Variability of grade and stage in simultaneous paired liver biopsies in patients with hepatitis C.

BACKGROUND: Grading and staging of liver biopsies in patients with chronic hepatitis remains an inexact "gold standard" that is influenced by variabilities in scoring systems, sampling, observer agreement and expertise. Spatial disease variability relative to markers of the adequacy of biopsy has not been studied previously. METHODS: Paired liver biopsy specimens were obtained from the right and left hepatic lobes of 60 patients with chronic hepatitis C. Histological grade and disease stage were assessed according to the Ludwig scoring system, and scores were evaluated in relation to differences in size and number of portal tracts in all paired samples. RESULTS: The relative difference (%) in aggregate biopsy size and number of portal tracts was similar between paired samples with and without a difference in grade. Paired samples with a difference in stage showed a larger relative difference in biopsy size (p = 0.09) and in the number of portal tracts (p = 0.016). CONCLUSIONS: Our study shows a difference of one grade or one stage in 30% of paired liver biopsies, due to a combination of sampling variability and observer variability. Acknowledgment of "built-in" variability in grading and staging chronic hepatitis C by both clinicians and pathologists is essential for managing the individual patient with chronic hepatitis C.

Synchronous adenocarcinoma and mantle cell lymphoma of the colon.

Synchronous occurrence of malignant lymphoma and carcinoma, both located in the intestinal tract, is unusual. We report a unique case of an adenocarcinoma of the cecum and a simultaneous mantle cell lymphoma of the colon, terminal ileum, and regional lymph nodes in an 85-year-old man. Grossly, the adenocarcinoma was identified as a cecal mass. Lymphomatous involvement of the gastrointestinal tract was evident only on microscopic examination. The terminal ileum and colon showed microscopic disseminated multiple mucosal nodules, with involvement of the regional lymph nodes. There was no involvement of distant organs, suggesting that the mantle cell lymphoma was early in its evolution without formation of polyps or a mass lesion. To our knowledge, this is the fourth reported case with this association and the second case that showed early involvement of the gastrointestinal tract with mantle cell lymphoma without polyp formation.

Histopathological features of the terminal ileum in lymphocytic and collagenous colitis: a study of 32 cases and review of literature.

Biopsy specimens from the terminal ileum of 32 patients with the histopathological diagnosis of lymphocytic colitis or collagenous colitis and 11 control individuals were evaluated for the presence or absence of ileal mucosal abnormalities and for the number of intraepithelial lymphocytes, assessed by immunohistochemical stains for the pan T-cell marker, CD3. We found that the mean CD3 counts in patients with lymphocytic/collagenous colitis were significantly higher than those in the control group. Seven of 14 patients with collagenous colitis and 14 of 18 patients with lymphocytic colitis revealed an increase in intraepithelial T lymphocytes when compared with the control group (P =.001). Other notable changes included ileal villous atrophy in one case of lymphocytic colitis and in three cases of collagenous colitis and epithelial damage with thickened subepithelial collagen in two cases of collagenous colitis.

Diet modulates the toxicity of cancer chemotherapy in rats.

The effects of diet and folate status on cyclophosphamide or 5-fluorouracil toxicity were studied in Fischer 344 rats maintained on either a cereal-based diet or a purified diet (AIN-93G). The rats fed the purified diet were divided into 3 groups: folate deficient (no dietary folic acid), folate replete (2 mg folic acid/kg diet), and high folate (2 mg folic acid/kg diet plus 50 mg/kg body weight folic acid intraperitoneally daily). The LD50 for cyclophosphamide was significantly higher for the cereal diet than for the purified diets, but there was no difference among the purified diets. Deaths were predicted by dose, diet, white blood cell count, and BUN on Day 4 after treatment. In the saline-treated rats fed the purified diet, hepatic total glutathione levels increased in the following order: folate deficient < folate replete < high folate. There was no significant difference in aldehyde dehydogenase activities or of microsomal P450 levels in livers from rats on the different diets. In the rats treated with 5-fluorouracil, the high folate rats developed more severe anemia, azotemia, and leukopenia than the other groups. Weight, white blood cell count, hematocrit, and BUN were important predictors of death. The kidneys from rats fed the cereal-based diet were histologically normal, but rats ingesting the purified diet had increasing renal pathology that correlated with folate intake. These results indicate that diet has an important influence on the toxicity of cyclophosphamide and 5-fluorouracil and that folate status modulates hepatic glutathione levels, which is a major cellular defense against oxidant and alkylating agent damage.