1135
CLINICAL PRACTICE
Gallstone formation after major abdominal surgery
84 patients underwent multiple abdominal ultrasound examinations over a median of 36 months (range 6-140). 11 had gallstones at their first ultrasound examination, and were excluded from further analysis. Of the remaining 73 patients, 12 of 47 who underwent major abdominal surgery had gallstones within 14-36 months of operation, compared with 0 of 26 who did not undergo such surgery. The cumulative prevalence of new gallstones within 3 years of major surgery was 28%; no new gallstones were seen from 36 to up to 140 months postoperatively. By univariate and logistic regression analysis, age and major abdominal surgery were the only significant clinical determinants for the appearance of gallstones during follow-up. The findings of this retrospective study indicate that major abdominal surgery may accelerate the development of gallstones in some patients. If confirmed in a prospective study, it may be possible to define groups at high risk of gallstones after surgery and to institute prophylactic measures. Lancet 1991; 337: 1135-37.
Introduction
Although gallstones are associated with previous total parenteral nutrition and intensive care,1-3 open heart surgery,’ surgery for morbid obesity,s ileal resection or bypass,6 partiaF and total8 gastrectomy, and, possibly, vagotomy,9-12 it remains unclear whether major abdominal surgery is itself a cause of or a precipitating factor for their formation. We retrospectively studied a group of patients who had undergone serial ultrasound examinations to identify the prevalence and clinical associations of gallstones that appeared during follow-up. Materials and methods We reviewed 84 consecutive patients (39 males, 45 females; mean age 46years, range 11-84) who underwent at least 2 ultrasound examinations separated by 6 months or longer. No patient had ever received treatment at any time by total parenteral nutrition, and none was morbidly obese. Patients were divided into two main groups. 47 had undergone major abdominal surgery, defined as abdominal surgery that required at least 48 h postoperative fasting: 43 had surgery to the upper abdomen for hydatid or other liver disease, both benign and malignant; 4 underwent major abdominal surgery to other regions (colectomy for carcinoma [1], pelvic clearance for uterine carcinoma [1], and removal of abdominal or pelvic hydatid cysts [2]). 37 patients who had not had major abdominal surgery were also followed up: 15 had hepatic hydatid
cysts and 22 had confirmed haemangiomas. The median follow-up period was 36 months (range 15-140). Dummy variables were created by use of these categories and age, sex, and observation period. For statistical analysis we used contingency table analyses, non-parametric Mann-Whitney tests, and logistic regression. Cumulative prevalence of gallstones was calculated by standard actuarial techniques and comparisons made between groups by log-rank xz tests.
Results The total prevalence of stones among all 84 patients throughout the study was 27% (23/84). However, this figure includes 11 who were noted to have gallstones at their first ultrasound examination; these 11 patients are excluded from further analysis. Stones developed in 12 of the 73 patients who did not have gallstones at the first examination, a crude prevalence of 16%. The cumulative prevalence, calculated by the life-table method, was 19 % by 3 years; no new stones have been observed after this interval. Univariate statistical analysis to determine the clinical factors associated with gallstone formation assessed variables of age, sex, time of follow-up, the presence of hepatic hydatid disease, and occurrence of major abdominal surgery. Only age at presentation (56 vs 44 years; p 0-0080, Mann-Whitney test) and occurrence of major abdominal surgery (12 of 47 vs 0 of 26, p = 0-0059, two-tailed Fisher test) were significantly different between patients in whom stones developed and those in whom they did not. Logistic regression was used to determine the factors that might predict the occurrence of stones during the study period among the 73 patients initially free of gallstones. Factors included in the first model were age, sex, duration of follow-up, hepatic hydatid disease, and major abdominal surgery. Age and major abdominal surgery were the only independent predictors of statistical significance (p 0.0001 for all variables, p 0-0072 for age, and p 0-0004 for major =
=
=
=
surgery). 12 of 47 patients who underwent major abdominal surgery had stones within 14-36 months of surgery. The cumulative prevalence of new gallstones, calculated by the life-table method, was 28% by 3 years, whereas no stones occurred in patients who did not undergo striking and significant difference surgery-a
(log-rank XI 7-091, p < 0-01;
figure). The prevalence of
ADDRESS Department of Surgery, Westmead Hospital, and University of Sydney, New South Wales, Australia (Prof J. M. Little, FRACS, J. Avramovic, MB) Correspondence to Prof J M. Little, Department of Surgery, Westmead Hospital, Westmead NSW 2145, Australia.
1136
gastrectomy,7 total gastrectomy,8 and vagotomy9-12 may also increase the prevalence of gallstones. No patient in our study had morbid obesity, had received total parenteral nutrition, or had undergone vagotomy, gastric resection, or open heart surgery.
However,
we
do
not
have information
on
milder
obesity, family history, dietary habits, plasma lipid concentrations, or smoking and drinking habits. The prevalence of new stones within 3 years of major abdominal surgery was close to the prevalence of stones over 10 years predicted from Swedish figures standardised for age and sex.l3 The cumulative prevalence of 28% is similar to the 20% over a median follow-up of 30 months reported by Lorusso et al’ in patients who underwent Bilroth type II gastrectomy, but is lower than the 47% within 2 years reported by Hauters and colleagues8 among 30 patients who underwent total gastrectomy. Hauters et al8 noted that age or sex did not affect the postoperative prevalence of gallstones in their Cumulative prevalence of new gallstones from entry into study after major surgery (0-O) and in controls (W-———W). All 73 patients were followed for 18 months. At 18, 30, 42, and 60 months the numbers of patients after major abdominal surgery were 47, 33, 28, and 16, and of controls were 26, 11, 8, and 4, respectively.
gallstones increased with age, with a cumulative prevalence of 44% of all patients by 60 years. All new gallstones formed in patients who underwent major abdominal surgery, in whom the prevalence reached 58% by 60 years of age. The difference in prevalence between the surgical and nonsurgical groups by age at entry to the study was statistically significant (log-rank X2 46037, p < 005). 7 of the 12 patients in whom gallstones developed during follow-up had associated biliary colic; so far 3 have required cholecystectomy and 1 has undergone endoscopic removal =
of a stone from the
common
bileduct.
Discussion
Comparison of the prevalence of gallstones among different populations is notoriously difficult, not only because of differences in the availability of diagnostic facilities and attitudes to treatment, but because many patients who have gallstones remain syrnptom-free. Of available data, those from Sweden apparently reflect a high
population prevalence:13 if applied to the 73 patients in our study, they would predict that cholelithiasis would develop in 7 patients within 10 years, whereas we observed gallstones in 12 patients in a median follow-up of 3 years. Although the patients we studied are not representative of all patients who undergo major abdominal surgery (43 of the 47 operations included hepatic surgery), it is striking that 12 of 47 had stones within 14-36 months, compared with 0 of 26 controls. The controls were younger at presentation; no doubt gallstones will be observed among the patients who did not undergo surgery with longer follow-up, but the findings of this retrospective survey indicate a possible increased susceptibility to gallstones after major abdominal surgery.
Many other factors may influence the development of gallstones in patients who undergo surgery, including sex,14,15 family history, 14,15 dietary habits (particularly total fat and calorie intake),16 obesity,16 abnormal cholesterol metabolism,17 and episodes of fasting18 or total parenteral nutrition.1-3 Open heart surgery,4 surgical treatment of morbid obesity,s ileal resection or bypassBilroth type II
patients. Lorusso et aF observed an excess prevalence only among men, but few women were included in their study. By what mechanisms could major abdominal surgeryoutside the biliary tract-predispose to gallstone formation? Subjects who fast for 24 h or more develop sludge in the gallbladder visible on ultrasonography. 1920 Lee and colleagues21 have investigated the composition and fate of this material, which consists of mucus, calcium bilirubinate, and cholesterol crystals: in 96 patients followed for more than 2 years the sludge disappeared completely in 17, disappeared and reappeared repeatedly in 58, and preceded gallstone formation in 14, 6 of whom needed cholecystectomy for symptoms; subtotal fasting for 2 weeks did not cause sludge to appear. The appearance of gallbladder sludge has been observed during total parenteral nutrition;12 progression to stone formation, usually pigment stones, has been recorded,3but resumption of oral feeding usually causes the sludge to disappear within 4 weeks.1 Harrison and colleagues4 observed that in patients with rheumatic cardiac valve disease the crude prevalence of gallstones was 39% among those who underwent valvereplacement surgery, compared with about 12% in those who had no surgery; age, sex, and race were not individual determinants for gallstone development. Harrison et al4 speculated that excess haemolysis might lead to gallstone formation, but there were no differences in the presence or degree of haemolysis between surgical and non-surgical groups and they did not record the chemical composition of the stones, which were detected by oral cholecystogram or at necropsy. With our findings these observations indicate that major surgery may itself be an important determinant of gallstones soon after operation. It may be that sludge formation during fasting is the common pathway, perhaps with other factors associated with the stress of surgery in general. The physiological disturbances of certain abdominal operations-such as ileal resection, which interferes with the normal enterohepatic bile salt cycle’ -may produce metabolic disturbances particularly likely to lead to gallstone formation. Our observation that the 10-year predicted prevalence of new stones was detected within 3 years of surgery may indicate that major abdominal surgery accelerates the development of gallstones in people at risk. The findings of this retrospective study need further examination in a larger, prospective trial with careful stratification of patients and examination of possible risk factors to identify groups at particularly high risk. If 1 person in 4 develops gallstones within a few years of major surgery, and more than half of those with gallstones have
1137
are major economic and practical The treatment of gallstones is expensive,z2 and implications. the advent of the extracorporeal shock-wave despite other and non-surgical techniques, ttie potential lithotripsy another of risk operation within a few years of major surgery be would distressing for patients and their surgeonsparticularly if the original procedure was to treat cancer or cardiac disease. If those at high risk of postoperative gallstones could be identified, it may be possible to institute prophylactic measures such as the use of cholecystokinin23 or early feeding1 to empty the gallbladder of the sludge seen on ultrasonography in fasting patients,18,19 and which may be the precursor of stones.2o
symptoms, there
REFERENCES 1. Messing
B, Bories C, Kunstlinger F, Bernier JJ. Does total parenteral
nutrition
induce gallbladder sludge formation and lithiasis? Gastroenterology 1983; 84: 1012-19. 2. Roslyn JJ, Pitt HA, Mann LL, Fonklesrud EW, DenBesten L. Parenteral nutrition-induced gallbladder disease: a reason for early cholecystectomy. Am J Surg 1984; 148: 58-63. 3. Pitt HA, Berquist WE, Mann LL, et al. Parenteral nutrition induces calcium bilirubinate gallstones. Gastroenterology 1983; 84: 1274. 4. Harrison EC, Roschke EJ, Meyers HI, et al. Cholelithiasis: a frequent complication of artificial heart valve replacement. Am Heart J 1978; 95: 483-88. 5. Deitel M, Petrov I. Incidence of symptomatic gallstones after bariatric operations. Surg Gynecol Obstet 1987; 164: 549-52. 6. Heaton KW, Read AE. Gallstones m patients with disorders of the terminal ileum and disturbed bile salt metabolism. Br Med J 1969; iii: 494-96. 7. Lorusso D, Misciagnia G, Noviello MR, Tarantino S. Cholelithiasis after Bilroth II gastric resection. Surgery 1988; 103: 579-83. 8. Hauters P, de Neve de Roden A, Pourbaix A, Aupaix F, Coumans P,
Therasse G. Cholelithiasis: a serious complication after total gastrectomy. Br J Surg 1988; 75: 899-900. 9. Miller MC. Cholelithiasis developing after vagotomy. Can Med Assoc J 1968; 98: 350-54. 10. Tompkms R, Kraft AR, Zimmerman E, Lichtenstein JE, Zollinger RM. Clinical and biochemical evidence of increased gallstone formation after complete vagotomy. Surgery 1972; 71: 196-99. 11. Cowie AGA, Clark CG. The lithogenic effect of vagotomy. Br J Surg 1972; 59: 365-67. 12. Ihasz M, Griffith CA. Gallstone after vagotomy. Am J Surg 1981; 141: 48-50. 13. Lindstrom CG. Frequency of gallstone disease in a well-defined Swedish population. A prospective necropsy study in Malmo. ScandJ Gastroenterol 1977; 12: 341-46. 14. Bennion LJ, Grundy SM. Risk factors for the development of cholelithiasis in man. N Engl J Med 1978; 299: 1161-67. 15. Bennion LJ, Grundy SM. Risk factors for the development of cholelithiasis in man. N Engl J Med 1978; 299: 1221-27. 16. Bennion LJ, Grundy SM. Effects of obesity and caloric intake on biliary lipid metabolism in man. J Clin Invest 1975; 56: 996-1011. 17. Salen G, Nicolau G, Shefer S, Mosbach EH. Hepatic cholesterol metabolism in patients with gallstones. Gastroenterology 1975; 69: 676-84. 18. Duane WC, Ginsberg RL, Bennion LJ. Effects of fasting on bile acid metabolism and biliary lipid composition in man. J Lipid Res 1976; 17: 211-19. 19. Gosbink BR, Leopold GR. Ultrasound and the gallbladder. Semin Radiol 1976; 11: 185-89. 20. Bolondi L, Gaiani S, Testa S, Labo G. Gallbladder sludge formation during prolonged fasting after gastrointestinal tract surgery. Gut 1985; 26: 734-38. 21. Lee SP, Maher K, Nicholas JF. Origin and fate of biliary sludge. Gastroenterology 1988; 94: 170-76. 22. Bengmark S, Lindgren B, Sorbris R. Economic aspects of gallstone disease and its management. In: Blumgart LH, ed. The biliary tract. Edinburgh: Churchill Livingstone, 1982: 270-81. 23. Doty JE, Pitt HA, Porter-Fink V, DenBesten L. Cholecystokinin prophylaxis of parenteral nutrition-induced gallbladder disease. Ann
Surg 1985; 20: 76-80.
Treatment of systemic vasculitis with intravenous immunoglobulin
therapeutic effect of a course of high-dose, pooled, intravenous immunoglobulin (IVIg) on disease activity and circulating antineutrophil cytoplasm antibodies (ANCA) was investigated in 7 patients with systemic vasculitis. 5 had active disease despite conventional immunosuppression, and 2 The
had not received any treatment. All 7 had clinical improvement, which was sustained in 6 and transient in 1. The fall in ANCA concentrations to a mean of 51% of the pre-treatment values was maintained during follow-up. C-reactive protein concentration also dropped considerably. IVIg seemed to confer a useful therapeutic effect without adverse reaction. Lancet 1991; 337: 1137-39.
Introduction The
of the systemic vasculitides by with corticosteroid and cytotoxic drugs produces clinical improvement in up to 90% of patients but complete remission in only 50-70%.1 Furthermore, the need for continuing treatment exposes the patient to the risks of long-term immunosuppressive treatment
immunosuppression
pooled
therapy. 1,2 Limited
success
such A. cyclosporin 3,4
sulfamethoxazole/trimethoprim
treatments
as
has been
reported with and
Antineutrophil cytoplasm antibodies (ANCA) are present in the serum of patients with systemic vasculitis, and ANCA titre and isotype have been linked to disease severity and distribution.5,6 Direct evidence of a pathogenetic role for ANCA has come from in-vitro study of the effects of ANCA on neutrophil function.7 Pooled intravenous immunoglobulin (IVIg) has been used in several autoimmune conditions, including Kawasaki disease, an ANCA-positive vasculitis, but the mechanisms its effect are unclear and may vary between conditions.8-10 In diseases mediated by autoantibodies an interaction with the idiotypic network has been proposed. This interaction has been demonstrated in anti-factor VIII for
Department of Medicine, School of Clinical Medicine, University of Cambridge, Cambridge (D. R W. Jayne, MRCP, C. M. Lockwood, FRCP); Department of Medicine, Ipswich Hospital, Ipswich (M J Davies, MRCP); Department of Medicine, Northampton General Hospital, Northampton (C J. V. Fox, FRCP); Department of Rheumatology, Royal Free Hospital, London, UK (C. M Black, FRCP). Correspondence to Dr D. R W. Jayne, Department of Medicine, School of Clinical Medicine, Hills Road, Cambridge CB2 2QQ, UK.
ADDRESSES
CLINICAL PRACTICE
Gallstone formation after major abdominal surgery
84 patients underwent multiple abdominal ultrasound examinations over a median of 36 months (range 6-140). 11 had gallstones at their first ultrasound examination, and were excluded from further analysis. Of the remaining 73 patients, 12 of 47 who underwent major abdominal surgery had gallstones within 14-36 months of operation, compared with 0 of 26 who did not undergo such surgery. The cumulative prevalence of new gallstones within 3 years of major surgery was 28%; no new gallstones were seen from 36 to up to 140 months postoperatively. By univariate and logistic regression analysis, age and major abdominal surgery were the only significant clinical determinants for the appearance of gallstones during follow-up. The findings of this retrospective study indicate that major abdominal surgery may accelerate the development of gallstones in some patients. If confirmed in a prospective study, it may be possible to define groups at high risk of gallstones after surgery and to institute prophylactic measures. Lancet 1991; 337: 1135-37.
Introduction
Although gallstones are associated with previous total parenteral nutrition and intensive care,1-3 open heart surgery,’ surgery for morbid obesity,s ileal resection or bypass,6 partiaF and total8 gastrectomy, and, possibly, vagotomy,9-12 it remains unclear whether major abdominal surgery is itself a cause of or a precipitating factor for their formation. We retrospectively studied a group of patients who had undergone serial ultrasound examinations to identify the prevalence and clinical associations of gallstones that appeared during follow-up. Materials and methods We reviewed 84 consecutive patients (39 males, 45 females; mean age 46years, range 11-84) who underwent at least 2 ultrasound examinations separated by 6 months or longer. No patient had ever received treatment at any time by total parenteral nutrition, and none was morbidly obese. Patients were divided into two main groups. 47 had undergone major abdominal surgery, defined as abdominal surgery that required at least 48 h postoperative fasting: 43 had surgery to the upper abdomen for hydatid or other liver disease, both benign and malignant; 4 underwent major abdominal surgery to other regions (colectomy for carcinoma [1], pelvic clearance for uterine carcinoma [1], and removal of abdominal or pelvic hydatid cysts [2]). 37 patients who had not had major abdominal surgery were also followed up: 15 had hepatic hydatid
cysts and 22 had confirmed haemangiomas. The median follow-up period was 36 months (range 15-140). Dummy variables were created by use of these categories and age, sex, and observation period. For statistical analysis we used contingency table analyses, non-parametric Mann-Whitney tests, and logistic regression. Cumulative prevalence of gallstones was calculated by standard actuarial techniques and comparisons made between groups by log-rank xz tests.
Results The total prevalence of stones among all 84 patients throughout the study was 27% (23/84). However, this figure includes 11 who were noted to have gallstones at their first ultrasound examination; these 11 patients are excluded from further analysis. Stones developed in 12 of the 73 patients who did not have gallstones at the first examination, a crude prevalence of 16%. The cumulative prevalence, calculated by the life-table method, was 19 % by 3 years; no new stones have been observed after this interval. Univariate statistical analysis to determine the clinical factors associated with gallstone formation assessed variables of age, sex, time of follow-up, the presence of hepatic hydatid disease, and occurrence of major abdominal surgery. Only age at presentation (56 vs 44 years; p 0-0080, Mann-Whitney test) and occurrence of major abdominal surgery (12 of 47 vs 0 of 26, p = 0-0059, two-tailed Fisher test) were significantly different between patients in whom stones developed and those in whom they did not. Logistic regression was used to determine the factors that might predict the occurrence of stones during the study period among the 73 patients initially free of gallstones. Factors included in the first model were age, sex, duration of follow-up, hepatic hydatid disease, and major abdominal surgery. Age and major abdominal surgery were the only independent predictors of statistical significance (p 0.0001 for all variables, p 0-0072 for age, and p 0-0004 for major =
=
=
=
surgery). 12 of 47 patients who underwent major abdominal surgery had stones within 14-36 months of surgery. The cumulative prevalence of new gallstones, calculated by the life-table method, was 28% by 3 years, whereas no stones occurred in patients who did not undergo striking and significant difference surgery-a
(log-rank XI 7-091, p < 0-01;
figure). The prevalence of
ADDRESS Department of Surgery, Westmead Hospital, and University of Sydney, New South Wales, Australia (Prof J. M. Little, FRACS, J. Avramovic, MB) Correspondence to Prof J M. Little, Department of Surgery, Westmead Hospital, Westmead NSW 2145, Australia.
1136
gastrectomy,7 total gastrectomy,8 and vagotomy9-12 may also increase the prevalence of gallstones. No patient in our study had morbid obesity, had received total parenteral nutrition, or had undergone vagotomy, gastric resection, or open heart surgery.
However,
we
do
not
have information
on
milder
obesity, family history, dietary habits, plasma lipid concentrations, or smoking and drinking habits. The prevalence of new stones within 3 years of major abdominal surgery was close to the prevalence of stones over 10 years predicted from Swedish figures standardised for age and sex.l3 The cumulative prevalence of 28% is similar to the 20% over a median follow-up of 30 months reported by Lorusso et al’ in patients who underwent Bilroth type II gastrectomy, but is lower than the 47% within 2 years reported by Hauters and colleagues8 among 30 patients who underwent total gastrectomy. Hauters et al8 noted that age or sex did not affect the postoperative prevalence of gallstones in their Cumulative prevalence of new gallstones from entry into study after major surgery (0-O) and in controls (W-———W). All 73 patients were followed for 18 months. At 18, 30, 42, and 60 months the numbers of patients after major abdominal surgery were 47, 33, 28, and 16, and of controls were 26, 11, 8, and 4, respectively.
gallstones increased with age, with a cumulative prevalence of 44% of all patients by 60 years. All new gallstones formed in patients who underwent major abdominal surgery, in whom the prevalence reached 58% by 60 years of age. The difference in prevalence between the surgical and nonsurgical groups by age at entry to the study was statistically significant (log-rank X2 46037, p < 005). 7 of the 12 patients in whom gallstones developed during follow-up had associated biliary colic; so far 3 have required cholecystectomy and 1 has undergone endoscopic removal =
of a stone from the
common
bileduct.
Discussion
Comparison of the prevalence of gallstones among different populations is notoriously difficult, not only because of differences in the availability of diagnostic facilities and attitudes to treatment, but because many patients who have gallstones remain syrnptom-free. Of available data, those from Sweden apparently reflect a high
population prevalence:13 if applied to the 73 patients in our study, they would predict that cholelithiasis would develop in 7 patients within 10 years, whereas we observed gallstones in 12 patients in a median follow-up of 3 years. Although the patients we studied are not representative of all patients who undergo major abdominal surgery (43 of the 47 operations included hepatic surgery), it is striking that 12 of 47 had stones within 14-36 months, compared with 0 of 26 controls. The controls were younger at presentation; no doubt gallstones will be observed among the patients who did not undergo surgery with longer follow-up, but the findings of this retrospective survey indicate a possible increased susceptibility to gallstones after major abdominal surgery.
Many other factors may influence the development of gallstones in patients who undergo surgery, including sex,14,15 family history, 14,15 dietary habits (particularly total fat and calorie intake),16 obesity,16 abnormal cholesterol metabolism,17 and episodes of fasting18 or total parenteral nutrition.1-3 Open heart surgery,4 surgical treatment of morbid obesity,s ileal resection or bypassBilroth type II
patients. Lorusso et aF observed an excess prevalence only among men, but few women were included in their study. By what mechanisms could major abdominal surgeryoutside the biliary tract-predispose to gallstone formation? Subjects who fast for 24 h or more develop sludge in the gallbladder visible on ultrasonography. 1920 Lee and colleagues21 have investigated the composition and fate of this material, which consists of mucus, calcium bilirubinate, and cholesterol crystals: in 96 patients followed for more than 2 years the sludge disappeared completely in 17, disappeared and reappeared repeatedly in 58, and preceded gallstone formation in 14, 6 of whom needed cholecystectomy for symptoms; subtotal fasting for 2 weeks did not cause sludge to appear. The appearance of gallbladder sludge has been observed during total parenteral nutrition;12 progression to stone formation, usually pigment stones, has been recorded,3but resumption of oral feeding usually causes the sludge to disappear within 4 weeks.1 Harrison and colleagues4 observed that in patients with rheumatic cardiac valve disease the crude prevalence of gallstones was 39% among those who underwent valvereplacement surgery, compared with about 12% in those who had no surgery; age, sex, and race were not individual determinants for gallstone development. Harrison et al4 speculated that excess haemolysis might lead to gallstone formation, but there were no differences in the presence or degree of haemolysis between surgical and non-surgical groups and they did not record the chemical composition of the stones, which were detected by oral cholecystogram or at necropsy. With our findings these observations indicate that major surgery may itself be an important determinant of gallstones soon after operation. It may be that sludge formation during fasting is the common pathway, perhaps with other factors associated with the stress of surgery in general. The physiological disturbances of certain abdominal operations-such as ileal resection, which interferes with the normal enterohepatic bile salt cycle’ -may produce metabolic disturbances particularly likely to lead to gallstone formation. Our observation that the 10-year predicted prevalence of new stones was detected within 3 years of surgery may indicate that major abdominal surgery accelerates the development of gallstones in people at risk. The findings of this retrospective study need further examination in a larger, prospective trial with careful stratification of patients and examination of possible risk factors to identify groups at particularly high risk. If 1 person in 4 develops gallstones within a few years of major surgery, and more than half of those with gallstones have
1137
are major economic and practical The treatment of gallstones is expensive,z2 and implications. the advent of the extracorporeal shock-wave despite other and non-surgical techniques, ttie potential lithotripsy another of risk operation within a few years of major surgery be would distressing for patients and their surgeonsparticularly if the original procedure was to treat cancer or cardiac disease. If those at high risk of postoperative gallstones could be identified, it may be possible to institute prophylactic measures such as the use of cholecystokinin23 or early feeding1 to empty the gallbladder of the sludge seen on ultrasonography in fasting patients,18,19 and which may be the precursor of stones.2o
symptoms, there
REFERENCES 1. Messing
B, Bories C, Kunstlinger F, Bernier JJ. Does total parenteral
nutrition
induce gallbladder sludge formation and lithiasis? Gastroenterology 1983; 84: 1012-19. 2. Roslyn JJ, Pitt HA, Mann LL, Fonklesrud EW, DenBesten L. Parenteral nutrition-induced gallbladder disease: a reason for early cholecystectomy. Am J Surg 1984; 148: 58-63. 3. Pitt HA, Berquist WE, Mann LL, et al. Parenteral nutrition induces calcium bilirubinate gallstones. Gastroenterology 1983; 84: 1274. 4. Harrison EC, Roschke EJ, Meyers HI, et al. Cholelithiasis: a frequent complication of artificial heart valve replacement. Am Heart J 1978; 95: 483-88. 5. Deitel M, Petrov I. Incidence of symptomatic gallstones after bariatric operations. Surg Gynecol Obstet 1987; 164: 549-52. 6. Heaton KW, Read AE. Gallstones m patients with disorders of the terminal ileum and disturbed bile salt metabolism. Br Med J 1969; iii: 494-96. 7. Lorusso D, Misciagnia G, Noviello MR, Tarantino S. Cholelithiasis after Bilroth II gastric resection. Surgery 1988; 103: 579-83. 8. Hauters P, de Neve de Roden A, Pourbaix A, Aupaix F, Coumans P,
Therasse G. Cholelithiasis: a serious complication after total gastrectomy. Br J Surg 1988; 75: 899-900. 9. Miller MC. Cholelithiasis developing after vagotomy. Can Med Assoc J 1968; 98: 350-54. 10. Tompkms R, Kraft AR, Zimmerman E, Lichtenstein JE, Zollinger RM. Clinical and biochemical evidence of increased gallstone formation after complete vagotomy. Surgery 1972; 71: 196-99. 11. Cowie AGA, Clark CG. The lithogenic effect of vagotomy. Br J Surg 1972; 59: 365-67. 12. Ihasz M, Griffith CA. Gallstone after vagotomy. Am J Surg 1981; 141: 48-50. 13. Lindstrom CG. Frequency of gallstone disease in a well-defined Swedish population. A prospective necropsy study in Malmo. ScandJ Gastroenterol 1977; 12: 341-46. 14. Bennion LJ, Grundy SM. Risk factors for the development of cholelithiasis in man. N Engl J Med 1978; 299: 1161-67. 15. Bennion LJ, Grundy SM. Risk factors for the development of cholelithiasis in man. N Engl J Med 1978; 299: 1221-27. 16. Bennion LJ, Grundy SM. Effects of obesity and caloric intake on biliary lipid metabolism in man. J Clin Invest 1975; 56: 996-1011. 17. Salen G, Nicolau G, Shefer S, Mosbach EH. Hepatic cholesterol metabolism in patients with gallstones. Gastroenterology 1975; 69: 676-84. 18. Duane WC, Ginsberg RL, Bennion LJ. Effects of fasting on bile acid metabolism and biliary lipid composition in man. J Lipid Res 1976; 17: 211-19. 19. Gosbink BR, Leopold GR. Ultrasound and the gallbladder. Semin Radiol 1976; 11: 185-89. 20. Bolondi L, Gaiani S, Testa S, Labo G. Gallbladder sludge formation during prolonged fasting after gastrointestinal tract surgery. Gut 1985; 26: 734-38. 21. Lee SP, Maher K, Nicholas JF. Origin and fate of biliary sludge. Gastroenterology 1988; 94: 170-76. 22. Bengmark S, Lindgren B, Sorbris R. Economic aspects of gallstone disease and its management. In: Blumgart LH, ed. The biliary tract. Edinburgh: Churchill Livingstone, 1982: 270-81. 23. Doty JE, Pitt HA, Porter-Fink V, DenBesten L. Cholecystokinin prophylaxis of parenteral nutrition-induced gallbladder disease. Ann
Surg 1985; 20: 76-80.
Treatment of systemic vasculitis with intravenous immunoglobulin
therapeutic effect of a course of high-dose, pooled, intravenous immunoglobulin (IVIg) on disease activity and circulating antineutrophil cytoplasm antibodies (ANCA) was investigated in 7 patients with systemic vasculitis. 5 had active disease despite conventional immunosuppression, and 2 The
had not received any treatment. All 7 had clinical improvement, which was sustained in 6 and transient in 1. The fall in ANCA concentrations to a mean of 51% of the pre-treatment values was maintained during follow-up. C-reactive protein concentration also dropped considerably. IVIg seemed to confer a useful therapeutic effect without adverse reaction. Lancet 1991; 337: 1137-39.
Introduction The
of the systemic vasculitides by with corticosteroid and cytotoxic drugs produces clinical improvement in up to 90% of patients but complete remission in only 50-70%.1 Furthermore, the need for continuing treatment exposes the patient to the risks of long-term immunosuppressive treatment
immunosuppression
pooled
therapy. 1,2 Limited
success
such A. cyclosporin 3,4
sulfamethoxazole/trimethoprim
treatments
as
has been
reported with and
Antineutrophil cytoplasm antibodies (ANCA) are present in the serum of patients with systemic vasculitis, and ANCA titre and isotype have been linked to disease severity and distribution.5,6 Direct evidence of a pathogenetic role for ANCA has come from in-vitro study of the effects of ANCA on neutrophil function.7 Pooled intravenous immunoglobulin (IVIg) has been used in several autoimmune conditions, including Kawasaki disease, an ANCA-positive vasculitis, but the mechanisms its effect are unclear and may vary between conditions.8-10 In diseases mediated by autoantibodies an interaction with the idiotypic network has been proposed. This interaction has been demonstrated in anti-factor VIII for
Department of Medicine, School of Clinical Medicine, University of Cambridge, Cambridge (D. R W. Jayne, MRCP, C. M. Lockwood, FRCP); Department of Medicine, Ipswich Hospital, Ipswich (M J Davies, MRCP); Department of Medicine, Northampton General Hospital, Northampton (C J. V. Fox, FRCP); Department of Rheumatology, Royal Free Hospital, London, UK (C. M Black, FRCP). Correspondence to Dr D. R W. Jayne, Department of Medicine, School of Clinical Medicine, Hills Road, Cambridge CB2 2QQ, UK.
ADDRESSES
