Transient lesions of the splenium of the corpus callosum following rapid withdrawal of levetiracetam

Transient lesions of the splenium of the corpus callosum are characterized by MRI findings. The lesions are very rare, but significant from a clinical standpoint as differential diagnoses include serious conditions such as encephalitis, meningitis, and neuroleptic malignant syndrome. In addition, it is reported that some are attributed to the withdrawal of antiepileptic drugs. Here, we present a case of transient lesions of the splenium of the corpus callosum following rapid withdrawal of levetiracetam alone. To the best of our knowledge, this is the first report of such a case. Moreover, it is reported that cases of incidental transient lesions of the splenium of the corpus callosum are detected in Japan more often than in other countries, and as a result are prone to over‐triage. Taking this into consideration, in the event of transient lesions of the splenium of the corpus callosum, the utmost attention must be paid to clinical symptoms and history relating to any of the aforementioned serious conditions.     

Randomized phase II study comparing dose escalated weekly paclitaxel vs. standard dose weekly paclitaxel for patients with previously treated advanced gastric cancer

Weekly paclitaxel is an effective and widely used regimen for patients with advanced gastric cancer, with main dose-limiting toxicities of neutropenia and neurotoxicity. Neutropenia during weekly paclitaxel administration was reported to be associated with better survival. The aim of this study is to evaluate prospectively whether dosing adjustments based on the occurrence of neutropenia may improve chemotherapy efficacy. A total of 90 patients will be randomized to receive either a standard dose of weekly paclitaxel (80 mg/m(2)) or an escalated dose of weekly paclitaxel (80 mg/m(2) initially followed by 100 and 120 mg/m(2) unless severe toxicity is observed). The primary endpoint is overall survival. Secondary endpoints include progression-free survival, response rate, disease control rate and adverse events.     

Alcohol drinking and esophageal cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population

Although alcohol drinking is considered as an important risk factor for esophageal cancer, the magnitude of the association might be varied among geographic areas. Therefore, we reviewed epidemiologic studies on the association between alcohol drinking and esophageal cancer among the Japanese population. Original data were obtained from MEDLINE, searched using PubMed or from searches of the Ichushi database, complemented with manual searches. Evaluation of associations was based on the strength of evidence ('convincing', 'probable', 'possible' or 'insufficient') and the magnitude of association ('strong', 'moderate', 'weak' or 'no association'), together with biological plausibility as previously evaluated by the International Agency of Research on Cancer. We identified four cohort studies and nine case-control studies. All cohort studies and case-control studies showed strong positive associations between esophageal cancer and alcohol drinking. All cohort studies and six case-control studies showed that alcohol drinking had the dose- or frequency-response relationships with esophageal cancer. In addition, four case-control studies showed that acetaldehyde dehydrogenase Glu504Lys polymorphism had strong effect modification with alcohol drinking. We conclude that there is convincing evidence that alcohol drinking increases the risk of esophageal cancer in the Japanese population.     

Comparison between self‐reported facial flushing after alcohol consumption and ALDH2 Glu504Lys polymorphism for risk of upper aerodigestive tract cancer in a Japanese population

Some Japanese exhibit facial flushing after drinking alcohol. Facial flushing was considered to be caused by acetaldehydemia. The concentration of blood acetaldehyde was concerned with the catalytic activity of acetaldehyde dehydrogenase (ALDH). Acetaldehyde dehydrogenase (ALDH)‐2 polymorphism (rs671, Glu504Lys) was known to be associated with upper aerodigestive tract (UAT) cancer due to modulation of ALDH2 enzyme activity. It remains controversial whether facial flushing is useful in predicting UAT cancer risk as a surrogate marker of ALDH2 polymorphism. We conducted a case–control study to assess the risk of UAT cancer and facial flushing and ALDH2 polymorphism. Cases and controls were 585 UAT cancer patients and matched 1170 noncancer outpatients of Aichi Cancer Center Hospital. Information on facial flushing and other lifestyle factors was collected via a self‐administered questionnaire. Association between facial flushing, polymorphism, and UAT cancer was assessed by odds ratios and 95% confidence intervals by using conditional logistic regression models. The facial flushing had no significant association with UAT cancer, although ALDH2 Lys allele was significantly associated with UAT cancer. No significant interaction between facial flushing and alcohol consumption was observed in this study, whereas ALDH2 Lys allele had significant association with UAT cancer. The misclassification between facial flushing and ALDH2 genotype was observed in 18% of controls with ALDH2 Glu/Glu genotype and in 16% of controls with ALDH2 Glu/Lys genotype. Facial flushing was less useful to predict UAT cancer risk than genotyping ALDH2 polymorphism. (Cancer Sci 2010)     

Association between <Emphasis Type="Italic">ALDH2</Emphasis> and <Emphasis Type="Italic">ADH1B</Emphasis> polymorphisms,alcohol drinking and gastric cancer: a replication and mediation analysis

Background

Aldehyde dehydrogenase 2 (ALDH2; rs671, Glu504Lys) and alcohol dehydrogenase 1B (ADH1B; rs1229984, His47Arg) polymorphisms have a strong impact on carcinogenic acetaldehyde accumulation after alcohol drinking. To date, however, evidence for a significant ALDH2–alcohol drinking interaction and a mediation effect of ALDH2/ADH1B through alcohol drinking on gastric cancer have remained unclear. We conducted two case–control studies to validate the interaction and to estimate the mediation effect on gastric cancer.

Methods

We calculated odds ratios (OR) and 95% confidence intervals (CI) for ALDH2/ADH1B genotypes and alcohol drinking using conditional logistic regression models after adjustment for potential confounding in the HERPACC-2 (697 cases and 1372 controls) and HERPACC-3 studies (678 cases and 678 controls). We also conducted a mediation analysis of the combination of the two studies to assess whether the effects of these polymorphisms operated through alcohol drinking or through other pathways.

Results

ALDH2 Lys alleles had a higher risk with increased alcohol consumption compared with ALDH2 Glu/Glu (OR for heavy drinking, 3.57; 95% CI 2.04–6.27; P for trend?=?0.007), indicating a significant ALDH2–alcohol drinking interaction (P_interaction?=?0.024). The mediation analysis indicated a significant positive direct effect (OR 1.67; 95% CI 1.38–2.03) and a protective indirect effect (OR 0.84; 95% CI 0.76–0.92) of the ALDH2 Lys alleles with the ALDH2–alcohol drinking interaction. No significant association of ADH1B with gastric cancer was observed.

Conclusion

The observed ALDH2–alcohol drinking interaction and the direct effect of ALDH2 Lys alleles may suggest the involvement of acetaldehyde in the development of gastric cancer.

     

Smoking and subsequent risk of acute myeloid leukaemia: A pooled analysis of 9 cohort studies in Japan

Smoking has been identified as a significant risk factor for acute myeloid leukaemia (AML). However, epidemiological evidence for the effect of smoking on the risk of AML among Asians is scarce. Here, we investigated the impact of smoking habits on the risk of AML by conducting a pooled analysis of 9 population‐based prospective cohort studies in Japan. We analysed original data on smoking habits at baseline from 9 cohort studies. Hazard ratios (HRs) in the individual studies were calculated using a Cox proportional hazard model adjusted for potential confounders and combined using a random‐effects model. During 4 808 175 person‐years of follow‐up for a total of 344 676 participants (165 567 men and 179 109 women), 245 AML cases (139 men and 106 women) were identified. For both sexes combined, current smokers had a marginally significant increased risk of AML compared to never smokers (HR = 1.44, 95% confidence interval [CI], 0.97‐2.14). Ever smokers with more than 30 pack‐years had a statistically significant increased risk of AML compared to never smokers among both sexes combined (HR = 1.66, 95% CI, 1.06‐2.63). By sex, this significant association was observed only among men, with an HR of 1.69 (95% CI, 1.00‐2.87) for ever smokers with more than 30 pack‐years relative to never smokers. In conclusion, this study confirmed that cigarette smoking increases the risk of AML in Japanese. This study provides important evidence that smoking increases the risk of AML among Asians, which has already been shown in Western populations.     

New potential therapy for orthotopic bladder carcinoma by combining HVJ envelope with doxorubicin

Purpose To establish a new therapeutic method to treat bladder carcinoma, we investigated the therapeutic potential of doxorubicin hydrochloride (DXR) combined with hemagglutinating virus of Japan-envelope vector (HVJ-E) in an orthotropic mouse bladder cancer model. Methods DXR and/or HVJ-E were instilled into the bladder after implantation of MB49 cells. Antitumor effects of combination therapy were evaluated by histological analysis of the bladder on day 14 after tumor implantation. The survival rate of MB49-disseminated mice was examined for 60 days after single or double administration of DXR alone or DXR/HVJ-E. The surviving mice were re-challenged with intravesical injection of MB49 cells, and the bladder was observed after 3 weeks. Results Combined intravesical instillation of HVJ-E and DXR resulted in a significantly higher rate of tumor-free mice (11/21) compared with mice treated using DXR alone (3/19, P < 0.05). Median survival was >60 days for intravesical instillation of HVJ-E and DXR, compared with the 29 days for DXR instillation alone (P < 0.05). After combination therapy, surviving mice formed no tumors in the bladder following intravesical re-instillation of MB49. Conclusions HVJ-E increased antitumor effects in combination with chemotherapeutic agent (DXR). Antitumor immunity appeared to be enhanced using HVJ-E.     

Folate, alcohol, and aldehyde dehydrogenase 2 polymorphism and the risk of oral and pharyngeal cancer in Japanese

Folate consumption is inversely associated with the risk of oral and pharyngeal cancer (OPC) and potentially interacts with alcohol drinking in the risk of OPC. Aldehyde dehydrogenase 2 (ALDH2) gene polymorphism is known to interact with alcohol consumption. The aim of this study was to investigate potential interaction between folate, alcohol drinking, and ALDH2 polymorphism in the risk of OPC in a Japanese population. The study group comprised 409 head and neck cancer cases and 1227 age-matched and sex-matched noncancer controls; of these, 251 cases and 759 controls were evaluated for ALDH rs671 polymorphism. Associations were assessed by odds ratios and 95% confidence intervals in multiple logistic regression models. We observed an inverse association between folate consumption and OPC risk. The odds ratio for high folate intake was 0.53 (95% confidence interval: 0.36-0.77) relative to low intake (P trend=0.003). This association was consistent across strata of sex, age, smoking, and ALDH2 genotypes. Interaction between folate consumption, drinking, and ALDH2 genotype was remarkable (three-way interaction, P<0.001). We observed significant interaction among folate, drinking, and ALDH2 genotype in the Japanese population.     

Effect of recombinant human bone morphogenetic protein-2 on mandibular distraction osteogenesis

The purpose of this investigation was to study the effects of recombinant human bone morphogenetic protein-2 (rhBMP-2) on bone formation of mandibular distraction osteogenesis. Six skeletally mature sheep underwent 10 mm of bilateral mandibular distraction osteogenesis via a custom-made distractor. Three micrograms of rhBMP-2 with a collagen carrier was implanted in the osteotomy site of one side of the mandible during the osteotomy phase. The contralateral side was used as the control group, and no material was implanted into the distracted area. At 10 days after the end of distraction, all animals were killed, and the distracted calluses were harvested for radiologic and histologic analysis. New bone was generated in the distracted zone in all groups. Histologic and radiologic examination showed that the new bone formation was greater in the rhBMP-2 group than in the control group. Quantitative computed tomography evaluation, however, did not demonstrate a significantly different mean bone density of the regenerates between the 2 groups. The results indicate that application of a rhBMP-2/collagen implant during the osteotomy phase of distraction osteogenesis increased bone formation but did not have a significant effect on bone density of the regenerates.