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Key Words: NSAIDs, colonic ulcer.
Introduction:
History: A 60 year old male with a history of alcohol abuse, cocaine dependence, chronic hepatitis C infection, degenerative joint disease, left hemicolectomy in 1994 for adenocarcinoma of the sigmoid colon and cholecystectomy in 1997 was seen prior to this presentation for iron deficiency anemia, and then presented to the emergency department with right lower quadrant pain and other symptoms spanning five days. He reported having watery diarrhea for the first two days of symptoms, after eating at a vendor. The watery diarrhea resolved, but his abdominal pain continued, with an additional symptom the day of presentation of formed stool with specks of blood.
Physical Exam:
On physical examination, his vital signs were within normal limits and BMI=25.4. Right lower quadrant tenderness was noted, but without rebound or guarding. Bowel sounds were present. A rectal exam revealed dark brown stool.
Laboratory Studies:
WBC=10.4 K/cmm (nml)
RBC=5.08 M/cmm (nml)
Hemoglobin=14.5 g/dL (nml)
HCT=44.5 % (nml)
MCV=87.6 cmu (nml)
RDW=22.9 % (high)
PLT=174 K/cmm (nml)
Glucose=104 mg/dl (nml)
BUN=13 mg/dl (nml)
Creatinine=0.9 mg/dl (nml)
SGOT=232 IU/L (high)
SGPT=89 U/L (high)
Alkaline Phosphatase=59 U/L (nml)
Amylase=38 U/L (nml)
Lipase=39.3 U/L (nml)
Radiology Studies:
A CT scan revealed circumferential annular mural thickening of the entire ascending colon, which resembled a long-segment apple-core like lesion.
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Figure 2A |
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Figure 2C |
Endoscopy Studies:
Endoscopy was performed and revealed a circumferential lesion with ulcerated areas, consistent with colon cancer, in the ascending colon. Surgical resection was recommended.
Procedure:
The patient underwent a right hemicolectomy.
Gross Pathology:
In the ascending colon, there was an indurated, circumscribed, poorly delineated cobblestone like lesion located 3cm distal to the upper lip of the ileocecal valve. This lesion measured 2.5cm. in length and 3cm. in width. The lesion was composed of moderately broad firm rugae with multiple intervening narrow ulcers that measured in average 1mm. The mucosa of the broad rugae was shiny and ended in a sharp well defined manner at the margins of the ulcers. The cut surface of this lesion showed gross preservation of the bowel layers with the expected small distortions caused by the ulcers.
Histology:
The sections from a 3cm indurated area of colon described grossly show submucosal fibrosis and crypt disarray, consistent with healing ulcers, as well as ulcers that lack mucosa and have a small amount of associated active inflammation. Overall, there is a paucity of inflammation, which is typical in cases of non-steroidal anti-inflammatory drug (NSAID)-induced damage; however, there are scattered crypt abscesses and foci of cryptitis with prominent eosinophils. It is unclear whether they are part of the process or secondary to the stenosis. There are also areas of glandular atypia, but these are usually adjacent to healing erosions, the atypical areas are located in the regenerative zone and the epithelium matures at the surface, indicating regenerative atypia.
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Discussion:
NSAIDs are the most commonly prescribed drugs in the Western world, but they are not without risks. There is a five fold increased risk of gastrointestinal hemorrhage or perforation in women over 75 who routinely use NSAIDs,1,2 and there is a ten to thirty fold increased risk of chronic refractory peptic ulcer in patients on long term NSAID therapy.1,3 However, the use of lower NSAID doses, proton pump inhibitors and the introduction of cyclooxygenase 2 (COX-2) specific inhibitors have caused a decrease in serious gastrointestinal injury due to NSAID use. Although ulceration of the stomach and duodenum have been associated with NSAID use for quite some time,4,5 the toxicity effects of these drugs on the small and large intestine have only been investigated relatively recently.5,6,7,8
The endoscopic appearance of the colon in a patient using NSAIDs may be normal, or may display erosions, ulcers or mucosal diaphragms, which are believed to be pathognomonic of NSAID-induced injury.9,10 The luminal diameter of such mucosal diaphragms may be as small as 1mm. Circumferential linear ulcers are proposed to be the precursors to these mucosal diaphragms.11 To our knowledge, cases of “apple-core” lesions, such as ours, have not yet been described in the literature. The most common microscopic manifestation of NSAID-induced colonic pathology is that of non-specific mucosal ulceration, but focal colonic crypt injury, such as cryptitis or crypt abscesses, is also common.1 NSAID-induced colitis may morphologically mimic other forms of colitis, including inflammatory bowel disease, collagenous colitis, eosinophilic colitis and pseudomembranous colitis1; however, features that favor NSAID-induced injury include an increase in apoptotic bodies, intraepithelial lymphocytosis (similar to lymphocytic colitis) and unexpected tissue eosinophilia.1,12 In our case the lack of significant lamina propria inflammation and prominence of eosinophils within crypt abscesses are histologic clues to the correct diagnosis. The presence of ulceration in a background relatively devoid of increased inflammation is sometimes described as “clean ulceration” and is a typical finding in cases of NSAID-induced colitis. The clinical history provided by the contributor was also supportive of the diagnosis. The patient had a three month history of aspirin use to alleviate joint pain.
The opinions and assertions contained herein are the private views of the authors, and are not to be construed as official, or as reflecting the views of the Departments of the Army and Defense.
References:
1. Noffsinger A, Fenoglio-Preiser C, Maru D, Gilinsky N. Gastrointestinal Diseases. Washington, DC: American Registry of Pathlogy, 2007.
2. Wilcox CM, Shalek KA, Cotsonis G. Striking prevalence of over-the-counter nonsteroidal anti-inflammatory drug use in patients with upper gastrointestinal hemorrhage. Arch Intern Med 1994;154:42-46.
3. Hawky CJ. Non-steroidal anti-inflammatory drug gastropathy: causes and treatment. Scand J Gastroenterol 1996;220:124-127.
4. Silvoso G, Ivey KJ, Butt J. Incidence of gastric lesions in patients with rheumatic disease on chronic aspirin therapy. Ann Intern Med 1979;91:517-520
5. Odze R, Goldblum J, Crawford J. Surgical Pathology of the GI Tract, Liver, Biliary Tract and Pancreas. Philadelphia: Saunders, 2004.
6. Allison, MC, Howatson AG, Torrance CJ, et al. Gastrointestinal damage associated with the use of non-steroidal anti-inflammatory drugs. N Engl J Med 1992;327:749-754.
7. Davies NM, Saleh, JY. Detection and prevention of NSAID-induced enteropathy. J Pharm. Pharmaceut Sci 2000;3:137-155.
8. Bjarnason I, Hayllar J, MacPherson AJ, et al. Side effects of non-steroidal anti-inflammatory drugs on the small and large intestine in humans. Gastroenterology 1993;104:1832-1847.
9. Lang J, Price AB, Levi AJ, Burke M, Gumpel JM, Bjarnason I. Diaphragm disease: pathology of disease of the small intestine induced by non-steroidal anti-inflammatory drugs. J Clin Pathol 1988;41:516-526.
10. Robinson MH, Wheatley T, Leach IH. Nonsteroidal anti-inflammatory drug-induced colonic stricture: an unusual cause of large bowel obstruction and perforation. Dig Dis Sci 1995;40:315-319.
11.Going JJ, Canvin J, Sturrock R. Possible precursor of diaphragm disease in the small intestine. Lancet 1993;341:638-639.
12. Lee FD. Importance of apoptosis in the histopathology of drug-related lesions in the large intestine. J Clin Pathol 1993;46:118-122.
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