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Unusual causes of occult bleeding from the gastrointestinal tract
Unusual Causes of Occult Bleeding from the Gastrointestinal
Tract EDWARD S STAFFORD, MD, Baltimore, GEORGE D ZUIDEMA,
MD, Baltimore,
JOHN L CAMERON, MD, Baltimore,
The purpose of this report is to present a logical method for the discovery of the source of bleeding in patients whose only demonstrable evidences of disease are the symptoms and signs of severe microcytic anemia and blood in the stool. The common sources of gastrointestinal hemorrhage are as follows: esophageal varices, esophagitis due to reflux of gastric secretion, gastroesophageal mucosal tear (Mallory-Weiss syndrome), gastric ulcer, neoplasm of stomach, gastritis, duodenal ulcer, stoma1 ulcer, neoplasms of colon and rectum, ulcerative colitis, diverticular disease of colon, hemorrhoids, and disorders of the blood. These are well known and are usually recognizable both before and during surgery and hence do not form the basis of this report. Instead the unusual causes will be discussed, some of which cannot be demonstrated before surgery and may be overlooked unless the surgeon knows what he is searching for. About twenty-five years ago, Stone [I] related his experience with seventy-two patients. He was unable to account for the bleeding or to locate its source in nearly half of these, and could positively identify the source of the bleeding in only twenty-one. Stone concluded that early laparotomy was not advisable unless the hemorrhage was life-threatening. It is noteworthy that, in discussing this report, Ochsner pointed out that aspirin ingestion might account for some of the unexplained instances of melena, and Truesdale called attention to the possibility of unrecognized ulceration of esophageal hiatus hernia as a source of the bleeding. To define the magnitude of the problem a study was made from the diagnostic index of all patients admitted to The Johns Hopkins Hospital during the years 1952-1968. In this period 290 patients were admitted because of microcytic anemia accompanied by bleeding from the gastrointestinal tract of undisclosed origin; of this group, 203 were subjected to laparotomy. The source of the bleeding was not found in 141 of these patients, a result nearly exactly comparable to that of Stone, although the category of patients studied is somewhat different. From the Department of Surgery. The Johns Hopkins University and The Johns Hopkins Hospital, Baltimore, Maryland 21205. Presented at the Tenth Annual Meeting of the Society for Surgery of the Alimentary Tract. New York. New York, July 12 and 13. 1969.
Maryland Maryland
Maryland
The relative significance of these figures is certainly open to question because of the inherent errors in the preparation of a diagnostic index, but the actual number of patients who underwent laparotomy without discovery of the source of bleeding is large enough to point substantially to the need for improvement of method. From the standpoint of aid to diagnosis, there is nothing helpful to be found in the age, sex, or race of these patients. The value of careful history-taking has been emphasized ad nauseam but apparently not to the point of no longer needing emphasis. In particular, information concerning the use of drugs is important, and it is especially important to know if the patient has taken aspirin. It is a fact that many patients, who deny taking any medicine, have in fact ingested aspirin as such or in one of the many pharmaceutical preparations in which it is included, never thinking of aspirin as medicine. The medicaments known to cause bleeding from the ailmentary tract are as follows: acetylsalicylic acid, antibiotics, anticoagulants, arsenic compounds, DDT, phenylbutazone, quinine and quinidine, and steroids (adrenocortical). A partial list of readily available pharmacologic products containing aspirin is as follows: Ascodeen@-30, Ascriptin@, Bayer3 Aspirin, Buff-A Comp., Bufferin@, Cirin, Codempirala, Cope, Coricidin@, Covangesic, Daprisaln, Darvona, Decagesi@, Derfule@, Drocogesic No. 3, Duragesic, Ecotrin@, Edrisal@, Empiral@, Empirin@, Emprazilm, Equagesica, Excedrin@, Fiorinalm, Measurin, Medaprin@, Monaceta Compound, Norgesica, Novahistinem with APC, Pabirin@ Buffered Tablets, Paradol, Pentagesic@, PercobarbB, Percodan@, Persistin@, PhenaphenQ, Phenodyne, Predisal, Robaxisalm, Supac, Synalgos@, Synirin@, Tetrex@-APC, Trance-gesics, Vanquish, Zactirin Compound 100. In the case of a patient who is discovered to have used one of these drugs immediately preceding and during the present illness, and if the patient is not in a precarious condition, a brief period of observation for a few days after withdrawal of the suspected drug may confirm the diagnosis, in the absence of other positive findings. All available diagnostic methods must be employed, of course, including direct visual inspection of the upper The
American
Journal
of Surgery
Occult
and lower portions of the tract, and radiographic visualization of the entire tract with both opaque and air contrast media. Cine studies help to resolve the pertinence of questionable findings from standard radiographic examinations, as does also the use of such special technics as acid barium, the “hamburger meal,” and morphine. The cause of bleeding will be found by these means in many patients. Additional methods of occasional usefulness are the string test [2] and angiography [3]. The string test may demonstrate the distance of the source of bleeding below the front teeth, whereas direct angiography (usually transaortic) may demonstrate a tumor stain, or, in a case of active bleeding, extravasation of the contrast media into the lumen of the tract [4]. There will remain, however, numerous patients in whom none of the foregoing studies is effective in discovering the lesion, and for whom but one antemortem diagnostic procedure remains : surgical exploration. In the majority of patients of the kind under discussion this means laparotomy, but, infrequently, thoracotomy may be necessary. Because it is easier to recognize that which has been seen before than to recognize a lesion of which one is entirely unaware, the operating surgeon must have in mind as complete a descriptive inventory as possible of the numerous unusual sources of bleeding. In the performance of laparotomy we find it helpful to follow a systematic routine unless the lesion is immediately apparent. Beginning at the esophagogastric junction, the status of the esophageal hiatus is investigated, and then the tract is carefully inspected and palpated from top to bottom. Transillumination is used to help find intraluminal lesions. Alternate compression and relaxation of successive segments of the gut can make unseen diverticula stand out [5]. Gastrotomy and/or enterotomy incisions are to be made on the least suspicion of abnormality, so that biopsy specimens may be sent to the surgical pathology laboratory for immediate examination. A sterile sigmoidoscope should be available for introduction into enterotomy incisions, making possible direct inspection of the mucosal surface. In the event that nothing abnormal is located, if the condition of the patient permits, the whole examination should be repeated, even more carefully. To be sturdily resisted is the temptation to remove this or that segment of the alimentary tract because it might be the source of bleeding. Some of the unusual causes of anemia due to occult bleeding from the alimentary tract drawn from our own experience are as follows (the arrangement is in anatomic order and not related to relative frequency of occurrence): ectopic gastric mucosa in esophagus; esophageal bleeding due to reflux of gastric contents; aspirin ingestion; hemangioma; diverticula of small Vol. 119, February
1970
Bleeding
from
Gastrointestinal
Tract
intestine, including Meckel’s; blind pouches of small intestine resulting from surgery; stricture of small intestine; neoplasms of small intestine; enteric cyst (duplication) ; internal hemorrhoids. Illustrative case reports are as follows: Case
Reports
CASE I. The patient (JHH, # 1022749) was a seven year old girl known to have severe persistent microcytic anemia
since the age of eighteen months. The source of bleeding was not disclosed by laparotomy at age six. After persistent guaiac-positive stools and anemia for the next several months, a presumptive diagnosis of portal hypertension with bleeding varices was made. Laparotomy was again undertaken and portal pressure measured; again no bleeding lesion was found so the incision was extended into the chest and the esophagus exposed. The lower portion seemed thicker than normal; it was opened and a biopsy specimen taken which showed gastric mucosa. The lower third was resected and a penetrating peptic ulcer was found. Nearfy all of the lining of the lower esophagus was composed of gastric mucosa. A segment of jejunum was used to restore continuity. Seven years later, at age fourteen, the patient is well.
Comment: This is our only patient with peptic ulcer in an esophagus in which there was ectopic gastric mucosa. After five and a half years of searching and two unrewarding laparotomies, the lesion was found in the chest and removed. Microcytic anemia caused by esophageal bleeding of an occult nature due to gastric reflux, with or without esophageal hiatus hernia, on the other hand, is seen more often. This was noted eleven times in our diagnostic index during the period studied, and may have occurred more often. Turning to the stomach as a source of microcytic anemia secondary to occult blood loss, the ingestion of aspirin in some form or other is a frequent cause, and possibly the cause most often overlooked [6]. CASE II. The patient (JHH, #481999), an elderly surgical laboratory technician, began ingesting aspirin in large amounts to ease the pain of arthritic joints. He appeared in the emergency department complaining of weakness and shortness of breath, and was found to be anemic. He had stools heavily positive to guaiac. He was admitted to the hospital with a presumptive diagnosis of bleeding gastric ulcer, but no lesion could be demonstrated. After a similar episode five years later, he was advised not to take aspirin, but after another interval of two years he had a third episode of anemia and guaiac-positive stools, this time after using Bufferin for his joint pains. Again all diagnostic studies were negative or normal and he recovered promptly.
Comment: In our present state of knowledge diagnosis can only be made empirically. If aspirin gestion is stopped, and the bleeding and anemia not recur, the assumption is made that aspirin was cause. We have seen numerous patients in whom
the indo the
this
Stafford,
Zuidema,
was the case,
and
and Cameron
this
may
be the most
convincing
reason for not undertaking immediate laparotomy in the kind of situation presented in this report. Although bleeding is usually not life-threatening, aspirin can sometimes produce quite alarming hemorrhage. Attention should also be called to the possibility of aspirininduced bleeding in patients who have had gastric surgery and who, by virtue of the anemia and occult blood in the stool, may be erroneously thought to have stoma1 ulcer. Hemangiomas may be found anywhere in the alimentary tract, but we have encountered these as causes of chronic anemia only in the small intestine
[71. CASE III. The patient (JHH, # 1080520) was first noted to have anemia secondary to gastrointestinal tract bleeding when she was ten years of age. For the next eight years her schooling was interrupted by many episodes of bleeding, and during this time all diagnostic studies of the gastrointestinal tract failed to disclose any lesion. She had numerous transfusions. At laparotomy four large intramural hemangiomas were found and removed. These varied from 1 to 4 cm in diameter and were widely dispersed in the jejunum and ileum. She has been perfectly well during the five years since operation.
Comment: Similar lesions of the skin have been noted in some of our patients, but this is not constant. Removal of these intestinal lesions, which are usually easy to find, especially if transillumination is employed, results in cure, but not always permanently since tiny lesions may enlarge or new ones develop. Although it is easy to understand how the delicate surface of a mucosal hemangioma may become eroded and bleed, there are three types of lesions of the small bowel which also cause anemia-producing bleeding and which are much harder to explain. Diverticula, including Meckel’s, are among the more frequent of the unusual causes. CASE IV. The patient (JHH, #561732) was a seventeen year old boy who had had episodes of anemia and guaiacpositive stools for at least five years prior to laparotomy. A large Meckel’s diverticulum was removed, and ulceration of the mucosa demonstrated. This patient has been followed up for eighteen years and there has been no recurrence of the bleeding or anemia.
Comment: The second type of small bowel lesion is the blind pouch of gut resulting from side to side anastomosis or bypassing operations, now less commonly seen because surgeons usually construct end to end anastomoses [a]. CASE v. The patient (JHH, #309565), a thirty-seven year old physician, underwent resection of gangrenous bowel, which was caused by herniation through a mesenteric defect, when he was twelve years old. At the age of twenty-four he was noted to be anemic and found to 210
have occasional guaiac-positive stools. For years he uas treated on a presumptive diagnosis of ulcerative colitis although no direct or radiologic evidence was found. After resection of a blind pouch adjacent to the old anastomocis he has been well for nine years without anemia. Chronic ulceration was demonstrated in the resected ileal stump.
Comment: Bleeding
from an ulcerated blind pouch is not the only cause of anemia associated with such pouches since bacterial overgrowth and interference with adequate absorption of vitamin B,, may also cause anemia. This, however, is different in type from the microcytic anemia seen after bleeding. The third type of small bowel lesion is the circular stricture, sometimes the result of trauma, but occasionally found to be of spontaneous or unknown origin, even before the use of enteric-coated capsules containing potassium [9]. CASE VI. The patient (JHH, #638297), a fifty-nine year old spinster who had had neither previous surgery nor recallable injury to the abdomen, was subjected to laparotomy because of persistent severe microcytic anemia with guaiac-positive stools. An annular constriction was found in the distal ileum and was resected. The stricture proved to be fibrous scar tissue and not an infiltrating neoplasm as had been suspected by the surgeon. There was a small chronic ulcer immediately proximal to the stricture. The patient had not had symptoms of obstruction. When last seen twelve years later she was quite well.
Comment: Although the bleeding point may not be found at the time of removal of the diverticulum, blind pouch, or stricture, cure of anemia will result. It is of interest to note that normally functioning blind pouches (appendix, cecum) and narrowings of the lumen ileocecal valve) are not productive of (pylorus, chronic anemia from occult bleeding. That various neoplastic lesions such as carcinoma, lymphoma, and leiomyosarcoma of the small intestine may become manifest only upon exploration for the cause of an anemia is well known [IO]. Enteric cyst (duplication) may also produce this same clinical picture. Benign and malignant neoplasms of the stomach and colon, however, do not fall into the group under discussion because, although bleeding and anemia are usual, such lesions are regularly demonstrable by available diagnostic methods. There is one very ordinary bleeding lesion of the alimentary tract which cannot be left out of this discussion; namely, internal hemorrhoids. It is surprising but true that occasionally a patient appears with the symptoms of anemia and either denies or does not realize that there has been hemorrhoidal bleeding. In some instances the bleeding is so trivial, over such a prolonged period, that the patient has accepted it as a fact of life to be ignored. In such patients the appearance of the hemorrhoids during proctoscopic examination is not different from that of many patients The American Journal of Surgery
Occult
with bleeding hemorrhoids who do not have anemia. Although it is perfectly possible for a patient to have both mild bleeding hemorrhoids and a bleeding lesion higher in the alimentary tract, it would seem wiser to postpone laparotomy until the potentially beneficial effect of hemorrhoidectomy has been evaluated. Summary
The patient who presents only the signs and symptoms of microcytic anemia due to bleeding from the alimentary tract must be subjected to a very careful search for all information which might lead to a diagnosis, with special emphasis on history of drug ingestion and on those diagnostic procedures available for direct and indirect visualization of the tract. Surgical exploration will be the ultimate diagnostic procedure for many such patients but should be postponed until all other diagnostic methods have been employed and until there has been ample opportunity to make certain that the bleeding persists despite withdrawal of all drugs which might be causative. Because it is easier to recognize a known cause of bleeding, we have presented examples of unusual causes from our own experience. References 1. Stone HB: targe 2.
3.
4.
5.
6. 7. 8.
9.
10.
melena of obscure origin. Ann Surg 120: 582, 1944. Traphagen DW and Karlan M: Flourescein string test for localization of upper gastrointestinal hemorrhage. Surgery 44: 644, 1958. Margulis AR, Heinbecker P, and Bernard HR: Operative mesenteric arteriography in the search for the site of bleeding in unexplained gastrointestinal hemorrhage. Surgery 48: 534. 1960. Evans TN, Zuidema GD, Anderson DG, and Bookstein JJ: Metastatic choreoadenoma destruens with intestinal hemorrhage. Obst 81 Gynec 26: 570, 1965. Shackelford RT and Marcus WY: Jejunal diverticula. A cause of gastrointestinal hemorrhage. Ann Surg 151: 930, 1960. Summerskill WHJ and Alvarez AS: Salicylate anemia. Lancet 2: 925, 1958. Calem WS and Jimenez FA: Vascular malformations of the intestine. Arch Surg 86: 571, 1963. Whitaker WG and Shepard D: Late complications of side to side intestinal anastomoses; case reports. Ann Surg 161: 824, 1965. Teicher I, Arlen M, Muehlbauer M, and Allen AC: The clinical pathologic spectrum of primary ulcers of the small intestine. Surg Gynec & Obst 116: 196, 1963. Ebert PA and Zuidema GD: Primary tumors of the small intestine. Arch Surg 91: 452, 1965.
Discussion of Papers by Drs Stahl and Stafford CHARLES F FREY (Ann Arbor, Mich.): I am glad that both authors have emphasized the usefulness of arteriography in the diagnosis of occult gastrointestinal hemorrhage. We recently had occasion at the University of Michigan to review our experience with selective arteriography in the diagnosis of occult gastrointestinal hemorrhage. We have examined forty-five patients with active bleeding Vol. 119, February 1970
Bleeding
from
Gastrointestinal
Tract
and thirty-nine patients with intermittent or chronic bleeding. In those patients examined witb active bleeding, we were able to identify the source of bleeding in patients who had bleeding gastric, duodenal, or marginal ulcers, the Mallory-Weiss syndrome, bleeding from diverticulosis of the colon, bleeding from superficial ulcerations of the small and large bowel, and in patients who had uremia. In the patients with chronic or intermittent bleeding we were able to identify the source of bleeding in patients
with arteriovenous malformations, telangiectasias, aneurysms, and arteriosclerotic infarcts. Our approach to these problems is very similar to that described by Dr Stahl. The patients who come in with massive bleeding, in whom the cause is not readily recognized on the basis of history and physical examination, are subjected initially to arteriography. The other group of patients in whom we use arteriography initially are those who have previously been admitted with hemorrhage; the hemorrhage stopped; they were evaluated with conventional studies, left the hospital, and returned again with hemorrhage. The patients with chronic or inactive bleeding, because there is no necessity for performing surgery immediately, are all examined with conventional barium studies. We resort to arteriography only when the results of those studies are uninformative. RICHARDK GILCHRIST (Chicago, Ill): I would add one drug to Dr Stafford’s series. Aspirin is not the only salicylate to cause bleeding. One of the drugs used for arthritis by some patients is theobromine sodium salicylate. I know of one case in which there was bleeding which stopped when the drug was withdrawn. From persona1 experience, when I was clearing specimens with methyl salicylate and inhaling large amounts of it and in contact with it frequently for three years, I finally had such nasal bleeding that my nose had to be packed front and back for nine days, and still the bleeding did not stop. Finally 150 or 200 cc. of whole uncitrated blood had to be injected into the abdominal wall, which stopped the bleeding. Each time I started working with methyl salicylate again, bleeding began again. In the patients with bleeding from salicylate ingestion, if the bleeding cannot be stopped any other way and you wish to delay surgery, the patient might be given one or two units of whole unmodified uncitrated blood by the multiple syringe method. It certainly worked in my case and I know it has worked in one other, which was not due to salicylate ingestion but in which the bleeding could not be stopped otherwise. RICHARD SHACKELFORD(Baltimore, Md) : I would like to make a few additions to Dr Stafford’s series of bleeding from unusual sites which I think are worth looking for. In one case a woman who had had an apparently very small aneurysm of the hepatic artery, who had been explored elsewhere three times, was explored by me but nothing was found. Six months later Dr Ravdin told me she had gone to the Pennsylvania Hospital where they did not have a chance to operate. At autopsy they found a small aneurysm of the hepatic artery which had ruptured into the common duct. The second patient had had common duct exploration 211
Stafford,
Zuidema,
and
Cameron
elsewhere in which the duct had been explored rather carelessly. The patient came to us because of gastrointestinal bleeding. We found that the bleeding was coming from an artery-common duct fistula which was leaking slowly.
212
The third patient, who had had numerous explorations at various hospitals in the country districts of Maryland, was bleeding on admission. At exploration we found a very small benign polyp in the ampulla of Vater which was the source of bleeding.
The American
Journal
of Surgery
Tract EDWARD S STAFFORD, MD, Baltimore, GEORGE D ZUIDEMA,
MD, Baltimore,
JOHN L CAMERON, MD, Baltimore,
The purpose of this report is to present a logical method for the discovery of the source of bleeding in patients whose only demonstrable evidences of disease are the symptoms and signs of severe microcytic anemia and blood in the stool. The common sources of gastrointestinal hemorrhage are as follows: esophageal varices, esophagitis due to reflux of gastric secretion, gastroesophageal mucosal tear (Mallory-Weiss syndrome), gastric ulcer, neoplasm of stomach, gastritis, duodenal ulcer, stoma1 ulcer, neoplasms of colon and rectum, ulcerative colitis, diverticular disease of colon, hemorrhoids, and disorders of the blood. These are well known and are usually recognizable both before and during surgery and hence do not form the basis of this report. Instead the unusual causes will be discussed, some of which cannot be demonstrated before surgery and may be overlooked unless the surgeon knows what he is searching for. About twenty-five years ago, Stone [I] related his experience with seventy-two patients. He was unable to account for the bleeding or to locate its source in nearly half of these, and could positively identify the source of the bleeding in only twenty-one. Stone concluded that early laparotomy was not advisable unless the hemorrhage was life-threatening. It is noteworthy that, in discussing this report, Ochsner pointed out that aspirin ingestion might account for some of the unexplained instances of melena, and Truesdale called attention to the possibility of unrecognized ulceration of esophageal hiatus hernia as a source of the bleeding. To define the magnitude of the problem a study was made from the diagnostic index of all patients admitted to The Johns Hopkins Hospital during the years 1952-1968. In this period 290 patients were admitted because of microcytic anemia accompanied by bleeding from the gastrointestinal tract of undisclosed origin; of this group, 203 were subjected to laparotomy. The source of the bleeding was not found in 141 of these patients, a result nearly exactly comparable to that of Stone, although the category of patients studied is somewhat different. From the Department of Surgery. The Johns Hopkins University and The Johns Hopkins Hospital, Baltimore, Maryland 21205. Presented at the Tenth Annual Meeting of the Society for Surgery of the Alimentary Tract. New York. New York, July 12 and 13. 1969.
Maryland Maryland
Maryland
The relative significance of these figures is certainly open to question because of the inherent errors in the preparation of a diagnostic index, but the actual number of patients who underwent laparotomy without discovery of the source of bleeding is large enough to point substantially to the need for improvement of method. From the standpoint of aid to diagnosis, there is nothing helpful to be found in the age, sex, or race of these patients. The value of careful history-taking has been emphasized ad nauseam but apparently not to the point of no longer needing emphasis. In particular, information concerning the use of drugs is important, and it is especially important to know if the patient has taken aspirin. It is a fact that many patients, who deny taking any medicine, have in fact ingested aspirin as such or in one of the many pharmaceutical preparations in which it is included, never thinking of aspirin as medicine. The medicaments known to cause bleeding from the ailmentary tract are as follows: acetylsalicylic acid, antibiotics, anticoagulants, arsenic compounds, DDT, phenylbutazone, quinine and quinidine, and steroids (adrenocortical). A partial list of readily available pharmacologic products containing aspirin is as follows: Ascodeen@-30, Ascriptin@, Bayer3 Aspirin, Buff-A Comp., Bufferin@, Cirin, Codempirala, Cope, Coricidin@, Covangesic, Daprisaln, Darvona, Decagesi@, Derfule@, Drocogesic No. 3, Duragesic, Ecotrin@, Edrisal@, Empiral@, Empirin@, Emprazilm, Equagesica, Excedrin@, Fiorinalm, Measurin, Medaprin@, Monaceta Compound, Norgesica, Novahistinem with APC, Pabirin@ Buffered Tablets, Paradol, Pentagesic@, PercobarbB, Percodan@, Persistin@, PhenaphenQ, Phenodyne, Predisal, Robaxisalm, Supac, Synalgos@, Synirin@, Tetrex@-APC, Trance-gesics, Vanquish, Zactirin Compound 100. In the case of a patient who is discovered to have used one of these drugs immediately preceding and during the present illness, and if the patient is not in a precarious condition, a brief period of observation for a few days after withdrawal of the suspected drug may confirm the diagnosis, in the absence of other positive findings. All available diagnostic methods must be employed, of course, including direct visual inspection of the upper The
American
Journal
of Surgery
Occult
and lower portions of the tract, and radiographic visualization of the entire tract with both opaque and air contrast media. Cine studies help to resolve the pertinence of questionable findings from standard radiographic examinations, as does also the use of such special technics as acid barium, the “hamburger meal,” and morphine. The cause of bleeding will be found by these means in many patients. Additional methods of occasional usefulness are the string test [2] and angiography [3]. The string test may demonstrate the distance of the source of bleeding below the front teeth, whereas direct angiography (usually transaortic) may demonstrate a tumor stain, or, in a case of active bleeding, extravasation of the contrast media into the lumen of the tract [4]. There will remain, however, numerous patients in whom none of the foregoing studies is effective in discovering the lesion, and for whom but one antemortem diagnostic procedure remains : surgical exploration. In the majority of patients of the kind under discussion this means laparotomy, but, infrequently, thoracotomy may be necessary. Because it is easier to recognize that which has been seen before than to recognize a lesion of which one is entirely unaware, the operating surgeon must have in mind as complete a descriptive inventory as possible of the numerous unusual sources of bleeding. In the performance of laparotomy we find it helpful to follow a systematic routine unless the lesion is immediately apparent. Beginning at the esophagogastric junction, the status of the esophageal hiatus is investigated, and then the tract is carefully inspected and palpated from top to bottom. Transillumination is used to help find intraluminal lesions. Alternate compression and relaxation of successive segments of the gut can make unseen diverticula stand out [5]. Gastrotomy and/or enterotomy incisions are to be made on the least suspicion of abnormality, so that biopsy specimens may be sent to the surgical pathology laboratory for immediate examination. A sterile sigmoidoscope should be available for introduction into enterotomy incisions, making possible direct inspection of the mucosal surface. In the event that nothing abnormal is located, if the condition of the patient permits, the whole examination should be repeated, even more carefully. To be sturdily resisted is the temptation to remove this or that segment of the alimentary tract because it might be the source of bleeding. Some of the unusual causes of anemia due to occult bleeding from the alimentary tract drawn from our own experience are as follows (the arrangement is in anatomic order and not related to relative frequency of occurrence): ectopic gastric mucosa in esophagus; esophageal bleeding due to reflux of gastric contents; aspirin ingestion; hemangioma; diverticula of small Vol. 119, February
1970
Bleeding
from
Gastrointestinal
Tract
intestine, including Meckel’s; blind pouches of small intestine resulting from surgery; stricture of small intestine; neoplasms of small intestine; enteric cyst (duplication) ; internal hemorrhoids. Illustrative case reports are as follows: Case
Reports
CASE I. The patient (JHH, # 1022749) was a seven year old girl known to have severe persistent microcytic anemia
since the age of eighteen months. The source of bleeding was not disclosed by laparotomy at age six. After persistent guaiac-positive stools and anemia for the next several months, a presumptive diagnosis of portal hypertension with bleeding varices was made. Laparotomy was again undertaken and portal pressure measured; again no bleeding lesion was found so the incision was extended into the chest and the esophagus exposed. The lower portion seemed thicker than normal; it was opened and a biopsy specimen taken which showed gastric mucosa. The lower third was resected and a penetrating peptic ulcer was found. Nearfy all of the lining of the lower esophagus was composed of gastric mucosa. A segment of jejunum was used to restore continuity. Seven years later, at age fourteen, the patient is well.
Comment: This is our only patient with peptic ulcer in an esophagus in which there was ectopic gastric mucosa. After five and a half years of searching and two unrewarding laparotomies, the lesion was found in the chest and removed. Microcytic anemia caused by esophageal bleeding of an occult nature due to gastric reflux, with or without esophageal hiatus hernia, on the other hand, is seen more often. This was noted eleven times in our diagnostic index during the period studied, and may have occurred more often. Turning to the stomach as a source of microcytic anemia secondary to occult blood loss, the ingestion of aspirin in some form or other is a frequent cause, and possibly the cause most often overlooked [6]. CASE II. The patient (JHH, #481999), an elderly surgical laboratory technician, began ingesting aspirin in large amounts to ease the pain of arthritic joints. He appeared in the emergency department complaining of weakness and shortness of breath, and was found to be anemic. He had stools heavily positive to guaiac. He was admitted to the hospital with a presumptive diagnosis of bleeding gastric ulcer, but no lesion could be demonstrated. After a similar episode five years later, he was advised not to take aspirin, but after another interval of two years he had a third episode of anemia and guaiac-positive stools, this time after using Bufferin for his joint pains. Again all diagnostic studies were negative or normal and he recovered promptly.
Comment: In our present state of knowledge diagnosis can only be made empirically. If aspirin gestion is stopped, and the bleeding and anemia not recur, the assumption is made that aspirin was cause. We have seen numerous patients in whom
the indo the
this
Stafford,
Zuidema,
was the case,
and
and Cameron
this
may
be the most
convincing
reason for not undertaking immediate laparotomy in the kind of situation presented in this report. Although bleeding is usually not life-threatening, aspirin can sometimes produce quite alarming hemorrhage. Attention should also be called to the possibility of aspirininduced bleeding in patients who have had gastric surgery and who, by virtue of the anemia and occult blood in the stool, may be erroneously thought to have stoma1 ulcer. Hemangiomas may be found anywhere in the alimentary tract, but we have encountered these as causes of chronic anemia only in the small intestine
[71. CASE III. The patient (JHH, # 1080520) was first noted to have anemia secondary to gastrointestinal tract bleeding when she was ten years of age. For the next eight years her schooling was interrupted by many episodes of bleeding, and during this time all diagnostic studies of the gastrointestinal tract failed to disclose any lesion. She had numerous transfusions. At laparotomy four large intramural hemangiomas were found and removed. These varied from 1 to 4 cm in diameter and were widely dispersed in the jejunum and ileum. She has been perfectly well during the five years since operation.
Comment: Similar lesions of the skin have been noted in some of our patients, but this is not constant. Removal of these intestinal lesions, which are usually easy to find, especially if transillumination is employed, results in cure, but not always permanently since tiny lesions may enlarge or new ones develop. Although it is easy to understand how the delicate surface of a mucosal hemangioma may become eroded and bleed, there are three types of lesions of the small bowel which also cause anemia-producing bleeding and which are much harder to explain. Diverticula, including Meckel’s, are among the more frequent of the unusual causes. CASE IV. The patient (JHH, #561732) was a seventeen year old boy who had had episodes of anemia and guaiacpositive stools for at least five years prior to laparotomy. A large Meckel’s diverticulum was removed, and ulceration of the mucosa demonstrated. This patient has been followed up for eighteen years and there has been no recurrence of the bleeding or anemia.
Comment: The second type of small bowel lesion is the blind pouch of gut resulting from side to side anastomosis or bypassing operations, now less commonly seen because surgeons usually construct end to end anastomoses [a]. CASE v. The patient (JHH, #309565), a thirty-seven year old physician, underwent resection of gangrenous bowel, which was caused by herniation through a mesenteric defect, when he was twelve years old. At the age of twenty-four he was noted to be anemic and found to 210
have occasional guaiac-positive stools. For years he uas treated on a presumptive diagnosis of ulcerative colitis although no direct or radiologic evidence was found. After resection of a blind pouch adjacent to the old anastomocis he has been well for nine years without anemia. Chronic ulceration was demonstrated in the resected ileal stump.
Comment: Bleeding
from an ulcerated blind pouch is not the only cause of anemia associated with such pouches since bacterial overgrowth and interference with adequate absorption of vitamin B,, may also cause anemia. This, however, is different in type from the microcytic anemia seen after bleeding. The third type of small bowel lesion is the circular stricture, sometimes the result of trauma, but occasionally found to be of spontaneous or unknown origin, even before the use of enteric-coated capsules containing potassium [9]. CASE VI. The patient (JHH, #638297), a fifty-nine year old spinster who had had neither previous surgery nor recallable injury to the abdomen, was subjected to laparotomy because of persistent severe microcytic anemia with guaiac-positive stools. An annular constriction was found in the distal ileum and was resected. The stricture proved to be fibrous scar tissue and not an infiltrating neoplasm as had been suspected by the surgeon. There was a small chronic ulcer immediately proximal to the stricture. The patient had not had symptoms of obstruction. When last seen twelve years later she was quite well.
Comment: Although the bleeding point may not be found at the time of removal of the diverticulum, blind pouch, or stricture, cure of anemia will result. It is of interest to note that normally functioning blind pouches (appendix, cecum) and narrowings of the lumen ileocecal valve) are not productive of (pylorus, chronic anemia from occult bleeding. That various neoplastic lesions such as carcinoma, lymphoma, and leiomyosarcoma of the small intestine may become manifest only upon exploration for the cause of an anemia is well known [IO]. Enteric cyst (duplication) may also produce this same clinical picture. Benign and malignant neoplasms of the stomach and colon, however, do not fall into the group under discussion because, although bleeding and anemia are usual, such lesions are regularly demonstrable by available diagnostic methods. There is one very ordinary bleeding lesion of the alimentary tract which cannot be left out of this discussion; namely, internal hemorrhoids. It is surprising but true that occasionally a patient appears with the symptoms of anemia and either denies or does not realize that there has been hemorrhoidal bleeding. In some instances the bleeding is so trivial, over such a prolonged period, that the patient has accepted it as a fact of life to be ignored. In such patients the appearance of the hemorrhoids during proctoscopic examination is not different from that of many patients The American Journal of Surgery
Occult
with bleeding hemorrhoids who do not have anemia. Although it is perfectly possible for a patient to have both mild bleeding hemorrhoids and a bleeding lesion higher in the alimentary tract, it would seem wiser to postpone laparotomy until the potentially beneficial effect of hemorrhoidectomy has been evaluated. Summary
The patient who presents only the signs and symptoms of microcytic anemia due to bleeding from the alimentary tract must be subjected to a very careful search for all information which might lead to a diagnosis, with special emphasis on history of drug ingestion and on those diagnostic procedures available for direct and indirect visualization of the tract. Surgical exploration will be the ultimate diagnostic procedure for many such patients but should be postponed until all other diagnostic methods have been employed and until there has been ample opportunity to make certain that the bleeding persists despite withdrawal of all drugs which might be causative. Because it is easier to recognize a known cause of bleeding, we have presented examples of unusual causes from our own experience. References 1. Stone HB: targe 2.
3.
4.
5.
6. 7. 8.
9.
10.
melena of obscure origin. Ann Surg 120: 582, 1944. Traphagen DW and Karlan M: Flourescein string test for localization of upper gastrointestinal hemorrhage. Surgery 44: 644, 1958. Margulis AR, Heinbecker P, and Bernard HR: Operative mesenteric arteriography in the search for the site of bleeding in unexplained gastrointestinal hemorrhage. Surgery 48: 534. 1960. Evans TN, Zuidema GD, Anderson DG, and Bookstein JJ: Metastatic choreoadenoma destruens with intestinal hemorrhage. Obst 81 Gynec 26: 570, 1965. Shackelford RT and Marcus WY: Jejunal diverticula. A cause of gastrointestinal hemorrhage. Ann Surg 151: 930, 1960. Summerskill WHJ and Alvarez AS: Salicylate anemia. Lancet 2: 925, 1958. Calem WS and Jimenez FA: Vascular malformations of the intestine. Arch Surg 86: 571, 1963. Whitaker WG and Shepard D: Late complications of side to side intestinal anastomoses; case reports. Ann Surg 161: 824, 1965. Teicher I, Arlen M, Muehlbauer M, and Allen AC: The clinical pathologic spectrum of primary ulcers of the small intestine. Surg Gynec & Obst 116: 196, 1963. Ebert PA and Zuidema GD: Primary tumors of the small intestine. Arch Surg 91: 452, 1965.
Discussion of Papers by Drs Stahl and Stafford CHARLES F FREY (Ann Arbor, Mich.): I am glad that both authors have emphasized the usefulness of arteriography in the diagnosis of occult gastrointestinal hemorrhage. We recently had occasion at the University of Michigan to review our experience with selective arteriography in the diagnosis of occult gastrointestinal hemorrhage. We have examined forty-five patients with active bleeding Vol. 119, February 1970
Bleeding
from
Gastrointestinal
Tract
and thirty-nine patients with intermittent or chronic bleeding. In those patients examined witb active bleeding, we were able to identify the source of bleeding in patients who had bleeding gastric, duodenal, or marginal ulcers, the Mallory-Weiss syndrome, bleeding from diverticulosis of the colon, bleeding from superficial ulcerations of the small and large bowel, and in patients who had uremia. In the patients with chronic or intermittent bleeding we were able to identify the source of bleeding in patients
with arteriovenous malformations, telangiectasias, aneurysms, and arteriosclerotic infarcts. Our approach to these problems is very similar to that described by Dr Stahl. The patients who come in with massive bleeding, in whom the cause is not readily recognized on the basis of history and physical examination, are subjected initially to arteriography. The other group of patients in whom we use arteriography initially are those who have previously been admitted with hemorrhage; the hemorrhage stopped; they were evaluated with conventional studies, left the hospital, and returned again with hemorrhage. The patients with chronic or inactive bleeding, because there is no necessity for performing surgery immediately, are all examined with conventional barium studies. We resort to arteriography only when the results of those studies are uninformative. RICHARDK GILCHRIST (Chicago, Ill): I would add one drug to Dr Stafford’s series. Aspirin is not the only salicylate to cause bleeding. One of the drugs used for arthritis by some patients is theobromine sodium salicylate. I know of one case in which there was bleeding which stopped when the drug was withdrawn. From persona1 experience, when I was clearing specimens with methyl salicylate and inhaling large amounts of it and in contact with it frequently for three years, I finally had such nasal bleeding that my nose had to be packed front and back for nine days, and still the bleeding did not stop. Finally 150 or 200 cc. of whole uncitrated blood had to be injected into the abdominal wall, which stopped the bleeding. Each time I started working with methyl salicylate again, bleeding began again. In the patients with bleeding from salicylate ingestion, if the bleeding cannot be stopped any other way and you wish to delay surgery, the patient might be given one or two units of whole unmodified uncitrated blood by the multiple syringe method. It certainly worked in my case and I know it has worked in one other, which was not due to salicylate ingestion but in which the bleeding could not be stopped otherwise. RICHARD SHACKELFORD(Baltimore, Md) : I would like to make a few additions to Dr Stafford’s series of bleeding from unusual sites which I think are worth looking for. In one case a woman who had had an apparently very small aneurysm of the hepatic artery, who had been explored elsewhere three times, was explored by me but nothing was found. Six months later Dr Ravdin told me she had gone to the Pennsylvania Hospital where they did not have a chance to operate. At autopsy they found a small aneurysm of the hepatic artery which had ruptured into the common duct. The second patient had had common duct exploration 211
Stafford,
Zuidema,
and
Cameron
elsewhere in which the duct had been explored rather carelessly. The patient came to us because of gastrointestinal bleeding. We found that the bleeding was coming from an artery-common duct fistula which was leaking slowly.
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The third patient, who had had numerous explorations at various hospitals in the country districts of Maryland, was bleeding on admission. At exploration we found a very small benign polyp in the ampulla of Vater which was the source of bleeding.
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of Surgery