Histopathological phenotypes of early gastric cancer and its background mucosa

Recent advances in endoscopic submucosal dissection (ESD) techniques contribute to endoscopic treatment of early gastric cancer (EGC). Recognition of chronic atrophic gastritis as the background is important for high-quality detection and diagnosis of EGC. But, relationships between EGC and atrophy of the background gastric mucosa caused by Helicobacter pylori are not well understood. The present study demonstrated histopathological phenotypes of EGC, as well as chronic atrophic gastritis as background mucosa of EGC. We evaluated mucosal heights, number of glands, and degree of intestinal metaplasia (IM) of the background gastric mucosa, using 81 cases of EGC resected by ESD. Gastric phenotype cancer cases showed IM of the background gastric mucosa less frequently, compared with intestinal phenotype cancer cases (score of IM, 1.15 vs. 1.65, P = 0.012). The average mucosal heights around EGC were lower in moderately to poorly differentiated adenocarcinoma cases than well differentiated adenocarcinoma cases (442.6 μm vs. 500.2 μm, P = 0.011). The mucosal atrophy indicated by average heights of background mucosa was low in the gastric phenotype cancer cases, compared with the intestinal phenotype cancercases (452.8 μm vs. 505.6 μm, P = 0.018). In the fundic gland area, the mucosal heights were low in the gastric phenotype cancer cases, compared with the intestinal phenotype cancer cases (413.2 μm vs. 495.5 μm, P = 0.015). Our results using EGC specimens indicated that gastric phenotype cancer and moderately to poorly differentiated adenocarcinoma had atrophic background mucosa with lower mucosal heights and less IM. The atrophic gastric mucosa with less IM is thought to play an important role in gastric carcinogenesis, especially tumoriogenesis of gastricphenotype cancer.     

Reliability and validity of a Japanese version of the Cambridge depersonalization scale as a screening instrument for depersonalization disorder

Aims:  The Cambridge Depersonalization Scale (CDS) is an instrument that has obtained reliability and validity in some countries for use in detecting depersonalization disorder under clinical conditions, but not yet in Japan under non-psychiatric conditions. The purposes of this study were to develop a Japanese version of the CDS (J-CDS) and to examine its reliability and validity as an instrument for screening depersonalization disorder under non-clinical conditions.
Methods:  The CDS was translated from English into Japanese and then back-translated into English by a native English-speaking American. After making the J-CDS, we examined its reliability and validity. Questionnaires that were composed of J-CDS, the Dissociative Experience Scale (DES), the Zung self-rating scale and the Maudsley Obsessional–Compulsive Inventory were administrated to 59 participants (12 patients with depersonalization disorder, 11 individuals who had recovered from depersonalization and 36 healthy controls).
Results:  Cronbach's alpha and split-half reliability were 0.94 and 0.93, respectively. The J-CDS score in the depersonalization group was significantly higher than in the healthy control group. The J-CDS score was significantly correlated with scores of total DES, and DES-depersonalization. The best compromise between the true positive and false negative rate was at a cut-off point of 60, yielding a sensitivity of 1.00 and a specificity of 0.96.
Conclusions:  In this study, J-CDS showed good reliability and validity. The best cut-off point, when we use this for distinguishing individuals with depersonalization disorder from individuals without psychiatric disorders, is 60 points.     

A possible method using baseline hormonal levels to prescribe the appropriate oral therapeutic radioiodine dosage for Graves' disease

Objective The purpose of this study was to retrospectively examine the correlations of hormonal ratios with radioiodine I-131 therapeutic parameters and the potentiality of prescribing the therapeutic I-131 target dosage for an individual patient with Graves' disease using baseline serum levels of thyroid hormones. Materials and methods Serum T3, T4, and FT4 levels 6 and 12 months after I-131 therapy/baseline levels (hormonal ratios) were calculated for a total of 68 therapeutic courses in 57 patients with Graves' disease. The therapeutic parameters were absorbed dose (Gy), dose concentration (μCi/g) and oral dose (mCi). Linear regression analysis was performed for correlating hormonal ratios (X) and therapeutic parameters (Y). Results Significant (P < 0.05) negative correlations of the hormonal ratios were observed with absorbed dose (R −0.50 for T3, −0.61 for T4, and −0.46 for FT4 at 6 months, and −0.29 for T3, −0.44 for T4 at 12 months) and dose concentration (R −0.57 for T3, −0.58 for T4, and −0.49 for FT4 at 6 months and −0.27 for T3, −0.27 for T4 at 12 months), but not with oral dose at 6 months and 12 months or the absorbed dose and dose concentration for FT4 at 12 months. The correlations were higher at 6 months than at 12 months and in serum T4 than in serum T3 and FT4. The formulae for serum T4 at 6 months were as follows: Y (Gy) = 109 − 53X and Y (μCi/g) = 109 − 52X. Conclusions These results suggest that the hormonal ratios are significantly correlated with the absorbed dose and dose concentration. The formulae for serum T4 at 6 months may serve to prescribe the individual oral dosage for Graves' disease, although the correlation coefficients are about −0.6.     

A case of pathological complete response after treatment with uracil/tegafur (UFT) and folinate (Leucovorin) for liver metastasis of colon cancer

The patient is a 62-year-old female who underwent a right hemicolectomy for type-2 ascending colon cancer (moderately-differentiated adenocarcinoma, ss, n0, H0, P0, M0, stage II). Six months after the surgery, a solitary metastatic focus was expressed in the liver S3. Because schizophrenia was present concurrently, tegafur and uracil/folinate (UFT/Leucovorin) treatment was selected and performed for 3 months. Because the tumor shrank afterward, a partial hepatectomy was performed to obtain a curative resection. In a pathological examination of the resected focus, cicatricial/necrotic findings were observed, but no cancer cells were observed; hence, it was determined to be a pathological complete response (CR). In regard to chemotherapy for distant metastasis of colorectal cancer, many molecular-targeted agents are being introduced, thus resulting in more treatment options; however, depending on the patient's background, UFT/LV treatment can be an effective treatment option.     

Expression levels of drug-metabolizing enzyme, transporter, and nuclear receptor mRNAs in a novel three-dimensional culture system for human hepatocytes using micro-space plates

We evaluated a novel three-dimensional primary culture system using micro-space plates to determine the expression levels of 61 target (drug-metabolizing enzymes, transporters, and nuclear receptors) mRNAs in human hepatocytes. We measured mRNA expression levels of many target genes in four lots of cryopreserved human hepatocyte primary cells after 120 h of culture and compared differences in mRNA expression levels between cultures using traditional plates and those using micro-space plates. In this study, we show that the mRNA levels of many experimental targets in human hepatocytes before inoculation resemble the levels inside the human liver. Furthermore, we show that the rate of change of expression levels of many target mRNAs relative to the value before inoculation of the hepatocytes into micro-space plates was relatively smaller than the rate of change in hepatocytes inoculated into traditional plates. Pharmacokinetics-related examinations using this system are possible within a time frame of 120 h. We report that this novel three-dimensional culture system reproduces mRNA expression levels that are nearer to those in the liver in vivo and is an excellent platform for maintaining mRNA expression levels of drug-metabolizing enzymes and transporters when compared to common monolayer cultures.     

Clinicopathological analysis for recurrence of stage Ib gastric cancer (according to the second English edition of the Japanese classification of gastric carcinoma)

Background  

The prognosis for patients with stage Ib (second English edition of the Japanese classification of gastric carcinoma) gastric cancer is promising, with an expected 5-year survival of 90%. Despite this relatively high survival rate, the outcome for patients who experience recurrence is poor. To date, however, prognostic and recurrence factors for stage Ib gastric cancer are poorly understood, and appropriate adjuvant chemotherapy protocols have not been developed.     

Comprehensive analyses and characterization of haemophagocytic lymphohistiocytosis in Vietnamese children

Haemophagocytic lymphohistiocytosis (HLH) is a fatal haematological disorder with diverse aetiology. This prospective study was undertaken to characterize HLH cases in Vietnamese children. Clinical and laboratory data, genetic analyses and outcome of the HLH patients were analysed. A total of 33 patients were enrolled from March 2007 to December 2008, with a median age of 3 years. Mutations of the SH2D1A ( SAP ) and PRF1 genes were detected in one patient, respectively. The virus association was high, up to 63·6% (21/33), including Epstein–Barr virus (19/33), cytomegalovirus (2/33) and dengue virus (2/33). Five patients had malignant lymphoma and two had autoimmune diseases. Twenty-eight patients were treated according to the HLH-2004 protocol. The first response rate was 64·3% (18/28), with an early death rate of 35·7% (10/28). High levels of interferon-γ, interleukin-10, MIG and interferon-inducible protein-10 (IP-10) were associated with early mortality ( P  <   0·05). Reactivation among the responders was high (9/18) and the uneventful resolution was low (3/18) after a median follow-up of 35 weeks. In conclusion, the majority of HLH cases are associated with virus infections in Vietnamese children. Familial HLH is rare. The frequent reactivation and high mortality demands a more appropriate therapeutic regimen in tropical areas like Vietnam.     

Paradoxical increases in serum levels of highly chlorinated PCBs in aged women in clear contrast to robust decreases in dietary intakes from 1980 to 2003 in Japan

Objective  Exposure to polychlorinated biphenyls (PCBs) is considered to have culminated between 1950 and 1970 in Japan, and exposure through diet, the major exposure route, has decreased significantly over the last 10 years. The primary goal of the present study was to investigate the long-term trends and congener profiles of serum and dietary levels of PCBs using historical samples. Methods  Using banked samples collected in 1980, 1995, and 2003 surveys, we determined the daily intakes and serum concentrations of 13 PCB congeners (#74, #99, #118, #138, #146, #153, #156, #163, #164, #170, #180, #182, and #187) in women. Results  The total daily PCB intake [ng/day, geometric mean (geometric standard deviation)] decreased significantly from 523 (2.5) in 1980 to 63 (3.2) in 2003. The serum total PCB level (ng/g lipid) in women <40 years of age decreased significantly from 185 (1.8) in 1980 to 68 (1.8) in 2003. In contrast, the level in women >50 years of age increased significantly from 125 (1.7) in 1980 to 242 (1.7) in 2003. Specifically, the serum concentrations of hexa (#138, #146, #153, #156, #163, and #164) and hepta (#170, #180, #182, and #187) congeners increased significantly. A comparison of the serum PCB levels of women born from 1940 to 1953 revealed that their serum total PCB level was significantly higher in the 2003 survey [242 (1.7), n = 9] than in the 1995 [128 (2.0), n = 17] surveys. This increase in the total PCB level was attributable to increases in the hepta congener groups. Conclusion  Present results suggest a decreased rate of elimination of hepta congeners with aging in females, rather than a birth-generation phenomenon.