LETTERS TO THE EDITOR
Response to Galassi et al, “A 5-Year Experience of Benign Pancreatic Hyperenzymemia”
We agree that many patients with chronic asymptomatic pancreatic hyperenzymemia have Gullo syndrome, but we cannot exclude pancreatic abnormalities, also clinically relevant, in a significant proportion of cases.
To the Editor: e read with great interest the study by Galassi et al investigating 207 subjects with benign pancreatic hyperenzymemia.1 In this study, they analyzed the degree of elevation of pancreatic enzymes, the dayto-day fluctuations, and the frequency of familial forms of subjects enrolled from 2004 to 2008. In this cohort of subjects, pancreatic abnormalities were found in 15 (7.2%) subjects of 207, in particular 6 cases of pancreas divisum, 6 cases with intraductal papillary mucinous neoplasia, 2 cases with pancreatic cyst, and 1 case with congenital anomaly of the Wirsung. Previous studies found 50% of pancreatic abnormalities in subjects with chronic asymptomatic pancreatic hyperenzymemia who underwent magnetic resonance imaging with secretin stimulation.2–6 Galassi et al explained that the high frequency of pancreatic abnormalities observed in our previous study could depend by the presence of abdominal pain.5 The inclusion criteria clearly state that the absence of pancreatic symptoms (“absence of upper abdominal or back pain”) and all patients at the time of enrollment are pain free. Patients reported previous aspecific symptoms (dyspepsia, diarrhea), including aspecific abdominal pain. Furthermore, and more significantly, pancreatic abnormalities were found in a significant lower frequency in patients with previous symptoms (any) than in asymptomatics (respectively 47/52 [57%] vs 33/78 [42%]; P = 0.041). We would stress also that only 1 pancreatic cancer was diagnosed in our subjects, and endocrine neoplasia was diagnosed in the other 4 subjects. The low rate of pancreatic abnormalities observed in the study by Galassi et al is probably because, in our opinion, of 2 factors: (1) there is a selection bias because nearly 40% of the subjects are components of families affected by benign pancreatic hyperenzymemia; and (2) subjects were not investigated by magnetic resonance imaging with secretin stimulation, which allows a better visualization of the pancreatic ductal system and may diagnose pancreatic ductal abnormalities (eg, pancreas divisum).7
The authors declare no conflict of interest.
W
Pancreas • Volume 44, Number 5, July 2015
Antonio Amodio, MD, PhD Department of Medicine Pancreas Centre Verona, Italy [email protected]
Luca Frulloni, MD, PhD Department of Medicine Pancreas Centre Verona, Italy
REFERENCES 1. Galassi E, Birtolo C, Migliori M, et al. A 5-year experience of benign pancreatic hyperenzymemia. Pancreas. 2014; 43:874–878. 2. Mortelé KJ, Ros PR. Magnetic resonance imaging of the exocrine pancreas. Rays. 2001; 26:117–126. 3. Pezzilli R, Morselli-Labate AM, Casadei R, et al. Chronic asymptomatic pancreatic hyperenzymemia is a benign condition in only half of the cases: a prospective study. Scand J Gastroenterol. 2009;44:888–893. 4. Testoni PA, Mariani A, Curioni S, et al. Pancreatic ductal abnormalities documented by secretin-enhanced MRCP in asymptomatic subjects with chronic pancreatic hyperenzymemia. Am J Gastroenterol. 2009;104:1780–1786. 5. Amodio A, Manfredi R, Katsotourchi AM, et al. Prospective evaluation of subjects with chronic asymptomatic pancreatic hyperenzymemia. Am J Gastroenterol. 2012;107:1089–1095. 6. Donati F, Boraschi P, Gigoni R, et al. Secretin-stimulated MR cholangio-pancreatography in the evaluation of asymptomatic patients with non-specific pancreatic hyperenzymemia. Eur J Radiol. 2010;75:e38–e44. 7. Sherman S, Freeman ML, Tarnasky PR, et al. Administration of secretin (RG1068) increases the sensitivity of detection of duct abnormalities by magnetic resonance cholangiopancreatography in patients with pancreatitis. Gastroenterology. 2014;147: 646–654.e2.
Reply: e read with great interest the letter by Amodio and Frulloni to our study based on 207 subjects with benign pancreatic hyperenzymemia (also referred to as Gullo syndrome)1 and in comparison with their recently published experience.2 We fully agree with the 2 comments raised by Amodio and Frulloni, in particular with the evidence that most of the recruited patients had a familial form of benign pancreatic hyperenzymemia. However, concerning the second comment, we would like to state that in our study, the magnetic resonance imaging with secretin stimulation was performed only in those cases with not well established (ie, considered “doubtful”) pancreatic abnormalities (all tested negative). In addition, we would like to point out that the clinical follow-up should be regarded as a valuable tool for establishing the actual existence of the benign pancreatic hyperenzymemia. Indeed, in our study, most of the subjects (94 of 207) had a 4- to 10-year follow-up and after that long period of observation, they were all consistently negative for any pancreatic lesion. Thus, we strongly believe that a careful monitoring of these subjects along with the use of standard magnetic resonance imaging and/or advanced 3-dimensional computed tomographic scan would be a valuable, costeffective strategy to demonstrate that otherwise asymptomatic subjects (and not patients) can be labeled as affected by the Gullo syndrome.
W
ACKNOWLEDGMENT This study was supported by the Italian Ministry of Education, University and Research Grant (PRIN2009) from Fondazione Del Monte di Bologna e Ravenna, Italy (to R.D.G.) and the University of Bologna Funds (to R.D.G.). The authors declare no conflict of interest.
Marina Migliori, MD Department of Digestive System Saint Orsola-Malphigi Hospital Bologna, Italy Department of Medical and Surgical Sciences Internal Medicine Unit University of Bologna Saint Orsola-Malpighi Hospital Bologna, Italy [email protected] www.pancreasjournal.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
831
Pancreas • Volume 44, Number 5, July 2015
Letters to the Editor
Roberto De Giorgio, MD, PhD, AGAF Department of Digestive System Saint Orsola-Malphigi Hospital Bologna, Italy Department of Medical and Surgical Sciences Internal Medicine Unit University of Bologna Saint Orsola-Malpighi Hospital Bologna, Italy [email protected]
REFERENCES 1. Galassi E, Birtolo C, Migliori M, et al. A 5-year experience of benign pancreatic hyperenzymemia. Pancreas. 2014;43:874–878. 2. Amodio A, Manfredi R, Katsotourchi AM, et al. Prospective evaluation of subjects with chronic asymptomatic pancreatic hyperenzymemia. Am J Gastroenterol. 2012; 107:1089–1095.
The Effects of Beverage Type on Pancreatitis Mortality Rate in Russia To the Editor: ince an association between alcohol abuse and pancreatitis was reported by Friedreich,1 many studies have confirmed that excessive alcohol consumption is a major risk factor for both acute and chronic pancreatitis.2–4 A recent systematic review and meta-analysis of epidemiologic studies on alcohol consumption and pancreatitis published between 1980 and 2008 found a monotonic and approximately exponential dose-response relationship between the average volume of alcohol consumption and the risk of pancreatitis.5 The risk curve between alcohol consumption and pancreatitis was relatively flat at low levels of alcohol consumption, and it increased markedly with increasing levels of consumption. Collectively, these findings suggest that the total amount of alcohol consumed is a critical factor in producing chronic alcoholinduced pancreatic damage. There is, however, evidence that the pattern of drinking and beverage preference may have a modifying influence on pancreatitis risk independently of the amount of alcohol consumed. A follow-up study from Sweden revealed a dose-response association between the amount of spirits consumed on a single occasion and the risk of acute pancreatitis.6 Similarly, Nakamura et al7 reported that the higher risk for chronic pancreatitis in alcohol-dependent men was associated with drinking spirits rather than with drinking beverages with lower alcohol content. The level of alcohol consumption in Russia is among the highest in the world,
S
832
www.pancreasjournal.com
with an annual sales rate about 10 L of pure alcohol per capita, whereas independent estimates show a figure as high as 17 L.8,9 The distinctive trait of Russian drinking culture is a high overall level of alcohol consumption and the heavy episodic (binge) drinking pattern of strong spirits (vodka).10 This is a good reason to expect a positive association between vodka sale and pancreatitis mortality at the aggregate level. In this study, we will test the hypothesis of beverage-specific effect on pancreatitis mortality by analyzing Russian’s time series data between 1970 and 2005. The results of ARIMA (autoregressive integrated moving average) time-series analysis suggest that of the 3 beverages vodka alone was associated with pancreatitis mortality in Russia. The estimated effects of vodka sales on the pancreatitis mortality rate are clearly statistically significant for both sexes; a 1-L increase in vodka sales would result to a 10.3% increase in the male pancreatitis mortality rate and to a 3.2% increase in female pancreatitis mortality rate. It is important to point out that the size of the bivariate association between vodka sale and pancreatitis mortality for men is substantially greater than for women. Beverage preference and harmful drinking pattern might be responsible for the sex difference in pancreatitis mortality rate because vodka continues to be the drink of choice for most men in Russia, whereas women not only drink less often than men, but those who do drink consume vodka less frequently than men.9 The effects of drinking spirits may also be exacerbated by the way they are drunk because a heavy episodic drinking pattern is widespread. Moreover, this pattern of consuming alcohol is much more frequent when drinking spirits than other types of beverage among both men and women in Russia.10 These findings provide indirect support for the binge drinking hypothesis, suggesting that episodic heavy drinking of spirits is an important determinant of pancreatitis mortality in Russia. It should be emphasized that the results suggest a fairly quick response of pancreatitis mortality rates to changes in vodka sale. The instantaneous response in mortality rates from chronic alcohol-related diseases seems quite surprising when considering the long latency period at the individual level.2 There is reasonable explanation for this seeming inconsistency. It is well recognized that pancreatitis mortality is the classical indicator of the harmful effect of long-term heavy drinking (chronic pancreatitis) and is also associated with episodic heavy drinking (acute pancreatitis), thus reflecting the immediate and long-term consequences of heavy drinking.3–5 Therefore, the contemporaneous association between
the 2 variables may support the point that substantial proportions of pancreatitis deaths in Russia are due to the immediate effect of binge drinking. In conclusion, the present study suggests that pancreatitis mortality tend to be more responsive to changes in spirits consumption per capita than to the wine or beer consumption. Assuming that drinking vodka is usually associated with intoxication episodes, these findings provide indirect evidence that that substantial proportions of pancreatitis deaths in Russia are due to the immediate effect of binge drinking. The findings from the present study have important implications as regards alcohol policy in Russia, suggesting that any attempts to reduce overall consumption should also be linked with efforts through differential taxation to shift beverage preference away from spirits. The author declares no conflict of interest. Yury E. Razvodovsky, MD, PhD Department of Pathological Physiology Grodno State Medical University Grodno, Belarus [email protected] [email protected]
REFERENCES 1. Friedreich N. Diseases of the pancreas. In: Ziemssen H, ed. Cyclopedia of the Practice of Medicine. London, United Kingdom: Sampson Low; 1878;8:551. 2. Ramstedt M. Alcohol and pancreatitis mortality at the population level: experiences from 14 western countries. Addiction. 2004;99: 1255–1261. 3. Herreros-Villanueva M, Hijona E, Bañales JM, et al. Alcohol consumption on pancreatic diseases. World J Gastroenterol. 2013;19: 638–647. 4. Gullo L. Alcohol and chronic pancreatitis: leading or secondary etiopathogenic role? JOP. 2005;6:68–72. 5. Irving HM, Samokhvalov AV, Rehm J. Alcohol as a risk factor for pancreatitis: a systematic review and meta-analysis. JOP. 2012;10: 387–392. 6. Sadr Azodi O, Orsini N, Andrén-Sandberg A. Effect of type of alcoholic beverage in causing acute pancreatitis. Br J Surg. 2011;98: 1609–1616. 7. Nakamura Y, Ishikawa A, Sekiguchi S, et al. Spirits and gastroectomy increase risk for chronic pancreatitis in Japanese male alcoholics. Pancreas. 2003;26:27–31. 8. Razvodovsky YE. Estimation of the level of alcohol consumption in Russia. ICAP Periodic Rev Drinking Cult. 2013;8:6–10.
© 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Response to Galassi et al, “A 5-Year Experience of Benign Pancreatic Hyperenzymemia”
We agree that many patients with chronic asymptomatic pancreatic hyperenzymemia have Gullo syndrome, but we cannot exclude pancreatic abnormalities, also clinically relevant, in a significant proportion of cases.
To the Editor: e read with great interest the study by Galassi et al investigating 207 subjects with benign pancreatic hyperenzymemia.1 In this study, they analyzed the degree of elevation of pancreatic enzymes, the dayto-day fluctuations, and the frequency of familial forms of subjects enrolled from 2004 to 2008. In this cohort of subjects, pancreatic abnormalities were found in 15 (7.2%) subjects of 207, in particular 6 cases of pancreas divisum, 6 cases with intraductal papillary mucinous neoplasia, 2 cases with pancreatic cyst, and 1 case with congenital anomaly of the Wirsung. Previous studies found 50% of pancreatic abnormalities in subjects with chronic asymptomatic pancreatic hyperenzymemia who underwent magnetic resonance imaging with secretin stimulation.2–6 Galassi et al explained that the high frequency of pancreatic abnormalities observed in our previous study could depend by the presence of abdominal pain.5 The inclusion criteria clearly state that the absence of pancreatic symptoms (“absence of upper abdominal or back pain”) and all patients at the time of enrollment are pain free. Patients reported previous aspecific symptoms (dyspepsia, diarrhea), including aspecific abdominal pain. Furthermore, and more significantly, pancreatic abnormalities were found in a significant lower frequency in patients with previous symptoms (any) than in asymptomatics (respectively 47/52 [57%] vs 33/78 [42%]; P = 0.041). We would stress also that only 1 pancreatic cancer was diagnosed in our subjects, and endocrine neoplasia was diagnosed in the other 4 subjects. The low rate of pancreatic abnormalities observed in the study by Galassi et al is probably because, in our opinion, of 2 factors: (1) there is a selection bias because nearly 40% of the subjects are components of families affected by benign pancreatic hyperenzymemia; and (2) subjects were not investigated by magnetic resonance imaging with secretin stimulation, which allows a better visualization of the pancreatic ductal system and may diagnose pancreatic ductal abnormalities (eg, pancreas divisum).7
The authors declare no conflict of interest.
W
Pancreas • Volume 44, Number 5, July 2015
Antonio Amodio, MD, PhD Department of Medicine Pancreas Centre Verona, Italy [email protected]
Luca Frulloni, MD, PhD Department of Medicine Pancreas Centre Verona, Italy
REFERENCES 1. Galassi E, Birtolo C, Migliori M, et al. A 5-year experience of benign pancreatic hyperenzymemia. Pancreas. 2014; 43:874–878. 2. Mortelé KJ, Ros PR. Magnetic resonance imaging of the exocrine pancreas. Rays. 2001; 26:117–126. 3. Pezzilli R, Morselli-Labate AM, Casadei R, et al. Chronic asymptomatic pancreatic hyperenzymemia is a benign condition in only half of the cases: a prospective study. Scand J Gastroenterol. 2009;44:888–893. 4. Testoni PA, Mariani A, Curioni S, et al. Pancreatic ductal abnormalities documented by secretin-enhanced MRCP in asymptomatic subjects with chronic pancreatic hyperenzymemia. Am J Gastroenterol. 2009;104:1780–1786. 5. Amodio A, Manfredi R, Katsotourchi AM, et al. Prospective evaluation of subjects with chronic asymptomatic pancreatic hyperenzymemia. Am J Gastroenterol. 2012;107:1089–1095. 6. Donati F, Boraschi P, Gigoni R, et al. Secretin-stimulated MR cholangio-pancreatography in the evaluation of asymptomatic patients with non-specific pancreatic hyperenzymemia. Eur J Radiol. 2010;75:e38–e44. 7. Sherman S, Freeman ML, Tarnasky PR, et al. Administration of secretin (RG1068) increases the sensitivity of detection of duct abnormalities by magnetic resonance cholangiopancreatography in patients with pancreatitis. Gastroenterology. 2014;147: 646–654.e2.
Reply: e read with great interest the letter by Amodio and Frulloni to our study based on 207 subjects with benign pancreatic hyperenzymemia (also referred to as Gullo syndrome)1 and in comparison with their recently published experience.2 We fully agree with the 2 comments raised by Amodio and Frulloni, in particular with the evidence that most of the recruited patients had a familial form of benign pancreatic hyperenzymemia. However, concerning the second comment, we would like to state that in our study, the magnetic resonance imaging with secretin stimulation was performed only in those cases with not well established (ie, considered “doubtful”) pancreatic abnormalities (all tested negative). In addition, we would like to point out that the clinical follow-up should be regarded as a valuable tool for establishing the actual existence of the benign pancreatic hyperenzymemia. Indeed, in our study, most of the subjects (94 of 207) had a 4- to 10-year follow-up and after that long period of observation, they were all consistently negative for any pancreatic lesion. Thus, we strongly believe that a careful monitoring of these subjects along with the use of standard magnetic resonance imaging and/or advanced 3-dimensional computed tomographic scan would be a valuable, costeffective strategy to demonstrate that otherwise asymptomatic subjects (and not patients) can be labeled as affected by the Gullo syndrome.
W
ACKNOWLEDGMENT This study was supported by the Italian Ministry of Education, University and Research Grant (PRIN2009) from Fondazione Del Monte di Bologna e Ravenna, Italy (to R.D.G.) and the University of Bologna Funds (to R.D.G.). The authors declare no conflict of interest.
Marina Migliori, MD Department of Digestive System Saint Orsola-Malphigi Hospital Bologna, Italy Department of Medical and Surgical Sciences Internal Medicine Unit University of Bologna Saint Orsola-Malpighi Hospital Bologna, Italy [email protected] www.pancreasjournal.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
831
Pancreas • Volume 44, Number 5, July 2015
Letters to the Editor
Roberto De Giorgio, MD, PhD, AGAF Department of Digestive System Saint Orsola-Malphigi Hospital Bologna, Italy Department of Medical and Surgical Sciences Internal Medicine Unit University of Bologna Saint Orsola-Malpighi Hospital Bologna, Italy [email protected]
REFERENCES 1. Galassi E, Birtolo C, Migliori M, et al. A 5-year experience of benign pancreatic hyperenzymemia. Pancreas. 2014;43:874–878. 2. Amodio A, Manfredi R, Katsotourchi AM, et al. Prospective evaluation of subjects with chronic asymptomatic pancreatic hyperenzymemia. Am J Gastroenterol. 2012; 107:1089–1095.
The Effects of Beverage Type on Pancreatitis Mortality Rate in Russia To the Editor: ince an association between alcohol abuse and pancreatitis was reported by Friedreich,1 many studies have confirmed that excessive alcohol consumption is a major risk factor for both acute and chronic pancreatitis.2–4 A recent systematic review and meta-analysis of epidemiologic studies on alcohol consumption and pancreatitis published between 1980 and 2008 found a monotonic and approximately exponential dose-response relationship between the average volume of alcohol consumption and the risk of pancreatitis.5 The risk curve between alcohol consumption and pancreatitis was relatively flat at low levels of alcohol consumption, and it increased markedly with increasing levels of consumption. Collectively, these findings suggest that the total amount of alcohol consumed is a critical factor in producing chronic alcoholinduced pancreatic damage. There is, however, evidence that the pattern of drinking and beverage preference may have a modifying influence on pancreatitis risk independently of the amount of alcohol consumed. A follow-up study from Sweden revealed a dose-response association between the amount of spirits consumed on a single occasion and the risk of acute pancreatitis.6 Similarly, Nakamura et al7 reported that the higher risk for chronic pancreatitis in alcohol-dependent men was associated with drinking spirits rather than with drinking beverages with lower alcohol content. The level of alcohol consumption in Russia is among the highest in the world,
S
832
www.pancreasjournal.com
with an annual sales rate about 10 L of pure alcohol per capita, whereas independent estimates show a figure as high as 17 L.8,9 The distinctive trait of Russian drinking culture is a high overall level of alcohol consumption and the heavy episodic (binge) drinking pattern of strong spirits (vodka).10 This is a good reason to expect a positive association between vodka sale and pancreatitis mortality at the aggregate level. In this study, we will test the hypothesis of beverage-specific effect on pancreatitis mortality by analyzing Russian’s time series data between 1970 and 2005. The results of ARIMA (autoregressive integrated moving average) time-series analysis suggest that of the 3 beverages vodka alone was associated with pancreatitis mortality in Russia. The estimated effects of vodka sales on the pancreatitis mortality rate are clearly statistically significant for both sexes; a 1-L increase in vodka sales would result to a 10.3% increase in the male pancreatitis mortality rate and to a 3.2% increase in female pancreatitis mortality rate. It is important to point out that the size of the bivariate association between vodka sale and pancreatitis mortality for men is substantially greater than for women. Beverage preference and harmful drinking pattern might be responsible for the sex difference in pancreatitis mortality rate because vodka continues to be the drink of choice for most men in Russia, whereas women not only drink less often than men, but those who do drink consume vodka less frequently than men.9 The effects of drinking spirits may also be exacerbated by the way they are drunk because a heavy episodic drinking pattern is widespread. Moreover, this pattern of consuming alcohol is much more frequent when drinking spirits than other types of beverage among both men and women in Russia.10 These findings provide indirect support for the binge drinking hypothesis, suggesting that episodic heavy drinking of spirits is an important determinant of pancreatitis mortality in Russia. It should be emphasized that the results suggest a fairly quick response of pancreatitis mortality rates to changes in vodka sale. The instantaneous response in mortality rates from chronic alcohol-related diseases seems quite surprising when considering the long latency period at the individual level.2 There is reasonable explanation for this seeming inconsistency. It is well recognized that pancreatitis mortality is the classical indicator of the harmful effect of long-term heavy drinking (chronic pancreatitis) and is also associated with episodic heavy drinking (acute pancreatitis), thus reflecting the immediate and long-term consequences of heavy drinking.3–5 Therefore, the contemporaneous association between
the 2 variables may support the point that substantial proportions of pancreatitis deaths in Russia are due to the immediate effect of binge drinking. In conclusion, the present study suggests that pancreatitis mortality tend to be more responsive to changes in spirits consumption per capita than to the wine or beer consumption. Assuming that drinking vodka is usually associated with intoxication episodes, these findings provide indirect evidence that that substantial proportions of pancreatitis deaths in Russia are due to the immediate effect of binge drinking. The findings from the present study have important implications as regards alcohol policy in Russia, suggesting that any attempts to reduce overall consumption should also be linked with efforts through differential taxation to shift beverage preference away from spirits. The author declares no conflict of interest. Yury E. Razvodovsky, MD, PhD Department of Pathological Physiology Grodno State Medical University Grodno, Belarus [email protected] [email protected]
REFERENCES 1. Friedreich N. Diseases of the pancreas. In: Ziemssen H, ed. Cyclopedia of the Practice of Medicine. London, United Kingdom: Sampson Low; 1878;8:551. 2. Ramstedt M. Alcohol and pancreatitis mortality at the population level: experiences from 14 western countries. Addiction. 2004;99: 1255–1261. 3. Herreros-Villanueva M, Hijona E, Bañales JM, et al. Alcohol consumption on pancreatic diseases. World J Gastroenterol. 2013;19: 638–647. 4. Gullo L. Alcohol and chronic pancreatitis: leading or secondary etiopathogenic role? JOP. 2005;6:68–72. 5. Irving HM, Samokhvalov AV, Rehm J. Alcohol as a risk factor for pancreatitis: a systematic review and meta-analysis. JOP. 2012;10: 387–392. 6. Sadr Azodi O, Orsini N, Andrén-Sandberg A. Effect of type of alcoholic beverage in causing acute pancreatitis. Br J Surg. 2011;98: 1609–1616. 7. Nakamura Y, Ishikawa A, Sekiguchi S, et al. Spirits and gastroectomy increase risk for chronic pancreatitis in Japanese male alcoholics. Pancreas. 2003;26:27–31. 8. Razvodovsky YE. Estimation of the level of alcohol consumption in Russia. ICAP Periodic Rev Drinking Cult. 2013;8:6–10.
© 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
