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Colonoscopic findings in a leukemic patient
occur at these sites. Factors leading to a decrease in the normal wall thickness may include advancing age, bowel ulceration, malnutrition,.and mucosal atrophy. Other factors such as inflammation, fibrosis, and neoplasia may cause a thickening in the bowel wall and enhance the safety margin. Large angiomas requiring multiple probe applications would be expected to have a higher complication ratio associated with coagulation therapy. This is suggested experimentally in the canine model. l2 Despite these concerns, there has been, to date, a good safety record for endoscopic treatment of colonic vascular lesions. One case of cecal perforation with monopolar electrocoagulation6 and another case with argon laser photocoagulation9 have appeared in the literature. To my knowledge, no cases of colonic perforation with BICAJ>® treatment have previously been reported. In our patient, the size of the treated lesion and bowel wall thinness probably contributed to this complication. The larger angioma in this case was approximately 1 em in diameter. Because of this, multiple probe applications were required to obliterate the lesion. The location of the vascular abnormalities was in the normally thin-walled right colon. In addition, the patient's entire intestinal wall was felt to be thin by surgical estimation. This may have been related to the patient's age and somewhat poor nutritional state. Awareness of the potential risk for transmural injury and perforation complicating therapeutic coagulation of vascular lesions is obviously important. Technical factors are critical and, certainly, bowel overdistension and undue probe apposition pressure are to be avoided. In the regions where large angiomas are to be treated and/or the bowel wall is suspected to
Colonoscopic findings in a leukemic patient Nancy C. Manzione, MD Michael Kram, MD Luis Biempica, MD
Leukemic involvement of the gastrointestinal tract has been recognized for more than a century. The exact incidence is not known since most information is the result of autopsy studies that represent either terminal gastrointestinal complications or incidental findings. l Premortem lesions have been described raFrom the Departments of Gastroenterology and Pathology, Albert Einstein College of Medicine, Bronx, New York. Reprint requests: Dr. Nancy C. Manzione, Liver Research Center, Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461. VOLUME 34, NO.1, 1988
be thin, lower BICAJ>® settings should be considered to lessen the chances of this complication. Thus, for coagulation, one could start at a setting of 3 or 4 and gradually increase the setting to achieve coagulation at the lowest power.
REFERENCES 1. Fleischer D. Endoscopic therapy of upper gastrointestinal bleeding in humans. Gastroenterology 1986;90:217-34.
2. Forde KA. Colonoscopy in acute rectal bleeding. Gastrointest Endosc 1981;27:219-20. 3. Rossini FP, Ferrari A. Emergency colonoscopy. In: Hunt RH, Waye JD, eds. Colonoscopy: techniques, clinical practice and color atlas. London: Chapman and Hall, 1981:289-99. 4. Jensen DM, Machicado GA, Tapia JI. Emergent colonoscopy in patients with severe hematochezia (abstract). Gastrointest Endosc 1983;29:177. 5. Rogers BHG. Endoscopic electrocoagulation of vascular abnormalities of the gastrointestinal tract in 51 patients (abstract). Gastrointest Endosc 1982;28:142-3. 6. Howard OM, Buchanan JD, Hunt RH. Angiodysplasia of the colon: experience of 26 cases. Lancet 1982;2:16-9. 7. Marcon NE, Haber GB, Kortan PP, Cohen L. Neodymium: YAG laser coagulation of angiodysplasia in the gastrointestinal tract (abstract). Gastrointest Endosc 1985;31:169. 8. Jensen DM, Machicado GA. Bleeding colonic angioma: endoscopic coagulation and follow-up (abstract). Gastroenterology 1985;88:1433.
9. Cello JP, Grendell JH. Endoscopic laser treatment for gastrointestinal vascular ectasias. Ann Intern Moo 1986;104:352-4. 10. Johnston JH, Jensen DM, Mautner W. Comparison of endoscopic electrocoagulation and laser photocoagulation of bleeding canine gastric ulcers. Gastroenterology 1982;82:904-10. 11. Johnston JH, Jensen DM, Auth D. Comparison of endoscopic lasers, electrosurgery and the heater probe in coagulation of canine arteries (abstract). Gastrointest Endosc 1984;30:154. 12. Jensen DM, Shindel N, Brunetaud JM, Hirabayashi K, Harris L. Temperature profiles and transmural injury from heater probe vs BICA~ in the canine colon (abstract). Gastrointest Endosc 1986;32:140-1. 13. Jensen DM, Machicado GA, Tapia JI, Mautner W. Comparison of argon laser photocoagulation and bipolar electrocoagulation for endoscopic hemostasis in the canine colon (abstract). Gastrointest Endosc 1981;27:131.
diologically.2,3 With ·the advent of endoscopy, these lesions may be diagnosed even more frequently and earlier, so that therapeutic intervention can be taken. We present here the colonoscopic findings responsible for gastrointestinal bleeding in a patient with leukemia.
CASE REPORT A 61-year-old black man was admitted with sudden onset of painless hematochezia associated with dizziness. He was healthy except for some mild hypertension controlled with salt restriction and adult onset diabetes mellitus treated with insulin. Abdominal examination was negative. Digital rectal examination revealed red blood but no masses. Laboratory data were significant for his white blood cell count (139,000 with 53 polymorphonuclear cells, 15 bands, 14 lymphocytes, 1 monocyte, 2 eosinophils, 8 myelocytes, and 59
7 metamyelocytes). Hematocrit was 25% requiring transfusion with 2 units of packed red blood cells. 9!ltfc sulfa colloid scan did not reveal a bleeding site and bleeding ceased spontaneously. Bone marrow aspirate was consistent with chronic myelogenous leukemia. The predominant cells were myelocytic with numerous blasts present. Philadelphia chromosome was positive. Colonoscopic examination performed on the second hospital day revealed two pedunculated polyps 1 cm in diameter at the hepatic flexure, and in the descending colon at 50 cm from the anus. Also, two flat polyps 0.5 cm in diameter were seen in the cecum (Fig. 1) on a background of melanosis coli. These were removed since they were felt to be the source of bleeding. Whitish plaques adherent to the mucosa were noted in the rectosigmoid (Fig. 2). Microscopic examination of the pedunculated polyps showed tubulovillous adenomas. The stroma was made of densely packed cells, mostly of the myelocytic series, alternating with megakaryocytes, macrophages, lymphocytes, and plasma cells (Fig. 3). Similar leukemia infiltrates were seen in the flat cecal polyps. The whitish plaque proved to be a pseudomembrane. Immunocytochemical staining of the polyp and bone marrow with anti-leu M h a marker for Hodgkin's Reed-Sternberg cells and granulocytes was positive in many cells. The patient was treated with busulfan and prednisone and did well.
DISCUSSION
Pathologically, leukemic involvement of the gastrointestinal tract can be divided into four categories: leukemic inflltration, agranulocytic ulcers with bacterial invasion and occasional pseudomembrane formation, hemorrhagic necroses, and mycotic lesions.1 Leukemic inflltrates are frequently asymptomatic. They can, however, produce symptoms ranging from nausea, mild abdominal pain, and diarrhea to hemorrhage, perforation, intussusception, obstruction, 2 necrotizing enteritis, and protein losing enteropathy.3 Endoscopic examination with biopsy can help to elucidate the cause of abnormal filling defects on barium studies4- 7 or clarify the nature of gastrointestinal complaints. Agranulocytic necrosis is the result of bacterial invasion of the intestinal wall because of decreased host resistance. In the cecum, perforation is common.9 In the rectum, these ulcers can cause considerable pain and bleeding. 9 Pseudomembranes composed of leukocytes, red blood cells, fibrin, and bacterial colonies can be found in the distal ileum, jejunum, and cecum. However, more classic "colonic" pseudomembranes have been found especially with antibiotic use and have been responsive to vancomycin therapy.9,lo This patient had pseudomembranes in the rectum without prior antibiotic treatment. Morbidity from these necrotizing lesions can be high. l l However, adequate diagnostic measures such as flexible sigmoidoscopy and colonoscopy, if used earlier to investigate nonspecific diarrhea, fever of unknown origin, hematochezia, and nonspecific abdominal discomfort, may pick up less 60
Figure 1. CoI0n0scopic view of two O.5-cm polyps on backgroup of melanosis coli. Figure 2. CoIonoscopic view of white plaque adherent to mucosa. Biopsy showed pseudomembrane.
severe lesions so that effective therapy could be instituted early in the course of the disease. Hemorrhagic necrotic lesions are similar endoscopically to those seen with vascular insufficiency. These lesions, however, can be diffuse, not conforming to any vascular distribution and, indeed, there is no occlusion of vessels on microscopic examination. 13 Proctologic lesions can sometimes be the presenting complaint in leukemia, manifesting as rectal pain and mucosanguinous discharge. Endoscopically, ulcerated nodules, polypoid masses, friable mucosa, pseudoGASTROINTESTINAL ENDOSCOPY
ation can help elucidate the etiology as it did in this case. The role of endoscopy in the evaluation of leukemic patients with gastrointestinal symptoms may be an important one. Diarrhea with or without hematochezia, abdominal pain and distension, rectal pain with mucopurulent discharge, odynophagia, and gastrointestinal hemorrhage can indicate the presence of leukemic involvement ofthe gastrointestinal tract. These are potentially life-threatening. Early evaluation with the use of endoscopy may prove useful in hastening therapeutic intervention. In order to safely prepare patients for endoscopy, the authors recommend that neutropenic patients receive antibiotics in similar doses used for endocarditis prophylaxis. 14 If thrombocytopenic, platelets should be transfused prior to biopsy. ACKNOWLEDGMENT
The authors would like to thank Anna Caponigro for her excellent secretarial assistance.
REFERENCES 1. Prolla JC, Kirsner J. The gastrointestinal lesions and compli-
Figure 3. High power view of polyp. Glands are separated by a very cellular infiltrate. The glandular epithelium displays crowded nuclei with moderate to complete maturation and relatively normal looking goblet cells. The cellular component of the lamina propria is made up of a moderate population of lymphocytes, plasma cells, occasional macrophages, and numerous immature granulocytes (hematoxylin-eosin, x65).
membranes, or abscesses may be found, making it difficult sometimes to differentiate from rectal carcinoma or ulcerative or pseudomembranous colitis. Biopsies are diagnostic but carry with them the danger of bleeding. Gastrointestinal bleeding in leukemic patients can be massive if there is thrombocytopenia or sepsis. Stress-induced, as well as leukemic ulcers, hemorrhagic necrosis, pseudomembranous colitis, polyps and infiltrates, and varices secondary to liver and splenic infiltration are all possible causes. Endoscopic evalu-
VOLUME 34, NO.1, 1988
cations of the leukemias. Ann Intern Med 1964;61:1084-103. 2. Jarett SL, Tefet M, Drummord CP, Levitan R. Leukemic infiltration of the sigmoid. Report of a case similar to carcinoma with obstruction. Am J Dig Dis 1963;8:299-304. 3. Cockington RA. Leukemic infiltration of the gastrointestinal tract: an unusual case of protein-losing enteropathy. Moo J Aust 1975;1:103-5. 4. Boikan WS. Leukemic changes of the gastrointestinal tract. Arch Intern Moo 1931;47:42-57. 5. Rabin MS, Bledin AG, Lewis D. Polypoid leukemic infiltration of the large bowel. Am J RoentgenoI1978;131:723-4. 6. Limberakis AJ, MossIer JA, Roberts L, Jackson DC, Thompson WM. Leukemic infiltration of the colon. Am J Roentgenol 1978;0:725-8. 7. Blatt LJ, Chapman I. Multiple colonic polyps of leukemic origin. Dis Colon Rectum 1960;2:237-40. 8. Wagner ML, Rosenberg HS, Fernbach DJ, Singleton EB. Typhlitis: a complication of leukemia of childhood. Am J RoentgenoI1970;109:341-50. 9. Birnbaum W, Ahlquest R. Rectal infections and ulcerations associated with blood dyscrasias. Am J Surg 1955;90:367-72. 10. Milligan DW, Kelly JK. Pseudomembranous colitis in a leukemic unit: a report of five fatal cases. J Clin Pathol 1979;32:1237-43. 11. Dosik GM, Luna M, Valdivieso M, et al. Necrotizing colitis in patients with cancer. Am J Med 1979;67:646-56. 12. Freeman HJ, Rabeneck L, Owen D. Survival after necrotizing enterocolitis of leukemia treated with oral canomycin. Gastroenterology 1981;81:791-4. 13. Ming SC, Leviton R. Acute hemorrhagic necrosis of the gastrointestinal tract. N Engl J Moo 1960;263:59-64. 14. Kaye D. Prophylaxis for infective endocarditis: an update. Ann Intern Moo 1986;104:419-23.
61
Colonoscopic findings in a leukemic patient Nancy C. Manzione, MD Michael Kram, MD Luis Biempica, MD
Leukemic involvement of the gastrointestinal tract has been recognized for more than a century. The exact incidence is not known since most information is the result of autopsy studies that represent either terminal gastrointestinal complications or incidental findings. l Premortem lesions have been described raFrom the Departments of Gastroenterology and Pathology, Albert Einstein College of Medicine, Bronx, New York. Reprint requests: Dr. Nancy C. Manzione, Liver Research Center, Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461. VOLUME 34, NO.1, 1988
be thin, lower BICAJ>® settings should be considered to lessen the chances of this complication. Thus, for coagulation, one could start at a setting of 3 or 4 and gradually increase the setting to achieve coagulation at the lowest power.
REFERENCES 1. Fleischer D. Endoscopic therapy of upper gastrointestinal bleeding in humans. Gastroenterology 1986;90:217-34.
2. Forde KA. Colonoscopy in acute rectal bleeding. Gastrointest Endosc 1981;27:219-20. 3. Rossini FP, Ferrari A. Emergency colonoscopy. In: Hunt RH, Waye JD, eds. Colonoscopy: techniques, clinical practice and color atlas. London: Chapman and Hall, 1981:289-99. 4. Jensen DM, Machicado GA, Tapia JI. Emergent colonoscopy in patients with severe hematochezia (abstract). Gastrointest Endosc 1983;29:177. 5. Rogers BHG. Endoscopic electrocoagulation of vascular abnormalities of the gastrointestinal tract in 51 patients (abstract). Gastrointest Endosc 1982;28:142-3. 6. Howard OM, Buchanan JD, Hunt RH. Angiodysplasia of the colon: experience of 26 cases. Lancet 1982;2:16-9. 7. Marcon NE, Haber GB, Kortan PP, Cohen L. Neodymium: YAG laser coagulation of angiodysplasia in the gastrointestinal tract (abstract). Gastrointest Endosc 1985;31:169. 8. Jensen DM, Machicado GA. Bleeding colonic angioma: endoscopic coagulation and follow-up (abstract). Gastroenterology 1985;88:1433.
9. Cello JP, Grendell JH. Endoscopic laser treatment for gastrointestinal vascular ectasias. Ann Intern Moo 1986;104:352-4. 10. Johnston JH, Jensen DM, Mautner W. Comparison of endoscopic electrocoagulation and laser photocoagulation of bleeding canine gastric ulcers. Gastroenterology 1982;82:904-10. 11. Johnston JH, Jensen DM, Auth D. Comparison of endoscopic lasers, electrosurgery and the heater probe in coagulation of canine arteries (abstract). Gastrointest Endosc 1984;30:154. 12. Jensen DM, Shindel N, Brunetaud JM, Hirabayashi K, Harris L. Temperature profiles and transmural injury from heater probe vs BICA~ in the canine colon (abstract). Gastrointest Endosc 1986;32:140-1. 13. Jensen DM, Machicado GA, Tapia JI, Mautner W. Comparison of argon laser photocoagulation and bipolar electrocoagulation for endoscopic hemostasis in the canine colon (abstract). Gastrointest Endosc 1981;27:131.
diologically.2,3 With ·the advent of endoscopy, these lesions may be diagnosed even more frequently and earlier, so that therapeutic intervention can be taken. We present here the colonoscopic findings responsible for gastrointestinal bleeding in a patient with leukemia.
CASE REPORT A 61-year-old black man was admitted with sudden onset of painless hematochezia associated with dizziness. He was healthy except for some mild hypertension controlled with salt restriction and adult onset diabetes mellitus treated with insulin. Abdominal examination was negative. Digital rectal examination revealed red blood but no masses. Laboratory data were significant for his white blood cell count (139,000 with 53 polymorphonuclear cells, 15 bands, 14 lymphocytes, 1 monocyte, 2 eosinophils, 8 myelocytes, and 59
7 metamyelocytes). Hematocrit was 25% requiring transfusion with 2 units of packed red blood cells. 9!ltfc sulfa colloid scan did not reveal a bleeding site and bleeding ceased spontaneously. Bone marrow aspirate was consistent with chronic myelogenous leukemia. The predominant cells were myelocytic with numerous blasts present. Philadelphia chromosome was positive. Colonoscopic examination performed on the second hospital day revealed two pedunculated polyps 1 cm in diameter at the hepatic flexure, and in the descending colon at 50 cm from the anus. Also, two flat polyps 0.5 cm in diameter were seen in the cecum (Fig. 1) on a background of melanosis coli. These were removed since they were felt to be the source of bleeding. Whitish plaques adherent to the mucosa were noted in the rectosigmoid (Fig. 2). Microscopic examination of the pedunculated polyps showed tubulovillous adenomas. The stroma was made of densely packed cells, mostly of the myelocytic series, alternating with megakaryocytes, macrophages, lymphocytes, and plasma cells (Fig. 3). Similar leukemia infiltrates were seen in the flat cecal polyps. The whitish plaque proved to be a pseudomembrane. Immunocytochemical staining of the polyp and bone marrow with anti-leu M h a marker for Hodgkin's Reed-Sternberg cells and granulocytes was positive in many cells. The patient was treated with busulfan and prednisone and did well.
DISCUSSION
Pathologically, leukemic involvement of the gastrointestinal tract can be divided into four categories: leukemic inflltration, agranulocytic ulcers with bacterial invasion and occasional pseudomembrane formation, hemorrhagic necroses, and mycotic lesions.1 Leukemic inflltrates are frequently asymptomatic. They can, however, produce symptoms ranging from nausea, mild abdominal pain, and diarrhea to hemorrhage, perforation, intussusception, obstruction, 2 necrotizing enteritis, and protein losing enteropathy.3 Endoscopic examination with biopsy can help to elucidate the cause of abnormal filling defects on barium studies4- 7 or clarify the nature of gastrointestinal complaints. Agranulocytic necrosis is the result of bacterial invasion of the intestinal wall because of decreased host resistance. In the cecum, perforation is common.9 In the rectum, these ulcers can cause considerable pain and bleeding. 9 Pseudomembranes composed of leukocytes, red blood cells, fibrin, and bacterial colonies can be found in the distal ileum, jejunum, and cecum. However, more classic "colonic" pseudomembranes have been found especially with antibiotic use and have been responsive to vancomycin therapy.9,lo This patient had pseudomembranes in the rectum without prior antibiotic treatment. Morbidity from these necrotizing lesions can be high. l l However, adequate diagnostic measures such as flexible sigmoidoscopy and colonoscopy, if used earlier to investigate nonspecific diarrhea, fever of unknown origin, hematochezia, and nonspecific abdominal discomfort, may pick up less 60
Figure 1. CoI0n0scopic view of two O.5-cm polyps on backgroup of melanosis coli. Figure 2. CoIonoscopic view of white plaque adherent to mucosa. Biopsy showed pseudomembrane.
severe lesions so that effective therapy could be instituted early in the course of the disease. Hemorrhagic necrotic lesions are similar endoscopically to those seen with vascular insufficiency. These lesions, however, can be diffuse, not conforming to any vascular distribution and, indeed, there is no occlusion of vessels on microscopic examination. 13 Proctologic lesions can sometimes be the presenting complaint in leukemia, manifesting as rectal pain and mucosanguinous discharge. Endoscopically, ulcerated nodules, polypoid masses, friable mucosa, pseudoGASTROINTESTINAL ENDOSCOPY
ation can help elucidate the etiology as it did in this case. The role of endoscopy in the evaluation of leukemic patients with gastrointestinal symptoms may be an important one. Diarrhea with or without hematochezia, abdominal pain and distension, rectal pain with mucopurulent discharge, odynophagia, and gastrointestinal hemorrhage can indicate the presence of leukemic involvement ofthe gastrointestinal tract. These are potentially life-threatening. Early evaluation with the use of endoscopy may prove useful in hastening therapeutic intervention. In order to safely prepare patients for endoscopy, the authors recommend that neutropenic patients receive antibiotics in similar doses used for endocarditis prophylaxis. 14 If thrombocytopenic, platelets should be transfused prior to biopsy. ACKNOWLEDGMENT
The authors would like to thank Anna Caponigro for her excellent secretarial assistance.
REFERENCES 1. Prolla JC, Kirsner J. The gastrointestinal lesions and compli-
Figure 3. High power view of polyp. Glands are separated by a very cellular infiltrate. The glandular epithelium displays crowded nuclei with moderate to complete maturation and relatively normal looking goblet cells. The cellular component of the lamina propria is made up of a moderate population of lymphocytes, plasma cells, occasional macrophages, and numerous immature granulocytes (hematoxylin-eosin, x65).
membranes, or abscesses may be found, making it difficult sometimes to differentiate from rectal carcinoma or ulcerative or pseudomembranous colitis. Biopsies are diagnostic but carry with them the danger of bleeding. Gastrointestinal bleeding in leukemic patients can be massive if there is thrombocytopenia or sepsis. Stress-induced, as well as leukemic ulcers, hemorrhagic necrosis, pseudomembranous colitis, polyps and infiltrates, and varices secondary to liver and splenic infiltration are all possible causes. Endoscopic evalu-
VOLUME 34, NO.1, 1988
cations of the leukemias. Ann Intern Med 1964;61:1084-103. 2. Jarett SL, Tefet M, Drummord CP, Levitan R. Leukemic infiltration of the sigmoid. Report of a case similar to carcinoma with obstruction. Am J Dig Dis 1963;8:299-304. 3. Cockington RA. Leukemic infiltration of the gastrointestinal tract: an unusual case of protein-losing enteropathy. Moo J Aust 1975;1:103-5. 4. Boikan WS. Leukemic changes of the gastrointestinal tract. Arch Intern Moo 1931;47:42-57. 5. Rabin MS, Bledin AG, Lewis D. Polypoid leukemic infiltration of the large bowel. Am J RoentgenoI1978;131:723-4. 6. Limberakis AJ, MossIer JA, Roberts L, Jackson DC, Thompson WM. Leukemic infiltration of the colon. Am J Roentgenol 1978;0:725-8. 7. Blatt LJ, Chapman I. Multiple colonic polyps of leukemic origin. Dis Colon Rectum 1960;2:237-40. 8. Wagner ML, Rosenberg HS, Fernbach DJ, Singleton EB. Typhlitis: a complication of leukemia of childhood. Am J RoentgenoI1970;109:341-50. 9. Birnbaum W, Ahlquest R. Rectal infections and ulcerations associated with blood dyscrasias. Am J Surg 1955;90:367-72. 10. Milligan DW, Kelly JK. Pseudomembranous colitis in a leukemic unit: a report of five fatal cases. J Clin Pathol 1979;32:1237-43. 11. Dosik GM, Luna M, Valdivieso M, et al. Necrotizing colitis in patients with cancer. Am J Med 1979;67:646-56. 12. Freeman HJ, Rabeneck L, Owen D. Survival after necrotizing enterocolitis of leukemia treated with oral canomycin. Gastroenterology 1981;81:791-4. 13. Ming SC, Leviton R. Acute hemorrhagic necrosis of the gastrointestinal tract. N Engl J Moo 1960;263:59-64. 14. Kaye D. Prophylaxis for infective endocarditis: an update. Ann Intern Moo 1986;104:419-23.
61