·No text on this page.

·THE DIAGNOSIS OF PANCREATIC DISEASE

·No text on this page.

·THE DIAGNOSIS OF
PANCREATIC DISEASE
LOUIS BAUMAN, M.D.
Formerly Assistant Professor of Clinical Medicine,
Columbia University, and Assistant Visiting
Physician to the Presbyterian Hospital, New York
With a Foreword by
ALLEN O. WHIPPLE, M.D.
Philadelphia
London
I. B. LIPPINCOTT
Montreal
COMPANY

·COPYRIGHT, 1949
By J. B. LIPPINCOTT COMPANY
THIS BOOK IS FULLY PROTECTED BY COPYRICHIT
AND, WITH THE EXCEPTION OF BRIEF EXCERPTS
FOR REVIEW, NO PART OF IT MAY BE REPRODUCED
WITHOUT THE WRITTEN PERMISSION OF THE
PUBLISITERS.
SRINTED IN THE UNITED STATES OF AMERICA

·Foreword The advances of the last twenty years in the therapy of pancreatic lesions have emphasized the importance of accurate diagnosis and valid diagnostic tests. Fasting and blood-sugar determinations with levels below 50 mg. per cent have proved to be the most important laboratory tests in islet-cell tumors. Similarly, elevated serun amylase findings have been of the greatest help in the diagnosis of acute pancreatitis. In the obstructive lesions of the head of the pancreas and of the ampullary area, insufficient attention has been paid in this country to the work of the Stockholm school in developing duodenal intubation to determine the acinar activity of the pancreas. Dr. Bauman's experience during the past twenty-five years in the study of metabolic disease and pancreatic lesions, in association with the medical and surgical services at the Columbia-Presbyterian Clinic, eminently qualify him in his analysis of the large mass of clinical and laboratory data in these fields. His management is based upon carefully checked and followed clinical histories. It gives this writer great satisfaction to see these data analyzed and to have had the privilege of associating with Dr. Bauman in the study and the care of so many of the patients reported. This is a much-needed monograph and should stimulate further studies in the clinics of this country in pancreatic disease. ALLEN O. WHIPPLE, M.D.

·No text on this page.

·Preface During the last 20 years, three contributions have especially advanced our knowledge of the pancreas and its diseases. Starting with the preparation of secretin almost fifteen years ago, Agren, Hammarsten, Berglund, Lagerloef, and associates of the Stockholm school gradually developed a practical test of external pancreatic function. After the intravenous injection of the hormone, a dilute pancreatic secretion was aspirated from the duodenum with a specially constructed double tube. In this way, armixture of gastric secretion was avoided. A compilation of this work by H. O. Lagerloef entitled Pancreatic Function and Pancreatic Disease was published about six years ago. The author is pleased to acknowledge the help and the inspiration that he received from this book, which is a lasting contribution to the diagnosis of pancreatic disease. The medical world is also indebted to Robert Elman, of Washing. ton University, St. Louis, for demonstrating the value of the serum amylase test in the diagnosis of acute pancreatitis. Further tribute is due Dr. A. O. Whipple and his associates for progress in the surgery of the pancreas. This pioneer work has enabled surgeons to remove part or all of the organ in certain cases of hyper. insulínism, chronic pancreatitis and carcinoma. For the first time it was possible to observe the effects of the complete removal of the pancreas on human beings. In this monograph the writer has attempted to correlate the laboratory and clinical experience in pancreatic disease at the Presby. terian Hospital, New York, during the past ten years. For reasons to be discussed, the vagus stimulant mecholyl, was chosen to provoke pancreatic secretion. About 550 determinations were made on patients suffering from pancrcatic and nonpancreatic disease. LOUIS BAUMAN, M.D.

·No text on this page.

·Acknowledgments
The author is grateful to Dr. Allen O. Whipple for his kind
interest and for the opportunity to study his many patients with
pancreatic disease.
He is also indebted to the following for technical assistance:
Mrs. Margaret Hamlin Bacher
Mirs. Edith Bratti Larkin
Mrs. Margie Hoch
Miss Janice Super
Miss Gladys De Fillo
Dr. José Candela, of the University of Madrid, assisted in the
serum amylase tabulations. Dr. Virginia K. Frantz demonstrated the
pathologic anatomy of the specimens removed at operation. Dr. Ross
Golden and the staff of the x-ray department directed the duodenal
intubation. Dr. John W. Fertig gave valuable advice regarding the
statistical significance of the ferment values.
Mrs. Donald J. Huyssoon prepared the manuscript.
LOUIS BAUMAN, M.D.

·No text on this page.

·Contents 1 ABBREVIATIONS xiii INTRODUCTION XV 1. PANCREATIC FUNCTION TEST Functional Reserve of the Pancreas 7 Ferment Deficiency without Morphologic Change 9 Ferment Concentration of Pancreatic Juice 10 Nonpancreatic Disease 10 Acute Pancreatitis 14 Chronic Pancreatitis 19 Cancer of the Pancreas 27 Carcinoma of the Bile Ducts 36 Sprue 40 Pernicious Anemia 42 2. FAT ABSORPTION STUDIES IN PANCREATIC DEFICIENCY 45 Determination of Fat in the Stool 46 3. SERUM AMYLASE 47 Serum Amylase Determination 47 Serum Amylase in Acute Pancreatitis 50 Serum Amylase in Chronic Pancreatitis 56 Serum Amylase in Cancer of the Pancreas 56 Serum Amylase in Operated Cases of Gallbladder Disease .. 58 Serum Amylase in Patients with Stone in the Common Bile Duct 61 Serum Amylase in Duodenal Ulcer 63 Serum Amylase in Chronic Nephritis 64 Serum Amylase in Salivary Gland Diseases 64 Serum Amylase in Miscellaneous Abdominal Diseases 65 CONCLUSIONS 67 BIBLIOGRAPHY 68 INDEX 73

·No text on this page.

·Abbreviations
Ac. = Acute
C.B.D. = Common bile duct
Chr. Chronic
Ca. = Carcinoma
Diab.= Diabetic
Duod. =- Duodenum
D.U. =Duodenal ulcer
F.U.=Follow-up
G.B. = Gallbladder
G.T.T.= Glucose tolerance test
Hd. Head
J.= Jaundice
1. = LOW
P= Pancreas
Pctis.
Pancreatitis
P.D. = Pancreatic duct
P.F.T. Pancreatic function test
S.A. = Serum amylase
xui

·No text on this page.

·Introduction The purpose of this publication is to discuss the pancreatic function tests and their application in the diagnosis of pancreatic disease. Although the pancreas is the principal organ that is concerned with the digestion of starch, protein, and fat, an appraisal of its functional capacity was impractical until a few years ago. Recent progress in the surgery of the pancreas and the introduction of new laboratory methods have advanced our knowledge of this organ in health and disease. The need for a measure of acinar activity of the pancreas has long been apparent. Such a test should aid in diagnosing the cause of obstructive jaundice, steatorrhea, and other abdominal conditions. Clinicians are therefore indebted to Agren, Hammarsten, Lagerloef, and associates2-8 for developing a practical pancreatic function test. The results of the Swedish investigators have been confirmed in this country by Diamond and Siegal, Comfort and Osterberg, Pratt, Lake, and others. 7-16 Accurate determination of pancreatic ferment activity requires experience and familiarity with the properties of these remarkable high molecular catalysts. For example, considerable time was lost before the importance of collecting the pancreatic secretion in iced containers was realized. This was necessary to avoid reduction in ferment activity. On the other hand, the quantitative estimation of the end products of ferment activity, that is, reducing sugar, nonprotein nitrogen, and butyric acid, is fairly simple and commonplace. The serum amylase determination has been generally accepted as a means of differentiating acute pancreatitis from the other more common abdominal emergencies such as perforated duodenal ulcer, acute biliary tract conditions, acute appendicitis and intestinal obstruction. It seems probable that its usefulness will be extended in the future. According to Comfort and Osterberg, 17 serum ferment estimation is valuable in acute pancreatitis, carcinoma of the pancreas, and in XY ·xvi Introduction chronic pancreatitis as long as the inflammatory process is active and acinar tissue remains. In carcinoma, serum lipase was elevated in 28 of their 69 cases (40.5%), and serum amylase in 2 of 25 cases (8%). Fat absorption studies are helpful when the pancreatic juice is not obtainable for one reason or another. When fat absorption is inadequate, the effect of pancreatic preparations by mouth may be ascertained in this way. The astonishingly good far absorption noted at times in the absence of pancreatic juice is unexplained. Thanks to the pioneer work of A. O. Whipple and followers,18,18 the human pancreas is no longer considered an indispensable organ. It seems likely that more lives will be saved or made endurable as progress in the diagnosis and treatment of pancreatic disease continues. With the aid of commercial insulin and dried pancreas preparations, a depancreatized person may be maintained on an appropriate, balanced diet in a fair state of health.20,21,22 The mildness of the diabetes in depancreatized individuals was unexpected and is difficult to explain. Animal experimentation sugo gests that the pancreas produces an insulin-inhibiting agent. For example, an alloxan diabetic dog under comparable conditions requires more insulin before than after his pancreas has been removed.23 Most recently, Heard and coworkers obtained a fraction from pan. creatic extract that lowered liver glycogen and raised the blood sugar.se ·PART I Pancreatic Function Test In 1926, Chiray and his associates 4 studied the action of purified secretin, a protein hormone extracted from the mucous membrane of the small intestine, on the external secretion of the human pancreas. After duodenal intubation, 0.03 Gmn. of the product was injected intravenously. A definite increase in volume, protease, and lipase resulted. Ten years later, Chiray and Bolgerts, using a commercial secretin preparation*, noted a diminished output of ſerments in verified subacute pancreatitis and carcinoma. Later, in 1939, these authors extended their clinical studies. We are indebted to W. Hammarsten, E Agren, H. Lagerloef and their associates 2.8 for improving the technic and thus furnishing a practical method of testing the external secretion of the pancreas. At first a purified secretin was prepared; this, however, was too expensive for routine clinical use. A suitable commercial preparation was then developedt. Following its intravenous injection into a normal person, an average of 136 cc, of dilute pancreatic juice was secreted in 1: hour. When a satisfactory stimulant had been discovered the next problem was to prevent admixture of the pancreatic secretion with gastric juice, for it is well known that pant reatic enzymes are destroyed in an acid medium. The use of a conjoined double tube with the longer end entering the duodenum and the shorter end terminating in the stomach, permitted the separate aspiration of the two organs with minimal escape of acid into the duodenum. The results are discussed by H O. Lagerloef* A comparison of the volume, bicarbonate, and ferment content of the secretion in pancreatic and nonpancreatic diseases demonstrated the diagnostic value of the test. Diamond and Siegel7,8 confirmed these results in this country. They were impressed by the dilute character of the secretion after secretin in- •Formoduodenine, prepared by Maison Bila tilstra Laboratories of Soedertalje, Sweden 1 ·2 Pancreatic Function Test jection as contrasted with the more concentrated juice after vagal stimulants. These authors also noted that in pancreatic disease the enzyme production was first affected, Comfort and Osterbergs confirmed the difference in volume after the two types of stimulation. The average ten-minute volume before stimulation was from 7 to 8 cc. After secretin, 120 cc. of juice was aspirated in forty minutes, while after mecholy!* (vagus stimulant), an average of only 50 cc. was obtained (see Fig. 1). They conclude, "the increase in total ferments appeared to be due to a washing-out process in the case of secretia and to an active secretion of Before stimulation Atter stimulation Cu.cm 40 35 30 25 20 15 Secreion 10 5 Mechoty thlofsde 1 20 100 10 20 30 40 50 60 70 minutes Fig. 1. Average volume of duodenal contents per unit of time before and after stimulation with secretis and mecholyi chloride. (Comfort, M, W., and Osterberg, A E.: Arch Int. Nied. 66-688.) enzymes in the case of mecholyi... the concentration of ferments with mecholy? may prove to be a more reliable index of pancreatic function than the total values per unit of time after stimulation with erther secret or mecholyl." In a case of recurrent pancreatitis, Comfortio found that both secretin and mccholyl produced an abnormal increase in volume, a hyposecretion of anylase, and a hypersecretion of protease and lipase. This dissociation liad been noted by previous workers. T.* In advanced pancreatitis, all clc. *Pacholyl chloride us the trade name for acetyl (k'ta sactylcholiac Uloskle its properties are ilescribed in the MAMA, 124 860, 1911.

·Pancreatic Function Test 3 ments were below normal. He believes that both mecholyland secretin are powerful stimulants and that foods are less so. Necheles27 noted that the commercial secretin preparation deteriorated and became toxic on standing For the aforementioned reasons and because secretin was expensive or impossible to obtain, we used mecholyi as the pancreatic stimulant. A Miller-Abbott type of rubber tube 4 feet long and 16 french, divided into two longitudinal compartments by a central partition, was used. The duodenal end is provided with a perforated metal tip. The Wangensteen apparatus Stomach tube wr Duodenal tube Ice'container FIG. 2. The arrangement of the apparatus for the pancreatic function test. (Bauman, L.: Tests of the external pancreatic function, Nelson's New Loose Leaf Surgery, vol. 5, New York, Nelson, pp. 423-428.) gastric canal is perforated where it is in contact with the stomach wall; it has no connection with the duodenum. The tube is passed through the nose into the stomach (see Fig. 2) 26 This is best done the night before but may be inserted in the fasting state on the morning of the test. The patient rests on the right side, and the tube is manipulated into the duodenum under the fluoroscope by the roentgenologist. This may be difficult, time-consuming, or impossible. Pylorospasm, adhesions about the duodenum, or abnormal or unusual conformation of the stomach or duodenum may be the cause of failure. In several instances, 0.015 Gm.

·Pancreatic Function Test morphine hypodermically has enabled the passage of the tube into the duodenum. After the tube is in the duodenum, it is taped to the nose with adhesive plaster, and 10 cc. of a 25 per cent emulsion of finely powdered calcium carbonate in gum acacia solution is syringed into the stomach to neutralize excess acid. This must be repeated if the pancreatic juice fractions continue to be acid. The oral ends are joined to the receiving test tubes into which the juices are aspirated by constant gentle suction by means of a Wangensteen apparatus. The duodenal glass receiving tube must be iced to avoid destruction of ferments during collection. After obtaining the first ten-minute sample, 0.010 of mecholyl chloride is injected subcutaneously. Ten, 20, and 30 minutes later, three further tenminute fractions are collected. The fractions are preserved in ice until analyzed. The pH is determined with a Hellige pH meter. If the specimen is neutral or alkaline, its volume, amylase, protease and lipase concentrations are determined. It is suggested that a solution of atropine sulfate for hypodermic injection be at hand to anticipate undue sensitivity to the vagomimetic drug. Especial care in asthma and heart disease is advisable. How. ever, we have had very little trouble in this respect in over five hundred cases, Before publication of the Free and Myersas method, the concentration of ferments was determined by noting the least amount of juice required for active digestion of substrate. The amylase was estimated according to Wohlgemuth,29 che protease according to Gross,30 and the lipase according to Cherry and Crandall.32 The ferment activity was expressed as active (+), low (1), or absent (0). For optimum results with the more recent Free and Myers method, a mechanical shaker is desirable. For the determination of lipase, u ibułyrin, advocated by Free and Myers, gives more uniform results than emulsified olive oil. (Compare Tables 1 and 2). The range of values was from 4 to 21 cc. with tributyrin, and from 2 to 61 cc. with emulsified olive oil. The steps that are necessary to obtain four alkaline fractions and to determine their hydrogen ion and ferment concentrations consume de better part of a laboratory day. This expenditure of time may be shortened as experience increases. Ac any rate, the test promises to become a routine procedure in the hospital chemical laboratory. In this publication, an attempt has been made to correlate the results of approximately 550 pancrcaric function {ests with other ·Pancreatic Function Test 5 TABLE 1, LIPASE VALUES IN NONPANCREATIC DISEASE USING AN EMULSIFIED OLIVE OIL SUBSTRATE* FRACTIONS Cc.0.1 Normal Acid DIAGNOSIS AND RELARKS 1 ox సంవాదాలు+NNA-wరేయ 11 2 3 19 23 18 Stones in gallbladder-cholecystectomy 23 19 23 17 9 40 44 42 Stones in common bile duct-jaundiced 07 24 24 15 Normal Control 12 25 28 17 Lymphosarcoma 5 30 12 17 Cirrhosis of liver-biopsy pancreas=negative 15 15 13 Ca gallbladder--peritoneal metastases 4 8 9 Hanot's cirrhosis-explored 4 17 15 14 Biliary cirrhosis-unoperated 8 19 2 4 Control 2 11 37 Ca stomach at operation 35 20 38 Psychoneurosis--diarrhea 0.3 16 30 Control 2 14 22 Control 10 2 14 13 Ca lymph gland 3 25 29 0.5 Ca. colon 28 5 5 Exploration—undiagnosed 6 33 6 6 Control 02 29 43 74 Catarrhal jaundice or hepatitis 23 49 0.4 Exploration-biopsy pancreas=normal 17 39 48 52 Repeated 1 month later 2 41 2 Ulcer heel 2 23 9 7 Control 52 58 98 Control 40 27 8 54 Control 3 15 24 28 Hepatitis 53 74 61 25 Stone in common bile duct 36 97 79 Stones in gallbladder-cholecystectomy 06 8 58 33 Cholesterosis, operated 22 58 36 05 Cholecystectomy 41 18 45 Stricture of common bile duct 27 50 36 28 Stones in gallbladder 3 34 34 33 Stone in common bile duct-pancreas felt normal 01 20 18 07 Psychoneurosis The amylase and protease values were normal in all cases Fraction 1 obtained during the ten minutes before mccholyl was injected laboratory and clinical data and with the findings at operation and/or autopsy. In this connection, it is well to recall the large functional reserve of the pancreas. A minimal amount of healthy tissue can produce normal pancreatic juice. Furthermore, the nervous influence on pancreatic secretion must not be overlooked. An abnormal juice may indicate autonomic imbalance rather than parenchymal disease. 32 ·Pancreatic Function Test TABLE 2. LIPASE VALUES IN NONTANCREATIC DISEASE, USING TRIBUTYRIN AS A SUBSTRATE* FRACTIONS 0.1 N Butyric And 11 2 3 4 DIAGNOSIS AND REMARKS 13 10 13 15 16 14 16 13 13 12 14 17 12 th。如 11 15 17 19 10 12 17 15 16 18 17 14 13 11 151 15 16 16 24 Ca, of the stomach Stone in common bile duct P. felt normal Ca. of the storpach Arsphenaminc hepatitis Hepatitis Undiagnosed--unoperated Stones in gallbladdermp. felt normal Common bile duct obstruction by adhesions or enlarged glands-P. felt normal Anxiety neurosis Renal calculiautopsy Controlmunoperated Cholangitis Ca. of lung Stones in gallbladder cholecystectomy Stones in gallbladder--neighboring organs normal Cerebral thrombosis.munoperated Undiagnosed Regional ileitis Stones in common bile duct and gallbladder-P..normal Fistula between gallbladder and duodenuss Duodenal ulcer Unoperated-undiagnosed Unoperated Cicatricial stenosis common bile duct Undiagnosed 15 22 15 13 13 13 12 21 18 17 16 21 15 15 17 15 14 12 12 16 13 2 14 15 13 18 17 18 4 16 16 18 15 14 12 16 16 19 18 13 13 11 16 16 12 *Amylase and protease values were normal an all patients, Fraccion ) was obtained during ten minutes before mecholy, injection The estimation of pancreatic ferments in cyst or fistula fluids can assist the surgeon in determining the nature of an abdominal cyst and in the diagnosis of pancreatic fisculac. The results of the ferment determinations are expressed as follows: Amylase activity = mg. of glucose liberated from starch by 0.001 a. of pancreatic juice. Piotcase activity mg. of amino nitrogen liberated from casein by 1 cc. of pancreatic juice. Lipase activity the amount of 0.1 N. butyric acid libcratcd by 0.1 cc. of pancreatic juice.

·The Functional Reserve of the Pancreas 7 The accuracy of the test is affected by the unknown dilution with gastric, hepatic, and duodenal secretions and by the variable response of the pancreas in different people to the same stimulus. This is comparable with the behavior of the stomach after histamine injection. As will be seen, the pancreas, in common with the liver and other organs, has a large measure of functional reserve. Most of its parenchyma must be laid low before a discernible decrease in ferment concentration is demonstrable. However, in spite of these disturbing limitations, experience has shown that the procedure yields information which is of definite clinical value. For example, by demonstrating lessened ferment activity in the pancreatic juice, Andersen 32 showed that certain cases of celiac disease were actually due to pancreatic fibrosis. THE FUNCTIONAL RESERVE OF THE PANCREAS The following clinical reports demonstrate the remarkable functional accivity of a small remnant of the organ. Z. G., history number 512939, a woman of 45, was admitted in February, 1937, for attacks of unconsciousness and with a fasting blood sugar of 26 mg. per cent. The symptoms were prevented by food. Ac operation a subtotal pancreatectomy was done because an island-cell tumor could not be found. In the resected specimen, a small nodule in the tail of the pancreas proved to be an adenoma of the islands of Langerhans. Six months later, she was readmitted for increasing hunger. She had gained 30 pounds. The fasting blood sugar was 48; one month later it was 30. At the second operation, the remaining pancreatic tissue was smaller than expected; it measured 4 x 3 x 2 cm. When the duodenum was mobilized, a nodule was felt close to the papilla of Vater. It was removed. It proved to be another adenoma of the islands of Langerhans. During the 11 years that followed, she has had no further symptoms of hypoglycemia, and her fasting blood sugars have been normal. GLUCOSE TOLERANCE, TEST AFTER 100 GRABIS OF GLUCOSE Fasting 32 hr. 1 kr. 2 hr. 3 hr. 5 hr. 6 hr. March 1938 June 1940 95 90 167 133 142 127 70 76 84 166 178 With only a small remnant of the pancreas, this woman had no symp. toms of diabetes and an almost normal glucose tolerance test. Apparently ·6 Pancreatic Function Test TABLE 2. LIPASE VALUES IN NONPANCREATIC DISEASE, USING TRIBUTYRIN AS A SUBSTRATE FRACTIONS 0.1 N Butyric Acid 77 2 3 DIACNOSIS AND REMARKS 4 13 10 11 12 14 17 13 15 7 16 14 16 13 13 19 17 15 Ca. of the stomach Stone in common bile duct P. felt normal Ca, of the stomach Arsphenamine hepatitis Hepatitis 12 15 17 11-1. 10 12 14 19 16 17 16 18 17 14 24 15 15 16 15 13 11 11 13 13 13 12 14 15 14 12 12 16 13 2 14 16 17 21 18 17 16 25 14 15 13 18 15 15 17 22 15 16 16 18 15 14 12 16 16 19 18 13 Ihesions or enlarged glands-P. ſelt normal Anxiety neurosis Renal Calculi-autopsy Control -unoperated Cholangitis Ca. of lung Stones in gallbladder-cholecystectomy Stones in gallbladder-neighboring organs normal Cerebral thrombosis-unoperated Undiagnosed Regional ileitis Stones in common bile duct and gallbladder---P.=normal Fistula between gallbladder and duodenum Duodenal ulcer Unoperated-undiagnosed Unoperated Cicatricial stenosis common bile duct Undiagnosed 16 13 11 16 16 18 4 16 12 Amylase and prorcase values were normal in all patients. Fraction I was obtained during ten minutes before mecholyi injection The estimation of pancreatic ferments in cyst or fistula fluids can assist the surgeon in determining the nature of an abdominal cyst and in the diagnosis of pancreatic fistulae, The results of the ferment determinations are expressed as follows: Amylase activity mg, of glucose liberated from starch by 0.001 cc. of pancreatic juice. Protease activity mg. of amino nitrogen liberated from casein by I cc. of pancreatic juice. Lipase activity the amount of 0.1 N. butyric acid liberated by 0.1 cc. of pancreatic juice.

·to 90 Ferment Deficiency Without Morphologic Change stedt, 34 from his experience with dogs, thinks that removal of from 80 per cent of the pancreas causes no defect in carbohydrate metabolism or in the absorption of food stuffs. These facts suggest that in clinical cases, low ferment concentration in the pancreatic juice indicates extensive destruction of parenchyma. This is not always true, however. Greatly lowered function may be unassociated with morphologic change, nor does identical pancreatic pathology invariably produce the same functional disturbance. To quote Professor V.Kneeland Frantz,35 "In both benign and malignant tumors of islet-cells there are no histologic criteria by which we can distinguish those which are functional and those which are not. With an exceedingly small adenoma, a patient may be unconscious from hypoglycemia while with an even larger similar tumor in another case there may be no symptoms of hyperinsulinism." FERMENT DEFICIENCY WITHOUT MORPHOLOGIC CHANGE The following is an example of greatly lowered functional activity without morphologic change. M. M., a man of 48, history number 699889, complained of nausea, vague right upper quadrant and epigastric pain for two years and a weight loss of 30 lbs. Physical examination, glucose tolerance test, cholecystogram, roentgenogram of the stomach and intestine, were normal. The serum amylase was 33, and there was no acid in the stomach after histamine. The pancreatic function test was abnormal. PANCREATIC FUNCTION TEST Fraction 1 Fraction 2 Fraction 3 Fraction 4 Volume. pH.. Amylase Protease Lipase. 7 7.5 low low 3.0 25 7.5 low low 30 15 75 low low 30 8 75 low low 30 At operation, the surgeon thought that the pancreas was harder than normal and suggested cancer. A partial resection was done, but histological examination of the specimen was normal. He was followed for three years. He felt well and gained 20 pounds. Another somewhat similar case was P. L, history number 818088, an ·8 Pancreatic Function Test enough insulin was produced to meet the ordinary metabolic demands, What about the forment production by the alveolar cells? A pancreatic function test in December, 1946, gave the following results: FRACTION 1 Before Afecholl FRACTION 2 FRACTION 3 10 min. p. mech. 20 min.p.mech. FRACTION 4 30 min.p.mech. PH. Color Amylase. Protease.. Lipase.. Bile. 7.4 7.4 7.4 golden yellow brown-yellow brown-yellow 11.8 12.3 134. 141. 16.1 16.5 moderate amount large amount large amount 11.3 mg 113. ms. 15.5 cc. 7.4 golden yellow 8.4 71. 14.3 moderate amount The concentration of ferments in the pancreatic juice was normal. The following experience affords further evidence of the high funccional activity of a small remnant of pancreatic tissue. Mrs. H. S., history number 679309, aged 46, was explored for spells of unconsciousness associated with a blood sugar of 46 mg. per cent. No pancreatic tumor was found. Owing to technical difficulties, the contemplated pancreatectomy had to be abandoned. Symptoms of hyperinsulinism and low blood sugars persisted. At the sccond operation four years later, what appeared to be the entire pancreas was removed. The surgeon stated, however, that there was a possibility that a small tab of pancreatic tissue remained. The excised organ weighed 54 grams and was 15 cm. long. An islet-cell tumor was found in the substance of the gland. Soon after operation, blood sugars of 195, 192 and 176 were noted. During the following ten months, she had no symptoms. The blood sugar three hours after breakfast was 65 mg. per cent. One year after operation, the fasting blood sugar was 95 mg. per cent. The blood sugars one, two and three hours after 100 grams of glucose by mouth were 163, 192 and 86, respectively. Two years after operation, a pancreatic function test revealed the presence of all three ferments in the pancreatic juice. Unfortunately, only one alkalıne fraction was obtained, but this contained 2.1 amylase, 113 protease and 6.5 lipase. The fasting blood sugar now, two years after pancreatectomy, is 92 mg. per cent. In cystic fibrosis of the pancreas in infants, Andersen 32 observed that symptoms were absent unless 90 per cent of the organ was involved. In a dog, Coffey, Mann and Bollman33 found that a nodule weighing 1/40 of the normal gland maintained normal pancreatic function. Drag- ·Nonpancreatic Disease 11 The wide range of values results from unavoidable sources of error previously mentioned, namely, the variable individual response to mecholyl and the unknown dilution by other secretions. In the circumstances, the highest fractional value indicates the best functional activity. Ninety-two per cent of the amylase values were above 4 mg. of reducing sugar; per cent of the protease values were above 50 mg. of nonprotein nitrogen, and 96 per cent of the lipase values were above 8 cc. of 0.1 normal acid. 96 TABLE 3. THE FERMENT CONCENTRATION OF THE PANCREATIC JUICE IN NONPANCREATIC DISEASE PROTEASE Mg, nonprol. N. LIPASE cc.n/10 acid AMYLASE Mg, reducing sugar Fractions 1 2 3 4 DIAGNOSIS Fractions 2 3 Fractions 1 2 3 4 1 4 6 6 7 2 177 181 255 100 16 17 22 16 Stones gallbladder-Unoperated 2 6 2 5 15 18 16 18 Stone in gallbladder-Operated 6 9 8 108 180 168 15 17 15 Unoperated 4 10 6 8 67 146 199 177 14 17 18 17 Stones gallbladder and common bile duct-P.= normal 5 6 12 6 116 147 304 147 17 17 20 18 Unoperated 4 8 9 8 59 214 106 59 12 15 13 12 Lymphosarcomatous cervical gland 3 8 9 4 39 127 148 165 8 14 7 14 Unoperated 3 7 6 4 35 182 106 98 11 16 15 15 Unoperated-probably gallstones 10 11 19 13 134 176 252 185 15 17 18 18 Unoperated 2 11 10 11 8 17 15 16 Cicatricial stenosis common bile duct 6 14 2 3 14 16 13 12 Unoperated 18 11 10 15 13 13 Exploration P.-normal Cholangiolitis 6 9 7 11 101 182 120 95 14 14 15 12 Unoperated 10 14 17 108 158 181 15 16 16 Unoperated 4 10 11 6 60 181 146 42 13 15 13 13 Unoperated 18 18 17 189 155 56 15 13 12 Unoperated 6 15 7 15 15 16 Hepatitis 10 13 13 13 77 95 389 81 13 14 14 12 Retroperitoneal tumor 14 12 12 231 199 221 16 16 18 Unoperated 3 10 16 216 193 195 14 16 14 15 Unoperated 4 98 137 300 168 14 16 16 Unoperated 4 18 13 8 274 236 509 584 14 15 14 17 Unoperated 7 14 15 14 35 35 405 519 8 17 17 13 Unoperated-nervous diarrhea 2 4 9 61 165 314 4 15 16 Stone in common bile duct 4 5 11 6 89 90 109 118 11 11 13 13 Ca transverse colon 8 13 17 16 143 194 146 152 12 13 12 11 Unoperated-melancholia 6 6 7 7 285 238 350 315 11 12 11 11 Unoperated-hepatitis ·10 Pancreatic Function Test unmarried girl of 31 with a typical history of gallbladder disease but with a normal rocntgenogram of the gallbladder and gastro-intestinal tract except for moderate pylorospasm. Serum amylase was normal. PANCREATIC FUNCTION TEST-MAY 17, 1946 Fraction 1 Fraction 2 Fraction 3 Fraction 4 28 7.1 Volume... pH... Amylase. Proteasc. Lipase 44 7.0 1.0 11.0 20 80 7.1 13.0 420 30 56 7.1 10.0 20.0 2.0 140 2.0 PANCREATIC FUNCTION Test ---July 5, 1946 Fraction 1 Fraction 2 Fraction 3 Fraction 4 Volume. PH... Amylase. Protease. Lipase.. 38.0 7.3 30 29.0 4.0 26.0 7.3 15.0 20.0 4.0 24.0 7.3 15.0 238.0 6.0 25.0 7.3 150 2180 6.0 On 6/4/46, the seriim amylase was 36 (minimal normal values: amylase 4, protease 50, lipase 8). No abnormalities were found at exploratory laparotomy. Both of these patients suggested a psychosomatic disorder. Was there an abnormal vagus influence? FERMENT CONCENTRATION OF PANCREATIC JUICE NONPANCREATIC DISEASE Volume. See Table 4. The volume of each of the four alkaline ten-minute fractions was determined in 169 nonpancreatic patients. It varied widely both before and after mecholyl injection, yet in 82 per cent it was below 30 cc. The mean and median values were higher in the second and third fractions than in the others. The mean for all fractions was 18.6 cc. Comfort and Osterbergo determined the ten-minute volume after mecholyl in eight normal subjects. It averaged 13.6 cc. Reaction. The pH of the pancreatic juice after mecholyl was between 7 and 8. Acid fractions were discarded. Ferment Concentration. The ferment concentrations in nonpancreatic diseases are tabulated and charted. (See Table 3, Figs. 4-6.)

·13 Nonpancreatic Disease TABLE 3 (Continued). THE FERMENT CONCENTRATION OF THE PANCREATIC JUICE IN NONPANCREATIC DISEASE PROTEASE Afg. nonprot. N. LIPASE cc. n/10 acid AMYLASE Mg. reducing sugar Fractions 1 2 3 4 DIAGNOSIS Fractions Fractions 1 2 3 4 1 2 3 4 6 15 14 7 89 155 45 59 10 16 8 6 Unoperated 3 13 11 21 64 239 342 104 16 25 26 18 Chronic enteritis 8 6 4 321 212 176 16 16 14 Unoperated 6 8 7 7 221 336 239 277 15 19 16 17 Unoperated 16 18 15 319 373 248 18 20 17 Unoperated 11 11 11 11 114 97 110 80 14 14 14 14 Stone common bile duct- P.=normal 6 5 5 47 92 84 10 30 9 Unoperated 11 12.12 8 112 134 141 71 15 16 17 14 Hyperinsulinism, partial pancreatectomy 15 15 7 160 136 16 17 18 3 Unoperated 4 6 10 10 70 108 203 269 17 17 20 20 Enteritis, sprue 3 9 6 4 47 134 114 63 8 15 10 9 Hepatitis 6 11 9 7 193 279 238 224 12 24 17 10 Stones in gallbladder cholecystostomy 4 14 14 9 67 276 281 154 4 17 16 14 Stone common bile duct-P. felt normal 12 12 12 12 7 122 108 1 11 13 Unoperated 5 15 10 9 53 91 63 61 9 12 13 13 Cicatricial stenosis common bile duct 6 11 10 91 308 101 15 18 15 Stones in gallbladder and common bile duct 3 12 9 10 13 15 14 14 Stones in common bile duct 7 10 9 16 12 18 18 17 Retroperitoneal sarcoma 14 14 14 14 110 378 188 9 21 18 Hepatitis 12 12 12 12 288 383 278 17 16 16 15 Diarrhea 5 58 265 15 18 Cirrhosis 9 8 14 8 126 147 196 107 16 17 18 17 Unoperated 7 7 6 37 266 272 182 7 19 19 18 Diarrhea 7 10 10 10 101 237 242 199 14 18 17 16 Hepatitis 1 6 6 45 105 109 12 16 14 Psychoneurosis 6 16 14 9 141 287 273 192 9 14 12 11 Unoperated 18 19 19 19 147 271 293 208 21 18 18 17 Unoperated 5 6 6 6 60 103 94 90 6 9 9 8 Stones in gallbladder 10 10 10 10 157 226 152 15 18 18 Stones in gallbladder and common bile duct 3 11 5 3 62 191 104 67 11 15 12 11 Duodenal ulcer 2 2 6 6 62 63 99 151 12 11 13 16 Anorexia nervosa 7 ·12 Pancreatic Function Test TABLE 3 (Continued). THE FERMENT CONCENTRATION OF THE PANCREATIC JUICE IN NONPANCREATIC DISEASE PROTEASE Alg. nonprot. N. LIPASE 66. n/10 acid AMYLASE Mg. reducing sugar Fractions 1 2 3 4 DIAGNOSIS Fractions 2 3 Fractions 1 2 3 4 4 ܝܝ 9 2 3 16 16 15 33 116 116 1 2 17 19 Ca. adrenal 2 14 14 14 50 426 186 267 7 17 13 13 Unoperated-stones in gallbladder 7 8 10 10 132 353 482 454 10 12 10 11 Stones in common bile duct 2 6 6 6 88 287 343 301 8 14 14 13 Unoperated 3 16 16 16 15 279 458 388 6 8 15 15 Unoperated 9 18 16 8 168 197 320 283 10 10 10 10 Unoperated 12 15 14 236 227 233 15 14 14 Hepatitis 12 21 15 11 120 195 173 122 9 13 12 10 Diverticulum esophagus 11 15 20 24 20 56 86 133 3 9 12 14 Unoperated 10 12 14 14 79 243 105 151 12 16 14 15 Stone in common bile duct 4 4 9 4 28 148 91 72 2 10 56 Cirrhosis, Laennec 14 14 14 14 203 272 235 291 14 15 14 15 Ca, of stomach 6 9 7 96 165 87 6 15 12 Ca liver 3 10 8 4 69 214 207 53 7 17 12 8 Unoperated 1 6 6 4 16 130 134 87 10 14 15 11 Unoperated 2 6 5 50 300 14 50 5 15 4 1 Unoperated 8 13 13 15 138 210 215 219 11 14 14 14 Glomerulonephritis 5 14 13 15 28 171 156 126 5 13 14 13 Ca, stomach 4 12 11 6 87 132 164 101 7 10 12 10 Unoperated 1 4 5 3 34 115 146 141 5 11 12 11 Cirrhosis liver 9 84 79 11 11 Stones gallbladder and common bile duct-P.=normal 2 7 9 84 19 176 13 5 15 Unoperated 3 7 4 43 91 92 10 13 11 Unoperated 1 9 4 78 155 101 63 8 9 10 9 Biliary cirrhosis-operated 13 7 202 137 15 13 Unoperated 14 17 21 77 213 127 9 11 10 Unoperated 15 15 7 160 136 17 18 3 Unoperated 10 16 216 193 195 14 15 14 15 Unoperated 18 18 17 189 155 50 15 13 12 Unoperated 6 5 10 13 53 115 84 149 8 9 8 9 Anxiety neurosis 3 8 3 60 54 151 48 6 13 11 Stones in gallbladder-P. felt normal 4 14 14 14 309 18094 1 13 9 9 Unoperated 2 12 12 12 53 203 210 172 7 16 16 15 Unoperated 15 8 12 8 160 113 102 112 17 15 15 14 Unoperated 5 15 10 9 53 91 63 61 9 12 13 13 Stricture common bile duct-. cicatricial 2 7 8 8 102 176 155 83 15 11 14 14 Hepatitis 5 5 5 5 67 34 80 131 13 11 14 10 Unoperated 6 9 7 5 157 67 103 133 16 11 11 14 Cicatricial stricture common bile duct 6 9 6 7 85 130 99 123 15 15 14 15 Cirrhosis, Laennec ·Acute Pancreatitis 15 No. of fractions 220 210 200 190 180 170 160 150 140 130 120 110 100 90 BO 70 60 50 30 20 10 0 Volume cc. 10 20 30 40 50 60 70 FIG. 3. Frequency distribution of the volumes of 10-minute fractions of pancreatic juice before and after mecholyl injection in nonpancreatic disease. No. of patients 17 16 15 14 13 12 II 10 9 8 1 12 14 Mg reducing sugar 2 4 6 8 16 is zo za Fic. 4. Frequency distribution of amylase concentration in the pancreatic juice in nonpancreatic disease during 10 minutes after mecholyl injection.

·14 Pancreatic Function Test TABLE 4. THE RANGE, MEAN AND MEDIAN VALUES OF THE VOLUMES OF THE FOUR FRACTIONS OF PANCREATIC JUICE IN 169 NONPANCREATIC PATIENTS FRACTION RANCE CC. MEAN VALUE CC. MEDIAN VALUE cc. 1 2 3 4 1-66 1-104 2-58 1-65 17.4 20.8 20.0 16.0 474.2 18.5 15.7 18.5 16 2 13.0 4)63.4 15.2 TABLE 5. FERMENT CONCENTRATIONS IN NONPANCREATIC DISEASE RANCE MEAN MEDIAN 6 10.4 10.7 4.8 10. 10.3 9.2 9.3 Amylase Fraction 1 mg. sugar. 1-18 2... 2-21 2-21 4... 3-21 Protease Fraction 1 mg, nonprot. N........ 7-285 2. 34-426 3. 14-509 4..... 16-584 Lipase Fraction 1 cc. n/10 acid., 1-21 2 2-25 3 4-30 4... 3-20 92 188 183 156 86 182 161 136 10.8 14.8 14.2 13.2 10.7 14. 13 4 12.8 ACUTE PANCREATITIS During the height of an attack of acute pancreatitis it is obviously undesirable to add the discomfort of the pancreatic function test to the suffering of the patient. Lagerloef's experience in acute pancreatitis using secretin stimulation points to a rapid return of normal function after subsidence of the acute phase of the disease (see Table 6). Regeneration after an acute attack may be rapid and complete. In several patients that were explored for acute pancreatitis, the pancreas was enlarged and nodular, but at a subsequent operation, no abnormality was found.

·Acute Pancreatitis 17 had diabetes. The third attack occurred in July, 1946. He then had epigastric pain and spasm, a serum amylase of 237, and a white count of 17,000. No. of patients 33 32 31 30 29 - 28 27 — 26 — 25 — 24 23 22 21 - 20- 19 18 17 16- 15 13- 1. 1 12. 1 Cc. N/Io ocide is lo Éz za 26 FIG. 6. Frequency distribution of lipase concentration in the pancreatic juice in nonpancreatic disease during 10 minutes after mecholyl injection ·16 Pancreatic Function Test In recurrent pancreatitis, enough parenchyma may have been destroyed prior to the last attack to permanently lower function, In acute pancreatitis, the scrum amylase and lipase values are of greater Clinical importance than any other laboratory test. The effect of repeated acute inflammation is seen in the case of J. T., history number 707520, a man of 53. On April 21, 1943, he had sudden epigastric pain, nausca, vomiting, tenderness in the epigastrium, a white No.of potients 23 22 21 20- 19 17 16 ! 50 100 150 200 250 300 350 400 450 M9, nongrot N. FIG $. Frequency distribution of protease concentration in the pancreatic juice in nonpancreatic disease during 10 minutes after mecholyl injection. blood count of 22,000 and a serum amylase of 244, this is, eight times the normal value. His serum phosphatase was 4, and serum bilirubin only a trace. The cholecystogram showed stones. A cholecystectomy was done. Numerous areas of fat necrosis were seen. The head of the pancreas was indurated. In December, 1943, there was a recurrence of upper abdominal pain, a white count of 18,000 a serum amylase of 288, serum phosphatase of 6.7, and a serum bilirubin of 1.4. He nos ·Chronic Pancreatitis 19 The established predisposing causes of acute pancreatitis are gallstones or biliary tract disease and alchohol indulgence. The ease with which radio-opaque material enters the pancreatic ducts when it is in. jected into the common bile duct suggests the possibility that bile reflux may also be a cause of acute pancreatitis, especially when there is spasm of the sphincter of Oddi.se. 37.86 CHRONIC PANCREATITIS The results of the pancreatic function test in chronic pancreatitis are listed in Table 7. While the average volume of the fractions was elevated, their pH was within normal limits. The concentration of ferments is proportional to the degree of destruction of acinar tissue. Fifteen of the 20 cases (75 per cent) had a diminished ferment concentration. In a series reported by H. Lagerloef& after secretin stimulation, 21 of 28 patients had low ferment values. With the same stimulant, Comfort, Gambill, and Bagenstoss reported low values in all of 8 patients with chronic pancreatitis. The combined evidence from three sources indicates that extensive destruction of acinar cells is common in this disease. It is noteworthy that the juice remains alkaline even in advanced pancreatic disease and that the concentration of each of the three ferments is not uniformly diminished. This irregularity is frequently encountered in pancreatic disease. Chronic pancreatitis, secondary to obstruction of the duct system by carcinoma of the head of the pancreas, is partly responsible for the diminished function in the latter condition. The known contributory causes of chronic pancreatitis are similar to those of acute pancreatitis, namely, gallstones and alcoholism. Of 29 cases of chronic relapsing pancreatitis recently reported, 68 per cent used alcohol, and 33 per cent were heavy imbibers. The calcification so frequently seen in long-standing cases may be a secondary deposition or actual pancreaticolithiasis.39 About one half of the cases in the present series had calcification. In this condition, the roentgenogram shows clusters of opacities within the confines of the pancreas. This may well be the first intimation of the disease. The components of these pancreatic calculi are calcium and carbonic acid. Normal pancreatic juice contains 138 milli-equivalents of sodium, from 2.2 to 3.2 milli-equivalents of calcium, from 60 to 80 of chlorine, and from 60 to 75 of bicarbonate. 10 It is conceivable that stone formation ·18 Pancreatic Function Test TABLE 6. PANCREATIC FUNCTION TESTS IN ACUTE PANCREATITIS, USING SECRETIN (H. Lagerloef*) DAYS CASE AFTER No. ONSET BLOOD AMYLASE Vol. Sod. BICARB. AMYLASE PROTEASE LIPASE CC, c. 0,1 normal units units units 69 70 218 151 42 13 29 10 201 71 226 299 189 196 8.7 9.7 .222 54 48 63 356 727 374 348 847 125 72 9.3 7.7 357 194 264 183 123 227 122 98 276 234 34 37 45 first attack 74 24 0 5 9 15 37 2 10 19 4 6 13 20 37 0 5 61 15 6 42 0 7 13 4.4 7.1 39 second attack 262 265 244 252 939 628 115 91 2362 75 17.0 835 265 278 70 73 77 78 81 261 257 254 238 129 107 340 537 597 131 342 168 149 79 30 282 196 165 117 187 342 65 56 1300 Normal Values 2-4 202 180 634 87 179 Tancreatic Function and Pancreatic Disease, New York, Macmillan, The first pancreatic function test taken on Oct. 19, 1943, was normal One of the fractions of the pancreatic juice had a pH of 7.6 and normal concentrations of the three ferments. After the third attack (July 24, 1946), the juice was low in lipase. The pancreatic function test done at that time was as follows: Fraction 2 3 4 Volume cc PH... Amylase Protease. Lipase*.. 7 75 3 35 3 5 7.5 4 74 4 10 7.5 4 64 3 2 7.5 4 46 4 Minimal normal 8 cc ·Chronic Pancreatitis 21 Case II. A colored woman of 25 had from ten to fifteen bowel movements a day and crampy abdominal pains for four months. The stools were large, light yellow, fatty, and at times contained blood. The patient had indulged freely in alcohol. The weight loss was 16 pounds in six months. Physical examination was negative except for generalized tenderness over the abdomen. A roentgenogram showed alcification in the region of the pancreas. The serum amylase was normal. The glucose tolerance test indicated latent diabetes. The pancreatic juice after mecholyl stimulation was alkaline but contained only traces of ferments, PANCREATIC FUNCTION TEST 2 3 Fraction 4 PH. Volume co.. Amylase, Protease, Lipase... 7.5 15. 0.8 low 7.6 12. 2.8 low 7.7 9. 1. low very low very low very low The pancreas was completely removed; it was hard and nodular and contained numerous calculi, some of which blocked the duct. The stones were pure white and on analysis were found to be almost pure calcium carbonate. Microscopically, the organ showed complete replacement of parenchyma by fibrous tissue. After the pancreatectomy, 75 per cent of ingested fat was absorbed; this was increased to 81 per cent when five panteric pills were taken with each meal. The diabetes was controlled on a diet of 300 grams of carbohydrate, 70 of protein, and 75 of fat, by 60 units of globin insulin. Later, the insulin was reduced to 30 units without glycosuria and with blood sugars of 194 and 112. Repeated attacks of acute inflammation may eventually destroy sufficient acinar tissue to lower the ferment concentration in the pancreatic juice. Case III. A man, aged 54, had severe epigastric pain and vomiting in June, 1944. His abdomen was boardlike and exquisitely tender in the epigastrium. White blood count was 28,000. Serum amylase was markedly elevated. Fever and symptoms persisted, and a mass developed in the upper abdomen. Drainage liberated 1,000 cc. of purulent fluid containing flecks of necrotic fat. He recovered and was discharged in September, 1944.

·20 Pancreatic Function Test in the duct is primary in certain patients. Nothmann'l has recently found a considerable phosphatase content in the pancreatic juice of dogs, and a rise in serum phosphatase after ligation of the pancreatic duct. The average phosphatase of the serum of dogs (Bodansky units) is 2 before and 13.8 from four to ten days after the operation. He also observed an clevated serum phosphatase in to patients with steatorrhea and other evidence of chronic pancreatitis. The presenting symptom of chronic pancreatitis may be epigastric pain, persistent or intermittent diarrhea, large fatty stools, weight loss, or jaundice. As the islands of Langerhans resist the inflammatory process Jonger than the acini, diabetes is usually a late symptom and is indicative of widespread destruction. The following cases are illustrative. Case 1. The first symptom of this woman of 46 was bulky stools, and this was followed by epigastric pain. The roentgenogram showed calcified areas in the pancreas. Exploratory operation at another hospital revealed the presence of sacs of sand in the pancreas. The pancreatic secretion was almost devoid of ferments. PANCREATIC FUNCTION TEST Fraction 10 min. 20 min 30 min. p. mecholy! 22 17 7.2 6.7 Volume cc... PH.... Amylase. . Protease. Lipase. 16 7.9 0.1 low low low very law very low Very low The serum amylase of 32 was high, considering the minimal amylase values in the pancreatic juice. The lipase was inadequate for normal fat digestion. Of 103 grams of fat consumed in a three-day period, 64 grams were recovered in the stoo). A complete pancreatectomy was done. The pancreas measured 16 cm. by 4.5 cm. On section, the ducts were blocked by white calcareous material resembling coral. The dilated duct of Wirsung was surrounded by dense connectire tissue. Cross section showed a number of small, round openings surrounded by dense fibrous tissue. Asícroscopically, no normal tissue was seen. The calculus contained 38.2 per cent of calcium. The theoretical amount for calcium carbonate is 40 per cent. The pathologist concluded that the fibrosis was secondary to the duct occlusion.

·Chronic Pancreatitis 23 - In spite of the many episodes of inflammation and objective evidence of pancreatitis, the pancreatic function test was normal indicating regression or regeneration. Roentgenogram of the upper abdomen at this time showed no calcification. At the last operation, in January, 1947, the main body of the pancreas was soft and normal. The terminal 3 or 4 cm. of the tail felt lumpy and was resected. It showed fibrosis microscopically. The diagnostic value of the pancreatic function test is well illustrated in cases V and VI. Case V. A man of 50 had six weeks of epigastric pain unrelieved by food. The pain was also felt in the back and in both upper quadrants. Aside from a blood pressure of 280/180, physical examination and roentgen examination of the gastro-intestinal tract, including the colon, were negative. Serum phosphatase and bilirubin were normal. The electrocardiogram showed myocardial damage. The glucose tolerance test indicated mild diabetes. The amylase concentration was below the normal minimal value of 4. PANCREATIC FUNCTION TEST Fractions 1 2 3 4 Volume cc. PH.. Amylase Protease Lipase 15 7.2 0.7 60.0 80 9 70 20 22.0 13.0 20 7.3 20 130 12.0 40 6.8 2.0 21.0 90 At exploration, the surgeon felt only questionable thickening of the head of the pancreas. The pain continued after operation. The patient died one month later of cerebral hemorrhage. At autopsy, the body and tail of the pancreas were unusually firm, and the head appeared to be a fibrotic collar about the duct of Wirsung, averaging about 4 mm. in thickness. About 2 cm. distal to the duodenum, all that remained was a cystic mass about 1.5 cm. in diameter. Its walls were hemorrhagic, and it was filled with chalky, cheesy material. Small areas of fat necrosis were seen in the serosal fat over the pancreas. Death was due to hemorrhage involving the right caudate nucleus, internal capsule and putamen. The difficulty of diagnosing disease of the pancreas by surgical exploration is repeatedly mentioned in the literature.

·22 Pancreatic Function Test In January, 1945, he suffered an attack of right upper quadrant pain with localized tenderness and spasm. An enlarged gallbladder with stones was removed. In November, 1946, he had another attack of acute pain associated with a mass in the upper abdomen. A pancreatic cyst was drained. The fuid mcasured 750 cc. and contained the three pancreatic ferments. During convalescence, a pancreatic function test gave the following results: Fraction 7 2 3 4 7.0 PH.. Amylase Protease. Lipase. Volume. 8.5 2.9 21.0 8.0 35 7.1 2.3 81.0 80 24 37,0 6.0 24 7.0 0.3 7.0 60 21 COMMENT. Minimal normal values-amylase 4, protease 50, lipase 8. The recuperative power of the pancreas is illustrated in another case. Case IV. M. G., aged 38, was first scen in February, 1938. He had had moderate epigastric distress for several years which had recently increased. White blood count was 22,000. During the next month he had fever and jaundice. Serum bilirubin was 5.3 and serum amylase 73 (normal 30). At operation, the gallbladder and common bile duct contained stones: The head of the pancreas was enlarged and firm. Though cholecystectomy and choledochotomy were done, episodes of a similar nature recurred. In November, 1940, he was re-explored. At this time there were no stones in the common duct, but the head of the pancreas was hard, and the lower end of the common duct was narrowed. In January, 1942, a division of this stricture of the papilla was donc. After several lesser attacks, a severe, acute seizure occurred in November, 1946. PANCREATIC FUNCTION TEST 2 Fraction 1 3 4 Acid Alkaline Reaction.. Amylase, Protease. Lipase. Alkaline 11 223 233 17 Alkalinc 11 81 14 ·+ - 8 1. + ac 7.9 7.8 7.1 + 18 21 6 1 + + 6. 7.0 7.8 7.0 1. 1. qns 1. qns. 15 4 1 8 08 2.8 1. 0 7.5 76 7.7 0 0 15 1 12 9 Ac 7.2 7.9 6.7 0 Ac. 16.5 16 22 0 0.1 0.1 1. 1. 1. 07 20 20 2.2 60 22 7.2 7.3 7.3 68 13 16 21 20 40 9 07 01 03 15 10 7 21 3.2 73 73 7.3 75 7 1.4 13 41 7 6 65 48 98 5 25 25 79 54 7.5 7.5 75 7.5 8 3 81 79 84 0.7 2007 + + + 6 19 + + 2 + 3.5 13 10 Calcification and cyst formation. Normal P. F.T. 7 7 3 Fibrosis and calcification-later diabetes 0.4 0.5 0.5 Stones in P. duct, fibrosis and cystic degeneration. Complete pancreatectomy 0.9 1.4 2.1 Calcification. Fat absorption ca. 38% 8.7 12.8 12.3 9.4 Diab. G.T.T. Autopsy. Fibrosis and cyst formation 2.3 1.4 23 1.7 (Calcification and cyst formation. Diabetes- 56 1.4 2.0 3.5 S A. 81 20 20 2.0 10 Relapsing Pctis. 3 operations. False cyst. P. hard & thick. Diab. G. T.T. 05 05 0.6 06 Calcification. Partial pancreatectomy 6.0 12. 5.0 13 Calcified P. Cyst of body of P. Autopsy – Chr. Pctis with some normal tissue in head of P. 06 4.2 2.5 Calcification. Alcoholic 14 12 12 13 Gallstones. P. large and firm. Stones in ampulla C.B.D. 1. 0.95 1. 1. Unoperated. Had acute attack followed by calcification of P. 30 4.8 5.9 39 8.9 30 3 5 ac. 7.0 7.0 62 03 0.4 1.1 0.4 32 11.6 15 6 126 36 100 4 30 70 7.0 7.4 72 24 28 46 117 c. 68 16 10 36 59 35 65 75 7.5 7.0 10.3 17 18 7.5 7.5 7 5 70 10.7 10.7 10 7 10.7 75 7. 35 72 43 32 36 11 47 13 75 7.3 7.1 7.1 13 .03 13 5 6 11 10 ( 25 ) ·TABLE 7. PANCREATIC JUICE IN OPERATED CASES OF CHRONIC PANCREATITIS [ 24 ] PH VOLUME CC. Fractions 2 3 Fractions 1 2 3 4 AMYLASE CONCENTRATION Fractions 2 3 4 PROTEASE CONCENTRATION Fractions 7 2 3 LIPASE CONCENTRATION Fractions 1 2 3 DIAGNOSIS AND REMARKS 7 40 33 8 5 6.8 8. 8. 8. low + + + + 36 26 10 7. 8. 8. + 40 36 56 53 72 7.5 73 ac. 0 0 0 0 0 3 a 40 26 25 15 7.5 7.5 7.5 7.5 0 0 0 0 0 0 0 0 0.7 3 1.6 0 Stones in G.B. and c. B.D. Biopsy showed 0.4 05 0.5 patchy thickening in the head of P. Low lipasc. Chr. Pctis. 2. 10. 4 Resection hd. and body of P. which showed cal. cifcation 21 28 22 21 Diab. G.T.T.--SA. 49. Pancreaticoduodenec. ectomy. P. duct contained numerous cal. culi, Extensive fibrosis of P. 2 10 Nodular body and tail P. histol.--fibrosis 0.8 06 0.7 5.5 J.--diab --Palpable G. B. 6. 11. 4. 0 J.--S.A. 70. At opera: tion P. large and hard 5 3 0.2 0,3 Stones in G.B. Hd. P. thickened. Diab. G.T.T. Normal P.F.T. Obstructive J. S. A, 237. Numerous hard areas in P. 34 34 44 36 7.5 7.5 7.5 7.5 0 + + + 0 0 0 0 N 5.5 14.5 69 7.5 75 75 ac © o 1. 1. 1. 11 15 7 1 75 75 7.5 7.5 1. 1, 1. 0 0 0 0 0 26 41 30 4 ac. 7.5 7.5 7.5 1. + + + I. 1. 1. + ·Carcinoma of the Pancreas 27 common bile duct reported by Walter 13 were due to chronic pancreatitis, yet recently Peterson and Cole14 described three and Bisgard15 ho such cases in which the common bile duct was stenosed by inflammatory tissue in the pancreas. CANCER OF THE PANCREAS Surgical exploration does not always furnish the exact diagnosis in suspected cases of carcinoma of the pancreas. The value of a diag. nostic exploration depends largely on the experience of the surgeon. Palpation of the organ may be misleading because the normal pancreas varies in size and consistency. As we shall see, even a biopsy may be deceptive; because of the danger involved, it is at best a questionable procedure. The operator may be unable to distinguish between a primary tumor of the head of the pancreas and one that arises in the duodenum or ampulla and invades the adjoining organ. If metastases are obvious, the surgeon may decide to close the abdomen without further investigation, or if the growth is extensive, it may be impossible to determine its primary site. In the 22 cases of verified carcinoma of the head of the pancreas, the pancreatic juice was abnormal in 20 (90 per cent). (See Table 8.) In exceptional cases, the pancreatic juice may be normal when the organ is extensively diseased, if a modicum of uninvolved tissue remains. This may be the case in tumors arising in the body and extending to the right. A tumor of the lower part of the head may gTow downward without involving either duct. Eusterman and Wilbur46 speak of 11 cases of carcinoma of the head without jaundice. An interesting and instructive discussion of the clinical and laboratory features of carcinoma of the pancreas is given by Pratt.47 Patient P. R., aged 58, had upper abdominal pain, jaundice, an enlarged liver, moderate anemia and clay-colored stools. The pancreatic function test was normal. The first two fractions were acid. PANCREATIC FUNCTION TEST Fractions 3 4 6 7.5 Volume cc. pH. Amylase Protease.. Lipase cc. 0.1 N acid.. 11 7.5 Normal High 12.0 Normal High 10.0 ·26 Pancreatic Function Test Case VI was a woman of 50 who was admitted in Feb., 1944, For 2 months she had complained of pain in the right gluteal region, right lower and upper quadrants with vomiting and fever. Elevation of the right diaphragm and a pushing down of the right kidney by a mass was noted. Tenderness was maximum in the upper midabdomen. White blood count was 15,000, with 64 per cent polynuclear cells. The serum amylase was normal. Rocntgen cxamination of the gastro-intestinal tract showed that the antrum and pylorus were displaced upward, and that there was a widening of the duodenal loop suggesting a mass in the head of the pancreas. Blood chemistry was normal. The diagnosis ' of acute pancreatitis with abscess or pancrcatic cyst was favored. The pancreatic function test was normal. PANCREATIC FUNCTION TEST 2 Fractions 1 3 4 Volumes cc... 10 18 15 9 H 8.1 7.9 8.0 8.3 Amylase. 7.0 100 9.0 17.0 Protease Normal Normal Normal Normal Lipase.. 12.0 18.0 18.0 17.0 Minimal normal values-amylase 4, protease 50, and lipase 8. At operation, the pancreas was pushed forward by a mass the size of a grapefruit which was attached to the posterior abdominal wall. Biopsy revealed lymphosarcoma. Complete destruction of the pancreas by fibrosis and calcification may occur without pain. Pasternakreports the case of a man of 57 with intractable diarrhea, emaciation, diabetes, and calcification without pain, demonstrated by roentgenogram. At autopsy, the gallbladder was distended with white bile, but the bile ducts were normal and patent. The pancreas weighed about five times the normal, due to stones and sand. Many cysts were present. His second case was a man of 46 with active pulmonary tuberculosis and diabetes. He had no abdominal symptoms or diarrhea. Postmortem showed bilateral tuberculosis of the lungs and a pancreas weighing 180 grams, that is, more than livice the normal. The latter was hard and gritty. The ducts were filled with calculi. Histologic examination showed extensive fibrosis and cyst formation. Jaundice due to stenosis of the common bile duct by chronic pancreatitis is a rare condition. None of the eighty cases of stenosis of the ·Carcinoma of the Pancreas 29 PANCREATIC FUNCTION TEST 2 3 Fractions 1 4 Normal Minimum 14 7.0 Volume cc. PH. Amylase. Protease. Lipase.. 10 7.0 0.03 28.0 6.0 20 7.0 1.2 36.0 7.0 001 290 7.0 11 7.0 0.7 34.0 7.0 4.0 50.0 8.0 glandular by fibrous tissue. There was no evidence of carcinoma. She was readmitted in April, 1946, for continuous epigastric pain and tenderness. The serum phosphatase was 14, serum bilirubin negative, cholesterol 199, and serum amylase 32. Exploration revealed metastases in the omentum and elsewhere and a large amount of fluid in the peritoneal cavity. At autopsy, the head of the pancreas was the seat of - an undifferentiated carcinoma which had spread to the regional lymph nodes, liver and peritoneum. Bile and pancreatic ducts were obstructed. The body and tail of the pancreas showed atrophy and mild chronic inflammatory changes In the next patient, carcinoma may have been superimposed on chronic pancreatitis. R. S., aged 50, complained of fullness after meals, Roentgen examination of the gastro-intestinal tract was negative. The gallbladder showed poor concentration. At exploration in another city in the latter part of 1942, the gallbladder was thickened, and the head of the pancreas was enlarged and edematous but not hard. The gallbladder was anastomosed to the duodenum in the assumption that the patient had a chronic pancreatitis. He entered the Presbyterian Hospital two and a half years later. He had no jaundice and a normal serum phosphatase. The pancreatic function test was normal. PANCREATIC FUNCTION TEST 2 Fraction 1 3 4 Volume PH.. Amylase Protease. Lipase... 6 82 100 770 130 6 85 130 950 14 0 4.5 86 13.0 389 0 140 30 82 130 81 0 12.0 Attacks of upper abdominal pain, mild fever and leukocytosis persisted. In February, 1946, he had a diabetic glucose tolerance test. Stools contained large amounts of neutral fat. He reentered the Presby- ·28 Pancreatic Function Test A partial pancreatectony was done. The growth in the head involved the common bile duct but not the pancreatic duct. Here, as cisewhere, the unusual location or spread of a cancer may increase the difficulty of diagnosis. There is a possibility that carcinoma may arise in a chronically inflamed or fibrotic pancreas, as it does in a cirrhotic liver. For cxample, H. K. was admitted in May, 1945, for nine years of periodic midabdominal colicky pain increasing in severity and radiating to the left upper quadrant and back. The pancreatic juice was low in amylase only. In August, 1945, the pain had extended to the lower abdomen, low back, and right upper quadrant. There was tenderness in the epigastrium. At operation, the body and tail were infiltrated by cancer, as well as the posterior abdominal wall. A metastatic mass in the omentum showed carcinoma. Brocq and Miginiac+8 refer to a case of carcinoma of the head, secondary to severe chronic pancreatitis. Presumably the fibrosis had destroyed the islets and produced diabetes before the development of the cancer. These authors maintain that the differentiation of carcinoma of the head from chronic pancreatitis is at times impossible, despite biopsy and other diagnostic procedures. This conclusion is supported by experience in this and other institutions. The fibrosis commonly associated with carcinoma of the head of the pancreas may completely conceal the growth and thus deceive the surgeon. The diagnosis of cancer may be well established on clinical and laboratory grounds. At exploration, the entire organ is uniformly hard, and the frozen section shows only fibrosis. A short-circuiting operation relieves the jaundice, and the patient may regain full health for a remarkably long period. Indeed, several years may elapse before the progression of the malignant process becomes apparent. Mirs. B. belongs in this category. In April, 1945, she devcloped pain in the cpigastrium radiating to the costa] margins and back. Colon and gastro-intestinal roentgenograms were negative, as was a special study of the small intestines. She had achlorhydria, a diabetic glucose tolerance curve and an elevated serum amylase on two occasions (50 and 61). (Normal maximum = 30.) The pancreatic function test was definitely abnormal. At operation on December 3, 1945, the entire pancreas was hard and contracted, and the common bile duct enlarged to about 1 cm. A cholecystenterostomy was done. Biopsy showed a replacement of ·Carcinoma of the Pancreas 31 PANCREATIC FUNCTION TEST 2 Fraction 1 3 4 Volume cc.... pH... Amylase Protease.. Lipase.. 4 7 05 Ans. 4 7.2 0.6 low 22 7.6 0.5 low very low 8 8 0.9 low normal very low very low very low The pancreatic function test showed almost complete absence of ferments though the pH of the fractions varied between 7 and 8. At operation, the head felt hard and nodular, but the body and tail were also hard and cystic. A radical pancreaticoduodenectomy was done. The specimen showed no obstruction of the pancreatic duct. The common bile duct showed soft swelling of its wall but could be probed down to the papilla of Vater without meeting an obstacle. Histologically, the pancreas showed much fibrosis with cystic dilation of some of the pancreatic ducts. There was no evidence of malignancy. After operation, on a known fat intake he absorbed 89 per cent of the ingested fat. Mild diabetes was present. In August, 1946, he was admitted for recurrent pyrexia and diabetes. Diarrhea and hematemesis developed later. Serum amylase was 25, phosphatase 50, and serum bilirubin 1.7. On careful review of the sections of November, 1944, adenocarinoma was discovered. At the autopsy, in January, 1947, carcinoma in different parts of the upper abdomen was found. In cancer of the body of the pancreas, there is usually enough uninvolved tissue to the right of the lesion to provide normal pancreatic juice. The close proximity of the body to the celiac plexus accounts for the frequency of epigastric and back pain in carcinoma of the body in contrast to carcinoma of the head, where obstructive jaundice is the usual presenting symptom. In 99 of 113 cases of carcinoma of the head reported by Walters and Dehne, 49 painless jaundice was the initial symptom. Cattell50 had a similar experience in 14 of the 15 patients with carcinoma of the head of the pancreas. Grauer, 51 on the other hand, found that epigastric pain was an early symptom in 20 of 34 autopsied cases According to Berk,62 pain occurs more frequently and earlier than jaundice. Of the 6 tabulated cases of carcinoma of the body, 5 had normal pancreatic juice. The difficulty in the diagnosis of carcinoma of the body is well exemplified by the case on page 34.

·30 Pancreatic Function Test terian Hospital in April, 1946, for epigastric pain and fever. The second pancreatic function test (April 11, 1946) was abnormal. Fractions 1 and 2 were acid. PANCREATIC FUNCTION TEST Fraction 3 7.3 Volume. PH..... Amylase. Protease Lipase... 7.0 7.3 7,0 45.0 42.0 4.0 Roentgen cxamination showed no enlargement of the duodenal loop but metastases in the lungs. At operation, metastases in the liver and infiltrating carcinoma of the head of the pancreas were found. Was this a slow-growing tumor from the outset, or was it a cancer superimposed on chronic pancreatitis? Even a biopsy from the head of the pancreas may not disclose the underlying pathology. G. B, a woman aged 56, was admitted in August, 1943, for ten days of painless jaundice with an enlarged gallbladder and chemical evidence of obstructive jaundice. Roentgers examination of the gastro-intestinal tract was negative. The pancreatic juice had an abnormally low lipase concentration, indicating malfunction. The serum amylase was slightly elevated. At operation, the gallbladder and common duct were distended. The entire pancreas felt hard, like carcinoma, but a biopsy from the lread of the pancreas showed only fibrosis. A cholecystenterostomy was done. She was readmitted in December, 1944, for pain in the upper abdomen and a mass in this location. She now had diabetes. The serum phosphatase was 10.7, and roentgen examination showed a narrowing of the second part of the duodenum. The second operation revealed metastases in the liver. The predominance of fibrous tissue may incerfere with accurate histologic diagnosis even in the pancreatectomy specimen. The following case is most instructive. L. C., aged 60, was admitted in November, 1944, for painless obstructive jaundice. Roentgen examination of the stomach and duodenum was negative. The liver was palpable two fingers below the costal margin.

·6 15 6 4 4 5 3 6 5 8 2 8.5 86 8.2 56 7.2 8 2 8.5 9 7 13.3 13 3 13.3 77 6 7 1.2 1.9 10 195 15 389 10 81 31 6 31 4 6 11 14 2 1 33 20 5 4 7.1 7.1 7.1 7 2 7.8 70 7.8 70 11 29 ac. 75 7.5 75 8.5 45 75 7.5 7.5 7.5 &c. 8.3 0 1. .04 .04 .04 ac. 6. 17 17 43 + + + 6 36 1. + 3 76 1. + 19 98 1. + + 1. qns. + + 3. 10 ac - + 7.2 71 ac. 159 - 139 12 41 5 ac 28 ac 7.5 8.5 17 8 47 7 6. 5.5 6.5 3 6.7 ac. 71 8. 78 7.5 7.5 79 82 75 7.5 7.5 7.5 72 72 72 7.2 3 41 3 25 19 2.1 1.3 5 9 15 + 5.3 5.1 29 61 4 5 2.3 48 5. 8.6 7.6 41 21 43 + 95 55 24 91 129 42 itaas 92 45 13. 14. 14. 12. Ca head of P. 1. 1.5 1.4 3.3 Ca. head of P. with secondary fibrosis ac. 0.5 0.7 0.7 Ca, head of P. 34 3.5 3.0 2.5 Ca, head of P. ans. 16 8 17.6 1. Ca, head of P. 7.4 4. 2. Metastatic Ca. in. volving P. 17.5 14.6 Ca. body of P. with metastases - 14 12 Ca. P. 9.5 12.6 16.4 16 8 Ca. body of P. 11.7 13. Ca. body of P. 7.3 7.0 10. 8.4 Ca, body of P. 1.3 2.9 6.3 3.5 Ca. P. entire autopsy 0.5 4.7 22 Ca. body of P. with extension into head, Autopsy 0.7 0.8 0.8 0.8 Ca, stomach mctastases to P. 1.1 1.1 .9 Ca. head of P. 13 14 12 12 Ca. head of P. 0.4 0.4 0.4 0.4 Ca. head of P. 0.8 0.9 0.4 0.4 Ca. head of P. 7. 5.08 14 Ca. body and tail of P. 11. 13 14. Ca. head of P. Not donc Ca. head of P. 2 0 5 2 7.4 0 7.9 7.9 38 106 11.3 7. 0 107 47 6.5 8.5 12 7 7.2 7.2 7.2 7.2 1 8 22 36 33 2. 6 لیا 7 ac. 17 13 6 26 14 22 25 13 7 11 34 14 45 8 15 15 3 27 14 ac 73 74 70 01.003 04 72 74 7.4 7.3 6.2 80 5.9 7.4 6 8 75 75 75 02 06 05 02 75 75 7.5 7.5 0.9 1.2 01 0.1 7.0 7.1 73 73 10 6 10 15 46 1.4 7 90 9.4 12. 92 120 1.6 1.4 12 6 98 120 10. 95 1.2 6 146 3 18 15 9 5 27 7 57 ac 8 5 7.7 71 ac. 7.2 75 75 ac 4.6 5.6 2.7 1.0 09 11 36 33 62 41 81 36 Minimum Normal Values: Abbreviations P. Pancreas Ca - Cancer C.B. Common bile P.D - Pancreatic duct 1.-low Amylase 4 Protcase 50 Lipase 8 [ 33 ] ·7 1 + TABLE 8. PANCREATIC JUICE IN OPERATED CASES OF CARCINOMA OF THE PANCREAS (32) VOLUIE PH ANIYLASE PROTEASE LIPASE DIAGNOSIS C CONCENTRATION CONCENTRATION CONCENTRATION AND Fractions Fractions Fractions Fractions Fractions 7 2 REMARKS 3 4 1 2 3 7 2 3 2 3 1 4 18 6 ac. 7.5 7.5 7.5 0 0 0 O 32 10 Ca. head of P. obstructing C.B. but not P.D. 18 36 25 ac, 75 7.5 75 + 0 O B 1. 2. 5. 9. 5. Ca. head of P. 16 24 24 27 ac. 7.5 75 4.5 ac. 1. ac. 0 3. 2.8 Ca. head of P. marked fibrosis 26 16 13 13 75 7.5 7.5 7.5 0 0 + 3. 9. 6. 9. Ca. head of P. no jaundice 7 5 17 ac. 7.5 7.5 ac ac. ac. 1. 1. 1. 3. 106 7. 7.4 ac. Ca. head of P.. Autopsy 3 4 S 7.5 7.5 7.5 7.5 1. 1. 0 1. 1.8 Ca. head of P. Autopsy 35 6 6 5 7.5 7.5 7.5 7.5 0 0 0 0 0 0 0 07 0.7 0.7 0.8 Ca. head of P. Autopsy 9 5 10 7.5 7.5 7.5 7.5 t + 0.2 1.0 4.0 4.0 Ca, head of P. 16 2 36 8.0 70 7.3 ac. 1. 1. 1. 0.2 0 Ca. head of P. 7 jaundiced 4.5 8 ac. ac. 7.6 7.4 3.8 3.3 Ca. head of P. Autopsy ac. ac. 7 15 ac ac. 73 7.5 1. 04 0.5 Ca. head of P. 3 6 7.4 79 - 3. 2.8 5.6 12.5 13 Ca. head of P. 4 - 7.2 7.0 7.6 0 0 0 10 20 14 2.6 1.8 Ca. head of P. 7.0 7.0 7.0 7.0 03 1.2 67 28 36 29 5.7 5.8 7.3 6.8 Ca. head, body and tail of P. Atrophy 8.5 4. 12 and fibrosis 7.5 6.6 7.9 7.8 79 2.1 .7 .6 1.7 4 5 4 13 3 1.7 1.6 .7 1.7 Ca. head of P. 12 7. 47 6.9 7.3 8.1 7.2 2.7 4 1 16.7 16.7 35.3 44 181 37 3.5 2.9 2.5 2.5 Ca. head and body of P. 6 5 4.5 20 7.3 7.3 7.3 7.3 7.8 8.1 10.6 9.1 103 101 167 79 6.3 7.5 5.0 CA, head of P. 4 + +++ ili + 11 Som + ++ tttt + ܝܕܝܨܗܐ ·No.of patients 16 15 13 12 10 9 Mo. sugor 2 Fic. 7. Frequency distribution of amylase concentration in the pancreatic juice during 10 minutes after mecholyl injection in proved cases of carcinoma of the head of the pancreas and chronic pancreatitis. No. of patients 19 18 - 17 - 16 - 15- 14 12 - 10- 8- 7 6- 5- 4- Mg.nonprotein N, 50 100 150 200 Fig. 8. Frequency distribution of protease concentration in the pancreatic juice during 10 minutes after mecholyi injection in proved cases of carcinoma of the head of the pancreas and chronic pancreatitis. ( 35 ) ·34 Pancreatic Function Test A. A., aged 56, was admitted in December, 1941, for ten weeks of generalized abdominal pain. The pain was most intense in the back, right lower, and left upper quadrants of the abdomen and was associated with anorexia, nausea and diarrhea. Roentgen 'examinations of the alimentary tract, intravenous pyelogram, serum amylase and pancreatic function test were normal. Two fractions of alkaline juice were obtained with high concentrations of amylase, protease and lipase. Exploration revealed a thickened cecum. All other organs, including the pancreas, seemed to be normal. Pain persisted after the operation. After visiting various clinics, it was concluded that he was suffering from a psychosomatic or an allergic disorder. His symptoms continued, and in June, 1942, a mass was palpable in the right lower quadrant. He died in July, 1942. At the autopsy, an adenocarcinoma of the body and tail of the pancreas was found. The growth had invaded the abdominal wall, peritoneum, lymph nodes, mesentery, left adrenal, and retroperitoneal tissues. The second case was a man of 68, a coal miner with diffuse lower abdominal pain, who was admitted in July, 1945. He had lost 36 pounds and had recently developed diabetes. Roentgen examination of the alimentary canal was negative. Serum amylase was 21. In the pancreatic function test, only the third and fourth fractions were obtained. PANCREATIC FUNCTION TEST 3 Fractrons 4 Volume cc. PH Amylase Protease Lipase 8 7.9 5.3 low normal law normal 82 5. low normal low normal The concentrations of the ferments were on the low side of normal. At operation, the body of the pancreas was replaced by tumor, but the head was not completely involved. Biopsy of a nodule in the omentum showed carcinoma. The concentration of ferments in the combined series of proven cases of chronic pancreatitis and carcinoma of the head of the pancreas has been graphed in Figures 7, 8 and 9. The difference in the frequency distribution of ferment values in nonpancreatic and pancreatic disease is obvious from a comparison with Figures 4, 5 and 6.

·Carcinoma of the Bile Ducts 37 suggests an ampullary lesion, as does intermittent jaundice. Roentgen examination of the duodenum may be helpful, but on the whole the symptoms and signs of the two conditions are similar. The pancreatic function test provides the best means of differentiation. In 18 operated cases of carcinoma of the bile ducts, the pancreatic juice was normal in 15 (83 per cent) whereas in carcinoma of the head of the pancreas it was normal in 10 per cent. Andrus and associatesld report two cases of obstructive jaundice with normal pancreatic juice. The one had a carcinoma of the bile duct proximal to the ampulla, the other had a carcinoma of the duodenum completely obstructing the opening of the ampulla but with a large accessory pancreatic duct 5 cm. proximal to it. In carcinoma of the papilla of Vater, the results of the pancreatic function test depend on the patency and anatomy of the ducts. In three of four normal people, both ducts are patent. The unusual re. sult in patient 686471 was due to an anatomic anomaly. A man of 56 had upper abdominal pain, vomiting, an enlarged liver, and jaundice. Serum phosphatase was 71, and serum bilirubin was 9 The ferment concentration in the pancreatic juice was normal. Ing. Fractions 2 3 4 2.5 Volume cc. PH Amylase conc. Protease conc. Lipase 11 7.5 high normal 100 20 7.5 high normal 14 10 75 high normal 15 75 high normal 12 The pancreatic juice contained blood. At operation the gallbladder was markedly distended and did not empty on pressure. The common duct was wide, measuring from 2 to 3 cm, in diameter. Its contents could not be expressed through the ampulla. The head of the pancreas did not feel indurated, but a definite nodule was felt in the region of the ampulla. The surgeon thought the findings were conflicting. Normal pancreatic juice had been obtained, yet the opening of the ampulla was obstructed. A resection of the head of the pancreas, duodenum, and antrum of the stomach was done. In the specimen, the pancreatic duct ended in a duodenal papilla about 2 cm. proximal to the ampulla without an apparent opening.

·36 Pancreatic Function Test No.of patients 10 m 9 8 6 Cc, OIN acid 2 B 10 12 14 Fig. 9. Frequency distribution of lipase concentration in the pancreatic juice during 10 minutes after mecholyl injection in proved cases of carcinoma of the head of the pancreas and chronic pancreatitis. At the Presbyterian Hospital, most of the cases of carcinoma of the pancreas are found to be inoperable. Patients with vague upper abdominal symptoms (such as anorexia, epigastric or lumbar pain) and weight loss should be explored if the usual diagnostic measures are negative. Only thus is there a possibility that partial or complete pancreatectomy may become 3 life-saving procedure. CARCINOMA OF THE BILE DUCTS In Ransoms53 series of 109 cases of verified tumors of the pancreas or extrahepatic bile duces, 49 involved the head of the pancreas, and 26 the bile ducts. The operative diagnosis was not always confirmed at necropsy. In 10 operated cases, 6 were thought to involve the pancreas and 3 the bile ducts, but at necropsy it was found that 7 originated in the ducts and only 3 in the pancreas. In a study of necropsy material al a large urban hospital, Shapiro and Lifdendahls: found that carcinoma of the bile ducts was three times as frequent as carcinoma of the pancreas. There is obviously a disparity between clinical and pathologic experience. Heretofore, it has been difficult or impossible to distinguish between the two conditions. The presence of blood in the duodenal secretion ·Corcinoma of the Bile Ducts 37 suggests an ampullary lesion, as docs intermittent jaundice. Roentgen examination of the duodenum may be helpful, but on the whole the symptoms and signs of the two conditions are similar. The pancreatic function test provides the best means of differentiation. In 18 operated cases of carcinoma of the bile ducts, the pancreatic juice was normal in 15 (83 per cent) whereas in carcinoma of the head of the pancreas it was normal in 10 per cent. Andrus and associates 14 report two cases of obstructive jaundice with normal pancreatic juice. The one had a carcinoma of the bile duct proximal to the ampulla, the other had a carcinoma of the duodenum completely obstructing the opening of the ampulla but with a large accessory pancreatic duct 5 cm. proximal to it. In carcinoma of the papilla of Vater, the results of the pancreatic function test depend on the patency and anatomy of the ducts. In three of four normal people, both ducts are patent. The unusual result in patient 686471 was due to an anatomic anomaly. A man of 56 had upper abdominal pain, vomiting, an enlarged liver, and jaundice. Serum phosphatase was 71, and serum bilirubin was 9 mg. The ferment concentration in the pancreatic juice was normal. Fractions 1 2 3 4 Volume cc. pH.. Amylase conc. Protease conc. Lipase 11 7.5 high normal 100 20 75 high normal 14 10 7.5 high normal 15 2.5 7.5 high normal 12 The pancreatic juice contained blood. At operation the gallbladder was markedly distended and did not empty on pressure. The common duct was wide, measuring from 2 to 3 cm. in diameter. Its contents could not be expressed through the ampulla. The head of the pancreas did not feel indurated, but a definite nodule was felt in the region of the ampulla. The surgeon thought the findings were conflicting. Normal pancreatic juice had been obtained, yet the opening of the ampulla was obstructed. A resection of the head of the pancreas, duodenum, and antrum of the stomach was done. In the specimen, the pancreatic duct ended in a duodenal papilla about 2 cm, proximal to the ampulla without an apparent opening.

·VOLUME 16. Fractions 2 [38] 1 TABLE 9. PANCREATIC JUICE IN OPERATED CASES OF CARCINOMA OF THE BILE DUCTS PH AUYLASE PROTEASE LIPASE CONCENTRATION CONCENTRATION CONCENTRATION DIAGNOSES Fractions Fractions Fractions Fractions AND 1 2 3 4 7 2 2 4 7 2 7 2 3 4 REMARKS 24 10 11 28 7.5 7.5 7.5 7.5 + + 30 ac. 20 16 6 25 19 17 20 20 35 ac. 7.5 7.5 ac. 13 8 7.5 7.5 7.5 75 23 13 7.5 7.5 7.5 6.8 6 15 7.5 7.5 7.5 7.5 10 25 7.5 7.5 7.5 7.5 + + + + + + + + to to to of + + ttttt + + + + + +++ to ac. 18 3.4 10 12 18 15 17 10 14 3C. 15 15 18 16 16 14 15 12 21 13 15 7.5 7.5 75 ac. + + 29 + + + 69 13 8.4 10.8 5.5 ac. ac. + 39 49 ac. 7.5 7.5 ac. 2 16 8.1 8.1 8.1 79 + 2c. + + + 1. Ca. lower C.B.D. without involvement of ampulla Ca. hepatic duct Ca. C.B.D. Ca. C.B.D. Ca. C.B.D. Ca. ampulla. P. duct entered 2 cm, above papilla and was patent. Blood in drainage Ca. G.B. with nodes in. volving C.B.D. Ca. common hepatic duct Ca. C.B.D.-P. duct not involved. Low lipase unexplained Ca. common hepatic duct Ca. C.B.D. Ca. ampulla Ca. CB.D. 2 cm, distal to cystic duct Ca. CB.D. Ca. G.B. involving CB.D ac. 21.7 8.4 Ac. 1 7 G 2 + 20 25 15 95 7.3 7.6 76 7.6 + + 6.5 2 500 8.0 8.1 7.60 9 8 4 7.2 8,1 8.1 8.3 13 5 30 7.5 7.9 8.3 6.9 1. + 0 tttt + + + 1. 1. + 1. 1. 3, + + 12 12 12 12 0 14.5 12.8 11 15 17 11 15 13 14 13.7 13 44 3 12 13 8 35 7.0 7.0 7.5 7.0 2 3 3 2 27 9 8.1 8.1 7.3 7.2 4.4 13.7 11.5 10.8 44.8 182 185 129 10 19 14 17 15 17 13 ·8 10.7 9.9 8 5 44 34 7.0 7.1 7.0 7.0 2.9 49 5.6 46 35 51 66 75 56 22 55 65 35 70 7.0 7 2 7.3 70 5.9 139 8.7 95 131 0 19 6 450 6.7 7.3 7.5 O 2.6 38 6.4 0 235 279 106 13.7 14.4 15 12.5 39 20 101 0 8.6 66 13.1 10 3 22 ac. ac 39 - 7.3 7.5 7 10.5 6.5 ac. 45 8.2 82 ac. 8.2 24 1 139 91 1. ac. I. 14 1. 0.9 1. . ac. ac. 1. Ca. ampulla with patent Santorini and Wirsung ducts Ca, C.B.D. Ca, ampulla No. pan. creatic duct obstruction. Blood in pancreatic juice. Painless jaundice. Ca. C.B.D. Ca. duod. at ampulla P. and C.B.D. dilated. Extreme fibrosis P. Stoolguiac+ 3 yr. later (Feb., 1948) well after mastec. tomy for ca. breast Ca. duod. involving ampulla of Vater Ca. C.B.D. Ca. of the papilla of Vater. C.B. and P. ducts dilated. Microscopic-little fibro. sis but marked dilatation of ducts Autopsy. Ca. C.B.D. Ca. CB.D. Autopsy 7.0 45 20 7.5 81 74 72 5.9 5.7 4.1 + 14 15 14 15 20 23 + 3 10 10 8 + 0.2 0.3 01 + 18 + + + 12 11 1 2 O 7.0 70 7.00 1 ܫܕ 1 86 24 15 14 18 30 16 8 6 7.5 75 ac. 7.5 5 7 5 6 71 19 20 7.1 6.7 7.0 6.5 34 8.5 63 7.1 106 133 107 99 13 207 165 193 14 14 16 16 15 15 NOTE: All patients had obstructive jaundice. Abbreviations: G.B =gallbladder ca.cancer 1.=low C.B.D. =common bile duct P.pancreas ( 391 ·40 Pancreatic Function Test Microscopically, however, a number of branching ducts penetrated the papilla, thus providing an outlet for the pancreatic juice into the duodenum (see Fig. 10). Duodenum Common bila dvct Pancreos Duct of Wirsung Papillaryopening of duci of Wisung Carcinoma of ampullo Fig. 10. Diagram of the specimen removed from patient 686471. The duct of Wirsung enters the duodenum through separate microscopic openings. SPRUE The malabsorption of foodstuffs, vitamins and minerals is responsible for the anemia, avitaminosis, low serum protein, low serum calcium, tetany, steatorrhea, diarrhea and emaciation so characteristic of this disease. In most cases of adult sprue, the pancreas does not appear to be involved. To quote Comfort, Parker and Osterberg, 11 "the constant finding of pancreatic enzymes in normal amounts in cases of sprue is of considerable importance in the differential diagnosis " Childs and Dick 55 also found normal pancreatic juice in typical sprue. H. O. Lagerloef& cites two cases in which the pancreatic function test was of diagnostic value. The investigation of A. C. Frazer and associates 56,57 indicates that soluble soaps are absorbed by the portal blood vessels, and that finely divided fat enters the blood stream through the lymphatics. In sprue, the latter process, that is, the "particulate absorption" of fat, is interfered with. It is noteworthy that these authors found large numbers of bacteria in the upper part of the small intestinal tract only in cases of sprue. In Table 10, fourteen cases of nontropical sprue are listed. All but per cent, had normal pancreatic ferment concentrations. The first case was a man aged 33 who was admitted April 2, 1913, for intermittent diarrhea, which he had had all his life. He also had one, about 93 ·TABLE 10. PANCREATIC JUICE IN NONTROPICAL SPRUE PH VOLUME CC. Fractions 2 3 AMY LASE CONCENTRATION Fractions 2 3 PROTEASE CONCENTRATION Fractions 2 3 LIPASE CONCENTRATION Fractions 1 2 3 Fractions 2 3 4 4 1 7 7 + 1.0 + 0.8 9. + + 10 19 22 40 25 0 0 0 1 1 11 45 11 6 0 0 1.0 06 08 3.0 28.0 15. 1.0 12.0 11.0 0.7 + 7.5 7.5 7.5 6.9 ac. 70 7.5 7.5 6.5 7.5 7.5 7.5 80 7.6 7.5 61 75 7.5 7.5 7.5 + + 15 11 5 60 29 + 1 1 8 21 32 55 + 7.0 13.0 12.0 9.7 + 0 1. 75 60 63 23 13 18.0 17 40 55 46 33 60 63 6.8 + o toto to +++ = ac. ac. + 1 + + + + + + + + + + 14 5 14 150 5 21 16 79 7.9 7.7 7.9 1.0 + + + + + + + + 11 14 13 12 77 79 7.8 7.8 25 15 + 31 12 + + 19 12 14 18 27 49 85 69 72 72 64 + 23 + + 22 22 10 20 18 22 79 80 7.0 73 23 22 10 10 5 + + 255 302 400 62 76 7.8 8.0 7. 15 17 17 9.5 12 15 5 15 6 23 75 7.5 7.5 7.5 55 9 14.5 17 7.6 33 7.8 25 12 61 237 273 89 10.8 11.8 11.2 13.7 + 25 15 13 31 7.7 79 78 7.8 + 12 + + 160 188 321 276 7.7 7.7 7.8 7.7 20 16 9.1 11.3 65 96 13.5 15.2 10.4 9 74 7.4 7.4 7.4 16 1.5 20 3.2 14 21.0 68 30 4.0 93 203 93 7 13 5 5 Alinimum normal values: Amylase 4 Protease 50 Lipase 8 [ 41 ] ·42 Pancreatic Function Test had clubbing of the fingers and toes as long as he could remember. Additional symptoms were weakness, stiffness in the arms and legs and polyuria. Roentgen examination showed a marked deficiency pattern of the small intestine. Colon roentgenogram was negative. Stool was negative for ova and parasites. Serum calcium was 4 mg. per cent, serum albumin 5.4, and globulin 2.6. The glucose tolerance curve was flat, fasting blood sugar 91, 12 hour 91, 1 hour 103, 2 hours 75, and 3 hours 82. Anacidity after histamine injection. The red blood count was 3,520,000, the hemoglobin 12 grams per cent, and the white count was 8,700. The pancreatic juice was essentially normal. The fat absorption was 87 per cent. Urine was negative. While in the hospital under treatment, his food consumption reached 5,000 calories, his weight increased by 15 pounds, and the serum calcium rose to 8.7 mg. per cent. By March, 1945, his initial weight of 110 had risen to 154 pounds and his serum calcium to 9.1. Relapses occurred when he went off his diet. In June, 1946, he entered the hospital in a depleted state and died of a terminal pneumonia. Autopsy showed a normal pancreas and marked atrophy of the alimentary canal. PERNICIOUS ANEMIA In pernicious anemia, the absence of hydrochloric acid prevents gastric digestion and deprives the patient of the secretin activator. It therefore seemed desirable to ascertain the pancreatic response to the vagus stimulant, mecholyl, in this condition. According to Table 11, the pancreatic juice was normal in seven of eight pernicious anemia patients.

·1 TABLE 11. PANCREATIC JUICE IN PERNICIOUS ANEMIA PH VOLUME CC. Fractions 2 3 AMYLASE CONCENTRATION Fractions 7 2 3 4 PROTEASE CONCENTRATION Fractions 1 2 3 LIPASE CONCENTRATION Fractions 2 Fractions 2 3 7 4 1 9 12 7 9 13 17 23 23 7.9 80 7.5 7.0 7.5 7.5 7.5 + + + + + + 2 15 8 58 2 16 17 16 3 7.8 7.8 7.9 7.9 11 17 14 12 35 + + 7.9 7.6 7.7 7.8 +++++++ + + + + + + + 0.5 21 12 10 10 21 78 15 17 6 5 14 45 0.5 0.8 13 + + + 1. + + + 1. + + + + 1. + + + + + 1. + + + + + + 81 98 96 82 14 23 21 7.2 7.5 7.6 7.9 7.8 7.6 80 0.47 2 3 3 6 + + + + + + + + 11 22 17 20 6 14 12 29 15 49 12 8 18 64 175 7.6 7.7 7.7 8.0 7.7 7.9 7.5 7.8 5 17 11 8.7 Alinimın normal values: Amylase 4 Protease 50 Lipase 8 [ 43 ]

·No text on this page.

·PART II Fat Absorption Studies in Pancreatic Deficiency In the absence of jaundice, the determination of fat absorption is of diagnostic value in pancreatic disease. The results of fat balance studies in man after removal of the head of the pancreas or the entire organ have been surprisingly vari. able.50.60 They are comparable to the experience in dogs deprived of their pancreatic juice.58 Brunschwiggi resected the head of the pancreas and tied off the ducts in tvvo macacus rhesus monkeys. The one lived normally for 1 year and was then sacrificed. The liver was normal; the body and tail of the pancreas formed a cyst but many of the islands of Langerhans were well preserved The other animal lived in excellent condition for 14 months on the usual diet. TABLE 12. THE FAT ABSORPTION IN 7 PATIENTS IN WHOM THE HEAD OF THE PANCREAS AND DUODENUM OR THE ENTIRE GLAND HAD BEEN REMOVED PATIENT No FAT INTAKE GRAMS ABSORPTION Fat % PANCREATECTOMY 2 3 4 4 Partial Partial Partial Partial Partial 100 130 75 75 75 968 89.0 87.0 25 0 920-Taking 9 capsules pancreatin od. 750 81 -Taking 15 capsules pancreatin o d. 48 6 51 0 5 Complete Complete 75 75 6 7 70 Complete Complete 100 Of the seven patients without pancreatic juice, three had normal fat absorption. In two others, the absorption became satisfactory when 45 ·46 Fat Absorption Studies in Pancreatic Deficiency dried pancreas was added to the diet. Cases 6 and 7 were reported from the Mayo Clinic.22 This individual variation is inexplicable at the present time. According to Free and Myers, 28 human intestinal juice obtained from an isolated segment of intestine with a Miller-Abbott tube possessed no ferment activity. Even in completely depancreatized dogs, Vermeulen et al.85 found that the absorption of triolein varied considerably. A number of observers22, 32, 58 have noted a gratifying increase in fat absorption following the use of dried pancreas in cases of pancreatic juice deficiency. Most recently, additional fat and protein absorption studies were done on ten patients after resection of the head of the pancreas. Absorption was better when the pancreatic duct was reunited with the small intestine than when it was ligated. The beneficial effect of giving dried pancreas with meals was confirmed. 62 DETERMINATION OF FAT IN THE STOOL The patient is given a diet of 200 carbohydrate, 70 protein and 75 grams of fat. After several days, a purgative, for example, 0.6 of cascara or 20 Gm. epsom salts, is administered, and the resulting stool is discarded. During the following three days, the stool is collected, united, emulsified with water by means of an electric stirrer and then diluted to a convenient volume. An aliquot of from 10 to 20 cc. is used for the fat determination. It is introduced into a 100-cc. separating funnel, and 1 cc. of concentrated hydrochloric acid and 20 cc. of water are added. The fat is extracted with successive 20-cc. portions of ether until evaporation of a small amount of ether extract leaves no residue. A little alcohol may be added to facilitate the separation of the ethereal from the aqueous layer. The ether extracts are evaporated. The residue is dried in a vacuum desiccator, and then extracted three times with petroleum ether. The combined extracts are united and filtered into a weighed beaker of from 100 to 150 cc. capacity. The filter paper is washed with petroleum ether. The extract is evaporated and dried in a vacuum desiccator and weighed. Total Volume of Fecal Emulsion x Weight of Fat in Aliquot - Fat in 3 days' stool Volume of Aliquot ·PART III Serum Amylase The starch-splitting activity of the serum is due to amylases chiefly elaborated by the pancreas and salivary glands. Total extirpation of the pancreas causes an immediate 50 per cent decrease in serum amylase activity.83 The amount (or percentage) of reducing sugar liberated by a known quantity of serum from a known amount of starch is the index of amylolytic activity. In the hospital laboratory, we have used the method of Myers and Killian,64 The results are expressed as the percentage of 10 mg. or more of starch converted into sugar by 2 cc. of serum, SERUM AMYLASE DETERMINATION It is important to guard against the entrance of saliva into the measuring pipettes by aspirating through a connecting rubber tube containing cotton wool. Solutions Required: 1. A standard solution of 0.02 per cent glucose in saturated picric acid is stored in the refrigerator in a brown glass bottle. 2. Saturated picric acid solution is prepared by dissolving approximately 1.5 Gm. picric acid in 100 cc. of water Mix, allow to dissolve overnight, filter, and preserve in a brown boule. 3. A 1 per cent starch solution is prepared by making a paste of 1 Gm, of soluble starch with a few drops of cold water and adding about 95 cc. of boiling distilled water. Cool and bring to volume. The solution keeps for about two weeks in the refrigerator, Method: Prepare four tubes as follows: Tube A05 05cc serum 85 cc. distilled water Tube B 2 cc serum 7 cc distilled water 47 ·46 Fat Absorption Studies in Pancreatic Deficiency dried pancreas was added to the diet. Cases 6 and 7 were reported from the Mayo Clinic.22 This individual variation is inexplicable at the present time. According to Free and Myers, 28 human intestinal juice obtained from an isolated segment of intestine with a Miller-Abbott tube possessed no ferment activity. Even in completely depancreatized dogs, Vermeulen et al.85 found that the absorption of triolein varied considerably. A number of observers22, 32, 68 have noted a gratifying increase in fat absorption following the use of dried pancreas in cases of pancreatic juice deficiency. Most recently, additional fat and protein absorption studies were done on ten patients after resection of the head of the pancreas. Absorption was better when the pancreatic duct was reunited with the small intestine than when it was ligated. The beneficial effect of giving dried pancreas with meals was confirmed.92 DETERMINATION OF FAT IN THE STOOL The patient is given a diet of 200 carbohydrate, 70 protein and 75 grams of fat. After several days, a purgative, for example, 0.6 of cascara or 20 Gm. epsom salts, is administered, and the resulting stool is discarded. During the following three days, the stool is collected, united, emulsified with water by means of an electric stirrer and then diluted to a convenient volume. An aliquot of from 10 to 20 cc. is used for the fat determination. It is introduced into a 100-cc. separating funnel, and I cc. of concentrated hydrochloric acid and 20 cc. of water are added. The fat is extracted with successive 20-cc. portions of ether until evaporation of a small amount of ether extract leaves no residue. A little alcohol may be added to facilitate the separation of the ethereal from the aqueous layer. The ether extracts are evaporated. The residue is dried in a vacuum desiccator, and then extracted three times with petroleum ether. The combined extracts are united and filtered into a weighed beaker of from 100 to 150 cc. capacity. The filter paper is washed with petroleum ether. The extract is evaporated and dried in a vacuum desiccator and weighed. Total Volume of Fecal Emulsion X Weight of Fat in Aliquot Volume of Aliquot =Fat in 3 days' stool ·Serum Amylase Determination 49 Two cc. of normal serum contains from 10 to 30 Myers and Killian units, comparable to from 16 to 36 Somogyi units. The test is rather simple, and the results can be obtained in from one-half to one hour, depending on the experience of the technician. Recently, Myers, Free and Rosinski65 have modified the original method. In acute inflammation of the pancreas or salivary glands, the swollen tissue obstructs the duct system sufficiently to increase the rate of ferment reabsorption and thus raise the level of amylase in the serum. Rarely is the destruction of parenchyma so extensive that ferment production is reduced sufficiently to lower the serum amylase level. In 1908, Schlesinger88 observed a rise in the blood amylase in rabbits after tying off the pancreatic duct. About the same time, Wohlgemuth7 discovered an increase of amylase in the urine in acute pancreatitis. In advanced renal disease, retention may cause an elevation of amylase in the blood. The diagnostic value of the determination of amylase in the serum in acute pancreatitis was pointed out by Elman and associates 68 20 years ago and has been amply confirmed by subsequent workers. Since good surgical judgment is opposed to immediate intervention in most cases of acute pancreatitis, the estimation of serum amylase has become a decisive and important diagnostic procedure. It is also valuable in determining involvement of the pancreas in upper abdominal injuries. Difficulty in the differential diagnosis of acute upper abdominal conditions is a common experience in the surgical emergency service of a large hospital. Before the introduction of the serum amylase test, French observers 48 report that in 468 cases of acute pancreatitis, a preoperative diagnosis was stated in 192, and of these only 39 were correct. Though not nearly as common as appendicitis, gallbladder disease, perforated duodenal ulcer, or intestinal obstruction, acute pancreatitis is a possibility that merits consideration. With rare exception, an elevated serum amylase is conclusive evidence of pancreatic edema or inflammation. In the tables that follow, the serum amylase values in about 400 patients have been correlated with other laboratory and clinical data and tabulated according to the underlying disease. Some patients were followed for over ten years in the outpatient ·48 Serum Amylase Tube A 1 1 cc. serum 8 cc. distilled water Tube A 2 2 cc. serum 7 cc. distilled water Place these and a tube containing approximately 5 cc. of starch solution in a bath at 40° for ten minutes. Clear the starch solution by heating before using and place a stirring rod in each tube. Add I cc. of starch to tubes A 0.5, A I, and A 2. Incubate in constant temperature water bath for exactly fifteen minutes, mixing well, then immerse the tubes in an ice bath and add from 12 to 1 Gm. of solid picric acid. Stir well, and keep in the ice bath until each tube has a uniform yellow color; then add 1 cc. of starch to the blank tube B. Filter all four tubes through regular Whatman filter paper. Place 3 cc. of each filtrate in a Folin-Wu sugar tube and 3 cc. of the standard in a fifth tube. Add 1 cc. of 20 per cent sodium carbonate to each tube; shake vigorously and heat in a boiling water bath for fifteen minutes. Cool. Dilute the tubes to the 25 cc. mark with distilled water and read in the colorimeter. The color is stable. Calculations. Set the standard at 20. Tube A 05 20 1 * *06* * 0.15. = Total mg glucose per cc of serum or blood Tube A 1 20 R X 0.62 x R 1 0.31 = Total mg. glucose per cc of serum or blood Tube A 2 - 20 R *0.69 1 06 Total mg. glucose per cc. of serum or blood Tube B Same as Tube A 2 R = Reading of unknown a = Amount of glucose in standard glucose solution b = Amount of serum used The amylase value in units is obtained by subtracting the results of B tube from the average of the three A tubes and multiplying by 20.

·Serum Amylase in Acute Pancreatitis 51 Patient No. 6 of the unoperated group was of special interest. He had received a single massive dose of arsphenamine for syphilis which resulted in inflammation of the brain, liver and pancreas. Branch?1 described a similar case of pancreatic necrosis following the application of arsenious acid paste to a patient with carcinoma of the breast. The diagnosis was verified at necropsy. The advantage of delaying operation in acute pancreatitis is illustrated by the behavier of two men, history No. 713114 and No. 748633, who were admitted to the surgical ward at the same time with the classical, clinical and laboratory features of acute pancreatitis. E. R., aged 54, had severe epigastric pain, tenderness, fever, vomiting and a white blood count of 28,000. Serum Amylase 6/11... ..120 6/15. 6/12. 142 6/19 6/12.. ..216 6/13 7/2. 6/14....... 94 6/27.. ..33 34 .36 83 ..173 On July 3rd, about three weeks after admission, a mass in the left epigastrium became palpable. One thousand cc. of purulent fluid were removed from the lesser sac, and this was followed by recovery. The second patient, T. H., aged 40, had epigastric pain associated with nausea and vomiting, spasm in the right upper quadrant, tenderness in the epigastrium, fever and a white blood count of 17,000. Serum Amylase Serum Bilirubin Serum Lipase trace normal (1.2 cc.) 6/11 6/12 6/14 6/19 6/26 .130 ..110 46 92 46 On June 26th he was asymptomatic. Cholecystogram was normal. He was discharged. He was in good health six months later, More rarely, the condition is very serious, with widespread hemor. rhage and necrosis accompanied by shock, spreading peritonitis and exitus.

·50 Serum Amylase department; in others, additional information was obtained at a later operation or at autopsy. SERUM AMYLASE IN ACUTE PANCREATITIS The values in 47 operated cases (see Table 13) confirm the well known elevation of serum amylase in acute edema and inflammation of the pancreas. Lagerloefs found the amylase elevated in 21 patients with acute and chronic relapsing pancreatitis. A decline to normal levels is apt to occur in 48 hours. This may be the result of rapid excretion by the kidney, subsidence of the edema or inflammation, or relief of blockage of the ampulla of Vater by a movable stone, or relaxation of spasm of the sphincter of Oddi. The decline in serum amylase may not coincide with clinical subsidence of the inflammatory features. Acute edema may disappear so rapidly that at operation 2 few days after onset, no abnormality of the pancreas is found. Occasionally, the clevation persists without other clinical or laboratory evidence of continued inflammation. Bilirubinemia is frequent, though not invariable. It results from pressure on the common bile duct or concomitant blockage by stone. The association of pancreatitis with stones in the gallbladder is frequent. Brocq48 found stones in the common bile duct in 146 of 228 explored cases of pancreatitis (64 per cent). Of these only 11 had a stone wedged in the ampulla. Griesmanney found that 94 per cent of acute pancreatitis cases had gallbladder or biliary duct disease and 79 per cent had stones in the gallbladder. If possible, a cholecystogram should be done in every case before discharge. If stones in the gallbladder are present, cholecystectomy usually prevents future attacks. Recurrences after removal of the gall. bladder are probably due to lighting up to residual foci of infection within the pancreas or neighboring lymphatics. Evidence is accumulating that alcohol indulgence is a causal factor in both acute and chronic pancreatitis.70, 71 Carter72 found edema of the pancreas in alcoholics with abdominal symptoms and an elevated serum amylase. Clark70 cites 36 cases of pancreatitis in alcoholics with cirrhosis or fatty liver. (See also Weiner and Tennant.73) The restoration of pancreatic function after an acute attack is usually complete, unless the process has been too severe and extensive or preceding bouts have caused widespread replacement of parenchyma by fibrous tissue. 38 ·Serum Amylase in Acute Pancreatitis 53 Table 13 (Continued). SERUM AMYLASE VALUES IN OPERATED CASES OF ACUTE PANCREATITIS SERUBE No SERUM DAYS AMYLASE LATER CONDITION FOUND AT OPERATION Plase Bili. 13. 14. 4.8 7.4 27 28 29 30 31 32 146 39 138 129 88 82 3. 1. 33 37 17. 38 P. firm Nodules head of P., stones in gallbladder 2 days after removal body and tail of P. Blocked drainage, marsupialized cyst Ac. pctis. with fat necrosis Ac. pctis. with fat necrosis, gallbladder normal P. large and hard, biopsy fibrosis, stones in gallbladder P. enlarged, edematous Head P. enlarged, nodular, stones in gallbladder Ac. pctis , pancreatic cyst, stones in gallbladder P. firm, stones in gallbladder P. enlarged, stones in gallbladder 34 35 143 208 3.9 2.1 4. 36 122 39. 1.9 191 17.4 64 37 38 39 40 41 42 160 42 41 116 133 2. (Ser, Lipase 17.4) 10.7 5.1 43 43 44 380 8 99 3 45 90 P. felt normal P. enlarged, stones in gallbladder 1 day post partial p'ectomy for ca. of papilla Vater, autopsy=Fat necrosis around cut end of P. Much edema about gallbladder, stones in gallbladder, P. unexplored Stones in gallbladder, P. felt normal, F. U. 9 yrs. = patient well Stones and ca. gallbladder, P felt normal F. U. 11 yrs = patient well 46 50 47 61 26 47 47 36 26 2 8 ·52 Serum Amylase TABLE 13. SERUM AMYLASE VALUES IN OPERATED CASES OF ACUTE PANCREATITIS SERUM SERUM No. DAYS AMYLASE LATER CONDITION FOUND AT OPERATION Plase Bili. 1 186 4.6 3.7 Ac. pctis. fat necrosis, ac. gangrenous cho lecystitis 1 1 1 2 112 16 52 2 14. 3 74 11.9 Head P. enlarged, fat necrosis, stones in gallbladder Hemorrhagic petis., fat necrosis, stones in gallbladder Acute pctis., fat necrosis, stones in gall. bladder 4 137 ܝܢ Trace 3.8 13 3 3 3. 1. 2 4 5 6 7 8 8 9 9 10 11 12 13 13 14 14 15 16 17 17 18 19 19 20 114 88 66 76 229 28 82 27 64 94 91 165 100 244 288 100 199 172 27 87 216 33 96 3.6 7. 8.1 Edema and abscess head of P., gallstones Abscess P. P. enlarged, cyst formation Indurated head P., stones in gallbladder Abdominal exudate, fat necrosis P. abscess Ac. pctis., fat necrosis Ac. pctis., stones in gallbladder Nodular enlarged P. Bullet wound P. and stomach P. head hard, stones in gallbladder 2nd attack 8 mos after cholecystectomy Bullet wound P. and stomach Ac. necrotic pctis (autopsy) P. enlarged, stones in gallbladder Nodular masses in P., stones in gallbladder Ac. pctis., abscess in lesser sac First day after partial resection P. for adenoma 4. 1.7 1.5 8. 2 7. 11. 3 2 2 20 21 21 22 23 23 24 43 134 45 80 70 19 174 2 Head P. enlarged, fat necrosis Head P. enlarged, fat necrosis Head P. very large, stones in gallbladder P. firm, several nodules in head, stones in gallbladder Fat necrosis, stones in gallbladder Nodules body and head of P, 2 24 25 26 32 130 102 3.

·Serum Amylase in Acute Pancreatitis 55 TABLE 14 (Continued). SERUM AMYLASE IN UNOPERATED CASES OF ACUTE PANCREATITIS SERUM No. S.A. DAYS LATER GALL- BLADDER X-RAY WEC. CLINICAL FEATURES AND REMARKS Plase Brli. 14 204 1.1 Gallbladder out 3 wks ago, now epig pain, vomiting, jaundice, P. function test normal 3 14 15 54 87 7.0 16 59 17 49 48. 18 19 50 71 11.0 Abnormal R.UQ: pain, jaundice, P. function test normal Normal 5,250 Epig. pain, gallbladder out 2 mos ago 3.5 RU.Q. pain after chole. cystectomy 20,000 LU.Q. pain Appearance 19,250 Mid abd. pain, fever, epig. of intest. tender, gallbladder out obstruction 5 yr. ago, P.=normal, FU 2 yr. bouts of abd. pain. In Mar, 1948, developed ac necrotic pancreatitis with fat necrosis 4 19 20 21 34 77 57 63 Trace Abnormal 23,800 22 59 11 2 57 20,300 RUQ pain, vomiting Epig. pain, vomiting, gallbladder out 3 mos ago, Pfunction test-normal RUQ pain, vomiting, jaundice, stones in common bile duct and GB.- Op 6 mos ago 22 23 41 66 123 21 P. function test--abnormal Pressure on duodenum 4 8 156 24 Trace Normal 24 25 70 13 Epig. pain, alcoholic, P. function test abnormal, FU. 6 mos patient well Cholecystectomy gs RU. Q. pain 3 days after op. FU 1 mo. satisfactory 112 32 86 7 26 Epig. pain, vomiting, mass in epig tender, ac pctis absorption of contents false cyst 12 4 ·54 Serum Amylase TABLE 14, SERUM AMYLASE VALUES IN UNOPERATED CASES OF ACUTE PANCREATITIS SERUM DAYS No. S.A. LATER GALL- BLADDER X-RAY WBC. CLINICAL FEATURES AND REMARKS Plase Bili. 1 76 Trace Normal 14,600 Epig pain, fever, tender abdomen 1 4 1 2 3 3 4 7 199 47 79 45 75 2 Recurrence 7 yrs. later 4.7 Abnormal 5,200 Epig. pain, fever L.U Q. pain, fever, stones L.U Q. tender Trace Normal 16,500 Epig pain, F.U = minor pains for several years, indeterminate 10.4 6 71 66 5 13,500 Attacks epig. pain for 16 yrs., pancreatic function test abnormal-recurring pctis. 7 11.4 Trace 5 6 45 250 Abd. pain after intensive arsphenamine treatment, petis, hepatitis, encephalitis, normal pancreatic function test N 6 7 192 200 19,650 R.UQ pain, 1 mo. after cholecystectomy F.U. = no symptoms 7 7 8 37 34 75 45 66 12,000 Epig. pain N 9 Normal Epig R.UQ pain, pancre. atic function test normal 3 54 200 10 2.1 1 Epig. pain, gallbladder out for stones i mo, ago, F.U. 18 yrs, no recurrence 3 39 127 117 11 12 20,200 3.7 05 Abd. pain, vomiting Gallbladder out for stones, 1 mo. later pain, vomiting, common bile duct in satisfactory condition 90 12 13 64 24 20,300 RUQ. and LU.Q. pain, vomiting, jaundice, had cholecystectomy in past ·Serum Amylase in Cancer of the Pancreas 57 TABLE 15. SERUM AMYLASE IN CHRONIC PANCREATITIS SERUSI No. PANCREATIC FUNCTION TEST FINDINGS AT OPERATION, PANCREAS Amylase P'tase Buli. Abnormal Abnormal Trace Trace Abnormal Abnormal Abnormal 31 32 31 51 28 42 16 22 63 31 39 49 8 2 3 4 5 6 7* 8 9 10 11 12 13 1.7 Abnormal Trace Abnormal Abnormal Hard, nodular P. Fibrosis, calcification Hard, nodular Unoperated Fibrosis, calculi Fibrosis, calculi Fibrosis, fat necrosis Unoperated Fibrosis (biopsy) Fibrosis, calcification Fibrosis, gallstones Fibrosis, gallstones Fibrosis, necrosis gallstones Fibrosis, calcification Fibrosis, gallstones Unoperated Fibrosis, calcification Unoperated Fibrosis (biopsy) 14. 7.4 6 30 Abnormal 14 15 16 17 18 19 21 32 26 39 10 20 Abnormal Abnormal Abnormal 4.7 *The serum amylase determined between attacks found in the same conditions and during the same period of time as an elevated amylase. He prefers the latter, as it is less time-consuming and more accurate. McCall and Reinhold76 also found that in cancer of the pancreas the serum lipase was more frequently elevated than the amylase and suggest that a normal amylase, associated with an elevated lipase, points to cancer. An obvious element in the controversy is the lack of agreement amongst authors about the upper normal limit of serum amylase concentration. For example, Comfort and Osterberg74 accept 320 Somogyi units, which is about twice as high as the commonly observed value in nonpancreatic disease. Final judgment will be possible when more figures are available, It is conceivable that amylase is more rapidly eliminated by the kidneys than lipase. A probable case of cancerous proliferation of functioning acinar tissue is described by M. W. Comfort and associates.? It was characterized by extremely high concentrations of serum amylase and lipase.

·56 Serum Amylase TABLE 14 (Continued). SERUM AMYLASE IN UNOFERATED CASES OF ACUTE PANCREATITIS SERUM No. S.A DAYS LATER GALL- BLADDER WBC. X-RAY CLINICAL FEATURES AND REMARKS Plase Bili. 27 90 15.5 3.2 28 100 29 123 30 43 2.0 31 39 Abnormal R.U.Q. epig, pain tender, autopsy 8 yrs. later P. normal, stone gallbladder 1 mo. after cholecystectomy for gallstones epig pain, vomiting Epig. R.U Q. pain, stones gallbladder, P. normal Epig. pain, stones gallblad der, P. not explored R.U.Q. pain, vomiting, stones, gallbladder perforated R.U.Q: pain, 1 mo, later gallbladder out. Stones Mid. abd. pain, fever, F.V. no symptoms Epig. L.U.Q. pain, stones in gallbladder 5 wks, later P. firm Blocked drainage, P. cyst posttraumatic 32 107 5.2 33 72 Normal 34 191 Stones in gallbladder 35 129 22 35 25 9 THE SERUM AMYLASE IN CHRONIC PANCREATITIS The serum amylase in chronic pancreatitis is usually below or slightly above the upper limit of normal (30). In this condition, the pancreatic function test is of greater diagnostic value. If sufficient uninvolved acinar tissue remains, the serum amylase rises during acute relapses or during subacute smoldering activity. SERUM AMYLASE IN CANCER OF THE PANCREAS The serum amylase was above normal in about one half of the cases (Table 16). Seventeen of the 22 cases were jaundiced. The serum amylase and pancreatic ferment values are influenced by the site and size of the tumor. Comfort and Osterbergii found that the serum lipase was more frequently elevated in carcinoma than the serum amylase, whereas Lagerloef73 states that an elevated serum lipase is ·Serum Amylase in Operated Cases of Gallbladder Disease 59 TABLE 17. SERUM AMYLASE IN OPERATED GALLBLADDER DISEASE SERUS No. FINDINGS AT OPERATION Amylase Bilsubin 1 Stones in gallbladder Stones in gallbladder Chr. cholecystitis, head of P. normal Stones in gallbladder, head of P. normal Stones in gallbladder Ca. gallbladder and liver Acute cholecystitis 16.5 :- --11L1. 1.8 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 29 27 29 25 27 16 27 23 16 20 21 23 16 15 13 29 15 29 17 25 12 23 23 Stones in gallbladder, P. normal Stones in gallbladder Stones in gallbladder Acute cholecystitis Suvar!. -Tili.is - T 26 4.2 24 25 26 27 28 29 30 31 32 33 16 13 16 14 20 39 35 34 33 39 53 120 39 31 Trace 136 unaitu Stones in gall bladder Stones in gallbladder Stones in gallbladder, P. normal Stones in gallbladder Stones in gallbladder, Ca gallbladder Stones in gallbladder, P normal Stones in gallbladder Stones in gallbladder Stones in gallbladder Stones in gallbladder, Ca. common bile duct Stones in gallbladder Stones in gallbladder, P. normal Stones in gallbladder Stones in gallbladder, Common bile duct thick-FU. 8 yrs. OK Stones in gallbladder, P. normal Stones in gallbladder Stones in gallbladder Stones in gallbladder Stones in gallbladder 34* 357 36 37 32 38 39 40 41 421 33 35 31 33 48 •The elevated amylase occurred 8 days after cholecystectomy for stones and was accompanied by epigastric pain, vomiting and jaundice Cholecystectomy 18 days after amylase determination. Epigastric pain and serum amylase 41 three years before ·58 Serum Amylase TABLE 16. SERUM AMYLASE IN CANCER OF THE PANCREAS Seruut No. Amylase Plase PANCREATIC FUNCTION TEST FINDINGS AT OPERATION 2.8 2.7 2 3 4 5 47 36 55 87 108 Normal Abnormal Normal Abnormal Abnormal 18 2 11.5 9.2 Normal Abnormal 10. 19 36 18 6 7 8 9 10 11 12 13 52 37 67 52 81 18 12 15 69 18.5 17 22 6.9 12. Abnormal Ca. of the duodenum and head of P. Ca, entire P. Movable mass head P. Ca. head of P. Ca. duodenum blocked P. duct, secondary fibrosis P. Ca. stomach involving P. Ca. P., metastases to peritoneum Ca. head P. Ca. head and body P. Ca, entire P. Ca. head of P Ca. head of P. Ca. P., metastases liver, peritoneum (autopsy) Ca. head and tail P. (autopsy) Ca. head of P. Ca. ampulla vater Retroperitoneal mass, metastases liver, possibly ca. body P. Ca, head P. Ca. head P. Ca. head P. Ca. ampulla, partial occlusion P. duct. Biopsy=fibrosis, Ca head P. Abnormaal 14 15 16 17 25 10 24 27 19 9.4 24 11. 6.8 11.3 Abnormal 18 19 20 21 21 25 30 16 14.5 22 19.6 32 82 12.6 13. 9.6 Abnormal Normal Abnormal 22 29 34 24. SERUM AMYLASE IN OPERATED CASES OF GALLBLADDER DISEASE In 42 operated cases of gallbladder discase (Table 17), the serum amylase was under or slightly over 30. In several jaundiced patients, exploration of the common bile duct was negative; in 12, palpation of the pancreas was also negative. Transitory edema of the head of the pancreas probably accounts for the occasional rise of amylase in this condition. While stones in the gallbladder are common in pancreatitis, panzcreatitis is uncommon in the ordinary case of gallstones. It is more likely to occur in the long-standing cases with pericholecystitis and lymphatic spread.

·Serum Amylase in Operated Cases of Gallbladder Disease 59 TABLE 17. SERUM AMYLASE IN OPERATED GALLBLADDER DISEASE SERUM No. FINDINGS AT OPERATION Amylase Bilirubin Stones in gallbladder - 11L1.11. 16.5 1.8 2 3 4 5 6 7 8 9 - 10 11 12 13 14 15 16 17 18 19 20 21 22 23 29 27 29 25 27 16 27 23 16 20 21 23 16 15 13 29 15 29 17 25 12 23 23 Acute cholecystitis Stones in gallbladder Stones in gallbladder Cholesterosis of gallbladder Stones in gallbladder Stones in gallbladder, P. normal Stones in gallbladder, P. normal Stones in gallbladder Stones in cystic duct, residual Stones in gallbladder, P. normal Stones in gallbladder Stones in gallbladder Acute cholecystitis 26 4.2 24 25 26 27 28 29 30 31 32 33 34* 16 13 16 14 20 39 35 34 33 39 53 120 39 31 Trace Stones in gallbladder, H. nonna, Loumon Pue uult dilated Stones in gall bladder Stones in gallbladder Stones in gallbladder, P normal Stones in gallbladder Stones in gallbladder, Ca gallbladder Stones in gallbladder, P. normal Stones in gallbladder Stones in gallbladder Stones in gallbladder Stones in gallbladder, Ca. common bile duct Stones in gallbladder Stones in gallbladder, P. norinal Stones in gallbladder Stones in gallbladder, Common bile duct thick-FU. 8 yrs. O K Stones in gallbladder, P. normal Stones in gallbladder Stones in gallbladder Stones in gallbladder Stones in gallbladder 13 6 357 36 37 32 38 39 40 41 421 33 35 31 33 48 *The elevated amylase occurred 8 days after cholecystectomy for stones and was accompaniel by epigastric pain vomiting and jaundice Cholecystectomy 18 days after amylase determination Epigastric pain and serum amylase 44 three years before ·58 Serum Amylase TABLE 16. SERUM AMYLASE IN CANCER OF THE PANCREAS SERUM No. Amylase P'tase PANCREATIC FUNCTION TEST FINDINGS AT OPERATION Bili. 2.8 2.7 1 2 3 4 5 47 36 55 87 108 Normal Abnormal Normal Abnormal Abnormal 18 9 11.5 9.2 Normal Abnormal 19 36 18 10. 6.9 18.5 6 7 8 9 10 11 12 13 52 37 67 52 81 18 12 15 17 22 6.9 12. Abnormal Ca. of the duodenum and head of P. Ca, entire P. Movable mass head P. Ca. head of P. Ca. duodenum blocked P. duct, secondary fibrosis P. Ca. stomach involving P. Ca. P., metastases to peritoneum Ca. head P. Ca. head and body P. Ca. entire P. Ca. head of P. Ca. head of P. Ca P., metastases liver, peritoneum (autopsy) Ca. head and tail P. (autopsy) Ca. head of P. Ca. ampulla vater Retroperitoneal mass, metastases liver, possibly ca. body P. Ca, head P. Ca. head P. Ca. head P. Ca ampulla, partial occlusion P. duct. Biopsy=fibrosis, Ca. head P. Abnormal 14 15 16 17 25 10 24 27 19 9.4 24 11. 6.8 11.3 Abnormal 18 19 20 21 21 25 30 16 145 22 19.6 32 82 12.6 13. 96 Abnormal Normal Abnormal 22 29 34 24. SERUM AMYLASE IN OPERATED CASES OF GALLBLADDER DISEASE In 42 operated cases of gallbladder disease (Table 17), the serum amylase was under or slightly over 30. In several jaundiced patients, exploration of the common bile duct was negative; in 12, palpation of the pancreas was also negative. Transitory edema of the head of the pancreas probably accounts for the occasional rise of amylase in this condicion. While stones in the gallbladder are common in pancreatitis, pan. creatitis is uncommon in the ordinary case of gallstones. It is more likely to occur in the long-standing cases with pericholecystitis and lymphatic spread.

·Serum Amylase in Patients with Stone in the Common Bile Duct 61 SERUM AJIYLASE IN PATIEXTS WITH STOVE IN THE COMMON BILE DUCT The amylase was above normal in 28 of 40 patients (70 per cent) with stone in the common duct. The surgcon examined the pancreas in 19 of these 28 patients. He found induration, enlargement or fat necrosis in 15 (79 per cent). As in acute pancreatitis without common duct stone, the decline of serum amylase was usually rapid. In 26 patients (65 per cent), measurable amounts of bilirubin were found in the serum. Pancreatic function tests were carried out in 12 patients: S were normal (66 per cent). The association of pancreatitis with common duct stone is frequent. The generally accepted cause of this complication is the entrance of bile into the pancreatic duct, the so-called common channel theory. In support of this time-honored conception is the fact that in human cholangiograms the contrast melium injected into the common bile duct occasionally enters the pancreatic duct. Levens7 saw the pancreatic duct in 23 per cent of 91 cholangiograins. In a few instances, actual blockage of the opening of the pancreatic duct by a stone in the ampulla may account for an elevated amylase. The follow-up experience indicates that removal of the stone results in permanent cure in the larger number of patients. TABLE 19. NORMAL SERUM ANYLASE IX PROVED CASES OF COMMON DUCT STONE SERUST No. PANCREATIC FUNCTION TEST CONDITION OF HEAD OF PANCREAS AT OPERATION REMARKS Amylase plase Bili. 1 21 0 7.9 7.3 1.6 9.4 Abnormal Normal Normal Abnormal Normal 2 3 4 5 6 7 8 9 10 11 13 16 30 28 22 17 12 16 12 15 23 4.0 Abnormal Normal Normal Abnormal Normal 3.2 5.1 12 5 54 63 60 8.4 T.U. 6 yrs. uncientful Serum lipasc 1.2 (norinal) F.U. 5 yrs uneventful 12 12 81 ·60 Serum Amylase Table 18. ELEVATED SERUM AMYLASE IN OPERATED CASES OF COMMON BILE DUCT STONE No. S.A. DAYS LATER SERUBI PANCREATIC CONDITION OF Phos. Bili. FUNCTION THE HEAD OF phalase rubin TEST PANCREAS REMARKS 1 39.0 Trace Normal Normal Normal Abnormal Norrnal Normal 20 38 2 36 3 211 29 4 32 5 118 6 112 7 150 35 8 36 9 56 5.0 Trace 42.0 0.2 1.8 Abnormal Normal Abnormal Abnormal 2.8 4 4.7 Trace 120 3.0 Abnormal Autopsy-Fat necrosis, P. necrosis 4 10 4.6 Abnormal 2 4 15.0 Normal Abnormal Abnormal Normal Abnormal 4.9 1 6.1 5.6 1 26 10 93 36 73 11 82 12 73 13 67 14 43 15 15 31 16 94 22 17 36 18 31 19 55 20 136 23 21 51 42 22 45 23 269 58 24 88 25 38 26 80 27 94 28 40 2.9 48 88 Normal Normal Trace 3.4 1.5 28 Normal Normal Normal Normal 3 11.0 14.0 Abnormal Abnormal 2 11.0 5,0 Trace Abnormal Abnormal Scrum lipase 14.2* Serum lipase 4 1 1 2.7 2.2 11.6 14.0 8.3 1.2 3.0 20.0 Abnormal F.U. 14 yrs. uneventful Abnormal FU. 6 yrs, uneventful 6.0 •The elevation of the lipase and amylase was about ten times the normal. This patient had to bouts of pancreatitis in succeeding years ·Serum Amylase in Patients with Stone in the Common Bile Duct 61 SERUM AMYLASE IN PATIENTS WITH STONE IN THE COMMON BILE DUCT The amylase was above normal in 28 of 40 patients (70 per cent) with stone in the common duct. The surgeon examined the pancreas in 19 of these 28 patients. He found induration, enlargement or fat necrosis in 15 (79 per cent). As in acute pancreatitis without comninon duct stone, the decline of serum amylase was usually rapid. In 26 patients (65 per cent), measurable amounts of bilirubin were found in the serum, Pancreatic function tests were carried out in 12 patients; 8 were normal (66 per cent). The association of pancreatitis with common duct stone is frequent. The generally accepted cause of this complication is the entrance of bile into the pancreatic duct, the so-called common channel theory. In support of this time-honored conception is the fact that in human cholangiograms the contrast medium injected into the common bile duct occasionally enters the pancreatic duct. Leven37 saw the pancreatic duct in 23 per cent of 91 cholangiograms. In a few instances, actual blockage of the opening of the pancreatic duct by a stone in the ampulla may account for an elevated amylase. The follow-up experience indicates that removal of the stone results permanent cure in the larger number of patients. in TABLE 19. NORMAL SERUM AMYLASE IN PROVED CASES OF COMMON Duct STONE SERUM No. PANCREATIC FUNCTION TEST CONDITION OF HEAD OF PANCREAS AT OPERATION REMARKS Amylase Plase Bult. 21 0 7.9 73 1.6 9.4 1 2 3 4 5 6 Abnormal Normal Normal Abnormal Normal 13 16 30 28 22 17 12 16 12 15 23 4.0 Abnormal Normal Normal Abnormal Normal 60 32 51 12 5 54 6.3 8 9 10 11 84 F.U. 6 yrs. uneventful Serum lipase 1.2 (normal) F.U. 5 yrs uneventful 12 12 81 ·62 Serum Amylase The causal relationship between gallstones and pancreatitis is one of several good reasons for advising cholecystectomy, once the diagnosis of gallstones has been established. Common duct stones, suppurative cholecystitis, cholangitis, perforation of the gallbladder and carcinoma of the gallbladder are other possible complications of stones in the gallbladder. Not too rarely, these complications occur late in life, forty or more years after the disease first made its presence known, when the operative risk is potentiated, and the choice of surgeon and hospital is not optional. TABLE 20. NORMAL SERUM AMYLASE IN DUODENAL ULCER No. S.A. SYMPTOMS OF D.U. X-RAY EVIDENCE OPERATION REMARKS OF D.U 1 2 3 4 5 6 7 30 21 20 12 22 13 30 ++ +++ + + 8 9 10 11 12 13 14 15 16 17 18 19 20 25 26 17 26 20 19 19 30 17 26 29 17 21 +++++++ ++++ ++++++++ + +++++ + Partial gastrectomy Pancreas normal None Suture Perforating ulcer None Suture Perforating ulcer None Partial gastrectomy Ulcerpenetrating into head of pancreas Partial gastrectomy Partial gastrectomy Suture Perforating gastric ulcer None Suture Perforating duodenal ulcer Suture Perforating duodenal ulcer Suture Perforating duodenal ulcer None None None None None Partial gastrectomy Inflammation about head pancreas Partial gastrectomy Penetrating ulcer, firmn head pancreas None Partial gastrectomy Partial gastrectomy Pancreas normal Partial gastrectomy Perforating duodenal ulcer None +++++ 21 23 22 23 24 25 26 26 26 28 30 19 + ++++ 27 17 + ·Serum Amylase in Duodenal Vlcer 63 TABLE 21. ELEVATED SERUM AMYLASE IN DUODENAL ULCER SYMPTOMES No. SA X-RAY EVIDENCE OF D.U. OPERATION REMARKS OF D.U. 1 + 46 74 42 65 31 34 33 None None Partial gastrectomy Ulcer adherent to pancreas None 2 3 4 5 6 7 8 9 10 31 59 129 89 48 56 157 53 十十十十十十十十十十十十十十十 12 13 15 16 51 None Partial gastrectomy Ulcer penetrating into pancreas Partial gastrectomy Partial gastrectomy Partial gastrectomy Ulcer adherent to pancreas Partial gastrectomy Ulcer adherent to pancreas Partial gastrectomy Ulcer post. wall, prepyloric Partial gastrectomy Ulcer adherent to pancreas Partial gastrectomy Ulcer adherent to pancreas Partial gastrectomy Ulcer pylorus penetrating pancreas Repair of prepyloric perforating ulcer Repair of perforating duodes, ulcer Partial gastrectomy Ulcer adherent to pancreas Partial gastrectomy Perforating ulcer scaled by pancreas None Partial gastrectomy Penetrating ulcer Drainage subphren. Perforating ulcer abscess Partial gastrectory 17 32 18 19 157 56 20 21 22 41 151 65 ++ +++ + + 23 33 + SERUM AMYLASE IN DUODENAL ULCER As the posterior and inferior surfaces of the duodenal bulb are contiguous with the head of the pancreas, penetration of a posterior ulcer may result in sufficient inflammatory swelling of the pancreas to interfere with the outflow of pancreatic juice and thus raise the serum amylase level. Comfort and Osterberg74 report serum lipase determinations in 102 cases of duodenal and 3 cases of gastric ulcer. In only 7 was the lipase elevated, and in all the ulcer had penetrated into the pancreas. The lipase was also elevated in 2 of 31 cases of carcinoma of the stomach, and here also the tumor had invaded the paricreas.

·64 Serum Amylase The serum amylase is usually normal in duodenal or gastric ulcer. An elevated serum amylase in a patient with chronic duodenal ulcer is an argument in favor of partial gastrectomy. SERUM AMYLASE IN CHRONIC NEPHRITIS The elevation of serum amylase in kidney disease in obviously due to its dimished elimination. The practical value of this test would have to be determined on a larger series. Whether the glomeruli alone participate in the elimination or whether there is tubular secretion or reabsorption of amylase is not known. From his studies in experimental uranium nephritis, Fitz78 con. cluded that the amylase excretion test was similar but less delicate than the 'phthalein test.' Geyelin79 found that the amylase and phenolsulfonphthalein excretion were comparable in human kidney disease. Heilitz et al. 80 observed that the serum amylase was elevated in 70 per cent of 111 cases of renal insufficiency. Recently a patient suffering from chronic nephritis, hypertension and urea retention developed upper abdominal pain, leukocytosis and an elevated serum amylase. Exploration revealed a subcapsular hemorrhage of the liver instead of the expected acute pancreatitis. The elevated serum amylase was apparently due to retention. TABLE 22. ELEVATED SERUM AMYLASE IN KIDNEY DISEASE No. S.A. UREA Nitrogent CLINICAL FEATURES SERUM Phosphatase REMARKS mg. % mg. % 11.7 57 Autopsy Autopsy 2 3 4 5 43 85 32 82 146 Chronic glomer nephritis Chronic glomer, nephritis Chronic glomer, nephritis Nephrosclerosis Chr. glomer, nephritis 185 23 15 57 110 Autopsy Autopsy SERUM AMYLASE IN SALIVARY GLAND DISEASES A considerable part of the amylase in the serum is furnished by the salivary glands. In dogs, Pratt12 and associates observed high serum amylase values when little or no pancreatic parenchyma remained. When there is obstruction of the salivary duct system by tumor, ·Serum Amylase in Miscellaneous Abdominal Diseases 65 calculus, or inflammation, reabsorption increases sufficiently to raise the amylase level in the serum. Recently, Wolman and his associates81 reported a series of amylase tests in 101 cases of adult mumps. An elevation occurred during the first week which faded during the second week. Zelman82 found that 73 per cent of mumps cases have an elevated amylase. In doubtful cases of sialadenitis, the test should have diagnostic value. TABLE 23. ELEVATED SERUM AMYLASE IN SALIVARY GLAND DISEASE No. S.A. CLINICAL FEATURES AND REMARKS 2 3 34 35 49 56 92 Parotitis Mumps Tumor of the parotid (composite) Swelling of submaxillary gland-removal of calculus from duct Mumps SERUM AMYLASE IN MISCELLANEOUS ABDOMINAL DISEASES Lewison 83 found that the serum amylase was normal in 94 per cent of 720 patients who were not afflicted with pancreatic, salivary, or biliary tract disease. In our series of miscellaneous operated abdominal cases (Table 24), the serum amylase was usually below 30, the upper limit of normal. Slight elevations are not always easy to explain. TABLE 24. SERUM AMYLASE IN MISCELLANEOUS ABDOMINAL DISEASES SERUM No. Ceph. CLINICAL FEATURES AND REMARKS Amylase Plase Bili. Floc. 1 20 11. 2 3 23 25 24 17 26 6.7 60 100 20 15 11 4 17. 18. 19. 4+ Jaundice, no operation, hepatitis, normal P. Function Test Jaundice, ca. hepatic duct Jaundice, hepatitis, no operation 3+ Jaundice, hepatitis, no operation 3+ Jaundice, hepatitis, no operation Jaundice, hepatitis, no operation, normal P. function test Jaundice, epigastric pain, stenosis rt. hepatic duct, normal P. function test 5 6 7 23 Trace ·66 Serum Amylase TABLE 24 (Continued). SERUM AMYLASE IN MISCELLANEOUS ABDOMINAL DISEASES SERUM No. Ceph. Floc. CLINICAL FEATURES AND REMARKS Amylase P'lase Bili. 8 23 4.5 9.7 9 10 10 23 4.7 10.8 Jaundice, hepatitis, no operation, normal P. function test 4+ Jaundice, hepatitis, no operation Jaundice, R.U.Q. pain, stenosis of common bile duct, no operation Jaundice, ca. ovary, Inetast. region pancreas 0 Hepatitis, chğlangitis, exploratory, jaundice 44 39 7.0 26 1.6 5.7 10.4 12 13 14 15 16 17 18 11 34 32 47 20 27 21 18 . 19 20 27 8 Pain ant. chest, myoc. in infarction, no operation Epig. pain, dissect. aneurism, no operation Epig. pain, amebic hepatitis, ameb, stool, no operation Abd. pain, distention, dilated small intestine Left abd. pain, ca. sigmoid mnal 16 15 atamanah 21 22 23 24 25 26 9.6 16 33 36 7.2 2.3 tion 9 27 28 29 30 31 32 13 24 21 33 34 18 28 Gland enlarged, autopsy-Hodgkins disease Acute appendicitis Epig. mass, normal pancreatic function test, retroperitoneal sarcoma Acute intestinal obstruction Large liver, spleen, no operation, cirrhosis of liver Acute appendicitis Partial gastrectomy, small ulcer, 100% gastric retention and vomiting, Mid. abd, mass, retroperitoneal sarcoma 35 36 31 75 37 35 In patient No. 52, disease of the pancreas was suspected, En ... LI ·Conclusions 67 CONCLUSIONS Our knowledge of the pathologic physiology of the pancreas has been furthered by chemical laboratory procedures. The minimal ferment activity of the pancreatic juice by the Free and Myers method after mecholyl stimulation in nonpancreatic disease is 4 mg. of reducing sugar for amylase, 50 mg. of nonprotein nitrogen for protease, and 8 cc. of 0.1 normal butyric acid for lipase. The determination of ferment concentration in the pancreatic juice is helpful in the diagnosis of obstructive jaundice, chronic pancreatitis and sprue. As the pancreas has a large functional reserve, marked diminution of ferment concentration indicates widespread disturbance. Rarely, autonomic imbalance may alter ferment concentration through abnormal vagal influence. In nonjaundiced patients, the determination of fecal fat is helpful in the diagnosis of pancreatic disease and in ascertaining the effect of orally administered ferments. An elevated serum amylase is diagnostic of acute inflamation or edema of the pancreas and thus serves to differentiate this from other acute abdominal conditions. The serum amylase may also be elevated in duodenal ulcer penetrating into the pancreas, in inflammation of the salivary glands, and in advanced kidney disease.

·68 Bibliography BIBLIOGRAPHY 1. Agren, G., and Wilander, O.: Reinigung von Sekretín, Biochem. Ztschr. 259:365-373, 1933. 2. Agren, G.: On the properties of sccretin, J. Physiol. 91:553–559, 1938, 1939. 3. Agren, G., and Lagerloef, H.: The pancreatic secretion in man after intra. venous administration of secretin, Acta. med. Scandinav, 90:1-29, 1936. 4. Hammarsten, E., Agren, G, and Lagerlocf, H.: The correlation between secretin dose and pancreatic ellect in man, Acta. med. Scandinav. 92:256– 266, 1937. 5. Lagerloef, H,: Secretin test of pancreatic function, Quart. J. Med., New Series: 8:115-126, 1939. 6. Lagerloef, H.: Pancreatic Function and Pancreatic Disease, New York, Macmillan, 1942, pp. 157, 164 ff. 7. Diamond, J. S., Siegel, S. A., Gall, M. G., and Karſen, S.: The use of secretin as a clinical test of pancreatic function, Am. J. Digest Dis. 6:366– 372, 1939. 8. Diamond, J. S, and Siegel, S A.: Clinical application of secrctin in the study of pancrcatic function, New York State J. Med. 41:869-875, 1941. 9. Comfort, M. W., and Osterberg. A. E.: Pancreatic secretion in man after stimulation with sccrctin and acetyl-beta methyl choline chloride. Comparative study. Arch. Int. Nied. 66-688-706, 1910. 10. Comfort, M. W.. Test of pancreatic function, J A. M. A. 115:2014-2050, 1940. 11. Comfort, M. W, Parker, P. L., and Osterberg, A. E.: Concentration of pancreatic enzymes in duodenum of normal persons and persons with disease of the upper abdomen, Am J. Digest Dis 6 249–254, 1939. 12. Pratt, J. H.: Diagnosis of pancrcatic disease, New York State ). Nied. 43: 1847-1855, 1913. 13. Pratt, J. H. Pancreatic discase, J. A. M, A. 120.175-182, 1912. 14. Andrus, w. Delv., Lord, I w., Jr., and Lake, M.: Test of hepatic and panaeatic function in 1.0. on of patients with lesion of the bil 1942. 15. Pollard, H. M., Miller study of the secretin test, Am J. Digest Dis 9.68-73, 1942 16. Bauman, L., and Whipple, A. O: The diagnostic value of pancreatic function tests in 47 surgically treated cases, Am ). M, Sc 207.281-290, 1914. 17. Comfort, M. W., and Osterberg, A. E.: Serum amylase and serum lipase in diagnosis of disease of the pancreas, M. Clin. North America 24:1137- 1140, 1940 18. Whipple, A, O, Parsons, W. B., and Mullins, C. R: Treatment of car. cinoma of the ampulla of Vater, Ann, Surg 102:763-779, 1935. 19. Whipple, A. O. Surgical treatment of carcinoma of the ampullary region and head of the pancreas, Am J Surg. 40:260-263, 1938. 20. Priestley, J. T, Comfort, M. W, and Radcliff, J. Jr.: Total pancrcatectomy for hyperinsulinism due so an islet-cell adenoma, Ann. Surg. 119 211- 221, 1944. 21. Dixon, C. F., Comfort, M, W., Lichtman, A. L, and Benson, R. E.: Total pancreatectomy in a diabetic person for carcinoma of the pancreas, Arch. Surg. 52:619-639, 1916. .

·Bibliography 69 22. Waugh, J. M., Dixon, C. F., Clagett, 0. T., Bollman, L., Sprague, R. G., and Comfort, M. W.: Total pancreatectomy: a symposium presenting 4 successful cases and a report on metabolic observations, Proc. Staff Meet., Mayo Clin, 21.25–46, 1946. 23. Thorogood, E., and Zimmermann, B: The effects of pancreatectomy on glycosuria and ketosis in dogs made diabetic by alloxan, Endocrinology 37:191-200, 1943. 24. Chiray, M., Jeandel-Mercier, and Salmon, A R.: Action de la sécrétin purifiée sur la sécrétion externe du pancréas de l'homme, Bullet mém. Soc. méd. d. hộp. de Paris 50.1417-1426, 1926. 25. Chiray, M., and Bolgert, M.; Le test de la sécrétion dans les affections du pancréas, Arch. d. mal. de l'app digestif. 29.5–32, 1939. 26. Bauman, L.: Tests of the external pancreatic function, Nelson's New Loose Leaf Surgery, Vol. 5, New York, Nelson, 1946, pp. 423-428. 27. Necheles, H: Discussion of Comfort (see No. 10), J. A. M. A. 115:2054, 1940. 28. Free, A H., and Myers, V. C: The estimation of enzymes, amylase, proteinase, and lipase in duodenal contests, J. Lab. & Clin. Med. 28:1387– 1398, 1943. 29. Wohlgemuth, J. Ueber eine neue Methode zur Bestimmung quantitativen des diastatischen Fermentes, Biochem. Ztschr. 9 1-9, 1908 30 Gross, O.: Die Wirksamkeit des Trypsins und eine einfache Methode zu ihrer Bestimmung, Arch. f. exper. Path. u. Pharmakol. 58 157-166, 1908 31. Cherry, I. S., and Crandall, L A., fr: Specificity of pancreatic lipase; its appearance in blood after pancreatic injury, Am. J Physiol. 100:266– 273, 1932. 32. Andersen, D. H. Cystic fibrosis of the pancreas and its relation to celiac disease, Am. J. Dis. Child. 56.344-399, 1938. 33. Coffey, R. J. Mann, F C., and Bollman, J, L., III: The influence of the pancreas on the utilization of foodstuffs, Am. J. Digest Dis 7 144-149, 1940. 34 Dragstedt, L. R.: Some physiologic problems in surgery of the pancreas, Ann. Surg. 118:576–589, 1943. 35. Frantz, V Kneeland: Personal communication, 36 Colp, , and Doubilet, H. clinical significance of pancreatic reflux, Ann Surg: 108-243-259, 1938. 37. Leven, N. L. Reflux into major pancreatic duct during cholangiography, Proc. Soc Exper. Biol. & Med. 38 808–809, 1938 38. Comfort, MW, Gambill, E. E., and Bagenstoss, A H.: Chronic relapsing pancreatitis. A study of 29 cases without associated disease of the biliary or 39. 40. Miller, J. M, and Wiper, T. B.: Physiological observations on patients with !" 41. 42. Pasternak, J. G. Calcareous pancreatitis Report of 3 cases with autopsies, Ann. Int. Med. 19.757–767, 1943. 43. Walters, W Strictures and injuries of the bile ducts, J A. M. A 113:209– 213, 1939.

·70 Bibliography 44. Peterson, L. W., and Cole, W. H.: Chronic sclerosing pancreatitis causing complete stenosis of the common bile duct, Arch, Surg. 51:15-21, 1945. 15. Bisgard, T. D.: Pancreatitis as a cause of complete obstruction of the common bile duct, Ann. Surg. 124:1009--1017, 1916. 46. Eusterman, G. B, and Wilbur, D, L.: Primary malignant neoplasm of the pancreas, South. M. J. 26:875-883, 1933. 47. Pratt, J. H.: Diagnosis of pancreatic disease, New York State J. Med. 43: 1847-1855, 1943. 48. Brocq, B., and Miginiac, G., Chirurgie due pancreas, Paris, Masson, 1931, p. 65 ft. 49. Walters, w, and Dehne, E. A.: Jaundice caused by pancreatic lesions; Surg., Gynec. & Obst. 54.832-835, 1932. 50. Cattell, R. B.: Pancreaticoduodenal resection; preliminary report of 18 cases, New England J. Med. 232:521-526, 1945. 51. Grauer, F. W.: Pancreatic carcinoma. A review of 34 autopsies. Arch. Int. Med. 63:884-898, 1939. 52. Berk, J. E.: Diagnosis of carcinoma of the pancreas, Arch. Int. Med. 68: 884-898, 1939. 53. Ransom, H. K.: Carcinomna of the pancreas and extrahepatic bile duct, Am. J. Surg 40:264-281, 1938. 54. Shapiro, P. F., and Lifdendahl, R. A.: Tumor of extrahepatic bile duct, Ann. Surg. 94:61-79, 1931, 55. Childs, A., and Dick, G. F.: Pancreatic function in a case of nontropical sprue, Arch. Int. Med. 66.833-847, 1941. 56. Frazer, A. C., and Sammons, H. G.: The formation of mono- and diglycerides during the hydrolysis of triglyceride by pancreatic lipase, Biochem. J. 39:122-128, 1945. 57. Frazer, A. C.: The absorption of triglyceride fat from the intestine, Physiol. Rev. 26:103-109, 1946. 58. Whipple, A. O, and Bauman, L: Observation on the pathologic physiology of the insular and external secretory functions of the human pancreas, Am. J. M. Sc. 201-629-636, 1941. 59. Handelsman, M. H.: The digestive and absorptive function of the external secretion of the pancreas, Ann Int. Med. 11:1479-1497, 1938 60. Brunschwig. A. The surgery of pancreatic tumors, St. Louis, Mosby, 1942, p. 57. 61. Brunschwig, A., and Allen, J. G: Occlusion of the external pancreatic secretion in man, Proc. Soc. Exper. Biol. & Med. 53:43-47, 1943. 62. Wollaeger, E. E., Comfort, M. W., Clagett, O. T., and Osterberg, A. E.: Efficiency of the gastrointestinal tract after resection of the head of the pancreas, J. A. M. A. 137 838-848, 1948. G3. Friedman, I., and Thompson, W.R: Induced and spontaneous changes in blood amylase, particularly in relationship to the pancreas, Ann Surg 104: 388-401, 1936. 64. Myers, V C., and Killian, J. A. Studies on animal diastases. 1. The increased diastatic activity of the blood in diabetes and nephritis, J. Biol. Chem. 29 179-189, 1917 65. Myers, V. C., Free, A. H., and Rosinski, E. E.: Studies on animal diastases. 6. The determination of diastase (amylase) in blood, J. Biol. Chem. 154: 99-48, 1944.

·Bibliography 71 66. Schlesinger, W.: Ueber den Ursprung des diastatischen Fermentes in Blute und uber seine Beziehungen zum Diabetes Melitus, Deutsche med. Wchnschr. 34-593–595, 1908. 67. Wohlgemuth, J.: Beitrag zur funktionellen Diagnostik des Pankreas, Klin. Wchnschr. 47:92-95, 1910. 68. Elman, R.: Surgical aspects of acute pancreatitis with especial reference to its frequency as revealed by serum amylase test, J. A. M. A. 118:1265– 1268, 1942. 69. Griesmann, H.: Zur Diagnose and Therapie der akuten Pankreas erkankungen, Deutsche Ztschr, f. Chir. 252 19-40, 1939. 70. Clark, E: Pancreatitis in acute and chronic alcoholism, Am. J. Digest Dis. 9:428-431, 1942. 71. Branch, A: Pancreatic necrosis in ethyl alcohol, methyl alcohol, and arsenic poisoning, Canad. M. A. J. 51:428-430, 1944. 72. Carter, S. J.: Serum amylase in chronic alcoholism with acute abdominal symptoms, Ann. Surg. 122.117–121, 1945. 73. Weiner, H. A., and Tennant, R. A.: A statistical study of acute hemorrhagic pancreatitis, Am. J. M. Sc. 196-167–176, 1938. 74. Comfort, M. W., and Osterberg, A. E.: The value of determination of serum amylase and serum lipase in the diagnosis of disease of the pancreas, Proc. Staff Meet., Mayo Clin. 15:427-432, 1940. 75. Lagerloef, H.: Personal communication (1947). 76. McCall, M. L., and Reinhold, J. G: An evaluation of the clinical significance of serum amylase and lipase determinations, Surg., Gynec. & Obst. 80.434-440, 1915. 77. Comfort, M. W., Butt, H. R., Bagenstoss, A, H., Osterberg, A. E, and Priestley, J T.: Acinar cell cancer of pancreas' report of a case in which function of carcinomatous cells was suspected, Ann. Int. Med. 19:808- 816, 1943. 78. Fitz, R.: The relation between amylase retention and excretion and nonprotein nitrogen retention in experimental uranium nephritis, Arch. Int. Med. 15-524–542, 1915. 79. Geyelin, H. R: A clinical study of amylase in the urine, Arch. Int Med. 13.96-120, 1913 80 Heifitz, C. J., Probstein, J G., and Gray, S. H: Clinical studies on blood diastase. Significance of increased blood diastase, Arch. Int. Med. 67. 819-827, 1941. 81. Wolman, 1. J.. Evans, B, Lasker, S., and Jaegge, K Amylase levels during mumps. Findings in blood and saliva, Am J. M. Sc. 213:477–481, 1947. 82. Zelman, S.: Blood diastase values in mumps and pancreatitis, Am. J. M. Sc. 207:461-464, 1944 83. Lewison, E. F.: Clinical value of the serum amylase test, Surg., Gynec. & Obst. 80:435–440, 1945 84. Heard, R D. H, Lozinski, E., Stewart, L, and Stewart, R D An alpha celi hormone of the islets of Langerhans, J Biol Chem. 172 857-858, 1948. 85. Vermeulen, C., Owens, M. F., Jr., and Dragstedt, L R.: The effect of pancreatectomy on fat absorption from the intestines, Am. J. Physiol. 138: 792-896, 1942-1943 86. Doubilet, H., and Mulholland, J. H.: Surgical treatment of recurrent acute pancreatitis by endocholedochal sphincterectomy, Surg, Gynec. & Obst. 86:295-806, 1948.

·9, 65 ft. 70 Bibliography 44. Peterson, L. W., and Cole, W. H.: Chronic sclerosing pancreatitis causing complete stenosis of the common bile duct, Arch. Surg. 51:15-21, 1915. 45. Bisgard, T. D.: Pancreatitis as a cause of complete obstruction of the com mon bile duct, Ann. Surg. 124:1009-1017, 1946. 46. Eusterman, G. B, and Wilbur, D. L.: Primary malignant neoplasm of the pancreas, South. M. J. 26:875–883, 1933. 47. Pratt, J. H.: Diagnosis of pancreatic disease, New York State J. Med. 43: 1847-1855, 1943. 48. Brocq, B., and Miginiac, G.: Chirurgie due pancreas, Paris, Masson, 1934, 49. Walters, W., and Dehne, E. A.: Jaundice caused by pancreatic lesions; Surg., Gynec, & Obst. 54.832-835, 1932. 50. Cattell, R. B.: Pancreaticoduodenal resection; preliminary report of 18 cases, New England J. Med. 232:521-526, 1945. 51. Grauer, F. W.: Pancreatic carcinoma. A review of 34 autopsies Arch. Int. Med. 63:884-898, 1939. 52. Berk, J. E.: Diagnosis of carcinoma of the pancreas, Arch. Int. Med. 68: 884-898, 1939. 53. Ransom, H. K.: Carcinoma of the pancreas and extrahepatic bile duct, Am. J. Surg, 40:264-281, 1938. 54. Shapiro, P. F., and Lifdendahl, R. A: Tumor of extrahepatic bile duct, Ann. Surg. 94:61-79, 1931. 55. Childs, A., and Dick, G. F.: Pancreatic function in a case of nontropical sprue, Arch. Int. Med 66.833-847, 1941. 56. Frazer, A. C, and Sammons, H. G: The formation of mono- and diglycerides during the hydrolysis of triglyceride by pancreatic lipase, Biochem. J. 39:122-128, 1945. 57. Frazer, A. C.: The absorption of triglyceride fat from the intestine, Physiol. Rev. 26-103-109, 1946. 58. Whipple, A. O., and Bauman, L.: Observation on the pathologic physiology of the insular and external secretory functions of the human pancreas, Am. J. M. Sc. 201:629-636, 1941. 59. Handelsman, M. H.: The digestive and absorptive function of the external secretion of the pancreas, Ann. Int. Med, 11.1479-1497, 1938. 60. Brunschwig. A.: The surgery of pancreatic tumors, St. Louis, Mosby, 1942, p. 57. 61. Brunschwig, A., and Allen, J. G.: Occlusion of the external pancreatic secretion in man, Proc. Soc. Exper. Biol. & Med. 53:43-47, 1943. 62. Wollaeger, E. E., Comfort, M. W., Clagett, 0. T., and Osterberg, A. E.: Efficiency of the gastrointestinal tract after resection of the head of the pancreas, J. A. M. A. 137 838-848, 1918. 63. Friedman, I., and Thompson, W. R. Induced and spontaneous changes in blood amylase, particularly in relationship to the pancreas, Ann. Surg. 104: 388-401, 1936, 64. Myers, V. C., and Killian, J. A: Studies on animal diastases. I. The in. creased diastatic activity of the blood in diabetes and nephritis, J. Biol. Chem. 29,179-189, 1917. 65. Afyers, V. C., Free, A. H., and Rosinski, E E.: Studies on animal diastases. 6. The determination of diastase (amylase) in blood, J. Biol. Chem. 154: 39-48, 1944.

·Index Atropine, antidote to mecholyl chloride, 4 Bile duct carcinoma, 36-40 ampullary with anomalous duct system, case report, 37, 40 differential diagnosis, 36-37 incidence, 36 pancreatic juice in proved cases, 37-39 Biliary tract disease, incidence of pancreatitis, 50, 58 Cancer of the pancreas, 27-36 behavior of patient after complete pancreatectomy, 21 body of pancreas tumors, 31, 34 case reports, 27, 28, 29, 30, 34 diagnostic value of exploration and biopsy, 27 fibrosis in, 28 influence of the site of turnor on pancreatic secretion, 27 inoperability of the majority of cases, 86 pancreatic juice in, 27, 32 secondary to chronic pancreatitis, 28, 29 Diabetes, in chronic pancreatitis, 20 after complete pancreatectomy, 21 Duodenal intubation, special tube for, 3 Fat, 45, 46 absorption in the absence of pancreatic juice and the effect of dried pancreas by mouth, 45, 46 determination in stool, 46 particulate absorption theory, 46 Insulin, inhibitor in the pancreas, last page of introduction Lipase, comparison of the substrates, tributyrin and emulsified olive oil, 4-6 Pancreas, functional impairment with. out morphologic change, case reports, 9, 10 functional reserve, case reports, 7-9 Pancreatic cyst fluid, 6 Pancreatic fistula fluid, 6, 19 Pancreatic function test, 1-43 apparatus for, 3, 4 methods used, 4 neutralization of gastric acidity with calcium carbonate, 4 sources of error in, 7 Pancreatic juice, 10-14 electrolyte concentration, 19 frequency distribution of volume and ferment concentration in nonpancreatic and pancreatic disease, 11-17, 35, 36 phosphatase in, 20 quantities used for ferment determination, 6 reaction of, 10 volume comparison after secretin and mecholyl, 2, 3, 18 Pancreatitis, acute, 14-19 diagnostic value of serum amylase in, 16, 50-56 causes of, 19, 50 common channel theory, 19 conservative treatment in, case report, 49, 51 incidence of gallstones in, 19. 50 pancreatic function in, 14 prevention of, 50 recurrent pancreatitis, 16 reflux of radio-opaque material into the pancreatic duct, 19 regeneration of the pancreas after an attack of, 14 73

·No text on this page.

·No text on this page.

·Index Pancreatitis chronic, 19-27 in common bile duct stones, 61-62 calcification in, 19, 20 determination by Myers and Killian case reports, 20-27 method, 47-49 causes of, 19 diagnostic value, 49 composition of pancreatic calculi, 19, expression of activity, 47 20 in functioning acinar carcinoma of cystic fibrosis in children, 8 the pancreas, 57 dissociation of ferment concentration in miscellaneous abdominal condi. in, 19, 24, 25 tions, 65-66 persistence of alkaline juice in, 19 normal limits, 49 recuperative power of the pancreas in penetrating duodenal ulcer, 63-64 in. Case report, 22 in renal disease, 64 secondary to duct obstruction by car. in salivary gland disease, 64-65 cinoma, 28 site of formation, 47 symptoms of, 20 in stones in the gallbladder, 58-60 Pernicious anemia, pancieatic juice in, Serum lipase, in carcinoma of the pan. 42, 43 creas, 56, 57 Serum amylase, 47-67 in duodenal ulcer, 69 in acute pancreatitis, case reports, 50. Sprue, 40-42 56 case report with autopsy, 40-42 in carcinoma of the pancreas, 56-58 fat absorption in, 40, 42 in chronic pancreatitis, 56 pancreatic juice in, 4042