608 BRITISH MEDICAL JOURNAL 30 MARCH 1974

to that obtained under the same experimental conditions withhuman menopausal gonadotrophin and human chorionicgnnadotr.ophin.

We thank Miss Elena Altieri for urinary pregnanediol determina-tions, Mrs. Elizabeth Grassau for help with the manuscript, andMr. Rene Roy for photography and illustrations.The compounds used in this study were generously supplied as

follows: Synthetic FSH/LH-RH (AY-24031) from Dr. M. Gah-wyler, Ayerst International, New York, N.Y., U.S.A., Medroxy.progesterone Acetate (Depo-Provera) The Upjohn Company, Kal-amazoo, Michigan, U.S.A., Chlormadinone Acetate (Gestafortin)Merck, Darmstadt, West Germany.

ReferencesAkande, E. O., et al. (1972). Lancet, 2, 112.Kastin, A. J., Schally, A. V., Gual, C., and Arimura, A. (1972 a). Journal of

Clinical Endocrinology and Metabolism, 34, 753.Kastin, A. J., Gual, C., and Schally, A. V. (1972 b). Recent Progress in

Hormone Research, 28, 201.Schally, A. V., et al. (1971 a). Science, 173, 1036.Schally, A. V., Kastin, A. J., and Arimura, A. (1971 b). Fertility and

Sterility, 22, 703.Schally, A. V., Kastin, A. J., and Arimura, A. (1972). American Journal of

Obstetrics and Gynecology, 114, 423.Sulimovici, S., Lunenfeld, S., and Shelesnyak, M. C. (1965). Acta Endo-

crinologica K,obenhavn, 49, 97.Yen, S. S. C., et al. (1972).J'ournal of Clinical Endocrinology and Metabolism,

34, 1108.Zanartu, J., Dabancens, A., Kastin, A. J., and Schally, A. V. (1974).

In press.Zanartu, J., et al. (1970). Fertility and Sterility, 21, 525.Zanartu, J., and Onetto, E. (1974). Australian and New Zealand Journal of

Obstetrics and Gynaecology. In press.Zarate, A., Canales, E. S., Schally, A. V., Ayala-Valdez, L., and Kastin, A.

(1972). Journal of Fertility and Sterility, 23, 672.

Endoscopic Pancreatography in Management of RelapsingAcute Pancreatitis

P. B. COTTON, J. S. M. BEALES

British Medical3Journal, 1974, 1, 608-611

Summary

Endoscopic retrograde cholangiopancreatography (E.R.C.P.)was attempted in 31 patients suffering from repeated attacksof acute pancreatitis. Pancreatograms were obtained in 25patients. Twelve showed definite "surgical lesions" (obstruc-tions, strictures, or pseudocysts). In at least three patientsfailure to obtain a pancreatogram was due to obstruction ofpancreatic duct close to the papilla. Two patients, both withpseudocysts, developed a mild relapse of pancreatitis afterthe procedure. Surgical intervention based on the x-ray find-ings seemed beneficial in the short follow-up period.Endoscopic pancreatography can be of value in deciding

when surgery is advisable for patients with relapsing acutepancreatitis and in determining the operative appreach. It isan advance in the management of a difficult clinical con-dition.

Introduction

In Britain about one-third of patients who survive an attackof acute pancreatitis have at least one recurrence (Trapnell,1966). In some of them a previously overlooked contributoryfactor (such as gall stones or alcoholism) is found which maybe remediable. In others, however, there is no apparent ex-plition for their recurrent acute relapses. These cases poseproblems in management-in panticular, whether to recom-mend surgery and what operaion. Infor£mtion about thestate of the pancreaitic duct and its drainage should be ofhelp. Until recely pancreatography was possible only atlaparotomy (DouWbet et al., 1959) after a duodenotomy, which

St. Thomas's Hospital, London SE1 7EHP. B. COTTON, M.D., M.R.C.P., Senior Medical Registrar (Present appoint-

ment: Consultant Physician, Middlesex Hospital, London W.1)J. S. M. BEALES, M.R.C.P., F.F.R., Consultant Radiologist (Present appoint-

ment: Consultant Radiologist, Royal United Hospital, Bath)

increased the risk of explanatory surgery. Owing to therecent developmen-t of fibreoptic duodenoscopes the papillaof Vaster can now be cannulated by endoscopy in conscious,sedated patients and contrast medium for radiography in-jected into the pancreatic ducts and biliary system. After theoriginal Japanese studies (Ogoshi et al., 1970; Oi et al., 1970;Takagi et al., 1970; Kasugai et al., 1972) many encouragingreports of the technique came from Western Europe andNorth America (Jean-pierre et al., 1971; Blumgart et al.,1972; Classen et al., 1972; Cotton et al., 1972; Cotton, 1972;Vennes and Silvis, 1972). In experienced hands the successrate is about 90%.Endoscopic retrograde cholangiography has obvious poten-

tal in rthe diagnosis of patients with difficul-t jaundice (Blum-gart et al., 1972) but the clinical role of endoscopic reto-grade pancreatography has yet to be defined. This paperreports our use of i-t in cases of relapsing acute pancreatitisand our experience of its value as a guide to their man-agement.

Patients and Methods

A ftotal of 31 patients were investigated. Five were women(aged 63, 58, 62, 23, and 79 years respectively) and 26 weremen (mean age 43 years, range 21-72 years). Two patientscame from India, one from Iceland, and the remainder fromthe United Kingdom and Ireland. Five had had only onemajor attack of acute pancreatitiis but had contnued to haverecurrent episodes of pain needing furither hospital investiga-tion. The remaining patients had had from two Ito 20 attacksof acute pancreatitis over a period of up to 15 years. Fourpatients had undergone cholecysteotomy for stones andanother paient had been suspected of having a gall bladderstone on cholecystography. Fifteen of the patients drankalcohol rarely, if at all, nine drank alcohol every day but notexcessively, and seven patiens regularly drank more than onelitre of beer or three (English) measures of spirits daily. Noneof the patien-ts had hypercalcaemia and none out of 21 patientstested had any striking abnormalty of serum cholesterol ortriglycerides. Two paitients were being treated with thiazidediuretics. Two patients had had surgery for peptic ulcera-

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BRITISH MEDICAL JOURNAL 30 MARCH 1974

tion (Billroth I gastrectomy and vagotomy and pyloroplasty);nine had undergone diagnostic laparotomy during an attackof pancreatitis; ithree had had an elective sphinoteroplasty;and one had had a repair of a peripapillary diverticulum. Oralcholecystography or intravenous cholangiography had beencarried out in all paients with negative resul(ts, except in thecase mentioned above. In none of the patients did bariummeal radiography suggest the presence of a pseudocyst.

All the patients were admitted to hospital and were ex-amined in the ,standard manner in the x-ray departmentunder diazepam edation (Cotton, 1972). An Olympus JFBduodenoscope was passed {through the 'stomadi and duodenalbulb into the descending duodenum. After careful examina-tin of these organs and (takilg specimens for biopsy when

indicated the instrumen was adjusted to provide a face-onview of the papilla of Vater. A Teflon catheter (1-7 mmdiameter) was passed 'through the instrument and guided intothe papilla. Urografin (sodium and megluniine diatrizoates)60% was then injected slowly under fluoroscopic control toopacify the pancreatic duct and its major branches. Radio-graphs were itaken in appropriate positions. The time for thewhole procedure was usually between 30 and 45 minutes.

Results

The endoscopic appearance of the duodenal loop was abnor-mal in only 11 patients. In 'seven the mucosa of the floor ofthe bulb and the medial wall of the descending duodenumshowed abnormally large or congested folds but in only oneof these cases was the biopsy specimen definitely abnormal.In ithree patients the papilla of Vater was abnormal becauseof previous sphinoteroplasty and in another there was scar-ring from repair of a divertculunL In one patient a previous-ly unsuspected diverticulum obscured the papilla and pre-vented cannulation. Apart from ithi-s case the papilla was seenand cannulated in all the patients. Subsequent injection ofcontrast medium resulted in a pancreatogram in 25 patients,but in the remaining five no medium passed up the pan-creatic duct despite repeated attempts.

Thirteen of ithe 25 parearograms showed no "surgicallesion" (,table). The appearances were nrmal, in four (seefig. 1) and the other nine showed minor variaitions inl ductcalibre (figs. 2 and 3). In two of these only-the branch ductswere abnormal. The remaining 12 pancreatogranbs showeda "surgical lesion." In four cases there was complete obstruc-tion of the main pancreaic duot (fig. 4). In five there were

localized strictures (four juxtapapillary and one in the body;fig. 5) and in the remaining three strictures were associatedwith pseudocysts (two in the body and one in the (tail; fig. 6).There were no striking differences between the radiologicalappearances of patients who abused alcohol and those whodid not.

Results of Pancreatography in patients with Relapsing Acute Pancreatitis

Normal ducts 4 13Minor changes in branch ducts ..2 no "surgical lesion"Minor changes in main duct and branches 7Complete obstruction (head 2, body 2) 4 12Stricture+ pseudocvst (body 2, tail 1) 3 "surgical lesion"Stricture (juxtapapillary 4, body 1). 5Cannulation but no pancreatogram. .. 5 lNo cannulation (diverticulum) I failed

Total patients 31

Retrograde Cholangiography.-Injection of cOtrastmedium into the papilla resulited in cholangiograms as well

as pancreatograms in 13 of ithe 31 patients. In one case the

cholangiogram confirmed the suspicion of a gall bladderstone reported at previous cholangiography. The r iing

examinations ishowed no significant abnormality. Retrograde

609

FIG. 1-Normal pancreatogram in man aged 39 with history of five attacks ofacute pancreatitis. Tip of cannula is at papilla of Vater (arrowed).

FIG. 2-Pancreatogram m man aged 31 with persistent pain after attack ofacute pancreatitis. Slight irregularity of main pancreatic duct in head ofpancreas (arrowed) with no filling of the branches from the abnormalsegment. No surgical lesion.

cholangiograPhy was not attempted as a routine in everypatient, snce the results of previous cholecystograms or in-fusion cholangiograms had been normal in all of -them (apartfrom the one already mentioned).Complications.-Two patiens had mild relapses of pan-

creatis after the exination; both had previously beenhaving frequent attacks of pain and both were shown to havepseudocysts. Treatment with antibiotics was followed byelective surgery within a week.

Pancreaidc ftuncton Studies.-A secretin/pancreozymintest was p edsIr^16 pats and 10 o£iem were sub-sequently shown to have"asurgical lesions" f- the pancreas.Bicarbonate an enzyme secretion was normal in four ofthese 10 patients, equivocal in one, andd grossly amalin five.

SUBSEQUENT PROGRESS

The clinical progress of the paties was followed overperiods of from the nmnthis to two years. Many of themwere from other hospitals and they were subsequently treatedby the clinicians who had referred them. Their decisions were

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BRITISH MEDICAL JOURNAL 30 MARCH 1974I . ............~~~~~~~~.... .......i-.FIG. 5-Pancreatogram in man aged 43 who suffered four attacks of acutepancreatitis in two years. Main pancreatic duct (mpd) next to papilla dis-placed in smooth sweeping curve and narrowed (arrowed). Some branchducts also displaced. Main pancreatic duct distal to the structure dilated.Common bile duct (cbd) filled.

FIG. 3-Pancreatogram in man aged 34 who suffered seven attacks of acutepancreatitis in three years. Tip of cannula is at papilla of Vater (arrowed).Main pancreatic duct (mpd) and branch ducts show minor irregularitiesand cai bre variations. No surgical lesion.

FIG. 4-Pancreatogram in man aged 44 who suffered three episodes- ofpancreatitis. Complete obstruction of main pancreatic duct (double arrows)about 3 cm from papilla (single arrow). Branch ducts in head of pancreasirregular. At laparotomy distal part of pancreatic duct was found to be dilatedand was anastomosed to stomach.

FIG. 6-Pancreatogram showing stricture of main pancreatic duct (mpd;single arrow) with small associated cyst. Duct proximal to stricture dilated.Larger cyst in tail (double arrow). Common bile duct (cbd) and cystic duct(cd) filled.

guided by the findings at pancreatography. Only one of the13 patients whose pancreatogram showed no "surgical lesion"was operated on. This was because of recurrent severe pain.The pancreatogram had shown only minor changes in theductal system and at laparotomy the pancreas appeared nor-mal, but needle biopsy showed histological evidence of re-solving pancreatitis. No other procedure was performed andthe patiet had further astacks of pancreatitis.Of the seven patients with complete duct obstruction or a

stroture and pseudocyst five underwen-t -the operation indica-ted by the pancreatogram-distal pancreateotomy or internaldrainage of a pseudocyst-with good results. One patient withmain duct obstruction in the mid-body was not operated onand symptoms persisted 18 months later. Another with a simi-lar lesion had only a sphincterotomy and continued to haveattacks one year later. Two of the patients with juxtapapillarystrictures underwent sphincteroplasty with good results andthe remaining three with strictures conitinued under obser-vato.Of the six patiens in whom a pancreatograam was not

obtained three came to surgery and in each the duct was

610

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BRITISH MEDICAL JOURNAL 30 MARCH 1974 611

obstructed close to the papilla. The remaining three patientshave continued under observation and all have had furtherepisodes of pancreatitis. Failure to obtain a pancreatogrammay be due to technical problems bu-t in experienced handsfailure certainly suggests -the presence of a lesion in thepapillary area.

Discussion

Our study showed that about half of a group of 31 patientswith relapsing acute pancreatitis had a "surgical lesion" ofthe pancreatic duot (obstruction, stricture, or pseudocyst) andthat most of these could be shown by endoscopic pancreat-graphy. These lesions were assumed to resulit from earlierattacks of pancreatirtis and to have perpetuated the disease.Logically, therefore, the surgical approach should be basedon -the pancreatographic findings, and the subsequent courseof these patients so far supports that contention. Endoscopicretrograde cholangiopancreatography (E.R.C.P.) is not a simpleprocedure and needs much experience with fibreoptic endo-scopes. High quality radiographs are essential and even thenthe interpretation of pancreatograms can be difficult. Never-theless, this procedure seems to be the only way, short ofoperation, to iden.tify a surgical lesion in the pancreatic duct.Though the numbers in our study were small the results

of measuremenTt of pancreatic function suggested that this isnot a good way of distingushing patients with ductal diseasefrom those without, and our experience of pancreatic scan-ning is equally disappointing. An alternative approach wouldbe to perform laparotomy, duodenotomy, and operative pan-creatography in every case. But operative pancreatography isnot without hazard, and dhis can be avoided by endoscopicpancreatography. While the demonstration of a normal orvirtually normal duct does not help in deternining the sur-gical approach it clarifies the position and should suggest aneed for further search for a cause of parenchymal diseasesuch as alcohol abuse, drug ingestion, or hy.perlipidaemia. Ina few such patients endoscopic retrograde cholangiopancreato-graphy may be the only way of clearly showing the presenceof gall stones.

Endoscopic pancreatography resulted in mild aotacks ofpancreatitis in two patients in the present series. They werethe only such conplications we have seen in over 300 exam-inations. Other experienced observers have emnphasized thepotential risk in patients with relapsing pancreatitis and par-

ticularly in ithose who have pseudocysts. In these cases noattempt should be made to outline the entire cyst and thepatient should be considered for surgery within the next fewdays. Pancreatography is contraindicated during an attackof acute pancreatiis. In patients with relapsing pancreaitiswe recommend waiting for two weeks af£ter the acute episode.Endoscopic retrograde cholangiopancreatography should al-ways be an inpatien procedure.We have reported on the value of endoscopic pancreato-

graphy in a small but well-defined group of patients. Ourexperience with patienits with painful chronic pancreais sug-gests that the procedure is equally useful in determiingtheir surgical management. Gross abnormalities of the pan-creatic duct system are more commonly seen (Kasugai et al.,1972; Classen et al., 1972). The role of endoscopic pancreato-graphy in the diagnosis of pancreatic disease is more con-troversial and is currently under investigation. Evidentlypancreatiftis can occur in the absence of ductal changes andnormal radiographs have been described in a few patientslater shown to have carcinoma (Koch et al., 1973). Thus anormal endoscopic pancreatogram does not completely ex-clude pancreaic disease jus(t as a normal pyelogram does notexclude renal disease. Neventheles;s, the present study showsthat endoscopic retrograde pancreatography can provide im-poartant clinical information in patients with known relapsingpancreatlts.

References

Blumgart, L. H., et al. (1972). Lancet, 2, 1269.Classen, M., Koch, H., Fruhmorgen, P., Grabner, W., and Demling, L.

(1972). Acta GastroEnterologica (Japan), 7, 141.Cotton, P. B., et al. (1972). Lancet, 1, 53.Cotton, P. B. (1972). Gut, 13, 1014.Cotton, P. B., Beales, J. S. M., and Cole, J. A. (1973). In Endoscopy of the

Small Intestine with Retrograde Pancreato-Cholangiography, ed. L.Demling and M. Classen, p. 74. Stuttgart, Georg Thieme.

Doubilet, H., Poppel, M. H., and Mulholland, J. H. (1959). Annals of NewYork Academy of Science, 78, 829.

Jean-pierre, R., et al. (1971). Archives Francaises des Maladies de L'AppareilDigestif, 60, 525.

Kasugai, T., Kuno, N., Kobayashi, S., and Hattori, K. (1972). Gastro-enterology, 63, 217.

Koch, H., Classen, M., and Demling, L. (1973). In Endoscopy of the SmallIntestine with Retrograde Pancreato-Cholangiography, ed. L. Demlingand M. Classen, p. 90. Stuttgart, Georg Thieme.

Ogoshi, K., Tobita, Y., and Hara, Y. (1970). Gastroenterological Endoscopy(Tokyo), 12, 83.

Oi, I., Kobayashi, S., and Kondo, T. (1970). Endoscopy, 2, 103.Takagi, K., et al. (1970). Gastroenterology, 59, 445.Trapnell, J. E. (1966). Annals of the Royal College of Surgeons of England,

38, 265.Vennes, J. A., and Silvis, S. E. (1972). Gastrointestinal Endoscopy, 18, 149.

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