The Differential Diagnosis of Duodenal Ulcer*

Medical Clinics of North America January, 1943. Chicago Number

THE DIFFERENTIAL DIAGNOSIS OF DUODENAL ULCER* LEON ORRIS JACOBSON, M.D.t

and WALTER LINCOLN PALMER, Ph. D., M.D., F.A.C.P.* THE differential diagnosis of acute and chronic diseases of the abdomen is one of the most difficult and interesting in medicine. Practically all such diseases have recognized classical signs and symptoms amply described in the textbooks, but deviation from these occur not infrequently and every possible diagnostic aid may be necessary for correct evaluation. The following three cases are presented to illustrate this fact. CASE I. DUODENAL ULCER SIMULATING CARCINOMA OF THE PANCREAS

A. ]., a forty-three-year-old male photo-engraver, entered the hospital on January 10, 1941, complaining of nausea, vomiting, anorexia, weight loss, progressive weakness, and dull to severe boring pain in the upper lumbar region of his back for a period of four months. Beginning in June, 1940, the patient began to have attacks of nausea and vomiting occurring about once a month and noted that the sight of food occasionally nauseated him. On September 17, 1940, the nausea became constant and vomiting occurred about every hour. In addition, he developed a constant pain in the upper lumbar region which varied in intensity from dull to a deep, severe, boring pain. He was able to retain little food or water, got relief from nothing but morphine, and- after several days was taken to a hospital where x-rays were made of the gallbladder, stomach and duodenum. The patient was told his difficulty came from the gallbladder and operation was advised. • From the Frank Billings Medical Clinic, Department of Medicine, University of Chicago. ·t Instructor in Medicine, University of Chicago School of Medicine; Attending Physician, Albert Merritt Billings Hospital. t Professor of Medicine, University of Chicago School of Medicine; Attending Physician, Albert Merritt Billings Hospital. 195

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On September 30, 1940, the surgeon found the gallbladder normal but described the pancreas as hard and nodular and without biopsy closed the abdomen. The patient was told that the pancreas was diseased but his wife was informed that the patient had an inoperable carcinoma of the pancreas. For a few days after the operation the patient felt better but nausea, vomiting and back pain soon recurred and codeine and morphine were necessary for relief. Three weeks later an unsuccessful attempt was made to alleviate the back pain by a paravertebral block. The patient was referred to our clinic specifically for another attempt at neurosurgical intervention for the alleviation of back pain. There was no history of vomiting of blood, black bloody or tarry stools, jaundice, chills, or fever.There had been weight loss of 15 to 20 pounds in the six months preceding admission. The past history and inquiry by systems were essentially negative. The patient was a well developed, only moderately undernourished male writhing in bed, characteristically assuming a sitting position and complaining bitterly of severe pain in the upper lumbar region of his back. The physical examination was essentially negative. No palpable abdominal mass or jaundice was noted. The blood pressure was 118 systolic and 80 diastolic; the pulse rate was 80; temperature, 99° F. The urine was negative; the red blood count was 4.29 million, hemoglobin 13.5 gm., and white cell count 9300 with a normal differential. The Wassermann and Kahn tests. were negative. A histamine test disclosed a maximum gastric secretion of 108 clinical units in fifty minutes. The blood amylase was 104 units, a normal value. There was no serum hyperbilirubinemia as judged by the quantitative van den Bergh test. The gallbladder, stomach, duodenum and colon were reported normal roentgenologically. However, a deformity of the duodenal bulb compatible with a diagnosis of duodenal ulcer was seen in one of the films.

On the basis of the roentgen findings the patient was placed on ulcer management consisting of milk and cream, of each 90 cc. each hour between 7 A.M. and 7 P.M. with 2 gm. of calcium carbonate every hour and 0.5 mg. of atropine sulfate four times daily as a therapeutic test. The patient obtained no relief from this regimen, however, and hypodermic injections of morphine were necessary. The failure of ulcer management to relieve the pain spoke strongly against the

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tentative diagnosis of duodenal ulcer provided the amount of antacid (milk and cream and calcium carbonate) used was adequate to neutralize the free acidity of the gastric secretion. In order to ascertain definitely that the pain would continue unrelieved by the continued neutralization of the acid, the stomach. was aspirated by means of a Rehfuss tube (free acid was present). Continuous aspiration was maintained for a few minutes followed by the washing of the stomach with a solution of sodium bicarbonate. During the course of twenty to thirty minutes there occurred a gradual but nevertheless dramatic transition from the severe boring lumbar pain to a dull lumbar pain which slowly disappeared and the patient became symptom-free. The relief was so surprising and so complete that it was decided to maintain the regimen of continuous aspiration of the stomach together with the hourly administration of calcium carbonate, 4 gm., by mouth. In no other way did we succeed in maintaining complete neutralization of the very abundant and highly acid gastric secretion and in controlling the pain. The hourly milk and cream (90 cc.) and powder (calcium carbonate 2 gm.) program as mentioned previously had proved entirely inadequate. During the first several days, discontinuance of the alkali at any time would result in a recurrence of the dull back pain but not of the severe boring lumbar pain. Fluid and electrolyte balance were maintained by the subcutaneous and intravenous normal salt solution. An "acid test" 1 was performed a number of days later by instilling into the empty stomach 200 cc. of a 0.5 per cent hydrochloric acid solution. Immediately the old back pain recurred in all of its original severity. Aspiration and lavage with a bicarbonate solution alleviated the distress after a brief time. This test was repeated with similar results on several occaSIOns. After several days of continuous stomach aspiration plus alkalies and intravenous electrolytes, the patient was placed on milk and cream of each 90 cc. each hour from 7 A.M. to 7 P.M., 0.5 mg. of atropine every four hours and 4 gm. of calcium carbonate or magnesium carbonate every hour, day and night. The tolerance for atropine was amazing, 8 mg. per

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day being given without signs of toxicity. The large doses of alkalies were essential to neutralize the acid and to prevent back pain. The patient gradually improved and after several weeks a regular modified ulcer regimen with milk, cream, powders and atropine maintained him symptom-free. The gastroduodenal x-ray was repeated and a duodenal ulcer crater was noted. The stools, which were positive for occult blood during the initial weeks of observation, gradually became negative. The patient has been back at work but under observation for the past year. The ulcer crater in the duodenum found on the second examination has disappeared and there has been no recurrence of symptoms. In fact, the patient's health has been excellent. CASE 11. LYMPHOSARCOMA WITH ULCERATION OF THE DUODENUM SIMULATING DUODENAL ULCER

R. K., a forty-two-year-old housewife, was admitted on January 17, 1941, complaining of intermittent gnawing to burning midepigastric pain for four years, severe cramplike upper abdominal distress alternating with a feeling of fullness, and burning back pain for eight days with localization of distress to the right upper quadrant of the abdomen for three days. Beginning in 1936, the patient began to have gnawing and burning epigastric distress coming on two to three hours after meals and relieved by food, milk and soda. Her private physician presumably demonstrated a duodenal ulcer by roentgen examination at that time and the patient was placed on milk, cream and powders apparently with inconstant relief, as she went to several physicians during the next three to four years and at various times took Amphojel, Sippy powders, and injection therapy. In the fall of 1940, for a brief period of one day, and again on January 2, 1941, the patient had diffuse and severe cramplike epigastric pain coming on in attacks during the day, lasting thirty to forty-five minutes, and receding only to appear again in about one hour. Except for the usual epigastric distress the patient remained relatively well until January 11, 1941, when she awakened in the morning with severe, knifelike, colicky epigastric pain associated with belching, nausea, occasional sour eructations and a dull, burning pain in the upper lumbar region of the back. The upper abdominal. distress continued unabated until three days

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before admission to the hospital, when it shifted to the right upper quadrant. There was no history of jaundice, chills or fever, or of bloody, black, or clay colored stools. Physical examination revealed an acutely ill, well developed, well nourished female. The temperature was 98.2° F., pulse rate 80, blood pressure 110 systolic and 70 diastolic, and respiratory rate 20. There was generalized abdominal tenderness, a moderate muscular rigidity in the upper right quadrant, and an ovoid 8-cm. mass palpable just to the right and above the umbilicus. There was no abdominal distention or visible evidence of peristalsis. No regional lymphadenopathy was present. The laboratory examination on admission revealed a red blood count of 4 million, hemoglobin 13 gm., white count 9750. The differential count was polymorphonuclears 62, small and large lymphocytes 30, eosinophils 3, and basophils 1. The urine was negative; the van den Bergh test, both direct and indirect, was negative. The blood Wassermann and Kahn tests were negative.

This case was not considered to be a surgical emergency and conservative therapy was instituted until further knowledge of the process could be ascertained. A histamine test revealed a maximum free acidity of 90 units in thirty minutes. Five stools were consistently positive for occult blood. X-ray examinations revealed a normal retrograde pyelogram, normal esophagus, stomach and colon, and normal visualization of the gallbladder without stone, but the entire medial margin of the gallbladder shadow was smoothly indented as if by a soft round tissue mass pressing upon it. The first and second and a questionable part of the third portion of the duodenum had an unusual appearance. The mucosal folds appeared irregular and thick. The lumen decreased in size. In the second portion of the duodenum a small projection could be seen just opposite the region of the ampulla of Vater with a small fleck and associated radiating folds. (see Fig. 18). On the eighth hospital day, operation by Dr. Keith Grimson revealed a large mass behind the stomach, pancreas and duodenum, pushing the latter forward so it lay almost immediately behind the anterior abdominal wall. The mass so involved the head of the pancreas and duodenum that some degree of obstruction was present and therefore a posterior

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gastro-enterostomy was performed. A large lymph node in the region of the head of the pancreas was removed for biopsy, which revealed a lymphosarcoma. For the first thirteen days postoperatively the patient was quite comfortable, but abdominal distress then appeared again, she became increasingly jaundiced, had a daily temperature elevation and finally developed a marked leukopenia. She died on the thirty-fourth postoperative day. The postmortem examination" revealed an emaciated, deeply jaundiced female with numerous petechiae over the

Fig. ls.-'-Two roentgen views of the duodenum showing the bizarre mucosal, pattern with a complete loss of the normal folds and markings in the second portion.

body but sparse on the face, a generalized lymphadenopathy and a large, firm mass immediately behind a right upper rectus surgical scar. Except for enlarged hilar, peribronchial, inferior and superior mediastinal lymph nodes and deeply bile-stained pleural fluid, the gross pathological changes of . interest were chiefly within the abdomen where there was also about 200 cc. of deeply bile-stained fluid. The liver was enlarged. The gallbladder' was adherent to the right border of the mass which was roughly globular and incorporated the pyloric end of the stomach, the proximal two thirds of the • Postmortem examination conducted by Dr. Eleanor Humphreys.

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duodenum, the pancreas, the root of the mesentery and adjacent lymph nodes, and measured 15 to 20 cm. in its various diameters. The core of the mass on cut section was composed of colorless elastic neoplastic tissue in parts of which the outlInes of lymph nodes were vaguely preserved. This central portion lay near the head of the pancreas and at the site of the lymph nodes in the root of the mesentery. The pancreas was largely replaced by pale tissue which seemed to invade it from the surrounding lymph nodes. The pyloric end of the stomach and the proximal duodenum curved about the mass and were partially embedded in it. Their walls were irregularly thickened by pale neoplastic tissue and their linings projected irregularly and were focally eroded. There was no gross evidence of a healed ulcer. There were no deep ulcers. The extrahepatic bile ducts, which were surrounded by discrete large nodes near tJle liver, ran through the periphery of the mass. The common duct had grossly invaded walls, an: irregular lining and a narrowed lumen. Microscopically, the spleen, liver, kidney, adrenals and bone marrow were all invaded by abnormal cells. All the lymph nodes examined from the pulmonary, mediastinal, axillary, gastric, pancreatic and mesenteric areas were invaded or replaced by abnormal cells. The pancreas was extensively invaded by abnormal cells and contained encapsulated areas of fat necrosis and focal areas of fibrosis and atrophy. The stomach was involved only focally and necrotic ulcers were seen in regions where the mucosa was infiltrated. The duo dermm was involved in all its coats (see Fig. 19), superficial ulceration being present. This was also true of the jejurmm. The abnormal cells which involved the structures as described above were rather pleomorphic and in many places the character was marked by degeneration. Most of them were relatively lymphocytoid, round, oval, or polyhedral without recognizable (H and E) processes or fibril formation. However, a few were spindle shaped. The bluish cytoplasm was nongranular. Many of the nuclei were vesicular with large nucleoli. The. nuclei were round, oval or indented, and cells with multilobular or multiple nuclei were fairly numerous. In some regions, especially in the lymph nodes,

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there was extensive nuclear degeneration. The systemic. distribution in both lymphatic and myeloid organs was widespread. The behavior of the local tumor was neoplastic (see Fig. 19).

Fig.

19.-Photomicro~raph (x 525) of ulceration ID the duodenum.

a section taken through the largest

Only a portion is shown.

The diagnosis anatomically was systemic lymphoblastoma (lymphosarcoma type) with generalized involvement of the lymph nodes and bone marrow and focal involvement of the liver, spleen, pancreas, adrenals, kidneys and gastro-intestinal tract. The major tumor centered about the root of the mesentery, pancreas, duodenum and pylorus of the stomach.

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CASE Ill. DUODENAL ULCER SIMULATING GALLBLADDER DISEASE

A. L., a seventy-five-year-old housewife, was admitted to the hospital complaining of attacks of severe, lancinating pain in the right upper abdominal quadrant and posterior subscapular region, with nausea, vomiting and jaundice recurrent for twenty-six years, and a weight loss of 60 pourids in the six months preceding admission. In 1914 the patient had her first attack of pain in the right upper quadrant, which came on abruptly and radiated through to the back. The pain was severe and colicky in nature, and was associated with nausea and vomiting and presumably with jaundice. She was hospitalized and cholecystostomy was done. Following the operation the patient was well for about six months and then had a recurrence of similar abdominal pain with nausea and vomiting, lasting two to four days and frequently requiring morphine. Attacks recurred two to three times yearly but the patient was clinically well between attacks. However, beginning about two years before admission and especially in the last six months, attacks of pain in the right upper quadrant had increased in frequency. In the six months preceding admission she was free of this· discomfort for only short intervals, felt weak and easily fatigued, lost 60 pounds in weight and pain was never relieved by food or alkalies. On two occasions her local physician advised cholecystectomy, which was steadfastly refused. On admission her temperature was 99 0 F.; pulse rate 100; respiratory rate 20. The blood pressure in millimeters of mercury was 100 systolic and 50 diastolic. Physical examination disclosed . a chronically ill, emaciated, dehydrated female without clinical icterus. There was considerable tenderness and resistance to palpation in the right upper abdominal quadrant but no palpable mass. The blood Wassermann and Kahn. tests were negative. The urinalysis was normal. The red blood count was 4.36 million, hemoglobin 13 gm. per 100 cc. of blood, and white count 13,800. The van den Bergh test was normal. The patient was unable to retain food and was given parenteral nourishment. She had a continuous aching pain in the right upper quadrant, with recurrent attacks of cramplike, colicky epigastric pain which was relieved only by morphine. Stools were found to be persistently positive for occult blood; a histamine test revealed tree acid present; and an x-ray examination disclosed faint visualization of the gallbladder without stone, and a

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normal esophagus, stomach and colon. A stenosing duodenal ulcer with crater was seen. The patient was placed on ulcer management with powders, milk and cream, and aspirations, and immediate relief of abdominal symptoms was obtained. However, she continued to have considerable retention, failed to gain weight or strength, and her appetite remained poor. On April 12, 1941, a posterior gastro-enterostomy was performed by Dr. Lester R. Dragstedt. At operation, scar tissue was observed around the duodenum. with duodenal stenosis and a moderately enlarged and thickened stomach. The patient made an uneventful but slow recovery from operation and was discharged on May 10, 1941, on three-meal modified ulcer management which included the use of atropine. Since operation and until the present time, the patient has remained symptom-free, her appetite is excellent and she has regained weight. COMMENT

The differential diagnosis of peptic ulcer need not be discussed in detail, but it should be emphasized that the larger percentage of cases of peptic ulcer show the classical symptom: chronic, periodic gnawing, aching or burning epigastric pain coming on one to four hours after meals and characteristically relieved by alkalies or food. Other cases of peptic ulcer manifest themselves in bizarre fashions: indefinite abdominal distress, acute gastro-intestinal bleeding with or without abdominal symptoms, periodic vomiting, or occasional acute perforation. Severe pain in peptic ulcer is unusual, and continuous severe pain is even more uncommon. Back pain (upper lumbar) may be associated with epigastric pain in peptic ulceration or may occur as the only symptom. However, the chronicity, periodicity, relationship to meals and responsiveness to the ordinary measures of treatment usually serve to identify the lesion clinically. Continuous, severe back pain or deep-seated, boring epigastric pain which does not respond to such measures has been mentioned by Risnhoff and Lewis2 as a point in differentiating carcinoma of the pancreas from gastro-intestinal

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ulceration. Chauffard,3 in an early description of the symptomatology of carcinoma of the pancreas, emphasized upper lumbar pain as an early and prominent symptom. Bourne4 points out that pain may be the only clinical manifestation of carcinoma of the pancrea~ for as long as two years, and may suggest disease of the vertebrae or disease affecting the sensory roots of the spinal cord. Hick and Mortimer5 studied fifty cases of carcinoma of the pancreas and concluded that pain, which is invariably present, is characteristically located in the lower dorsal and upper lumbar region of the back. Other authors (Kiefer,6 Dunphy,7 Grauer,8 and Levy and Lichtman9 ) have called attention to back pain in carcinoma of the pancreas. Kiefer6 and Adlero have pointed out the occasional presence of occult blood in the stools of patients with pancreatic carcinoma due to secondary gastro-intestinal ulceration. Grauer8 noted that in thirty-two cases of pancreatic carcinoma proved at autopsy, the symptoms of four were typical of peptic ulcer but no ulceration was demonstrable at postmortem examination. Primary lymphosarcoma of the stomach and duodenum has been reported by Prey, Foster and Dennis,l1 Strauss, Bloch, Friedman and Hamburger,12 Present13 and others. These authors described no characteristic symptomatology. One of Present's two patients had a history of typical peptic ulcer distress of one year's duration. Autopsy showed multiple ulceration of the duodenum. Keys and Walker 4 reported a case of an abdominal (retroperitoneal) lymphosarcoma proved at autopsy. Numerous small ulcers were present in the walls of the stomach and duodenum. The symptoms had extended over a five-year period and were "typical of a duodenal ulcer." Madding15 reported five cases of Hodgkin's disease of the stomach which could not be clinically distinguished from peptic ulcer or carcinoma of the stomach. One of the cases was diagnosed roentgenologically as duodenal ulcer with obstruction. The constant association of acid gastric juice in peptic ulcer as well as its role in the production of pain has recently been reviewed by Palmer.16 Whatever may be the primary

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cause of the original ulceration of the gastro-intestinal tract exposed to acid gastric juice, the mechanism of pain is clear, but the severity of the distress and its direction of radiation are dependent upon the sensitivity of the ulceration to acid gastric juice and the anatomical relationship of the lesion, respectively. Case III is of interest because it shows how easily the symptomatology of gallbladder disease and peptic ulcer may be confused, as indicated by the communications of Judd,17 MacLaren and Oerting,18 Mix,19 Bruce20 and others. Their reports dealt with cases in which peptic ulcers and gallbladder disease existed concomitantly. Incidentally, reference may also be made to the fact that duodenal ulcer may simulate "the great imitator." Wilbur and Cutler21 and Eusterman22 reported three and five cases respectively of duodenal ulcer with recurrent attacks of abdominal pain, nausea and vomiting over periods of years simulating the gastric crisis of tabes. Indeed, tabes and duodenal ulcer may coexist. SUMMARY

Two cases of duodenal ulcer and one case of lymphosarcoma with secondary gastric and duodenal ulceration are presented to illustrate the occasional problem arising in the differential diagnosis of the duodenal ulcer. BIBLIOGRAPHY

1. PaImer, Walter Lincoln: The Acid Test in Gastric and Duodenal Ulcer. J.A.M.A .. 88:1778-1780 (June) 1927. 2. Risnhoff, W. F. and Lewis, Dean: Surgical Affections of the Pancreas Met with in Johns Hopkins Hospital from 1899 to 1932, Including a Report of a Case of Adenoma of the Islands of Langerhans and a Case of Pancreatolithiasis. Bull. Johns Hopkins Hosp., ;4:386, 1934. 3. Chauffard, A. M.: Le Cancer du Corps du Pancreas. Bull. Acad. d'Med., Par 60:242, 1908; 4. Bowne, G.: Pain as the Only Sign of Pancreatic Carcinoma. Lancet, 2: 1326, 1936. 5. Hick, F. K. and Mortimer, H. M.: Carcinoma of the Pancreas. J. Lab. lit ain. Med .. 19:1058-1067, 1934. 6. Kiefer, E. D.: Carcinoma of the Pancreas. Arch. Int. Med.,4O:1 (July) 1927. 7. Dunphy, J. ~.: The. Early Diagnosis of Carcinoma of the Pancreas. Am. J. DIgest. DlS., 7:69, 1940.

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8. Grauer, F. W.: Pancreatic Carcinoma. A Review of 34 Autopsies. Arch. Int. Med., 63:884-898 (May) 1939. 9. Levy, H. and Lichtman, S. S.: Qinical Characterization of Primary Carcinoma of the Body and Tail of the Pancreas. Arch. Int. Med., 65:607 (March) 1940. 10. Adler, F. H.: Carcinoma of the Pancreas with Ulceration into the Gastro-intestinal Tract. JA.MA., 76:158 (Jan. IS) 1921. 11. Prey, D., Foster, J. M., Jr. and Dennis, W.: Primary Sarcoma of the Duodenum. Arch. Surg., 30:675-684, 1935. 12. Strauss, A. A., Bloch, L., Friedman, J. C. and Hamburger, W. W.: Sarcoma of the Duodenum and Stomach. SURG. CLlN. N. AM., 5: 977, 1925. . . 13. Present, A. J.: Primary Lymphosarcoma of the Duodenum. Am. J. Roentgenol., 41:545-548, 1939. 14. Keys, S. and Walker, W. W.: Lymphosarcoma Simulating Duodenal Ulcer. Lancet, 1:1168-1170 (May 18) 1937. 15. Madding, G. F.: Hodgkin's Disease of the Stomach: Report of Six Cases. Staff Meet., ¥-ayo Clin., 13:618-623, 1938. 16. Palmer, Walter Lincoln: Peptic Ulcer and Gastric Secretion. Arch. Surg., 44:452, 472 (March) 1942. 17. Judd, E. S.: Bleeding Ulcer of the Duodenum Associated with Cholecystitis. Ann. Surg., 75:459, 1922. 18. MacLaren, A. and Oetting, H.: The Coexistence of Cholecystitis and Duodenal Ulcer in the Same Case. Surg., Gynec. at Obst., 38:92-

95, 1924. 19. Mix, C. L.: Duodenal Ulcer Combined with Cholecystitis. MED. CLIN. N. AM., 7:337-348, 1923. 20. Bruce, H. A.: Association of Cholecystitis with Duodenal Ulcer. Ann. Surg., 84:387, 1926. 21. Wilbur, D. L. and Curler, H. H.: Crisis Type of Abdominal Pain Due

to Gastric and Duodenal Ulceration. Staff Meet., Mayo 26-29, 1938.

am.,

13:

22. Eusterman, G. 0.: Duodenal Ulcer Simulating the Gastric Crisis of Tabes: Report of Five Cases. South. Med. l., 18:319-232 (May) 1925.