Effectiveness of endoscopic screening for gastric cancer: The Japan Public Health Center‐based Prospective Study

Upper gastrointestinal endoscopy for gastric cancer screening has been implemented in Japan. However, its effectiveness for gastric cancer prevention has not been fully studied. We aimed to investigate the effectiveness of endoscopic screening to reduce mortality from gastric cancer. In a large prospective population‐based cohort study including 80,272 participants, we compared the risk of mortality and incidence of gastric cancer among participants who underwent endoscopic or radiographic screening compared with those who did not undergo any screening using multivariable Cox proportional hazards models. In the 1,023,364 person‐year observation period (median; 13.0 years), 1977 cases of gastric cancer were diagnosed, and 783 patients with gastric cancer died. In the endoscopic screening group, the mortality from gastric cancer and incidence of advanced gastric cancer were reduced by 61% (hazard ratio [HR] = 0.39 [95% CI: 0.30–0.51]) and 22% (HR = 0.78 [95% CI: 0.67–0.90]), respectively. The radiographic screening reduced the mortality from gastric cancer (HR = 0.63 [95% CI: 0.54–0.73]), but its effectiveness was lower than that of endoscopic screening. In conclusion, endoscopic screening reduced the incidence of advanced gastric cancer and mortality from gastric cancer in the Japanese population.     

Isoflavone, polymorphisms in estrogen receptor genes and breast cancer risk in case-control studies in Japanese, Japanese Brazilians and non-Japanese Brazilians

Epidemiologic studies have shown an inverse association between isoflavones and breast cancer risk. Because isoflavones bind estrogen receptors, we hypothesized that polymorphisms in the estrogen receptor genes might modify the association between isoflavone intake and breast cancer risk. We conducted hospital-based case-control studies of patients aged 20–74 years with primary, incident, histologically confirmed invasive breast cancer, and matched controls from among medical checkup examinees in Nagano, Japan, and from cancer-free patients in São Paulo, Brazil. A total of 846 pairs (388 Japanese, 79 Japanese Brazilians and 379 non-Japanese Brazilians) completed validated food frequency questionnaires, and provided blood samples. Five single nucleotide polymorphisms in the estrogen receptor alpha (rs9340799, rs1913474, and rs2234693) and beta (rs4986938 and rs1256049) genes were genotyped. We found no consistent association between the five single nucleotide polymorphisms and breast cancer risk among the three populations. In analyses of combinations of isoflavone intake and single nucleotide polymorphisms, an inverse association between intake and risk was limited to women with the GG genotype of the rs4986938 polymorphism for postmenopausal Japanese (odds ratio for highest versus lowest tertile = 0.47; P for trend = 0.01), Japanese Brazilians (odds ratio for highest versus lowest median = 0.31) and non-Japanese Brazilians (odds ratio for consumers versus non-consumers = 0.37) ( P for interaction = 0.11, 0.08, and 0.21, respectively). We found no remarkable difference for the other four polymorphisms. Our findings suggest that polymorphisms in the estrogen receptor beta gene may modify the association between isoflavone intake and breast cancer risk. ( Cancer Sci 2009; 100: 927–933)     

Short communication: sclerosing meningioma in the deep sylvian fissure

Sclerosing meningioma is a rare type of meningeal tumor with extensive collagen depositions. Deep sylvian meningioma, a tumor that is unattached to the dura mater, is also unusual. The biological activity of both is controversial, as are therapeutic strategies. A heterogeneous contrast-enhanced mass in the right sylvian fissure of a 10-year-old boy with a 3-year history of epilepsy was identified via magnetic resonance imaging. The patient underwent partial surgical resection because the tumor was hard and contained numerous perforators arising from the right middle cerebral artery. The tumor was histologically diagnosed as sclerosing meningioma. Twelve months after surgery, the patient was asymptomatic and did not require any additional therapies. This case is the first report of a sclerosing meningioma arising in the deep sylvian fissure. We discuss the therapeutic dilemma of this case with respect to the current literature.     

A nuclear receptor-mediated choleretic action of fibrates is associated with enhanced canalicular membrane fluidity and transporter activity mediating bile acid-independent bile secretion

Fibrates are commonly used lipid-lowering agents that act via PPARalpha, a member of the nuclear hormone receptor superfamily. The mechanism(s) of fibrate-induced changes in the hepatic canalicular membrane and bile lipids are still unknown. Therefore, the aim of this study was to investigate the influence of fibrates on hepatic lipid metabolism and to assess the hepatocellular cytoprotective effect on hepatocyte canalicular membrane. Male ICR mice were fed standard chow with or without bezafibrate (100 mg/kg) for 6 days. The expression of canalicular membrane transporters (Mdr2 and Mrp2) was evaluated by RT-PCR and Western blotting. Canalicular membrane fluidity was also investigated. Canalicular membrane fluidity was markedly increased by fibrates. The expression of mdr 2 and mrp2 mRNA and protein showed a significant increase in fibrate-treated mice. These results suggested that fibrates improve liver function by enhancing bile secretion. The mechanism of the choleretic action of fibrate therapy might involve the enhancement of bile acid-independent bile secretion, since increased expression of Mdr2 and Mrp2 was found in fibrate-treated animals. These changes were very likely mediated by PPARalpha, and the increase of canalicular membrane fluidity may have been partly associated with enhancement of this transporter activity.     

Cytokine and endotoxin removal in critically Ill patients

Endotoxin and cytokine removal by blood purification is one of the most effective treatments for critical illness such as systemic inflammatory response syndrome (SIRS), sepsis and septic shock. SIRS and sepsis frequently associates with hepatic failure, renal failure, respiratory failure, cardiac failure, disseminated intravascular coagulation (DIC) and gastrointestinal bleeding. In these diseases endotoxin and several mediators such as inflammatory cytokines play important roles in clinical course and pathophysiology. The role of blood purification is to remove endotoxin and cytokines, to correct cytokine balance, and to modulate humoral conditions. We use 2 methods of blood purification. One is direct hemoperfusion using Toraymyxin developed by Kodama and Tani in Shiga University of Medical Science. Toraymyxin composed of a Polymyxin B immobilized, can remove endotoxin and can be applied to patients with endotoxemia or suspected bacteremia. The most impressive clinical effectiveness is the improvement of hemodynamic abnormalities. Blood pressure, cardiac index and oxygen consumption index improve after treatment by Toraymyxin. Furthermore inflammatory mediators such as TNF, IL‐6, IL‐10 and plasminogen activator inhibitor‐1 (PAI‐1) are significantly decreased either after 2 h or by the following day in survivors. An immediate mediator, endogenous cannabinoid which is generated by activated monocytes / macrophages and causes septic shock, is also reduced by Toraymyxin treatment. Another method of blood purification is continuous hemofiltration (CHF) and continuous hemodiafiltration (CHDF). CHF and CHDF have been applied only with renal indication, but recently it is widely applied with nonrenal indication for patients with critical illness. The main purpose of CHF and CHDF is to reduce humoral mediators level in blood. As in SIRS patients, inflammatory cytokines are continuously produced in inflammatory regions, the continuous therapy is recommended in ICU. Sometimes inflammatory cytokines are not so reduced in the blood level. The change in the blood level of cytokines depends on the balance between the generation rate and the removal rate of cytokines with continuous therapy. We have some successful results in patients with sepsis and SIRS, but further studies are required to make standardized strategy with blood purification and to have better survival rate.