Duodenitis: an endoscopist’s ruminations

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AISIGIE Annual Lecture, 1972

Duodenitis: an endoscopist's ruminations Joseph P. Reiber, M.D. Martinez, California

Before attacking a subject as indigestible as duodenitis promises to be, I wish to approach it by circumvention. I shall whet the appetite by singing the praises of duodenoscopy, and then, after choking a bit on peptic ulcer disease, finally reach my main course. I hope I shall not suffer the fate of the physician who innocently underestimates the potentialities of the problem. It has been truly inspiring to have followed the growth of duodenoscopy since its birth in 1958 with the development of the fiberoptic endoscope; to have witnessed its troubled early childhood when claims and counterclaims of its feasibility threatened its very existence; to have been involved in its later childhood when a limited percentage of success was considered a great triumph, and endoscopists talked about getting into the bulb with all the enthusiasm of the youngster with his first two-wheeler who loudly proclaims, "Look, Mom, no hands!" It was an achievement, but I am afraid it was looked upon by many as a stunt of little practical importance. Why go to all that trouble just to get into the duodenal bulb? All you could expect to see was a duodenal ulcer or a scar. After all, cancer wasn't involved, and besides there was x-ray. But many were not entirely satisfied with the information they were getting from radiology. Correlation with symptoms left something to be desired. Patients could exacerbate and remit with little change in their x-ray and in some cases without demonstration of a crater at all. For those physicians who treated their patients purely on the basis of symptoms this was no problem, but it played havoc with clinical research into the natural history or the therapy of duodenal ulcer. What was really going on in those symptomatic but poorly documented cases who were often excluded from investigational studies because they did not have a demonstrable crater? And so we continued to nurture our growing child. Then, with the advent of the first short-tipped, deflecting endoscope, 'Doctor Belber is the recipient of the 1972 Rudolph Schindler Award.

we were suddenly thrust into brash adolescence. We were able to flex our muscles, take on the competition, and come away with at least a draw. As our physical equipment developed further, we finally saw duodenoscopy approach maturity, althoug by no means its ultimate potentiality. We saw it become the definitive procedure for duodenal diagnosis. What is our current capability? With our versatile polydirectiona I endoscopes we can enter the duodenum at will, explore the nooks and crannies of the deformed duodenal bulb, biopsy if necessary, examine the rest of the duodenum about as simply as we now examine the esophagus, and even cannulate the papilla of Vater. Now, far be it from me to suggest that these performances are always easy or that they can be accomplished with a single universal endoscope after 6 easy lessons. This is just not true. It takes experience to be able to visualize all portions of the difficult and deformed duodenal bulb, and in some cases it may require the use of both a forward-viewing and a side-viewing instrument to be sure that we have been completely thorough; and we must be sure and we must be thorough if our opinion is going to be worth anything. Then, as we demonstrate our reliability the demand for duodenoscopy is going to increase well beyond our present capacity to deliver it. Now what should be the function of duodenoscopy? Where do we fit in? With regard to peptic disease the endoscopist should be the prime evaluator of the patient's morphologic state. He can determine the nature and degree of deformity, the presence or absence of ulcer, and the pattern and degree of associated duodenitis; and he is the only one who can determine all 3 features. Studies of ulcer disease in the past, whether statistical, therapeutic, or whatever, have been deficient in lacking certainty about the presence or absence of ulcer unless a crater was unequivocally demonstrated radiologically-but even more important by these studies we could not have been aware of, and therefore could not take into consideration, the pattern or intensity of inflammation

From the Gastroenterology Section Medical Service, Veterans Administration Hospital, Martinez, California 94553. VOLUME 19, NO.2, 7972

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present in addition to the ulcer and whether it persisted or cleared as symptoms improved. After viewing large numbers of ulcer-bearing duodenal bulbs, I have become impressed by the common association of duodenitis with ulceration, and I think it reasonable to assume that such duodenitis is as basic a part of duodenal ulcer disease as the crater itself. I suggest that the response of the duodenitis may be a useful indication of the effectiveness of antacid or other therapy. Failure to cause the duodenitis to subside, even if the ulcer heals, may represent inadequate medical management, regardless of the patient's symptomatic state. After all, patients become asymptomatic even while their pathology remains florid; not only in the duodenum, but in the stomach and esophagus as well. Loss of symptoms may be a good omen, but it is not necessarily the decisive one. Persistence of duodenitis, on the other hand, might furnish us an indicator to tell us which patients may need additional help to recover from the ulcer diathesis and even suggest which patients may benefit from vagotomy or antrectomy. The commonest duodenal deformity we encounter is the midbulb constriction deformity. In its simplest form it may only be a persistent incisura partially encircling the lumen. In more advanced form there may be a ring which completely encircles the lumen, and if pseudodiverticula develop the classic cloverleaf deformity results. Not infrequently the deformity appears less constricting endoscopically than radiologically, but in severe cases it may be responsible for significant stenosis and obstruction. I suggest that the deformity itself may be creating a more favorable environment for peptic disease and may be influential in altering the subsequent course of disease and may even be responsible for its perpetuation. I bring this up because of the endoscopic characteristics of peptic disease in the presence of constriction is diffusely inflamed, and the area distal to it is much less involved. Ulcers tend to be small and superficial and may be located near the apex of the constricting ring where one might anticipate their occurrence, but some are found more proximally than I would have expected if they were to be responsible for increasing the degree of stenosis. They rarely occur beyond the constriction. The degree of inflammation proximal to the constriction often seems to be out of proportion to the size of the ulcer itself. Is it the ulcer which augments the deformity, or is it the longstanding effect of chronic peptic duodenitis? It is logical to assume that the deformity acts as a barrier which helps retain acid-pepsin containing gastric content on its proximal side and makes it difficult for neutralizing alkaline duodenal content to reflux back to where it may be most needed. There are other deformities which may similarly interfere with neutralization, and, of course, there are exceptions. We see patients with grossly deformed duodenal bulbs which show no inflammation and other patients with virtually no deformity who have frequent ulcer recurrence. Obviously, other factors of major importance are involved in the production of duodenal peptic disease including acid levels, blood supply, nervous, or humoral influences upon which I haven't touched at all. I acknowledge that I have been highly specula-

tive, and the situation is not as simplistic as I have made it appear, but it is representative of some of the channels of investigation that may be opened by direct duodenal bulb visualization. I do not agree with the attitude that once a diagnosis of duodenal ulcer is made there is no need for subsequent investigation of the patient's anatomic status unless his symptoms alter drastically, or the theory that "Once an ulcer always an ulcer". Such an attitude is a block to enlarging our knowledge of this very commonplace but poorly understood disease. I believe that we should follow the patient endoscopically over a sustained period. I acknowledge that this may create financial problems but I do not consider that we unduly inconvenience or distress our patients by performin~ endoscopy repeatedly, and I do not believe it is any longer appropriate to talk of "subjecting" a patient to endoscopy. We encounter too many patients who prefer endoscopy with adequate premedication to the misery of getting rid of a gut full of barium. Why do I suggest frequent endoscopic followup examinations? They may help us evaluate the effectiveness of our therapy both upon ulcer healing and subsidence of duodenitis and may lead us to intensify a treatment regimen which we had thought was adequate but may not be; or they may indicate those patients who will be medical treatment failures because of a deformity which unfavorably influences the course of their disease. I certainly would not recommend surgery purely on the basis of persistent duodenitis, but if the pattern of the patient's disease were significantly interfering with his life style then it would furnish objective support for advising surgery. Conversely, if the complaining patient had nothing to show for his complaints, I would be most reluctant to consider surgery. So far I have discussed duodenitis as a significant element of peptic disease, and I have alluded to its potential significance in one specific deformity, but I have not yet made any attempt to describe it. Endoscopically, duodenitis is considered to be present if there is obvious mucosal abnormality manifested by hyperemia, intramural hemorrhage, mucosal swelling, or erosion. Any or all of these abnormalities may be present in a given case. Microscopically, duodenitis is characterized by vascular engorgement, intramural hemorrhage, edema, and a cellular infiltrate which may be superficial or may extend well into the Brunner's gland area. Erosion may be present in some specimens. The cellular infiltrate is composed primarily of lymphocytes, plasma cells, and eosinophils. Polymorphonuclear leukocytes are not regularly present in appreciable numbers, although in an occasional case their presence is noteworthy. The degree of vascular engorgement and intramural hemorrhage may be quite intense in some sections. In other sections red blood cells m.ay appear to be passing directly through the unbroken mucosa. Many biopsy specimens are clear-cut and obviously represent inflammation; however, there may be obstacles confronting the endoscopist in his attempts to corroborate his diagnosis by endoscopic biopsy. The borderline between normal and excessive numbers of round cells and eosinophils is a tenuous GASTROINTESTINAL ENDOSCOPY

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one, and differences in interpretation are inevitable, especially in mild cases of duodenitis or in those cases biopsied several days after the pathologic process has begun to recede. Although endoscopic biopsies can be taken from a pinpointed location, they may be tangential and may not be amenable to the excellent orientation possible with a suction biopsy specimen. This further increases the difficulties in interpretation, particularly of minor degrees of inflammation. Finally, the presence of vascular engorgement or intramural hemorrhage in the superficial layers of mucosa may be interpreted by the pathologist as an artifact even when a specimen was taken from an area because there was visible congestion and intramural hemorrhage. Part of our dilemma is semantic. What can we properly call duodenitis? Certainly, localized areas of intense vascular congestion, intramural hemorrhage, or erosions are not simply variants of normal; nor is diffuse hyperemia merely an example of internal blushing by a mucosa which is suddenly exposed to the naked eye of the endoscopist. I think we can appropriately label these findings as duodenitis, at least in the broad sense of the term, even in the absence of excessive numbers of inflammatory cells microscopically. I acknowledge that I do not know the origin of these lesions. Some of them are a part of peptic disease, others are due to the effects of alcohol, salicylates, or other noxious agents. Some lesions undoubtedly are contusions brought on by the violent stress of vomiting. But it is appropriate that we recognize their existence and strive toward a clearer understanding of their pathogenesis. I would refrain from designating as pathologic a finely mammilated mucosa or one possessing folds which appear somewhat larger than average, in the absence of obvious evidence of associated inflammation. Certainly all of us should recognize the hemorrhagic artifacts produced by the tip of the instrument or by over-vigorous suction and avoid calling these lesions "duodenitis." Duodenitis shows considerable variation in distribution. It tends to occur in linear or ovoid patches, but it may be diffuse. It may be confined primarily to a zone immediately surrounding an ulceration, or it may be widespread throughout the bulb. It certainly occurs in the total absence of ulcer. It may be limited to the area proximal to a constriction deformity, or it may be concentrated at the superior flexure, rarely extending more than a few centimeters into the descending duodenum. Two broad types of duodenitis are generally seen. The first tends to be macular with little distortion of mucosal contour and is usually not recognizeable radiologically. I have referred to it as "superficial" duodenitis. The modifying terms "hemorrhagic" or "erosive" may be appended when these features are striking. The second type consists of localized swellings which appear as hyperemic mammilations when located on smooth mucosa, or as reddened beads or nodes when they occur on folds. Superficial erosion may also be present on some of these lesions. This type of abnormality is loosly referred to as "nodal" duodenitis and is usually raiologically recognizeable as coarsening of the fold pattern. However, not all radiologically enlarged folds are associated with endoscopic evidence of inflammation. Microscopically, VOLUME 19, NO.2, 1972

the superficial type and the nodal type are generally similar, and the distinction may be an artificial one. It is possible that the nodal or beaded appearance may be only the result of a quantitative difference in certain components, for example, increased edema or increased cellular elements; or from associated abnormalities including glandular hypertrophy, glandular dilatation, or cystic formation; or possibly even from localized muscle spasm. Even grossly, the differences between the 2 types are not always clear cut. I have made the distinction, however, since it is conceivable that in the future we may establish an important difference in etiology or pathogenesis which will be clinically significant; for example, the nodal form more commonly occurs in alcoholics and less commonly occurs in association with peptic ulcer. In occasional patients the endoscopist encounters multiple intramural nodules, many of which show marked hyperemia on their apices. Radiologically these are readily visualized and have been diagnosed as hypertrophy of Brunner's glands. Perhaps they are, but endoscopic biopsy of several of these cases has revealed an inflammatory infiltrate extending into the Brunner's gland zone. The designation of "hypertrophic duodenitis" might be more appropriate for this lesion. Full thickness surgical biopsies may be helpful in further categorizing this condition. This lesion, too, seems to occur more frequently in alcoholics, and it is interesting to speculate that there may be a cause-and-effect relationship. Occasionally one may expect to encounter more unusual forms of duodenitis. One of these I will label as "pepper and salt" duodenitis, following a designation suggested by Oi, although I am not sure if we are referring to the same lesion, The particular lesion, which I have seen only rarely, consists of small, white, eroded areas interspersed with red, hemorrhagic, petechial areas, both on a hyperemic base. I have encountered it both in the presence or absence of ulcer. The ulcers accompanying it have been superficial and small. Microscopically there has been an intense inflammatory infiltrate extending to considerable depth in addition to edema, erosion, and hemorrhage. More specific disease entities may be encountered; for example, granulomatous or regional enteritis. The list of pathologic possibilities is too long to consider at this time. Certainly, any unusual appearing lesion warrants biopsy. Much of what I have said has been speculative, but my speciation is based on a conservative nature and hundreds of observations. My principle objective has been to focus upon the problems which may be clarified by duodenoscopy in the hope that it will contribute materially to a better understanding of peptic disease and to the elucidation of other inflammatory or nodular duodenal lesions which are probably not a part of the peptic ulcer diathesis but may nevertheless be of considerable clinical significance. There is need for large scale, carefully controlled studies into all aspects of duodenal disease in the light of our new endoscopic observations, and I am sure that as the number of capable duodenoscopists swells, such investigations will be undertaken.