Faculty Bibliography

OBJECTIVES: Reports of Crohn's disease (CD)-associated colorectal carcinoma are being cited in the medical literature with increasing frequency. Our aim was to identify subgroups of patients with risk factors that may account for this. METHODS: We reviewed the medical records of 16 patients with the simultaneous diagnosis of CD and colorectal carcinoma and, in addition, reviewed previously reported cases of CD-associated colorectal carcinoma. RESULTS: Eight male and eight female patients presented with 18 carcinomas: four right colon, four transverse, two descending colon, and eight rectal lesions. Median age at presentation was 48 yr. The mean duration of CD before presentation of carcinoma was 19.7 yr. Two lesions were discovered in strictured bowel segments. Two patients had multiple cancers. One had simultaneous cecal and left colon adenocarcinomas. The other underwent resection of a right colon lesion and 5 yr later presented with transverse colon carcinoma. Eight patients had rectal cancer; all were diagnosed preoperatively. Six of these patients had a history of severe perianal CD. Six had undergone multiple incision and drainage procedures for perirectal abscesses and fistulas. Two developed malignancies in defunctionalized rectal stumps. One of these patients presented with simultaneous squamous rectal carcinoma and papillary bile duct cholangiocarcinoma. CONCLUSIONS: Gastrointestinal malignancy in association with CD has been reported. Symptoms of chronic inflammatory disease may obscure clinical manifestations of occult malignancy and thereby delay diagnosis. Crohn's patients with long-standing anorectal or perianal disease and stricture may well warrant surveillance endoscopy and biopsy of involved areas with the hope of earlier detection and treatment of these rectal cancers

PURPOSE: A prospective study of colorectal cancer (1987-1991) using flow cytometry was performed to determine the relationship of age with DNA index (DNA-I), sites of disease, Dukes stage, grade, and survival. METHODS: The flow cytometry was performed on 138 fresh, unfixed, surgical specimens using 4',6'-diamidino-2-phenylindole, a DNA fluorochrome. RESULTS: The mean age was 66.9 (42.8 percent > or = 70; range, 22-92; median, 68) years, and 48.6 percent were female. The patients' stages were (in percent): A, 4.4; B, 53.0; C, 38.2; D, 4.4. Tumor grades of differentiation (in percent) were well, 14.4; moderate, 68.9; poor, 16.7; and sites (in percent) were: rectum, 19.6; sigmoid/left, 50.7; transverse/right, 29.0. Aneuploidy (DNA-I not equal to 1.0; CV, 3.5 percent) was found in 58.8 percent. Age (by decade of presentation) was compared with site and Dukes stage. Older patients had more transverse/right-sided lesions (P = 0.003). Patients with Dukes C and D tumors had a lower age (by decade of presentation) than patients with B2 lesions (P = 0.03). Age was not related to DNA-I or grade or DNA-I with sex, grade, site, stage, or survival (P > 0.05). CONCLUSIONS: This prospective study suggests that colorectal cancer tends to present at an earlier stage and in the more proximal colon in the older population. Because right-sided lesions are beyond the reach of sigmoidoscopy, these findings have prognostic and screening implications

PBC is a cholestatic liver disease of unknown etiology with autoimmune features that is often associated with other autoimmune diseases. We analyzed peripheral blood T-cell subsets in patients groups with PBC (n = 11), non-PBC hepatobiliary disease (n = 11) and an age and sex matched control group (n = 11) by two color FACS-analysis. Seven out of eleven PBC patients exhibited markedly lowered and nearly undetectable levels of gamma delta T-cells (< 0.8%). None of the individuals in the non-PBC hepatobiliary disease (HBD) group or the normal control group had gamma delta values below 1%. The other four individuals in the PBC group had gamma delta values within the normal range. Overall, the PBC group had a statistically significant, lowered mean percentage of gamma delta T-cells (1.50%) as compared to the hepatobiliary disease group (3.76%) and the control group (4.22%, p = 0.01). The percentages of CD4+ and CD8+ and alpha beta TCR+ CD4-CD8- double negative cells in PBC patients did not differ from the control group. PBC patients with normal gamma delta cell counts did not differ from the PBC group with low gamma delta values in autoantibody titers, liver tests or treatment of the disease. As a possible cause for the observed decrease of gamma delta T-cells three sera of PBC patients with low gamma delta T-cell counts were screened by single color, indirect immunofluorescence for antibodies to gamma delta T-cell enriched lymphocytes, but no differences to control sera were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Pancreatitis has rarely been reported as a complication of Crohn's disease. We report our experience with two cases of pancreatitis associated with Crohn's disease. In one, the pancreatitis occurred secondary to duodenal Crohn's disease involving the ampulla of Vater. Endoscopic retrograde pancreatography demonstrated involvement of the ampulla, with marked dilation and delayed drainage of the pancreatic duct, suggesting mechanical obstruction. In the second patient, Crohn's disease was localized to the ileum and colon. We conclude that duodenal Crohn's can cause pancreatitis, and this may, in some cases, be on an obstructive basis. In addition, non-duodenal Crohn's disease can be associated with pancreatitis as well. In a patient with a history of Crohn's disease presenting with an atypical exacerbation, pancreatitis should be considered

Bacterial peritonitis has been known to complicate severe liver disease. Aerobic organisms are responsible for the vast majority of cases, whereas anaerobic bacteria are responsible for less than 5% of all cases reported in the literature. We now report a case of Clostridium cadaveris anaerobic bacterial peritonitis in a 58-yr-old female, an organism that to our knowledge has not been previously implicated as an infectious agent in this entity

Aneuploidy, abnormal nuclear DNA content, has been demonstrated in most malignant processes, including gastric malignancies. Utilizing flow cytometry on endoscopic biopsies, we have attempted to characterize the prevalence of aneuploidy and to investigate the prognostic implications of gastric biopsy DNA content with regard to survival. DNA aneuploidy was detected in 71% of specimens revealing malignancy by histologic evaluation. When aneuploidy was demonstrated, 63% of the specimens proved to be positive for malignancy (positive predictive value). However, the absence of aneuploidy had a negative predictive value for malignancy of 93%. Patients with diploid adenocarcinomas had a median survival of 32 months, compared to a median survival of 4 months in the group with DNA aneuploidy. Conclusions: 1) The prevalence of aneuploidy in endoscopically obtained specimens compares favorably with other previously reported series. 2) The presence of aneuploidy in gastric malignancies appears to correlate with decreased survival and may be helpful in making therapeutic decisions.

Barrett's esophagus is a premalignant condition; endoscopic surveillance is often performed to search for early adenocarcinoma of the esophagus. In an attempt to detect early changes of malignancy, we have added the use of flow cytometry to routine endoscopic surveillance procedures. DNA histograms were generated from biopsy samples by utilizing a specific DNA fluorochrome (4',6-diamidino-2-phenylindole) and flow cytometry. Sixty-three samples from patients with esophagitis, Barrett's esophagus, and esophageal malignancy were analyzed. An abnormal DNA histogram (aneuploidy) was detected in 79% of esophageal malignancies. In addition, aneuploidy was detected in seven patients with Barrett's esophagus, two of whom had dysplasia. DNA quantification with flow cytometry may be a useful adjunct in screening patients with Barrett's esophagus for early malignant change

The diagnosis of peritoneal carcinomatosis is often dependent on the finding of malignant cells in ascitic fluid analysis by a trained cytologist. Other methods are needed to increase the current diagnostic yield of 60-90%. Abnormal DNA content is characteristic of most malignancies. In an attempt to detect aneuploidy, we used high-resolution DNA histogram analysis with fluorescent DNA-specific stains and flow cytometry to evaluate 33 ascitic fluid samples. Of 13 patients with malignant ascites, aneuploidy was demonstrated in 10. Six patients with proven peritoneal carcinomatosis and normal cytologic examination had abnormal DNA histograms. DNA quantitation and cytologic examination agreed in 24 of 33 cases. These findings suggest that flow cytometry is a rapid and useful technique in the diagnosis of malignant ascites. The presence of aneuploidy in cells from ascitic fluid is highly suspicious for peritoneal carcinomatosis and suggests the need for further evaluation for malignancy