Sex Differences in
Gallstone Pancreatitis
T. V. TAYLOR, F.R.C.S., S. RIMMER, F.R.C.R., S. HOLT, M.R.C.P., J. JEACOCK, B.Sc., and S. LUCAS, PH.D.
From a computerized database comprising 28 pertinent items in each of a consecutive series of 664 patients with cholelithiasis, differences were studied between men and women. In 52 patients there was a documented attack of acute pancreatitis (7.8%). Twenty-five of 174 men had pancreatitis, compared with 27 of 490 women (p < 0.0001). Men developed gallstones later in life than women, but suffered gallstone pancreatitis earlier in life and in the course of their gallstone-related disease. A history of flatulent dyspepsia, chronic cholecystitis, and biliary colic was less common in men than in women with pancreatitis (p < 0.0001). Men with pancreatitis had fewer stones in their gallbladders than did women (p = 0.0002). The cystic duct and the common bile duct in the pancreatitic patient were more likely to be dilated (p < 0.0001). In the nonpancreatitic group, these ducts were larger in men. Pancreatic duct reflux on operative cholangiography was more common both in patients with pancreatitis 62% cf 14% (p < 0.0001), and in men (p < 0.001). Predisposition to pancreatitis relates to duct size rather than stone size per se. Men are more susceptible to gallstone migration at an early stage of their disease. In addition they have a larger diameter duct system and possibly a different anatomic disposition of the sphincter of Oddi, which predisposes them to a higher incidence of pancreatitis than women. The data suggest that it is cystic duct size that is critical in the pathogenesis of gallstone pancreatitis.
G
AALLSTONES ARE THE most common causative factor in acute pancreatitis in the Western world. 1'2 Although it is now established that the onset of gallstone pancreatitis coincides with gallstone migration and that small stones are usually responsible, the factors that predispose to the migration of gallstones remain ill understood, and the exact pathogenesis remains an enigma. Differences exist between the sexes in their predisposition toward gallstone pancreatitis.3 Men and women have been further studied separately to see if additional factors, of pathogenetic significance in this condition, may emerge. Address reprint requests to T. V. Taylor, F.R.C.S., Department of Surgery, Manchester Royal Infirmary, Oxford Road, Manchester, England. Accepted for publication April 1, 1991.
667
From the Manchester Royal Infirmary and Medical School, Manchester, United Kingdom
Patients and Methods A consecutive series of 664 patients undergoing biliary tract surgery for gallstones and their complications has been studied. All the collected data were stored on a computer in the Department of Computation at the Manchester University Medical School. Twenty-eight items of information were recorded on each patient (Table 1), and emphasis was placed on differences that could be identified between the two sexes. Obtaining a satisfactory operative cholangiogram was a prerequisite to data storage. Cholangiography was performed with the patient supine by injecting 3, 8, and 16 mL 25% Hypaque (Winthrop Pharmaceuticals, New York, NY) and taking three films accordingly. Injection pressures were not measured, but the same injection technique was employed throughout the study in both sexes and in those with and without pancreatitis. If cannulation of the cystic duct proved unsuccessful, direct needle puncture of the common bile duct was employed. Approximately 10% of patients had been previously excluded because of failure to obtain a technically satisfactory operative cholangiogram. This was either as a result of extravasation of dye, poor positioning of the patient, or poor film penetration. After exclusion ofthese, the data was complete with the possible exception of operative findings relating to the pancreas, which are often subjective and difficult to interpret, and not always recorded even in those with a history of previous pancreatitis. Patients in the pancreatitis group had a documented attack of acute pancreatitis with a serum amylase recorded in excess of 1000 IU during the course of their disease. The number of gallbladder stones was categorized by the exact integer up to 10, but patients with more numerous stones were merely categorized as having multiple stones.
Ann. SUrg * December 1991
TAYLOR AND OTHERS
668
TABLE 3. Age at Cholecystectomy
TABLE 1. Variables Assessed in the Initial Database Age Sex Length of history Presentation Biliary dyspepsia Acute cholecystitis Chronic cholecystitis Biliary colic Pancreatitis Back pain Jaundice Cholangitis Oral cholecystogram or ultrasound scan No. of stones Wall thickened Nonfunction Gallbladder at operation No. of stones Wall thickened Empyema (mucocoele) Mucosal disease Findings on operative cholangiography Duct filling Duct diameter Presence of stones Common channel Pancreatic duct reflux Duodenal filling Operative measurements Common bile duct Dilated (>10 mm) Stones palpable Pancreas Normal Abnormal
1 2 3 4
Results Of the 664 patients, 52 had pancreatitis (7.8%). The range of the length of patients' histories attributable to gallstones was from 1 week to 25 years, with a median of 1 year. Although gallstones occurred in three times as TABLE 2. Incidence of Pancreatitis by Sex
Chi square
=
12.8; p < 0.0001.
M M F F
Mean Age Median SD (yr) Age (yr) (yr)
No pancreatitis Pancreatitis No pancreatitis
55.7 51.8 48.8 55.5
Pancreatitis
13.8 14.6 15.1 17.5
58 51 50 63
n
149 25 463 27
Differences: group 1 vs. group, p = 0.2; group 3 vs. group 4, p = 0.02, z = -2.4; group 2 vs. group 4, p = 0.3; group 1 vs. group 3, p = 0.001, z = -5.1. Mann-Whitney U test.
The range of gallstone size in each individual case was recorded, as was the number of common bile duct stones, from both the operative cholangiogram and the exploratory findings. The timing of surgery in relation to an attack of acute pancreatitis varied over the duration of the study from deferred surgery early in the study, to early surgery in the most recent cases. There were 174 men and 490 women (1:2.8). No difference existed regarding the attitude to surgical treatment of the two sexes.
No pancreatitis Pancreatitis
Diagnosis
Group Sex
M
F
149 25
463 27
many women as men, acute pancreatitis was a significantly more common complication of gallstones in men (p < 0.0001) than in women (Table 2). Women underwent surgery for uncomplicated gallstones at a mean age of 48.8 years (Table 3). Although women developed pancreatitis when 6.7 years older than the average age at which they underwent elective cholecystectomy, men had surgery for gallstone pancreatitis 4 years earlier than those who underwent cholecystectomy for uncomplicated disease, and also 4 years earlier than women with pancreatitis. Thus not only are men more prone to pancreatitis, but they suffer this complication earlier in the course of their gallstone disease than do women. There was no significant difference overall in the length of history of gallstone-related symptoms between the pancreatitis and nonpancreatitis groups. A previous history of biliary dyspepsia was much less frequent in men and women with pancreatitis than in those without this complication (p < 0.0001) (Table 4). Biliary colic had occurred much more frequently in both men and women who presented with no history of pancreatitis, this was particularly the case in men. A history of chronic cholecystitis was present in only 4% of men, compared with 35% of women with pancreatitis; in the TABLE 4. Symptom Complexes at Time of Presentation M
Presenting Features
Biliary dyspepsia No dyspepsia Dyspepsia Chi square p
Biliary colic No colic Colic Chi square p Chronic cholecystitis No cholecystitis
Cholecystitis Chi square p
No Pancreatitis
F Pancreatitis
No Pancreatitis
Pancreatitis
85 64 15.2
Gallstone Pancreatitis
T. V. TAYLOR, F.R.C.S., S. RIMMER, F.R.C.R., S. HOLT, M.R.C.P., J. JEACOCK, B.Sc., and S. LUCAS, PH.D.
From a computerized database comprising 28 pertinent items in each of a consecutive series of 664 patients with cholelithiasis, differences were studied between men and women. In 52 patients there was a documented attack of acute pancreatitis (7.8%). Twenty-five of 174 men had pancreatitis, compared with 27 of 490 women (p < 0.0001). Men developed gallstones later in life than women, but suffered gallstone pancreatitis earlier in life and in the course of their gallstone-related disease. A history of flatulent dyspepsia, chronic cholecystitis, and biliary colic was less common in men than in women with pancreatitis (p < 0.0001). Men with pancreatitis had fewer stones in their gallbladders than did women (p = 0.0002). The cystic duct and the common bile duct in the pancreatitic patient were more likely to be dilated (p < 0.0001). In the nonpancreatitic group, these ducts were larger in men. Pancreatic duct reflux on operative cholangiography was more common both in patients with pancreatitis 62% cf 14% (p < 0.0001), and in men (p < 0.001). Predisposition to pancreatitis relates to duct size rather than stone size per se. Men are more susceptible to gallstone migration at an early stage of their disease. In addition they have a larger diameter duct system and possibly a different anatomic disposition of the sphincter of Oddi, which predisposes them to a higher incidence of pancreatitis than women. The data suggest that it is cystic duct size that is critical in the pathogenesis of gallstone pancreatitis.
G
AALLSTONES ARE THE most common causative factor in acute pancreatitis in the Western world. 1'2 Although it is now established that the onset of gallstone pancreatitis coincides with gallstone migration and that small stones are usually responsible, the factors that predispose to the migration of gallstones remain ill understood, and the exact pathogenesis remains an enigma. Differences exist between the sexes in their predisposition toward gallstone pancreatitis.3 Men and women have been further studied separately to see if additional factors, of pathogenetic significance in this condition, may emerge. Address reprint requests to T. V. Taylor, F.R.C.S., Department of Surgery, Manchester Royal Infirmary, Oxford Road, Manchester, England. Accepted for publication April 1, 1991.
667
From the Manchester Royal Infirmary and Medical School, Manchester, United Kingdom
Patients and Methods A consecutive series of 664 patients undergoing biliary tract surgery for gallstones and their complications has been studied. All the collected data were stored on a computer in the Department of Computation at the Manchester University Medical School. Twenty-eight items of information were recorded on each patient (Table 1), and emphasis was placed on differences that could be identified between the two sexes. Obtaining a satisfactory operative cholangiogram was a prerequisite to data storage. Cholangiography was performed with the patient supine by injecting 3, 8, and 16 mL 25% Hypaque (Winthrop Pharmaceuticals, New York, NY) and taking three films accordingly. Injection pressures were not measured, but the same injection technique was employed throughout the study in both sexes and in those with and without pancreatitis. If cannulation of the cystic duct proved unsuccessful, direct needle puncture of the common bile duct was employed. Approximately 10% of patients had been previously excluded because of failure to obtain a technically satisfactory operative cholangiogram. This was either as a result of extravasation of dye, poor positioning of the patient, or poor film penetration. After exclusion ofthese, the data was complete with the possible exception of operative findings relating to the pancreas, which are often subjective and difficult to interpret, and not always recorded even in those with a history of previous pancreatitis. Patients in the pancreatitis group had a documented attack of acute pancreatitis with a serum amylase recorded in excess of 1000 IU during the course of their disease. The number of gallbladder stones was categorized by the exact integer up to 10, but patients with more numerous stones were merely categorized as having multiple stones.
Ann. SUrg * December 1991
TAYLOR AND OTHERS
668
TABLE 3. Age at Cholecystectomy
TABLE 1. Variables Assessed in the Initial Database Age Sex Length of history Presentation Biliary dyspepsia Acute cholecystitis Chronic cholecystitis Biliary colic Pancreatitis Back pain Jaundice Cholangitis Oral cholecystogram or ultrasound scan No. of stones Wall thickened Nonfunction Gallbladder at operation No. of stones Wall thickened Empyema (mucocoele) Mucosal disease Findings on operative cholangiography Duct filling Duct diameter Presence of stones Common channel Pancreatic duct reflux Duodenal filling Operative measurements Common bile duct Dilated (>10 mm) Stones palpable Pancreas Normal Abnormal
1 2 3 4
Results Of the 664 patients, 52 had pancreatitis (7.8%). The range of the length of patients' histories attributable to gallstones was from 1 week to 25 years, with a median of 1 year. Although gallstones occurred in three times as TABLE 2. Incidence of Pancreatitis by Sex
Chi square
=
12.8; p < 0.0001.
M M F F
Mean Age Median SD (yr) Age (yr) (yr)
No pancreatitis Pancreatitis No pancreatitis
55.7 51.8 48.8 55.5
Pancreatitis
13.8 14.6 15.1 17.5
58 51 50 63
n
149 25 463 27
Differences: group 1 vs. group, p = 0.2; group 3 vs. group 4, p = 0.02, z = -2.4; group 2 vs. group 4, p = 0.3; group 1 vs. group 3, p = 0.001, z = -5.1. Mann-Whitney U test.
The range of gallstone size in each individual case was recorded, as was the number of common bile duct stones, from both the operative cholangiogram and the exploratory findings. The timing of surgery in relation to an attack of acute pancreatitis varied over the duration of the study from deferred surgery early in the study, to early surgery in the most recent cases. There were 174 men and 490 women (1:2.8). No difference existed regarding the attitude to surgical treatment of the two sexes.
No pancreatitis Pancreatitis
Diagnosis
Group Sex
M
F
149 25
463 27
many women as men, acute pancreatitis was a significantly more common complication of gallstones in men (p < 0.0001) than in women (Table 2). Women underwent surgery for uncomplicated gallstones at a mean age of 48.8 years (Table 3). Although women developed pancreatitis when 6.7 years older than the average age at which they underwent elective cholecystectomy, men had surgery for gallstone pancreatitis 4 years earlier than those who underwent cholecystectomy for uncomplicated disease, and also 4 years earlier than women with pancreatitis. Thus not only are men more prone to pancreatitis, but they suffer this complication earlier in the course of their gallstone disease than do women. There was no significant difference overall in the length of history of gallstone-related symptoms between the pancreatitis and nonpancreatitis groups. A previous history of biliary dyspepsia was much less frequent in men and women with pancreatitis than in those without this complication (p < 0.0001) (Table 4). Biliary colic had occurred much more frequently in both men and women who presented with no history of pancreatitis, this was particularly the case in men. A history of chronic cholecystitis was present in only 4% of men, compared with 35% of women with pancreatitis; in the TABLE 4. Symptom Complexes at Time of Presentation M
Presenting Features
Biliary dyspepsia No dyspepsia Dyspepsia Chi square p
Biliary colic No colic Colic Chi square p Chronic cholecystitis No cholecystitis
Cholecystitis Chi square p
No Pancreatitis
F Pancreatitis
No Pancreatitis
Pancreatitis
85 64 15.2
