The
n e w e ng l a n d j o u r na l
conditions (Charlson comorbidity index and the Framingham Stroke Risk Profile) in all regression models. Pratik P. Pandharipande, M.D., M.S.C.I. Timothy D. Girard, M.D., M.S.C.I. E. Wesley Ely, M.D., M.P.H. Vanderbilt University Medical Center Nashville, TN [email protected]
of
m e dic i n e
Since publication of their article, the authors report no further potential conflict of interest. 1. Haenggi M, Blum S, Brechbuehl R, Brunello A, Jakob SM,
Takala J. Effect of sedation level on the prevalence of delirium when assessed with CAM-ICU and ICDSC. Intensive Care Med 2013;39:2171-9. 2. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington, VA: American Psychiatric Association, 2013. 3. Ely EW, Shintani A, Truman B, et al. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA 2004;291:1753-62. DOI: 10.1056/NEJMc1313886
Pancreatic Atrophy from Sorafenib To the Editor: Before concluding that sorafenib can cause diarrhea owing to pancreatic atrophy, clinicians need to know what sorafenib does to pancreatic secretion. Hescot et al. (Oct. 10 issue)1 mention that the level of steatorrhea in one patient was 7.5 g per 24 hours — a trivial level of pancreatic steatorrhea. They also note that the patient’s fecal elastase level was twice the upper limit of the normal range. These findings do not support a diagnosis of pancreatic exocrine insufficiency, since the fecal elastase level should be decreased, not increased. Finally, the traditional view is that 90% or more of pancreatic lipase secretion must be lost before symptomatic steatorrhea occurs.2 Clinicians need to know that the 20% and 35% decreases in the volume of the pancreas on volumetric computed tomography in the patients described by Hescot et al. actually represent a clinically significant loss of pancreatic lipase secretion. Stephen Sullivan, M.D. University of Victoria Victoria, BC, Canada [email protected] No potential conflict of interest relevant to this letter was reported. 1. Hescot S, Vignaux O, Goldwasser F. Pancreatic atrophy — a
new late toxic effect of sorafenib. N Engl J Med 2013;369:1475-6.
The Authors Reply: From our point of view, as mentioned in the title of our letter (“Pancreatic Atrophy — A New Late Toxic Effect of Sorafenib”), the take-home message to our colleagues is that sorafenib may induce pancreatic atrophy and not exclusively thyroid atrophy. With regard to pancreatic function, our patients did not receive sorafenib long enough after the emergence of symptoms of exocrine dysfunction for us to observe irreversible toxicity. We interrupted the treatment with sorafenib as soon as pancreatic atrophy was documented. After the interruption of treatment, the clinical symptoms, steatorrhea, and their biologic correlates resolved within 2 weeks; this confirms that pancreatic atrophy remained associated with residual active pancreatic parenchyma and that the pancreatic exocrine dysfunction was probably induced by sorafenib. Ségolène Hescot, M.D. Olivier Vignaux, M.D. François Goldwasser, M.D., Ph.D. Université Paris Descartes Paris, France [email protected]
2. DiMagno EP, Go VLW, Summerskill WHJ. Relations between
Since publication of their letter, the authors report no further potential conflict of interest.
DOI: 10.1056/NEJMc1313753
DOI: 10.1056/NEJMc1313753
pancreatic enzyme outputs and malabsorption in severe pancreatic insufficiency. N Engl J Med 1973;288:813-5.
Meta-Analysis and the Surgeon General’s Report on Smoking and Health To the Editor: Fifty years ago, on January 11, Luther L. Terry. That report made substantial use 1964, the landmark report on smoking and of a meta-analysis performed by statistician Wilhealth1 was made public by U.S. Surgeon General liam G. Cochran,2,3 who was a professor of sta186
n engl j med 370;2 nejm.org january 9, 2014
The New England Journal of Medicine Downloaded from nejm.org on April 26, 2015. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
n e w e ng l a n d j o u r na l
conditions (Charlson comorbidity index and the Framingham Stroke Risk Profile) in all regression models. Pratik P. Pandharipande, M.D., M.S.C.I. Timothy D. Girard, M.D., M.S.C.I. E. Wesley Ely, M.D., M.P.H. Vanderbilt University Medical Center Nashville, TN [email protected]
of
m e dic i n e
Since publication of their article, the authors report no further potential conflict of interest. 1. Haenggi M, Blum S, Brechbuehl R, Brunello A, Jakob SM,
Takala J. Effect of sedation level on the prevalence of delirium when assessed with CAM-ICU and ICDSC. Intensive Care Med 2013;39:2171-9. 2. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington, VA: American Psychiatric Association, 2013. 3. Ely EW, Shintani A, Truman B, et al. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA 2004;291:1753-62. DOI: 10.1056/NEJMc1313886
Pancreatic Atrophy from Sorafenib To the Editor: Before concluding that sorafenib can cause diarrhea owing to pancreatic atrophy, clinicians need to know what sorafenib does to pancreatic secretion. Hescot et al. (Oct. 10 issue)1 mention that the level of steatorrhea in one patient was 7.5 g per 24 hours — a trivial level of pancreatic steatorrhea. They also note that the patient’s fecal elastase level was twice the upper limit of the normal range. These findings do not support a diagnosis of pancreatic exocrine insufficiency, since the fecal elastase level should be decreased, not increased. Finally, the traditional view is that 90% or more of pancreatic lipase secretion must be lost before symptomatic steatorrhea occurs.2 Clinicians need to know that the 20% and 35% decreases in the volume of the pancreas on volumetric computed tomography in the patients described by Hescot et al. actually represent a clinically significant loss of pancreatic lipase secretion. Stephen Sullivan, M.D. University of Victoria Victoria, BC, Canada [email protected] No potential conflict of interest relevant to this letter was reported. 1. Hescot S, Vignaux O, Goldwasser F. Pancreatic atrophy — a
new late toxic effect of sorafenib. N Engl J Med 2013;369:1475-6.
The Authors Reply: From our point of view, as mentioned in the title of our letter (“Pancreatic Atrophy — A New Late Toxic Effect of Sorafenib”), the take-home message to our colleagues is that sorafenib may induce pancreatic atrophy and not exclusively thyroid atrophy. With regard to pancreatic function, our patients did not receive sorafenib long enough after the emergence of symptoms of exocrine dysfunction for us to observe irreversible toxicity. We interrupted the treatment with sorafenib as soon as pancreatic atrophy was documented. After the interruption of treatment, the clinical symptoms, steatorrhea, and their biologic correlates resolved within 2 weeks; this confirms that pancreatic atrophy remained associated with residual active pancreatic parenchyma and that the pancreatic exocrine dysfunction was probably induced by sorafenib. Ségolène Hescot, M.D. Olivier Vignaux, M.D. François Goldwasser, M.D., Ph.D. Université Paris Descartes Paris, France [email protected]
2. DiMagno EP, Go VLW, Summerskill WHJ. Relations between
Since publication of their letter, the authors report no further potential conflict of interest.
DOI: 10.1056/NEJMc1313753
DOI: 10.1056/NEJMc1313753
pancreatic enzyme outputs and malabsorption in severe pancreatic insufficiency. N Engl J Med 1973;288:813-5.
Meta-Analysis and the Surgeon General’s Report on Smoking and Health To the Editor: Fifty years ago, on January 11, Luther L. Terry. That report made substantial use 1964, the landmark report on smoking and of a meta-analysis performed by statistician Wilhealth1 was made public by U.S. Surgeon General liam G. Cochran,2,3 who was a professor of sta186
n engl j med 370;2 nejm.org january 9, 2014
The New England Journal of Medicine Downloaded from nejm.org on April 26, 2015. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
