Morphologic and functional changes in nontumorous liver tissue after radiofrequency ablation in an in vivo model: comparison of 18F-FDG PET/CT, MRI, ultrasound, and CT.

Rimlike contrast enhancement on morphologic imaging and increased tracer uptake on (18)F-FDG PET in the periphery of the necrosis can hamper differentiation of residual tumor from regenerative tissue after radiofrequency ablation of liver lesions. This study used MRI, CT, ultrasound, and (18)F-FDG PET/CT to assess the typical appearance of lesions in nontumorous animal liver tissue after radiofrequency ablation. METHODS: Lesions were created by radiofrequency ablation of normal liver parenchyma in 21 minipigs. Follow-up was performed by 3 contrast-enhanced morphologic modalities-MRI, CT, and ultrasound-and by (18)F-FDG PET/CT immediately, 3 and 10 d, and 1, 2, 3, and 6 mo after radiofrequency ablation. Images were evaluated qualitatively for areas of increased enhancement and regions of elevated tracer uptake. Furthermore, all images were assessed quantitatively by determination of ratios comparing enhancement/tracer uptake in the periphery of the necrosis with enhancement/tracer uptake in normal liver parenchyma. Imaging findings were compared with histopathology findings. RESULTS: Immediately after radiofrequency ablation, no increase in (18)F-FDG uptake was visible, whereas elevated enhancement was noticed in the periphery of the necrosis on all morphologic imaging procedures. At further follow-up, an area of rimlike increase in (18)F-FDG uptake surrounding the necrosis was detected on PET/CT. The rimlike pattern of increased enhancement in the arterial phase was present for all liver lesions on CT, MRI, and ultrasound, especially between day 3 and month 1 after the radiofrequency ablation. Both elevated glucose metabolism and enhancement persisted for 6 mo postinterventionally. Histologic examination showed a hemorrhagic border converting into a regeneration capsule. CONCLUSION: If performed immediately after radiofrequency ablation, (18)F-FDG PET/CT probably has benefits over those of morphologic imaging procedures when assessing liver tissue for residual tumor. Later follow-up may be hampered by visualization of peripheral hyperperfusion and tissue regeneration. Further studies on a patient population are essential.     

Eradication of Helicobacter pylori heals atrophic corpus gastritis caused by long-term treatment with omeprazole

 Long-term treatment with proton pump inhibitors in patients with Helicobacter pylori gastritis can lead to atrophic changes in the corpus mucosa. What is still unclear, however, is whether this atrophy can regress in response to Helicobacter pylori eradication. We report on a male patient with Helicobacter pylori gastritis receiving long-term treatment (4 years) with omeprazole for gastro-oesophageal reflux disease, who developed autoaggressive gastritis with progressive atrophy, hypochlorhydria, hypergastrinaemia and nodular ECL-cell hyperplasia. To determine whether these changes might be induced to regress, Helicobacter pylori eradication therapy was administered. Ten months after Helicobacter pylori eradication autoaggressive lymphocytic infiltrates were no longer detectable, and the glands in the corpus mucosa had normalised despite continued treatment with omeprazole – a finding that was confirmed at two further follow-up surveys performed at 6-month intervals. This case report shows that atrophy of the corpus mucosa developing under long-term treatment with a proton pump inhibitor can be cured by eradicating Helicobacter pylori. Received: 21 April 1998 / Accepted: 10 August 1998     

Topographic association between active gastritis and Campylobacter pylori colonisation.

One thousand biopsy specimens obtained from 10 sites in the stomachs of 50 patients were examined for the presence of active chronic gastritis and Campylobacter pylori. All 32 patients with active chronic gastritis at 234 out of 320 sites were positive for C pylori: 227 showed colonisation with C pylori by the Warthin-Starry stain; and 222 were positive by culture. C pylori was not found in 18 patients with inactive chronic gastritis or histologically normal mucosa. The area of C pylori colonisation was larger than the area of active chronic gastritis in 289 positive specimens on culture and 261 on staining, respectively, suggesting that C pylori colonisation may precede the development of active chronic gastritis. It is concluded that patchy distribution of active chronic gastritis and C pylori colonisation must be considered, particularly in serology or breath test studies where the histological examination serves as a reference. Furthermore, it may have important implications for the follow up of patients after antibacterial treatment. The topographic and specific association of C pylori and active chronic gastritis provides further evidence for the pathogenic role of C pylori in active chronic gastritis.     

Inhibition of interleukin-6 synthesis in an animal model of septic shock by anti-C5a monoclonal antibodies

The complement activation fragment C5a was recently shown to induce interleukin (IL)-6 synthesis by peripheral blood mononuclear cells. To understand better the role of C5a in cytokine regulation in vivo, we investigated the effects of complement depletion by cobra venom factor (CVF) or of anti-C5a monoclonal antibodies (mAb) on IL-6 generation in an animal model of septic shock. Complement-depleted pigs which were subsequently challenged with Escherichia coli generated significantly (p < 0.05) less IL-6 during the 6-h observation period than complement-sufficient controls. To address specifically the role of C5a in IL-6 regulation, we produced a C5a(57–74) peptide-specific mAb (T13/9) which neutralizes the bioactivity of porcine C5a. The mAb T13/9 does not crossreact with the precursor protein C5. The pretreatment of pigs with anti-C5a mAb T13/9 prior to the induction of sepsis resulted in a decrease of over 75 % in serum IL-6 bioactivity compared to control animals (p < 0.0001). These results indicate a role for C5a in the modulation of IL-6 synthesis in Gram-negative bacteremia.     

Applications of a rat multiple tissue gene expression data set

With the sequencing and assembly of the rat genome comes the difficult task of assigning functions to genes. Tissue localization of gene expression gives some information about the potential role of a gene in physiology. Various examples of the utility of multiple tissue gene expression data sets are illustrated here. First, we highlight their use in finding genes that might play an important role in a particular tissue on the basis of exclusive expression in that tissue or coexpression with a gene or genes with known function. Second, we show how this data might be used to explain known phenotypic differences between strains. Third, we show how expression patterns of genes in a genomic interval might identify candidate genes in quantitative trait loci (QTL) mapping studies. Lastly, we show how multiple tissue and species data can help researchers prioritize follow up studies to microarray experiments. All of these applications of multiple tissue gene expression data sets will play a role in functionally annotating the rat genome.     

Helicobacter pylori gastritis and primary gastric non-Hodgkin's lymphomas.

AIMS--To evaluate further the relation between gastric malignant lymphoma of the mucosa associated lymphoid tissue (MALT) and Helicobacter pylori. METHODS--One hundred and sixty two surgical specimens of MALT lymphoma were retrospectively investigated to determine tumour type and inflammatory patterns. In 121 cases biopsy specimens obtained before surgery were available and stained with haematoxylin and eosin, periodic acid Schiff, Giemsa and Warthin-Starry stains. RESULTS--Residual lymphoid follicles were found less often in high grade malignant than in low grade malignant MALT lymphomas. Chronic active gastritis was shown within the mucosa at some distance from the tumours in 143 of 146 specimens. In all the cases for which biopsy specimens could be evaluated, colonisation of the mucosa by H pylori had occurred. Lymphoid follicles and lymphoid aggregates were detected in 82.7% of the antral, and in 85% of the body mucosa specimens. CONCLUSIONS--These data support the hypothesis that H pylori has an important role in the development of MALT lymphomas. Furthermore, the chronic inflammation preceding malignant transformation might enhance the probability of malignant transformation via chronic stimulation of the lymphoid tissue. This might in part indicate why MALT lymphomas occur most often in the stomach.     

Reliable detection of macrolide-resistant Helicobacter pylori via fluorescence in situ hybridization in formalin-fixed tissue.

Macrolide-resistant Helicobacter (H.) pylori represent an increasing therapeutic problem. Macrolide resistance is usually determined phenotypically in vitro with methods such as E-test or agar dilution test. A prerequisite for those tests, however, is bacterial culture that is not routinely set up in the course of gastroscopy. In contrast, formalin-fixed, paraffin-embedded biopsies are regularly available from patients who have undergone gastroscopy. In such biopsies macrolide-resistant H. pylori can be detected by the genotype-based technique of fluorescence in situ hybridization (FISH). Experience gained by this new method, however, is still extremely limited, especially in formalin-fixed tissue. Therefore, we retrospectively investigated formalin-fixed, paraffin-embedded biopsy specimens by FISH in 104 patients suffering from therapy-resistant H. pylori gastritis. To test the accuracy of FISH, we initially examined specimens from 53 patients for whom results of the E-test were available. Next we analyzed biopsies from another 51 patients that had been selected since phenotypical resistance testing had failed despite documented culturing attempts. In all 104 patients, H. pylori was detected by FISH and could thus be investigated for macrolide resistance. Overall, macrolide-resistant bacteria were found in 71 patients (68.3%). In 49 of 53 patients (92.4%), FISH and E-test returned identical results (no significant discordance according to McNemar's chi(2)-test). Taken together, our study demonstrates that FISH is a highly sensitive and reliable method for detecting macrolide-resistant H. pylori in formalin-fixed, paraffin-embedded biopsy specimens, which represents the routine method of processing tissue obtained upon gastroscopy.     

Histopathological diagnosis of Barrett's mucosa and associated neoplasias. Results of a consensus conference of the Working Group for "Gastroenterological Pathology of the German Society for Pathology" on 22 September 2001

There are a number of difficulties regarding the diagnosis of Barrett's mucosa and the varying grades of neoplasia that may be associated with it. It was therefore the aim of a consensus conference of the "Working Group for Gastroenterological Pathology within the German Society of Pathology" to achieve standardization regarding the following issues: definition and diagnostic criteria for Barrett's mucosa and its discrimination from intestinal metaplasia of the cardia, diagnostic criteria for intraepithelial neoplasia, number of biopsies necessary to establish the diagnosis, significance of additional immunohistochemical and/or molecular biological methods as well as importance of a second opinion in the diagnosis of intraepithelial neoplasia.