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$: Exocrine pancreatic function tests: A reviewdownloads.hindawi.com/journals/cjgh/1989/412302.pdf · Exocrine pancreatic function tests: A review Ynt \'.': I.I, 1'-1[), STI-I'l If\$
REVIEW

Exocrine pancreatic function tests: A review

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ABSTRACT: Exou111c pancreatic funcunn tcsh (PFfs) remn111 ti valuL' 1n the ,l1agnosb nnd assessment of ch ronic pancre,1tic d1scast'. Direct 1111uhmi11n PI-Ts, u,mg sccrctin/1..hnlcL ystokmin m ,ccrct111/cncrule111 ,h the stimul.mts, contmuc w he the 'gold standard', although they arc in vasl\-c, cxpcnsl\e and time u11Nm1111g. Tubeless 111d1rccr tcsb, 1c, the N-ben:oyl l t yrnsyl-para-am111oht·n:01c acid anJ pancrcolauryl tc,t, ha,·c gaim·d incrL·,1:.ing ncccptan..:c pan 1cul.1rly ,1, ,creenmg tc.,ts. The fecal mca,urcmcnt of chym1)tryps111 rem.1111~ a usdul screening test fm pancreat ic msufficicnC) nnd fecal far testi ng standard fnr ,tcatorrhca. R,1d1oisoropt' tests arc now ourdatcd. Esrimat 1011 1if pane rent 1c markers 111 scrum, urine and hndy fluids arc useful when ahntirmal hut miss mild J,,casc. Comh111 ing PFTs with imag111g redrn i<.1ucs pro, iJcs a rauonal approach IO 1·arly d iagnosb and gives a better assessment of the patient ll'ith ch ronic r;mucam dhcase. Can J Gai:,troentcrol 1989;3( 4 ): 15 3-161

Key Words: F11ncrion test.~. Pancreatic, Ret•icw

Tests de l'exploration fonctionnellc pancreatique exocrine

RESUME: L1·s tests de l'explornulln fonuillnnclk pan..:rcmique exllcnne (P~Ts) rcstent lllik's dans le diagnostic ct l\:valuauon des alkcuons chmn1ques du pancreas. Les eprcuvcs par 111 t uhat ion d ircctc qui utilisenr la sccrctine/CCK ,1u In scuctine/ccrulcmc comme sumu lants, conrinucnt i't ctn:' Jc rigueur htL'n qu'dlc~ srncn t invasive, crn."iteuses ct longues. Le 1, cpretl\'L's ind11cctL's :-ans tuhage, .1u NBT-PABA ct le te:st pancrcolauryl, par cxunple, gagncn1 en popul.mtc, au 111\'e,lll du dcp1sragc surtout. L'cxamen coprolog1que rL·ste uulc: 1.i mc,urc de la d1ymotry psinc sen a Jccclcr l',muffisancc pan<..rcat1quc L'l 1..cllcs de, gra1ssL", kc,1les, ;'1 reconnaitre la ,Le,11orrhcc. Les eprcuvcs ,1t1x rndioisotopL'' Mmt aujourd'hui dcp,1ssees. L'e,t imauon des marqueurs p,1rn:reauqucs d.uh k· scrum, l\mne ct lcs l1qu1dcs nrgan ,qucs est unle L'n ca~ J',m111naltc mais nc Lkp1ste pas b affect ions peu graves. Combiner le, PFT s ct lcs techniques J'11n.1gcnc fournll une apprnchc r,1t1onnclk au d iagnosllc raptdc ct dnnnc unc mc1llcure eYa luat 1011 Ju pat ient attcint d'une affection chnmiquc Ju p,111crcas.

/)1v1wm (Jr (imOnt'lltl'l'l//(lg,·, I\ k1\fmtl'r l 1111n:r,1"' M<!d1cal ( :l'lltrl', I l11n11lton, ( )11tcffl(I C.orres/mmlt?11cl' Dr l<id1,ml 11 I I 11111, l'ro/,•s,or, I lt!,ul. D1t'l\l11ll of l },1.,o-oL'IHl'rol11g,·.

McMmter l ,11111'1.'rlll\ ,\fo/1rcil C<.'ntn.'. U11tm1 .J\\ 't'>, 1.?l\11\f,1111 ~O<'L'! \\''.·\l, / lm111lro11, ( J111,m11 Lo.\/ 3::5 T "'L'/>h1111< ( .J l (l) 'i 21 21 l\1 L'\t (1.Jl'-J

Recen•cd (m [>11h/1c,,rw11./an11,1r,• 17, / 989 Acn·/itc,I ./1111<' 6, / <l,•,t)

S I~l , nt1 r1u:--.1 rn "run1 r" t ,, .

( 'hirn\ l't al ;md Lag1.·rlot' rL'('OrtL·,1 111 1930 (I) ,md llJ42 (2), .1 ,,mety nl 1'\<11.nt11.' p,1111.rl'at1L funlt11111 tL',t, (Pl·T,) 1111.ludmg 111tuhat1,1J1 and tuht· less tl'lhn,quc, h,I\L' hcL'l1 ,k·,·l· lnp1·d ,ind appl1l'd 10 dm11.,1I pra, t llL'. h11 thl' d1.ll.!l1(1'(S nf p,ll1ll'l';lll( di,easc, r~T, ,lrl' 11l'l'dl'd Ill i\SSL'SS I hl' Hllll llll)l of fun, 11, 11,al ,l. 11n,1gL' ( 3). In 1h1 past tw11 dl'L,tdcs, 1hc dL'\l'lnpmcnt nl m·11 1m:1g-111g lL'Lht11quc, such as ultr,Niuml, cnm pulcLI t111nng1 ,t ph\, 1.•ndosL <lJ)IL r1.·tn1gr,tdl' 1'anue.11,1gr,1ph~ (!·RP), .irtL'nogrnphy ,md 111.1gnl'tll rl',onanL1.' 1m.1g111g h,1,·c m,1dc pnss1hll' 11l'II ,IJ' · prn;1chcs tci thl· d,agno,i, ,,t ,,nnll'l'nl ll d,,,.,1,c. I l1111c,cr, e,,iultlL' pa1Krl'at11. funu 1un nwy h,· imp,iin.:d hehirl' mrnph11l,1g11..,1 l 1.h,mgc, .irl' ,een wuh the,c 1ed1111quc, (4 8); PFf, m;1y thu, 1.kteu Jy,fun1..uun at ,Ill carlll·r st,lgl'. In stlllll' urcumstanccs the discrcpanul's hcrwt'L'll funL llona I tc.,t, and 111nrph11lug1 c,,I a ltcra11uns .ire rl'mark.ihk (9. 10), thl' u1mhm,1uun 111 !'IT, and 1111.1g111g 11.•c hniqucs may improve t h1·1 r 111-1.II\ 1du.1l w1Nt" ll \ {4, 11, 12 ).

Rl'Cen1 ly a ,en1.•, ,if cnmprchcnsl\ l' rl', 11·,,·, rq.:ard Ing Pl· Ts h,l\'l' heL·n puh l1shL·d (~. I ~-16 ). Tim pap1·1 11 ill hndly re, 1c11 thl' nik·, 11f PFTs hut d1,u1,s m11rt· C\IL'tbl\t'h thL· 11L'II ,kvc l11p· llll'l1h ol t11hl'kss P!-T,.

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TABLE 1 Exocrine pancreatic function tests

Intubation tests Direct secretory tests

Secretin test Secretin-CCK test Secretin-caerulein test Secretin-bombesin test

Lundh meal Direct synthetic tests

75Se-methionine test Determinations In pure pancreatic juice or duodenal aspiration

Viscosity Enzymes lsoenzymes Lactoferrin

Tubeless tests Indirect tests

NBT·PABA test Pancreolauryl test

Fecal tests Microscopic sedimentation Fat and nitrogen determination Chymotrypsin estimation

Radioisotope methods Triolein test Breath test Dual-label Schlll1ng test

Estimation of blood. urine or body fluids Evocative test Parotid saliva test Trypsin-like lmmunoreativity Pancreatic isoamylase Plasma panc reatic polypeptides PlasmaCCK Serum cationic trypsinogen Plasma amino acids

CCK Cholecystok1rnn: NBT-PABA N-benzoyl-t· tyrosyt-poro-ominobenzoic ocid

INTUBATION TESTS Direct secretory tests: Alth11ugh intuhminn tests a rc in vasive , cxpen~i\'e and time consu ming, direct sccrcrnry tests continue to prt, ,·idc the 'gold standard' h,r I he csrimat ion o f cx1 ,crinc pancreati c funct ion (3 ). For nptimnl perfomance, the rest~ rcqu ire: the com

ple te collec tio n o( sccrec ed pancreat ic juice in to the duodenum without con

tammrition hy gastr ic juice; and the ad-111 in is trn t inn of sec retagogue o r cnmhinariun nf sccretagogues, which can s timulat e m ax imal pancreatic secretio n .

The comple te collec t inn 1l uncontaminated duodenal juice rem:iins a

major pmhbn hut scvernl techniques

hav.e heen generally accepted. Separate aspiration can he achieved hy the cnm-

154

hirnmun of a vented gastric tuhe (Sakm gastrii.: tube) ,,nd ,1 du11den,1l tuhc (Ander~on duodenal tuhc ), or a ~i nglc double-lumen ,lir , ·entcd tubc w11h

gastric and duodenal aspirnt i1m huks (Dreiling gastroduudennl tuhe). It has hccn pm\'cn t hm c,ircful t,nsir i1H1 ing uf the g,1striL tuhe 111 the mt1,t dependent tian o( the ant rum can adrn.:,·c ,l ne,1 r compl ete collccl iun li( rhc gastm: ct1n -1cn1 and rhm dut1dc11<1l reflux is neg[, . gihk ( I 7 - 19). A l"L'Cl WL'ry r,nc nf ahn\'C ti5'fo fn,m duudcnal a,pirat1,m 1, widely

accepted as ind1<..:ating a sn ti, f,Ktory rn llcctio n (1, 1 3 ,14) . When chi , rcCl l\'ery ,, ,Kh lC\'ed, pcrfu,1,m l 1f non

;1h,t1rhahlc lff r;1d1lllahcl led m,1rker, 10 1ndiL ,lle i.:omplctcnes., 11f dunden,11 cnl

lcct in n m ay hL' unn ccc,sary ( 14,20). Balloun ,1cclu~i1,n nf the p~ lt1ru, and the dista l duodenum h as hecn consid ered, hu t int e rfere, with mot ility ,md secretion ( l 3 ). Endoscopic cannulnunn

of the pancreattc duct to ctlllect pure pancreauc juice nlone n llt1ws only intcrmittcnrsampling (2 l) and rhe result:, arc likely to he atfrctcd hy pre-cndnsctlpy med ic.ition , thus it is nllt recrnnmcndcd for ruutine use.

There is considc rnblc disagreement about whii.:h secrctagogue m crnnhin,1-tinn ,,f sccrctagogues and which d\lsc and r11u1e of adminbtrntiun, sh\lu ld he used t11 ,1hcain rhc he,t c,·aluatilln ()(

pancreai ic insufficiency. St:vcral direct tests ha\'t: been suggest ed (Tnblt: l ).

Procedures from each centre arc so difterent that only ,1 few of them nrc c,,mparable (Table 2). The sensitivi ty and

specific ity reported (or differe nt st udtes arc affected hy the severity of d isc,N: in

differing study arms and rhe quality of tht: concmls. Fabe negat ives a rc most likely to derive from mild cases; whereas fa lse positives me seen in pati ents with celiac sprue, diabetes m c llitus, subtotal gas trectomy, hepat ic cirrh ,,s is .i nd bilia ry d iseases (22-27).

Obviously there is a need tll standardize procedure,, hut the most satbfactory technique has not hcen c lc,irly defined. The European Panc reatic C luh

has cried to stnndardi;:e the test procedures, hut the pi lot study of this p roiect

shuwed rhnt the en:yme assays from

multiple centre, agreed too pliorly t11 make an y cnmpnrbnn ( 28). C urrently

the mn,r commonly used d1rccr tc,1 m

c l1n1 ca l pr,lCllCt: IS the .SL'Crcltll • cho lecystokin1n (CCK) test ll'lth ,cn, 1ti\'lt)' a nd spei.:i fiLity r,m ging lrom 74 t() 97% and 80 tn 98'\,, respectl\t·l1 ( 3,13 - 15). The sei.:rL' t ll1 -CCK 1,·,1 prm·idt:, addiuunal inf unnni 10n ot lll·

:yme output comp.ired to the ,nrc11n test alnne, 111 which lll1 ly pantrcalit

ilo\\', h1c.1rhon,llc umccnirat1on ,md nutpul i.:an he c,u m ,1tcd. In ,omc

pnncrcat ic d i,ordcr., 1 mp;med sccrcuun nf cn:yme, 11LCtir, t:,1rl1er than an dk,1 on nilu m l' and hic.irh11natc ou1p11t (29,10), Ml thar the scnsilt \'i ty of the 'L'Crl'lln-<. '('K 1c,1 may hl' cxpL'Ued in

he h ighn th.111 1 hat uf I hl' SL'L rcun tl',1. I luwc\er, crossti\ e r u1mp,1nslln, of

1hc,c l\\'U l l'sts ;11-c hLkmg. C.1crulun h:b been L', lL'n,i\'L·ly u,cd in Europe tu rcpla<..:c CCK 1n I lw ,ccrcun -CCK ll',1 and pn"' idcs a sim ilar ,t 11nul.111nn ot pnncrc,ll ic c n:ym L' ,cc rel inn. It can be obtained in pure form nnd i, cheaper than CCK. A ,ccretin-homhc,m tc,1 has hcen introduced hut the role nf th1, procedure rcnwin, rn he e,tahli,hnl (3, l ~ ). Lund h meal: The Lundh meal i, in

indirect PFT in volving the assessmt·t11 nf the pancrea tic ~ecrc tmy rcspons~ 1u the test mL·a l and thus ltl the end,,. genuu, release u f gut hormn ncs. The procedure is simple r tha n thn,e ,1fd1rt:Lt

sccrctury tests, hccnu,c only en:ymc ac· ti vity is measured ,iml sampl ing of a

sma ll frac tion b relinhlc ( 14). ThL' 1c,1 pcrh,1ps pnw1dcs more physin log1cal 111-fo rmmio n than direct tests, however,

the results arc influenced by such non· pancreat ic factors as gast ril L'lllptymg,

intraduod cnal pH and the cndllgciwu, rcbi,e of gul hormone~ (3,13). In 1he

presence of intestinal mucosa! d1sea,c, eg, cc liac sprue, the test may he invalid because of rhc impairment o f mcdiahlr

hormone released from the nhnormal mucos;i {3 1, 32 ). In c,1mparison \1·1th the sccre tin-CCK tc:,1, l he Lundh mc,11 ha:, usually been shown rn he less sc11'1· tivc, especia ll y in detect in g mil.I pancreatic insufficiency ( 33,34). hir, thermmL\ it cannm ,, n w ide pancrca11c ju ice fo r cytt1 lt1gy it carci nom,1 1,

suspected.

Direct synthetic tests: Radil1lahdlcJ aminn ac id, have been used to est 1mate

C:\N J c.;1bTR1.ll.NTI Rt )I V111 ~ No 4 S1 l'Tl:Mf1rn 1%9

TABLE 2 Data of the exocrine pancreatic function tests

PFTs Sensitivity Specificity Key elements Comments being tested

Intubation tests Secret in 80-90% 80-90% 1 volume Initial test

2 bicarbonate Secretin-CCK 74-97% 80-98% 1 volume Gold standard

2 bicarbonate 3enzymes

Secretin- Similar to secretin CCK test coerulein

Secretin Similar to secretin CCK test Needs evaluation bombesin

Lundh meal 66-94% Lower than Enzymes Less expensive above Less sensitive

Radio- Poor Poor Synthetic More Invasive methionine capacity

'Tubeless indirec t tests PABA 60-90% 70-90% Chymotrypsin Screening test FDT 75-93% 46-97% Est erases Screening test

'Fecal tests Fat or nitrogen Low Low Li poses Standard test

tests Trypsin for steotorrheo Chymotrypsin Inconvenient

Chymotryps1n 41-100% 62-97% Chymotryps1n Screening test test

Radioisotope methods Triolein tests >90%? >90%? Li poses Outdated

(in steotorrheo) Breath test >90%? >90%? Lipase Outdo led

(in steotorrheo)

Estimation of serum, urine and body fluids lrypsin-llke 33-65% ? Trypsin Convenient

RIA Insensitive ooomylose 13-71% ? lsoomylose Some as above Pancreatic 90-100% ? Pancreatic Some as above

polypeptide (in steotorrheo) polypeptide Cationic >90% 86% Trypsinogen Convenient

tryps1nogen (in steotorrheo) New study Amino acids 67-91% ? Amino acids Convenient

New study

'The sensitivity and spec1fict1y ore compared with ·gold standard ,ntubofion test. FDT Ftuorescein diJourole test PABA Poro aminobenzoic acid RIA Rod101mmunoossoy

the capauty nf thc pancreas to ~yn-h J 75s l e:,ize igeH1,·e enzyme,. , e-

merh1on111e, given 1nrra,·enou:,ly 1, rapic.lly r:ikcn up hy pancrealtL acinar ,clb anJ incorpmated into newly :,ynthe~1:ed pancn:<1t1c enzymes, :,uh,e4ucntly secreted into the dunJenum. r~ncreallc secreuon may be ,timulatcd hi cnher a Lundh meal or ~ecreunCCK. The protl'in hound 75se rndioacuvity 111 the duoJcnal aspirate 1~ u:,cd .i, an indl'x of exocrine pancreat 1c (unv non. Some studies have reported satisf~cmry d1scnminm inn herween healthy

com rob and paticnts wtlh pancrcat1<.: dbease ( 35,36), but mher studies fodcd to Clmfirm the ,ensll1v1ty of the test ( 37, 38). Morenver, it b more invasivc hecausc hoch mtuharnm ,md radioacll\'lty arc 11woh-ed, thus this test seems w confer no adv,mtagl' unless ,m estimation nf thl' c1pacit y o( pancreatic synthe~1s 1s required ( 3 ). Det e rmina tio n in pure pan c reatic ju ice o r d uodenal asp irates: Determmmions of the v1swsit y {39-41 ), en:ymes (21 AZ-44). isoamylasc (45) or h1c1oternn (46-50) in duodenal Juice or

Exocrine pancreatic function tests

111 rure p,11Krcatic 1u1ce aspirated via ERP wtth nr wnhnut sccrcnn-Cl'K st1mularion, prov1dL· .m ide.1! approach for rcscard1 stud ies but not for rouune pr,K!ICC, because of the invasive nature of the procedures nnd considcrahle o,·erlap 111 the measured 111d1Cc hetween normal and ahnorm.il ( 3 ).

TUBELES TESTS Tubeless indirect tests: Two tubeless indireu PF-Ts arc frequently used: the N-henzoyl-1 -tymsyl-p.1ra-,1m1nl1he1m11c acid test (NBT-PARA, hcnt1rnm1dc) and t hl' fluoresce111 ddaur:1tc test ( rDT, lpancreolauryl test, PL Tl). In bmh procedures, thc pntiems are given orally a substrate merahol 1:ed hy pancreatic cn:ymcs mto two or more products, onc nf wh1<.h 1s absorbed from the 1ncesnne, conjugated in the liver and excreted 111

urmc where it can he measured. The cxcre1 ion rate of the tracer clcmems 111

ur ine over time reflects the in t rnlummal en:ymc activity and, 111J1rl'ctly, the exocrine p,1nucat1c lunct ion. Thesc tuheless tesh require no medical ,upL'rv1s1on, arc less expensive, more convenient ,rnd more acceptable to

pallL'nts than intubation procedures. Thcy ha\'c hcen gammg mcrensing 111-

terc,t and h.1vc been widely used as screening tests ( I 1,16.51).

The NRT-PABA test was iniually rcpmtcd in man in 1976 (52-54) and is valuable fur the d1agnos1s of pancreauc insufficicncy. The test substrate, N BTPA BA (Chymex; Adria Laboratories), a synt heuc mpepude is cleaved by pancrcatiL t.hymotryp:,in into N-bcn:oyl-1.-ryr,1s1ne (NBT) and paraammohenzoic ac id (PABA). PARA excrcteJ 111 urine Lan be determined and used a~ an index of exoc r ine pancreanc function. Test procedure:, have not hel·n completely srnnJardized, buL most studies arc done according to

rhe following pmtn<.ol. The test 1~ performed after an over

night fast and pancreatic enzyme supplements should he discontinued at least five days prior LO the !>Ludy. Drug~ or fond rc~ulung in a high urinary cxcreuon of aromatic ammo ,1L 1ds mw,t he avoided beforehand. The NBT-PABA givcn in a dose hetwccn 0. 5 and I g provide~ the greatest sensnivity (55-

155

Lt cc al

57). A test meal is recommended to

s timulat e pancreatic secret ion (52,54 ,58-60); tea or mineral water is encouraged tu ensure sufficient diuresis and urine collection over 6 his generally sufficient (60,61 ).

Sensitivity of the test rnnges from 37 tn 100%, with most studies herwcen 60 and 90'X,. Sp,xificity ranges (r()m 39 ll' 100%, with the majority uf tests over 70l}(, against tlw 'gold standard', the direct inruharion rests ( 13, 16). Several nonr,rncreatic factors such as gast rectomy, small lxl,~el diseases (ccliac sprue, Crnhn 's disease), impaired liver or renal function and diabetes mcllitu, may cause false positive results (58,62-67).

Some modificauons uf the test have hccn developed to overcome the high incidence of the false positives. A control test on an additional study day hy administering free PABA instead of NBT-PARA is commonly used (58). From the PARA excretion rnce ,ma test day (T) and a control day (C), the PABA excretion index (PEI) is derived (PEI= T/C). Nonpancrearic disease will influence hoth T a nd C, while pancreatic dysfunction only T, thus by using PEL false positives can he minimized. A PEI value of greater than 82% b cons idered nurmal (20). A si ngle day NRT-PABA test has been developed as an alternative in order tn obrnin a PEI from one study day. The subjects are given free 14C-PABA (67-70) or paramninosalicylic acid (PAS) (71,72) in addit ion to the normal administration of NBT-PABA. The excretion rate of PABA and 14C-PABA or PAS are determined respectively. PEI is the ratio of PABA :14PABA or PABA:PAS. But the assay techniques in these rests arc more complex and rewlts can be inval idatcd hy drug or isotopic in terference ( J 6). The measu rement of PABA in scrum at between 90 and 150 mins after the administration of NBTPABA is a convenient alternative to char of urine col lection, especial ly in children, elderly pauents or those with renal disorders. In most studies results have been sa tisfoctmy (73-79) while the simulrnneous scrum and unnary measurements of PABA may also improve the specificity hut nm the sensitivity of the NBT-PABA test (56,80).

156

The tluorcsccin Jdaurate test (FDT [pancreolauryl test, PLTJ) was first descrihed in 1969 (81 ), but has 1mly recently ncrractcd widespread interest. The principle of the test is similar t0

that of the NBT-PABA test. Fluorcsccin Jih1urate, a poorly water soluble synthetic ester, is given orally and cleaved hy pancreatic cstcrnses to l,1u ric acid and tree tl unresccin, which is water soluble nnJ excreted m urine. In comparison with the NRT-PABA test, FDT undergoes less interference fmm drugs or scrum components, t1nly requires simple hydrolysis and is more independent of renal function ( 16). The FDT test has hccn standardized and is commercially ,l\'ailablc (Temmler; Mnrburg, West Germany).

The test is performed after fasting, and pancreatic supplements or vi tamin B preparati1ms, which interfere with fluorcscein measurements, have to he stopped. On the test Jay a capsule conmining 0. 5 mmol flunrescein dilaurntc b administered together with breakfast, while on the cont1\)I Jay 0.5 mmol free fluoresccin b given. Free fluids and a normal lunch are encouraged LO mainr;iin an adequate diuresis. Urine is collected tWer 10 h . Un nary flunresccin on the test (T) and control day (C) is measured photometrically n r flut1rometrically and the fluorcsccin exc reti on index (FEI) obtained (FEl=T/C). An FEI over 30'10 rndicates normal; less than 20% ahnormal; between 20 and 30% requires a repeated test. If the rereatcd test shows a ratio of less than 30%, it b considered abnormal. Recent studies til FDT rndicme a sensitivity ranging from 46 co 100% with most studies between 75 and 93%, and specificity between 46 and 97% ( 13, 16). Diseases assoc iated with false posi tive results arc similar to those for the NBT-PABA test. Most studies show the sensitivity ofFDT w he surenor to that nfNBT-PABA test (59,82-84 ).

In order co shonen the test period and avoid the need to collect urine, fluorescein determinati,ms in scrum ha\'c been dcvelliped. Optimal flu,irescein scrum concentrations arc found hetwcen 4 and 6 h after oral ingestion. Scrum testing seems to offer scnsnivn y and specificity similar w those o( the

urine test (79,85-87). A modified FDT with fluorescein serum determination following merocloprnmide 10 enhance g::istric emptying ,rnd secrcun stimulation appears superior w the urine test (88). Feca l tests: Fecal micrnscopic cx

aminatitm ,la random ,totil sample rs simple but unrel iable. Fecal fat and nitrogen tests have con tinued as routine tests for assessing steatorrhca, hut they c,mnnt d istrngu ish pancr<::atlt from nonpancrcatic disease. Stemm rhea and azotorrhea me late symptnniof pancreatic d isease, and llllly occur when the lipase 11u tput tall, hehm 10'\, of norm,il (99). The degree of pan. creatic impairment, as measured hy the intuharron 1es1s, may not reflect the scverit y of Mcatorrhe,1. Therefore, for sophisticated C\'aluatinn of the func tional reserve capacity nl the exocri1w pancreas both int uha1 ion tests and fecal tests have been considcrl·d neces,ary (90). Fecal fat estimation of 72 h srool col lection remains the srnndarJ teM to quantify fat malahsorption (3, I 3,91 ). The measurement llf fecal nitrogen docs nor improve further the sensitivity, since pancreatogenic a:otor rhea occurs only in patients with steatorrhea (89,92,93). In order 10 overcome the time cnnsuming and 1111·

pleasant lahorntnry methods llf quantifying stool fat, nuclear magneu, resonance (NMR) spectrometry has been recently introduced (94).

Fecal c hymc)trypstn measurcrnems can he dtme on random stool sample, (95-97), a lthough a 24 h collecnon ot feces may provide ~lightly better result, (98,99). From the present data the measurements still remarn a useful screening I CM lllr cxllcrine pancrear1C insufficiency. Recently, new photo· metric methods using standard lahoratory equipment have been developed, which make th1, test even more accessible than rhe traditional titrimetric method ( I 00-103 ). The sen. sitivr t y of the test ranges from 72 to 90",, and specif"icity from 62 to 90% {3-13). Stoo l samples col lected from l'lll·

pat ients can he marled to the diagnostic c.:entre perform mg the assay w1rhou1 affecting test results. The test mc1y, therefore. he partirnlarly helpful in follow-up studies.

Ci\N J lJ1\STRt1ENTLRl)L Vl11 ~ Nt) 4 Sl:l'TLMBl::R 19!19

Radioisotope methods: T nolem tests have hcen investigated 111 an attempt to

replace the more cumbcrsrnnc kcal f,1t tem. The oral admi nbtmt ion uf J,1uhlc labelled rmlin.1cti1•c fab inLl ude thl·

., I 1 ' 1 I . I / I\ 11 I eas1 y mca,urc~ -tnn l'ln -o c1c acid given nn separate day, ur more recently the stahle 14c'-tnnle1n/ lHoleic add gil'en ,imult,rnCllusly. Lipase deficiency in pancre,n1L Jbease 11\Hild only affect triglyccnJe hyJrnlysis hut not fatty acid ahsorptinn, thlJ', pancreatic ,tcatorrhc.1 clluld he distinguished frnm uthcr disorders. Srnm.· ,wdics have reported a fol'ourahlc scnsiu1•1ty and spcc1f1c ny uf ahnut 90% in chedctcct1<m ofsteatnrrhca ( 104- 106). To avoid f<.:cal collcc uon , me.1surcmcnts llf scrum rndioa<..til'it y have hecn developed, hut the rc,ult, arc slimenme~ distmted hy kinetics unrelated to the assimilation of the label (105).

The 14C02 hrcath test is another alccrnatil'c to focal fat testing. Sc, crnl r,1diolabellcd rnglycerides han: been recommended as tes1 suhstratcs, ,1f which 14C-triolcin showed the hcst ,cnsitiviry and spccifkity ( 107). ft is given orallv LOgerlll'r ll'ith a standard hrcakfast and is digested hy pancn.·at iL lipdSC, The cxha lat 1011 of 14C02 measured in hrcath n.:fkct~ the 1rn1l.1hsorpt ion of fat. Scnsi ti l'i t y and 1pecific ity hal'e hcen reponed tn rcaLh over 90'l'o in , tcatorrhca ( l 06). False positive results come frnm nonpancreatic factors such as intcstin.11 mucosa! ahsorruon. her,11ic mctahuli>m, pulmonary dhorJers and metabolic Ji~()rdcr~. cg, h yperthyroi di sm , ,liabetcs meflitus and obesity ( 106). M(x.lificat ions, such as repeating the test on a separate day together with the adminisrrat inn lit' pancreatic en:ymcs (108) or reph1cmg the test suh~trnte hy a 'mixed ' triglyceride that c,msists of one medium chain fa11 y acid in position 2 and I\\\) long chain fatty acids in

positions l and 3 ( I 09), have hecn developed tu improvc the specificit y. A recently developed cholestcry l ocranoate breach tcM shortens the ,1 udy Juration from 6 h to hct ween 60 and 90 mms(l 10).

T he dual label Schilli ng test I . 1- . °>7(' /°'R( ' measure~ t 1c rnC10 o urmary -ll , o

after the administration nf inrrinsk

1\:o-cobalam 111c and h,1g-R-prmein

'i8C I I · I . h 1· o-co ,a amme toget 1cr wit 1-ec 111-

trinsic factor ( l l l ), hut has not hecn further cn1luared.

fn gcnern l , hccausc \l l the unrek1hdity of thL' tesb and the involvement of clahorate 1srnnpc technique,, radioi.,otnpc mcthnds have been outdated by ,1ther tuhclcss PFTs (3, l 06). Estimation of scrum, urine and body fluids: Est 1matinn ot CXt)Crinc pancreatic funct ion hy measuring the le,·cb of cn:ymes, hormones or m her Cl>mponcnts in serum, urine or s,ili,·a 1s ,1ttnict11 c, because i1 1s simple and nonin\'asive. Measuring scrum cn:ymes after in1ravetHH1, stim11lat1on wnh pancreatic ,ecrewgogues, the 'e\'lica-1 ivc tests', has proven neither scns1uvc nur ~1wc1hL (29,112,113}. Me,1suring sal11·ary bicarbonate and amylase outputs balsonflinlcdia1,.>11nst ic \aluc (114,115).

Fast mg scrum ll)'psm-likc immunurL·au iv it> is sign ificantly luwcr in p,ltients with chronic pancrcmius, hut 1he scns1t11·1ty of this test onl> reaches 3 3 ro 65(\,. Mc,1suring fastmg pnncrcnllc isoamylase in ,num or other hody f1111ds ,111d measuring secrctagogue stimulat ed panucm iL polypcpt idc in plasma ha, similar prnhlcm., of low ,cmitivity (3, l 3). Therefore, these tests me only rcliahle 111 sc1·e1-c exocrine pancrcatil insufficiency \\'1th stcatnrrhca.

Plasma CCK LnnLen tratilrn, arc elevated 111 patients with pancrca1 ic insufficiency ( 116-1 19), hut this ha, nm been confi rmed hy ,I study using sequence specific radioimmunoassay ( 120). Several reports have shnwn I hat serum immunoreact11·e cauonic tryp,111,1gL'fl meawremcnt may he prom1s-1 ng. ln p.itients wILh panucatic insufficiency the lel'cls deLlinc with age ,l11LI are low ur undetectable after five to .,ix years of age. At that time low levels l iccur 111 pat 1cnts with mmlcrately or se1·crdy unpai red exncnne pancreauc funct inn irrespective of the origmal disease. The sensiuvi ty o( the test extends above the steatorrhue1c threshold. ln the presence of stemorrhca o( unknown ctilllogy, ll,w levels o( cationic trypsinl1gcn indicate a pancreatic ct inlogy (121 - 124). Serum 1mmunnrcacti1-e pancreatic lipase levels abn decrease in ,1 s11n ilar way in pmicnr, with exocrmc

Exocrine pancreatic f4nction tests

pancreatic 1nsuffic1ency and can be used as an index. although less sensitive th,m u nionic trypsinogen ( 12 3 ).

One study reported a l,1\1·cr reduct 1011 of plasma amino acid level, 111

rmicnts wnh exocrine pancreatic insufficiency than in controls after ,tim ula-11on hy sccreun-CCK. Thl' ,en,itivit> of this test wa, 1-c11ortcd 10 he 671\ti 111

mild case, and 91°b in mlldcrmc or ,e,·cre cases. The ,cn,it il' it y impnwes if ~e\'cra l indil'idual nmino aci ds are me;1surcd ( 125).

CONCLUSION Dirccr secretory tests, us111g ,euetin

CCK o r the scc rc t111 -c;1crulc in a, ,11mu l,111ts, remain the 'gold , tandard ' for the assessmen t u( L'Xncrine pancreatic funct ion. The pancreolnuryl tl'st and the NBT- PARA test (or perhaps the determination, of fecal Ll1ymorrypsin) can he recommended as ,crcen1ng tests. The other tests miss almnst all patienb with pancrea1 ic dy;,funcuon without steatorrhea and arc llnly useful in the a,,cs,ment o( ad-1·,mced disease. The es timation nf panueatiL marker, 111 scrum, urine or hudy nu1ds can supply informatio n when abnormal, and require better el'alu.111,in.

It is app,1renr that nn one test is entirely sat isfaclllry, thus rhe diagnosi~ , ho uld he ha;.ed on a comhination of PFTs with other techniques. A rational approach w the d iagnosi, of chronic pancreatic disease is demi led helnw, al though ench centre can assess its own resource, and requirements. For the d1ag11tlsis of patients with chronic ,1hdom111,1' p,11n suspected of having p,mcrcatic di,ease, a suitable screening procedure might he ult rasonography initiall y, 1( negative, then a tuhcles, te,t, (NRT-PABA or pancrcolauryl test) or fecal chymocrypsm which arc noninvasive and relatil'cly inexpensive. A positive result warrants confirmatio n hy either computed tomography scan, ERP or a secrctin-CCK test . Ancriography cou ld he substi tuted for ERP in the event of failure or unavailahility of ERP, when pnncreat ic carcinoma 1s suspec ted. Ultrasound or computed tomography guided fine needle hiop,y and cytnlogic evaluat ion in pancreat ic

157

LI et al

Jutce from ERP shoulJ he rerformed. For functional assessment of a patient with chronic pm,crcatic 111suffic1cncy, if

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69. T,•tlm1 VA, Kc$.;, I krman 11. Rragan~.1 J~t D1,1gno,ttL ,Keuraq llf

(AN J VASTllUENTl:J\()J Vt )J 3 Nl) 4 Sl.l'TI \\Bf'R I 9H9

Exocrine pancreatic function tests

the !'A.Br\ exuc·t11m 111de, (uS1ng 1\;. PABA)(,uc J981;22A441

70. Rrilgan:,1 J~L "-·'\ UI I. T,·tlow VA, I krm,m KJ ()h,cr1·,1t 1lln, llf tlw HT PABt\/t\ '-PAHA tuhl'k'" tl·,t of p.mcreat 1c.: funcrnm ( 'Im ( 'him Act,1 I%);( 30: B9 47.

71 Beri.: Jl), ( 'hL•snl'r lt-.t, t\lle·n-Narh·r RA, Buckky BM. l..111',1111 N. b1Krml' pane rl'at IL lune 11011 ,1, dl't erm llll'd Ill a "1111L' d"y tcM w1rh U'l' of hent1rom1dc .ind l'-:llllll1\lS,lhLVhl ,Ktcl. ( '[111 ( 0 hl'ln 1986; 32: 1010 2.

72. I loe·k FJ, Van -den-Bergh Ft\, Kk,n-1:.lh, ir,r JT, L't al. I mpnwe·d SJ'L'L lfiut) nf rhl' PAHA test with p-:11111nu,;1ltcyl1e :tl'td (PAS). Gut 1%7;21H68-7l

73. Dockter(;, Nac.:u I, Knhlherger I:. I kterm111,1tillll ,,f pmteil'l' cle•.ivL•d p· am11whl'n:ll1C ,1ud (!'AB,$ 111 scrum ahl·r oral adm1111,cr.n 1on llf N hen:1 >\ ll.-t \ rn~yl-P-am111oh,·nm1L aud (PABApep11de) 111 ch tldrl'l1 Eur J Pl'd1atr 1981;135:277 9.

74 ( ;no,lc· I IF. h>stl'r PN, "cllehc·r J, l't .ti. Cnmpan,on nf ,erum p A I\A lllL'.Nlre·· ment and the unnar\ PABA l'XLret11m mdc·x m the diagnns,, (,f panncattc 111-suthuency. [)1ge•st1on 1984: 30: 111.

7'> WL·1:man Z. Furstncr G, ( ,askm K. Korwlm,111 11, Wnng S, Durie P. lknurnnude te,t for ,t,sc,,mg pancrc.1t1L dy,funcuon usmg analy,,, of p-:1111111nhen:111e aud m pl.1'111;1 and unnl'. C,a,tmcnterol.11-,,y I 985;89:596-604.

76 Uharho SA, Boyer JA, Williamson MJ. ( \ilnrunctnc plasma assay fr,r the hL·n· rnun11dc te,t (BT-PA BA) t,ir cx1Kr111c panl rL'at I< 1muffic1ency. An;il B1nc.:hcm 1985; 148:228- 32.

77 Helknrnn1 S. Umcnd1 A, Rmnld, M, er al. RT-paba te,t m thl• d1;1gnosts nf panLre,tt IL l'XOtrllll' 111,uff1c1enq 111

c.: yst tL fibrnsts: Urinary and scrum dcrcrmmaunn, compared. Eur J Pl·dt,1tr 1984; 14 3: 145-8.

78. T;ikL·,I;, Y, Am,1t,u T, T.1d.1 11, et al Valul' of the BT-PA BA test wnh ,erum PABA a, a pancreatic function rc,t. N 1ppon Shokak1hyo Uakka, Zas,h, 1985;82:1742-7.

79. Lank1sch l'Ci, Brauneis J, Otto J, Gokc B. P.mc.:rcol.1uryl and NBT-PABA re,t,. Are scrum te,t, more prau,cahle alternatl\'C, tn unne tc,ts 111 the dmgnosis of exncrmc pa nncat ll m,uffiuency ! Gasrroenrerology 1986;90: 350-4.

80. Ddchier JC, Soule JC. BT-PA BA test with plasma PABA m..:asurcmenrs: Ev,1 luarnm of ,cn,111v1ry and ,peuhC11y. Gut 1983;24:)18-25.

81. Kafformk 11. Meyer Berrmrnth JCi. Zur methodik uml klinisc.:hen hcdl'l1tung l'll1l', ncttl'n pankrea,ltpa,e-tcsts mn f1uc 1rcsce1 n-d I launn-,aurce,ter. KI 111 W,1d1enschr 1969;47:22 l -3.

82 C,l\'all1111 l,, P,uhello W, Brnccn (;, ,·t ,,1. Rd1,1hil1ty nf the B:-Ty l'AllA

159

LI t'lal

anJ the rancreoh1uryl rc,t m rhe a"e"· ment ,If exncnnc ranc rcauc func!Hlll . Digcsrion 198 );27: 129- 17.

83. Vmcrucci M, Daniele C, fh rrnlucc1 C, ct al. Evaluat1,m ,if pancrenlauryl te,t (PL T), PABA rest and ,erum pancreatic en:vmc, m I he d1,1gn,1,is nf cxocrinc pancrcmtc in~uffic1cncy. Oigc,tion 1982:25:73.

84. Vcnrrucc1 M, Gulln L, Dan1<: lc C. Priori P, Labo G. P,mcrcolauryl test fu1 p,mcrcaric exocrine 111'ufhc icncy. Am J Gastrnc ntcn1l l 98 >;78:806-9.

85. Cavallini G, Piuhcll,i W, Broce,, C, ct al. Bcha,·1our ol scrum PA BA and fluoresce in ( FL) 111 the cour,c of BT-PABA anJ pancrcanlauryl (PL) test in exocrine p:mcrcattc in,uffic1ency (EPI) paucnt,. Digcsrilln 1983;28:l 7.

86. Balagucr JV, Ap;irbi L, R,>drigo JM, ct al. Influence of renal funcuon on rc~ults in scrum and urme nf the PABA anJ panucolauryl rests. Digestion 1984;30: l 14.

87. Laggner A. 8,1,rnm L, Prager J, ct al. Pankreas-funk rions-d ianost1 k verc1 nfachrcs sc rcenmg mit flunrcszc111-dilaurat durch scrumkon:enrrat ion,he,nmmungcn. Fon,chr Med 1981 ;99:589-9 1.

88. Malfcrtheincr P, Buchler M, Muller A, D1tschuneit 11. The ilunrcsce111 dilauratc scrum res1 foll,1w111g meroclopn.m1dc and ,ecrerin stimul,1-tion for evaluating pancreatic function . Contnbuuon to the diagnosis ,11 chronic pancreatiti:,. Z Gasrrocnreml 1987;25:225-32.

89. DiM,1gno EP, G,1 VLW, Summer,kill WHJ . Rclarinm herwccn pancrc,1 11c enzyme output s anJ mal,1hsorpL1on 111

:,cvcrc pancrcntic 111,ufficicncy. N Engl J MeJ 1973;288:8 I l-5.

90. Lankisch PG, Lembcke R, Wcmkcn Ci, CrcuczfclJc W . Funcnonal reserve capacity of exocrine pancrca,. Digestion 1986; 15: I 75-8 l.

91. V.in Je Kamer J 11, Ten Bnckel 11. Weijer~ HA. Rapid methoJ for the dcterminatinn of fat in fecc,. J Biol C hem 1949;177:H7-55.

92. Dnrnherger GT, Comfort MW, Wollacgcr EE, Power MH. Total fecal :,oliJ~. fat and nitrogen. IV. A :,tudy of patient, with chronic rclapsi ng pancrcam1s. Gasrrocnterology 1948; 11:691 -700.

93. llenkc WJ, VaccaJB, Van Grncbenhoven GE, Knight WA. Evalumion of pancreatic function test:, in confi nm:d pancreatic Jisease. Ga,tnienterology 1961;41:233-41.

94. SchneiJcr MU, Demaling L, Jone, SA, ct al. NMR ,pectromctry. A new method for meal stool fat quantification in chnmic p,111cre,1titi, . Dig Di, Sci 1987;32:494-9.

160

lJ'i. r\mmann RW, T.1g\\'Crchcr E, K,1,h1ll'ag1 H, Roscnmund 11. Diai..~1ost1L rnluc uf feca l chymorryps in and 11 ypsin .i"c"ml'nl I, ,r Jctl'Cl 1011 of pannc,ll 1L cli,ca,c. Am J l) 1g Dis 1968; I >: 12 3-46.

%. I lavc rhad. HJ , Dyce BJ, O utcnrag PJ. Mlmtgnnll'ry DW. Mc,1,uremcnr nf rryp,1n and chymutryp,in 111 sro,11: A d1agnu,t1L rc,t t,1r pancreatic c,ocrmc lunclllm. Ga,tn>entcrolugy 196 >;44: 588-97.

97. Sale JK, Golhcry l)M, Th1,1dlct("on B, Wonm,lcy KU. T ryp,111 and chym,nryp, m in d11odcnal a,p1r,Hc and Ltccc, in re,pnnsc tu ,ccrct1n and Lhnlccy,-lllk inin-pancreo:ymin. Gu t 1974; 15: I 32-8.

9H. Mullcr L, W1,11il:ll':,k1 ZS, 11.m, ky J. Thl' measurement tif foec;1l Lhymotryp,1n: A screening test for pancremic cxocrinc 111,uftkicncy. Au,t Ann Med 1970;19:47-9.

99. L)yck W, Ammann RW. Quantitative dcrcrminat1<m oftecal chymocrypsin a, a snccning rc,t for r,mcrcmu: cxncrmc 1nsuffic1ency. Am J Oig l)i:, 1965: IOSl0-45.

100. Ka:,pcr P. Moller C, Wahlcfcld AW, Staehler F. A new photometric method for determinat 1011 ,if chymotryp, in in ,tool. Fre,cnius Zcit,chrifr fur Analyu,chc Chemic 1982;3 11 :39 1-2.

I(\ I. Sch Iaege r R, Rohr A. Faecal chymncrypsm: A new phoromcltlc mcchnd u,mg N -acctyl-L-tyro,inc ethyl este r as ,ulnratc. J Clm C hem C lin Biochcm 1982;20: 147-50.

I 02. D,,cktcr G, I luppe-Scylcr F, Appel W, S1t:m.1nn rl). Dererm111m1on of chymntryp,111 111 feces hy ,I m:w plwrumctnc method. Pcd1mr raJol I 98'i;20:2'i7-65.

101. Ehrhardt-Schmcl:erS, OnoJ, Sch Iaeger R, L:111k 1sch PU. Face.ii chymo cryp:.. 111 for 111vcsr1gatinn of exocrine r,1ncrc;1tic tune, inn: A compari son of rwu new ly developed tests ll'llh the titrimccric methoJ. Z Ga,crc,enterlll 1984:22:64 7-5 1.

104. Lembcke B, Losier A, Caspary WF, ct al. C lirncal value of a dual isotope lat ahsurpt inn tCbt system (FATS~ using glycerol 1211-tnob1tc ,md I Serriethcr. Dig L)i:, Sci 1986; 31 :822-8.

105. Pcdcr,cn NT, Halgreen H. S1mulrnne11us a,se,,menr of fat mald1gcst1on and fot malabsmption by a doubleisotope methnd usmg fecal rad10-activ1ty. Ga,tmcntcrology 1985:88:4 7 -54.

106. Lankisch PG, Lcmhcke R. lnJircct p:rncrcauc funct ion re,t:,: C hem ical and radio isotnpe method,. In : C rcut !fcldr W, ed. C lmio, in Gastmcmcrology. Vol I 3, No l. London: WB Saunder:, Cu, 1984: 7 1 7 -l7.

107. Ncll'cnme1 Al), I lofm.inn A l-, l), M,1gn11 l:P, Thnma, l'I, l '..111'011 UL. Trinlc111 hreal h IL''': A ,L·nsil I IT and , pL'L'ltk rc,1 fur lat m,il,1hsurp11u11 Ua" mL'ntcr,1l,1g, 1979; 7fr6-1 l.

108. CioffJS .. Twn,tagc 1nnk1n hrL·,irh IL'sl cliffcrcnti,ncs pancrl'at1L imulliuc·ncy Imm mhcr <..misc, 111 m,ilahorp11,H1. lJastnicntemlogy l lJ82:1' 3:44-6.

109. C.~ ho1>s YF, Vantrappcn UR. RutgccrtP, Schurn1an, ['C. A 1111xL·drnglycc·ndc hrcarh tc•,1 fnr 111tralun11nal lat d,gc,ll\'l' ,K ti\'l t\. 1)1gc,11on 1981 :22:ZW-47.

110. Ct1le SG, Russi S, Srcrn A, I lotm,mn AF.(. ' holc,tcryl ouanoatc• brc.irh 1~,1 l'rcl1m111ary ,1ud1c., 1H1 a ncll' no11111-1·as1,·c test ,,t human p:111Lre,ll ll C\l>· crme function. C,:1,1 roen tL'nilogy 1987;9>:I ,72-80.

111. Bruggc WR, (,,,tt JS, Allt:n NC. ct al Dcvclup111ent llf tlw dual lahc l ',chdl 111g test for pancrc•,1t 1c c·x,1uit1c funct ion ha,cd 011 the d1llcrL' nll,il absmpt 1<m ,if u1hal,11rnn hound to 111 tnmic fact,1r and R pmtc·111. c._;;1,tn>cnteml, ,gy I lJ80: 7 8:9 l 7-49.

11 2. Munch R, Keh l 0, Buh ler 11, McJ,u T, Ammann RW. Chang.: 111 thl' serum pancrea, cn:ynw t,,IIPll'lllg 1.v. st imulauon 11·1th sL'Lrcr111 in s11h1eus with a n,>rmal pancreas. Schwe1: Med Wochen,chr 19H7;J 17:756-60.

11 3. Schmidt 11 , W 1t1hofi C. Wen de., Prnvokat1<m, (En1brinns) tesrs fur cl,~ pankrca,d iagm>stik. Lcbc:r M,tgcn D.i rm I 976;6:227- 34.

I 14. Lankisch PC.,. Ch il l.1 R, Luer,,,,cn E, Koop I l, Arglehl' C, Creutzfeldt W. Parocid sal iva rest m the• d1agnosi, of chmnJC pnncrc;11 11 1,. l)1gc,t1<H1 1979; 19:52-5.

115 . L)olml l.1 (,, Vak·nt in1 M, Fil1pp1111 M, c, al. Study uf pan>t1d and m1M'd ,ali1:1 111 thedi:1gn,>:,1sofchmn1c pancre,ll1t1,.1)1gest1lln ILJ79; 19:180-5.

l 16. I Jarvcy RF, Dowscll L, I lanag M, Read AE. A rad1<11mm11nn:1,s.1y f1,r cholcL ystnk in1n-pannco:y111 m. L,111<:1·r 197 );11:826-8.

I J 7. I larvc, RF, Rey J F, l loll'ard JM. t'l ,1L Scrum clrnlccystok Ill 111 111 pancrcallL cl1sca.,c. Gut 1976;17:827.

11 8. l larvay RF, Rey JF, 1 lmv,ird JM, ct al B10.issay and rmliu1111munoass;1y ,If scrum ch,ilecy,r,>k min in pat 1cnrs wnh panuc.1r1c disca,c'. RL:ml (,a,trm:ntc•rol 1977;9: 15-6.

l 19. Elderlc A, Vant1ni I, I hirvay RF, c1 aL Fastmg ,erum chlllccystok 111in lc\'cls in

chronic n:lap111g pancrcat1t 1s. Ir J Med Sc, 1977;146:lO.

I 20 . .I amen J B, 11, ,p1m111 WP, LamL:rs ( 'R. PL1sma ch, 1k-cyswk In m cunu.:111 r,tllllns 111 patient, wirh pancrc,11 1c 111,uff1ucn cy mcasun:d hy scqucncc-,pcc1i1L rnd1 oimm1mua,say,. l)jg Di, Sci 1984;29:1109-17.

CAN J GA:-;TRLlFNTl'Rlll V\ )) l N\ 1 4 SEPTll-tfll R 1989

121. Mnon' DJ, Largm,,n C, Kopelman I IR, Wong SS, l)une PR. Ahnnnnalitie, of L 1rculm mg 1mmunl HT.1t1vc pannt'.1t1t ,11111,111L tr\'f1'11logc•n 111 q,t1L t1hn"1,: An a:,:,a\ .irtcfact Jul' to cro"· fl'.!Cl mg :,crum ant 1hlld1e,. ( '1111 f\1oche111 1986;19:303-7.

122. Cleghorn GJ, Bcn1am111 L, ( :,m:y M, F,mmcr GC,, Dan 1-, l)um: PR. Age· related ,tltl·r:ll 1(111, in immunt>rL'aCtl\'l' pan.:rcat 1L lip,N: .111cl l.tt111mL tr\ p,m-

,igL·n 111 young children w1th q,t it tihro,1,.J Ped1tnr 1985;107:377-81.

12 3. ( 'legh,1rn ( ,J. Bcn1,11111t, L, C.1re1 M, hir,rner C,U. D.1t1 F. Dune PR. Serum 11nmunorL'alt 1,·e pannl'illlL I 1pa,l' ,md cat ionic trypsinogcn for the ,1ss,·,,mcnr "f l'\,icnne p,111crcatiL funcmin Ill ,iklcr p.it1cni- ,, 1rh cy,t IL hhnis1,. l'L·d 1m nc, 1986; 7 7 :.30 I -6.

124. M, ,ore DJ, F,ir,tncr l,U, L1rgm.m C, ( 'kghorn UJ. W,ing SS. [)uril' PR.

Exocrine pancreatic h,mction tests

Serum 1111111unorl',1Lll\'l' L.it1,111K tryp· .,inogc'n: A u,ctul 1ndic11,n ,1f ,c,·l·r,· exoum,· dy,funu 1nn 111 pae,liamL p,1t 1L·n1s ,, nh, 1111 l ,,ric f1hro,1,. t iut 1986;27,1362 -8.

125. L\misLhkc S, I kptner (,, Klllh S, S,uler I). Schne1Lk-r MU, l\,m-chke \XI Dcut'<l'l' 111 pl,1,m,1 ,1m111<1 .iud k,·el ,1frcr ,ccrc·rin .md p,11K rcll7\ mm a, ,111 i11d1c11or of l'XOlfll1l' p,tntfl'illlL lul1L· t11111 l \Mro,:nterology 1986;90: IO 31 ,h

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