Influence of antimicrobial treatment for Helicobacter pylori infection on the intestinal microflora in Japanese macaques.

Eradication treatment for Helicobacter pylori is known to cause mild but relatively frequent adverse effects. Some adverse effects such as diarrhoea and soft stools are related to disruption of the composition of the intestinal microflora. This study investigated the microfloral changes resulting from administration of an eradication regimen using proton pump inhibitor (PPI), amoxycillin and clarithromycin. Twenty-eight laboratory-bred Japanese macaques either were administered eradication treatment by this regimen for 7 days or received no medication. Faecal samples were collected for analysis on days 0, 8 and 15, and both aerobic and anaerobic cultures were performed. Among aerobic bacteria, Streptococcus had significantly decreased by day 8, while Enterococcus and Enterobacteriaceae had significantly increased. However, the total number of aerobic bacteria was not significantly decreased from pretreatment levels 1 day after completion of treatment. The number of anaerobic bacteria did not change significantly by day 8. However, the number of Lactobacillus and the detection rate of Bifidobacterium, Peptostreptococcus and Veillonella significantly decreased by day 8, although the number of Bifidobacterium, Peptostreptococcus and Veillonella had almost recovered up to the pretreatment levels 1 week after completion of treatment (day 15). These results suggest that the alterations in the composition of the intestinal microflora caused by the antimicrobial regimen that excludes metronidazole are different from those caused by the regimen including this drug. However, the alterations in bacterial microflora had almost reversed 7 days after completion of treatment in these macaques, which supports clinical findings that diarrhoea or soft stools in humans resolve relatively quickly after a similar treatment.

Development of multicentric hepatocellular carcinoma after completion of interferon therapy.

We report a case of multicentric hepatocellular carcinoma that developed in a 74-year-old man 3 and 6 years after interferon (IFN) treatment for chronic hepatitis C, despite sustained virologic, biochemical, and histological improvement. Initially, serum hepatitis C virus RNA was positive and the patients' serum level of alanine aminotransferase (ALT; 82 IU/ml) was abnormal. Hepatitis B virus (HBV) in the serum was negative for surface antigen, surface antibody, core antibody, and DNA. The patient was started on 10 x 10(6) international units (IU) of IFNalpha, 3 days a week for a total of 24 weeks. After the IFN therapy, the patient demonstrated a normal serum ALT level, and was continuously negative for HCV-RNA, and histology improved from chronic active hepatitis to chronic persistent hepatitis. Follow-up studies with ultrasonography (US) every 3 months and computed tomography (CT) every 6 months revealed no space-occupying lesion (SOL) for 3 years after IFN treatment.US-guided biopsies of two 15-mm hypoechoic SOLs in segments eight (S8) and seven (S7) 34 and 74 months, respectively, after IFN treatment showed well-differentiated hepatocellular carcinoma (HCC). Clinical data, imaging studies, and histologic examinations showed that both tumors were multicentric HCC. Further studies may provide insights into the possible role of HCV in hepatocarcinogenesis in patients demonstrating HCV eradication by IFN treatment.

CEA producing primary hepatic carcinoid.

Imaging studies of a hepatic tumor in a 53-year-old woman with elevated serum levels of neuron-specific enolase (NSE), carcinoembryonic antigen (CEA) and 5-hydroxyindole acetic acid (5HIAA) revealed a hypervascular tumor in the right lobe. Grossly, the brownish tumor was measured 13.5x12 cm with four daughter nodules. Microscopically, the majority of these columnar and round tumor cells had ribbon-or rosette-like patterns with the expression of neuroendocrine marker proteins, such as Grimelius, NSE, chromogranin A, and synaptophysin, and moderate expression of CEA but without the expression of cytokeratin nos 7,8,14,18,19 and OV-6; the minority had glandular patterns with a strong expression of CEA but without the expression of cytokeratin nos 7,8,14,18,19 and OV-6. Ultrastructurally, most tumor cells contained populations of electron-dense core granules ranging between 100 and 200 nm in diameter. After hepatectomy, serum CEA, NSE, and 5HIAA reverted to normal ranges and persisted for 19 months. These findings suggested that the diagnosis of primary hepatic carcinoid was tenable and that the tumor might derive from hepatic stem cells which acquired the additional nature of producing CEA without cytokeratins characteristic of hepatocytes or bile duct cells. Some molecular based approaches have attributed unique biological behavior and histogenesis to this carcinoid tumor.