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Digestive Disease as a National Problem
Vol. 55, No. I Printed in U.S.A.
GASTROENTEROLOGY
Copyright © 1968 by The Williams & Wilkins Co.
DIGESTIVE DISEASE AS A NATIONAL PROBLEM V. Gallstones FRANZ
J.
lNGELFINGER,
M .D.
Boston, M assachusetls
If there is any illness characteristic of our recent presidents, it is gallstones. President Johnson and President Eisenhower had gallstones removed in 1965 and 1966, President Hoover in 1958, and President Truman in 1954. Although it is apparent that important people are the unhappy possessors of gallstones, there is little evidence that accomplishment begets gallstones. In the matter of having this disease, our presidents are mere examples of what is also true of lesser folk. Stones, particularly the variety containing large amounts of cholesterol, tend to form in the gall bladders of many, many Americans and Europeans, and their frequency increases progressively with age. Perhaps the most telling figures to remember arc those of the prevalence of gallstones in the age group 55 to 64. In this decade, just before we get under the umbrella of Medicare, 10% of men and 20% of women have gallstones. In absolute numbers, this means that between 2.5 and 3.0 million of our people aged 55 to 64-the time of greatest productivity for many-arc so afflicted. In the entire United States population, some 15 million people must be carrying stones in the little bag that stores bilr. Reeei ved February 26, 1968. Ace.cpted February 27, 1968. Address re()uests for reprints to: Dr. Franz J. lngelfinger, 10 Shattuck Strcd., Boston. Massaehusetts 02115. This paper was prepared for presentation at the Conference on Digestive Disease as a N ationa! Problem, Bethesda, Maryland, February 5 to 7, 1967. The conference was sponsored jointly by The American Gastroenterological Asso ciation, The Digestive Disease Foundation, and tlH' National Institute of Arthritis and Mctaboli<' DiseasPs.
What is being done about this-obviously one of the most prevalent disorders affecting our people? In a purely clinical way, a great deal is being done because the standard treatment of gallstones that cause symptoms is the surgical removal of these stones including the gall bladders in which they formed-even as was done so successfully in presidents, but with more unhappy results in Sir Anthony Eden. Removing gall bladders is big business: about one-third of a million are removed annually, according to the National Center of Health Statistics. The hospitalization and medical expense that this entails must come close to half of a billion dollars. The mortality ascribed to gallstone disease is, however, relatively low-around 6000 annually. These statistic:; indicate that tho:;e gall:;tones which make their presence known by causing pain , inflammation, or jaundice ran he removed with great surgical skill. In other words, we hav(• a satisfactory capability of defeating the enemy, but only after h(~ is well established and is causing trouble. The battle, furthermore, is expensive and not without its casualtil's. In contrast, attempt:; at prevention of this disease have beL'n quite infrequent. Very few have tried to find out how gallstonl',; form, u·ha t causes them to form, and whether their formation could be prcnnted or reversed by dietary or medicina I means. Although the situation is rapidly improving, there are probably not more than five laboratories in this country that are both interested in the biophysical mechanisms underlying human gallston<' formation and, at the same time , intellectually and physically equipped to tackle 102
103
DIGESTIVE DISEASE. V
J u ly 1968
these problems, in short, one basic research facility per 3 million gallstone carriers. Currently these facilities are analyzing and determinin g the proport iona l interrelations among water, cholesterol , bile salts, and lecit hin that main tain bile in its normal liquid phase, or that induce on e or more solid or semisolid phases. The role of protein a nd pigment in th ese phenomena is not known. In addition , little is known of the forces that cause aggregat:on of precipitated solids into ston es of various sizes. When I say 15 million Americans have gallstones, I must admit th a t it is an estimate. Th e freque ncy of ga llstones at death ca n be determin ed, but t heir exact prevalence in the living is unknown . Ga llston es are ctiagnosed as a rule only afte r they have caused symptoms. To determin e the frequ ency of asymp tomatic-so-ca lled silent-stone!i, surveys of se lected population groups are necessary. Such surveys require the usc of sta ndard techniques employed in X-mying the ga ll bl adder , but they ca nno t be regard ed as diffi cult, da nge rous, or excl'ss ivc ly cos tly. However, such surveys of gallstone preva lence a relik e basic studies on gallston e form atio n -chiefly di::;tin gui shcd fo r their pau city. The purpose of surveys to clcte nninv the frequ eney of gallston e::; among t he livin g is no t mcr<'ly to amass dry demoT ,\ 1!1. (,;
graphic data. To the contrary, both long term theoretical and practical immedi ate ends could be served. There is the strong impressi on, for example, that gallstones are unusually preva lent among our Indians, such as the Na vajo a nd the Pima. If th is impressi on were confirmed by a precise survey, analyses of possibly related factors, such as India n ha bits, di et, a nd genetics, could be under tak en. As of t he present, some Indian t ribes sti ll live as homogeneous populations in quite circumsc ribed a reas. Th ese areas are not far a way in some in accessible jungle- they are righ t here in the Un ited States with topno tch technica l facilities close at hand. The hea lth of the Indi ans, moreover, is a lready a Public H ealth Service responsibili ty. If anythin g is to be made of th is opportunity, however, the t ime is now because In dia n t raits are disappea ring under the pressures of assi milation. Circumstances t hus would appear ideal -anct somewh at urgent--fo r carrying out several a ppropriate ::;mveys in short order. Unfortun ately, only on e group of inV<'stigators is at work on the problem, hut their progress is gratifying. A prelimin ary study comparin g clini cally manift•st ga llston e ct isease in Indi a ns with findings previously reported in a white population has a lready been published (tabl e 1) .1 More important is a prospective
1. JJrcvalcru:e of "definite" yall bladrlc r cl-isease in th e two s tudies" F ramingham group
Pima Indians
----- - - - · Ag-e at entry into study
Sex
With disease
With disease No. at risk
No. at ri!lk
No. "', I; - - - - - - · -- ·-- - - ---·
·- --··-- -· ··-----·
No.
%
1 1 7 9 16 20 21 57
2.0 2.2 12.3" 5.9" 35.6" 39 .2" 33.8" 36.0b
yr
30- 3\J 40-49 50- G2
M a les
T otals Fema les
832 779 725 233G 1037 9G3 873 2873
30-3\l 40- 4\J 50-62
T otal s - · - · · --
-
-
- -· - - - - -· - - - - - - - · - --
-
- ·_
1 7 23 31 24 58 88 170 _ _:....__ _ __
0.1 0.9 3.2 1.3 2.3 6.0 10.1 5.9
51 45 57 153 45 51 62 158
_ __ , _ _ __
_ _.....c__
_
" Hc produ ced by permiss ion of t he authors a nd 'J'h.e New En gland Journal of M edicin e. b p < 0.01.
_ __
_
_
104
DIGESTIVE DISEASE. V
study of total gallstone prevalence, asymptomatic as well as symptomatic, that is under way. Studies on the epidemiology of gallstones are not only directed at solving the riddle of their pathogenesis. They would, if available, help to settle some very practical problems. What advice, for example, should be given to the patient who has a silent, i.e., a symptomless gallstone, which was discovered incidentally by an abdomina l X-ray taken for some other purpose? The surgeon, mindful of t he threat of future complications, might advise immediate prophylactic cholecystectomy. The internist, on the other hand , may be equally positive in advocating a wait-and-see policy. Either advice is based on faith and hope-no more. No reliable information whatsoever is available to help the doctor decide whether the patient with a silent gallstone is better off doing nothing or having his gall bladder taken out. However, the needed information is, so to speak, just around the corner, waiting to be secured at relatively little effort and cost. A program of randomly selected population groups would quickly reveal who has gallstones, and a follow-up over the ensuing y ears would then give figures as to the likelihood of later symptoms, serious complications, and clinically necessary surgery. These data could then be compared with the advantages and risks
Vol. 55, No . 1
of immediate prophylactic surgery for the patient with a silent gallstone. Why has such a program not been carried out? Why, indeed, has t he study of gallstones been lagging in general? I n view of the prevalence of gallstones and the major disabilities that they cause, there is no satisfactory answer to this question. One can only conclude unhappily that gallstones have not been an "in" disease. They certainly have been neglected by us, the medical profession, but, in addition , their image has not had the benefit of public relations counsel, and they have not been viewed wit h due alarm by public spirited citizens such as the "Health Syndicate," 2 our Congressiona l Committees, or even the American Gastroenterological Association. In matters of health, the study of a disease should be supported on the basis of hard facts: its frequency, its importance as a cause of disability and death, and-from a practical viewpoint-the likelihood of obtainin g answers. Viewed in the ligh t of these criteria, the study of gallstones has been grossly neglected. REFERENCES 1. Comess, L. J., P. H. Bennett, and T . A. Burell. 1967. Clinical gallbladder disease in Pima Indians : its hi gh prevalence in contrast to Framingham, Massach usf'tts. New Eng . J. Med. 277 : 894-898. 2. Drew, E. B . 1967. H eath sy ndieate: Washin gton 's noble eonspirators. The Atlantic 220: 75--82.
GASTROENTEROLOGY
Copyright © 1968 by The Williams & Wilkins Co.
DIGESTIVE DISEASE AS A NATIONAL PROBLEM V. Gallstones FRANZ
J.
lNGELFINGER,
M .D.
Boston, M assachusetls
If there is any illness characteristic of our recent presidents, it is gallstones. President Johnson and President Eisenhower had gallstones removed in 1965 and 1966, President Hoover in 1958, and President Truman in 1954. Although it is apparent that important people are the unhappy possessors of gallstones, there is little evidence that accomplishment begets gallstones. In the matter of having this disease, our presidents are mere examples of what is also true of lesser folk. Stones, particularly the variety containing large amounts of cholesterol, tend to form in the gall bladders of many, many Americans and Europeans, and their frequency increases progressively with age. Perhaps the most telling figures to remember arc those of the prevalence of gallstones in the age group 55 to 64. In this decade, just before we get under the umbrella of Medicare, 10% of men and 20% of women have gallstones. In absolute numbers, this means that between 2.5 and 3.0 million of our people aged 55 to 64-the time of greatest productivity for many-arc so afflicted. In the entire United States population, some 15 million people must be carrying stones in the little bag that stores bilr. Reeei ved February 26, 1968. Ace.cpted February 27, 1968. Address re()uests for reprints to: Dr. Franz J. lngelfinger, 10 Shattuck Strcd., Boston. Massaehusetts 02115. This paper was prepared for presentation at the Conference on Digestive Disease as a N ationa! Problem, Bethesda, Maryland, February 5 to 7, 1967. The conference was sponsored jointly by The American Gastroenterological Asso ciation, The Digestive Disease Foundation, and tlH' National Institute of Arthritis and Mctaboli<' DiseasPs.
What is being done about this-obviously one of the most prevalent disorders affecting our people? In a purely clinical way, a great deal is being done because the standard treatment of gallstones that cause symptoms is the surgical removal of these stones including the gall bladders in which they formed-even as was done so successfully in presidents, but with more unhappy results in Sir Anthony Eden. Removing gall bladders is big business: about one-third of a million are removed annually, according to the National Center of Health Statistics. The hospitalization and medical expense that this entails must come close to half of a billion dollars. The mortality ascribed to gallstone disease is, however, relatively low-around 6000 annually. These statistic:; indicate that tho:;e gall:;tones which make their presence known by causing pain , inflammation, or jaundice ran he removed with great surgical skill. In other words, we hav(• a satisfactory capability of defeating the enemy, but only after h(~ is well established and is causing trouble. The battle, furthermore, is expensive and not without its casualtil's. In contrast, attempt:; at prevention of this disease have beL'n quite infrequent. Very few have tried to find out how gallstonl',; form, u·ha t causes them to form, and whether their formation could be prcnnted or reversed by dietary or medicina I means. Although the situation is rapidly improving, there are probably not more than five laboratories in this country that are both interested in the biophysical mechanisms underlying human gallston<' formation and, at the same time , intellectually and physically equipped to tackle 102
103
DIGESTIVE DISEASE. V
J u ly 1968
these problems, in short, one basic research facility per 3 million gallstone carriers. Currently these facilities are analyzing and determinin g the proport iona l interrelations among water, cholesterol , bile salts, and lecit hin that main tain bile in its normal liquid phase, or that induce on e or more solid or semisolid phases. The role of protein a nd pigment in th ese phenomena is not known. In addition , little is known of the forces that cause aggregat:on of precipitated solids into ston es of various sizes. When I say 15 million Americans have gallstones, I must admit th a t it is an estimate. Th e freque ncy of ga llstones at death ca n be determin ed, but t heir exact prevalence in the living is unknown . Ga llston es are ctiagnosed as a rule only afte r they have caused symptoms. To determin e the frequ ency of asymp tomatic-so-ca lled silent-stone!i, surveys of se lected population groups are necessary. Such surveys require the usc of sta ndard techniques employed in X-mying the ga ll bl adder , but they ca nno t be regard ed as diffi cult, da nge rous, or excl'ss ivc ly cos tly. However, such surveys of gallstone preva lence a relik e basic studies on gallston e form atio n -chiefly di::;tin gui shcd fo r their pau city. The purpose of surveys to clcte nninv the frequ eney of gallston e::; among t he livin g is no t mcr<'ly to amass dry demoT ,\ 1!1. (,;
graphic data. To the contrary, both long term theoretical and practical immedi ate ends could be served. There is the strong impressi on, for example, that gallstones are unusually preva lent among our Indians, such as the Na vajo a nd the Pima. If th is impressi on were confirmed by a precise survey, analyses of possibly related factors, such as India n ha bits, di et, a nd genetics, could be under tak en. As of t he present, some Indian t ribes sti ll live as homogeneous populations in quite circumsc ribed a reas. Th ese areas are not far a way in some in accessible jungle- they are righ t here in the Un ited States with topno tch technica l facilities close at hand. The hea lth of the Indi ans, moreover, is a lready a Public H ealth Service responsibili ty. If anythin g is to be made of th is opportunity, however, the t ime is now because In dia n t raits are disappea ring under the pressures of assi milation. Circumstances t hus would appear ideal -anct somewh at urgent--fo r carrying out several a ppropriate ::;mveys in short order. Unfortun ately, only on e group of inV<'stigators is at work on the problem, hut their progress is gratifying. A prelimin ary study comparin g clini cally manift•st ga llston e ct isease in Indi a ns with findings previously reported in a white population has a lready been published (tabl e 1) .1 More important is a prospective
1. JJrcvalcru:e of "definite" yall bladrlc r cl-isease in th e two s tudies" F ramingham group
Pima Indians
----- - - - · Ag-e at entry into study
Sex
With disease
With disease No. at risk
No. at ri!lk
No. "', I; - - - - - - · -- ·-- - - ---·
·- --··-- -· ··-----·
No.
%
1 1 7 9 16 20 21 57
2.0 2.2 12.3" 5.9" 35.6" 39 .2" 33.8" 36.0b
yr
30- 3\J 40-49 50- G2
M a les
T otals Fema les
832 779 725 233G 1037 9G3 873 2873
30-3\l 40- 4\J 50-62
T otal s - · - · · --
-
-
- -· - - - - -· - - - - - - - · - --
-
- ·_
1 7 23 31 24 58 88 170 _ _:....__ _ __
0.1 0.9 3.2 1.3 2.3 6.0 10.1 5.9
51 45 57 153 45 51 62 158
_ __ , _ _ __
_ _.....c__
_
" Hc produ ced by permiss ion of t he authors a nd 'J'h.e New En gland Journal of M edicin e. b p < 0.01.
_ __
_
_
104
DIGESTIVE DISEASE. V
study of total gallstone prevalence, asymptomatic as well as symptomatic, that is under way. Studies on the epidemiology of gallstones are not only directed at solving the riddle of their pathogenesis. They would, if available, help to settle some very practical problems. What advice, for example, should be given to the patient who has a silent, i.e., a symptomless gallstone, which was discovered incidentally by an abdomina l X-ray taken for some other purpose? The surgeon, mindful of t he threat of future complications, might advise immediate prophylactic cholecystectomy. The internist, on the other hand , may be equally positive in advocating a wait-and-see policy. Either advice is based on faith and hope-no more. No reliable information whatsoever is available to help the doctor decide whether the patient with a silent gallstone is better off doing nothing or having his gall bladder taken out. However, the needed information is, so to speak, just around the corner, waiting to be secured at relatively little effort and cost. A program of randomly selected population groups would quickly reveal who has gallstones, and a follow-up over the ensuing y ears would then give figures as to the likelihood of later symptoms, serious complications, and clinically necessary surgery. These data could then be compared with the advantages and risks
Vol. 55, No . 1
of immediate prophylactic surgery for the patient with a silent gallstone. Why has such a program not been carried out? Why, indeed, has t he study of gallstones been lagging in general? I n view of the prevalence of gallstones and the major disabilities that they cause, there is no satisfactory answer to this question. One can only conclude unhappily that gallstones have not been an "in" disease. They certainly have been neglected by us, the medical profession, but, in addition , their image has not had the benefit of public relations counsel, and they have not been viewed wit h due alarm by public spirited citizens such as the "Health Syndicate," 2 our Congressiona l Committees, or even the American Gastroenterological Association. In matters of health, the study of a disease should be supported on the basis of hard facts: its frequency, its importance as a cause of disability and death, and-from a practical viewpoint-the likelihood of obtainin g answers. Viewed in the ligh t of these criteria, the study of gallstones has been grossly neglected. REFERENCES 1. Comess, L. J., P. H. Bennett, and T . A. Burell. 1967. Clinical gallbladder disease in Pima Indians : its hi gh prevalence in contrast to Framingham, Massach usf'tts. New Eng . J. Med. 277 : 894-898. 2. Drew, E. B . 1967. H eath sy ndieate: Washin gton 's noble eonspirators. The Atlantic 220: 75--82.