All patients had their initial examinations after oralphenoborbital therapy (5 mg/kg-day) for at least 3 days

(3—15 days). The infants were given nothing by mouth

for 3 hr before the examination. Fluid was supplied intravenously. A radiopaque infant-size duodenal tube waspositioned between the second and third portions of theduodenum, as confirmed by brief fluoroscopy. Duodenaljuice was collected by aspiration through the duodenaltube. One millicurie of Tc-99m DISIDA was given intravenously after the initial collection of duodenal juice.Then 1 to 2 ml of duodenal juice was collected at 5, 15,30, and 45 mm after injection, and at 1, 2, 3, and 4 hr.After adequate mixing, paired samples of 100 jsl of duodenal juice were obtained from each collection. Allsamples were counted by gamma counter at 5 hr afterinjection. We recorded the average values of compatiblepaired data, sampling again if they were not compatible.The results were plotted into a time-activity curve foreach patient.

Sequential anterior scintigrams of the abdomen were

also obtained 1, 5, 15, and 30 mm after injection, and atI, 2, and 4 hr. Delayed images were obtained at 24 hr ifthere were still nonvisualization of gallbladder or bowelactivity by 4 hr.

RESULTS

Nineteen patients finally proved to have neonatalhepatitis, and four had biliary atresia. In the group ofneonatal hepatitis, the images showed the gallbladderactivity in only three cases, bowel activity in only eight

Neonates with prolonged obstructive jaundice pose

a diagnostic problem that may remain unsolved byroutine clinical and laboratory examinations, especiallyin the commonly encountered neonatal hepatitis and

biliary atresia. Reliable discrimination between these twoentities is ofgreat clinical importance. Infants with bil

iary atresia must be operated on as early as possible toavoid an otherwise fatal outcome (1—3).On the otherhand, neonatal hepatitis is a self-limited disease, andlaparotomy would increase morbidity and mortality(4,5). Technetium-99m cholescintigraphy was thought

to be the most sensitive way to separate these two entities,(6—JO)but the specificity is not fully satisfactory. In the

present study we attempted to establish a more reliablemethod by analyzing the radioactivity in duodenal juicein conjunction with di-isopropylphenylcarbamoyl

methylimidodiacetic acid (Tc-99m DISI DA) chole

scintigraphy.

MATERIALS AND METHODS

Twenty-three infants with prolonged obstructivejaundice were studied prospectively. The patients rangedin age from 40 to 105 days. The sex, serum bilirubinlevels, and final diagnoses are summarized in Table I.The diagnoses were individually confirmed by laparotomy, liver biopsy, and/or by following the clinical

course.Received July 25, 1983@revision accepted Oct. 3, 1983.For reprints contact: Twci-Shiun Jaw, MD, Dept. of Radiology,

Kaohsiung Medical College Hospital, Kaohsiung, Taiwan, Republicof China.

360 THE JOURNAL OF NUCLEAR MEDICINE

Diagnosisof ObstructiveJaundicein Infants:Tc-99mDISIDAinDuodenalJuice

Twei-ShiunJaw, Chung-ChiengWu, Yau-HuiHo,Bih-LiangHuang,and Chu-ChongLu

KaohsiungMedical College Hospital, Kaohsiung, Taiwan, Republic of China

Technetlum-99m dl-Isopropylphenylcarbamoylmethylimldodlacetlc acid cholescintigraphy,togetherwith measurementsof radloactivftyIn duodenalJuice,wasused to evaluate 23 infants wIth prolongedobstructiveJaundice.Four patientsprovedto have biliary atresia. The remainderhad neonatalhepatitis.There wasdistinctdifferentiationof biliaryatresiafrom neonatalhepatitiswhenthe time-actlvity curves were analyzed. in neonatal hepatitis the radioactivityin duodenaljuice is obviously higher, peaking above 1500 cpm/100 0 per mCi dose. in biliaryatresia the paftern is flattened, with maximal activity below 500 cpm/100 j@ipermCi dose.

J NucI Med 25: 360—363,1984

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MaximalradioactivityPatientExamAgeBilirubin

(mg/dI)ImagefindingsBile-stained

induodenalin

1001ulofduodenal

juiceFinalGallbladderTracerNo.Sex No.(days)total/directvisualized in boweljuice(cpm/mCi)diagnosis

PRELIMINARY NOTES

TABLE1. CLINICALAND LABORATORY DATA IN 23 INFANTS WITh PROLONGED OBSTRUCTIVEJAUNDICE

1 F 1 402 F 1 72

3 M 1 852 91

4 M 1 105

13.2/8.415. 1/9.5

8.2/5.58.8/6.59.8/3.9

427173474484151

Biliary atresiaBiliary atresiaBiliary atresia

Biliary atresia

5 F 1 846 M 1 697 M 1 428 M 1 459 M 1 58

10 M 1 4111 M 1 59

2 6312 M 1 8113 M 1 44

14 M 1 4415 M 1 5816 M 1 4917 F 1 5218 M 1 7519 M 1 44

2 5620 F 1 75

2 8421 M 1 4922 M 1 6423 M 1 59

8.3/6.14.8/3.25.6/3.88.4/5.28.7/5.99.5/6.54.8/3.7

+ ++ ++ ++ +— +

— +

— +

+++++++++++

++

27,46846,48483.311

2,20467,865111,0042,228

22,74553,6804,301

12,6191,639

3,8822,7252,1973,4512,3812,238

13,9562,1381,5761,855

NeonatalhepatitisNeonatalhepatitisNeonatal hepatitisNeonatalhepatitisNeonatalhepatitisNeonatal hepatitisNeonatalhepatitis

7.5/5.211.2/7.37.1/4.8

10.4/6.8

19.8/13.67.9/5.7

11.1/8.14.0/3.14.0/3.29.2/5.87.8/5.6

12.3/7.95.1/4.05.8/3.8

- +

++— +

— +

— +

— +

+

Neonatal hepatitisNeonatalhepatitisNeonatalhepatitisNeonatalhepatitisNeonatalhepatitisNeonatalhepatitisNeonatalhepatitisNeonatalhepatitis

Neonatalhepatitis

NeonatalhepatitisNeonatalhepatitisNeonatalhepatitis

cases, and both in four cases. The remaining four casesof neonatal hepatitis showed neither gallbladder norbowel activity by 24 hr. All of the patients with biliaryatresia failed to visualize either gallbladder or bowelactivity (Table I ). For the diagnosis of biliary atresia,the sensitivity is 100% but the specificity is only 78.9%.The accuracy is 82.6%, and the positive predictive valueis 50%.

None of four cases with biliary atresia had bile stainin the duodenal juice. On the other hand, I 2 out of I 9cases of neonatal hepatitis showed bile staining. Basedon the appearance of positive or negative bile staining,the sensitivity of diagnosis is 100%, the specificity is63.2%, the accuracy is 69.6%, and the positive predictivevalue is 36.4%.

With analysis of the time-activity curves from duodenal juice, cases of neonatal hepatitis had maximalactivities varying from I ,576 to I 1 1,040 cpm/ I00 sl ofduodenal juice per mCi dose, whereas cases of biliaryatresia had maximal activities varying from I51 to 484

cpm/ I00 @tl-mCi(Table I ). Biliary atresia gave a flattened pattern, but neonatal hepatitis showed obvious riseof activity after 30 mm (Fig. I ). The method thereforeprovides clear discrimination between neonatal hepatitisandbiliaryatresia.

DISCUSSION

About 75% of cholestasis in neonates fall into the twocategories of biliary atresia and neonatal hepatitis (II).Although Landing ( I974) proposed that neonatal hepatitis and biliary atresia represent different responses tosimilar perinatal insults, presumably infectious, (12) themanagement and prognosis of neonatal hepatitis andbiliary atresia differ. Neonatal hepatitis is a self-limiteddisease without specific therapy and with a cited mor

tality of 10% to 40% (11). Untreated biliary atresia isbound to be fatal, with 95% of the patients dying beforeage 2 (4,11,13). Portoenterostomy (Kasai procedure)has dramatically improved the survival of infants with

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JAW, WU, HO. HUANG, AND LU

(CPM/mCi/100pl)

>

UCe

0

CO

0 5 15 30 45 60 90Ti@ 120

—.—.— Normal infant

150 180 210 240 (mm.)

io6 Neonatal hepati ti s

——-——Biliary atresia

?.@—-@....—--- - °@

@-=z@t @:‘ o

@@ @====:io2

FIG. 1. Time-activitycurvesof duodenaljuice in 23 infantswithprolongedobstructivejaundice

biliary atresia, (/4) and there is now a 30% to 40% 4-yrsurvival rate (15). Kasai et al. report long-term survivalof more than 22 yr (/4,16). The age of the patient at thetime of surgery is crucial. Long-term follow-up studiesindicate that results are significantly better when surgeryis performed before 10 wk ofage (16). Although lapa

rotomy with operative cholangiography can provide adirect and definite diagnosis, (17,18) it increases the riskof cirrhosis and mortality in cases of neonatal hepatitis(5). Thus it is very important to differentiate these two

entities early and accurately by noninvasive methods.Routine clinical and laboratory studies pose a diag

nostic dilemma. Many tests have been used to evaluateprolonged obstructive jaundice in infants, includingclinical scoring, alpha-fetoprotein, lipoprotein-x, serumgamma glutamyl transpeptidase, liver aspiration biopsy,laparoscopy, and fecal excretion of I- I31 rose bengal(/9—24). No single test or combination of tests has

proven infallible. Recently Tc-99m cholescintigraphyhas been considered the most accurate method of diag

nosis (6—10).The sensitivity is good, but the specificityvaries with the Tc-99m labeled radiopharmaceutical

used. Studies in baboons have shown that agents similarto Tc-99m DISIDA are superior hepatobiliary radiopharmaceuticals (25,26). Clinical studies in a varietyof hepatobiliary diseases have also showed that Tc-99mDISIDA rapidly clears from the blood, yielding satisfactory to excellent images of the biliary system withminimal interference from renal activity (27,28). In the

present study, the sensitivity is 100% and specificity is

78.9%. Four of our 23 cases could not be differentiatedby observation of Tc-99m DISIDA cholescintigrams.

Greene et al. report that accurate differentiation between biliary atresia and neonatal hepatitis can beachieved by observing a 24-hr collection of duodenaljuice for the presence of bilirubin staining (29). In thepresent series, however, we failed to detect visible bilirubin staining of the duodenal juice in seven cases ofneonatal hepatitis.

Serial measurements of radioactivity in duodenal juiceoffer a time-activity curve, corresponding to the biliarydynamics. They separate biliary atresia from neonatalhepatitis without difficulty. Biliary atresia yields aflattened time-activity curve with the maximal activityin duodenaljuice below 500 cpm/l00 jsl per mCi of dose.In neonatal hepatitis the activity of duodenal juice increases progressively after administration of Tc-99mDISIDA, and after 30 mm it reaches a maximum thatis usually higher than 1,500 cpm/l00 id-mCi. There wasa clear-cut discrimination between the two entities.

Regarding the insertion of the duodenal tube, wefound that the procedure was safe and easily done. Thecommon practice of duodenal feeding in many neonatalunits attests to the ease with which duodenal tubeplacement can be achieved. Gastric insufflation of airand a right decubitus position of the infants greatly aidpassage of the tube into the duodenum (30,31 ). Theentire procedure usually requires less than 10 mm. Al

though morbidity associated with prolonged use of apolyvinyl feeding tube has been reported, (32) we have

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PRELIMINARY NOTES

observed no major complication of duodenal intubationin the present series as well as elsewhere in our neonatalunit. Sneezing and rhinorrhea due to irritation by thetubes occurred only in some cases, and, these symptomsusually subsided promptly without therapy.

Brief fluoroscopy was performed to document theposition of the duodenal tube. It involves the risk of increased radiation dose to the infants, but the durationof exposure can be minimized by other ways of confirming the position of the tube in the duodenum beforefluroscopy, such as by determining the pH of the aspirateor by failure to aspirate air (31).

It is emphasized, therefore, that serial analysis of radioactivity in the duodenal juice after administration ofTc-99m DISIDA may offer a highly specific and sensitive method for differential diagnosis of biliary atresiafrom neonatal hepatitis. More cases will be studied toevaluate the accuracy of this examination.

ACKNOWLEDGMENTS

WethankMr.Tyen-JanHwangand MissChing-ShwuHer fortheirtechnical assistance.

REFERENCES

I. KASAI M, SUZUKI H, OHASHI E, Ctal: Technique and resultsofoperative managementofbiliary atresia. WorldJSurg2:571—580,1978

2. HAYS DM, SNyDER WH: Life-span in untreated biliaryatresia. Surgery 54:373—375,1963

3. ADELMAN S: Prognosis of uncorrected biliary atresia: anupdate.J PediatrSurg 13:389—391, 1978

4. THALER MM, GELLIS SS: Studiesin neonatalhepatitisandbiliaryatresia1.Long-termprognosisof neonatalhepatitis.AmfDisChild 116:257—261,1968

5. THALERMM, GELLISSS: Studiesin neonatalhepatitisandbiliary atresia. II. The effect of diagnostic laparotomy onlong-term prOgnosis of neonatal hepatitis. Am J Dis Child116:262—270,1968

6. MILLERJH,SINATRAFR,THOMASDW: Biliaryexcretiondisordersin infants:evaluationusing99mTc@PIPIDA.AmIRoentgenol 135:47—52,1981

7. MAiD M, REBARC, ALTMAN RP: Hepatobiliaryscintigraphy with 99mTc.PIPIDA in the evaluation of neonataljaundice.Pediatrics67:140—145,1981

8. HITCHDC, LEONARDJC,PYSHERTi, etal: Differentiation of cholestaticjaundice in infants: Utility of diethyl-IDA.AmfSurg 142:671—677,1981

9. MAiDM,REBARC,ALTMANRP:Effectofphenobarbitalon 99mTC.IDAscintigraphy in the evaluation of neonataljaundice.SeminNuclMed 11:194-204,1981

10. COLLIER BD, TREVES S, DAVIS MA, et al: Simultaneous99mTc.p.butyl4DA and ‘311-rosebengal scintigraphy inneonataljaundice. Radiology 134:719—722,1980

Ii. MOWAT AP, PSACHAROPOULOS HT, WILLIAMS R:Extrahepatic biliary atresia versus neonatal hepatitis—Reviewof 137 prospectivelyinvestigatedinfants.Arch Dis Child51:763—770,1976

12. LANDING BH: Considerations of the pathogenesis of neo

natal hepatitis, biliary atresia, and choledochal cyst: Theconceptofinfantileobstructivecholangiopathy.ProgPediatrSurg6:113-139,1974

13. DANKS DM, CAMPBELL PE, SMITH AL, Ct al: Prognosisof babies with neonatal hepatitis. Arch Dis Child 52:368—372,I977

14. KASAI M, KIMURA 5, ASAKURA Y, et al: Surgical treatment of biliary atresia. I Pediatric Surg 3:665-675, 1968

15. HITCH DC, SHIKES RH, LILLY JR: Determinants of survivalafter Kasai's operation for biliaryatresia usingactuarialanalysis. J Pediatr Surg 14:310—314, 1979

16. KASAI M, WATANABE I, OHI R: Follow-up studies of longterm survivors after hepatic portoenterostomy for “non-correctable―biliary atresia. I Pediatr Surg 10:173—182,1975

17. HAYS DM, WOLLEY MM, SNYDER WH, et al: Diagnosisof biliary atresia: Relative accuracy of percutaneous liverbiopsy, open liver biopsy, and operative cholangiography. IPediatr71:598—607,1967

18. LAWSON EE, BOGGS iD: Long-term follow-up of neonatalhepatitis: safety and value of surgical exploration. Pediatrics53:650—655,1974

19. CHIBA T, KASAI M: An attempt to determine surgical indicationforbiliaryatresiabylaboratoryexamination.TohokuJExpMed 115:345—353,1975

20. ZELTSER PM, NEERHOUT RC, FONKALSRUD EW,STIEHAM ER: Differentiation between neonatal hepatitisand biliary atresia by measuring serum-alphafeto-protein.Lancet2:197-199,1974

21. CAMPBELL DR. POLEY iR, ALAUPOVIC P, et al: The differential diagnosis of neonatal hepatitis and biliary atresia.I Pediatr Surg 9:699—705,1974

22. WRIGHT K, CHRISTIE DL: Use of ‘y-glutamyltranspeptidase in the diagnosis of biliary atresia. Am I Dis Child 135:134—146,1981

23. HIRSIG i, PICKHAM PP: Early differential diagnosis between neonatal hepatitis and biliary atresia. I Pediatr Surg15:13—15,1980

24. HAYDEN PW, RUDD TG, CHRISTIE DL: Rose bengal sodium I 131 studies in infants with suspected biliary atresia.AmlDisChild 133:834—837,1981

25. WISTOW BW, SUBRAMANIAN G, VAN HEERTUM RL, etal: An evaluation of @mTc.1abeIedhepatobiliary agents. JNuclMed 18:455—461,1977

26. WIsTow BW, SUBRAMANIAN G, GAGNE GM, Ct al:Experimental and clinical trials of new 99mTc.labeledhepatobiliary agents. Radiology 128:793—794,1978

27. KLINGENSMITH WC III, FRITZBERG AR, SPITZER VM,et al: Clinical comparison of diisopropyl-IDA Tc 99m andDiethyl-IDA Tc 99m for evaluation of hepatobiliary system.Radiology 140:791—795,1981

28. STADALNIK RC, MATOLO NM, JANSHOLT AL, et al:Clinical experience with @mTc.Disofeninas a cholescintigraphicagent.Radiology140:797—800,1981

29. GREENE HL, HELINEK GL, MORAN R: A diagnostic approach to prolonged obstructivejaundice by 24-hour collectionofduodenal fluid. I Pediatr 95:412-414, 1979

30. SCHAFF-BLASSE, KUHNS LR, WYMAN ML: Gastric airinsufflation as an aid to placement of oroduodenal tubes. IPediatr89:954-955,1976

31. HUGHES WALTER WT: Pediatric Procedures. (2nd Edition).Philadelphia, London, Toronto, W. B. Saunders Company,1980, pp 247-248

32. HAYHURST EG, WYMAN M: Morbidity associated withprolonged use of polyvinyl feeding tubes. Am I Dis Child129:72—74,1975

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1984;25:360-363.J Nucl Med.   Twei-Shiun Jaw, Chung-Chieng Wu, Yao-Hui Ho, Bih-Liang Huang and Chu-Chong Lu  Diagnosis of Obstructive Jaundice in Infants: Tc-99m DISIDA in Duodenal Juice

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