RESUMO
Objective@#Elucidation of clonal origin of synchronous endometrial and ovarian cancers (SEOs). @*Methods@#We reviewed 852 patients who diagnosed endometrial and/or ovarian cancer. Forty-five (5.3%) patients were diagnosed as SEOs. We evaluated blood and tissue samples from 17 patients. We analyzed the clonal origins of 41 samples from 17 patients by gene sequencing, mismatch microsatellite instability (MSI) polymerase chain reaction assay and immunohistochemical (IHC) staining of 4 repair genes. @*Results@#Sixteen of 17 patients had at least 2 or more trunk mutations shared between endometrial and ovarian cancer suggesting the identical clonal origins. The shared trunk mutation are frequently found in endometrial cancer of the uterus, suggesting the uterine primary. Four out of 17 (24%) SEOs had mismatch repair (MMR) protein deficiency and MSI-high (MSI-H) states. One case was an endometrial carcinoma with local loss of MSH6 protein expression by IHC staining, and the result of MSI analysis using the whole formalin-fixed, paraffin-embedded specimen was microsatellite stable. In contrast, ovarian tissue was deficient MMR and MSI-H in the whole specimen. This indicated that MMR protein deficiency could occur during the progression of disease. @*Conclusion@#Most SEOs are likely to be a single tumor with metastasis instead of double primaries, and their origin could be endometrium. In addition, SEOs have a high frequency of MMR gene abnormalities. These findings not only can support the notion of uterine primary, but also can help to expect the benefit for patients with SEOs by immuno-oncology treatment.
RESUMO
BACKGROUND@#More than 140 million people drink arsenic-contaminated groundwater. It is unknown how much arsenic exposure is necessary to cause neurological impairment. Here, we evaluate the relationship between neurological impairments and the arsenic concentration in drinking water (ACDW).@*PARTICIPANTS AND METHODS@#A cross-sectional study design was employed. We performed medical examinations of 1867 residents in seven villages in the Thabaung township in Myanmar. Medical examinations consisted of interviews regarding subjective neurological symptoms and objective neurological examinations of sensory disturbances. For subjective neurological symptoms, we ascertained the presence or absence of defects in smell, vision, taste, and hearing; the feeling of weakness; and chronic numbness or pain. For objective sensory disturbances, we examined defects in pain sensation, vibration sensation, and two-point discrimination. We analyzed the relationship between the subjective symptoms, objective sensory disturbances, and ACDW.@*RESULTS@#Residents with ACDW ≥ 10 parts per billion (ppb) had experienced a "feeling of weakness" and "chronic numbness or pain" significantly more often than those with ACDW 50 ppb). These data suggest a threshold for the occurrence of peripheral neuropathy due to arsenic exposure, and indicate that the arsenic concentration in drinking water should be less than 10 ppb to ensure human health.