- Email: [email protected]
Capsule endoscopy in obscure GI bleeding: better to be negative, but let us not be too positive
Letters to the Editor
Response:
DISCLOSURE
We have reviewed the comments by Drs Kopylov et al1 regarding our recently published meta-analysis.2 The authors raised important points about the use of patency capsules, which are now recommended in current guidelines for patients with inflammatory bowel disease (IBD) before they undergo video capsule endoscopy because of the increased risk of retention in this patient cohort.3 The use of CT enterography (CTE), MR enterography (MRE), or both has also shown similar sensitivity and specificity for small-bowel strictures when compared with the use of the patency capsule.4 However, the use of the patency capsule is limited in the United States because many patients cannot obtain access to centers that perform these studies, do not have insurance coverage for its use, or both; therefore, most patients with potential small-bowel strictures undergo enterography examinations before video capsule endoscopy (VCE). The major concerns raised by the authors regarding our meta-analysis were that the rates calculated for VCE retention in patients with suspected (3.6%) and established (8.2%) IBD might be inaccurate because not all patients underwent patency capsule examinations or CTE first. We had several reasons for the design of our meta-analysis. First, after a thorough literature search, the authors of most studies providing data on VCE retention rates unfortunately had not performed an initial patency capsule study or CTE in the IBD patients. Therefore, had we not included performance of a patency capsule study as an exclusion criterion, we would have been able to analyze a total of only 8 studies for the indication of VCE in IBD patients, resulting in exclusion of the majority of included studies. To reconcile this issue, we decided to exclude primary performance of a patency capsule study in the main analysis of VCE retention in established and suspected IBD patients. However, to the authors’ point, we did perform a subanalysis to include the 8 published studies that provided sufficient information on retention rates in patients with IBD undergoing initial patency capsule examinations or MRE/CTE before VCE. Although the initial retention rate was 12% in this population, subsequent VCE examinations showed that the retention rate was reduced to 2.7%. Because small-bowel patency capsule studies and MRE/CTE have now been integrated as part of the standard evaluation of IBD patients before VCE is performed, we agree that our subanalysis retention rates confirm that VCE can be safely performed in IBD patients, although there still remains a small risk of retention even after both of those studies have been performed. By performance of our meta-analysis, we demonstrated that VCE retention rates could be reduced from 3.6% to 2.7% in patients with suspected IBD and from 8.2% to 2.7% in patients with established IBD. With future anticipated advances in radiographic techniques, we can hope that the detection rate for strictures can be further increased.
Dr Gerson is a consultant for Olympus America, Inc., and Capsovision. All other authors disclosed no financial relationships relevant to this publication.
574 GASTROINTESTINAL ENDOSCOPY Volume 86, No. 3 : 2017
Mona Rezapour, MD Lauren B. Gerson, MD, MSc California Pacific Medical Center San Francisco, California, USA REFERENCES 1. Kopylov U, Yung DE, Koulaouzidis A, et al. Retention rate in small-bowel capsule endoscopy. Gastrointest Endosc 2017;86:573. 2. Rezapour M, Ahmadi C, Gerson LB. Retention associated with video capsule endoscopy: systematic review and meta-analysis. Gastrointest Endosc 2017;85:1157-68.e2. 3. Gerson LB, Fidler JL, Cave DR, et al. ACG Clinical Guideline: diagnosis and management of small bowel bleeding. Am J Gastroenterol 2015;110:1265-87. 4. Yadav A, Heigh RI, Hara AK, et al. Performance of the patency capsule compared with nonenteroclysis radiologic examinations in patients with known or suspected intestinal strictures. Gastrointest Endosc 2011;74:834-9. http://dx.doi.org/10.1016/j.gie.2017.05.021
Capsule endoscopy in obscure GI bleeding: better to be negative, but let us not be too positive To the Editor: It was with great interest that we read the systematic review and meta-analysis of Yung et al1 on the clinical outcomes of negative small-bowel (SB) capsule endoscopy (CE) in obscure GI bleeding (OGIB). This is the first review analyzing the pooled rate of rebleeding after negative CE results (ie, .19; [.14-.25]; P < .0001) and positive CE results (ie, .29; [.23-.36]; P < .001) for the indication of OGIB, with significantly higher rebleeding rates after positive examination results (P < .001). In their conclusion, Yung et al1 provide the reader with very useful guidance in the management of OGIB in CEnegative patients. However, the meta-analysis showed a subsequently low risk of rebleeding in CE-negative patients. With this writing, we wish to add our knowledge to the current evidence. In our recently published study on 211 CE-negative patients with OGIB,2 68.7% of CE-negative patients receiving nonspecific therapy (ie, watchful waiting, iron supplementation, or transfusions) showed spontaneous OGIB resolution during follow-up, which is in line with this meta-analysis. However, the risk of rebleeding remains substantial in the long term. In 34% of cases (median follow-up time, 51.7 months; range, 1.4-139.6 months), OGIB was present at the end of www.giejournal.org
Letters to the Editor
follow-up. In patients with continuation of OGIB who underwent further diagnostics, most bleeding origins were, however, situated outside the SB. In only 9% of negative CE results, an SB diagnosis for OGIB had not been visualized on initial CE (angiodysplasia, n Z 11; Meckel’s diverticulum, n Z 3; SB malignancy, n Z 3; jejunal erosions, n Z 1; and nonsteroidal anti-inflammatory drug–induced SB ulcerations, n Z 1). In conclusion, negative CE examination results should never reassure the treating physician. On the contrary, close monitoring is recommended, with careful deferment of further diagnostics, using a low threshold for repeating routine endoscopy to identify possible non-SB lesions in patients with ongoing bleeding.
DISCLOSURE Dr De Looze is the recipient of speaker’s fees from Given Imaging. All other authors disclosed no financial relationships relevant to this publication. Cedric Van de Bruaene, MD Pieter Hindryckx, MD, PhD Danny De Looze, MD, PhD Department of Gastroenterology Ghent University Hospital Ghent, Belgium REFERENCES 1. Yung DE, Koulaouzidis A, Avni T, et al. Clinical outcomes of negative small-bowel capsule endoscopy for small-bowel bleeding: a systematic review and meta-analysis. Gastrointest Endosc 2017;85:305-17. 2. Van de Bruaene C, Hindryckx P, Snauwaert C, et al. The predictive value of negative capsule endoscopy for the indication of obscure gastrointestinal bleeding: no reassurance in the long term. Acta Gastroenterol Belg 2016;79:405-13. http://dx.doi.org/10.1016/j.gie.2017.04.012
Response: We read with interest the correspondence from van de Bruaene et al1 in response to our meta-analysis2 on rebleeding rates after negative results of small-bowel capsule endoscopy (SBCE) for small-bowel bleeding (SBB; previously OGIB). We would like to thank them for the information they provided.3,4 The authors mention that in the long term (>2 years), their patients had a high rate of rebleeding of 34%; however, it is interesting to note that most of those patients had a bleeding source outside the small bowel. This further supports the conclusion of our meta-analysis that patients with a negative SBCE result have a low rate of small-bowel rebleeding. Patients presenting with rebleeding after a prolonged period of follow-up should therefore be investigated as “new” cases, including consideration of repeated conventional endoscopy. Morewww.giejournal.org
over, emerging biomarkers for SBB, such as angiopoietin2, offer promise as potential noninvasive screening tools.5 Such markers, once refined, could be used to select patients for SBCE, therefore decreasing further the number of unnecessary investigations with negative results.
DISCLOSURE All authors disclosed no financial relationships relevant to this publication. Diana E. Yung, MBChB Anastasios Koulaouzidis, MD, FEBG, FACG, FASGE John N. Plevris, MD, PhD(E), DM, FRCPE, FEBGH Centre for Liver and Digestive Disorders The Royal Infirmary of Edinburgh Edinburgh, United Kingdom REFERENCES 1. Van de Bruaene C, Hindryckx P, De Looze D. Capsule endoscopy in obscure GI bleeding: better to be negative, but let us not be too positive. Gastrointest Endosc 2017;86:574-5. 2. Yung DE, Koulaouzidis A, Avni T, et al. Clinical outcomes of negative small-bowel capsule endoscopy for small-bowel bleeding: a systematic review and meta-analysis. Gastrointest Endosc 2017;85:305-17. 3. Van De Bruaene C, Hindryckx P, Snauwaert C, et al. Long-term follow-up in patients with OGIB and normal capsule endoscopy [abstract]. Gastrointest Endosc 2015;81:AB138. 4. Van de Bruaene C, Hindryckx P, Snauwaert C, et al. The predictive value of negative capsule endoscopy for the indication of obscure gastrointestinal bleeding: no reassurance in the long term. Acta Gastroenterol Belg 2015;79:405-13. 5. Holleran G, Hall B, O’Regan M, et al. Expression of angiogenic factors in patients with sporadic small bowel angiodysplasia. J Clin Gastroenterol 2015;49:831-6. http://dx.doi.org/10.1016/j.gie.2017.05.020
Efficacy and safety of endoscopic submucosal tunnel dissection for superficial esophageal squamous cell carcinoma: a propensity score matching analysis: methodologic issues To the Editor: We read the valuable article by Huang and colleagues1 published in Gastrointestinal Endoscopy in 2017 with great interest. The authors’ purpose was to assess the efficacy of the tunnel technique in endoscopic submucosal dissection (ESD) of superficial esophageal squamous cell carcinoma. They found that the ESD procedure time was significantly shorter in the tunnel ESD group than in the conventional ESD group. Also, they found that specimen size smaller than 40 mm was significantly and strongly associated with shorter procedure times both in the Volume 86, No. 3 : 2017 GASTROINTESTINAL ENDOSCOPY 575
Response:
DISCLOSURE
We have reviewed the comments by Drs Kopylov et al1 regarding our recently published meta-analysis.2 The authors raised important points about the use of patency capsules, which are now recommended in current guidelines for patients with inflammatory bowel disease (IBD) before they undergo video capsule endoscopy because of the increased risk of retention in this patient cohort.3 The use of CT enterography (CTE), MR enterography (MRE), or both has also shown similar sensitivity and specificity for small-bowel strictures when compared with the use of the patency capsule.4 However, the use of the patency capsule is limited in the United States because many patients cannot obtain access to centers that perform these studies, do not have insurance coverage for its use, or both; therefore, most patients with potential small-bowel strictures undergo enterography examinations before video capsule endoscopy (VCE). The major concerns raised by the authors regarding our meta-analysis were that the rates calculated for VCE retention in patients with suspected (3.6%) and established (8.2%) IBD might be inaccurate because not all patients underwent patency capsule examinations or CTE first. We had several reasons for the design of our meta-analysis. First, after a thorough literature search, the authors of most studies providing data on VCE retention rates unfortunately had not performed an initial patency capsule study or CTE in the IBD patients. Therefore, had we not included performance of a patency capsule study as an exclusion criterion, we would have been able to analyze a total of only 8 studies for the indication of VCE in IBD patients, resulting in exclusion of the majority of included studies. To reconcile this issue, we decided to exclude primary performance of a patency capsule study in the main analysis of VCE retention in established and suspected IBD patients. However, to the authors’ point, we did perform a subanalysis to include the 8 published studies that provided sufficient information on retention rates in patients with IBD undergoing initial patency capsule examinations or MRE/CTE before VCE. Although the initial retention rate was 12% in this population, subsequent VCE examinations showed that the retention rate was reduced to 2.7%. Because small-bowel patency capsule studies and MRE/CTE have now been integrated as part of the standard evaluation of IBD patients before VCE is performed, we agree that our subanalysis retention rates confirm that VCE can be safely performed in IBD patients, although there still remains a small risk of retention even after both of those studies have been performed. By performance of our meta-analysis, we demonstrated that VCE retention rates could be reduced from 3.6% to 2.7% in patients with suspected IBD and from 8.2% to 2.7% in patients with established IBD. With future anticipated advances in radiographic techniques, we can hope that the detection rate for strictures can be further increased.
Dr Gerson is a consultant for Olympus America, Inc., and Capsovision. All other authors disclosed no financial relationships relevant to this publication.
574 GASTROINTESTINAL ENDOSCOPY Volume 86, No. 3 : 2017
Mona Rezapour, MD Lauren B. Gerson, MD, MSc California Pacific Medical Center San Francisco, California, USA REFERENCES 1. Kopylov U, Yung DE, Koulaouzidis A, et al. Retention rate in small-bowel capsule endoscopy. Gastrointest Endosc 2017;86:573. 2. Rezapour M, Ahmadi C, Gerson LB. Retention associated with video capsule endoscopy: systematic review and meta-analysis. Gastrointest Endosc 2017;85:1157-68.e2. 3. Gerson LB, Fidler JL, Cave DR, et al. ACG Clinical Guideline: diagnosis and management of small bowel bleeding. Am J Gastroenterol 2015;110:1265-87. 4. Yadav A, Heigh RI, Hara AK, et al. Performance of the patency capsule compared with nonenteroclysis radiologic examinations in patients with known or suspected intestinal strictures. Gastrointest Endosc 2011;74:834-9. http://dx.doi.org/10.1016/j.gie.2017.05.021
Capsule endoscopy in obscure GI bleeding: better to be negative, but let us not be too positive To the Editor: It was with great interest that we read the systematic review and meta-analysis of Yung et al1 on the clinical outcomes of negative small-bowel (SB) capsule endoscopy (CE) in obscure GI bleeding (OGIB). This is the first review analyzing the pooled rate of rebleeding after negative CE results (ie, .19; [.14-.25]; P < .0001) and positive CE results (ie, .29; [.23-.36]; P < .001) for the indication of OGIB, with significantly higher rebleeding rates after positive examination results (P < .001). In their conclusion, Yung et al1 provide the reader with very useful guidance in the management of OGIB in CEnegative patients. However, the meta-analysis showed a subsequently low risk of rebleeding in CE-negative patients. With this writing, we wish to add our knowledge to the current evidence. In our recently published study on 211 CE-negative patients with OGIB,2 68.7% of CE-negative patients receiving nonspecific therapy (ie, watchful waiting, iron supplementation, or transfusions) showed spontaneous OGIB resolution during follow-up, which is in line with this meta-analysis. However, the risk of rebleeding remains substantial in the long term. In 34% of cases (median follow-up time, 51.7 months; range, 1.4-139.6 months), OGIB was present at the end of www.giejournal.org
Letters to the Editor
follow-up. In patients with continuation of OGIB who underwent further diagnostics, most bleeding origins were, however, situated outside the SB. In only 9% of negative CE results, an SB diagnosis for OGIB had not been visualized on initial CE (angiodysplasia, n Z 11; Meckel’s diverticulum, n Z 3; SB malignancy, n Z 3; jejunal erosions, n Z 1; and nonsteroidal anti-inflammatory drug–induced SB ulcerations, n Z 1). In conclusion, negative CE examination results should never reassure the treating physician. On the contrary, close monitoring is recommended, with careful deferment of further diagnostics, using a low threshold for repeating routine endoscopy to identify possible non-SB lesions in patients with ongoing bleeding.
DISCLOSURE Dr De Looze is the recipient of speaker’s fees from Given Imaging. All other authors disclosed no financial relationships relevant to this publication. Cedric Van de Bruaene, MD Pieter Hindryckx, MD, PhD Danny De Looze, MD, PhD Department of Gastroenterology Ghent University Hospital Ghent, Belgium REFERENCES 1. Yung DE, Koulaouzidis A, Avni T, et al. Clinical outcomes of negative small-bowel capsule endoscopy for small-bowel bleeding: a systematic review and meta-analysis. Gastrointest Endosc 2017;85:305-17. 2. Van de Bruaene C, Hindryckx P, Snauwaert C, et al. The predictive value of negative capsule endoscopy for the indication of obscure gastrointestinal bleeding: no reassurance in the long term. Acta Gastroenterol Belg 2016;79:405-13. http://dx.doi.org/10.1016/j.gie.2017.04.012
Response: We read with interest the correspondence from van de Bruaene et al1 in response to our meta-analysis2 on rebleeding rates after negative results of small-bowel capsule endoscopy (SBCE) for small-bowel bleeding (SBB; previously OGIB). We would like to thank them for the information they provided.3,4 The authors mention that in the long term (>2 years), their patients had a high rate of rebleeding of 34%; however, it is interesting to note that most of those patients had a bleeding source outside the small bowel. This further supports the conclusion of our meta-analysis that patients with a negative SBCE result have a low rate of small-bowel rebleeding. Patients presenting with rebleeding after a prolonged period of follow-up should therefore be investigated as “new” cases, including consideration of repeated conventional endoscopy. Morewww.giejournal.org
over, emerging biomarkers for SBB, such as angiopoietin2, offer promise as potential noninvasive screening tools.5 Such markers, once refined, could be used to select patients for SBCE, therefore decreasing further the number of unnecessary investigations with negative results.
DISCLOSURE All authors disclosed no financial relationships relevant to this publication. Diana E. Yung, MBChB Anastasios Koulaouzidis, MD, FEBG, FACG, FASGE John N. Plevris, MD, PhD(E), DM, FRCPE, FEBGH Centre for Liver and Digestive Disorders The Royal Infirmary of Edinburgh Edinburgh, United Kingdom REFERENCES 1. Van de Bruaene C, Hindryckx P, De Looze D. Capsule endoscopy in obscure GI bleeding: better to be negative, but let us not be too positive. Gastrointest Endosc 2017;86:574-5. 2. Yung DE, Koulaouzidis A, Avni T, et al. Clinical outcomes of negative small-bowel capsule endoscopy for small-bowel bleeding: a systematic review and meta-analysis. Gastrointest Endosc 2017;85:305-17. 3. Van De Bruaene C, Hindryckx P, Snauwaert C, et al. Long-term follow-up in patients with OGIB and normal capsule endoscopy [abstract]. Gastrointest Endosc 2015;81:AB138. 4. Van de Bruaene C, Hindryckx P, Snauwaert C, et al. The predictive value of negative capsule endoscopy for the indication of obscure gastrointestinal bleeding: no reassurance in the long term. Acta Gastroenterol Belg 2015;79:405-13. 5. Holleran G, Hall B, O’Regan M, et al. Expression of angiogenic factors in patients with sporadic small bowel angiodysplasia. J Clin Gastroenterol 2015;49:831-6. http://dx.doi.org/10.1016/j.gie.2017.05.020
Efficacy and safety of endoscopic submucosal tunnel dissection for superficial esophageal squamous cell carcinoma: a propensity score matching analysis: methodologic issues To the Editor: We read the valuable article by Huang and colleagues1 published in Gastrointestinal Endoscopy in 2017 with great interest. The authors’ purpose was to assess the efficacy of the tunnel technique in endoscopic submucosal dissection (ESD) of superficial esophageal squamous cell carcinoma. They found that the ESD procedure time was significantly shorter in the tunnel ESD group than in the conventional ESD group. Also, they found that specimen size smaller than 40 mm was significantly and strongly associated with shorter procedure times both in the Volume 86, No. 3 : 2017 GASTROINTESTINAL ENDOSCOPY 575