Pancreatology 14 (2014) 109e113
Contents lists available at ScienceDirect
Pancreatology journal homepage: www.elsevier.com/locate/pan
Original article
Analysis of risk factors for pancreatic duct stones formation in patients with alcoholic chronic pancreatitis Guo-wei Zhang*, Jian-hua Lin, Jian-ping Qian, Jie Zhou Department of Hepatobiliary Surgery, NanFang Hospital, Southern Medical University, No. 1838, North Guangzhou Avenue, Guangzhou 510515, PR China
a r t i c l e i n f o
a b s t r a c t
Article history: Received 7 November 2013 Received in revised form 20 January 2014 Accepted 21 January 2014
Background: Alcoholic chronic pancreatitis (ACP) is the dominant cause of chronic pancreatitis (CP). As a main complication of CP, the formation of pancreatic duct stones (PDS) compromises pancreatic function and symptomatic patients are often subjected to aggressive treatments. The present study aimed to identify PDS risk factors in patients with ACP. Methods: A retrospective analysis of 93 ACP patients was performed; patients were divided into two groups: ACP with PDS (n ¼ 48) and ACP without PDS (n ¼ 45). Fourteen potential factors were analyzed by univariate and multivariate analyses to identify independent risk factors of PDS formation in ACP patients. A comparison of demographic and clinical characteristics between ACP patients with PDS and non-ACP patients with PDS (n ¼ 43) was also carried out. Results: ACP accounted for 47.7% (93/195) of CP in this cohort. Among ACP patients, the morbidity of PDS was 51.6% (48/93). Significant risk factors of PDS formation for ACP patients included duration of drinking 24.7 years (OR, 9.036; 95% CI, 2.737e29.837; p < 0.001); daily alcohol consumption 147.0 g (OR, 3.147; 95% CI, 1.040e9.522; p ¼ 0.042); and MPD narrowing (OR, 7.245; 95% CI, 2.205e23.811; p ¼ 0.001). Shorter periods between diagnosis and PDS formation (PDP) were observed in ACP patients than nonACP patients. Conclusions: Alcohol consumption accelerates the progression of PDS formation in patients with CP. Copyright Ó 2014, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved.
Keywords: Risk factors Chronic pancreatitis Pancreatic duct stones Alcohol
1. Introduction Chronic pancreatitis is a progressive fibroinflammatory disease that can produce pain and other symptoms and, with sufficient tissue destruction, exocrine or endocrine insufficiency [1,2]. In addition to genetic, environmental, immunologic, and pathobiological factors leading to chronic pancreatitis, excessive alcohol consumption has been identified as the most common cause of CP, accounting for 70e80% of all cases in the Western world [3,4]. For Asian countries, CP causes vary depending on area and dietary habits. In Japan, alcoholism (69.7%) is the most common and idiopathic (21.0%) is the second most common cause of CP. The proportion of alcoholic CP has increased from 55.5% in 1994 [5]. In India, Idiopathic pancreatitis is the most common form of pancreatitis (60.2%) and ACP accounts for 38.7% of cases [6]. In China, the morbidity rate of CP has recently increased; the main etiology
* Corresponding author. Tel.: þ86 13600039982 (mobile); fax: þ86 02061641701. E-mail addresses: [email protected] (G.-w. Zhang), jianhualin66@ gmail.com (J.-h. Lin), [email protected] (J.-p. Qian), [email protected] (J. Zhou).
changed from biliary diseases in the 1990s (decreased from 36.8% to 28.1%) to alcohol abuse after the year 2000 (increased from 26.5% to 36.8%) [7]. Chronic alcohol consumption encourages calcium stone formation, possibly by disturbing the cholinergic regulation of pancreatic secretions and aggravating the loss of pancreatic endocrine and exocrine functions [8]. The risk of pancreatic cancer is markedly increased in CP patients in China compared with the general population, especially in older patients [9]. Noticeably, pancreatic malignancy develops mainly in patients with the alcoholic form of pancreatitis [10]. PDS has been thought to not only be one of the complications in CP but also to be a risk factor for pancreatic cancer [11]. Given the increased incidence of ACP, the high morbidity of PDS, and other severe outcomes, further studies clarifying risk factors are warranted. To our knowledge, no systematic studies have identified high risk factors for PDS formation in patients with ACP. The goal of the present study was to address these risk factors. Additionally, because it is not well known whether alcohol accelerates the progression of PDS formation in patients with CP, the present study also conducted a comparison between patients with PDS due to ACP and non-ACP.
1424-3903/$ e see front matter Copyright Ó 2014, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved. http://dx.doi.org/10.1016/j.pan.2014.01.002
110
G. Zhang et al. / Pancreatology 14 (2014) 109e113
2. Patients and methods 2.1. Definition and patient selection No universally accepted criteria exist to assign alcohol consumption as an etiology of pancreatitis. In present study, alcohol consumption over 50 g/day with a minimum duration of 5 years was set as the selection criteria of ACP because experts have used definitions varying from consumption of over 40e80 g/day with or without a minimum drinking duration [12e16]. All patients hospitalized in the Department of Hepatobiliary Surgery, NanFang Hospital, Southern Medical University, were diagnosed according to typical clinical history and lab examination. Fecal elastase-1 was measured to assess pancreatic exocrine function and pancreatic exocrine insufficiency was less than 200 kg/g. The presence of pancreatic calculi or ductal narrowing/parenchymal atrophy was determined at imaging using ultrasonography, CT scan, MRCP, ERCP or endoscopic ultrasound. The data of 195 CP patients from February 1999 to August 2013 were retrospectively analyzed. A total of 93 of these ACP patients fulfilled the following criteria: (1) Alcoholic consumption was over 50 g/day and duration of drinking was over 5 years. (2) Exocrine and endocrine functions of the pancreas were progressively lost. (3) Patients with pancreatic cancer were excluded. (4) Patients with CP due to other causes such as biliary diseases were also excluded. (5) Patients with complete and detailed medical files. The information of variables including duration of alcohol intake, laboratory tests, MPD narrowing and alcohol consumption was gathered in patients’ medical files and obtained at the first diagnosis of CP/PDS. 2.2. Statistical analysis SPSS 20.0 (SPSS, Chicago, IL, USA) for Windows was used for statistical analysis. Sixteen potential risk factors including age at onset, age at diagnosis, sex, BMI, smoking (>20 cigarettes per day), duration of drinking, daily alcohol consumption, duration of symptoms, diabetes mellitus, bouts of acute pancreatitis, serum amylase, lipase, total bilirubin (TBIL), pancreas swelling (diffused/ localized), MPD narrowing and diagnosis period, were analyzed by univariate and multivariate logistic regression analyses to identify independent risk factors for PDS formation in patients with ACP. Two-tailed t-tests and chi-square tests were utilized for the comparison of demographic and clinical characteristics between ACP patients with PDS and non-ACP patients with PDS. The results were considered statistically significant at a value of p < 0.05. 3. Results Clinical characteristics of the 195 CP patients are summarized in Table 1. The mean age at diagnosis was 48.9 9.5 years, age at onset was 43.1 12.9 years and 68.2% (133/195) of the patients were male. ACP accounted for 47.7% (93/195) and non-ACP accounted for 52.3% (102/195) of CP cases. PDS formation had occurred in 41.5% (81/195) of CP patients. The frequency of smoking patients was 62.1% (121/195). Abdominal pain was the most common symptom of CP, which occurred in 84.1% of patients, then steatorrhea (34.4%) and jaundice (31.8%). Associated co-morbidities of CP included diabetes mellitus (79.1%), liver cirrhosis (16.4%), ascites (10.8%), portal hypertension (14.9%), pseudocyst (21.5%), and cholelithiasis (29.2%). Surgeries were performed in 72 (36.9%) patients, ERCP in 25 (12.8%) and pharmacotherapy in 98 (50.3%) patients. The morbidity of PDS in ACP patients was 51.6% (48/93) while the morbidity of PDS among non-ACP patients was 32.4% (33/102). A total of 59.3% (48/81) of PDS were due to ACP and 40.7% (33/81)
Table 1 Demographics of 195 CP patients. Number (%) or mean SD
Factors Sex Male Female Age at onset (years) Age at diagnosis (years) Duration of symptoms (months) BMI Etiology ACP Non-ACP PDS formation Smoking Bouts of acute pancreatitis Symptoms Abdominal pain Steatorrhea Jaundice Associated co-morbidities Diabetes mellitus Liver cirrhosis Ascites Portal hypertension Pseudocyst Cholelithiasis Treatment Surgery ERCP Pharmacotherapy
133 (68.2%) 62 (31.8%) 43.1 12.9 48.9 9.5 54.2 39.5 22.5 3.3 93 (47.7%) 102 (52.3%) 81 (41.5%) 121 (62.1%) 115(59.0%) 164 (84.1%) 67 (34.4%) 62 (31.8%) 155 (79.1%) 32 (16.4%) 21 (10.8%) 29 (14.9%) 42 (21.5%) 57 (29.2%) 72 (36.9%) 25 (12.8%) 98 (50.3%)
were non-ACP. Among ACP patients, 75.3% (70/93) were male and 24.7% (23/93) were female; these patients had a mean age of 47.9 8.2 years (Tables 2 and 4). Potential risk factors were compared between ACP patients with and without PDS formation by univariate analysis (Table 2). MPD narrowing was found to be a significant risk factor for PDS formation (p < 0.001). Duration of drinking was significantly longer in patients with PDS than in those without (24.6 7.8 years vs. 20.5 4.8 years; p ¼ 0.004). Receivereoperator characteristic (ROC) curve analysis indicated that the optimal cutoff for duration of drinking was 24.7 years, yielding 60.4% sensitivity and 80.0%
Table 2 Univariate analysis of factors for pancreatic stone formation in patients with ACP. Factors
ACP with PDS (n ¼ 48)
ACP without PDS (n ¼ 45)
p value
Age at onset (years) Age at diagnosis (years) Sex (male/female) BMI Smoking (þ/) Duration of drinking (years) Daily alcohol consumption (g) Duration of symptoms (months) Diabetes mellitus (þ/) Bouts of acute pancreatitis (þ/) Lab examination Amylase (U/L) Lipase (U/L) TBIL (mg/dl) Pancreas swelling (diffused/localized) MPD narrowing (þ/) Diagnosis period 1999e2003 2004e2008 2009e2013
42.4 11.9 46.2 7.8 39/9 22.8 2.6 31/17 24.6 7.8 185.8 87.2 56.5 33.0 39/9 11/37
44.6 13.9 49.6 10.3 31/14 21.7 3.8 21/23 20.5 4.8 147.3 63.6 50.3 34.8 33/12 12/33
0.407 0.071 0.167 0.102 0.082 0.004a 0.017a 0.381 0.362 0.675
118.2 27.6 189.4 76.2 0.7 0.3 29/19 38/10
126.9 32.4 172.3 87.2 0.6 0.3 30/15 17/28
0.166 0.316 0.112 0.532 0.000a
10 12 23
9 13 23
0.924 0.673 0.758
MPD: main pancreatic duct. Data are expressed as n (%) or mean SD. a Statistically significant results (p < 0.05).
G. Zhang et al. / Pancreatology 14 (2014) 109e113
specificity for PDS formation. Quantity of daily alcohol consumption was significantly greater in patients with PDS formation than in those without (185.8 87.2 g vs. 147.3 63.6 g; p ¼ 0.017). ROC curve analysis indicated that the optimal cutoff value for daily alcohol consumption was 147.0 g, yielding 68.8% sensitivity and 57.8% specificity for PDS formation. Results of the ROC curve analyses are summarized in Fig. 1. Age at diagnosis, smoking and gender were included in the multivariable model as confounding variables. Independent risk factors of PDS formation for ACP patients, as assessed by multivariate analyses, were duration of drinking 24.7 years (OR, 9.036; 95% CI, 2.737e29.837; p < 0.001); daily alcohol consumption 147.0 g (OR, 3.147; 95% CI, 1.040e9.522; p ¼ 0.042); and MPD narrowing (OR, 7.245; 95% CI, 2.205e23.811; p ¼ 0.001) (Table 3). Fig. 2 revealed that PDS formation in MPD (Fig. 2c) and pseudocyst formation in pancreatic tail (Fig. 2d) were found in an ACP patient with MPD narrowing (Fig. 2a, b), after 3.27 years of follow-up. As shown in Table 4, compared with non-ACP patients, less time between diagnosis and PDS formation (PDP) elapsed in ACP patients (3.86 1.72 vs. 5.13 2.21 years; p ¼ 0.005). 4. Discussion In this single-institutional retrospective analysis of risk factors for PDS formation in ACP patients, we identified MPD narrowing, daily alcohol consumption of greater than 147.0 g and duration of drinking over 24.7 years as significant independent risk factors. Shorter periods between diagnosis of CP and pancreatic duct stones formation (PDP) were found in ACP patients than non-ACP patients. We reviewed the literature on “chronic pancreatitis” and “pancreatic duct stone” in PubMed, restricting the search to Englishlanguage publications. This is the first systematic, retrospective analysis of risk factors for PDS formation in ACP patients. ACP has been identified as a multi-factorial disease, where developmental, dietary, and environmental factors interact with the genetic profile of the individual [17]. Genetic contributions have been of special interest since the discovery that rare PRSS1, CFTR, and SPINK1 variants were associated with pancreatitis risk [18]. Recently, key findings, including the relationship between pancreas divisum and CFTR mutations, and the discovery of a pancreatitis modifier gene on the X chromosome, provided new clues to why
111
Table 3 Independent risk factors associated with PDS formation in ACP by multivariate analysis. Factors
OR (95%CI)
p value
Age at diagnosis (years) Sex Smoking Duration of drinking 24.7 years Daily alcohol consumption 360.2 g MPD narrowing
0.959 1.147 1.712 9.036 3.147 7.245
0.176 0.876 0.470
Contents lists available at ScienceDirect
Pancreatology journal homepage: www.elsevier.com/locate/pan
Original article
Analysis of risk factors for pancreatic duct stones formation in patients with alcoholic chronic pancreatitis Guo-wei Zhang*, Jian-hua Lin, Jian-ping Qian, Jie Zhou Department of Hepatobiliary Surgery, NanFang Hospital, Southern Medical University, No. 1838, North Guangzhou Avenue, Guangzhou 510515, PR China
a r t i c l e i n f o
a b s t r a c t
Article history: Received 7 November 2013 Received in revised form 20 January 2014 Accepted 21 January 2014
Background: Alcoholic chronic pancreatitis (ACP) is the dominant cause of chronic pancreatitis (CP). As a main complication of CP, the formation of pancreatic duct stones (PDS) compromises pancreatic function and symptomatic patients are often subjected to aggressive treatments. The present study aimed to identify PDS risk factors in patients with ACP. Methods: A retrospective analysis of 93 ACP patients was performed; patients were divided into two groups: ACP with PDS (n ¼ 48) and ACP without PDS (n ¼ 45). Fourteen potential factors were analyzed by univariate and multivariate analyses to identify independent risk factors of PDS formation in ACP patients. A comparison of demographic and clinical characteristics between ACP patients with PDS and non-ACP patients with PDS (n ¼ 43) was also carried out. Results: ACP accounted for 47.7% (93/195) of CP in this cohort. Among ACP patients, the morbidity of PDS was 51.6% (48/93). Significant risk factors of PDS formation for ACP patients included duration of drinking 24.7 years (OR, 9.036; 95% CI, 2.737e29.837; p < 0.001); daily alcohol consumption 147.0 g (OR, 3.147; 95% CI, 1.040e9.522; p ¼ 0.042); and MPD narrowing (OR, 7.245; 95% CI, 2.205e23.811; p ¼ 0.001). Shorter periods between diagnosis and PDS formation (PDP) were observed in ACP patients than nonACP patients. Conclusions: Alcohol consumption accelerates the progression of PDS formation in patients with CP. Copyright Ó 2014, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved.
Keywords: Risk factors Chronic pancreatitis Pancreatic duct stones Alcohol
1. Introduction Chronic pancreatitis is a progressive fibroinflammatory disease that can produce pain and other symptoms and, with sufficient tissue destruction, exocrine or endocrine insufficiency [1,2]. In addition to genetic, environmental, immunologic, and pathobiological factors leading to chronic pancreatitis, excessive alcohol consumption has been identified as the most common cause of CP, accounting for 70e80% of all cases in the Western world [3,4]. For Asian countries, CP causes vary depending on area and dietary habits. In Japan, alcoholism (69.7%) is the most common and idiopathic (21.0%) is the second most common cause of CP. The proportion of alcoholic CP has increased from 55.5% in 1994 [5]. In India, Idiopathic pancreatitis is the most common form of pancreatitis (60.2%) and ACP accounts for 38.7% of cases [6]. In China, the morbidity rate of CP has recently increased; the main etiology
* Corresponding author. Tel.: þ86 13600039982 (mobile); fax: þ86 02061641701. E-mail addresses: [email protected] (G.-w. Zhang), jianhualin66@ gmail.com (J.-h. Lin), [email protected] (J.-p. Qian), [email protected] (J. Zhou).
changed from biliary diseases in the 1990s (decreased from 36.8% to 28.1%) to alcohol abuse after the year 2000 (increased from 26.5% to 36.8%) [7]. Chronic alcohol consumption encourages calcium stone formation, possibly by disturbing the cholinergic regulation of pancreatic secretions and aggravating the loss of pancreatic endocrine and exocrine functions [8]. The risk of pancreatic cancer is markedly increased in CP patients in China compared with the general population, especially in older patients [9]. Noticeably, pancreatic malignancy develops mainly in patients with the alcoholic form of pancreatitis [10]. PDS has been thought to not only be one of the complications in CP but also to be a risk factor for pancreatic cancer [11]. Given the increased incidence of ACP, the high morbidity of PDS, and other severe outcomes, further studies clarifying risk factors are warranted. To our knowledge, no systematic studies have identified high risk factors for PDS formation in patients with ACP. The goal of the present study was to address these risk factors. Additionally, because it is not well known whether alcohol accelerates the progression of PDS formation in patients with CP, the present study also conducted a comparison between patients with PDS due to ACP and non-ACP.
1424-3903/$ e see front matter Copyright Ó 2014, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved. http://dx.doi.org/10.1016/j.pan.2014.01.002
110
G. Zhang et al. / Pancreatology 14 (2014) 109e113
2. Patients and methods 2.1. Definition and patient selection No universally accepted criteria exist to assign alcohol consumption as an etiology of pancreatitis. In present study, alcohol consumption over 50 g/day with a minimum duration of 5 years was set as the selection criteria of ACP because experts have used definitions varying from consumption of over 40e80 g/day with or without a minimum drinking duration [12e16]. All patients hospitalized in the Department of Hepatobiliary Surgery, NanFang Hospital, Southern Medical University, were diagnosed according to typical clinical history and lab examination. Fecal elastase-1 was measured to assess pancreatic exocrine function and pancreatic exocrine insufficiency was less than 200 kg/g. The presence of pancreatic calculi or ductal narrowing/parenchymal atrophy was determined at imaging using ultrasonography, CT scan, MRCP, ERCP or endoscopic ultrasound. The data of 195 CP patients from February 1999 to August 2013 were retrospectively analyzed. A total of 93 of these ACP patients fulfilled the following criteria: (1) Alcoholic consumption was over 50 g/day and duration of drinking was over 5 years. (2) Exocrine and endocrine functions of the pancreas were progressively lost. (3) Patients with pancreatic cancer were excluded. (4) Patients with CP due to other causes such as biliary diseases were also excluded. (5) Patients with complete and detailed medical files. The information of variables including duration of alcohol intake, laboratory tests, MPD narrowing and alcohol consumption was gathered in patients’ medical files and obtained at the first diagnosis of CP/PDS. 2.2. Statistical analysis SPSS 20.0 (SPSS, Chicago, IL, USA) for Windows was used for statistical analysis. Sixteen potential risk factors including age at onset, age at diagnosis, sex, BMI, smoking (>20 cigarettes per day), duration of drinking, daily alcohol consumption, duration of symptoms, diabetes mellitus, bouts of acute pancreatitis, serum amylase, lipase, total bilirubin (TBIL), pancreas swelling (diffused/ localized), MPD narrowing and diagnosis period, were analyzed by univariate and multivariate logistic regression analyses to identify independent risk factors for PDS formation in patients with ACP. Two-tailed t-tests and chi-square tests were utilized for the comparison of demographic and clinical characteristics between ACP patients with PDS and non-ACP patients with PDS. The results were considered statistically significant at a value of p < 0.05. 3. Results Clinical characteristics of the 195 CP patients are summarized in Table 1. The mean age at diagnosis was 48.9 9.5 years, age at onset was 43.1 12.9 years and 68.2% (133/195) of the patients were male. ACP accounted for 47.7% (93/195) and non-ACP accounted for 52.3% (102/195) of CP cases. PDS formation had occurred in 41.5% (81/195) of CP patients. The frequency of smoking patients was 62.1% (121/195). Abdominal pain was the most common symptom of CP, which occurred in 84.1% of patients, then steatorrhea (34.4%) and jaundice (31.8%). Associated co-morbidities of CP included diabetes mellitus (79.1%), liver cirrhosis (16.4%), ascites (10.8%), portal hypertension (14.9%), pseudocyst (21.5%), and cholelithiasis (29.2%). Surgeries were performed in 72 (36.9%) patients, ERCP in 25 (12.8%) and pharmacotherapy in 98 (50.3%) patients. The morbidity of PDS in ACP patients was 51.6% (48/93) while the morbidity of PDS among non-ACP patients was 32.4% (33/102). A total of 59.3% (48/81) of PDS were due to ACP and 40.7% (33/81)
Table 1 Demographics of 195 CP patients. Number (%) or mean SD
Factors Sex Male Female Age at onset (years) Age at diagnosis (years) Duration of symptoms (months) BMI Etiology ACP Non-ACP PDS formation Smoking Bouts of acute pancreatitis Symptoms Abdominal pain Steatorrhea Jaundice Associated co-morbidities Diabetes mellitus Liver cirrhosis Ascites Portal hypertension Pseudocyst Cholelithiasis Treatment Surgery ERCP Pharmacotherapy
133 (68.2%) 62 (31.8%) 43.1 12.9 48.9 9.5 54.2 39.5 22.5 3.3 93 (47.7%) 102 (52.3%) 81 (41.5%) 121 (62.1%) 115(59.0%) 164 (84.1%) 67 (34.4%) 62 (31.8%) 155 (79.1%) 32 (16.4%) 21 (10.8%) 29 (14.9%) 42 (21.5%) 57 (29.2%) 72 (36.9%) 25 (12.8%) 98 (50.3%)
were non-ACP. Among ACP patients, 75.3% (70/93) were male and 24.7% (23/93) were female; these patients had a mean age of 47.9 8.2 years (Tables 2 and 4). Potential risk factors were compared between ACP patients with and without PDS formation by univariate analysis (Table 2). MPD narrowing was found to be a significant risk factor for PDS formation (p < 0.001). Duration of drinking was significantly longer in patients with PDS than in those without (24.6 7.8 years vs. 20.5 4.8 years; p ¼ 0.004). Receivereoperator characteristic (ROC) curve analysis indicated that the optimal cutoff for duration of drinking was 24.7 years, yielding 60.4% sensitivity and 80.0%
Table 2 Univariate analysis of factors for pancreatic stone formation in patients with ACP. Factors
ACP with PDS (n ¼ 48)
ACP without PDS (n ¼ 45)
p value
Age at onset (years) Age at diagnosis (years) Sex (male/female) BMI Smoking (þ/) Duration of drinking (years) Daily alcohol consumption (g) Duration of symptoms (months) Diabetes mellitus (þ/) Bouts of acute pancreatitis (þ/) Lab examination Amylase (U/L) Lipase (U/L) TBIL (mg/dl) Pancreas swelling (diffused/localized) MPD narrowing (þ/) Diagnosis period 1999e2003 2004e2008 2009e2013
42.4 11.9 46.2 7.8 39/9 22.8 2.6 31/17 24.6 7.8 185.8 87.2 56.5 33.0 39/9 11/37
44.6 13.9 49.6 10.3 31/14 21.7 3.8 21/23 20.5 4.8 147.3 63.6 50.3 34.8 33/12 12/33
0.407 0.071 0.167 0.102 0.082 0.004a 0.017a 0.381 0.362 0.675
118.2 27.6 189.4 76.2 0.7 0.3 29/19 38/10
126.9 32.4 172.3 87.2 0.6 0.3 30/15 17/28
0.166 0.316 0.112 0.532 0.000a
10 12 23
9 13 23
0.924 0.673 0.758
MPD: main pancreatic duct. Data are expressed as n (%) or mean SD. a Statistically significant results (p < 0.05).
G. Zhang et al. / Pancreatology 14 (2014) 109e113
specificity for PDS formation. Quantity of daily alcohol consumption was significantly greater in patients with PDS formation than in those without (185.8 87.2 g vs. 147.3 63.6 g; p ¼ 0.017). ROC curve analysis indicated that the optimal cutoff value for daily alcohol consumption was 147.0 g, yielding 68.8% sensitivity and 57.8% specificity for PDS formation. Results of the ROC curve analyses are summarized in Fig. 1. Age at diagnosis, smoking and gender were included in the multivariable model as confounding variables. Independent risk factors of PDS formation for ACP patients, as assessed by multivariate analyses, were duration of drinking 24.7 years (OR, 9.036; 95% CI, 2.737e29.837; p < 0.001); daily alcohol consumption 147.0 g (OR, 3.147; 95% CI, 1.040e9.522; p ¼ 0.042); and MPD narrowing (OR, 7.245; 95% CI, 2.205e23.811; p ¼ 0.001) (Table 3). Fig. 2 revealed that PDS formation in MPD (Fig. 2c) and pseudocyst formation in pancreatic tail (Fig. 2d) were found in an ACP patient with MPD narrowing (Fig. 2a, b), after 3.27 years of follow-up. As shown in Table 4, compared with non-ACP patients, less time between diagnosis and PDS formation (PDP) elapsed in ACP patients (3.86 1.72 vs. 5.13 2.21 years; p ¼ 0.005). 4. Discussion In this single-institutional retrospective analysis of risk factors for PDS formation in ACP patients, we identified MPD narrowing, daily alcohol consumption of greater than 147.0 g and duration of drinking over 24.7 years as significant independent risk factors. Shorter periods between diagnosis of CP and pancreatic duct stones formation (PDP) were found in ACP patients than non-ACP patients. We reviewed the literature on “chronic pancreatitis” and “pancreatic duct stone” in PubMed, restricting the search to Englishlanguage publications. This is the first systematic, retrospective analysis of risk factors for PDS formation in ACP patients. ACP has been identified as a multi-factorial disease, where developmental, dietary, and environmental factors interact with the genetic profile of the individual [17]. Genetic contributions have been of special interest since the discovery that rare PRSS1, CFTR, and SPINK1 variants were associated with pancreatitis risk [18]. Recently, key findings, including the relationship between pancreas divisum and CFTR mutations, and the discovery of a pancreatitis modifier gene on the X chromosome, provided new clues to why
111
Table 3 Independent risk factors associated with PDS formation in ACP by multivariate analysis. Factors
OR (95%CI)
p value
Age at diagnosis (years) Sex Smoking Duration of drinking 24.7 years Daily alcohol consumption 360.2 g MPD narrowing
0.959 1.147 1.712 9.036 3.147 7.245
0.176 0.876 0.470
