correspondence
Figure 1 (facing page). Docking Conformations of Crizotinib and Ceritinib with Nonmutant and Mutant CD74–ROS1. In a simulation of the molecular docking of crizotinib (Panel A) and ceritinib (Panel B) with nonmutant and mutant CD74–ROS1, the steric effect of gatekeeper residue R2032 causes the conformation of crizotinib to become twisted in the G2032R mutant as compared with its counterpart in nonmutant ROS1; this change in conformation weakens the binding of the drug with its target and confers drug resistance. In comparison, when ceritinib interacts with the G2032R mutant, it maintains a conformation that is similar to the conformation seen when it interacts with nonmutant CD74– ROS1, which suggests that the effect of the G2032R mutation on the binding of this compound is negligible. The gatekeeper residues L2026 and G2032, shown in the binding pocket of CD74–ROS1, contribute to the docking conformations of crizotinib and ceritinib. The structure for CD74–ROS1 is adapted from that provided in the Protein Data Bank, entry 3ZBF.
interference with crizotinib binding.3 We speculate that this arginine would also clash sterically with ceritinib, preventing effective binding and inhibition of the kinase. Consistent with this notion, the analogous mutation in ALK (G1202R) causes resistance to ceritinib,4 and in cell-based assays performed in our laboratory, ceritinib is 5 to 10 times less active against ROS1 G2032R than against nonmutant ROS1. Thus, although ceritinib could have activity in ROS1-rearranged NSCLC, we believe that its efficacy would be impaired by the ROS1 G2032R mutation. Alice T. Shaw, M.D., Ph.D. Jeffrey A. Engelman, M.D., Ph.D. Massachusetts General Hospital Boston, MA [email protected] Since publication of their article, the authors report no further potential conflict of interest. 1. Marsilje TH, Pei W, Chen B, et al. Synthesis, structure-activity
tyrosine kinase related to ALK. In fact, previous work established that ceritinib targets both ALK and ROS1 at clinically relevant concentrations, although ceritinib has more potency against ALK.1,2 In ROS1-rearranged NSCLC, resistance to crizotinib may develop owing to the acquisition of a secondary mutation, such as ROS1 G2032R.3 On the basis of the crystal structure of the nonmutant ROS1 kinase domain bound to crizotinib, the substitution of glycine with the bulkier arginine at position 2032 is predicted to cause steric
relationships, and in vivo efficacy of the novel potent and selective anaplastic lymphoma kinase (ALK) inhibitor 5-chloro-N2-(2isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropyl sulfonyl)phenyl)pyrimidine-2,4-diamine (LDK378) currently in phase 1 and phase 2 clinical trials. J Med Chem 2013;56:567590. 2. Zykadia (package insert). East Hanover, NJ: Novartis Pharmaceuticals, 2014. 3. Awad MM, Katayama R, McTigue M, et al. Acquired resistance to crizotinib from a mutation in CD74–ROS1. N Engl J Med 2013; 368:2395-401. 4. Friboulet L, Li N, Katayama R, et al. The ALK inhibitor ceritinib overcomes crizotinib resistance in non-small cell lung cancer. Cancer Discov 2014 March 27 (Epub ahead of print). DOI: 10.1056/NEJMc1404894
Adenoma Detection Rate and Risk of Colorectal Cancer and Death To the Editor: The study by Corley and colleagues (April 3 issue)1 of the association between the adenoma detection rate of colonoscopists and the development of interval colorectal cancer has some noteworthy limitations. First, the central conclusion that the “risk of interval cancer decreased approximately linearly with increasing adenoma detection rates, without evidence of a threshold effect within the observed range of rates” was not supported by the study findings. The risk of interval cancer was in fact fairly uniform across the first three adenoma de-
tection rate quintiles, even though the corresponding quintile subgroups included 11 times as many events as in the entire study by Kaminski et al.,2 and only became significantly lower than the risk in the lowest quintile above a threshold of 28.4%. Indeed, a plot of the adjusted regression coefficients for interval colorectal cancer against the corresponding rate-quintile midpoints was consistent with a nonlinear association, with the numeric difference between the coefficients for the highest two quintiles being more than four times as high as that for the low-
n engl j med 370;26 nejm.org june 26, 2014
The New England Journal of Medicine Downloaded from nejm.org on March 4, 2015. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
2539
The
n e w e ng l a n d j o u r na l
Adjusted Regression Coefficient
m e dic i n e
into enhanced prevention of interval cancer should be tempered with the inherent susceptibility of this quality measure to “gaming,” as attested to by the wide disparities in the number of detected adenomas by colonoscopists with identical adenoma detection rates.5 Muhammad F. Dawwas, M.B., Ch.B.
0.0
−0.2
−0.4
−0.6
−0.8 0
10
20
30
40
50
Quintile Midpoint (%)
Figure 1. Adjusted Regression Coefficient for Interval Colorectal Cancer, According to the Quintile Midpoints of the Adenoma Detection Rates. Values of the adjusted regression coefficients for interval colorectal cancer were generated from the results of the multilevel Cox regression analysis (with adjustment for patient sex, age, Charlson comorbidity index score, and indication for colonoscopy with clustering according to physician), provided by Corley and colleagues.1 Midpoints of the adenoma detection rate quintiles were calculated from the quintile-range data in the article.
est two quintiles (Fig. 1). The use of fractional polynomials3 to analyze the data would have been worthwhile. Second, there is growing evidence that the adenoma detection rate has improved significantly during the study period,4,5 probably as a result of greater recognition of the high miss rate of colonoscopy for right-sided lesions, enhanced scope technology, superior bowel-preparation regimens, and rising compliance with professional societal guidelines. Thus, the fact that the analysis did not take into account the calendar period during which the procedure was undertaken makes it plausible that time-trend confounding resulting from the clustering of procedures with low adenoma yield in the earlier years of the study has potentially rendered the findings less relevant to current practice. Moreover, the lack of adjustment in the risk model for widely used colonoscopy-quality benchmarks with established correlation with the adenoma detection rate, such as cecal intubation rate and quality of bowel preparation,6 is a further limitation of the analysis. Third, the authors’ suggestion that increasing the adenoma detection rate is likely to translate 2540
of
University of Cambridge Cambridge, United Kingdom [email protected] No potential conflict of interest relevant to this letter was reported. 1. Corley DA, Jensen CD, Marks AR, et al. Adenoma detection
rate and risk of colorectal cancer and death. N Engl J Med 2014; 370:1298-306. 2. Kaminski MF, Regula J, Kraszewska E, et al. Quality indicators for colonoscopy and the risk of interval cancer. N Engl J Med 2010;362:1795-803. 3. Royston P, Sauerbrei W. Multivariable model-building: a pragmatic approach to regression analysis based on fractional polynomials for modelling continuous variables. Chichester, United Kingdom: John Wiley, 2008. 4. Gavin DR, Valori RM, Anderson JT, Donnelly MT, Williams JG, Swarbrick ET. The national colonoscopy audit: a nationwide assessment of the quality and safety of colonoscopy in the UK. Gut 2013;62:242-9. [Erratum, Gut 2013;62:249.] 5. Denis B, Sauleau EA, Gendre I, et al. The mean number of adenomas per procedure should become the gold standard to measure the neoplasia yield of colonoscopy: a population-based cohort study. Dig Liver Dis 2014;46:176-81. 6. Lee TJ, Rees CJ, Blanks RG, et al. Colonoscopic factors associated with adenoma detection in a national colorectal cancer screening program. Endoscopy 2014;46:203-11. DOI: 10.1056/NEJMc1405329
To the Editor: In the study by Corley et al., the overall incidence of interval colorectal cancer reached 7.7 cases per 10,000 person-years, whereas in two large studies, the incidences were 17 cases per 10,000 person-years1 and 18 cases per 10,000 colonoscopies per year.2 This discrepancy might be due to a higher adenoma detection rate found by Corley et al. (25.7%), as compared with others (14 to 19.4%).3,4 In addition, the cumulative hazard rates for interval colorectal cancer varied from 33.6 cases per 100,000 person-years when the adenoma detection rate was below 11%, to 2.4 cases per 100,000 person-years when the rate was more than 20%,3 and reached 4.8 cases per 10,000 person-years when the adenoma detection rate was 33.51% or more in the study by Corley et al. Among the colonoscopy-quality criteria, the adenoma detection rate mainly refers to the skills of the endoscopist, whereas other criteria (cecal intubation rate, quality of bowel preparation, and colonoscopy withdrawal >6 minutes) pertain to other aspects of the procedure. Focus-
n engl j med 370;26 nejm.org june 26, 2014
The New England Journal of Medicine Downloaded from nejm.org on March 4, 2015. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
correspondence
ing on the adenoma detection rate precludes the evaluation of the overall quality of the procedure. Therefore, it would be of interest to evaluate in this study other colonoscopy-quality criteria to confirm, as suggested by others,3 that the adenoma detection rate could become the sole quality indicator for colonoscopy. Maximilien Barret, M.D. Stanislas Chaussade, M.D., Ph.D. Romain Coriat, M.D., Ph.D. Université Paris Descartes Paris, France [email protected] No potential conflict of interest relevant to this letter was reported. 1. Robertson DJ, Lieberman DA, Winawer SJ, et al. Colorectal
cancers soon after colonoscopy: a pooled multicohort analysis. Gut 2014;63:649-56. 2. le Clercq CM, Bouwens MW, Rondagh EJ, et al. Postcolonoscopy colorectal cancers are preventable: a population-based study. Gut 2014;63:957-63. 3. Kaminski MF, Regula J, Kraszewska E, et al. Quality indicators for colonoscopy and the risk of interval cancer. N Engl J Med 2010;362:1795-803. 4. Pox CP, Altenhofen L, Brenner H, et al. Efficacy of a nationwide screening colonoscopy program for colorectal cancer. Gastroenterology 2012;142(7):1460.e2-1467.e2. DOI: 10.1056/NEJMc1405329
took place over a relatively short time interval (1998–2010), Kaiser Permanente has low physician turnover, and modern video equipment was used in all examinations. The high variability in rates throughout all the years of the study (data not shown) also suggests that temporal changes alone are unlikely to explain the differences found. Barret and colleagues suggest that the low rates of interval cancer we found may be due to the high adenoma detection rates observed within Kaiser Permanente. Although that is possible, the rates are not directly comparable between studies with different patient populations and different follow-up; two prior large population-based studies, for example, concentrated only on interval cancers that developed during the first few years after a colonoscopy.1,2 We concur that there may be other useful measures of colonoscopy quality besides the adenoma detection rate. In our article, we focused on a single metric associated with the performance of the endoscopist, although other factors, such as bowel preparation, certainly deserve attention. Finally, although any quality measure is imperfect, we would suggest that the adenoma detection rate, which uses an independent observer (the pathologist), is less susceptible to “gaming” than some other metrics, such as the withdrawal time, which may be modified without substantially affecting the detection of neoplasia.3,4 Douglas A. Corley, M.D., Ph.D. Theodore R. Levin, M.D.
The Authors Reply: We concur that the association between adenoma detection rates and intervalcancer risk is not perfectly linear; however, the relatively wide confidence intervals preclude precise comparisons between adjacent quintiles. We believe that the statement that the overall relationship is approximately linear is supported by Kaiser Permanente the data. We hope that future studies will pro- Oakland, CA vide better precision regarding the exact func- [email protected] Chyke A. Doubeni, M.D., M.P.H. tional form. of Pennsylvania Factors such as improved bowel preparations University Philadelphia, PA and scope technology may enhance detection Since publication of their article, the authors report no furrates, but these changes will probably affect all ther potential conflict of interest. patients, rather than differentially influence de- 1. Cooper GS, Xu F, Barnholtz Sloan JS, Schluchter MD, Kotection rates among physicians at any point in roukian SM. Prevalence and predictors of interval colorectal time. In addition, audits in our study population cancers in Medicare beneficiaries. Cancer 2012;118:3044-52. 2. Baxter NN, Sutradhar R, Forbes SS, Paszat LF, Saskin R, of 300 randomly selected colonoscopy reports Rabeneck L. Analysis of administrative data finds endoscopist have shown cecal intubation rates of 98% and quality measures associated with postcolonoscopy colorectal adequate-to-excellent bowel-preparation quality cancer. Gastroenterology 2011;140:65-72. 3. Sawhney MS, Cury MS, Neeman N, et al. Effect of institutionin 92%. Thus, these measures are unlikely to wide policy of colonoscopy withdrawal time > or = 7 minutes on explain the described variability and associations. polyp detection. Gastroenterology 2008;135:1892-8. We cannot exclude some temporal effects from 4. Lin OS, Kozarek RA, Arai A, et al. The effect of periodic monitoring and feedback on screening colonoscopy withdrawal comparing physicians who were in practice ear- times, polyp detection rates, and patient satisfaction scores. lier versus later in the time interval (and their Gastrointest Endosc 2010;71:1253-9. clustered patients). However, the colonoscopies DOI: 10.1056/NEJMc1405329
n engl j med 370;26 nejm.org june 26, 2014
The New England Journal of Medicine Downloaded from nejm.org on March 4, 2015. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
2541
Figure 1 (facing page). Docking Conformations of Crizotinib and Ceritinib with Nonmutant and Mutant CD74–ROS1. In a simulation of the molecular docking of crizotinib (Panel A) and ceritinib (Panel B) with nonmutant and mutant CD74–ROS1, the steric effect of gatekeeper residue R2032 causes the conformation of crizotinib to become twisted in the G2032R mutant as compared with its counterpart in nonmutant ROS1; this change in conformation weakens the binding of the drug with its target and confers drug resistance. In comparison, when ceritinib interacts with the G2032R mutant, it maintains a conformation that is similar to the conformation seen when it interacts with nonmutant CD74– ROS1, which suggests that the effect of the G2032R mutation on the binding of this compound is negligible. The gatekeeper residues L2026 and G2032, shown in the binding pocket of CD74–ROS1, contribute to the docking conformations of crizotinib and ceritinib. The structure for CD74–ROS1 is adapted from that provided in the Protein Data Bank, entry 3ZBF.
interference with crizotinib binding.3 We speculate that this arginine would also clash sterically with ceritinib, preventing effective binding and inhibition of the kinase. Consistent with this notion, the analogous mutation in ALK (G1202R) causes resistance to ceritinib,4 and in cell-based assays performed in our laboratory, ceritinib is 5 to 10 times less active against ROS1 G2032R than against nonmutant ROS1. Thus, although ceritinib could have activity in ROS1-rearranged NSCLC, we believe that its efficacy would be impaired by the ROS1 G2032R mutation. Alice T. Shaw, M.D., Ph.D. Jeffrey A. Engelman, M.D., Ph.D. Massachusetts General Hospital Boston, MA [email protected] Since publication of their article, the authors report no further potential conflict of interest. 1. Marsilje TH, Pei W, Chen B, et al. Synthesis, structure-activity
tyrosine kinase related to ALK. In fact, previous work established that ceritinib targets both ALK and ROS1 at clinically relevant concentrations, although ceritinib has more potency against ALK.1,2 In ROS1-rearranged NSCLC, resistance to crizotinib may develop owing to the acquisition of a secondary mutation, such as ROS1 G2032R.3 On the basis of the crystal structure of the nonmutant ROS1 kinase domain bound to crizotinib, the substitution of glycine with the bulkier arginine at position 2032 is predicted to cause steric
relationships, and in vivo efficacy of the novel potent and selective anaplastic lymphoma kinase (ALK) inhibitor 5-chloro-N2-(2isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropyl sulfonyl)phenyl)pyrimidine-2,4-diamine (LDK378) currently in phase 1 and phase 2 clinical trials. J Med Chem 2013;56:567590. 2. Zykadia (package insert). East Hanover, NJ: Novartis Pharmaceuticals, 2014. 3. Awad MM, Katayama R, McTigue M, et al. Acquired resistance to crizotinib from a mutation in CD74–ROS1. N Engl J Med 2013; 368:2395-401. 4. Friboulet L, Li N, Katayama R, et al. The ALK inhibitor ceritinib overcomes crizotinib resistance in non-small cell lung cancer. Cancer Discov 2014 March 27 (Epub ahead of print). DOI: 10.1056/NEJMc1404894
Adenoma Detection Rate and Risk of Colorectal Cancer and Death To the Editor: The study by Corley and colleagues (April 3 issue)1 of the association between the adenoma detection rate of colonoscopists and the development of interval colorectal cancer has some noteworthy limitations. First, the central conclusion that the “risk of interval cancer decreased approximately linearly with increasing adenoma detection rates, without evidence of a threshold effect within the observed range of rates” was not supported by the study findings. The risk of interval cancer was in fact fairly uniform across the first three adenoma de-
tection rate quintiles, even though the corresponding quintile subgroups included 11 times as many events as in the entire study by Kaminski et al.,2 and only became significantly lower than the risk in the lowest quintile above a threshold of 28.4%. Indeed, a plot of the adjusted regression coefficients for interval colorectal cancer against the corresponding rate-quintile midpoints was consistent with a nonlinear association, with the numeric difference between the coefficients for the highest two quintiles being more than four times as high as that for the low-
n engl j med 370;26 nejm.org june 26, 2014
The New England Journal of Medicine Downloaded from nejm.org on March 4, 2015. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
2539
The
n e w e ng l a n d j o u r na l
Adjusted Regression Coefficient
m e dic i n e
into enhanced prevention of interval cancer should be tempered with the inherent susceptibility of this quality measure to “gaming,” as attested to by the wide disparities in the number of detected adenomas by colonoscopists with identical adenoma detection rates.5 Muhammad F. Dawwas, M.B., Ch.B.
0.0
−0.2
−0.4
−0.6
−0.8 0
10
20
30
40
50
Quintile Midpoint (%)
Figure 1. Adjusted Regression Coefficient for Interval Colorectal Cancer, According to the Quintile Midpoints of the Adenoma Detection Rates. Values of the adjusted regression coefficients for interval colorectal cancer were generated from the results of the multilevel Cox regression analysis (with adjustment for patient sex, age, Charlson comorbidity index score, and indication for colonoscopy with clustering according to physician), provided by Corley and colleagues.1 Midpoints of the adenoma detection rate quintiles were calculated from the quintile-range data in the article.
est two quintiles (Fig. 1). The use of fractional polynomials3 to analyze the data would have been worthwhile. Second, there is growing evidence that the adenoma detection rate has improved significantly during the study period,4,5 probably as a result of greater recognition of the high miss rate of colonoscopy for right-sided lesions, enhanced scope technology, superior bowel-preparation regimens, and rising compliance with professional societal guidelines. Thus, the fact that the analysis did not take into account the calendar period during which the procedure was undertaken makes it plausible that time-trend confounding resulting from the clustering of procedures with low adenoma yield in the earlier years of the study has potentially rendered the findings less relevant to current practice. Moreover, the lack of adjustment in the risk model for widely used colonoscopy-quality benchmarks with established correlation with the adenoma detection rate, such as cecal intubation rate and quality of bowel preparation,6 is a further limitation of the analysis. Third, the authors’ suggestion that increasing the adenoma detection rate is likely to translate 2540
of
University of Cambridge Cambridge, United Kingdom [email protected] No potential conflict of interest relevant to this letter was reported. 1. Corley DA, Jensen CD, Marks AR, et al. Adenoma detection
rate and risk of colorectal cancer and death. N Engl J Med 2014; 370:1298-306. 2. Kaminski MF, Regula J, Kraszewska E, et al. Quality indicators for colonoscopy and the risk of interval cancer. N Engl J Med 2010;362:1795-803. 3. Royston P, Sauerbrei W. Multivariable model-building: a pragmatic approach to regression analysis based on fractional polynomials for modelling continuous variables. Chichester, United Kingdom: John Wiley, 2008. 4. Gavin DR, Valori RM, Anderson JT, Donnelly MT, Williams JG, Swarbrick ET. The national colonoscopy audit: a nationwide assessment of the quality and safety of colonoscopy in the UK. Gut 2013;62:242-9. [Erratum, Gut 2013;62:249.] 5. Denis B, Sauleau EA, Gendre I, et al. The mean number of adenomas per procedure should become the gold standard to measure the neoplasia yield of colonoscopy: a population-based cohort study. Dig Liver Dis 2014;46:176-81. 6. Lee TJ, Rees CJ, Blanks RG, et al. Colonoscopic factors associated with adenoma detection in a national colorectal cancer screening program. Endoscopy 2014;46:203-11. DOI: 10.1056/NEJMc1405329
To the Editor: In the study by Corley et al., the overall incidence of interval colorectal cancer reached 7.7 cases per 10,000 person-years, whereas in two large studies, the incidences were 17 cases per 10,000 person-years1 and 18 cases per 10,000 colonoscopies per year.2 This discrepancy might be due to a higher adenoma detection rate found by Corley et al. (25.7%), as compared with others (14 to 19.4%).3,4 In addition, the cumulative hazard rates for interval colorectal cancer varied from 33.6 cases per 100,000 person-years when the adenoma detection rate was below 11%, to 2.4 cases per 100,000 person-years when the rate was more than 20%,3 and reached 4.8 cases per 10,000 person-years when the adenoma detection rate was 33.51% or more in the study by Corley et al. Among the colonoscopy-quality criteria, the adenoma detection rate mainly refers to the skills of the endoscopist, whereas other criteria (cecal intubation rate, quality of bowel preparation, and colonoscopy withdrawal >6 minutes) pertain to other aspects of the procedure. Focus-
n engl j med 370;26 nejm.org june 26, 2014
The New England Journal of Medicine Downloaded from nejm.org on March 4, 2015. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
correspondence
ing on the adenoma detection rate precludes the evaluation of the overall quality of the procedure. Therefore, it would be of interest to evaluate in this study other colonoscopy-quality criteria to confirm, as suggested by others,3 that the adenoma detection rate could become the sole quality indicator for colonoscopy. Maximilien Barret, M.D. Stanislas Chaussade, M.D., Ph.D. Romain Coriat, M.D., Ph.D. Université Paris Descartes Paris, France [email protected] No potential conflict of interest relevant to this letter was reported. 1. Robertson DJ, Lieberman DA, Winawer SJ, et al. Colorectal
cancers soon after colonoscopy: a pooled multicohort analysis. Gut 2014;63:649-56. 2. le Clercq CM, Bouwens MW, Rondagh EJ, et al. Postcolonoscopy colorectal cancers are preventable: a population-based study. Gut 2014;63:957-63. 3. Kaminski MF, Regula J, Kraszewska E, et al. Quality indicators for colonoscopy and the risk of interval cancer. N Engl J Med 2010;362:1795-803. 4. Pox CP, Altenhofen L, Brenner H, et al. Efficacy of a nationwide screening colonoscopy program for colorectal cancer. Gastroenterology 2012;142(7):1460.e2-1467.e2. DOI: 10.1056/NEJMc1405329
took place over a relatively short time interval (1998–2010), Kaiser Permanente has low physician turnover, and modern video equipment was used in all examinations. The high variability in rates throughout all the years of the study (data not shown) also suggests that temporal changes alone are unlikely to explain the differences found. Barret and colleagues suggest that the low rates of interval cancer we found may be due to the high adenoma detection rates observed within Kaiser Permanente. Although that is possible, the rates are not directly comparable between studies with different patient populations and different follow-up; two prior large population-based studies, for example, concentrated only on interval cancers that developed during the first few years after a colonoscopy.1,2 We concur that there may be other useful measures of colonoscopy quality besides the adenoma detection rate. In our article, we focused on a single metric associated with the performance of the endoscopist, although other factors, such as bowel preparation, certainly deserve attention. Finally, although any quality measure is imperfect, we would suggest that the adenoma detection rate, which uses an independent observer (the pathologist), is less susceptible to “gaming” than some other metrics, such as the withdrawal time, which may be modified without substantially affecting the detection of neoplasia.3,4 Douglas A. Corley, M.D., Ph.D. Theodore R. Levin, M.D.
The Authors Reply: We concur that the association between adenoma detection rates and intervalcancer risk is not perfectly linear; however, the relatively wide confidence intervals preclude precise comparisons between adjacent quintiles. We believe that the statement that the overall relationship is approximately linear is supported by Kaiser Permanente the data. We hope that future studies will pro- Oakland, CA vide better precision regarding the exact func- [email protected] Chyke A. Doubeni, M.D., M.P.H. tional form. of Pennsylvania Factors such as improved bowel preparations University Philadelphia, PA and scope technology may enhance detection Since publication of their article, the authors report no furrates, but these changes will probably affect all ther potential conflict of interest. patients, rather than differentially influence de- 1. Cooper GS, Xu F, Barnholtz Sloan JS, Schluchter MD, Kotection rates among physicians at any point in roukian SM. Prevalence and predictors of interval colorectal time. In addition, audits in our study population cancers in Medicare beneficiaries. Cancer 2012;118:3044-52. 2. Baxter NN, Sutradhar R, Forbes SS, Paszat LF, Saskin R, of 300 randomly selected colonoscopy reports Rabeneck L. Analysis of administrative data finds endoscopist have shown cecal intubation rates of 98% and quality measures associated with postcolonoscopy colorectal adequate-to-excellent bowel-preparation quality cancer. Gastroenterology 2011;140:65-72. 3. Sawhney MS, Cury MS, Neeman N, et al. Effect of institutionin 92%. Thus, these measures are unlikely to wide policy of colonoscopy withdrawal time > or = 7 minutes on explain the described variability and associations. polyp detection. Gastroenterology 2008;135:1892-8. We cannot exclude some temporal effects from 4. Lin OS, Kozarek RA, Arai A, et al. The effect of periodic monitoring and feedback on screening colonoscopy withdrawal comparing physicians who were in practice ear- times, polyp detection rates, and patient satisfaction scores. lier versus later in the time interval (and their Gastrointest Endosc 2010;71:1253-9. clustered patients). However, the colonoscopies DOI: 10.1056/NEJMc1405329
n engl j med 370;26 nejm.org june 26, 2014
The New England Journal of Medicine Downloaded from nejm.org on March 4, 2015. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
2541
