A comparative clinical study of gallbladder tubular adenocarcinoma according to the grade of differentiation

Background We sought to elucidate differences in the clinical characteristics of gallbladder carcinoma according to the histological degree of glandular formation.Methods The subjects consisted of 66 autopsy cases out of 331 patients admitted for gallbladder carcinoma between 1975 and 2000. After identifying 49 tubular adenocarcinoma cases, we arbitrarily divided them into two categories: a well-differentiated type (group W; n = 41; well or moderately differentiated tubular adenocarcinoma), and a poorly differentiated type (group P, n = 8). The clinical features of the groups were compared.Results No significant differences were found with regard to sex, age, or serum carcinoembryonic antigen (CEA) levels between the two groups. Moreover, no intergroup difference was found in either the time interval from the initial symptoms to admission, or the grade of tumor progression on admission. Although the frequency of liver metastases on admission was similar in both groups, the frequency at autopsy was significantly higher in group W than in group P (73% vs 25%; P < 0.05). When survival was determined based on the duration after primary treatment, the longest and median periods were 48.7 months and 3.7 months, respectively, in group W, whereas none of the subjects in group P survived for over 2 months. This difference was statistically significant (P < 0.001).Conclusions Hematogenous metastasis was more prominent in group W. Poorly differentiated tubular adenocarcinoma can be closely associated with a poor prognosis.     

Usefulness of biopsying the major duodenal papilla to diagnose autoimmune pancreatitis: A prospective study using TgG4-immunostaining

AIM: To examine the histological and immunohistochemical findings of biopsy specimens taken from the major duodenal papilla of autoirnrnune pancreatitis (AIP)patients.METHODS: The major duodenal papilla in the resected pancreas of 3 patients with AIP and of 5 control patients [pancreatic carcinoma (n = 3) and chronic alcoholic pancreatitis (n = 2)] was irnrnunostained using anti-CD4-T cell, CD8-T cell and IgG4 antibodies. Forceps biopsy specimens taken from the major duodenal papilla of 2patients with AIP and 5 control patients with suspected papillitis were prospectively taken during duodenoscopy and immunohistochernically examined.RESULTS: Moderate or severe lyrnphoplasrnacytic infiltration including many CD4-positive or CD8-positive T lymphocytes and IgG4-positive plasma cells (≥10/HPF),was observed in the major duodenal papilla of all 3 patients with AIP. The same findings were also detected in the biopsy specimens taken from the major duodenal papilla of 2 patients with AIP, but in controls, there were only a few (≤3/HPF) IgG4-positive plasma cells infiltrating the major duodenal papilla.CONCLUSIONS: An abundant infiltration of IgG4-positive plasma cells is specifically detected in the major duodenal papilla of patients with AIP. Although this is a preliminary study, IgG4-irnmunostaining of biopsy specimens taken from the major duodenal papilla may support the diagnosis of AIP.     

Dietary Patterns and Serum Gamma-Glutamyl Transferase in Japanese Men and Women

Background

Although specific foods and nutrients have been examined as potential determinants of serum gamma-glutamyl transferase (GGT) concentrations, the relationship between dietary patterns and GGT remains unknown. The present cross-sectional study aimed to determine relationships between dietary patterns and GGT concentrations, and the effects of lifestyle factors on GGT.

Methods

Relationships between dietary patterns and GGT were analyzed in 9803 Japanese individuals (3723 men and 6080 women age 40–69 years) without a history of liver diseases or elevated serum aminotransferase. We examined major dietary patterns by factor analysis of 46 items determined from a validated, short food frequency questionnaire.

Results

We defined dietary patterns as healthy, Western, seafood, bread, and dessert. The healthy pattern was inversely related to GGT in men (odds ratio [OR] for highest vs lowest quartile, 0.72; 95% confidence interval [CI], 0.57–0.92; P < 0.01 for trend) and women (OR 0.82; 95% CI, 0.66–1.0; P = 0.05 for trend), whereas the seafood pattern was positively related to GGT in men (OR 1.27; 95% CI, 1.01–1.61; P = 0.03 for trend) and women (OR 1.21; 95% CI, 0.98–1.49; P = 0.05 for trend). Male-specific inverse associations with GGT were found for bread and dessert patterns (OR 0.63; 95% CI, 0.50–0.80 and OR 0.53; 95% CI, 0.41–0.68, respectively; P < 0.01 for both trends). Seafood or bread patterns and alcohol consumption significantly interacted with GGT in men (P = 0.03 and <0.01 for interaction, respectively) and between the dessert pattern and body mass index or smoking habit in women (P = 0.03 and <0.01, respectively, for interaction).

Conclusions

Dietary patterns may be important determinants of GGT, and their possible clinical implications warrant further investigation.Key words: dietary pattern, gamma-glutamyl transferase, factor analysis     

Final results from a multicenter prospective study (?JROSG 05–5) on postoperative radiotherapy for patients with ductal carcinoma in situ with an involved surgical margin or close margin widths of 1 mm or less

This multicenter prospective study ( Japanese Radiation Oncology Study Group: JROSG 05-5) aimed to evaluate the effectiveness of postoperative radiotherapy (PORT) in patients with ductal carcinoma in situ (DCIS) with an involved surgical margin or close margin widths of ≤1 mm or less. PORT consisted of whole-breast irradiation (50 Gy in 25 fractions) followed by boost irradiation (10 Gy in 5 fractions). Eligibility criteria were as follows: (i) DCIS without an invasive carcinoma component, (ii) age between 20 and 80 years old, (iii) involved margin or close margin widths of ≤1 mm, (iv) refusal of re-resection, (v) performance status of 0–2, and (vi) written informed consent. The primary endpoint was ipsilateral breast tumor recurrence (IBTR), and secondary endpoints were overall survival (OS), relapse-free survival (RFS), recurrence patterns, and adverse events. A total of 37 patients from 12 institutions were enrolled from January 2007 to May 2009. The median follow-up time was 62 months (range, 28–85 months). The median pathological tumor size was 2.5 cm (range, 0.3–8.5 cm). Of the 37 patients, 21 had involved margins, and 16 had close margins. The 5-year IBTR, OS and RFS rates were 6% (95% confidence interval [CI]: 2–21), 97% (95% CI: 83–99) and 91% (95% CI: 77–97), respectively. Two patients developed local recurrence at the original site after 39 and 58 months. No severe adverse events were found. Our study suggests that this PORT regimen could be a treatment option for patients with DCIS with involved margin or close margin who don''t desire re-resection.     

Delayed addition of tumor necrosis factor (TNF) antagonists inhibits the generation of CD11c+ dendritic cells derived from CD34+ cells exposed to TNF-α

We have developed a method that cells exhibiting typical dendritic cell (DC) characteristics are generated from human CD34⁺ cells and phagocytose cogenerating erythroid progenitor cells in the presence of tumor necrosis factor-α (TNF-α), interleukin-3, stem cell factor and erythropoietin. Using this system, we titrated the effects of TNF antagonists, etanercept and infliximab, on TNF-α activity. We found that 1 μg/ml etanercept dramatically inhibited the generation of CD11c⁺ cells accompanying with a complete recovery of the generation of erythroid progenitors. Infliximab at 200 μg/ml exhibited a similar effect to that observed for etanercept. The delayed addition of etanercept to this culture system at day five resulted in significant inhibitory effects on the generation of CD11c⁺, CD4⁺ and CD86⁺ cells. These results indicate that TNF antagonists administered at a concentration that is achievable in vivo, neutralize the biologic effects of TNF-α in generating CD11c⁺ cells and that a delay in the administration of these antagonists for as long as 5 days partially inhibits the biologic activity of TNF-α. These findings may contribute to a great understanding of anti-TNF therapy in patients with an overproduction of cytokines such as hemophagocytic syndromes.     

Reduction of liver stiffness by interferon treatment in the patients with chronic hepatitis C

Aim: To assess the regression of liver fibrosis after interferon (IFN) treatment in patients with chronic hepatitis C, liver stiffness (LS) was measured repeatedly and the factors associated with reduction of LS were assessed. Methods: LS was measured by transient elastography before treatment, at end of treatment (EOT), and 1 year and 2 years after EOT in 145 patients with chronic hepatitis C treated by IFN with or without ribavirin. Results: In the patients with sustained virological response (SVR) (n = 93) and relapsers (n = 28), LS significantly decreased at EOT (median, 5.4 [interquartile range, 4.0–8.6] kilopascals [kPa], P < 0.0001 and 6.8 [4.5–8.9] kPa, P = 0.0023) and 1 year after EOT (5.3 [4.2–7.0] kPa, P < 0.0001 and 6.8 [4.5–9.3] kPa, P = 0.0204) compared with baseline (8.0 [5.0–11.9] kPa and 10.6 [7.0–16.6] kPa). In SVR patients, LS significantly decreased 2 years after EOT (5.3 [4.1–6.3] kPa) compared with baseline (P < 0.0001) and LS at EOT (P = 0.0034). Two points or greater reduction of deduced stage at last LS measurement was observed in 78% of SVR patients, 59% of relapsers and 15% of patients with non‐virological response whose pretreatment deduced stages were F3–F4. Fibrosis stage, hyaluronic acid levels, duration of treatment, response to treatment and alanine aminotransferase levels were associated with a 2‐point or greater decrease of deduced fibrosis stage. Conclusion: IFN treatment reduced LS in SVR patients and relapsers. Significant reduction of LS is associated with milder fibrosis stage, lower hyaluronic acid levels, longer IFN treatment, virological response of SVR or relapse and higher alanine aminotransferase levels.     

Signaling pathway involved in cyclooxygenase-2 up-regulation by hepatocyte growth factor in endometrial cancer cells

Hepatocyte growth factor (HGF) is up-regulated in tissue repair and has been implicated in playing a role in this process through its anti-apoptotic and proliferative activities. Cyclooxygenase-2 (COX-2) is an inducible enzyme in the biosynthetic pathway of prostaglandins, and its activation has been shown to play an important role in cell growth. We previously reported that HGF significantly inhibited anoikis, possibly through the up-regulation of COX-2 expression in the endometrial RL95-2 cancer cell line. Here, we report that i) treatment of RL95-2 cells with HGF resulted in phosphorylation of the HGF receptor c-Met, activation of Akt and IκB, translocation of NF-κB into the nucleus, and up-regulation of COX-2 mRNA; ii) the IκB-α phosphorylation inhibitor BAY11-7082 and the selective COX-2 inhibitor CAY10452 blocked HGF-mediated anoikis resistance in RL95-2 cells; and iii) HGF induced migration and invasion in RL95-2 cells, while the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 and CAY10452 blocked these effects of HGF stimulation. Our data suggest that HGF possesses chemotactic ability, has anti-apoptosis action, and induces cellular infiltration via the PI3K/Akt pathway; it also triggers NF-κB activation and up-regulates COX-2 gene expression in endometrial cancer cells.