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Detection, Diagnosis, and Resection of Sessile Serrated Adenomas and Polyps
Accepted Manuscript Detection, Diagnosis and Resection of Sessile Serrated Adenomas/Polyps Jennifer M. Kolb, Roy M. Soetikno, Aarti K. Rao, Dean Fong, Robert V. Rouse, Tonya Kaltenbach
PII: DOI: Reference:
S0016-5085(17)35865-1 10.1053/j.gastro.2017.05.060 YGAST 61267
To appear in: Gastroenterology Accepted Date: 30 May 2017 Please cite this article as: Kolb JM, Soetikno RM, Rao AK, Fong D, Rouse RV, Kaltenbach T, Detection, Diagnosis and Resection of Sessile Serrated Adenomas/Polyps, Gastroenterology (2017), doi: 10.1053/ j.gastro.2017.05.060. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Detection, Diagnosis and Resection of Sessile Serrated Adenomas/Polyps
Jennifer M. Kolb1, Roy M. Soetikno2, Aarti K. Rao3, Dean Fong3, Robert V. Rouse3 and
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Tonya Kaltenbach4
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1. Icahn School of Medicine at Mount Sinai, Mount Sinai Hospital, New York, NY 2. Graduate School of Business, Stanford, California, USA
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3. Veterans Affairs Palo Alto Health Care System and Stanford University School of Medicine, Palo Alto, California
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4. University of California San Francisco, San Francisco Veterans Affairs Medical Center, San Francisco, California, USA
Grant Support: None
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Corresponding author: Tonya Kaltenbach MD MS Associate Professor of Clinical Medicine University of California, San Francisco Veterans Affairs Medical Center, San Francisco [email protected] Disclosures: Roy Soetikno and Tonya Kaltenbach have received non-salaried research support and are consultants for Olympus America, Inc. Jennifer Kolb, Aarti Rao, Robert Rouse, and Dean Fong have no conflicts of interest to declare. Writing assistance: none Author contributions:
1
ACCEPTED MANUSCRIPT
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Jennifer Kolb -drafting of the manuscript -critical revision of the manuscript for important intellectual content -video development -critical revision of the video for important intellectual content
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Roy Soetikno: -concept and design -supervision -drafting of the manuscript -critical revision of the manuscript for important intellectual content -endoscopy image acquisition -video development -critical revision of the video for important intellectual content
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Aarti Rao: -drafting of the manuscript -video development -critical revision of the video for important intellectual content
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Dean Fong: -pathology image acquisition -drafting of the manuscript -critical revision of the manuscript for important intellectual content -critical revision of the video for important intellectual content
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Robert V. Rouse: -drafting of the manuscript -critical revision of the manuscript for important intellectual content -critical revision of the video for important intellectual content
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Tonya Kaltenbach: -concept and design -supervision -drafting of the manuscript -critical revision of the manuscript for important intellectual content -endoscopy image acquisition -video development -critical revision of the video for important intellectual content Abstract : N/A Keywords: sessile serrated adenoma; sessile serrated polyp; endoscopic mucosal resection
2
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Sessile serrated adenomas/polyps (SSA/Ps), especially those in the proximal colon, are recognized as precursors to colorectal cancer (CRC), yet their detection, diagnosis and resection can still pose a challenge and are not widely known.1 Herein, we summarize
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the current knowledge on the endoscopic approach to detect, diagnose and treat
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SSA/Ps.
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Description of Technology
Detection
The detection of SSA/Ps requires careful colonoscopy.1 SSA/Ps can easily be missed because they are often flat and found in the large-diameter-proximal colon. Bowel
TE D
preparation must therefore be excellent. Potential SSA/P lesions are initially considered at long view and investigated at close-up view. At long view, the presence of SSA/P is suspected when there is a patch that appears nodular, reddish, covered with mucus,
EP
and/or circled by fine debris. The border of the lesion may be difficult to see, thus the lesion must be approached and the mucosa washed. At near view, the mucosal surface
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and vascular pattern of SSA/Ps are irregular: its mucosa appears to have a cloud-like surface with indistinct edges and often has lacy vessels coursing on it. Finally, at closeup view, using white light and under image-enhanced endoscopy (IEE), the surface pattern and vessels are examined. The mucosa has dark or white spots of uniform size: these spots are the openings of the pits. The vessels, if present, can be viewed more clearly coursing on the surface.2
3
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Endoscopic Diagnosis The distinction between SSA/P and hyperplastic polyp (HP) has been limited by poor
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inter-observer agreement in histopathologic evaluation. Without histology as gold
standard, endoscopic studies to distinguish SSA/P versus HP are difficult to perform. Thus, at present, especially in the right colon where large SSA/Ps are typically detected,
SC
endoscopic diagnosis can confirm the possibility that a lesion is SSA/P, but realizing that the lesion may be HP. Similarly, SSA/P with dysplasia cannot yet be differentiated
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reliably from those without dysplasia. Despite the current limitations, a number of features have been described as potentially helpful to diagnose possible SSA/Ps. The Type II-open pit pattern, which consists of rounder and larger pits reflecting dilated crypts and surrounding serrations, is characteristic of SSA/Ps because the pattern is not
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found in HP, normal or adenomatous tissues.3 The red cap sign has also been described as typical of only SSA/P lesions. Additional morphologic features of SSA/Ps include a cloud-like surface and indistinct borders. The NBI International Colorectal
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Endoscopic classification described features of type I lesion, which included HP and SSA/Ps, as distinct from those of type II lesion, which included adenomas.4 By training
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using still images of polyps visualized under NBI, endoscopists can increase their ability to recognize that a lesion is more likely to be SSA/P than an adenoma.5
Video description Treatment
4
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When possible, current practice is to remove all polyps. Small lesions, which may be SSA/Ps, can be removed using standard snare techniques. Large SSA/Ps, on the other hand, require additional techniques to allow their complete and reliable resection, thus
RI PT
preventing their potential malignant transformation. The author’s believe that
endoscopic mucosal resection (EMR) is the most suitable technique to remove large SSA/Ps; we and others have reported a low recurrence rate (3.6%) after EMR of large
SC
(≥ 1cm) proximal SSA/Ps.6 We use the inject-and-cut EMR technique and the dynamic injection of saline solution mixed with indigo carmine or methylene blue to create a
M AN U
submucosal bleb. We deploy a stiff electrosurgical snare around the lifted lesion, suction the lumen slightly and apply current. If possible, we resect en-bloc and include a rim of normal mucosa. If not, we resect piecemeal. In contrast to EMR, the conventional polypectomy methods, such as hot snare, seem unreliable particularly for large SSA/P;
Pathologic Diagnosis
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it has a high rate (approximately one-third) of incomplete resection.
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After biopsy/snare or mucosal resection, orientation of the specimen using a simple technique leads to a higher frequency of diagnosis of SSA/P versus HP, a higher
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interobserver agreement among pathologists, and a lower frequency of indeterminate diagnoses.7 Based on current consensus, a single distorted serrated crypt is sufficient for the pathologic diagnosis of SSA/P; the crypt base contains prominent serrations and is dilated with a signature “boot” or “T-” shape.8 SSA/Ps with cytological dysplasia contain a region with characteristic SSA/P histology and another region with cytologic dysplasia resembling a conventional adenoma. Recommendations for surveillance
5
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intervals for patients with SSA/P have been published, although they have not been validated.
RI PT
Take home message
A number of pathways exist that lead to the development of CRC; one of them is the serrated pathway. SSA/Ps, the CRC precursor in the serrated pathway, are most often
SC
flat and in the right colon, but can be detected, diagnosed, albeit with limitation, and removed. Thus, cancers arising from the serrated pathway can be prevented. The
M AN U
training provided here allows all readers to develop expertise in the detection and management of SSA/Ps.
Figure 1 Legend
Figure 2 Legend
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a. SSA/P with surrounding rim of debris b. Irregularly distributed dystrophic goblet cells c. SSA/P with inverted T-shaped crypts d. Proximal colon SSA/P with subtle nodular appearance of surface mucosa e. Dilated, boot shaped crypts f. Hyperplastic Polyp
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a. Endoscopic long-view of SSA/P with dysplasia. b. Corresponding pathology for SSA/P with dysplasia. Arrowhead: SSA/P with serration and basal crypt dilation. Arrow: hyperchromatic and crowded nuclei, irregular shaped glands of adenocarcinoma
6
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References: 1. Crockett SD, et al. Clin Gastroenterol Hepatol. 2015; Jan; 13(1):11-26
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2. Saito S, et al. World J Gastrointest Endosc. 2015 Jul 25;7(9):860-71
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3. T. Kimura, et al. Am. J. Gastroenterol. 2012 Mar;107(3):460-9
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4. Hewett DG, et al.. Gastroenterology. 2012 Sep;143(3):599-607
5. IJspeert, J. E. et al. Gut. 2016 Jun;65(6):963-70
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6. Rao, A. K. et al. Clin Gastroenterol Hepatol 2016 Apr;14(4):568-74
7. Kolb, J. M. et al. J Clin Gastroenterol. 2016 Mar;50(3):233-8
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8. Rex, D. K. et al. Am. J. Gastroenterol. 2012 Sep;107(9):1315-29
7
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ACCEPTED MANUSCRIPT
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ACCEPTED MANUSCRIPT
PII: DOI: Reference:
S0016-5085(17)35865-1 10.1053/j.gastro.2017.05.060 YGAST 61267
To appear in: Gastroenterology Accepted Date: 30 May 2017 Please cite this article as: Kolb JM, Soetikno RM, Rao AK, Fong D, Rouse RV, Kaltenbach T, Detection, Diagnosis and Resection of Sessile Serrated Adenomas/Polyps, Gastroenterology (2017), doi: 10.1053/ j.gastro.2017.05.060. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Detection, Diagnosis and Resection of Sessile Serrated Adenomas/Polyps
Jennifer M. Kolb1, Roy M. Soetikno2, Aarti K. Rao3, Dean Fong3, Robert V. Rouse3 and
RI PT
Tonya Kaltenbach4
SC
1. Icahn School of Medicine at Mount Sinai, Mount Sinai Hospital, New York, NY 2. Graduate School of Business, Stanford, California, USA
M AN U
3. Veterans Affairs Palo Alto Health Care System and Stanford University School of Medicine, Palo Alto, California
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4. University of California San Francisco, San Francisco Veterans Affairs Medical Center, San Francisco, California, USA
Grant Support: None
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Corresponding author: Tonya Kaltenbach MD MS Associate Professor of Clinical Medicine University of California, San Francisco Veterans Affairs Medical Center, San Francisco [email protected] Disclosures: Roy Soetikno and Tonya Kaltenbach have received non-salaried research support and are consultants for Olympus America, Inc. Jennifer Kolb, Aarti Rao, Robert Rouse, and Dean Fong have no conflicts of interest to declare. Writing assistance: none Author contributions:
1
ACCEPTED MANUSCRIPT
RI PT
Jennifer Kolb -drafting of the manuscript -critical revision of the manuscript for important intellectual content -video development -critical revision of the video for important intellectual content
SC
Roy Soetikno: -concept and design -supervision -drafting of the manuscript -critical revision of the manuscript for important intellectual content -endoscopy image acquisition -video development -critical revision of the video for important intellectual content
M AN U
Aarti Rao: -drafting of the manuscript -video development -critical revision of the video for important intellectual content
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Dean Fong: -pathology image acquisition -drafting of the manuscript -critical revision of the manuscript for important intellectual content -critical revision of the video for important intellectual content
EP
Robert V. Rouse: -drafting of the manuscript -critical revision of the manuscript for important intellectual content -critical revision of the video for important intellectual content
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Tonya Kaltenbach: -concept and design -supervision -drafting of the manuscript -critical revision of the manuscript for important intellectual content -endoscopy image acquisition -video development -critical revision of the video for important intellectual content Abstract : N/A Keywords: sessile serrated adenoma; sessile serrated polyp; endoscopic mucosal resection
2
ACCEPTED MANUSCRIPT
Sessile serrated adenomas/polyps (SSA/Ps), especially those in the proximal colon, are recognized as precursors to colorectal cancer (CRC), yet their detection, diagnosis and resection can still pose a challenge and are not widely known.1 Herein, we summarize
RI PT
the current knowledge on the endoscopic approach to detect, diagnose and treat
SC
SSA/Ps.
M AN U
Description of Technology
Detection
The detection of SSA/Ps requires careful colonoscopy.1 SSA/Ps can easily be missed because they are often flat and found in the large-diameter-proximal colon. Bowel
TE D
preparation must therefore be excellent. Potential SSA/P lesions are initially considered at long view and investigated at close-up view. At long view, the presence of SSA/P is suspected when there is a patch that appears nodular, reddish, covered with mucus,
EP
and/or circled by fine debris. The border of the lesion may be difficult to see, thus the lesion must be approached and the mucosa washed. At near view, the mucosal surface
AC C
and vascular pattern of SSA/Ps are irregular: its mucosa appears to have a cloud-like surface with indistinct edges and often has lacy vessels coursing on it. Finally, at closeup view, using white light and under image-enhanced endoscopy (IEE), the surface pattern and vessels are examined. The mucosa has dark or white spots of uniform size: these spots are the openings of the pits. The vessels, if present, can be viewed more clearly coursing on the surface.2
3
ACCEPTED MANUSCRIPT
Endoscopic Diagnosis The distinction between SSA/P and hyperplastic polyp (HP) has been limited by poor
RI PT
inter-observer agreement in histopathologic evaluation. Without histology as gold
standard, endoscopic studies to distinguish SSA/P versus HP are difficult to perform. Thus, at present, especially in the right colon where large SSA/Ps are typically detected,
SC
endoscopic diagnosis can confirm the possibility that a lesion is SSA/P, but realizing that the lesion may be HP. Similarly, SSA/P with dysplasia cannot yet be differentiated
M AN U
reliably from those without dysplasia. Despite the current limitations, a number of features have been described as potentially helpful to diagnose possible SSA/Ps. The Type II-open pit pattern, which consists of rounder and larger pits reflecting dilated crypts and surrounding serrations, is characteristic of SSA/Ps because the pattern is not
TE D
found in HP, normal or adenomatous tissues.3 The red cap sign has also been described as typical of only SSA/P lesions. Additional morphologic features of SSA/Ps include a cloud-like surface and indistinct borders. The NBI International Colorectal
EP
Endoscopic classification described features of type I lesion, which included HP and SSA/Ps, as distinct from those of type II lesion, which included adenomas.4 By training
AC C
using still images of polyps visualized under NBI, endoscopists can increase their ability to recognize that a lesion is more likely to be SSA/P than an adenoma.5
Video description Treatment
4
ACCEPTED MANUSCRIPT
When possible, current practice is to remove all polyps. Small lesions, which may be SSA/Ps, can be removed using standard snare techniques. Large SSA/Ps, on the other hand, require additional techniques to allow their complete and reliable resection, thus
RI PT
preventing their potential malignant transformation. The author’s believe that
endoscopic mucosal resection (EMR) is the most suitable technique to remove large SSA/Ps; we and others have reported a low recurrence rate (3.6%) after EMR of large
SC
(≥ 1cm) proximal SSA/Ps.6 We use the inject-and-cut EMR technique and the dynamic injection of saline solution mixed with indigo carmine or methylene blue to create a
M AN U
submucosal bleb. We deploy a stiff electrosurgical snare around the lifted lesion, suction the lumen slightly and apply current. If possible, we resect en-bloc and include a rim of normal mucosa. If not, we resect piecemeal. In contrast to EMR, the conventional polypectomy methods, such as hot snare, seem unreliable particularly for large SSA/P;
Pathologic Diagnosis
TE D
it has a high rate (approximately one-third) of incomplete resection.
EP
After biopsy/snare or mucosal resection, orientation of the specimen using a simple technique leads to a higher frequency of diagnosis of SSA/P versus HP, a higher
AC C
interobserver agreement among pathologists, and a lower frequency of indeterminate diagnoses.7 Based on current consensus, a single distorted serrated crypt is sufficient for the pathologic diagnosis of SSA/P; the crypt base contains prominent serrations and is dilated with a signature “boot” or “T-” shape.8 SSA/Ps with cytological dysplasia contain a region with characteristic SSA/P histology and another region with cytologic dysplasia resembling a conventional adenoma. Recommendations for surveillance
5
ACCEPTED MANUSCRIPT
intervals for patients with SSA/P have been published, although they have not been validated.
RI PT
Take home message
A number of pathways exist that lead to the development of CRC; one of them is the serrated pathway. SSA/Ps, the CRC precursor in the serrated pathway, are most often
SC
flat and in the right colon, but can be detected, diagnosed, albeit with limitation, and removed. Thus, cancers arising from the serrated pathway can be prevented. The
M AN U
training provided here allows all readers to develop expertise in the detection and management of SSA/Ps.
Figure 1 Legend
Figure 2 Legend
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a. SSA/P with surrounding rim of debris b. Irregularly distributed dystrophic goblet cells c. SSA/P with inverted T-shaped crypts d. Proximal colon SSA/P with subtle nodular appearance of surface mucosa e. Dilated, boot shaped crypts f. Hyperplastic Polyp
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a. Endoscopic long-view of SSA/P with dysplasia. b. Corresponding pathology for SSA/P with dysplasia. Arrowhead: SSA/P with serration and basal crypt dilation. Arrow: hyperchromatic and crowded nuclei, irregular shaped glands of adenocarcinoma
6
ACCEPTED MANUSCRIPT
References: 1. Crockett SD, et al. Clin Gastroenterol Hepatol. 2015; Jan; 13(1):11-26
RI PT
2. Saito S, et al. World J Gastrointest Endosc. 2015 Jul 25;7(9):860-71
SC
3. T. Kimura, et al. Am. J. Gastroenterol. 2012 Mar;107(3):460-9
M AN U
4. Hewett DG, et al.. Gastroenterology. 2012 Sep;143(3):599-607
5. IJspeert, J. E. et al. Gut. 2016 Jun;65(6):963-70
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6. Rao, A. K. et al. Clin Gastroenterol Hepatol 2016 Apr;14(4):568-74
7. Kolb, J. M. et al. J Clin Gastroenterol. 2016 Mar;50(3):233-8
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8. Rex, D. K. et al. Am. J. Gastroenterol. 2012 Sep;107(9):1315-29
7
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