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Percutaneous ethanol injection (PEI) was applied to 120 lesions in 95 patients with hepatocellular carcinomas (HCC) smaller than 3 cm in the past 6 years. All main target tumours, in 67 patients who had been followed by sonography for more than 6 months after PEI, decreased in size; 28 tumours (41.8%) became undetectable and have remained so until now. The 1-, 2-, 3-, 4- and 5-year survival rates calculated by the Kaplan-Meier method were 93%, 81%, 65%, 52% and 28% respectively. These survival rates were better than those of patients with HCC smaller than 3 cm who did not receive anticancer treatment (P less than 0.01). The survival of patients of the Child's A or Child's B status was better than that of those with Child's C disease. Recurrence occurred in areas within the liver different from the original lesion in 34% in one year, 61% in two years and 66% in three years after PEI. PEI was then repeated in 61% of such patients.

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Nodular hepatic lesions detected in 123 patients with chronic liver diseases were subjected to ultrasonically guided needle biopsy. Of these, 94 cases were diagnosed as hepatocellular carcinoma of a moderately or poorly differentiated type with classical histologic features of hepatocellular carcinoma. In 14 cases in whom hepatocytes had minimal atypical changes and were mostly of normotrabecular arrangement (one to two cells thick), a diagnosis of well-differentiated hepatocellular carcinoma was made on the basis of the following three histologic criteria: nuclear crowding, increased cytoplasmic basophilia and microacinar formation. The nodules which showed two or more of these findings were diagnosed as well-differentiated HCC. The diagnoses of these 14 cases were subsequently confirmed by clinical course, histology in the resected specimen and/or autopsy findings. The nodules that presented similar but equivocal changes were arbitrarily categorized as borderline lesions (five cases). The nodules showing the findings almost identical with those of pseudolobules were regarded as benign, large regenerative nodules (nine cases). The remaining one case had a hemangioma. Thus, these three histologic criteria proved to be useful in the biopsy diagnosis of nodular hepatic lesions, with certain limitations. Additionally, the majority of large regenerative nodules, borderline lesions and well-differentiated HCCs were found to be smaller than 2 cm.

The signal intensity of HCC on T1-weighted images is related to the degree of histologic differentiation, intratumoral copper content, and zinc content of surrounding hepatic parenchyma, whereas the signal intensity on T2-weighted images is related to the degree of histologic differentiation.

Expression of B lymphocyte-induced maturation protein 1 (Blimp-1) transcription factor is essential for promoting B cell differentiation into plasma cells. However, a critical transcription factor for Blimp-1 expression in activated B cells is unclear. When splenic B cells were stimulated with CD40 ligand (CD40L) and IL-4, terminal differentiation was induced in the B cells from c-fos transgenic (H2-c-fos) mice but barely in those from control littermates and from c-fos-deficient mice. AP-1 family and Blimp-1 mRNAs were transiently induced in the control B cells, and overexpression of c-Fos induced a sufficient amount of Blimp-1 for terminal differentiation in the H2-c-fos B cells. When normal and c-fos-deficient B cells were stimulated with LPS, a sufficient amount of Blimp-1 for terminal differentiation was induced in those B cells. However, expression of c-fos/AP-1 family mRNAs in LPS-stimulated normal B cells was similar to that of normal B cells stimulated with CD40L and IL-4. EMSA and chromatin immunoprecipitation assays using the AP-1-binding DNA sequence in the murine Blimp-1 promoter region demonstrated that AP-1-binding activity in nuclear protein of LPS-stimulated normal B cells was prolonged more than that in normal B cells stimulated with CD40L and IL-4. Furthermore, the percentage of CD138+ B cells within germinal center B cells in the spleen and the number of Ab-forming cells in the bone marrow of H2-c-fos mice was larger than that of control mice 12 days after immunization. Thus, although c-Fos is not essential for Blimp-1 expression, c-Fos/AP-1 positively regulates Blimp-1 expression and terminal differentiation of activated B cells.

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