Gut: first published as 10.1136/gut.4.3.193 on 1 September 1963. Downloaded from Gut, 1963, 4, 193 A clinical study of chronic pancreatitis OLIVER FITZGERALD, PATRICK FITZGERALD, JAMES FENNELLY1, JOSEPH P. McMULLIN, AND SYLVESTER J. BOLAND From St. Vincent's Hospital and the Departments of Medicine and Therapeutics and ofSurgery, University College, Dublin EDITORIAL SYNOPSIS A series of 53 cases of chronic pancreatic disease is described and attention drawn to the frequency with which symptoms are persistent rather than intermittent. A plea is made for the use of the term 'progressive' rather than 'relapsing' in describing many of these cases. Alcohol was an unimportant factor in the aetiology. The possibility of achieving an accurate and early diagnosis using the serum secretin/pancreozymin test is emphasized. The frequent relief of symptoms and the prevention of progress of the disease by surgery, especially sphincterotomy, is recorded. While pancreatitis has been recognized for over a (Howat, 1952; Burton, Hammond, Harper, Howat, century as a cause of gastro-intestinal disturbance, Scott, and Varley, 1960). much of the literature has dealt with acute rather In this paper we propose to describe our experi- than with chronic pancreatic disease. Reports on ence with 53 cases of chronic pancreatitis, laying the latter have been published by Comfort, Gambill, particular stress on the possibility and importance and Baggenstoss (1946), by Gambill, Comfort, and of early diagnosis of the condition, that is, when Baggenstoss (1948), and by Janowitz and Dreiling minimal damage to the acinar and islet tissues has http://gut.bmj.com/ (1958) but there is still disagreement as to the usual been caused. At this stage treatment is most effective aetiology, presentation, pathogenesis, and treatment. in the management of symptoms and in the pre- It has been generally thought that in chronic pan- vention of further pancreatic destruction. creatitis the patient typically suffers from recurrent In so far as early, developing, mild, or atypical episodes of upper abdominal pain with intervals of cases have been missed, mainly through lack of complete freedom and that there is evidence of one specific tests, the frequency of chronic pancreatitis or more of the major signs of pancreatic disease, has, we believe, been much underestimated. The on September 25, 2021 by guest. Protected copyright. such as a raised fasting level of serum amylase or 53 cases of our series have been encountered in lipase, steatorrhoea, pancreatic calcification, or eight years, 1952-1960. As they are drawn from a diabetes. Cases of this nature should present little small population we feel that the condition must be diagnostic difficulty to-day, but there are, we believe, a relatively common cause of upper abdominal many cases in which the pain and digestive distur- discomfort. bance may not be so confidently ascribed to pan- creatic dysfunction. This paper in the main endea- METHODS OF INVESTIGATION vours to elucidate the clinical aspects of such cases and to stress the value of evocative enzyme testing. The deep situation of the gland and its closeness to other It is agreed that earlier evocative tests 'provided organs makes confident early clinical or radiological little relevant information not obtainable by other diagnosis of pancreatitis difficult (McCollum, 1955). methods' (Joske, 1955) but this evaluation has to Laboratory and radiological investigations, which may be radically altered now. In 1943 Harper and Raper be divided into non-specific and specific tests, must be produced a purified pancreozymin which greatly relied upon. This differentiation cannot be water-tight increased the enzyme content of pancreatic juice as but it is of practical value. distinct from the increase in volume evoked by NON-SPECIFIC LABORATORY TESTS We used four. secretin. Both substances are currently combined 1 Glucose tolerance test A glucose tolerance test in the evocative secretin/pancreozymin (S/P) test was usually carried out, using I g. glucose per kilogram body weight. 'Now at the Medical Center, Jersey City, New Jersey. 2 Fat balance studies Up to two years ago we carried 193 Gut: first published as 10.1136/gut.4.3.193 on 1 September 1963. Downloaded from 194 Oliver FitzGerald and others out fat balance studies on patients on a 50-g. fat diet. in serum amylase activity was 0-2 mg./ml. (11 units) in Since then patients have been on free-choice ward diets the non-pancreatic cases. This is in agreement with the and we have used three-day collection periods. results of Sun and Shay (1960) and of Burton et al. 3 Vitamin A absorption tests See below. (1960). 4 Triolein 131I and oleic acid 131I studies. See below. 2 Vitamin A tests Vitamin A post-absorption curves are useful in the diagnosis of errors of absorption. The SPECIFIC LABORATORY TESTS contrast between post-absorption curves of vitamin A 1 Serum secretin/pancreozymin (SIP) test In the acetate and alcohol is helpful in deciding on the pre- diagnosis of early cases of chronic pancreatitis the serum sence ofmaldigestion, as the alcoholic form of the vitamin enzyme response to stimulation with secretin and pan- does not require any further breakdown which the creozymin is, in our experience, the most helpful test of acetate needs before absorption. The fasting serum all. Fasting amylase and lipase levels are often normal in vitamin A level normally varies between 100 and 300 quiescent phases of the disease. We used the method i.u. % and rises to over 800 i.u. % at peak absorption originally described by Howat (1952) and more recently time (three to five hours) after ingestion of 250,000 elaborated on by Burton et al. (1960) with minor modi- i.u. % in the case of both acetate and alcohol preparations fications as regards time. Serum specimens were assayed of vitamin A (FitzGerald, Fennelly, and Hingerty, 1961, for amylase and lipase according to the methods of 1962). Myers, Free, and Rosinski (1944) and of Cherry and 3 Triolein 131I and oleic acid 131I test This test has Crandall (1932) respectively. The development of pain been used following a method similar to that used by over the pancreatic area following the injection of Fennelly, FitzGerald, and Healy (1959). Triolein requires pancreozymin was noted, as it possibly indicated pan- to be digested by pancreatic lipase before absorption. creatic obstruction. The patient was asked to compare Hence, in conditions of pancreatic deficiency, it is poorly any pain which might occur with that of his original absorbed compared with oleic acid. We have relied complaint. upon serum levels following a test dose of the 1311 tagged To avoid the development of thrombophlebitis, the fat rather than urinary or faecal excretion. pancreozymin must be diluted to 20 ml. and must be injected slowly. In our experience of about 300 tests the NON-SPECIFIC RADIOLOGY Non-specific radiology, such worst reaction to the injection has been occasional as a barium meal or cholecystography, will often have moderately severe abdominal pain with vomiting. This been performed in the preliminary investigation of such pain always passed away within 20 minutes. cases. They rarely yield information directly helpful in We always avoided carrying out these tests on patients the establishment of a diagnosis of pancreatitis. One should, however, remember that the presence of patho- immediately after a suspected acute phase of pancreatitis; http://gut.bmj.com/ in many cases such tests would in any case be un- logy in associated organs does not rule out the possibility necessary as the patients would have shown increased of chronic pancreatitis. enzyme levels in the absence of stimulation. Repeated tests in the same patient never gave rise to any reaction SPECIFIC RADIOLOGY Before the administration of suggestive of hypersensitivity to the reagents. barium or of radio-opaque dyes an antero-posterior In 26 of 34 hospital patients with non-pancreatic radiograph of the abdomen is necessary to recognize the disease the fasting serum amylase varied between 0.56 presence of pancreatic calcification. It is essential to and 2-1 mg./ml. reducing sugar (31 to 115 units), and in demonstrate that the calcification is actually in the gland the other eight cases, which had higher amylase levels, itself, if necessary by a lateral film. on September 25, 2021 by guest. Protected copyright. portal hypertension, cholecystitis (2), biliary cirrhosis, Pa:.:creatography Per-operative pancreatography by hepatitis, coronary thrombosis (2), amyloidosis (1) were the method of Doubilet, Poppel, and Mulholland (1955) found. Bogoch, Roth, and Bockus (1954) reported is occasionally useful. We have used 5 to 7 ml. of 22% raised serum amylase levels in acute gall bladder disease, Uropac, and this should be injected slowly and gently. It perforated duodenal ulcer, uraemia, post-cholangio- is important to use minimal pressure, otherwise acute graphy, and after administration of morphine-like pancreatitis may be precipitated. Occasionally distal narcotics and parasympathomimetic drugs. pancreatography through the sectioned pancreatic tail In 24 (93%) of our 26 normal control cases fasting may be necessary. The information derived from these amylase figures were from 0.57 to 1.16 mg.lml. (31 to 64 pancreatograms has been of limited value in this series, units). According to Howat's (1952) series, the normal possibly due to the fact that the clinical material was, fasting amylase figures varied from 0.3 to 1-35 mg. re- generally speaking, early. ducing sugar/ml. serum (16 to 74 units). In 27 normal Our methods of investigation are summarized in controls the serum lipase range was 0-2 to 1-3 N/20 Na Table I. OH, of which the significance will be referred to later. Secretin/pancreozymin test In normal cases serum CASE MATERIAL amylase activity rose from the fasting level of 0.5 to 1.9 mg./ml.