Head and neck squamous cell carcinomas (HNSCCs) arise in the mucosal lining of the upper aerodigestive tract. Tobacco and alcohol use have been reported to be associated with HNSCC. Infection with high-risk human papillomaviruses (HPVs) has recently been implicated in the pathogenesis of HNSCCs. It is now widely accepted that high-risk HPV is a cause of almost all cervical cancers as well as some forms of HNSCCs. HPV-related HNSCCs are increasing. HPV-related HNSCCs and HPV-unrelated HNSCCs differ with respect to the molecular mechanisms underlying their oncogenic processes. HPV-related HNSCCs are known to have a better prognosis response to treatment as compared with HPV-unrelated HNSCCs. Therefore, in recent years, it has been required to accurately discriminate between HPV-related and HPV-unrelated HNSCCs. To diagnose the HPV-related HNSCCs, various methods including P16 immunohistochemistry, FISH, and genetic analyses of the HPV gene from histopathological and liquid biopsy specimens have been employed. Based on the results of the differential diagnosis, various treatments employing EGFR TKI and low-dose radiation have been employed. Here, we review the involvement of the HPV virus in HNSCCs as well as the molecular mechanism of carcinogenesis, classification, prognosis, diagnostic procedures, and therapy of the disease.

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A histological grading system of chromophobe renal cell carcinoma (chRCC) is highly desirable to identify approximately 5-10% of tumors at risk for progression. Validation studies failed to demonstrate a correlation between the four-tiered WHO/ISUP grade and outcome. Previous proposals with threetiered chromophobe grading systems could not be validated. In this study, the presence of sarcomatoid differentiation, necrosis, and mitosis was analyzed in a Swiss cohort (n = 42), an Italian cohort (n = 103), a German cohort (n = 54), a Japanese cohort (n = 119), and The Cancer Genome Atlas cohort (n = 64). All 3 histological parameters were significantly associated with shorter time to tumor progression and overall survival in univariate analysis. Interobserver variability for identification of these parameters was measured by Krippendorff's alpha coefficient and showed high concordance for the identification of sarcomatoid differentiation and tumor necrosis, but only low to medium concordance for the identification of mitosis. Therefore, we tested a two-tiered tumor grading system (low versus high grade) based only on the presence of sarcomatoid differentiation and/or necrosis finding in the combined cohorts (n = 382). pT stage, patient's age (> 65 vs 65), lymph node and/or distant metastasis, and the twotiered grading system (low versus high grade) were significantly associated with overall survival and were independent prognostic parameters in multivariate analysis (Cox proportional hazard). This multiinstitutional evaluation of prognostic parameters suggests tumor necrosis and sarcomatoid differentiation as reproducible components of a two-tiered chromophobe tumor grading system.

ABSTRACT. We have investigated 37 minor serogroup Shiga toxin-producing Eschrichia coli (STEC) strains other than O157, O26, and O111 isolated from human specimens in Osaka prefecture to determine their serological and biochemical characteristics, virulence-associated genes, and clinical signs in patients. The same serotype strains were genotyped by pulsed-field gel electrophoresis (PFGE). The O antigen of 33 strains were typed into 10 serogroups; O28, O63, O65, O91, O103, O119, O121, O126, O165, and O177, and other 4 strains were not agglutinated with any serum. Four different Shiga toxin (Stx) types (1, 2, 2c, and 2f) were distributed in these isolates.The intimin gene was present in 83.8% of the strains and subtyped into intimin α, β, ε, and ζ. STEC O165, O177, and OUT isolated from hemolytic uremic syndrome (HUS) patients revealed atypical biochemical characters; negative reaction for lysine decarboxylase and gas production from glucose. Eleven strains including the isolates from HUS patients generated no colonies on cefixime-tellurite (CT)-sorbitol-MacConkey agar plates, since they showed high sensitivity (MIC ≤ 1.25 µg/ml) to potassium tellurite. The finding show supportive information for use the selective agar plates with and without CT supplement for the isolation of minor serogroup STEC. PFGE analysis revealed that the strains isolated from family cases were closely related within the respective family, and it was useful for epidemiological analysis of minor serogroup STEC.

Little research has been conducted into the long-term effects of preeclampsia, despite its frequent occurrence. The aim of this review is to examine the association between preeclampsia and the development of hypertension and kidney diseases later in life. To achieve this aim, we evaluated three retrospective studies conducted in our department. In the first study, 52 women who suffered from preeclampsia during their first pregnancy were followed for 2 years after delivery for any long-term effects upon blood pressure. In the second study, we evaluated HOMA-R, pulse wave velocity and augmentation index in groups of 48 postmenopausal women with a past history of preeclampsia and 204 postmenopausal women without a past history of preeclampsia. In the third study, we examined the association between a past history of preeclampsia and chronic kidney disease based on biopsy in 127 postmenopausal women. From the first study, although there were no significant differences in age, blood pressure at the onset of preeclampsia, the levels of proteinuria and the birth weight of the child between women who remained hypertensive and those who became normotensive, body mass index was significantly larger in women who remained hypertensive compared to those who were normotensive. In the second study, we found that women with a past history of preeclampsia exhibited insulin resistance combined with reduced vascular elasticity. In the third study, of 32 patients with a past history of preeclampsia, 12 patients exhibited focal segmental glomerulosclerosis, 10 exhibited IgA nephropathy and 10 exhibited nephrosclerosis. In contrast, of the women without a past history of preeclampsia, 26 patients exhibited IgA nephropathy, 20 exhibited a minimal change in nephritic syndrome, 6 exhibited nephrosclerosis, 6 exhibited membranous nephropathy, 5 exhibited lupus nephritis, 5 exhibited diabetic nephropathy, and 27 exhibited various nephropathies. None of the women without a past history of preeclampsia exhibited focal segmental glomerulosclerosis. Taken together with previous results, these findings suggest that hypertension and chronic kidney disease in postmenopausal women are closely associated with a past history of preeclampsia.