the data from trials of the original colon capsule model, which was much less sensitive (64 per cent) in detecting polyps larger than 6 mm8 .
2013 BJS Society Ltd Published by John Wiley & Sons Ltd
149
It is thus now possible to visualize the whole GI tract using CE with a single capsule. Preliminary data suggest that adequate gastric examination can be achieved using a magnet to control capsule movement11 . Perhaps we are about to witness a change in practice, with remote imaging devices such as CE becoming the primary diagnostic tool, directing conventional (intubational) endoscopy to lesions for biopsy or therapy. The addition of tissue sampling and therapeutic CE is not yet a realistic clinical tool, but may not be many years behind7 .
5
6
7
Disclosure
The authors declare no conflict of interest. 8
References 1 Iddan G, Meron G, Glukhovsky A, Swain P. Wireless capsule endoscopy. Nature 2000; 405: 417. 2 McAlindon ME, Parker CE, Hendy P, Mosea H, Panter S, Davison C et al. Provision of service and training for small bowel endoscopy in the UK. Frontline Gastroenterol 2012; 3: 98–103. 3 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: 2407–2418. 4 Ladas SD, Triantafyllou K, Spada C, Riccioni ME, Rey JF, Niv Y et al; ESGE Clinical Guidelines Committee. European Society of Gastrointestinal Endoscopy (ESGE): recommendations (2009) on clinical
www.bjs.co.uk
9
10
11
use of video capsule endoscopy to investigate small-bowel, esophageal and colonic diseases. Endoscopy 2010; 42: 220–227. Yamamoto H, Sekine Y, Sato Y, Higashizawa T, Miyata T, Iino S et al. Total enteroscopy with a nonsurgical steerable double-balloon method. Gastrointest Endosc 2001; 53: 216–220. Sidhu R, Brunt LK, Morley SR, Sanders DS, McAlindon ME. Undisclosed use of nonsteroidal anti-inflammatory drugs may underlie small-bowel injury observed by capsule endoscopy. Clin Gastroenterol Hepatol 2010; 8: 992–995. Neumann H, Fry LC, Neurath MF. Review article on current applications and future concepts of capsule endoscopy. Digestion 2013; 87: 91–99. Spada C, De Vincentis F, Cesaro P, Hassan C, Riccioni ME, Minelli Grazioli L et al. Accuracy and safety of second-generation PillCam COLON capsule for colorectal polyp detection. Therap Adv Gastroenterol 2012; 5: 173–178. Heresbach D, Barrioz T, Lapalus MG, Coumaros D, Bauret P, Potier P et al. Miss rate for colorectal neoplastic polyps: a prospective multicenter study of back-to-back video colonoscopies. Endoscopy 2008; 40: 284–290. Hassan C, Zullo A, Winn S, Morini S. Cost-effectiveness of capsule endoscopy in screening for colorectal cancer. Endoscopy 2008; 40: 414–421. Keller J, Fibbe C, Volke F, Gerber J, Mosse AC, Reimann-Zawadzki M et al. Inspection of the human stomach using remote-controlled capsule endoscopy: a feasibility study in healthy volunteers (with videos). Gastrointest Endosc 2011; 73: 22–28.
BJS 2014; 101: 148–149
