The intraductal carcinoma component is a significant prognostic parameter in patients with invasive ductal carcinoma of the pancreas.

We have sometimes encountered invasive ductal carcinomas (IDCs) of the pancreas containing intraductal carcinoma components in the intra- and / or extra-tumor area. The purpose of this study was to investigate whether intraductal carcinoma components would be useful for predicting the outcome of IDC patients. Forty-seven surgically treated IDCs were examined, and all histological tumor sections were stained with Elastica to accurately confirm intraductal carcinoma components. Well-known clinicopathological parameters that exhibited a significant correlation in the univariate analyses for predicting disease-free survival (DFS) and overall survival (OS) were entered into the Cox proportional hazard multivariate analysis. Since the lowest P-value predicting DFS or OS periods was observed in IDCs with more than 10% intraductal carcinoma components and those with 10% or less intraductal carcinoma components (P = 0.028 and P = 0.019), we established the cutoff value of intraductal carcinoma components at 10%. In the multivariate analyses for DFS and OS, the presence of more than 10% intraductal carcinoma components showed a marginally significant increase in the hazard rate (HR) of tumor recurrence (P = 0.067) and significantly increased the HR of mortality (P = 0.040). The present study demonstrated that IDCs with more than 10% intraductal carcinoma components were associated with a significantly better patient outcome than those with 10% or less intraductal carcinoma components.     

The CADO-E I type endometrial applicator for RALS therapy

A dual stainless steel applicator (CADO-E I type) was developed for intracavitary radiotherapy of endometrial carcinoma using remotely controlled afterloader (RALS). An inverted pear-shaped isodose curve was obtained by means of this metallic applicator and Co-60 source with a stepwise movement. Reference point X was defined as 2 cm below the fundus and 2 cm lateral to the center line of the uterus to specify the dose absorbed to the uterine corpus with our endometrial applicator. Since cancer residua resulting from cold spots in dose distribution were recognized at the uterine fundus by histopathological investigation of serial sections in the hysterectomy specimens, we intend to develop an applicator with three metallic tubes (CADO-E II type).     

Functional plasticity of surround inhibition in the motor cortex during single finger contraction training

We investigated the functional changes in short intracortical inhibitory (SICI) circuits to determine whether surround inhibition is altered during a simple finger movement training. Using an electromyographic (EMG) feedback system linked to a computer monitor, participants practiced sustained index finger abduction by 40% maximum voluntary contraction of the first dorsal interosseous (FDI) while decreasing overflow EMG activity of the abductor digiti minimi (ADM) to less than 5% maximum voluntary contraction. Single transcranial magnetic stimuli (TMS) and paired-pulse TMS were applied to the left primary motor cortex to elicit motor-evoked potentials (MEPs) in the right FDI and ADM before/after training. In addition to recording MEPs from both muscles during voluntary FDI contraction, MEPs were recorded during motor imagery. MEPs from the FDI were not altered by training, indicating no functional changes in SICI circuits associated with the FDI field. In contrast, SICI circuits associated with ADM were significantly strengthened by training, as indicated by reduced baseline EMG activity during both actual FDI contraction and motor imagery and by reduced MEPs in response to post-training TMS. We propose that SICI circuits show functional plasticity during motor training and that surround circuit inhibition of nontarget muscle groups increases in proportion to the acquisition of motor skills.     

Carcinoid tumor of the gallbladder associated with adenocarcinoma

A case of carcinoid tumor of the gallbladder associated with adenocarcinoma in a 56-year-old man is reported and a review of the literature is made. The tumor was a polypoid mass with a size of 5.5 X 4.0 X 2.8 cm. Histologically, the tumor showed carcinoid and adenocarcinoma with areas of mucous change. Tumor cells containing argyrophil granules were observed in both carcinoidal and adenocarcinomatous areas, but no argentaffin granules were detected in either of the neoplastic areas. Some of the tumor cells had both argyrophil granules and mucin in the same cytoplasm. The electron microscopic study revealed several tumor cells containing neurosecretory granules; however, no clinical signs of hormonal activities of the tumor were observed. The patient died of generalized bone metastases 16 months after surgery. This appears to be the second case of composite tumor of the gallbladder.     

Cyclin D1 amplification correlates with early recurrence of squamous cell carcinoma of the tongue

Amplification of CCND1 was studied in 23 tongue carcinoma patients by fluorescence in situ hybridization (FISH) using a paraffin embedded specimen. All the patients received complete resection of the primary site with or without neck dissection. CCND1 amplification was positive in 13 (56.5%) out of 23 cases. Correlations between CCND1 amplification and histological grading, T category, N category, and Stages were not significant. The 5-year disease-free survival rate, which was 23.1% for CCND1 amplification positive patients and 80.0% for negative patients, was significantly better for the CCND1 amplification negative patients (P=0.0070). Nine patients were examined by dual-color FISH with the probe for centromere of chromosome 11 and 11q13. In five patients, who had positive amplification for CCND1, cell numbers with a larger number of signals for 11q13 than the centromere of chromosome 11 were significantly higher than those of CCND1 amplification negative patients (P=0.013). This indicates that amplification of 11q13 occurs more frequently than aberration of chromosome 11 in CCND1 amplification positive patients. From these results, the amplification of CCND1 is a key factor in predicting the aggressiveness of tongue cancer. Furthermore, FISH proved to be a useful method for such evaluation.     

Risk factors for Helicobacter pylori infection among a rural population in Japan: relation to living environment and medical history

BACKGROUND: Helicobacter pylori infection is related to several gastroduodenal diseases, though the route of transmission remains unclear. METHODS: A cross-sectional study that included 695 healthy people (males 308, females 387; median age 60 years) participating in a health checkup program in Yamagata Prefecture was conducted. H. pylori status was determined in all subjects by evaluation of serum anti-H. pylori immunoglobulin G antibody. Antibody against hepatitis A virus was used as a marker of fecal-oral exposure to assess the agreement between H. pylori infection and hepatitis A virus infection. Data on other factors known or suspected to be related to infection status were also collected using a questionnaire. RESULTS: Seroprevalence of H. pylori and hepatitis A virus was 60% and 70%, respectively. Kappa values for subjects aged 20-49 and aged 50 or older were 0.07 and 0.02, respectively, and agreement between the presences of both infections was assessed as slight. In the multivariate logistic regression analysis, H. pylori infection was significantly associated with availability of a sewage system in childhood (presence [reference], absence [odds ratio (OR) = 4.06, 95% confidence interval (CI): 1.36-13.94]) and the number of gastrointestinal endoscopies undergone (none [reference], once [OR = 1.64, 95% CI: 0.83-3.27], 2-3 times [OR = 3.11, 95% CI: 1.65-5.99], or 4 or more times [OR = 3.18, 95% CI: 1.71-6.03]), (p < 0.01 for trend). CONCLUSIONS: Our results suggest that poor hygiene in childhood is related to H. pylori infection. The fecal-oral route does not seem to be an important mode of transmission, but the possibility of transmission by gastrointestinal endoscopic examination exists.     

Hepatitis C virus down-regulates insulin receptor substrates 1 and 2 through up-regulation of suppressor of cytokine signaling 3

The pathogenesis of hepatitis C virus (HCV)-associated insulin resistance remains unclear. Therefore, we investigated mechanisms for HCV-associated insulin resistance. Homeostasis model assessment for insulin resistance was increased in patients with HCV infection. An increase in fasting insulin levels was associated with the presence of serum HCV core, the severity of hepatic fibrosis and a decrease in expression of insulin receptor substrate (IRS) 1 and IRS2, central molecules of the insulin-signaling cascade, in patients with HCV infection. Down-regulation of IRS1 and IRS2 was also seen in HCV core-transgenic mice livers and HCV core-transfected human hepatoma cells. Carbobenzoxy-l-leucyl-l-leucyl-l-leucinal, a potent proteosomal proteolysis inhibitor, blocked down-regulation of IRS1 and IRS2 in HCV core-transfected hepatoma cells. In human hepatoma cells, HCV core up-regulated suppressor of cytokine signaling (SOCS) 3 and caused ubiquitination of IRS1 and IRS2. HCV core-induced down-regulation of IRS1 and IRS2 was not seen in SOCS3(-/-) mouse embryonic fibroblast cells. Furthermore, HCV core suppressed insulin-induced phosphorylation of p85 subunit of phosphatidylinositol 3-kinase and Akt, activation of 6-phosphofructo-2-kinase, and glucose uptake. In conclusion, HCV infection changes a subset of hepatic molecules regulating glucose metabolism. A possible mechanism is that HCV core-induced SOCS3 promotes proteosomal degradation of IRS1 and IRS2 through ubiquitination.