Deficiency of Adenomatous Polyposis Coli protein in sporadic colorectal adenomas and its associations with clinical phenotype and histology.

AIM: To evaluate the frequency of the loss of the Adenomatous Polyposis Coli (APC) protein and to compare the APC status with the characteristics of colorectal adenomas. METHODS: Immunohistochemical analysis of the APC protein was performed on 118 adenomas and the results were compared with parameters of malignant potential, location of adenomas, macroscopic appearance and age of the patients. RESULTS: A complete loss of the APC protein was found in 28 (24%) adenomas, while 90 (76%) were APC positive. The mean size of adenomas was 13.5 +/- 14.2 mm (95% CI 10.5-16.5) in APC-positive, and 13.8 +/- 15.5 mm (95% CI 7.8-19.8) in APC-negative adenomas (P = 0.364). Statistical analysis revealed no difference between APC-positive and negative adenomas as to the histological type (P = 0.327) and grade of dysplasia (P = 0.494). We found that even advanced adenomas did not differ in their APC status from the non-advanced tumors (P = 0.414). Finally, no difference was found when the location (P = 0.157), macroscopic appearance (P = 0.571) and age of patients (P = 0.438) were analysed and compared between both APC positive and negative adenomas. CONCLUSION: Most adenomas expressed full-length APC protein, suggesting that protein expression is not a reliable marker for assessment of APC gene mutation. Complete loss of APC protein did not influence morphology, location, or appearance of adenomas, nor was it affected by the patient's age.

A multicenter assessment of liver toxicity by MRI and biopsy in IBD patients on 6-thioguanine.

BACKGROUND/AIMS: Although 6-thioguanine (6-TG) has been suggested as an effective treatment option for patients with inflammatory bowel disease (IBD), the recent description of its hepatotoxicity has led to the recommendation not to consider this drug. We initiated a multicenter safety study in IBD-patients treated with 6-TG to investigate hepatic changes by liver biopsy and magnetic resonance imaging (MRI). METHODS: Forty-five patients from three European centers treated with 6-TG (40-80 mg/d) at least for 8 weeks were enrolled. In all patients liver biopsy and MRI were performed. Slides and MR images were independently read by two pathologists and radiologists, respectively, and interpreted according to predefined criteria by consent. RESULTS: In 8 patients nodular regenerative hyperplasia (NRH) was diagnosed by liver biopsy, in 8 additional patients NRH could not be excluded due to equivocal pathological findings. MRI demonstrated a sensitivity of 77% and a specificity of 72% in the detection of pathohistological findings consistent with and/or possibly related to NRH. CONCLUSIONS: Our study suggests that 6-TG therapy in IBD patients is associated with NRH of the liver. Based on a special MRI protocol, non-invasive diagnosis of NRH with promising sensitivity and specificity was demonstrated.