Br. J. Surg. Vol. 63 (1976) 797-798
Acalculous gallbladder disease : a prospective study N I G E L C. K E D D I E , A. L. G O U G H A N D R. B. G A L L A N D * SUMMARY
A prospective study of 62 cases of acalculousgallbladder disease is reported. The clinical, radiological andpathological features are described as well as the results of cholecystecfomy with a minimum follow-up of 3 years. The results compare favourably with thosefor cakulous disease, and it is concluded that there is no clear-cut distinction between acalculous and calculous biliary disease. CALCULOUS gallbladder disease is generally accepted as a cause of symptoms, and the results of surgery are very satisfactory. In contrast, the clinical significance of acalculous gallbladder disease is controversial. Nevertheless, a common clinical problem is the patient with typical biliary pain but a ‘normal’ cholecystogram. This study was carried out to assess the clinical problem, to analyse the radiological changes on cholecystography, to review the various pathological changes in the gallbladder and to record the results of cholecystectomy.
Patients Sixty-two patients with acalculous gallbladder disease seen over a 5-year period have been studied prospectively. The minimum follow-up is 3 years and the maximum 8 years. During the same 5-year period 648 cases of calculous gallbladder disease were treated ; thus, the 62 patients with acalculous disease represent 8.7 per cent ofpatients with gallbladder disease. Table I shows the duration of symptoms and Table II the severity of pain. Mild pain did not interfere with the patients’ activities, moderate pain did and severe pain required parenteral analgesics. Associated symptoms are shown in Table IZZ. There was a greater proportion of patients with severe pain in a group with gallstones studied during the same period, but otherwise the symptoms did not differ greatly from those of patients with stones. Radiological findings The X-rays of 43 patients were reviewed. Nineteen patients had their X-rays done at other hospitals, and these have been excluded. Table ZV shows the radiological findings. Twenty patients had X-rays which were considered to be normal even at review. Fourteen per cent showed thickening of the wall of the gall bladder. In chronic cholecystitis fat is deposited around the gallbladder (Moynihan, 1905) and this is less translucent than normal. This appears as a halo around the gallbladder which is best seen on cholecystography, but can also be seen on retrospective review of some plain films. This so-called ‘fat sign’ is helpful in the diagnosis of chronic cholecystitis in some cases (Russell et al., 1976).
Table I: DURATION OF SYMPTOMS No. of cases Duration (yr)
16
24 16 10 6 3 3
% 39 25 16 10 5 5
Table 11: SEVERITY OF PAIN EXPERIENCED Pain Mild Moderate Severe
No. of cases 5 47 10
Table 111: ASSOCIATED SYMPTOMS Symptom No. of cases Fat intolerance Nausea Vomiting Flatulence Diarrhoea Constipation Weight loss
21 14 10 16 8 12 2
% 8 16 16
% 34 23 16 25.5 13 19 3
Table IV: INCIDENCE OF RADIOLOGICAL SIGNS IN 43 PATIENTS Radiological sign No. of cases % 5 12 N o opacification 6 14 Poor function 1 2 Cholesterol polyp 1 2 Adenomyomatosis 2 5 Septum 1 2 Blurring of outline 6 14 Fat sign Abnormal shape 1 2 N o abnormality seen 20 41
Pathological changes The pathological changes are shown in Table V. A point of interest is the frequency of adenomyomatosis in contrast to the frequency of this diagnosis by radiology. The chronic inflammatory changes were identical to those seen in calculous disease. Cholesterolosis was frequently seen in calculous gallbladders. Another interesting sequel of chronic inflammation was intestinal metaplasia. Results The results of cholecystectomy are shown in Table VI. The term ‘complete relief‘ applies to the pain suffered preoperatively. Some of the patients have continued to experience postprandial flatulence, but other associated symptoms have been relieved in the 90 per cent with relief of pain.
* Royal Infirmary, Manchester. 797
Nigel C. Keddie et al. Table V: PATHOLOGY Pathology Adenom yomatosis Chronic inflammation Cholesterolosis Acute inflammation
No. of cases 30 24 6 2
Table VI: RESULTS OF CHOLECYSTECTOMY Result No. of cases 56 Complete relief 6 No change
% 48 39 10 3
”/,
90 10
Table VII: RESULTS OF CHOLECYSTECTOMY IN SERIES OF CASES OF ACALCULOUS GALLBLADDER REPORTED IN THE LITERATURE Author ”/. ‘cured‘ Whipple (1926) 76.6 Muller (1927) 16.2 Mackey (1934) 60 Glenn and Mannix (1956) 65 78 Elfving et al. (1967) Munster and Brown (1967) 60 Anderson et al. (1971) 19 Gunn et al. (1973) 61
considerable. The new ‘fat sign’ described (Russell et al., 1976) has certainly been valuable, but only in a proportion of patients. This prospective study has focused attention on the difficult and controversial subject of acalculous gallbladder disease. It is important to appreciate that the distinction between calculous and acalculous disease is not always clear, and it is well established that stones can disappear either by dissolution or passage (Reid and Rogers, 1975). Some patients in this series may have had stones, although none was found at operation. There is no doubt that cholesterolosis and adenomyomatosis can be associated with calculi, and therefore the sharp distinction drawn between calculous and acalculous disease is quite artificial. The symptoms of calculous and acalculous disease are very similar and the treatment by cholecystectomy gives comparable results. Our conclusion, therefore, is that acalculous gallbladder disease must be accepted as an integral part of the problem of biliary tract pathology and not demarcated from calculous disease as though it were an entirely separate problem. Patients in whom no stones can be demonstrated should be subjected to cholecystectomy provided that other causes of chronic upper abdominal symptoms have been excluded. The results of operation will compare favourably with those for calculous disease.
Discussion The results of cholecystectomy in other series of acalculous gallbladder disease are shown in Table VIZ.The present series and that of Gunn et al. (1973) are the only prospective studies of this problem. Our results are much better than those of other series and References the reasons for this are puzzling. All our patients ANDERSON A., BERGDAHL L. and BOQUIST L. (1971) Acalculous cholecystitis. Am. J. Surg. 122, 3-7. really needed an operation. Many had been seen and investigated at other hospitals and were then referred ELFVING G., LEHTONEN T. and TIER H. (1967) Clinical significance of primary hyperplasia of gallbladder because of persistent symptoms. In over 60 per cent mucosa. Ann. Surg. 165, 61-69. persistent symptoms had been present for a year or more before cholecystectomy. There is a risk that GLENN F. and MANNIX H. (1956) The acalculous gallbladder. Ann. Surg. 144, 670-678. our results may encourage us to perform cholecystectomy too readily, with the risk of more disappointed GUNN A . , KEDDIE N. c. and FOX H. (1973) Acalculous gall-bladder disease. Br. J. Surg. 60, 213-21 5 . patients. There is certainly a need for more accurate radio- MACKEY w . A. (1934) Cholecystitis without stone. Br. J. Surg. 22, 274-295. logy of the gallbladder. Stones are missed all too easily when gallbladder function is good, but in MOYNIHAN v . G. A. (1905) Gall-stones and their Surgical Treatment. London, Saunders, p. 67. chronic inflammation without stone the diagnosis is missed by standard cholecystography in nearly 50 MULLER G. P. (1927) The noncalculous gall-bladder. JAMA 89, 786-789. per cent of cases. Detailed study of the X-rays may show irregularities of the gallbladder wall which are MUNSTER A . M. and BROWN J. R . (1967) Acalculous cholecystitis. Am. J. Surg. 113, 730-734. missed initially. These may represent cholesterolosis, inflammatory polypi or chronic inflammation in the REID D. R . K . and ROGERS I. M. (1975) The negative cholecystogram in gallbladder disease. Br. J. wall. There may be the classic changes of adenoSurg. 62, 581-583. myomatosis, but in this series this diagnosis was made on histology much more frequently than by RUSSELL J. G. B., KEDDIE N. c . , GOUGH A. L. et al. (1976) Radiology of acalculous gall-bladder diseaseradiology. A full discussion of the clinical significance a new sign. Br. J. Radiol. 49, 420424. of adenomyomatosis was given in an earlier report of a smaller number of cases (Gunn et al., 1973) because WHIPPLE A. c. (1926) Surgical criteria for cholecystectomy. Am. J . Surg. 38, 129-131. the radiological literature on this subject is very
798
Acalculous gallbladder disease : a prospective study N I G E L C. K E D D I E , A. L. G O U G H A N D R. B. G A L L A N D * SUMMARY
A prospective study of 62 cases of acalculousgallbladder disease is reported. The clinical, radiological andpathological features are described as well as the results of cholecystecfomy with a minimum follow-up of 3 years. The results compare favourably with thosefor cakulous disease, and it is concluded that there is no clear-cut distinction between acalculous and calculous biliary disease. CALCULOUS gallbladder disease is generally accepted as a cause of symptoms, and the results of surgery are very satisfactory. In contrast, the clinical significance of acalculous gallbladder disease is controversial. Nevertheless, a common clinical problem is the patient with typical biliary pain but a ‘normal’ cholecystogram. This study was carried out to assess the clinical problem, to analyse the radiological changes on cholecystography, to review the various pathological changes in the gallbladder and to record the results of cholecystectomy.
Patients Sixty-two patients with acalculous gallbladder disease seen over a 5-year period have been studied prospectively. The minimum follow-up is 3 years and the maximum 8 years. During the same 5-year period 648 cases of calculous gallbladder disease were treated ; thus, the 62 patients with acalculous disease represent 8.7 per cent ofpatients with gallbladder disease. Table I shows the duration of symptoms and Table II the severity of pain. Mild pain did not interfere with the patients’ activities, moderate pain did and severe pain required parenteral analgesics. Associated symptoms are shown in Table IZZ. There was a greater proportion of patients with severe pain in a group with gallstones studied during the same period, but otherwise the symptoms did not differ greatly from those of patients with stones. Radiological findings The X-rays of 43 patients were reviewed. Nineteen patients had their X-rays done at other hospitals, and these have been excluded. Table ZV shows the radiological findings. Twenty patients had X-rays which were considered to be normal even at review. Fourteen per cent showed thickening of the wall of the gall bladder. In chronic cholecystitis fat is deposited around the gallbladder (Moynihan, 1905) and this is less translucent than normal. This appears as a halo around the gallbladder which is best seen on cholecystography, but can also be seen on retrospective review of some plain films. This so-called ‘fat sign’ is helpful in the diagnosis of chronic cholecystitis in some cases (Russell et al., 1976).
Table I: DURATION OF SYMPTOMS No. of cases Duration (yr)
16
24 16 10 6 3 3
% 39 25 16 10 5 5
Table 11: SEVERITY OF PAIN EXPERIENCED Pain Mild Moderate Severe
No. of cases 5 47 10
Table 111: ASSOCIATED SYMPTOMS Symptom No. of cases Fat intolerance Nausea Vomiting Flatulence Diarrhoea Constipation Weight loss
21 14 10 16 8 12 2
% 8 16 16
% 34 23 16 25.5 13 19 3
Table IV: INCIDENCE OF RADIOLOGICAL SIGNS IN 43 PATIENTS Radiological sign No. of cases % 5 12 N o opacification 6 14 Poor function 1 2 Cholesterol polyp 1 2 Adenomyomatosis 2 5 Septum 1 2 Blurring of outline 6 14 Fat sign Abnormal shape 1 2 N o abnormality seen 20 41
Pathological changes The pathological changes are shown in Table V. A point of interest is the frequency of adenomyomatosis in contrast to the frequency of this diagnosis by radiology. The chronic inflammatory changes were identical to those seen in calculous disease. Cholesterolosis was frequently seen in calculous gallbladders. Another interesting sequel of chronic inflammation was intestinal metaplasia. Results The results of cholecystectomy are shown in Table VI. The term ‘complete relief‘ applies to the pain suffered preoperatively. Some of the patients have continued to experience postprandial flatulence, but other associated symptoms have been relieved in the 90 per cent with relief of pain.
* Royal Infirmary, Manchester. 797
Nigel C. Keddie et al. Table V: PATHOLOGY Pathology Adenom yomatosis Chronic inflammation Cholesterolosis Acute inflammation
No. of cases 30 24 6 2
Table VI: RESULTS OF CHOLECYSTECTOMY Result No. of cases 56 Complete relief 6 No change
% 48 39 10 3
”/,
90 10
Table VII: RESULTS OF CHOLECYSTECTOMY IN SERIES OF CASES OF ACALCULOUS GALLBLADDER REPORTED IN THE LITERATURE Author ”/. ‘cured‘ Whipple (1926) 76.6 Muller (1927) 16.2 Mackey (1934) 60 Glenn and Mannix (1956) 65 78 Elfving et al. (1967) Munster and Brown (1967) 60 Anderson et al. (1971) 19 Gunn et al. (1973) 61
considerable. The new ‘fat sign’ described (Russell et al., 1976) has certainly been valuable, but only in a proportion of patients. This prospective study has focused attention on the difficult and controversial subject of acalculous gallbladder disease. It is important to appreciate that the distinction between calculous and acalculous disease is not always clear, and it is well established that stones can disappear either by dissolution or passage (Reid and Rogers, 1975). Some patients in this series may have had stones, although none was found at operation. There is no doubt that cholesterolosis and adenomyomatosis can be associated with calculi, and therefore the sharp distinction drawn between calculous and acalculous disease is quite artificial. The symptoms of calculous and acalculous disease are very similar and the treatment by cholecystectomy gives comparable results. Our conclusion, therefore, is that acalculous gallbladder disease must be accepted as an integral part of the problem of biliary tract pathology and not demarcated from calculous disease as though it were an entirely separate problem. Patients in whom no stones can be demonstrated should be subjected to cholecystectomy provided that other causes of chronic upper abdominal symptoms have been excluded. The results of operation will compare favourably with those for calculous disease.
Discussion The results of cholecystectomy in other series of acalculous gallbladder disease are shown in Table VIZ.The present series and that of Gunn et al. (1973) are the only prospective studies of this problem. Our results are much better than those of other series and References the reasons for this are puzzling. All our patients ANDERSON A., BERGDAHL L. and BOQUIST L. (1971) Acalculous cholecystitis. Am. J. Surg. 122, 3-7. really needed an operation. Many had been seen and investigated at other hospitals and were then referred ELFVING G., LEHTONEN T. and TIER H. (1967) Clinical significance of primary hyperplasia of gallbladder because of persistent symptoms. In over 60 per cent mucosa. Ann. Surg. 165, 61-69. persistent symptoms had been present for a year or more before cholecystectomy. There is a risk that GLENN F. and MANNIX H. (1956) The acalculous gallbladder. Ann. Surg. 144, 670-678. our results may encourage us to perform cholecystectomy too readily, with the risk of more disappointed GUNN A . , KEDDIE N. c. and FOX H. (1973) Acalculous gall-bladder disease. Br. J. Surg. 60, 213-21 5 . patients. There is certainly a need for more accurate radio- MACKEY w . A. (1934) Cholecystitis without stone. Br. J. Surg. 22, 274-295. logy of the gallbladder. Stones are missed all too easily when gallbladder function is good, but in MOYNIHAN v . G. A. (1905) Gall-stones and their Surgical Treatment. London, Saunders, p. 67. chronic inflammation without stone the diagnosis is missed by standard cholecystography in nearly 50 MULLER G. P. (1927) The noncalculous gall-bladder. JAMA 89, 786-789. per cent of cases. Detailed study of the X-rays may show irregularities of the gallbladder wall which are MUNSTER A . M. and BROWN J. R . (1967) Acalculous cholecystitis. Am. J. Surg. 113, 730-734. missed initially. These may represent cholesterolosis, inflammatory polypi or chronic inflammation in the REID D. R . K . and ROGERS I. M. (1975) The negative cholecystogram in gallbladder disease. Br. J. wall. There may be the classic changes of adenoSurg. 62, 581-583. myomatosis, but in this series this diagnosis was made on histology much more frequently than by RUSSELL J. G. B., KEDDIE N. c . , GOUGH A. L. et al. (1976) Radiology of acalculous gall-bladder diseaseradiology. A full discussion of the clinical significance a new sign. Br. J. Radiol. 49, 420424. of adenomyomatosis was given in an earlier report of a smaller number of cases (Gunn et al., 1973) because WHIPPLE A. c. (1926) Surgical criteria for cholecystectomy. Am. J . Surg. 38, 129-131. the radiological literature on this subject is very
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