Clinical Gastroenterology and Hepatology 2015;13:1209–1212
LETTERS TO THE EDITOR Readers are encouraged to write letters to the editor concerning articles that have been published in Clinical Gastroenterology and Hepatology. Short, general comments are also considered, but use of the Letters to the Editor section for publication of original data in preliminary form is not encouraged. Letters should be typewritten and submitted electronically to http://www. editorialmanager.com/cgh.
Industry Payments to Gastroenterologists Across the United States Dear Editor: In September 2014, under the Physician Payments Sunshine Act, the Centers for Medicare and Medicaid Services released data for the months August to December 2013 detailing payments to physicians from drug and medical device companies.1,2 We reviewed all payments to gastroenterologists exceeding $100 and described the mean payments per physician for each state. The mean payment was calculated by dividing the total payments to all gastroenterologists within a state by the number of gastroenterologists practicing in that state. In total, 10,406 payments of more than $100 were made to gastroenterologists. There were significant differences in the mean payment per gastroenterologist across states, ranging from $4346 (Maine) to $0 (in 3 states) (Figure 1); the overall mean payment was $1244 per physician. The top 5 states (ME, TX, AR, WY, and KY) accounted for 33% of overall per-physician spending. As has been observed with other aspects of physician payments, these findings illustrate significant regional disparity in per-physician industry payments across the United States. Certain states appear to attract high payments, indicating that the pharmaceutical/device industry likely identifies certain states, or perhaps certain
Figure 1. Mean industry payment per gastroenterologist (in US$) for each state.
medical centers within certain states, that are strategically important in enhancing their business goals. Although this database provides a commentary on industry payment patterns during a brief window in time, it remains to be seen whether payments actually influence physician prescribing practices. GAVIN C. HAREWOOD, MD, MBA, MSC, FASGE TIMOTHY RYAN, MD SARAH LEWIS, MD Department of Gastroenterology Beaumont Hospital Beaumont, Dublin, Ireland
References 1.
OpenPaymentsData. Available at https://openpaymentsdata. cms.gov/. Accessed November 22, 2014.
2.
Feld LD, et al. Clin Gastroenterol Hepatol 2014;12:1587–1591.
Conflicts of interest The authors disclose no conflicts. http://dx.doi.org/10.1016/j.cgh.2014.12.031
Immunohistochemical Analysis of Eosinophilic Esophagitis Dear Editor: We read with great interest the recently published study by Dellon et al1 entitled “Markers of Eosinophilic Inflammation for Diagnosis of Eosinophilic Esophagitis and Proton Pump Inhibitor-Responsive Esophageal
1210 Letters to the Editor
Eosinophilia: A Prospective Study.” We have several comments regarding the immunohistochemistry methodology used in this study. There was no clear mention as to what constituted positive staining for any given marker. For example, for the inflammatory markers tryptase and major basic protein, which are expected to be found in inflammatory cells or their granules, it should be stated whether the cells located within papillary capillaries were accounted for in the analysis. By looking at the images provided in Figure 1 of the article, one can see that there is significantly more tryptase staining between the epithelial cells in the proton pump inhibitor–responsive esophageal eosinophilia than in the eosinophilic esophagitis case. In all likelihood, many of the tryptase-positive cells may be lying within the capillaries in the papillae as opposed to being interspersed between the epithelial cells. This difference is not easily appreciated using an automated digital system to score the immunohistochemistry results as chosen by the authors. Similarly, it was not stated which subcellular compartment was expected to stain for eotaxin-3. The images in Figure 1 seem to be illustrating a predominantly nuclear staining pattern. Eotaxin-3 is a chemokine and, as such, it should be present within the cytoplasm, the cell membrane, or the intercellular spaces. The staining within the nucleus is counterintuitive and an explanation of such phenomenon would have been helpful. Another point of interest was the method used to score the cases. The authors used a digital system that scored the number of positive cells/area. It is important to note that the density of positive staining cells was not the same in all cases. For example, a biopsy showing marked basal cell hyperplasia had many more cells/mm2 than one without marked basal cell hyperplasia owing to a decrease in the cytoplasmic area. A method in which the percentage of positive cells was interpreted could have provided a more reliable quantitative indication of the abundance or not of a certain marker. ANDRES MATOSO, MD MURRAY B. RESNICK, MD, PhD Department of Pathology and Laboratory Medicine Rhode Island Hospital Warren Alpert Medical School of Brown University Providence, Rhode Island
Reference 1.
Dellon ES, et al. Clin Gastroenterol Hepatol 2014;12:2015–2022.
Conflicts of interest The authors disclose no conflicts. http://dx.doi.org/10.1016/j.cgh.2014.12.024
Reply. We thank Matoso and Resnick for their interest in our recent article1 and for raising several important issues related to the immunohistochemistry methodology of our study.2 To address their points, a positively staining cell was defined as one detected at the highest threshold (strong positive) in the
Clinical Gastroenterology and Hepatology Vol. 13, No. 6
Aperio Positive Pixel Count Algorithm (version 9.1; Aperio Technologies, Vista, CA).3–5 We limited analysis to the epithelium, and when prominent papillary capillaries were present, these were excluded. However, we could not exclude all cells staining in these areas. Matoso and Resnick observe some increased intraepithelial tryptase staining in the papillae in Figure 1 in the article, and we agree that this subtle finding is not easily appreciated with the automated system. We did not perform a subanalysis of staining in these regions and cannot comment as to whether there are differences between eosinophilic esophagitis (EoE) and proton pump inhibitor–responsive esophageal eosinophilia related to this. For eotaxin-3, we did not differentiate nuclear vs cytoplasmic staining. We agree that eotaxin3 could be present in the cytoplasm or intracellularly, but we did not investigate a pathogenic explanation of the nuclear staining in this study. For our analysis, we quantified the number of cells/mm2 and did not normalize to the number of cells present on the biopsy specimen, as pointed out by Matoso and Resnick. The overall goal of our study was to validate measurement of the 3 stains as a method for EoE diagnosis. Although we acknowledge there are many nuances about staining patterns and distribution, it was not our aim to elucidate these, determine their clinical relevance, or investigate pathogenesis. Even with using relatively coarse methodology, our results show that these stains can distinguish EoE from non-EoE controls with a very high degree of accuracy. This suggests that the methods used are adequate for our purpose. We believe using an automatically quantified cell count provides clinical utility and allows this methodology to be adopted into practice. EVAN S. DELLON, MD, MPH Center for Esophageal Diseases and Swallowing and Center for Gastrointestinal Biology and Disease Division of Gastroenterology and Hepatology Department of Medicine University of North Carolina School of Medicine Chapel Hill, North Carolina
References 1.
Dellon ES, et al. Clin Gastroenterol Hepatol 2014;12:2015–2022.
2.
Matoso A, et al. Clin Gastroenterol Hepatol 2015.
3.
Dellon ES, et al. Am J Gastroenterol 2011;106:264–271.
4. 5.
Dellon ES, et al. Am J Gastroenterol 2012;107:1503–1511. Garcia-Rojo M, et al. Diagn Pathol 2014;9(Suppl 1):S7.
Conflicts of interest The authors disclose no conflicts. http://dx.doi.org/10.1016/j.cgh.2015.02.039
Study of Diabetic Gastroparesis Dear Editor: We thank Dr Pasricha for his editorial on our study of diabetic gastroparesis and its relationship with hyperglycemia.1,2 We wish to clarify 3 key issues.
LETTERS TO THE EDITOR Readers are encouraged to write letters to the editor concerning articles that have been published in Clinical Gastroenterology and Hepatology. Short, general comments are also considered, but use of the Letters to the Editor section for publication of original data in preliminary form is not encouraged. Letters should be typewritten and submitted electronically to http://www. editorialmanager.com/cgh.
Industry Payments to Gastroenterologists Across the United States Dear Editor: In September 2014, under the Physician Payments Sunshine Act, the Centers for Medicare and Medicaid Services released data for the months August to December 2013 detailing payments to physicians from drug and medical device companies.1,2 We reviewed all payments to gastroenterologists exceeding $100 and described the mean payments per physician for each state. The mean payment was calculated by dividing the total payments to all gastroenterologists within a state by the number of gastroenterologists practicing in that state. In total, 10,406 payments of more than $100 were made to gastroenterologists. There were significant differences in the mean payment per gastroenterologist across states, ranging from $4346 (Maine) to $0 (in 3 states) (Figure 1); the overall mean payment was $1244 per physician. The top 5 states (ME, TX, AR, WY, and KY) accounted for 33% of overall per-physician spending. As has been observed with other aspects of physician payments, these findings illustrate significant regional disparity in per-physician industry payments across the United States. Certain states appear to attract high payments, indicating that the pharmaceutical/device industry likely identifies certain states, or perhaps certain
Figure 1. Mean industry payment per gastroenterologist (in US$) for each state.
medical centers within certain states, that are strategically important in enhancing their business goals. Although this database provides a commentary on industry payment patterns during a brief window in time, it remains to be seen whether payments actually influence physician prescribing practices. GAVIN C. HAREWOOD, MD, MBA, MSC, FASGE TIMOTHY RYAN, MD SARAH LEWIS, MD Department of Gastroenterology Beaumont Hospital Beaumont, Dublin, Ireland
References 1.
OpenPaymentsData. Available at https://openpaymentsdata. cms.gov/. Accessed November 22, 2014.
2.
Feld LD, et al. Clin Gastroenterol Hepatol 2014;12:1587–1591.
Conflicts of interest The authors disclose no conflicts. http://dx.doi.org/10.1016/j.cgh.2014.12.031
Immunohistochemical Analysis of Eosinophilic Esophagitis Dear Editor: We read with great interest the recently published study by Dellon et al1 entitled “Markers of Eosinophilic Inflammation for Diagnosis of Eosinophilic Esophagitis and Proton Pump Inhibitor-Responsive Esophageal
1210 Letters to the Editor
Eosinophilia: A Prospective Study.” We have several comments regarding the immunohistochemistry methodology used in this study. There was no clear mention as to what constituted positive staining for any given marker. For example, for the inflammatory markers tryptase and major basic protein, which are expected to be found in inflammatory cells or their granules, it should be stated whether the cells located within papillary capillaries were accounted for in the analysis. By looking at the images provided in Figure 1 of the article, one can see that there is significantly more tryptase staining between the epithelial cells in the proton pump inhibitor–responsive esophageal eosinophilia than in the eosinophilic esophagitis case. In all likelihood, many of the tryptase-positive cells may be lying within the capillaries in the papillae as opposed to being interspersed between the epithelial cells. This difference is not easily appreciated using an automated digital system to score the immunohistochemistry results as chosen by the authors. Similarly, it was not stated which subcellular compartment was expected to stain for eotaxin-3. The images in Figure 1 seem to be illustrating a predominantly nuclear staining pattern. Eotaxin-3 is a chemokine and, as such, it should be present within the cytoplasm, the cell membrane, or the intercellular spaces. The staining within the nucleus is counterintuitive and an explanation of such phenomenon would have been helpful. Another point of interest was the method used to score the cases. The authors used a digital system that scored the number of positive cells/area. It is important to note that the density of positive staining cells was not the same in all cases. For example, a biopsy showing marked basal cell hyperplasia had many more cells/mm2 than one without marked basal cell hyperplasia owing to a decrease in the cytoplasmic area. A method in which the percentage of positive cells was interpreted could have provided a more reliable quantitative indication of the abundance or not of a certain marker. ANDRES MATOSO, MD MURRAY B. RESNICK, MD, PhD Department of Pathology and Laboratory Medicine Rhode Island Hospital Warren Alpert Medical School of Brown University Providence, Rhode Island
Reference 1.
Dellon ES, et al. Clin Gastroenterol Hepatol 2014;12:2015–2022.
Conflicts of interest The authors disclose no conflicts. http://dx.doi.org/10.1016/j.cgh.2014.12.024
Reply. We thank Matoso and Resnick for their interest in our recent article1 and for raising several important issues related to the immunohistochemistry methodology of our study.2 To address their points, a positively staining cell was defined as one detected at the highest threshold (strong positive) in the
Clinical Gastroenterology and Hepatology Vol. 13, No. 6
Aperio Positive Pixel Count Algorithm (version 9.1; Aperio Technologies, Vista, CA).3–5 We limited analysis to the epithelium, and when prominent papillary capillaries were present, these were excluded. However, we could not exclude all cells staining in these areas. Matoso and Resnick observe some increased intraepithelial tryptase staining in the papillae in Figure 1 in the article, and we agree that this subtle finding is not easily appreciated with the automated system. We did not perform a subanalysis of staining in these regions and cannot comment as to whether there are differences between eosinophilic esophagitis (EoE) and proton pump inhibitor–responsive esophageal eosinophilia related to this. For eotaxin-3, we did not differentiate nuclear vs cytoplasmic staining. We agree that eotaxin3 could be present in the cytoplasm or intracellularly, but we did not investigate a pathogenic explanation of the nuclear staining in this study. For our analysis, we quantified the number of cells/mm2 and did not normalize to the number of cells present on the biopsy specimen, as pointed out by Matoso and Resnick. The overall goal of our study was to validate measurement of the 3 stains as a method for EoE diagnosis. Although we acknowledge there are many nuances about staining patterns and distribution, it was not our aim to elucidate these, determine their clinical relevance, or investigate pathogenesis. Even with using relatively coarse methodology, our results show that these stains can distinguish EoE from non-EoE controls with a very high degree of accuracy. This suggests that the methods used are adequate for our purpose. We believe using an automatically quantified cell count provides clinical utility and allows this methodology to be adopted into practice. EVAN S. DELLON, MD, MPH Center for Esophageal Diseases and Swallowing and Center for Gastrointestinal Biology and Disease Division of Gastroenterology and Hepatology Department of Medicine University of North Carolina School of Medicine Chapel Hill, North Carolina
References 1.
Dellon ES, et al. Clin Gastroenterol Hepatol 2014;12:2015–2022.
2.
Matoso A, et al. Clin Gastroenterol Hepatol 2015.
3.
Dellon ES, et al. Am J Gastroenterol 2011;106:264–271.
4. 5.
Dellon ES, et al. Am J Gastroenterol 2012;107:1503–1511. Garcia-Rojo M, et al. Diagn Pathol 2014;9(Suppl 1):S7.
Conflicts of interest The authors disclose no conflicts. http://dx.doi.org/10.1016/j.cgh.2015.02.039
Study of Diabetic Gastroparesis Dear Editor: We thank Dr Pasricha for his editorial on our study of diabetic gastroparesis and its relationship with hyperglycemia.1,2 We wish to clarify 3 key issues.
