Letters to the Editor
nature publishing group
deficiency in Lynch syndrome-like tumors. Gastroenterology 2014;146:643–6. 1
Department of Pathology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands; 2Department of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. Correspondence: Winand N.M. Dinjens, PhD, Department of Pathology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, P.O. Box 2040, Rotterdam, CA 3000, The Netherlands, E-mail: [email protected]
Response to Dinjens et al. Francis M. Giardiello, MD1 on behalf of the US Multi-Society Task Force doi:10.1038/ajg.2014.341
To the Editor: We appreciate the comments and literature cited made by Drs Dinjens, Dubin, and Wagner (1) concerning the accuracy of MLH1 promoter hypermethylation analysis to discriminate between somatic and germline abnormalities of the MLH1 gene in colorectal cancers with loss of MLH1 and PMS2 proteins. As mentioned, the usefulness of MLH1 promoter hypermethylation testing in performing this distinction was discussed in the guidelines. Our guidelines give the reader the option of pursuing BRAF gene mutation testing or promoter hypermethylation analysis to perform this differentiation. The choice between the two strategies depends on which testing is competently and easily done in the clinician’s environment, and on the cost effectiveness of the test. While one test may be used on an individual basis, programmatic testing of all serially encountered colorectal cancers may be cost effective with the other. Increasingly, tumor panel testing for somatic mutations including BRAF is the standard of care to guide chemotherapeutic decisions and predict prognosis in those with colorectal cancer. While we cited data for a Markov model cost effectiveness analysis that recommends BRAF testing for this function, this calculation is always subject to change as the price of testing technology changes. © 2015 by the American College of Gastroenterology
In the future, ger mline testing of all colorectal cancer patients may be the most cost-effective approach to identify those with Lynch syndrome. CONFLICT OF INTEREST The author declares no conflict of interest. REFERENCE 1. Dinjens WNM, Dubbink HJ, Wagner A. Guidelines on genetic evaluation and management of Lynch syndrome. Am J Gastroenterol 2015;110:192–3 (this issue). 1
Johns Hopkins Hospital, Baltimore, Maryland, USA. Correspondence: Francis M. Giardiello, MD, Johns Hopkins Hospital, 1830 East Monument Street, Room 431, Baltimore, Maryland 21205, USA. E-mail: [email protected]
LETTER TO THE
Chromoendoscopy With Iodine Staining, as Well as Narrow-Band Imaging, Is Still Useful and Reliable for Screening of Early Esophageal Squamous Cell Carcinoma Yuichi Shimizu, MD1, Masakazu Takahashi, MD1, Takeshi Mizushima, MD1, Shouko Ono, MD2, Katsuhiro Mabe, MD2, Shunsuke Ohnishi, MD1, Mototsugu Kato, MD2, Masahiro Asaka, MD3 and Naoya Sakamoto, MD1 doi:10.1038/ajg.2014.371
To the Editor: We have read with great interest the article by Nagami et al., who evaluated the usefulness of non-magnifying narrow-band imaging (NM-NBI) in screening of early esophageal squamous cell carcinoma (SCC) (1). The authors compared NM-NBI and chromoendoscopy with iodine staining (CE-Iodine) in terms of the diagnostic performance in 202 patients with high-risk factors for esophageal SCC. They showed that the accuracy,
sensitivity, and specificity of NM-NBI were 77%, 88%, and 75%, respectively, while those for areas unstained by CE-Iodine were 68%, 94%, and 64%, respectively. The accuracy and specificity of NM-NBI were superior to those of CE-Iodine, and the authors concluded that NM-NBI was more useful and more reliable than CEIodine for the diagnosis of esophageal SCC and high-grade intraepithelial neoplasia (HGIN). However, we consider that the results of this study are inaccurate because diagnosis of unstained areas by CE-Iodine in the study did not take into account the finding of “pink color sign”. We previously reported that HGIN could be identified as more distinct and reddish iodine-unstained areas than unstained areas of low-grade intraepithelial neoplasia, inflammation, or epithelial atrophy after the brown color of iodine solution has faded (after a few minutes) because there is almost no remaining glycogencontaining epithelium in HGIN, and we named this phenomenon pink color sign (Figures 1 and 2) (2). We studied 79 patients who were found to have demarcated iodine unstained areas (121 lesions in total). Using pink color sign-positive as a diagnostic index for HGIN and SCC, sensitivity was 92% and specificity was 94% (2). As for this finding, Ishihara et al. (3) subsequently performed quantitative analysis of the color change after iodine staining for diagnosing esophageal HGIN and concluded that the pink color sign for diagnosing esophageal squamous neoplasms is accurate. The accuracy and specificity of CE-Iodine would be greatly improved by using the pink color sign. The authors described that many general hospitals usually do not have the resources to use magnifying endoscopy, and therefore non-magnifying endoscopy is frequently used for routine general screening. However, we consider that many general hospitals usually do not have the resources to use NBI, and therefore CE-iodine is frequently used for screening for patients with high-risk factors for esophageal SCC. Although CE-iodine causes discomfort for patients, we consider that CE-iodine still has a diagnostic ability that is equal to (or probably more sensitive than) that of NBI. The American Journal of GASTROENTEROLOGY
193
nature publishing group
deficiency in Lynch syndrome-like tumors. Gastroenterology 2014;146:643–6. 1
Department of Pathology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands; 2Department of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. Correspondence: Winand N.M. Dinjens, PhD, Department of Pathology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, P.O. Box 2040, Rotterdam, CA 3000, The Netherlands, E-mail: [email protected]
Response to Dinjens et al. Francis M. Giardiello, MD1 on behalf of the US Multi-Society Task Force doi:10.1038/ajg.2014.341
To the Editor: We appreciate the comments and literature cited made by Drs Dinjens, Dubin, and Wagner (1) concerning the accuracy of MLH1 promoter hypermethylation analysis to discriminate between somatic and germline abnormalities of the MLH1 gene in colorectal cancers with loss of MLH1 and PMS2 proteins. As mentioned, the usefulness of MLH1 promoter hypermethylation testing in performing this distinction was discussed in the guidelines. Our guidelines give the reader the option of pursuing BRAF gene mutation testing or promoter hypermethylation analysis to perform this differentiation. The choice between the two strategies depends on which testing is competently and easily done in the clinician’s environment, and on the cost effectiveness of the test. While one test may be used on an individual basis, programmatic testing of all serially encountered colorectal cancers may be cost effective with the other. Increasingly, tumor panel testing for somatic mutations including BRAF is the standard of care to guide chemotherapeutic decisions and predict prognosis in those with colorectal cancer. While we cited data for a Markov model cost effectiveness analysis that recommends BRAF testing for this function, this calculation is always subject to change as the price of testing technology changes. © 2015 by the American College of Gastroenterology
In the future, ger mline testing of all colorectal cancer patients may be the most cost-effective approach to identify those with Lynch syndrome. CONFLICT OF INTEREST The author declares no conflict of interest. REFERENCE 1. Dinjens WNM, Dubbink HJ, Wagner A. Guidelines on genetic evaluation and management of Lynch syndrome. Am J Gastroenterol 2015;110:192–3 (this issue). 1
Johns Hopkins Hospital, Baltimore, Maryland, USA. Correspondence: Francis M. Giardiello, MD, Johns Hopkins Hospital, 1830 East Monument Street, Room 431, Baltimore, Maryland 21205, USA. E-mail: [email protected]
LETTER TO THE
Chromoendoscopy With Iodine Staining, as Well as Narrow-Band Imaging, Is Still Useful and Reliable for Screening of Early Esophageal Squamous Cell Carcinoma Yuichi Shimizu, MD1, Masakazu Takahashi, MD1, Takeshi Mizushima, MD1, Shouko Ono, MD2, Katsuhiro Mabe, MD2, Shunsuke Ohnishi, MD1, Mototsugu Kato, MD2, Masahiro Asaka, MD3 and Naoya Sakamoto, MD1 doi:10.1038/ajg.2014.371
To the Editor: We have read with great interest the article by Nagami et al., who evaluated the usefulness of non-magnifying narrow-band imaging (NM-NBI) in screening of early esophageal squamous cell carcinoma (SCC) (1). The authors compared NM-NBI and chromoendoscopy with iodine staining (CE-Iodine) in terms of the diagnostic performance in 202 patients with high-risk factors for esophageal SCC. They showed that the accuracy,
sensitivity, and specificity of NM-NBI were 77%, 88%, and 75%, respectively, while those for areas unstained by CE-Iodine were 68%, 94%, and 64%, respectively. The accuracy and specificity of NM-NBI were superior to those of CE-Iodine, and the authors concluded that NM-NBI was more useful and more reliable than CEIodine for the diagnosis of esophageal SCC and high-grade intraepithelial neoplasia (HGIN). However, we consider that the results of this study are inaccurate because diagnosis of unstained areas by CE-Iodine in the study did not take into account the finding of “pink color sign”. We previously reported that HGIN could be identified as more distinct and reddish iodine-unstained areas than unstained areas of low-grade intraepithelial neoplasia, inflammation, or epithelial atrophy after the brown color of iodine solution has faded (after a few minutes) because there is almost no remaining glycogencontaining epithelium in HGIN, and we named this phenomenon pink color sign (Figures 1 and 2) (2). We studied 79 patients who were found to have demarcated iodine unstained areas (121 lesions in total). Using pink color sign-positive as a diagnostic index for HGIN and SCC, sensitivity was 92% and specificity was 94% (2). As for this finding, Ishihara et al. (3) subsequently performed quantitative analysis of the color change after iodine staining for diagnosing esophageal HGIN and concluded that the pink color sign for diagnosing esophageal squamous neoplasms is accurate. The accuracy and specificity of CE-Iodine would be greatly improved by using the pink color sign. The authors described that many general hospitals usually do not have the resources to use magnifying endoscopy, and therefore non-magnifying endoscopy is frequently used for routine general screening. However, we consider that many general hospitals usually do not have the resources to use NBI, and therefore CE-iodine is frequently used for screening for patients with high-risk factors for esophageal SCC. Although CE-iodine causes discomfort for patients, we consider that CE-iodine still has a diagnostic ability that is equal to (or probably more sensitive than) that of NBI. The American Journal of GASTROENTEROLOGY
193
