Gut, 1979, 20, 1066-1071

Clinical relevance of an unfused pancreatic duct systemC. J. MITCHELL,' D. J. LINTOTT, W. S. J. RUDDELL, M. S. LOSOWSKY, ANDA. T. R. AXON

From St. James's University Hospital, and the General Infirmary at Leeds

SUMMARY In man, the main pancreatic duct is normally derived from ventral and dorsal embryo-logical buds of the pancreas. In a minority of people, failure of fusion of the two buds results inseparate drainage of the dorsal and ventral pancreas, so that the accessory duct provides the maindrainage for the gland. Patients with this anomaly demonstrated at endoscopic retrograde pan-creatography (ERP) have been investigated to assess whether non-fusion of the main pancreatic ductpredisposes to the development of pancreatitis. A failure of fusion of the pancreatic ducts was seenin 21 out of 449 (4-7 %) successful pancreatograms; four of these 21 patients had definite clinicalevidence of pancreatitis and two patients had possible pancreatic disease, but in the remainder theanomaly was not considered to be clinically relevant. An abnormal pancreatogram suggestingpancreatitis was present in 116 out of the 428 patients (27.1 %) with a normally fused duct system.The anomaly was found as frequently in the whole series as it was seen in patients with pancreatitis.These findings suggest that embryological failure of pancreatic duct fusion does not predispose tothe development of pancreatitis. However, the presence of this anomaly may lead to misinterpretationof ultrasonographic and CT scan findings.

The pancreas is formed embryologically fromdistinct ventral and dorsal buds which arise from theduodenal diverticulum after rotation of the ventralbud and have fused by the seventh week of life(Meckel, 1812). Wirsung (1642) first demonstratedthe main pancreatic duct in man and Santorini(1775) accurately described the duct system anddemonstrated the accessory pancreatic duct.

Normally, the main pancreatic duct is derivedfrom both embryological parts of the pancreas; thedorsal pancreas provides the main duct in the tailand body of the gland with the ventral anlageproviding the main duct in the head of the gland.The accessory duct (of Santorini) is the remainingportion of the duct in the dorsal pancreas which maydrain through an accessory papilla more proximallyin the duodenal loop.

It is thus not surprising that anomalies of thepancreatic duct system occur and their frequencyhas been documented in large systematic necropsystudies by Baldwin (1911), Howard and Jones (1947),Rienhoff and Pickerell (1954), Kleitsch (1955), andBerman et al. (1960). The duct of Wirsung is the

"Address for correspondence: Dr C. J. Mitchell, Departmentof Medicine, St. James's Hospital, Leeds LS9 7TF.

Received for publication 16 May 1979

major pancreatic duct in 900% of specimens and anaccessory duct of Santorini is present in 85% withcommunication between the two ducts in 33-90% ofspecimens.

In a minority of cases (7%), the accessory ductprovides the main drainage system. Infrequently,the two ducts fail to fuse, with the duct of Santorini(1-7%) providing the main drainage for the gland.It is this anomaly which is the subject of thiscommunication.The development of endoscopic retrograde

pancreatography (ERP) has enabled demonstrationof the pancreatic duct system in large numbers ofpatients. When the duct system is not fused, onlythe ventral duct is demonstrated by cannulation ofthe main ampulla (Figs. 1 and 2). Previous reportsby Cotton and Kizu (1976) and Gregg (1977) haveshown that pancreatitis was present in a highproportion of patients with an unfused pancreaticduct system and suggested that the anomaly mightbe a cause of pancreatitis. However, Rosch et al.(1976), Kruse (1977), and Thompson et al. (1978)found that pancreatitis was present in only aminority of their patients with this anomaly. Noneof these studies has compared the incidence ofpancreatitis in patients who have an unfused ductsystem with the incidence seen in patients withnormal pancreatic anatomy demonstrated at ERP.

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Clinical relevance of an unfused pancreatic duct system

We report a series of patients in whom a failure offusion of the two ducts was demonstrated at ERPwho have been studied retrospectively. In order toassess whether the anomaly found could be relevantto the pathogenesis of pancreatitis, we have alsocompared these patients with those with pancreatitisand normal pancreatic duct anatomy demonstratedat ERP.

Methods

An Olympus JF-B duodenoscope was used to per-form ERP with injection of 65% Urografin (ScheringChemicals Ltd.) under television control. The pan-creatograms were assessed to identify patients withan unfused pancreatic duct system and to determinethe number of pancreatograms in which pancreatitiswas demonstrated in a normally fused duct system.The criteria used for diagnosing pancreatitis fromthe pancreatograms were those described byAshton et al. (1978).

Since the criteria for detecting pancreatic diseasein patients with non-fusion of the pancreatic ductswere the clinical, biochemical, and operativefindings, the patients with a normal duct system andpancreatitis at ERP were also assessed using thesame criteria.Lundh tests were performed using a standard

method (Mottaleb et al., 1973). Mean tryptic activity

Fig. 1 Pancreatogram ofan unfused ventralpancreatic duct system. The common bile duct (arrowed)which also drains through the main ampulla, has beenopacified as well.

S'. d~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~0Fig. 2 The pancreatogram of a more e.vtensiv'e unfusedventral pancreatic duct system.

(MTA) was measured by the method of Wiggins(1966) and the lower limit of normal in our laboratoryis 9-7 jiequiv/ml/min.

Results

PATIENTS WITH UNFUSEDPANCREATIC DUCTSOut of 449 consecutive patients in whom ERP wassuccessful, there were 21 patients with a separateventral pancreatic duct system. Details of patientsare summarised in the accompanying Table. Theunfused duct system showed abnormalities suggestiveof pancreatitis in only one patient, and was normalin the remaining 20 patients.Four patients had definite clinical evidence of

pancreatitis and we were unable to find a cause forthis, such as bilary tract disease or alcohol abuse.The first patient (L.G.) gave a two year history ofepigastric pain which was not relieved by cholecys-tectomy; full gastrointestinal investigation wasnormal, except for an impaired Lundh test MTAwithout pancreatic steatorrhoea, and she continuesto have recurrent attacks of epigastric pain. Thesecond patient (J.S.) has had three severe episodesof acute pancreatitis with serum amylase levels upto 6000 Somogyi i/ml and laparotomy confirmationof the diagnosis on one occasion; a Lundh test wasabnormal shortly after the last attack, but she hasremained well on follow-up for another 12 months.The third patient (A.B.) presented with diarrhoeaand weight loss and was found to have an abnormalLundh test and arteriographic signs suggestive ofpancreatitis; serum amylase levels, glucose tolerance,and faecal fat excretion were normal. The fourthpatient (D.M.) had a three year history of recurrentabdominal pain associated with marked hyper-

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C. J. Mitchell, D. J. Lintott, W. S. J. Ruddell, M. S. Losowsky, and A. T. R. Axon

Fig. 3 In this patient the main pancreatic drainagethrough the accessory ampulla has been demonstrated.Some residual contrast remains in the unfused ventralpancreatic duct (arrowed) from prior cannulation of themain ampulla.

amylasaemia on four occasions; this patient wasfound to have signs of pancreatitis in the unfusedventral duct system at ERP but has no evidence ofpancreatic insufficiency.

In another two patients, the evidence for thepresence of pancreatic disease is inconclusive. In oneof the patients (F.R.) the finding of an abnormalLundh test may not be significant, as the patient wasseverely ill at the time and had previously undergoneextensive small bowel resections for Crohn'sdisease; this was the only patient in whom we wereable to demonstrate a normal duct system from theaccessory ampulla (Fig. 3) and, although he madesome response to therapy with pancreatic supple-ments, his gross steatorrhoea was more dramaticallyimproved by a low fat diet with MCT supplements.The other patient (F.W.) was referred for ERP fromanother hospital; he had drunk considerablequantities of alcohol in the past and developeddiabetes in the preceding year. After a cerebro-vascular accident, he had an episode of severe upperabdominal pain, which was considered on clinicalgrounds to be due to pancreatitis, but serumamylase levels could not be measured during theacute attack and he has since had a normal Lundhtest.

In the remaining 15 patients the finding of anabnormal pancreatic duct system did not seemrelevant. Thirteen patients have become asympto-matic after either cholecystectomy (six), treatmentwith a high fibre diet (four), withdrawl of drugtherapy (two) or spontaneously (one); one patient

has been lost to follow-up (although she was wellwhen last seen) and another patient continues tohave epigastric pain in spite of full gastrointestinalinvestigations.Serum amylase levels were normal in all these

15 patients, six of whom had a normal pancreas atlaparotomy and a Lundh test was normal in sixpatients. In five patients neither laparotomy nor aLundh test had been performed; all of these fivepatients became asymptomatic on follow-up and anadequate explanation for their illness was found infour patients.

PATIENTS WITH NORMAL PANCREATICDUCT ANATOMYERP was successful in 449 patients. Out of 428patients with normal pancreatic duct anatomy, anormal pancreatogram was seen on 270 occasionsand evidence of pancreatic carcinoma was presentin an additional 42 patients.

Signs of pancreatitis at ERP were seen in 116 outof the 428 patients (27-1 %) with a completely fusedduct system. The aetiology of pancreatitis wasbilary tract disease (47 patients), alcohol abuse(14 patients), idiopathic (51 patients), drug-induced(two patients), traumatic (one patient), or familialpancreatitis (one patient).Acute pancreatitis was considered to be present in

39 of the 116 patients on the basis of episodes ofsevere upper abdominal pain with marked hyper-amylasaemia, 25 patients having suffered recurrentacute pancreatitis. Laparotomy confirmation of thediagnosis was available in six patients.The remaining 77 patients were considered to have

chronic pancreatitis. In 63 of these patients thediagnosis was supported by one or more of thefollowing criteria: an abnormal Lundh test (39patients); calcification on plain abdominal radio-graphy (11 patients); steatorrhoea in the absence ofsmall bowel or liver disease (16 patients); laparotomyfindings (22 patients). In the remaining 14 patientsthe diagnosis of chronic pancreatitis at ERP had noother confirmation; four of these patients hadgrossly abnormal pancreatograms (two patientswere alcoholics) and the other 10 patients with biliarytract disease were referred to us either for investiga-tion of jaundice or endoscopic sphincterotomy.

Discussion

In this study we have found non-fusion of thepancreatic duct system in 21 out of 449 successfulpancreatograms (4 7 %). This compares with anincidence of 1-3-6% (overall 3 7 %) for this anomalyin previous reports of pancreatic duct abnormalities

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found at ERCP (Phillip et al., 1974; R6sch et al.,1976; Gregg, 1977; Kruse, 1977; Thompson et al.,1978). Cannulation of the accessory ampulla istechnically extremely difficult and it was possibleto achieve this on only one occasion.

It is difficult to assess the significance of non-

fusion of the pancreatic ducts in relation to thedevelopment of pancreatic disease because ERCP isperformed upon a highly selected group of patients.Necropsy studies indicate an incidence of 1-7% forthis anomaly (Baldwin, 1911; Howard and Jones,1947; Rienhoff and Pickerell, 1954; Kleitsch, 1955;Berman et al., 1960), so that the frequency found inthis study is that which might be expected in a

normal population.In this study, the incidence of pancreatitis in the

group with non-fusion of the pancreatic ducts (19 %)was similar to that found in patients with a normallyfused duct system (271 %), although analysing thedata in this way may merely reflect the selection ofpatients for ERCP. An alternative method ofassessing the results is that out of 449 patients inwhom the pancreatic duct system was demonstrated,

there were 21 (4-7 %) patients with an unfusedduct system, whereas out of 120 patients withpancreatitis by clinical and/or ERP criteria, therewere four patients (3 3%) with an unfused ductsystem. Thus, pancreatitis with abnormal ductanatomy was seen no more commonly than the ductanomaly was found at ERP. Likewise, no significantdifferences between the groups emerged if the 14patients were excluded in whom evidence of pan-

creatitis was found only at ERP. On the basis of ourdata it is therefore not possible to implicate non-

fusion of the pancreatic ducts as a cause ofpancreatitis.

In contrast with this study, several authors havesuggested that the anomaly might be a cause ofpancreatitis. Cotton and Kizu (1976) and Gregg(1977) found that the incidence of pancreatitis inthese patients was 580% and 450% respectively.Heiss and Shea (1978) reported four patients withunfused pancreatic duct systems and pancreatitisbut give no details of the incidence of the anomalyfound at ERP. Kruse (1977) found that 20o% of hispatients with unfused pancreatic ducts had pan-

Table Details ofpatients

Name Age Sex Symptoms(yr)

L.G. 45

J.S. 36

A.B. 62

D.M.

F.R.

F.W.D.B.

J.w.

A.A.M.W.A.W.F.B.

18

35

5543

38

34312863

F

F

F

M

M

M

F

M

M

FFF

Ba. Endoscopy S Lundhmeal amylase Test

(jl/dt) (MTA)

Epigastric pain, Nprevious cholecystectomyThree attacks of acutepancreatitisWeight loss, diarrhoea N

Four attacks of acute NpancreatitisEpigastric pain, NsteatorrhoeaAbdominal pain, diabetes -Weight loss, diarrhoea, NcholelithiasisAbdominal pain, Nweight lossEpigrastric pain NAbdominal pain NCholestatic jaundiceCholestatic jaundice N

F.H. 54 F Weight loss. diarrhoea

L.K. 45 M Obstructive jaundice

H.E. 62 M Abdominal pain

A.B. 63 F Weigh loss,abdominal pain

C.S. 46 F Obstructive jaundice

B.B. 67 M Recurrent cholangitis

M.E. 36 F Epigastric painL.I. 65 F Abdominal pain,

diarrhoeaL.S. 58 F Epigastric pain

*Not measured in acute attack.

N

N

N

N

N

Oesophagitis

NN

N

NNNN

N

N

N

N N

Follow-up Time(months)

N 5 9 Persisting pain. No steatorrhoea

< 6000 2 5 No further attacks

N 7 8 Pancreatitis at arteriography,no steatorrhoea

< 2400 - No further attacks

N 5 2 Some response to pancreaticsupplements

N* N No further pain, no steatorrhoeaN N Pancreas normal at operation,

no further symptomsN N Recovered spontaneously,

arteriography normalN N Responded to high fibre dietN N Responded to high fibre dietN - Resolved with drug withdrawalN N Resolved with drug withdrawal,

pancreas normal at laparotomyN - Pancreas normal at cholecystectomy,

remains wellN - CBD stone with normal pancreas

at operation, remains wellN - Pancreas normal at

cholecystec'omy, remains wellN - Symptoms settled, lost to follow-up

- N N - CBD stone with normal pancreas atoperation, remains well

- N N - Amylase repeatedly normal; no

gallstones, settled spontaneouslyN N N - Responded to high fibre diet- Gastritis N - Responded to high fibre diet

3 GU N N Pain persists, ulcers healed

30

20

22

10

16

921

29

6181210

24

8

7

3

10

9

1815

12

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1070 C. J. Mitchell, D. J. Lintott, W. S. J. Ruddell, M. S. Losowsky, and A. T. R. Axon

creatitis and suggested that the anomaly might becausative, because this was a higher incidence thanthat found in the normal population; however, wehave encountered a higher incidence of pancreatitisat ERP in patients with a normally fused duct system.Other authors have also found that only a minority

of patients with unfused pancreatic systems hadpancreatitis; Rosch et al. (1976) quoted an incidenceof 19% and Thompson et al. (1978) found that onlyone of their 11 patients had definite evidence ofpancreatitis. In none of the reports quoted above isany information given as to the incidence of pan-creatitis at ERP in patients with normally fused ductsystems (which is considerable in our experience),so that it is difficult to interpret their findings.Another problem in assessing the patients with an

unfused ventral pancreatic duct is that we havebeen able to demonstrate the main drainage of thepancreas (via the accessory ampulla) in only onepatient. These patients could therefore still haveabnormalities of the main pancreatic duct whichhave not been detected, although in previous reportsthe presence of pancreatitis in these patients has beendetectable by standard methods other than ERP.We have tried to overcome this problem by assessingthese patients using clinical follow-up, amylaselevels, Lundh test results and operative findings-the only methods available if other morphologicaltests are unreliable in this situation (see below).Using these criteria, we feel that we have excluded ordetected the presence of pancreatic disease in mostof the 21 patients with non-fusion of the pancreaticducts. In the remaining five patients who had notpreviously had a Lundh test or laparotomy, we didnot feel that additional investigation was justifiedin this retrospective study, as they had all becomeasymptomatic and a reasonable explanation for theirsymptoms had been found. For comparison, thesame criteria have been applied to patients withpancreatitis and normal duct anatomy at ERP asto the patients with non-fused duct systems.The relevance of pancreatic duct anomalies to the

pathogenesis of pancreatitis must iemain debatableat present. Berman et al. (1960) suggested that thepresence of a communicating accessory duct mightreduce the incidence of pancreatitis by acting as asafety valve when the main duct was obstructed.This suggestion is supported to some extent byMairose et al. (1978) who found a three-foldincrease in the incidence of hyperamylasaemia afterERCP in patients with an absent accessory pancreaticduct.An additional point of particular interest is that

four of the patients with an unfused ventral pan-creatic duct system were referred for ERP becauseenlargement of the head of the pancreas had been

diagnosed by grey-scale ultrasonography (three) orCT scanning (one). In none of these patients was anyother evidence found to suggest the presence ofpancreatic disease and it is presumed that thefindings at ultrasonography and CT scanning weredue to the non-fusion of the pancreatic ducts thatwas found to be present. It may therefore be im-portant to identify the duct anomaly so that falselyabnormal results shown by morphological scanningtechniques can be identified. Two of the patientswith unfused ducts had pancreatic arteriograms andthese showed no vascular anomalies.

This study suggests that non-fusion of the pan-creatic duct system is not a factor in the pathogenesisof pancreatitis and does not support previoussuggestions to the contrary. However, a conclusiveanswer could be provided only by performance ofERP in a consecutive series of patients presentingwith acute and chronic pancreatitis.

We are grateful to the referring physicians andsurgeons for permission to include some of the casesreported in this study.

References

Ashton, M. G., Axon, A. T. R., and Lintott, D. J. (1978).Lundh test and ERCP in pancreatic disease. Gut, 19,910-915.

Baldwin, W. M. (1911). The pancreatic ducts in man,together with a study of the microscopic structure ofthe minor duodenal papilla. Anatomical Record, 5,197-228.

Berman, L. G., Prior, J. T., Abramow, S. M., andZiegler, D. D. (1960). A study of the pancreatic ductsystem in man by the use of vinyl acetate casts ofpostmortem preparations. Surgery, Gynecology, andObstetrics, 110, 391-403.

Cotton, P. B., and Kizu, M. (1977). Malfusion of dorsaland ventral pancreas; a cause of pancreatitis? Gut, 18,A400. (Abstract).

Gregg, J. A. (1977). Pancreas divisum: its associationwith pancreatitis. American Journal of Surgery, 134,539-543.

Heiss, F. W., and Shea, J. A. (1978). Association ofpancreatitis and variant ductal anatomy. AmericanJournal of Gastroenterology, 70, 158-162.

Howard, J., and Jones, R. (1947). The anatomy of thepancreatic ducts. American Journal ofMedical Science,214, 617-622.

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Mairose, U. B., Wurbs, D., and Classen, M. (1978).Santorini's duct-an insignificant variant from normalor an important overflow valve? Endoscopy, 10, 24-29.

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Phillip, J., Koch, H., and Classen, M. (1974). Variationsand anomalies of the papilla of Vater, the pancreasand the biliary duct system. Endoscopy, 6, 70-77.

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Wirsung, J. G. (1642). Figura Ductus Cuiusdam cumMultiplicibus suis Ramulis Noviter in Pancreate inDiversis Corporibus Humanis Observati. Padua.

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