Enzyme and Function Changes after ExtensiveLiver Resection in Man

0. ALMERSJ6, S. BENGMARK, L. 0. HAFSTROM, R. OLSSON

From Department of Surgery, University of Goteborg, Gothenburg, Sweden

NUMEROUS papers have considered thequestion of what causes increased serumactivity of hepatic enzymes in disease ofthe liver. Hypertransaminasemia was firstbelieved to be caused by a release of en-zyme from necrotic liver cells. Many stud-ies support this view.40 Later, it was real-ized that necrosis of liver cells was not asine qua non for hypertransaminasemia. Itwas also realized that the different patternof response of glutamic oxaloacetic trans-aminase (GOT) and of glutamic pyruvictransaminase (GPT) resulted from differ-ences not only in liberation from the hep-atocytes but also in the rate of eliminationfrom serum.40Concerning the cause of the increased

serum alkaline phosphatase activity (AP)in hepatic disease, two main theories havebeen advanced: The "retention theory" ar-gues that "extrahepatic" enzyme is retainedin the circulation because of failure of theliver to excrete it.5 The "regurgitation the-ory" postulates the increased serum alka-line phosphatase activity to be due to thedelivery of biliary material into the circu-lation by way of abnormal communicationsbetween the bile canaliculi and the sinu-soids.43 Both theories are contested.

In view of the many unresolved problemsregarding the cause of hyperenzymemia inliver disorders, it was considered of interestto analyze serum changes in "liver en-zymes" after major resections of the liverin man. A multitude of changes can be

anticipated after this operation; "mechani-cal" damage to hepatocytes at the sites ofthe resection, general disturbances of me-tabolism of the liver followed by steatosis,glycogen depletion etc., regenerative phe-nomena, and decreased excretory capacity,all of which have been considered as causesof hyperenzymemia.An attempt is made in the present study

to discover factors that could determinethe extent of the hyperenzymemia occur-ring postoperatively and to analyse thesefactors. A comparison is also made be-tween changes in serum enzyme activityand changes in "liver function tests" (se-rum bilirubin concentration and brom-sulphalein retention).

Material and Methods

The material consists of 12 patients whounderwent hepatic resections for differentindications. Determinations of serum en-zyme activities were performed before op-eration and up to 4 weeks postoperatively.At the same time, liver function was fol-lowed by means of determinations of serumbilirubin concentrations and bromsulpha-lein retention tests.The following methods were used:GOT (glutamic oxaloacetic transamin-

ase) and GPT (glutamic pyruvic trans-aminase) determinations according to Kar-men et al., modified by Ordell,42 OCT(ornithine carbamoyl transferase) accord-ing to Reichard,46 alkaline phosphatase ac-cording to Buch and Buch,12 bilirubin, ac-cording to Jendrassik and Grof,31 BSP(Bromsulphalein) retention 45 minutes after

Submitted for publication June 4, 1968.Reprint request: Dr. S. Bengmark, Dept. Surg.,

Sablgren Hospital, Gotbenburg 41345, Sweden.

111

112 ALMERSJO, BENGMARK, 1H

an injection according to Gaebler.27 Dur-ing the 12 hours immediately before op-eration, all patients received at least 1,000ml. of 10% glucose solution; and duringthe first 7-10 postoperative days, 40-60Gm. albumin per day in the form of al-bumin solution or plasma, and a mini-mum of 200 Gm. glucose per day. Mostoperations were performed as formallobectomies or segmentectomies (usuallycalled typical or anatomical resection) butsome were done as partial or subtotal lo-bectomies (usually called non-anatomicalor atypical resections). The operationswere performed under 02 + N20 anes-

thesia, in some cases with added Fluo-thane. (For further details regarding op-erative technic, see Bengmark.6)

Case ReportsCase 1. A 54-year-old woman who was pre-

viously operated upon for carcinoma of the largebowel had a typical left lobectomy (40% of theliver parenchyma) for solitary metastasis. Therewere no postoperative complications.

Case 2. A 20-year-old man who sustained bluntinjury to the right hepatic lobe in a traffic acci-dent had a typical right lobectomy (60% of theparenchyma) immediately after arrival at the hos-pital. There were no significant postoperativecomplications.

Case 3. A 71-year-old woman had severe car-diovascular symptoms from hepatic metastases ofintestinal carcinoid. To reduce the hormone pro-

ducing tumor mass, a typical right hepatic lobec-tomy (60%) was performed. The tumor masseshad probably reduced the size of the remainingleft lobe by at least 50 per cent. Pleuritis andgastric retention were complications one weekpostoperatively. The preoperative high HIAA levelwas normal postoperatively. However, progressivehypoalbuminemia could not be satisfactorily com-

pensated and the patient died after 3 weeks.Case 4. A 56-year-old woman with gastric

carcinoma invading the left lobe of the liver hada total gastrectomy plus typical resection of theleft lateral segment (20%). Other than pleuritispostoperatively, there were no complications.

Case 5. A 58-year-old man previously hadextirpation of a leiomyosarcoma in the omentumand ligation of the hepatic artery for metastasesin both lobes of the liver. Left lobectomy plus

IAFSTROM AND OLSSON Annals of SurgeryJanuary 1969

atypical resection of the remaining solitary metas-tasis in the right lobe (totally 50%) were per-formed. There were no postoperative complica-tions. (This patient has previously been reported.2)

Case 6. A 63-year-old woman had carcinomaof the gallbladder with invasion of right lobe ofthe liver demonstrated at previous laparotomy.Extended right lobectomy (80%) was performed.Other than wound infection, there were no post-operative complications.

Case 7. A 42-year-old woman had carcinomaof the gallbladder with invasion of the right liverlobe demonstrated at previous laparotomy. Ex-tended right lobectomy (80%o) was performedwith common duct drainage. There was a progres-sive increase of serum bilirubin and alkaline phos-phatase until the 14th postoperative day. Jaundicewas to some extent considered due to partial bili-ary stasis caused by an infrahepatic biliary ab-scess. Serum bilirubin decreased after drainage onthe 14th postoperative day.

Case 8. A 50-year-old woman had previouslybeen operated upon for carcinoma of the sigmoidcolon. Typical right lobectomy for solitary metas-tasis (60%o) was performed with common ductdrainage. Other than pleuritis there were no post-operative complications.

Case 9. A 55-year-old woman who had pre-viously been operated upon for carcinoma of thesigmoid colon had a left lobectomy for metastasis(40% resection) and common duct drainage. Therewere no postoperative complications.

Case 10. A 67-year-old woman had carcinomaof the gallbladder with metastases in the left he-patic lobe and deeply in the right lobe. Left lo-bectomy plus atypical resection of the right lobe(appr. 50%o resection) were performed and thecommon duct was drained. There were no post-operative complications.

Case 11. A 30-year-old woman who had pre-viously been operated upon for retroperitonealparaganglioma had atypical right lobectomy forsolitary mestatasis (60%o). Immediately postopera-tively, intra-abdominal bleeding necessitated re-laparotomy. Otherwise there were no postopera-tive complications.

Case 12. A 67-year-old woman had extendedright lobectomy for primary hepatic cancer (80%o).There were no postoperative complications.

ResultsTable 1 records the pattern of serum en-

zymes, bilirubin, and BSP changes in eachpatient. A surprisingly wide range of varia-

ENZYME AND FUNCTION CHANGES AFTER LIVER RESECTION

TABLE 1

Preop.Normal Values Values I d. 2 d. 3 d. 4 d. 5 d. 6 d. 7 d. 10 d. 14 d. 21 d. 28 d.

1. Bil. <0.4 mg./100 ml. 0.4 1.7 2.2 2.6 3.1GOT <25 u/ml. 40 900 1200 900 175GPT <40 u/ml. 37 806 27 800 445OCT <0.25 ug. N/ml. 51 88 91 41A. P. <9 u/ml. 44 27 22 15 15

2. Bil. <0.4 mg./100 ml. 3.8 2.7 1.8GOT <25 u/ml. 390 250 145GPT <40 u/ml. 416 246 130OCT <0.25 gg. N/ml. 38 30 23 11A. P. <9 u/ml. 7 5 8

3. Bil. <0.4 mg./100 ml. 0.2 0.7 4.3 5.2 4.1 4.4GOT <25 u/ml. 22 320 139 95 50 45GPT <40 u/ml. 11 350 300 205 155 88OCT <0.25 pg. N/ml. 18 48 48 23 15 6A. P. <9 u/ml. 14 10 10 10 10 12

4. Bil. <0.4 mg./100 ml. 0.2 0.6 0.7 0.7 0.6 0.4GOT <25 u/ml. 30 160 56 25 23 34GPT <40 u/ml. 63 500 260 130 95 88A. P. <9 u/ml. 12 15 12 13 20 16

5. Bil. <0.4 mg./100 ml. 1.0 1.5 1.8 4.0GOT <25 u/ml. 200 1320 850 415GPT <40 u/ml.OCT <0.25 pg. N/ml.A. P. <9 u/ml. 8

6. Bil. <0.4 mg./100 ml. 0.5GOT <25 u/ml. 27GPT <40 u/ml. 30OCT <0.25 pg. N/ml. 19A. P. <9 u/ml. 7

7. Bil. <0.4 mg./100 ml. 0.3GOT <25 u/ml. 30GPT <40 u/ml. 20A. P. <9 u/ml. S

8. Bil. <0.4 mg./100 ml. 0.5GOT <25 u/ml. 22GPT <40 u/ml. 23A. P. <9 u/ml. 12

9. Bil. <0.4 mg./100 ml. 0.4GOT <25 u/ml. 20GPT <40 u/ml. 19OCT <0.25 pg. N/ml.A. P. <9 u/ml. 7

10. Bil. <0.4 mg./100 ml. 0.3GOT <25 u/ml. 42GPT <40 u/ml. 20OCT <0.25 pg. N/ml. 6A. P. <9 u/ml. 24

11. Bil. <0.4 mg./100 ml. 0.5GOT <25 u/ml. 51GPT <40 u/ml. 47A. P. <9 u/ml. 51

12. Bil. <0.4 mg./100 ml. 0.4GOT <25 u/ml. 26GPT <40 u/mi. 32A. P. <9 u/ml. 13

108 225 1225

2.5 0.7 0.360 32 3891 45 282 414 18 28

1.4 0.9 0.8 0.5 0.347 60 43 37 4158 56 54 548 6 7 7 57 9 9 11 12

2.7 1.027 27

351.0

14 8

0.9 1.2 0.729 42 40 3037 43 36 3718 15 11

3.8 3.041 104165

82 91 30 8 118 8 9 9 12

7.2 8.7 10.1 7.9 9.2 9.1 8.4 12.2 6.1 3.3400 218 113 93 140 60 50 40 56 81570 380 220 140 200 100 79 42 67 85

10 15 0.5 7 5 4 4 6 99 8 8

7.4 11.6142 90137 886 5

0.3 5.5 5.160 54

20 1413 9 7

1.4 1.0 1.078 61 30

120 115 6026 40 187 6 4

0.6 0.865 4055 65

6312 11

4.262478

4.1 1.2 1.7 1.685 47 24 1255 45 20 128 6 5 7

7 8 8 9 10 16

20.2 12.8 10.5 7.2 27.0 14.564 70 55 63 54 61

40 33 30 35 227 9 12 18 10 8

8.0 5.468 4542 307 16 41

2.0 1.3 1.0 0.6 0.4 0.427 35 30 39 47 4034 63 60 60 60 3210 2 3 1 18 9 7 4 8 7

5.3 3.8 2.2 1.4 0.4 0.430 30 24 44 90 3440 25 20 30 25

13 11 14 25 19 11

8.4 3.0 1.090 45 4034 17 319 17 18

1.1 0.612 1019 135 9

Volume 169Number 1

PatientNo.

113

tions in maximum GOT and GPT activity others, serum activity remains normal orfollowed resections of the liver. There were almost normal. Marked elevations whichpronounced elevations in some cases; in occur are observed on the first or second

114% mg *.100,90to -

90 98 -

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FIG. 1. Comparison 1Bil., BSP, OCT, GOT, andnormalization of GOT ancliver resections. The patiering to the extent of the mmTo enable conclusions to binfluence of the extent of Iof operation, remaining rblood transfusions, and theof the T-tube, these are als

postoperative day. In scand in others the GPTpronounced elevation.for return to normalbears no relation topertransaminasemia. W

.MERSJO, BENGMARK, HAFSTROM AND OLSSON Annals of SurgeryJanuary 1969

Bilirubin nasemia is more pronounced the GPT re-BSp" turns to normal somewhat latcr than the

GOT, but this pattern is not apparent ininstances of less pronounced transaminase-mia. As Figure 1 shows, the extent of the

7 9l:,mo OCT GOT hypertransaminasemia appears to bear norelation to the extent or the type of resec-

Ffl tion, whether the procedure is typical oratypical, or on the right side or left side.

Time of normol'zo-_ _ _ a{ionof GOT Nor does it seem to be correlated with ageof the patients or to the presence or ab-

_4 _ sence of metastases in the hepatic remnant.Patients in whom Flurotane was used do

Maximal GOT not have more hypertransaminasemia than- - GPr - those in whom Flurotane is not used. The

number of pints of blood administered dur-ing operation or during the first 24 hourspostoperatively does not seem to be relatedto the degree of serum transaminase eleva-ltent of tion. An inverse relation seems to exist,however, between the duration of the op-eration and the degree of hypertransami-

7 9 10 8 112 nasemia. Similarly, the use of common ductDuratZionof drainage perhaps influences the degree of

hypertransaminasemia. Thus, common ductdrainage was not used in any of the sixpatients with maximum elevation of GOTand/or GPT above 300 units/ml., whereasit was used in five out of six patients withno elevation or an elevation below 300

1,2'~5S4322 3units/ml.Changes in the serum enzymes seem to

r^ _ be independent of simultaneous changes in)etween the maximum liver function measured by serum bilirubinCGPT and the time for and BSP determinations. The return to nor-

I GPT, after extensive mal of transaminase activity is not relatedits are ordered accord- to the degree of hypertransaminasemia, nor1aximum GOT activity.e drawn regarding the to any of the above-mentioned factors. Onliver resection, duration the other hand impairment of the livermetastases, number ofuse of anesthesia and function, as measured in bilirubin and BSP

o documented. determinations, seems to be roughly pro-portional to the extent of the resection.

3me cases, the GOT This is more apparent in Figure 2. Thedisplayed the most other factors mentioned above do not seemThe time necessary related to the degree of functional impair-varies greatly and ment.the extent of hy- Although the two most pronounced post-hen hypertransami- operative elevations of OCT activity are

rTV1F1Tf

-R

FT-F .

ENZYME AND FUNCTION CHANGES AFTER LIVER RESECTION

Time of normclizo-tion of GOT,-,

_ - and GPT -

I

days

282114

7

Time of normolizationof bilirubin12 11

7 8 6 10 5 tt I 3 9 2 4 12

80

60

40

20

*1.

mg 1.

t10

4-

8

6Mofsximal Bilirubin

-" BSP -

Estent ofliver resection

Case nujmber 6 7 3 8 2111 2 1 5 9 10 4

Fic. 2. Comparison between the maximumpostoperative Bil. and the extent of liver resection.For comparison, the maximum BSP and the timeof normalization of GOT and GPT are illustrated.

seen in the two patients who display themost marked serum transaminase eleva-tions, the pattern is not so uniform in theother patients. The time of return to nor-

mal is generally shorter and more uniformfor OCT than for the transaminase.

Alkaline phosphatase activity is onlyslightly affected by operation. Pronouncedchanges are seen only in three patientswith markedly elevated values preopera-

tively. A prompt decrease of the activityoccurs in these patients. Those with pre-

operative normal or slightly elevated valuesdisplay very small increases or decreases.As mentioned the use of common duct

drainage seems to have reduced the degreeof hypertransaminasemia. Concerning theliver "function tests," bilirubin and BSP, no

such effect of T-tube drainage is apparent

(Fig. 3).

Discussion

The consistent finding of marked hyper-transaminasemia after partial hepatectomyin experimental animals 8, 18, 19, 23, 24, 53 is notinvariable in the present human material.The reason for this dissimilarity is obscure.Differences in the operative procedure per

30

mg V. 20

10

6 7 8 3 2 1t 12 1 5 9 10 4

K

Moximot bitirubin duringtwo first postop. days

Maximal bilirubin duringthe whole period

7 6 11 8 3 10 2 5 12 1 9 4

T- tube S normal value not recorded0 during the period

FIG. 3. Effect of T-tube drainage on the extentand duration of the postoperative hyperbilirubin-emia.

se do not seem to be responsible, since dif-ferences in the extent of the resection inthe present observations do not influencethe degree of postoperative hypertransami-nasemia, which agrees with earlier experi-ments.19

A peculiar finding in man is the inverserelationship between maximum transami-nase levels and duration of operation. Sincethe same team performed all the opera-

tions, the duration of each operation is a

rough measure of the difficulties encoun-

tered. It therefore seemed important tofind out whether the amount of blood ad-ministered at operation and during the firstpostoperative hours could be a determinantin the degree of hypetransaminasemia.Analysis of the number of blood transfu-sions does not support the hypothesis thatlowered postoperative transaminase levelscould be due to dilution of the recipient'sblood.The other "positive" observation, the use

of T-tube drainage in patients with no or

only slightly transaminase elevations, couldbe more than coincidental. Several writers 3'54, 56, 57 recommend common duct drainageafter hepatic resection with the object ofdiminishing the pressure within the biliary

Volume 169Number 1

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21

14

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116 ALMERSJO, BENGMARK,

tree, thereby reducing leakage of bile fromthe cut surface. We do not know whetherthere is increased pressure within the bileducts postoperatively, but if so, this in-creased pressure could be a factor in hyper-transaminasemia. Experimental studies 11, 37demonstrate that a rapid rise in serumtransaminase activity occurs after suddenincrease in intraductal pressure. T-tubedrainage could prevent such a rise andavoid the transaminase elevation.The lack of beneficial effect of common

duct drainage on serum bilirubin elevation(Fig. 3) does not detract from the value ofthe T-tube, since the extent of resectionseems to be the important factor in serumbilirubin elevation. This view is based oncorrelations observed and on earlier stud-ies demonstrating decreased excretion ofbilirubin after partial hepatectomy,58 al-though excretion of bile per unit tissue ofliver remnant is increased.34

In Case 11, no postoperative hypertrans-aminasemia was observed, despite no T-tube drainage, but the large amount ofblood administered in connection with theoperation could have had a dilution effectand explains the lack of hypertransami-nasemia. Despite no proof of beneficialeffect by the common duct drainage onliver "function tests," we none the lessrecommend this step until further experi-ence has been obtained. Discrepancies be-tween postoperative hypertransaminasemiain experimental animals and the irregularpattern in man and differences in extentof hypertransaminasemia between patients,are unexplained because of imperfect un-derstanding of the cause of hypertransami-nasemia. Liberation of the enzyme fromdamaged liver cells at the site of the resec-tion seems improbable for several reasons:absence of hyperenzymemia in some pa-tients despite similar resections in patientswith hyperenzymemia; discrepancies be-tween levels of elevation of transaminases,GOT and GPT, and the almost purely he-patic enzyme OCT 46 in individual pa-

HAFSTROM AND OLSSON Annals of SurgeryJanuary 1969

tients; lack of significant increase of alka-line phosphatase despite its known pres-ence in cells in the liver.47 One explanationcould be liberation of enzymes from cellsin other parts of the liver. Opposed to thisis the experimental finding of largely un-changed GOT activity per mg. wet liverdespite pronounced elevation of serum ac-tivity.8 This finding indicates increased syn-thesis which can be either a response toincreased loss of enzyme from the livercells or a primary phenomenon. The as-sumption of increased synthesis is sup-ported by the finding of increased GOT ac-tivity per mg. of protein in mitochondrialas well as supernatant fraction.8 Similarly,Hauss et al.29 calculate that in some dis-orders enzyme activity in serum is greaterthan the total enzyme activity of the wholenon-diseased organ. Finally, it should bestressed that as we cannot determine en-zyme in weight units we cannot statewhether there is an increased amount ofenzyme or whether increased activity is aresult of activation of the enzyme.The lack of correlation between the time

of return to normal of transaminases andthe extent of resection indicates that thehuman liver is of little or no importancefor elimination of serum transaminases.This is consistent with earlier experimentalobservations that intravenously adminis-tered GOT disappears as rapidly in par-tially hepatectomized animals as in ani-mals with intact liver.,3 4, 23 Lack of corre-lation between the time of return to normaland bilirubin levels and BSP was not sur-prising because of the low transaminaseactivity in bile 7, 10, 21, 22, 25, 30, 36, 49, 52 whichexcludes the biliary tract as a way of elimi-nating serum transaminases. The long pe-riod before return to normal of serumtransaminase activity in some patients whohad slight elevations immediately postop-eratively, indicates either a continued re-lease of enzyme from the liver or a de-creased turnover of enzymes in the extra-vascular space."4

.s I

ENZYME AND FUNCTION CHANGES AFTER LIVER RESECTION

In experimental animals, partial hepa-tectomy almost always causes increasedserum AP activity.39 41 48 Lack of signifi-cant postoperative increase in the serum

AP in man stresses that animal experi-ments on serum AP in hepatic disordersare not directly applicable to man. Evi-dence has been presented that serum APis eliminated via the bile in dogs.16 17, 35Although no similar experiments have beenperformed in man, there is indirect evi-dence that this is true also in man.' If thisview is correct, the "reserve capacity"seems to be much greater for AP than forbilirubin since no significant postoperativehyperphosphatasemia was observed de-spite marked hyperbilirubinemia. Someanimal experiments indicate that elimina-tion or reduction of the excretory appa-

ratus is not responsible for hyperphos-phatasemia in biliary obstruction; althoughligation of one hepatic duct causes hyper-phosphatasemia 20' 28 excision of a liver seg-

ment drained by one hepatic duct doesnot.26 There are also clinical observationsindicating that large parts of the humanliver can be destroyed without impressivesucceeding hyperphosphatasemia.15 The un-

importance of the liver for elimination ofserum AP in man is also suggested by re-

cent studies showing that at least humanplacental AP is eliminated in much thesame way as injected plasma proteins.45Although these findings seem peculiarwhen considering the almost regular hy-perphosphatasemia after partial hepatec-tomy in animal experiments, they wouldexplain the lack of postoperative hyper-phosphatasemia in the present studies.

If obstruction at some point of elimina-tion is not the cause of hyperphosphatase-mia in hepato-biliary disorders, what is thecause? The hepatic origin of the enzymein biliary obstruction has been made per-

fectly clear by the studies of Sebesta et al.50These authors perfused isolated liver prepa-rations and observed a significant rise inthe AP activity in the perfusate after bili-

ary obstruction. The concept of a hepaticorigin of the enzyme in liver cancer is sup-

ported by the observed decrease of serum

activity after removal of the tumor in thosepatients with preoperatively elevated lev-els. The origin of enzyme within the liveris not known. Sherlock and Walshe51 andKritzler and Beaubieu33 described an in-creased AP activity in the vicinity of re-

generating liver cells in "active" cirrhosisindicating a release of enzyme from theregenerating or necrotic liver cells. Theseobservations have not been verified byother authors.'4'55 Another theory is thatproliferating bile duct cells are the source

of the AP activity. These cells display very

high AP activity.59 Popper et al.44 believethat proliferating bile ductules represent a

response by the liver to injury. Accordingto Burke 13 increased serum AP activity isan expression of regeneration of liver cells.

The results of the present studies do notsupport this view, since no hyperphos-phatasemia occurred despite marked re-

generation proved at second look opera-

tions and angiographic investigations.9

Summary

Determinations of serum GOT, GPT,OCT, and alkaline phosphatase activity, as

well as serum bilirubin concentration andbromsulphalein retention, were made be-fore and up to 4 weeks after extensive liverresection in 12 patients. The immedi-ate postoperative hypertransaminasemiaseemed to bear no relation to the extentof the resection, but to be inversely corre-

lated to the duration of operation. It was

far less pronounced when common ductdrainage was used postoperatively. Serumalkaline phosphatase activity was onlyslightly affected by operation, a markedalteration being observed only where therewere preoperatively pronounced elevations.Serum bilirubin concentration and brom-sulphalein retention appeared to dependon the extent of the resection.

Volume 169Number 1 117

118 ALMERSJO, BENGMARK, HAFSTROM AND OLSSON Annals of Surgery

References1. Allen, H. and Spellberg, M. A.: Alkaline Phos-

phatase in Bile and Urine. Excretion in Pa-tients with Hepatobiliary Disease. Arch. Int.Med., 120:667, 1967.

2. Almersjo, O., Bengmark, S., Engevik, L., Haf-str6m, L. 0. and Nilsson, L. A. V.: HepaticArtery Ligation as Pretreatment for LiverResection of Metastatic Cancer. Rev. Surg.(Phila.), 23:377, 1966.

3. Amelung, D.: Untersuchungen zur Grosse derEliminationsgeschwindigkeit von Fermentenaus dem Kaninchen-Serum. Hoppe Seyler Z.Physiol. Chem., 318:219, 1960.

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5. Armstrong, A. R., King, E. J. and Harris,R. J.: Phosphatase in Obstructive Jaundice.Canad. Med. Ass. J., 31:14, 1934.

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9. Bengmark, S., Engevik, L. and Rosengren, C.:Angiography of the Regenerating HumanLiver after Extensive Resections. Surgery. Inprint, 1968.

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11. Braun, P., Papp, M. and Horvath, I.: Deter-mination of Transaminase Activity in DogsSerum and Lymph after Hepatic Damagedue to Acute Biliary Obstruction. Nature(London), 183:48, 1959.

12. Buch, I. and Buch, H.: Improved King andArmstrong Method for Determination ofPhosphatase Activity in Blood Serum. ActaMed. Scand., 101:211, 1939.

13. Burke, J.: Serum Alkaline Phosphatase inLiver Disease: A Concept of Its Significance.Gastroenterology, 16:660, 1950.

14. Cleveland, F. P., Richfield, D. F., Gall, E. A.and Schiff, L.: Needle Biopsy of the Liver.V. Observations on the Distribution of Alka-line Phosphatase and Its Diagnostic Signifi-cance. Arch. Path. (Chicago), 49:333, 1950.

15. Cook, G. C. and Sherlock, S.: AetiologicalFactors in Acute Hepatic Necrosis in Man.In Therapeutic Agents and the Liver, Editedby McIntyre, N. and Sherlock, S. Black-well Scientific Publications, Oxford, 1965,p. 71.

16. Dalgaard, J. B.: Serum Phosphatase afterTransfusion of Phosphatase-Rich Blood toNormal Dogs. Acta Physiol. Scand., 22:193,1951a.

17. Dalgaard, J. B.: On the Cause of the Increasein Serum Phosphatase in Obstructive Jaun-dice. Acta Physiol. Scand., 22:200, 1951b.

18. Dessi, P. and Gianni, A. M.: RigenerazioneEpatica e Processi di Transaminazione. Speri-mentale, 107:104, 1957.

19. Di Paulo, E., Vancini, B. and Cenacchi, C.:L'attivita Transaminasica Sierica in Corso diRigenerazione Epatica. Arch. Pat. Clin. Med.,35:392, 1958.

20. Drill, V. A. and Ivy, A. C.: Comparative Valueof Bromsulphalein, Serum Phosphatase, Pro-thrombin Time, and Intravenous GalactoseTolerance Tests in Detecting Hepatic Dam-age Produced by Carbon Tetrachloride. J.Clin. Invest., 23:209, 1944.

21. Dubach, U. C.: Die Glutaminsaure-Oxalessig-saure-Transaminase in ihrer diagnostischenBedeutung. Z. klin. Med., 154:593, 1957.

22. Dunn, M., Martins, J. and Reissmann, K. R.:The Disappearance Rate of Glutamic Oxal-acetic Transaminase from the Circulationand Its Distribution in the Body's FluidCompartment and Secretions. J. Lab. Clin.Med., 51:259, 1958.

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