Changing state of gallstone disease in Japan

Changing state of gallstone disease in Japan

Changing State of Gallstone Disease in Japan Composition of the Stones and "Treatment of the Condition FUMIO NAKAYAMA, MD, MS, Fukuoka, Japan HIROSHI ...

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Changing State of Gallstone Disease in Japan Composition of the Stones and "Treatment of the Condition FUMIO NAKAYAMA, MD, MS, Fukuoka, Japan HIROSHI MIYAKE, MD, FACS, Fukuoka, Japan

There has been increasing awareness in recent years t h a t the composition of gallstones differs widely f r o m area to area. Recently Miyake and Johnston [1] described the difference in composition between gallstones from the E a s t and those from the West. They showed t h a t in a Chinese population in H o n g Kong bile pigment stone predominates, whereas in the United States, stones are almost exclusively composed of cholesterol. In Japan, the situation is somewhat i n t e r m e d i a t e and both types of stones occur with about the same frequency. It has been generally believed [2] t h a t the composition of gallstones in J a p a n is gradually changing to appi~ach t h a t of stones found in the West. If this is indeed the case, careful s c r u t i n y o f the changes in environmental factors t a k i n g place in present (lay J a p a n m a y d e m o n s t r a t e which. factors are responsible for the change in gallstone compo~tipn. However, to our knowledge, no detailed documentation of t h i s tr'end based on actual chemical analysis is so f a r available. In the present communication, changes in the composition of gallstones in J a p a n over a period of f o r t y years have been clearly documented and improved methods of operative t r e a t m e n t are presented.

Material and Method~ Gallstones were removed during billary tract surgery, washed with water, and briefly air-dried. Twenty cases each of gallstone samples collected in 1927 and in 1967-68 have been analyzed, the former by the late Professor It. Miyake, Sr, and the method of analysis used is descrilJed in detail in an earlier publication [8]. Reagents used were all reagent grade and redistilled before use. Gas chromatograph used was the PerkinElmer Model 801 equipped with dual glass column a n d hydrogen flame ionization detector. Gallstone was ground in a mortar and the poWder From the Department Of Surgery, Kyushu University Faculty of Medicine, and KYushu Central Hospital, Fukuoka, Japan. This work was supported in part by Research Grant AM-07049, National institutes of Health, United States Public Health Service. 794

was extracted with acidified chloroform-methanol 2:1. An aliquot was used for determination of bilirubin with diazo reaction. Another aliquot was used for determination of cholesterol, cholesterol ester, free fatty acids, and glycerides. After addition of water, the upper methanol-water layer ~ a ~ aspirated off. The lower chloroform layer was subjected to~ilica gel H column chromatography. Ten per cent chloroform in petroleum ether eluted cholesterol ester; 70 p e r cent chloroform in petroleum ether, cholesterol, free fatty acids, triand diglycerides; ether, monoglycerides, and methanol, phospolipids. Cholesterol ester was determined with Liebermann-Burchard reaction at 625 m/~ using Coleman Ultramicrocell Assembly after alkaline hydrolysis and digitonin precipitation. Seventy per cent chloroform in petroleum ether eluate combined with ether eluate was subjected to gas chromatography on a short glass capillary column containing 3 per cent OV-1 after methylation. Phospholipid phosphorus was determined by Bartlett's method.-For determination of bile acids. part of the acidified chloroform-methanol extract was evaporated to dryness and the residue was partitioned between petrbleum ether and 70 per cent ethanol. Seventy per cent ethanol layer containing bile acids was hydrolyzed with 5 per cent aqueous sodium hydroxide at 120°C for seven hours. After acidification, bile acids were extracted with ether and subjected to gas chromatography on 3 per cent cyclohexanedimethano] succinate column with cholestane as internal sthndard after methylation and silylation. Part of the powdered gallstone was digested in Sulfuric acid with the addition of hydrogen peroxide and was used for determination of calcium, sodium, and potassimn with flame photometry.

Results

Cha~ging

GaUstone Composition in Japan.

Composition of gallstones of t w e n t y cases each in 1927 and in 1967 to 1968 has been tabulated in Table I. The difference between the two groups is most pronounced i n bilirubin, cholesterol, and calcium content. In the gallstones removed in 1927, bilirubin and calcium contents were quite high in about h a l f of the cases, w i t h comparatively lower The American Journal of Surgery

C h o l e l i t h i a s i s in J a p a n TABLE !

Changing Gallstone Composition in Japan

Sample Number

CholesCholes- Unidenti- terol terot fled Ester"

Billrubin

Free Fatty Acid

67.5 174,8 297.2 429.6 372.6 1.5 0.4 274.8 241.1 219.3 1~.7 0.5 22.0 282.0 319.1 2.1 1.4 161.8 2.5 9.2 153.7~ 147.0

33.8 12.9 82.5 160.0 44.0 13.0 18.7 64.5 127.0 23.9 337.0 0.0 0.0 61.1 6.0 9.5 0.0 13.9 0.0 0.0 50.4~ 77.2

Mono- Diglycglyceride eride

Tri. glyceride

Total Bile Acidt

Phospho. lipid

Calcium

73.0 26.3 106.2 25.2 56,5 0.9 Tr 14.4 33.4 16.9 13.3 Tr 1.0 6.4 4.2 Tr 0.0 1.3 Tr 5.1 19.2i 28.6

1.3 1.9 1.3 0.9 1.9 0.2 0.1 2.1 i.I 1.5 1.2 0.4 0.4 1.0 1.1 0.5 0.6 0.9 0.7 0.4 1.0~ 0.4

49.2 8.5 15.8 14.1 10.9 4.1 0.8 64.6 42.0 38.4 37.2 6.0 1.6 13.7 10.3 15.2 1.2 7.6 4.1 1.7 17.4~ 18.5

12.3 9.8 12.2 11.4 9,7 4.8 6.5 6.6 7.8 5.7 6.7 2.8 2:4 6.4 9.5 2.8 2.8 11.7 1.8 3.4 ~9~ 3.6

0.7 1.1 I.I 1.0 0.9 1,0 0.8 1.0 0.9 0.9 2.1 0.9 0.9 0.9 2.4 0.5 0.6 1.6 0.5 0.4 1.0~ 0.5

24.6 507.7 1.0 31.6 1.0 55.8 2.1 25.9 2.6 82,1 3.5 19.7 0.6 17.4 1.3 74.4 5.5 80.7 3.1 126.3 0.9 63.7 5.7 34.1 0.2 14.9 0.9 55.4 2.1 134.0 1.6 65.5 0.3 Tr 13 349.8 1.6 Tr 0.9 54.1 3.1=E 8 9 . 6 ~ 5.3 124.3

SamplesTakenin1967~8 3.2 0.0 0.0 0.0 0.0 5.5 0.8 0.0 0.0 0.0 0.0 11.3 0.2 0.0 0.0 0.0 0.0 Tr 9.1 5.4 0.0 0.0 0.0 6.2 24.6 0.0 0.0 0.0 0,0 0.5 3.2 0.0 0.0 0.0 0.0 2.6 0.7 20.8 Tr 0.0 0.0 Tr 1.2 0.0 0.0 0.0 0.0 Tr 0.9 20.1 0.0 0.0 0.0 Tr 2.7 0.0 Tr 0.0 0.0 2.8 0.7 23.0 Tr 0.0 0.0 3.9 112.1 0.0 Tr 0.0 0.0 17.0 0.5 0.0 0.0 0.0 0.0 Tr 259.2 33.8 Tr 0.0 0,0 17.6 6.7 0.0 0.0 0.0 0.0 2.5 4.5 0.0 Tr 0.0 0.0 4.4 381.6 105.7 0.0 0,0 0.0 31.8 4.8 0.0 0.0 0.0 0.0 1.7 34.3 0.0 0.0 0.0 0.0 4.1 3.1 0.0 0.0 0.0 0.0 2.7 42.7=1= 10.4=t= 0 . 0 ~ 0 . 0 ~ 0 . 0 1 5.7~ 101.0 24.7 0.0 0.0 0.0 8.1

1.4 5.1 2.0 1.6 1.1 1.0 0.7 0.5 0.5 2.3 1.2 1.2 0.2 0.6 0.2 0.6 24.8 0.9 1.0 1.2 2.4± 5.4

0.6 0.5 11.9 0.6 12.2 1.i 168.2 6.8 54.5 0.0 0.3 59.3 0.3 23.0 0.5 0.4 18.9 92.3 51.2 0.2 25.1~ 42.3

3.7 3.2 4.6 3.8 '6.2 2,8 6.9 3.2 3.7 2.4 4.9 1.0 0.5 2,5 0.5 0.9 0.7 0.7 0.5 0.5 2.2:5 2.1

0.5 0.6 0.7 1.1 0.7 0.1 1.5 0.3 0.5 0.5 0.6 1.4 0.9 2.1 0.8 0.9 1.0 1.2 1.0 1.0 0.9~ 0.4

0.2 Tr 0.4 Tr 10.7 46.0 0.8 44.0 0.7 45.2 0,6 Tr 1.5 234.0 2.3 6.5 1.8 147.0 0.2 Tt 0.3 0.0 0.7 1~.6 0.1 Tr 6.2 353.6 0.2 Tr 0.1 19.2 3.1 1~.3 1.0 ~0.3 2.5 150.2 0.4 5.2 1.7± 82,0± 2.6 I09,0

Potas- PhosSodium s l u m phorus:~ Residue

Samples Taken in 1927 I- 1 2 3 4 5 I-6 7 8 9 10 1-11 12 13 14 15 1-16 17 48 19 20 Mean~= S.D.

II. 1 2 3 4 5 II- 6 7 8 9 i0 I1-11 12 13 14 15 II-16 17 I8 19 20 Mean± S.D.

74,7 Tr~ 543.2 4.4 70.2 7.0 83.0 15.7 95.9 17.4 909.8 0.0 980.6 Tr 29.6 3.4 41.7 3.5 57.8 3.2 98.5 2.4 885.5 0.0 874.5 0.0 59.9 5.1 50.5 Tr 803.0 Tr 855.9 0.0 77.1 3.5 776.1 0.0 783,6 0.0 407.5:~= 3.3:L 3~.5 5.0

1,002.0 951.0 831.0 920.2 872.7 955.7 16.9 916.0 641.0 1,028.1 968.1 409.1 1.013.7 56.4 995.8 900.2 72.1 550.3 715.0 927.5 737.1--t= 338.5

5.4 2.2 8.8 6.2 5.1 0.2 0.3 ].7 2.8 0.6 7.7 0.2 1.1 4.1 3.3 0.6 1.0 2.3 1.7 1.8 2.9~ 2.5

84.2 2.7 67.5 1.6 370.3 2.3 0.0 4,8 117.0 1.8 0.0 3.5 2.2 1.4 0.0 3.4 7.7 2.6 Tr 1.7 2.9 5.3 Tr 0.2 0.0 0.4 4.8 Tr 0.0 3.6 0.0 0.9 Tr 10.8 0.0 0.1 0.0 0.6 0.0 0.1 32.8=:r= 2 . 4 ± 86.5 2.5

0.0 21.2 0.0 0.0 0.0 Tr 0.0 Tr 3.8 Tr 0.0 0.0 0.0 11.0 0.0 0.0 0.0 2.9 0.0 0.0 2.0:~: 5.2

0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Q.0 0,0 0.0 0.O 0.0 4.8 0.0 5.1 0.0 4.7 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 .0.0 0.0 0.0 0.7:~ 0 . 0 ~ 1.8 0.0

Note: All values are expressed in milligrams per gram of dry weight. * Calculated as cholesteryl palmitate. t Sum of cholic, chenodeoxycholic, deoxycholic, and lithocholic acids. :~ Trace amount. § Inorganic phosphorus--total phosphorus minus phospholipid phosphorus.

cholesterol content. In contrast most of the stones removed between 1.967 and 1968 c,,-tained only m i n u t e amounts of bilirubin, larg.' ,.mounts of cholesterol, and small amounts o'f calcium. The difference betweei'l the two groups becomes more a p p a r e n t when composition of gallstones is plotted on t r i a n g u l a r coordinates of Cholesterol, bilirubin, Volume 120, December 1970

and calcium ( F i g u r e 1), in which the corners are respectively assigned to cholesterol stone (C), bile pit,~nent stone (B) and inorganic stone (I) u~ually composed mainly of calcium [~].* Thus in 1927 * In this d i a g r a m , r a t h e r rare. s t o n e s o f special cor, posltio~t s u c h as /att.lt acid s t o n e s , t h a t is. stone~ c o m p o s e d m a i n l y o~ l a r r y acid [5]. c a n n o t w e l l be i l l u s l r a t e d . 795

Nakayama and Miyake

3

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1958-1960

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1967-1968

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nine of t w e n t y cases w e r e o f cholesterol stones, w h e r e a s the stones r e m o v e d f r o m 1967-68 show t h a t 17 of 20 a r e composed m a i n l y of cholesterol. T h e c o n s e c u t i v e n a t u r e of this s h i f t in c o m p o s i t i o n of gallstones in~ J a l ) a n d u r i n g the past f o r t y y e a r s is c l e a r l y d e m o n s t r a b l e when t w e n t y cases in 1938 f r o m the r e p o r t b y , N i s h i m u r a [5] a n d one h u n d r e d cases f r o m 1958 thi'ough 1960 r e p o r t e d b y M i y a k e and J o h n s t o n [1] a r e plotted on the t r i a n g u l a r coo r d i n a t e a n d c o m p a r e d . ( F i g u r e 1.) G r a d u a l s h i f t of gallstone c o m p o s i t i o n in J a p a n o v e r the p a s t f o r t y y e a r s f r o m bile p i g m e n t to cholesterol is apTABLE !1

Change in C o m p o s i t i o n of Gallstones in J a p a n d u r i n g the Past Forty Years ( O p e r a t i v e Cases) Year 1927

Total n u m b e r of gallstone cases N u m b e r with cholesterol stones Percentage of cholesterol stones TABLE III

1938 1958[5] t960 Ill

20 26 9 9 45.0 34.6

19671968

100 61

20 17 85.0

61.0

A u t o p s y Incidence of Gallstones in J a p a n Year

N u m b e r of autopsies N u m b e r with gallstones Incidence ( p e r c e n t ) Over-all Cholesterol stone*

1913 {6]

1955-61 [71

8,406 257

35,028 1,536

3.1 1.7

4.4 2.7

p a r e n t ; t h a t is. the p r o p o r t i o n o f stones composed of ch olesterol to the total n u m b e r of gallstones a n a lyzed i n c r e a s e d f r o m 45,0 p e r c e n t in 1927 to 85.0 p e r cent in 1967-68. (T~ble II.) W h e n this s h i f t in c o m p o s i t i o n f r o m bile p i g m e n t to cholesterol is t a k e n i n t o a c c o u n t and the a u t o p s y incidences reported by Miyake, S r in 1913 [6], b y Maki et al in t 9 5 5 - 6 1 [7], and b y O k u d a i r a ir~ 1966-67 [8] a r e recalculated, the incidence o f cholesterol stones is noted to h a v e i n c r e a s e d f r o m 1.7 p e r cent in 1913 to 6.7 p e r cent in 1966-67. ( T a b l e l I I . ) T h e l a t t e r figure is a p p r o a c h i n g t h e a v e r a g e of 10 per cent in the g e n e r a l p o p u l a t i o n of t h e West, w h e r e m o s t of the stones r e m o v e d a r e s h o w n to be c o m p o s e d of cholesterol stone, such as an 88 p e r cent incidence in t h e U n i t e d S t a t e s [1]. C h a n g e i n Sex Ratio a~d A g e Distribution. In 1927 t h e over-all male to f e m a l e sex r a t i o in o p e r a tive cases was 1.0 tO 0.8 w h e r e a s in 1967-68 it bec a m e 1.0 to 2.7 ( T a b l e IV.) W h e n one c o n s i d e r s cholesterol stones alone, even in 1927 the r a t i o w a s f o u n d to be 1.0 to 2.0; in 1958-60 it was 1.0 to 1.2 [1], a n d in 1967-68 it w a s 1.0 to 2.3. No dist i n c t c h a n g e in a g e d i s t r i b u t i o n can be d e m o n strated.

1966-67 18{ 168 14 8.3 6.7

' Indicates percentages for cholesterol stone calculated from over-all incidence by applying the ratio of cholesterol stones to total n u m b e r of stones found in c o n t e m p o r a r y operative cases, that is, 11 of 20 (present c o m m u n i c a t i o n ) for 1913; 62 of 100 [1] for 1955-61; and 16 of 20 (present c o m m u n i c a t i o n ) for 1966--67.

796

Figure 1. Schematic representation of change of composition of gall. stones ~n Japan during the past forty years ( ~ 9 2 7 - 1 9 6 8 ) . Coordinates are expressed in weight per cent of the components shown. Triangular area in eacl¢ corner is assigned to cholesterol stone (C), bile pigment storm (B), and inorganic stone (I).

Comments

A l t h o u g h g e n e r a l a p p e a r a n c e a n d cut s u r f a c e of gallstones can be c o r r e l a t e d t o t h e i r composition, as p o i n t e d out by M i y a k e a n d J o h n s t o n [1], stones c o n t a i n i n g c o n s i d e r a b l e a m o u n t s of bile p i g m e n t as well a s l a r g e a m o u n t s o f Cholesterol can b e mist a k e n f o r bile p i g m e n t s t o n e s b e c a u s e o f t h e i r d a r k b r o w n color. W e h a v e t r i e d to t e s t o u r s e l v e s b y guessing the composition of gallstones r e m o v e d i n The American Journa| of Surgery

Cholelithiasis in Japan

1927 as well as that of gallstones removed in 196768 from their appearance as well as from their cut surface and found such confasion indeed occurred in samples I-2, 1-13, 11-12, and II-19. (Table I.) Hence, actual analysis of gallstone composition seems to be m a n d a t o r y for the accurate classification of gallstones. Gallstone research has been hampered by the lack of a suitable method of analysis for gallstones because of the presence of large amounts of bile pigment and inorganic substances. Recently, a quantitative microanalytical technic for gallstone has been developed in this laboratory [3] which is based on p2;eliminary solvent partition followed by column c h r o m a t o g r a p h y and gas chromatography, furnishing a wide range of information on different constituents, such as cholesterol, cholesterol ester, bilirubin, free f a t t y acids, phospholipids, bile acids, calcium, s o d i u m , potassium, and phosphorus. P a r t l y bec'mse of the variations in analytical t,dchnic it is difficult if not impossible to compare changes in gallstone composition in previous independent studies. In the present communication, such difficulty is circumvented by analyzing two groups of gallstone samples collected f o r t y years a p a r t using the same technic at the same laboratory, thus making their comparison more valid. The gradual change in gallstone composition in J a p a n over the past f o r t y years has been clearly demonstrated, showing t h a t stones were once predominantly composed of bile pigment whereas at present they are mostly composed of cholesterol, even though not m a n y cases were studied. F u r t h e r more, recalculation of the autopsy incidence of gallstones in J a p a n revealed t h a t the incidence of cholesterol stone, the predominant gallstone in the West [1], has almost quadrupled d u r i n g the past f o r t y years and is indeed approaching ~hat of the West. (Table III.) The factors responsible for this change have not been clearly understood. Maki and his co-workers [7] stressed that the increase of f a t and protein intake in recent y e a r s in J a p a n [9] m a y be one of the possible factors responsible. Infection of the biliary tree has long been regarded as a cause of the f o r m a t i o n of bile pigment stone. Recently, Maki [10] found increased bacterial fl-glucuronidase activity in bile h a r b o r i n g bile pigment stones. Hydrolysis of bilirubin glucuronide and coupling of free bilirubin with calcium m a y lead to bile pigment stone formation. As the process of urbanization in postwar J a p a n accelerates (more t h a n 75 per cent of the total population is expected t o live in cities by 1980 [ i i ] ) , the chance of bacterial cont a m i n a t i o n n a t u r a l l y decreases which m a y explain the decreasing incidence of bile pigment s t o n e . In Volume 120, December 1970

TABLE IV

Sex Ratio in Operative Cases of Gallstones in Japan (Male to Female) Year

Over-all Cholesterol stones

1921

1958-60 [1 ]

1,0:0.8 1,0:2.0

1.0:1,0 1.0:1.3

1967-68 1.0:1.9 1.0:2.3

* All cases of gallstones including cholesterol stone and bile pigment stone.

fact, marked decrease in bacterial incidence in bile has been noted in recent years [12]. (Table V.) The t r e a t m e n t for cholelithiasis should be determined by w h e t h e r the gallstone is composed of cholesterol or bile pigment. Disease ill those with cholesterol stones seems to be metabolic in origin, originates in the gallbladderl and does not usually show fever, severe liver damage, nonfunctioning gallbladder, or other inflammatory signs. Disease in which the stones are composed of bile pigment seems to be closely associated with bacterial infection, is present in the biliary t r a c t in general but mostly confined to the common duct, and usually results in fever, severe liver damage, and nonfunctioning gallbladder [1]. For t r e a t m e n t when the stone is composed of cholesterol, cholecystectomy occasionally combined with choledochostomy is the method of choice, whereas when the stone is composed of bile pjgment, t r e a t m e n t invariably involves common" duct exploration. Even when operative cholangiography is performed, recurrence of the disease is frequent, either because of overlooked stones or because of reformation of the stones in sitn.. In fact, rapid formation of gallstone has been reported repeatedly [13]. In 1913, 47 per cent of the patients with cholelithiasis underwent common duct exploration whereas f r o m 1948 to 1961, 71.8 per cent had exploration [14]. (Table VI.) This increase of c o r n TABLE V

Presence of Bacteria in Bile Year t913 [6]

Number of cases examine~ B,~cteria present N u m b e r of cases Percentage TABLE Vi

1955-61 112]

38

342

35 92. I

230 67.3

Frequency of Common Duct Exploration Year Frequency

1913 [6]

1948-6! [14]

Number of cases Common duct exploration Frequency per 100 operations for cholelithtasis

56 26

462 332

47

7;)

797

Nakayama and Miyake TABLE VII

Locationof Gallstones in Biliary Tract (Operative Cases) Year 1913 [6]

Location

194~-1951[t41

Number Per cent Number Per cent

Gallbladder only Common duct only Gallbladder plus common duct Common duct plus intrahepalic duct

25 26

44.6 ,~6.4

237 40

5] .3 8.7

2

3,6

130

28.1

3

5.4

55

11.9

mon duct explor~tion despite the minute change in incidence of common duct stones in the past (Table :VII) is p a r t l y due to the routine use of operative cholangiography which increases the chances of detecting common duct stones which would otherwise be missed, and partly due to the application o f more vigorous criteria for common duct exploration in order to reduce incidence of residual stones. The following twelve criteria for common duct exploration have been used [ I 5 ] : (1) common duct dilated over 10 m m ; (2) presence of jaundice in present or past h i s t o r y ; (3) dilated cystic duct or cystic duct jb!ning common duct at right angle; (4) presence o f cholangitis ; (5) frequent gallstone attacks ; (6) pre~ence of cirrhosis of the liver ; (7) hardening or inflammation of the pffncreas; (8) presence in the gallbladder of small gallstones, especially multiple stones; (9) finding stones o r bili a r y " m u d " in the severed end of the Cystic duct; (l 0) presence of stones in the c o m m o n duct proved by palpation or by operat:ixe:.cholangiogral)hy; (11) presence of scar tissue or anomalies in the bile duct; (12) presence of parasites in common duct. In Hong Kong, where bile pigment stones are still predominant, preservation of the gallbladder has been advocated by Ong [16] for later use in a b y p a s s procedure which is often ~found necessary because of the f r e q u e n t obstruction of the common duct by stones regenerated !~l.sit.~ ol: those c o m i n g from intrahepatic duct. However, O n g ' s a r g u , ment does n o t seem to b e too plausible, :since the f u r t h e r risk of r e ' f o r m a t i o n o f stones:in g a l l b l a d . der is added, and bypass can be provided by chote, d o c h o d u o d e n o s t o m y w i t h partial :gastrectomy (Billroth choledoChojejunost0my : ( R o u x ,

zI)or

TABLE VIii

Operative Mortality for Cholelithiasis Year Mortality

~13i61

Number of cases OPerated:: Operative death M0rtality (per cent )

56 15 27.1

798

en-Y) [1~]. Although the B i l l r o t h II procedure sounds an if it is teo drastic an operation, choledochoduodenos'~o~ny results in reflux of intestinal contents into the biliary tract and a g g r a v a t e s inflammation due to bacterial infection which is frequently present in case of bile pigment stones, resulting in severe choIangitis, liver abscess, or induction of intrahepatic stones. Thus, for common duct stones of bile pigment variety, combined partial gastrectomy (Bilh'oth If) is necessary to cope effectively with-this adverse effect on the biliary t'r.act by diversion of the food stream. Marked decrease in mortality (Table VIII) in recent years is partly due to the d e c r e a ~ of cases of bile pigment stones in which, in contrast to t h a t of cholesterol stones, mortality is usually high because of the presence of bacterial infection and the frequently accompanying liver damage. Decrease in m o r t a l i t y is also p a r t l y due to the application of sound criteria for surgical inte~'vehtion and public awarehess of s a f e t y of b i l i a r y ' t r a c t surgery, resulting in increasing numbers of patients with gallstones coming to s u r g e r y before serious complications, such as severe liver damage due to obstructive jaundice, cholangitis, perforation, and pancreatitis, can develop: F u r t h e r m o r e , improvement il) anes.thesia in recent .vears, improved knowledge of fluid and electrolyte balance, accurate assessm e n t of extent of liver damage present, availability of antibiotics, and use of operative cholangiography decreasi~lg the occurrence of post~ operative bile leakage in the peritoneal cavity du~ to residual common duct stones all add up to the receilt marked decrease in mortality in biliary t r a c t surgery. Intrahepatic stones, which pose the surgeon with seemingly formidable tasks, are not as r a r e as generally t h o u g h t and their presence is occasionally reported elsewhere [17]. In Japan, as m a n y as 20 per cent of t h e cases of common d u c t stones are found to be accompanied by intrahepatic stones [15] a s judged by the brown debris drained f r o m the Choledochostomy t u b e . Hence it is essential to provide good communication between the bile duct and intestinal t r a c t to forestall r e c u r r e n t obstructive j a u n d i c e b y sphincter0plasty, sphincterotomy,-choledochoduodenostomy with partial Billroth II gastrectomy, and ~choledochojejunost0my (Roux-en-Y). W h e n the stones are:localized in the left hepatic lobe, left h e p a t i c lobectomy is the operation o f choice.

ii948'1661~'[14]( 462 15 5i ~

Summary

The long held:impressio~ that:the :compOsition: of gailstones in:Zapdn is gradually~chaiiging :frbm Lhe The American Journa| Of SurKerv

Cholelithiasis in Japan

once predominant bile pigment to cholesterol, thus approaching that of the West, has been confirmed by actual chemical analysis of gallstonesamples collected forty years apart. Fa.ctors responsible for this change are no~ clearly know~ at present, but may include the rapidly proceeding urbanization and changing food habits in postwar Japan. These two. groups of stones, that is, cholesterol stone and bile pigment stone, should be considered as two separate entities having different etiologies, and operative treatment should therefore be instituted accordi ngly. A ck~mw/cdgmen~" We wish to thank Professor Haruo Saikachi, K y . s h u University Faculty of Pharmaceutical Sciences, for his continued interest and e.couragement during the investigation; Miss Hiroko Doi and Miss Yoko Tsukamoto for technical assistance; and Mrs Hanna Nakayama for compiling references and preparing the manuscript. References 1. ~Miyake H Jr, Johnston CG: Gallstones: ethnological studie~s. Digestion 1: 219, 1968. 2. Maki T, Matsushiro T, Nakamura N, Watanabe Y, Takahashi W: Change in cholelithiasis and recent operative result at the department. Therapy (Chiryo), 49: 1795, 1967. 3. Nakayama F: Quantitative microanalysis of gallstones. J Lab Clin Med 72: 602, 1968.

Volume 120, Decenlber: 1970

4. Sutor J, Wooley SE: Gallstone of unusual composition: calcite, aragonite and vaterite. Science 159: 1113, ] 968. 5. Nishimura M: Uber die ~:hemische Zusammensetzung der Galtensteine. J Biochem (Tokyo) 28: 256, 1938. 6. Miyake H St: Statistische, ktinische und chemische Studien zur Aetiologie der Gallensteine, mit besonderer Ber~icksichtigung der japanischen und deutschen Verh~ltnisse. Arch Klin Chit 101: 54, ]913. 7. Maki T, Sato T, Yamaguchi I, Sato Y: Autopsy incidence of gallstones in Japan. Tohoku J Exp Med 84: 37, 1964. 8. Okudaira M: Personal communication, 1968. 9. Insull W Jr, Oiso T, Tsuchiya K: Diet and nutritional status of Japanese. Am J Clin Nutr 21: 753, 1968. 10. Maki T: Pathogenesis of calcium bilirubinate gallstone: role of E. Coil, t~-£1ucuronidase and coagulation by inorganic ions, polyelectrolytes and agitation. Ann Surg 164: 90, 1966. 11. Japanese Government Economy Planning Board. Interim report regional section. 1968. 12. Higashituji H, Kodama M, Koltishi S, Sakaguchi N: Bacteriotogical studies on cholelithiasis and cholecystitis. Fukuoka Acta Med 59: 787, 1968. 13. Larmi T, Silvennoinen E: Rate of formation of c o m m o , bile duct stones from nonabsorbabte silkworm ~ut. Acta Chir Scand 134: 82, 1968, 14. Miyake H Jr, Mechanism of gallstone formation and its treatment, gap Med 1: 733, 1963. 15. Miyake H Jr: Operative indication for cholelithiasis, g Jap Surg Soc 67: 797, i 9 6 6 . 16. Ong GB: A study of recurrent pyogenic cholangitis. Arch Surg 84: 199, 1962. 17. Maki T, Sato T, Yamaguchi I, Sato T: Treatment of intrahepatic gallstones. Arch Surg 88: 260. 1964.

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