遺残胎盤組織：診断と臨床的取り扱いにおけるMRI所見の役割

OBJECTIVE:To assess the role of MRI in diagnosis and predicting clinical outcome in women with retained placental tissue. PATIENTS AND METHODS:Eleven patients with pathologically proven RPT were retrospectively studied. All underwent MRI. The following MRI parameters of RPT were studied: size, signal intensity on T1- and T2-weighted images, enhancement pattern on dynamic study, extent of attachment to the uterine myometrium, and myometrial thickness at the attachment site. Clinical reports were reviewed and MRI findings were compared with respect to outcome. RESULTS:RPT diameter varied from 30 to 102 mm. On T2-weighted images, 10 cases showed high intensity, while on T1-weighted images, seven cases showed high intensity. Nine cases were hypervascular. The myometrium was thinner at the attachment side than at the opposite side. All five cases in which RPT was delivered spontaneously showed an attachment area of less than a semicircle, hence broad attachment appears to impede detachment and necessitate additional therapy. After uterine arterial embolization, two patients showed complete infarction of RPT on enhanced MRI. CONCLUSION:MRI is useful for diagnosis and follow-up of RPT. The evaluation of extent of RPT attachment to the myometrium and vascularity on MRI can help the clinical assessment.博士（医学）・乙第1351号・平成26年12月3日© Springer Verlag. The definitive version is available at " http://dx.doi.org/10.1007/s00261-010-9604-x

Correlation of vascular endothelial cell proliferation with microvessel density and expression of vascular endothelial growth factor and basic fibroblast growth factor in hepatocellular carcinoma

Tumor-associated angiogenesis is essential for tumor growth or metastasis, and consists of multiple and sequential steps regulated by proangiogenic and antiangiogenic factors. Vascular endothelial cell proliferation is involved in this process. We investigated the correlation of vascular endothelial cell proliferation with microvessel density (MVD) and expression of major proangiogenic molecules, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in hepatocellular carcinoma (HCC). Formalin-fixed paraffin-embedded specimens of surgically resectedHCCfrom67 patients were used. Proliferating endothelial cells were detected by immunofluorescence double staining for CD34 and proliferating cell nuclear antigen (PCNA). The proliferation activity of endothelial cells was determined by the rate of PCNA-positive endothelial cells, and evaluated at the periphery and center of the tumors and adjacent non-neoplastic livers. MVD and the expression of VEGF and bFGF in the tumors were also examined immunohistochemically. The proliferation activity of endothelial cells at the periphery of the tumors was significantly higher than that at the center of the tumors (35.8% vs.12.7%, P<0.0001). The rate of PCNA positive endothelial cells in the tumors with higher bFGF expression was significantly higher than that in the tumors with lower bFGF expression (44.8% vs. 32.5%,P<0.005) at the periphery of the tumors. There was no significant correlation between the rate of PCNA-positive endothelial cells and clinicopathological findings or MVD. InHCC, the proliferation activity of vascular endothelial cells is suggested to be heterogeneous in the tumor and higher at the periphery of the tumor, and bFGF may play an important role in the positive regulation of tumor-associated vascular endothelial cell proliferation

Parental legacy and regulatory novelty in Brachypodium diurnal transcriptomes accompanying their polyploidy

Polyploidy is a widespread phenomenon in eukaryotes that can lead to phenotypic novelty and has important implications for evolution and diversification. The modification of phenotypes in polyploids relative to their diploid progenitors may be associated with altered gene expression. However, it is largely unknown how interactions between duplicated genes affect their diurnal expression in allopolyploid species. In this study, we explored parental legacy and hybrid novelty in the transcriptomes of an allopolyploid species and its diploid progenitors. We compared the diurnal transcriptomes of representative Brachypodium cytotypes, including the allotetraploid Brachypodium hybridum and its diploid progenitors Brachypodium distachyon and Brachypodium stacei. We also artificially induced an autotetraploid B. distachyon. We identified patterns of homoeolog expression bias (HEB) across Brachypodium cytotypes and time-dependent gain and loss of HEB in B. hybridum. Furthermore, we established that many genes with diurnal expression experienced HEB, while their expression patterns and peak times were correlated between homoeologs in B. hybridum relative to B. distachyon and B. stacei, suggesting diurnal synchronization of homoeolog expression in B. hybridum. Our findings provide insight into the parental legacy and hybrid novelty associated with polyploidy in Brachypodium, and highlight the evolutionary consequences of diurnal transcriptional regulation that accompanied allopolyploidy

Accurate and simple method for quantification of hepatic fat content using magnetic resonance imaging: a prospective study in biopsy-proven nonalcoholic fatty liver disease

To assess the degree of hepatic fat content, simple and noninvasive methods with high objectivity and reproducibility are required. Magnetic resonance imaging (MRI) is one such candidate, although its accuracy remains unclear. We aimed to validate an MRI method for quantifying hepatic fat content by calibrating MRI reading with a phantom and comparing MRI measurements in human subjects with estimates of liver fat content in liver biopsy specimens. The MRI method was performed by a combination of MRI calibration using a phantom and double-echo chemical shift gradient-echo sequence (double-echo fast low-angle shot sequence) that has been widely used on a 1.5-T scanner. Liver fat content in patients with nonalcoholic fatty liver disease (NAFLD, n = 26) was derived from a calibration curve generated by scanning the phantom. Liver fat was also estimated by optical image analysis. The correlation between the MRI measurements and liver histology findings was examined prospectively. Magnetic resonance imaging measurements showed a strong correlation with liver fat content estimated from the results of light microscopic examination (correlation coefficient 0.91, P < 0.001) regardless of the degree of hepatic steatosis. Moreover, the severity of lobular inflammation or fibrosis did not influence the MRI measurements. This MRI method is simple and noninvasive, has excellent ability to quantify hepatic fat content even in NAFLD patients with mild steatosis or advanced fibrosis, and can be performed easily without special devices.ArticleJOURNAL OF GASTROENTEROLOGY. 45(12):1263-1271 (2010)journal articl

Association between Skeletal Muscle Depletion and Sorafenib Treatment in Male Patients with Hepatocellular Carcinoma: A Retrospective Cohort Study

The effect of skeletal muscle mass (SMM) on the outcomes of sorafenib treatment for hepatocellular carcinoma (HCC) has not been established. We measured the SMM in HCC patients treated with sorafenib, evaluated the patients’ survival, and evaluated the association between skeletal muscle depletion and sorafenib treatment. Of the 97 HCC patients treated with sorafenib at our institution in the period from July 2009 to February 2015, our study included 69 patients (51 males, 18 females) who had received sorafenib for ≥ 8 weeks and whose follow-up data were available. SMM was calculated from computed tomography images at the mid-L3 level (cm2) and normalized to height (m2) to yield the L3 skeletal muscle index (L3-SMI, cm2/m2). The median L3-SMI value was higher in the males (43 cm2/m2) compared to the females (36 cm2/m2). In the males only, the multivariate Cox regression identified an L3-SMI <43 cm2/m2 as independently associated with higher mortality compared to an L3-SMI ≥43 cm2/m2 (hazard ratio 2.315, 95% confidence interval: 1.125-4.765, p=0.023). Skeletal muscle depletion is a factor predicting poor prognosis for male patients with advanced HCC treated with sorafenib

Adenosquamous Carcinoma of the Choledochus

The patient was an 86-year-old man who was admitted with obstructive jaundice. Computed tomography revealed a tumor in the hilar choledochus with peripheral hepatic duct dilatation. Endoscopic cholangiography (ERC) demonstrated the defect in the choledochus. Brushing cytology during ERC showed Orange-G-philic keratinized atypical cells, which led to a diagnosis of squamous cell carcinoma. Chemotherapy with tegafur-gimeracil-oteracil potassium was ineffective and was discontinued due to adverse effects. The patient died 5 months after the diagnosis and autopsy revealed tubular adenocarcinoma of the hilar bile duct with squamous cell carcinoma component. Progression of the disease might influence the distribution of adenosquamous carcinoma. The clinicopathological sequence of adenosquamous carcinoma of the choledochus was documented

AXL confers intrinsic resistance to osimertinib and advances the emergence of tolerant cells

A novel EGFR-tyrosine kinase inhibitor (TKI), osimertinib, has marked efficacy in patients with EGFR-mutated lung cancer. However, some patients show intrinsic resistance and an insufficient response to osimertinib. This study showed that osimertinib stimulated AXL by inhibiting a negative feedback loop. Activated AXL was associated with EGFR and HER3 in maintaining cell survival and inducing the emergence of cells tolerant to osimertinib. AXL inhibition reduced the viability of EGFR-mutated lung cancer cells overexpressing AXL that were exposed to osimertinib. The addition of an AXL inhibitor during either the initial or tolerant phases reduced tumor size and delayed tumor re-growth compared to osimertinib alone. AXL was highly expressed in clinical specimens of EGFR-mutated lung cancers and its high expression was associated with a low response rate to EGFR-TKI. These results indicated pivotal roles for AXL and its inhibition in the intrinsic resistance to osimertinib and the emergence of osimertinib-tolerant cells

Applicability of radiocolloids, blue dyes and fluorescent indocyanine green to sentinel node biopsy in melanoma

Patients with primary cutaneous melanoma underwent sentinel node (SN) mapping and biopsy at 25 facilities in Japan by the combination of radiocolloid with gamma probe and dye. Technetium-99m (99mTc)-tin colloid, 99mTc-phytate, 2% patent blue violet (PBV) and 0.4% indigo carmine were used as tracers. In some hospitals, 0.5% fluorescent indocyanine green, which allows visualization of the SN with an infrared camera, was concomitantly used and examined. A total of 673 patients were enrolled, and 562 cases were eligible. The detection rates of SN were 95.5% (147/154) with the combination of tin colloid and PBV, 98.9% (368/372) with the combination of phytate and PBV, and 97.2% (35/36) with the combination of tin colloid or phytate and indigo carmine. SN was not detected in 12 cases by the combination method, and the primary tumor was in the head and neck in six of those 12 cases. In eight of 526 cases (1.5%), SN was detected by PBV but not by radiocolloid. There were 13 cases (2.5%) in which SN was detected by radiocolloid but not by PBV. In 18 of 36 cases (50%), SN was detected by radiocolloid but not by indigo carmine. Concomitantly used fluorescent indocyanine green detected SN in all of 67 cases. Interference with transcutaneous oximetry by PVB was observed in some cases, although it caused no clinical trouble. Allergic reactions were not reported with any of the tracers. 99mTc-tin colloid, 99mTc-phytate, PBV and indocyanine green are useful tracers for SN mapping.ArticleJOURNAL OF DERMATOLOGY. 39(4):336-338 (2012)journal articl