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Closer examination of the nonbleeding visible vessel
EDITORIAL
Closer examination of the nonbleeding visible vessel The endoscopic appearance of a bleeding ulcer can be used to predict the likelihood of further upper GI bleeding based on the Forrest classification of stigmata of recent hemorrhage.1 High-risk lesions include those characterized by active spurting of blood (grade IA), oozing of blood (grade IB), a nonbleeding visible vessel (NBVV) (grade IIA), and an adherent clot (grade IIB). An NBVV is defined as “a pigmented protuberance in the ulcer.”2 The risk of further bleeding of an NBVV is 40% to 50%,3 which is less than active arterial spurting (55%-90%) but more than an adherent clot (20%-35%).4 A lesion visually identified on endoscopy as an NBVV represents a heterogeneous spectrum of pathology. Although a raised protuberance with an ulcer bed may indeed represent a visible vessel, this appearance may also be attributable to an adherent clot plugging a side hole in a vessel wall (sentinel clot) or a pseudoaneurysm. Given the high rate of NBVV rebleeding, it is critical that the endoscopist properly recognize this condition so that appropriate endoscopic therapy can be directed. Although this would seemingly not be a difficult task, in clinical practice, it can be challenging. In a study of an international panel of 14 expert endoscopists on the management of upper GI bleeding, there was poor agreement with a statistic of 0.34 ( ⱕ 0.4 indicates poor agreement) for the presence of an NBVV when shown videos of GI bleeding cases.5 In clinical practice, there is considerable interobserver disagreement in the interpretation of the presence of endoscopic stigmata of recent hemorrhage, especially for NBVVs. It is quite clear that not all NBVVs have the same risk of further bleeding because, although almost half of NBVVs identified will have further bleeding, by definition half of them will not further bleed. It is important to understand that an NBVV is a lesion that is part of a continuum from an actively bleeding ulcer to a clean ulcer. The natural history of peptic ulcer bleeding indicates that an NBVV represents an unstable and transient phase of ulcer healing after an initial bleed. As the NBVV progresses from its initial appearance when bleeding has ceased until the time that the lesion flattens out, its risk of further bleeding correspondingly decreases.
Copyright © 2010 by the American Society for Gastrointestinal Endoscopy 0016-5107/$36.00 doi:10.1016/j.gie.2010.03.1127
www.giejournal.org
There have been multiple attempts to further define which NBVVs are at high risk of further bleeding and which may be at lower risk.3,6 The risk of further bleeding for NBVVs has been studied based on the color, size, and location of the protuberance (vessel) within the ulcer. A white color of an NBVV has been one factor associated with a higher risk of further bleeding.3,6 When vessel color of NBVVs was evaluated, the most common color of an NBVV was red and dark red (54%), followed by black (23%), and then white (18%). The rate of further bleeding of an NBVV by color was white (48%-58%), red (27%47%), and black (18%-40%).3,6 This may reflect the evolution of an NBVV from an early lesion soon after bleeding with a white color (similar to a fibrin plug seen in esophageal varices) to a lesion of intermediate risk with red color and finally to the lowest risk NBVV with a black color. It has been speculated that the darkening of an NBVV indicates thrombus organization. Although the color of the vessel seems to be an important predictor of further bleeding, it is important to note that there is quite a large range of rebleeding rates within each NBVV color group, and the evolution of NBVV color is not predictable.
The natural history of peptic ulcer bleeding indicates that a nonbleeding visible vessel represents an unstable and transient phase of ulcer healing after an initial bleed.
Other factors identified with a higher risk of further bleeding are increasing vessel size and a peripheral location of the vessel within an ulcer crater.3,6 The most common diameter of an NBVV is 1 to 2 mm (70%). The rate of further bleeding directly correlates with the size of an NBVV, with a smaller NBVV having a lower rebleeding rate (1 mm, 34%; 2 mm, 44%; 3 mm, 52%; 4 mm, 60%; 5 mm, 67%; and ⬎6 mm, 100%).3 Furthermore, peripheral location within the ulcer of an NBVV is associated with a higher rate of further bleeding compared with an NBVV with a central ulcer location (56% vs 20%).6 In this issue of Gastrointestinal Endoscopy, Cipolletta et al7 characterize the appearance of NBVVs by using magnification endoscopy. The authors successfully evaluated 43 patients with an NBVV in 181 patients who presented with upper GI bleeding over a 12-month period. Two Volume 72, No. 2 : 2010 GASTROINTESTINAL ENDOSCOPY
419
Editorial
Liu & Saltzman
special procedures were used in the study that are not routinely used during endoscopy: the use of a soft-plastic hood with a magnification endoscope (80⫻ magnification) and chromoendoscopy with selective staining using 0.4% methylene blue in ulcers larger than 2 cm (performed in 9 patients). The use of the magnification endoscope with a soft-plastic hood required a change from the standard therapeutic endoscope initially used. The mean examination time of magnification endoscopy was 7 ⫾ 4 minutes, including application of the methylene blue stain. The magnified views were reported as providing a clear image that allowed visualization of the artery, the site of rupture, and the presence of a clot plugging the hole. Of note, the interobserver variability was excellent among the 3 operators with a statistic of 0.88. The 3 endoscopists, who are obviously experienced in managing GI bleeding, likely also received significant training before conducting the study. The authors initially characterized the risk of further bleeding by using NBVV color and protuberance into a high-risk group (protuberant, translucent, or pale) in 25 patients and a low-risk group (nonprotruding vessel through the ulcer floor, pigmented or dark red) in 18 patients. Based on the information provided from the magnification (and chromoendoscopy) examination, the authors reclassified the NBVV lesions. Patients with exposed vessels seen on magnification endoscopy were then classified as high risk (31 patients) or low risk (12 patients). Thus, in 6 cases initially labeled low risk, magnification endoscopy performed in this fashion led to a reclassification from the low-risk to the high-risk category, and the authors report a diagnostic gain of 33%. Successful endoscopic treatment of the NBVVs was achieved in all cases, and no recurrent GI bleeding occurred during follow-up. The clinical significance of this new NBVV classification system based on magnification endoscopy examinations is unclear. In this study, all patients received endoscopic intervention regardless of high- or low-risk classification, and all were reported to have a successful therapeutic endoscopy. Indeed, the findings on magnification endoscopy did not influence endoscopic therapy because the authors stated that “the distance between the 2 ends of the vessel was not so much to require separate applications of therapy.” Thus, whether magnification endoscopy truly identified patients at higher risk for further bleeding is not known. Risk stratification directly affects patient management in upper GI bleeding because high-risk patients are admitted to the hospital initially to a monitored setting or intensive care unit. Patients with endoscopic high-risk lesions currently receive both high-dose proton pump inhibitors and endoscopic hemostasis to reduce the rate of further bleeding, surgery, and mortality.8 Recommended endoscopic treatments of NBVVs include combination therapy using injection and thermal therapies and mechanical therapy 420 GASTROINTESTINAL ENDOSCOPY
Volume 72, No. 2 : 2010
using hemoclips.9,10 The endpoint of thermal therapy is the complete flattening of the vessel with no bleeding. The endpoint for hemoclip therapy is less defined, and treatment is usually stopped when the base of the vessel feeding the visible vessel has been ligated. Despite medical and endoscopic therapy, patients may experience recurrent bleeding, indicating suboptimal NBVV treatment. It is hoped that the development of new endoscopic therapies will provide more secure endoscopic treatments in the future. For NBVVs, more reliable predictors of which lesions should be treated (or not treated) and more secure endpoints of therapy are needed to indicate that adequate endoscopic therapy has been administered and to reduce rates of further bleeding. Doppler US through-theendoscope probes represent an advance in endoscopic technologies that allows further definition of NBVVs.11 These probes allow interrogation of an ulcer to determine whether and where there is blood flow. Studies using endoscopic Doppler US show that often NBVVs do not contain arterial flow. Endoscopic treatments should be performed on the patients with a positive Doppler signal and directed to the source of the Doppler signal. The use of Doppler US probes during endoscopy in patients with upper GI bleeding shows that Doppler-positive NBVVs have a much higher rate of recurrent bleeding than Doppler-negative NBVVs. Furthermore, ulcers that remain Doppler positive after endoscopic therapy are at significantly higher risk of recurrent bleeding.12 Thus, in the management of patients with acute upper GI bleeding, obliteration of the Doppler signal may provide a therapeutic endpoint for the endoscopic therapy of an NBVV.13 In patients with upper GI bleeding, endoscopists must interrogate ulcers when no active bleeding is seen to look for a possible NBVV. Raised protuberances within the ulcer bed should be presumed to be an NBVV. Close inspection of the vessel by using current high-definition endoscopes may help to further characterize the risk of further bleeding, including vessel size, color, and location within the ulcer bed. However, whether a vessel is determined visually to be at high or low risk of further bleeding, endoscopic therapy is appropriate to perform. The endoscopist should choose a proven endoscopic therapeutic hemostasis modality or combination of modalities. Traditional endpoints of endoscopic therapy should be achieved, and if Doppler probes are available, therapy should be performed until there is cessation of the Doppler signal. Medical therapy with proton pump inhibitors should be administered along with endoscopic therapy because this combination is most efficacious. The clinical significance of the findings on magnification endoscopy of NBVVs needs to be determined. Future studies are needed to better define the predictors of further bleeding of NBVVs and the optimal endpoints for NBVV endoscopic treatment. www.giejournal.org
Liu & Saltzman
Editorial
DISCLOSURE
3. Lin HJ, Perng CL, Lee FY, et al. Clinical courses and predictors for rebleeding in patients with peptic ulcers and non-bleeding visible vessels: a prospective study. Gut 1994;35:1389-93. 4. Adler DG, Leighton JA, Davila RE, et al. ASGE guideline: the role of endoscopy in acute non-variceal upper-GI hemorrhage. Gastrointest Endosc 2004;60:497-504. 5. Lau JY, Sung JJ, Chan AC, et al. Stigmata of hemorrhage in bleeding peptic ulcers: an interobserver agreement study among international experts. Gastrointest Endosc 1997;46:33-6. 6. Amano Y, Moriyama N, Suetsugu H, et al. Which types of non-bleeding visible vessels in gastric peptic ulcers should be treated by endoscopic hemostasis? J Gastroenterol Hepatol 2004;19:13-7. 7. Cipolletta L, Bianco MA, Salerno R, et al. Improved characterization of visible vessels in bleeding ulcers by using magnification endoscopy: results of a pilot study. Gastrointest Endosc 2010;72.413-8. 8. Gralnek IM, Barkun AN, Bardou M. Management of acute bleeding from a peptic ulcer. N Engl J Med 2008;359:928-37. 9. Laine L, McQuaid KR. Endoscopic therapy for bleeding ulcers: an evidence-based approach based on meta-analyses of randomized controlled trials. Clin Gastroenterol Hepatol 2009;7:33-47; quiz 1-2. 10. Barkun AN, Bardou M, Kuipers EJ, et al. International consensus recommendations on the management of patients with nonvariceal upper gastrointestinal bleeding. Ann Intern Med 2010;152:101-13. 11. Wong RC. Nonvariceal upper gastrointestinal hemorrhage: probing beneath the surface. Gastroenterology 2009;137:1897, 1902. 12. Wong RC. Endoscopic Doppler US probe for acute peptic ulcer hemorrhage. Gastrointest Endosc 2004;60:804-12. 13. Chen VK, Wong RC. Endoscopic Doppler ultrasound versus endoscopic stigmata-directed management of acute peptic ulcer hemorrhage: a multimodel cost analysis. Dig Dis Sci 2007;52:149-60.
The authors disclosed the following financial relationships relevant to this publication: J.J. Lin: Research grant from Olympus Corp. J.R. Saltzman: Research grant from Olympus Corp; consultant for Cook Endoscopy. Julia J. Liu, MD Gastroenterology Division University of Alberta Edmonton, Alberta, Canada John R. Saltzman, MD Endoscopy Center Brigham and Women’s Hospital Harvard Medical School Boston, Massachusetts, USA Abbreviation: NBVV, nonbleeding visible vessel.
REFERENCES 1. Forrest JA, Finlayson ND, Shearman DJ. Endoscopy in gastrointestinal bleeding. Lancet 1974;2:394-7. 2. Proceedings of the Consensus Conference on Therapeutic Endoscopy in Bleeding Ulcers. March 6-8, 1989. Gastrointest Endosc 1990;36:S1-65.
Registration of Human Clinical Trials Gastrointestinal Endoscopy follows the International Committee of Medical Journal Editors (ICMJE)’s Uniform Requirements for Manuscripts Submitted to Biomedical Journals. All prospective human clinical trials eventually submitted in GIE must have been registered through one of the registries approved by the ICMJE, and proof of that registration must be submitted to GIE along with the article. For further details and explanation of which trials need to be registered as well as a list of ICMJE-acceptable registries, please go to http://www.icmje.org.
www.giejournal.org
Volume 72, No. 2 : 2010 GASTROINTESTINAL ENDOSCOPY
421
Closer examination of the nonbleeding visible vessel The endoscopic appearance of a bleeding ulcer can be used to predict the likelihood of further upper GI bleeding based on the Forrest classification of stigmata of recent hemorrhage.1 High-risk lesions include those characterized by active spurting of blood (grade IA), oozing of blood (grade IB), a nonbleeding visible vessel (NBVV) (grade IIA), and an adherent clot (grade IIB). An NBVV is defined as “a pigmented protuberance in the ulcer.”2 The risk of further bleeding of an NBVV is 40% to 50%,3 which is less than active arterial spurting (55%-90%) but more than an adherent clot (20%-35%).4 A lesion visually identified on endoscopy as an NBVV represents a heterogeneous spectrum of pathology. Although a raised protuberance with an ulcer bed may indeed represent a visible vessel, this appearance may also be attributable to an adherent clot plugging a side hole in a vessel wall (sentinel clot) or a pseudoaneurysm. Given the high rate of NBVV rebleeding, it is critical that the endoscopist properly recognize this condition so that appropriate endoscopic therapy can be directed. Although this would seemingly not be a difficult task, in clinical practice, it can be challenging. In a study of an international panel of 14 expert endoscopists on the management of upper GI bleeding, there was poor agreement with a statistic of 0.34 ( ⱕ 0.4 indicates poor agreement) for the presence of an NBVV when shown videos of GI bleeding cases.5 In clinical practice, there is considerable interobserver disagreement in the interpretation of the presence of endoscopic stigmata of recent hemorrhage, especially for NBVVs. It is quite clear that not all NBVVs have the same risk of further bleeding because, although almost half of NBVVs identified will have further bleeding, by definition half of them will not further bleed. It is important to understand that an NBVV is a lesion that is part of a continuum from an actively bleeding ulcer to a clean ulcer. The natural history of peptic ulcer bleeding indicates that an NBVV represents an unstable and transient phase of ulcer healing after an initial bleed. As the NBVV progresses from its initial appearance when bleeding has ceased until the time that the lesion flattens out, its risk of further bleeding correspondingly decreases.
Copyright © 2010 by the American Society for Gastrointestinal Endoscopy 0016-5107/$36.00 doi:10.1016/j.gie.2010.03.1127
www.giejournal.org
There have been multiple attempts to further define which NBVVs are at high risk of further bleeding and which may be at lower risk.3,6 The risk of further bleeding for NBVVs has been studied based on the color, size, and location of the protuberance (vessel) within the ulcer. A white color of an NBVV has been one factor associated with a higher risk of further bleeding.3,6 When vessel color of NBVVs was evaluated, the most common color of an NBVV was red and dark red (54%), followed by black (23%), and then white (18%). The rate of further bleeding of an NBVV by color was white (48%-58%), red (27%47%), and black (18%-40%).3,6 This may reflect the evolution of an NBVV from an early lesion soon after bleeding with a white color (similar to a fibrin plug seen in esophageal varices) to a lesion of intermediate risk with red color and finally to the lowest risk NBVV with a black color. It has been speculated that the darkening of an NBVV indicates thrombus organization. Although the color of the vessel seems to be an important predictor of further bleeding, it is important to note that there is quite a large range of rebleeding rates within each NBVV color group, and the evolution of NBVV color is not predictable.
The natural history of peptic ulcer bleeding indicates that a nonbleeding visible vessel represents an unstable and transient phase of ulcer healing after an initial bleed.
Other factors identified with a higher risk of further bleeding are increasing vessel size and a peripheral location of the vessel within an ulcer crater.3,6 The most common diameter of an NBVV is 1 to 2 mm (70%). The rate of further bleeding directly correlates with the size of an NBVV, with a smaller NBVV having a lower rebleeding rate (1 mm, 34%; 2 mm, 44%; 3 mm, 52%; 4 mm, 60%; 5 mm, 67%; and ⬎6 mm, 100%).3 Furthermore, peripheral location within the ulcer of an NBVV is associated with a higher rate of further bleeding compared with an NBVV with a central ulcer location (56% vs 20%).6 In this issue of Gastrointestinal Endoscopy, Cipolletta et al7 characterize the appearance of NBVVs by using magnification endoscopy. The authors successfully evaluated 43 patients with an NBVV in 181 patients who presented with upper GI bleeding over a 12-month period. Two Volume 72, No. 2 : 2010 GASTROINTESTINAL ENDOSCOPY
419
Editorial
Liu & Saltzman
special procedures were used in the study that are not routinely used during endoscopy: the use of a soft-plastic hood with a magnification endoscope (80⫻ magnification) and chromoendoscopy with selective staining using 0.4% methylene blue in ulcers larger than 2 cm (performed in 9 patients). The use of the magnification endoscope with a soft-plastic hood required a change from the standard therapeutic endoscope initially used. The mean examination time of magnification endoscopy was 7 ⫾ 4 minutes, including application of the methylene blue stain. The magnified views were reported as providing a clear image that allowed visualization of the artery, the site of rupture, and the presence of a clot plugging the hole. Of note, the interobserver variability was excellent among the 3 operators with a statistic of 0.88. The 3 endoscopists, who are obviously experienced in managing GI bleeding, likely also received significant training before conducting the study. The authors initially characterized the risk of further bleeding by using NBVV color and protuberance into a high-risk group (protuberant, translucent, or pale) in 25 patients and a low-risk group (nonprotruding vessel through the ulcer floor, pigmented or dark red) in 18 patients. Based on the information provided from the magnification (and chromoendoscopy) examination, the authors reclassified the NBVV lesions. Patients with exposed vessels seen on magnification endoscopy were then classified as high risk (31 patients) or low risk (12 patients). Thus, in 6 cases initially labeled low risk, magnification endoscopy performed in this fashion led to a reclassification from the low-risk to the high-risk category, and the authors report a diagnostic gain of 33%. Successful endoscopic treatment of the NBVVs was achieved in all cases, and no recurrent GI bleeding occurred during follow-up. The clinical significance of this new NBVV classification system based on magnification endoscopy examinations is unclear. In this study, all patients received endoscopic intervention regardless of high- or low-risk classification, and all were reported to have a successful therapeutic endoscopy. Indeed, the findings on magnification endoscopy did not influence endoscopic therapy because the authors stated that “the distance between the 2 ends of the vessel was not so much to require separate applications of therapy.” Thus, whether magnification endoscopy truly identified patients at higher risk for further bleeding is not known. Risk stratification directly affects patient management in upper GI bleeding because high-risk patients are admitted to the hospital initially to a monitored setting or intensive care unit. Patients with endoscopic high-risk lesions currently receive both high-dose proton pump inhibitors and endoscopic hemostasis to reduce the rate of further bleeding, surgery, and mortality.8 Recommended endoscopic treatments of NBVVs include combination therapy using injection and thermal therapies and mechanical therapy 420 GASTROINTESTINAL ENDOSCOPY
Volume 72, No. 2 : 2010
using hemoclips.9,10 The endpoint of thermal therapy is the complete flattening of the vessel with no bleeding. The endpoint for hemoclip therapy is less defined, and treatment is usually stopped when the base of the vessel feeding the visible vessel has been ligated. Despite medical and endoscopic therapy, patients may experience recurrent bleeding, indicating suboptimal NBVV treatment. It is hoped that the development of new endoscopic therapies will provide more secure endoscopic treatments in the future. For NBVVs, more reliable predictors of which lesions should be treated (or not treated) and more secure endpoints of therapy are needed to indicate that adequate endoscopic therapy has been administered and to reduce rates of further bleeding. Doppler US through-theendoscope probes represent an advance in endoscopic technologies that allows further definition of NBVVs.11 These probes allow interrogation of an ulcer to determine whether and where there is blood flow. Studies using endoscopic Doppler US show that often NBVVs do not contain arterial flow. Endoscopic treatments should be performed on the patients with a positive Doppler signal and directed to the source of the Doppler signal. The use of Doppler US probes during endoscopy in patients with upper GI bleeding shows that Doppler-positive NBVVs have a much higher rate of recurrent bleeding than Doppler-negative NBVVs. Furthermore, ulcers that remain Doppler positive after endoscopic therapy are at significantly higher risk of recurrent bleeding.12 Thus, in the management of patients with acute upper GI bleeding, obliteration of the Doppler signal may provide a therapeutic endpoint for the endoscopic therapy of an NBVV.13 In patients with upper GI bleeding, endoscopists must interrogate ulcers when no active bleeding is seen to look for a possible NBVV. Raised protuberances within the ulcer bed should be presumed to be an NBVV. Close inspection of the vessel by using current high-definition endoscopes may help to further characterize the risk of further bleeding, including vessel size, color, and location within the ulcer bed. However, whether a vessel is determined visually to be at high or low risk of further bleeding, endoscopic therapy is appropriate to perform. The endoscopist should choose a proven endoscopic therapeutic hemostasis modality or combination of modalities. Traditional endpoints of endoscopic therapy should be achieved, and if Doppler probes are available, therapy should be performed until there is cessation of the Doppler signal. Medical therapy with proton pump inhibitors should be administered along with endoscopic therapy because this combination is most efficacious. The clinical significance of the findings on magnification endoscopy of NBVVs needs to be determined. Future studies are needed to better define the predictors of further bleeding of NBVVs and the optimal endpoints for NBVV endoscopic treatment. www.giejournal.org
Liu & Saltzman
Editorial
DISCLOSURE
3. Lin HJ, Perng CL, Lee FY, et al. Clinical courses and predictors for rebleeding in patients with peptic ulcers and non-bleeding visible vessels: a prospective study. Gut 1994;35:1389-93. 4. Adler DG, Leighton JA, Davila RE, et al. ASGE guideline: the role of endoscopy in acute non-variceal upper-GI hemorrhage. Gastrointest Endosc 2004;60:497-504. 5. Lau JY, Sung JJ, Chan AC, et al. Stigmata of hemorrhage in bleeding peptic ulcers: an interobserver agreement study among international experts. Gastrointest Endosc 1997;46:33-6. 6. Amano Y, Moriyama N, Suetsugu H, et al. Which types of non-bleeding visible vessels in gastric peptic ulcers should be treated by endoscopic hemostasis? J Gastroenterol Hepatol 2004;19:13-7. 7. Cipolletta L, Bianco MA, Salerno R, et al. Improved characterization of visible vessels in bleeding ulcers by using magnification endoscopy: results of a pilot study. Gastrointest Endosc 2010;72.413-8. 8. Gralnek IM, Barkun AN, Bardou M. Management of acute bleeding from a peptic ulcer. N Engl J Med 2008;359:928-37. 9. Laine L, McQuaid KR. Endoscopic therapy for bleeding ulcers: an evidence-based approach based on meta-analyses of randomized controlled trials. Clin Gastroenterol Hepatol 2009;7:33-47; quiz 1-2. 10. Barkun AN, Bardou M, Kuipers EJ, et al. International consensus recommendations on the management of patients with nonvariceal upper gastrointestinal bleeding. Ann Intern Med 2010;152:101-13. 11. Wong RC. Nonvariceal upper gastrointestinal hemorrhage: probing beneath the surface. Gastroenterology 2009;137:1897, 1902. 12. Wong RC. Endoscopic Doppler US probe for acute peptic ulcer hemorrhage. Gastrointest Endosc 2004;60:804-12. 13. Chen VK, Wong RC. Endoscopic Doppler ultrasound versus endoscopic stigmata-directed management of acute peptic ulcer hemorrhage: a multimodel cost analysis. Dig Dis Sci 2007;52:149-60.
The authors disclosed the following financial relationships relevant to this publication: J.J. Lin: Research grant from Olympus Corp. J.R. Saltzman: Research grant from Olympus Corp; consultant for Cook Endoscopy. Julia J. Liu, MD Gastroenterology Division University of Alberta Edmonton, Alberta, Canada John R. Saltzman, MD Endoscopy Center Brigham and Women’s Hospital Harvard Medical School Boston, Massachusetts, USA Abbreviation: NBVV, nonbleeding visible vessel.
REFERENCES 1. Forrest JA, Finlayson ND, Shearman DJ. Endoscopy in gastrointestinal bleeding. Lancet 1974;2:394-7. 2. Proceedings of the Consensus Conference on Therapeutic Endoscopy in Bleeding Ulcers. March 6-8, 1989. Gastrointest Endosc 1990;36:S1-65.
Registration of Human Clinical Trials Gastrointestinal Endoscopy follows the International Committee of Medical Journal Editors (ICMJE)’s Uniform Requirements for Manuscripts Submitted to Biomedical Journals. All prospective human clinical trials eventually submitted in GIE must have been registered through one of the registries approved by the ICMJE, and proof of that registration must be submitted to GIE along with the article. For further details and explanation of which trials need to be registered as well as a list of ICMJE-acceptable registries, please go to http://www.icmje.org.
www.giejournal.org
Volume 72, No. 2 : 2010 GASTROINTESTINAL ENDOSCOPY
421