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患者は71歳女性，4妊3産。不正性器出血と子宮内膜肥厚を認めた。子宮内膜細胞診で疑陽性であり，子宮体癌を疑われたため，当科紹介となった。経腟超音波検査では子宮内膜は11.5mmと肥厚を認めたが，両側付属器の腫大を認めなかった。続く子宮内膜全面掻爬による組織診では悪性所見を認めなかった。骨盤部MRIでは9mmの子宮内膜肥厚を認めたが，両側卵巣の腫大を認めなかった。血清エストラジオール（E2）は55pg/mLと高値であったが，CA125，CA19-9，CEAの上昇を認めなかった。ホルモン産生卵巣腫瘍を疑い，腹腔鏡下子宮全摘術，両側付属器切除術を施行した。卵巣に肉眼的に明らかな腫瘍性病変を認めなかったが，病理組織学的に右卵巣に1.5×1.5mm大のライディッヒ細胞腫を認めた。術後に血清E2の低下を認めた。閉経後の不正出血，子宮内膜肥厚では，画像検索で卵巣腫瘍を認めない場合にも臨床症状によりライディッヒ細胞腫を鑑別に置くことが肝要である。, A 71-year-old woman, gravida 4 para 3, presented with abnormal genital bleeding. Transvaginal ultrasonography showed a thickened endometrium of 11.5 mm, but no bilateral adnexal enlargement. Cervical cytology was negative for intraepithelial lesion or malignancy, and endometrial curettage was performed, and no malignant findings were found histologically. Pelvic MRI showed only 9 mm endometrial thickening and no ovarian tumor. Serum estradiol was elevated (55 pg/mL), and CA125, CA19-9, and CEA were not elevated. A hormone-producing ovarian tumor was suspected, and total laparoscopic hysterectomy and bilateral salpingo-oophorectomy were performed. Although no tumor was found macroscopically in the bilateral ovaries, histopathology revealed a 1.5 × 1.5 mm Leydig cell tumor in the right ovary. Serum E2 decreased after surgery. Thus, in cases with postmenopausal irregular bleeding and endometrial thickening, it is essential to consider Leydig cell tumor, even in the absence of ovarian tumors on imaging.

Cell adhesion proteins not only maintain tissue integrity, but also possess signaling abilities to organize diverse cellular events in a variety of physiologic and pathologic processes; however, the underlying mechanism remains obscure. Among cell adhesion molecules, the claudin (CLDN) family is often aberrantly expressed in various cancers, but the biological relevance and molecular basis for this observation have not yet been established. Here, we show that high CLDN6 expression accelerates cellular proliferation and migration in two distinct human endometrial cancer cell lines in vitro. Using a xenograft model, we also revealed that aberrant CLDN6 expression promotes tumor growth and invasion in endometrial cancer tissues. The second extracellular domain and Y196/200 of CLDN6 were required to recruit and activate Src-family kinases (SFK) and to stimulate malignant phenotypes. Knockout and overexpression of ESR1 in endometrial carcinoma cells showed that the CLDN6-adhesion signal links to estrogen receptor α (ERα) to advance tumor progression. In particular, aberrant CLDN6–ERα signaling contributed to collective cell behaviors in the leading front of endometrial cancer cells. Importantly, we demonstrate that CLDN6/SFK/PI3K-dependent AKT and SGK (serum- and glucocorticoid-regulated kinase) signaling in endometrial cancer cells targets Ser518 in the human ERα to activate ERα transcriptional activity in a ligand-independent manner, thereby promoting tumor progression. Furthermore, CLDN6, at least in part, also regulated gene expression in an ERα-independent manner.Implications:The identification of this machinery highlights regulation of the transcription factors by cell adhesion to advance tumor progression.

Supplementary Figures 1-3

S3. The SFK/PI3K-dependent AKT and SGK pathways are involved in the CLDN6-accelerated proliferation and migration of endometrial cancer cells.

Supplementary Table 2 - Primers

Supplementary Table 1 - Antibodies

Surgery can be curative treatment for pelvic locoregional recurrence of endometrial cancer; however, a cure is contingent on complete resection. Here, we report the case of a patient in whom recurrent endometrial tumor remained in the pelvis after resection; long-term control was achieved with postoperative administration of pembrolizumab.The patient had recurrent endometrial cancer of stage IA and was treated with chemotherapy and radiation, but tumor persisted in the pelvic cavity. We therefore attempted total pelvic exenteration, but the tumor was adherent to the pelvic wall and complete resection could not be achieved. However, postoperative administration of pembrolizumab controlled the residual tumor for more than two years without regrowth. We believe that since the resected tumor was MSI-High, the residual tumor responded well to pembrolizumab. It is not known whether cytoreductive surgery contributes to a long-term response to pembrolizumab, but at least in our patient, pembrolizumab appeared to be a very effective drug therapy for MSI-High endometrial cancer that was refractory to chemotherapy and radiotherapy.

The tight‑junction protein claudin‑9 (CLDN9) is barely distributed in normal adult tissues but is ectopically expressed in various cancer types. Although multiple databases indicated upregulation of CLDN9 in endometrial cancers at the mRNA level, its protein expression and biological roles remain obscure. In the present study, the prognostic significance of CLDN9 expression in endometrial cancer was evaluated by immunohistochemical staining and semi‑quantification using formalin‑fixed paraffin‑embedded specimens obtained from 248 endometrial carcinoma cases. A total of 43 cases (17.3%) had high CLDN9 expression, whereas 205 cases (82.7%) exhibited low CLDN9 expression. The 5‑year disease‑specific survival rates in the high and low CLDN9 expression groups were 62.8 and 87.8% (P0.001), respectively. In addition, multivariate analysis revealed that high CLDN9 expression was an independent prognostic factor (hazard ratio, 4.99; 95% CI, 1.96‑12.70; P0.001). Furthermore, CLDN9 expression was significantly correlated with the expression of CLDN6 (P0.001), which is the closest CLDN member to CLDN9 and a poor prognostic factor for endometrial carcinoma. The 5‑year disease‑specific survival rate of cases with CLDN6‑high/CLDN9‑high, CLDN6‑high/CLDN9‑low and CLDN6‑low/CLDN9‑high status was 30.0, 37.5 and 72.7%, respectively, whereas that of CLDN6‑low/CLDN9‑low was 89.8% (P=0.004). In conclusion, aberrant CLDN9 expression is a predictor of poor prognosis for endometrial cancer and may be utilized in combination with CLDN6 to achieve higher sensitivity.

Cell adhesion proteins not only maintain tissue integrity, but also possess signaling abilities to organize diverse cellular events in a variety of physiologic and pathologic processes; however, the underlying mechanism remains obscure. Among cell adhesion molecules, the claudin (CLDN) family is often aberrantly expressed in various cancers, but the biological relevance and molecular basis for this observation have not yet been established. Here, we show that high CLDN6 expression accelerates cellular proliferation and migration in two distinct human endometrial cancer cell lines in vitro. Using a xenograft model, we also revealed that aberrant CLDN6 expression promotes tumor growth and invasion in endometrial cancer tissues. The second extracellular domain and Y196/200 of CLDN6 were required to recruit and activate Src-family kinases (SFK) and to stimulate malignant phenotypes. Knockout and overexpression of ESR1 in endometrial carcinoma cells showed that the CLDN6-adhesion signal links to estrogen receptor α (ERα) to advance tumor progression. In particular, aberrant CLDN6–ERα signaling contributed to collective cell behaviors in the leading front of endometrial cancer cells. Importantly, we demonstrate that CLDN6/SFK/PI3K-dependent AKT and SGK (serum- and glucocorticoid-regulated kinase) signaling in endometrial cancer cells targets Ser518 in the human ERα to activate ERα transcriptional activity in a ligand-independent manner, thereby promoting tumor progression. Furthermore, CLDN6, at least in part, also regulated gene expression in an ERα-independent manner. Implications: The identification of this machinery highlights regulation of the transcription factors by cell adhesion to advance tumor progression.

Objective Epithelial ovarian cancer (EOC) is a heterogeneous disease with diverse clinicopathological features and behaviors, and its heterogeneity may be concerned with the accumulation of multiple somatic oncogenic mutations. The major goals of this study are to systematically perform the comprehensive mutational profiling in EOC patients, and investigate the associations between somatic mutations and clinicopathological characteristics. Methods A total of 80 surgical specimens were obtained from EOC patients who had previously undergone primary debulking surgery, and genomic DNAs were extracted from fresh-frozen tissues. We investigated mutational status in hot spot regions of 50 cancer-related genes by targeted next-generation sequencing using an Ion AmpliSeq Cancer Hotspot Panel v2 Kit. Results Validated mutations were detected in 66 of the 80 tumors (82.5%). The five most frequently mutated genes were TP53 (43.8%), PIK3CA (27.5%), KRAS (23.8%), PTEN (10%) and CTNNB1 (10%). PTEN and CTNNB1 mutations were associated with younger age. PIK3CA1, KRAS and CTNNB1 mutations were observed in early-stage, whereas TP53 mutations were more common in advanced stage. Significant associations were observed between TP53 mutation and serous carcinoma, and between KRAS mutation and mucinous carcinoma. Both PIK3CA mutation and CTNNB1 mutation were also significantly associated with endometrioid and clear cell carcinoma. The patients with PIK3CA and KRAS mutations were significantly associated with favorable progression free survival (PFS). In particular, PIK3CA mutations had more significant associations with favorable PFS than PIK3CA wild-type in the endometrioid subtype (P = 0.012). Patients with mutations only in TP53 were significantly associated with worse PFS. Conclusion EOCs were heterogeneous at the genomic level and harbored somatic oncogenic mutations. Our molecular profiling may have the potential for becoming a novel stratification within histological subtypes of EOC. Further studies are needed to define molecular classification for improved clinical outcomes and treatment of EOC patients in future.

Background/aim Pelvic exenteration is a radical procedure for certain advanced or recurrent gynaecological cancers, performed with curative or palliative intent. Its validity has evolved as operative mortality and morbidity have improved. This surgery was evaluated to determine the validity of these claims. Patients and methods The details of surgery and outcomes of 13 patients who underwent pelvic exenteration (6 curative intent, 7 palliative intent) for advanced or recurrent gynaecological cancers in our Department were retrospectively evaluated. Results There were no significant differences in blood loss, surgical time, hospital stay, and complications between curative pelvic exenteration and palliative pelvic exenteration. The curative intent group had a good prognosis; the palliative-intent group showed a trend to a worse prognosis. All patients' symptoms were relieved, but in patients with short survival, symptom relief lasted for up to 3 months. Conclusion Pelvic exenteration is an acceptable and valuable procedure for gynaecological cancers.

We developed a lanthanum-doped Pb(Zr0.4,Ti0.6)O3 (PLZT)-based ferroelectric capacitor (FE) aiming at low-voltage operation of ferroelectric random access memory at low temperatures down to −45 °C. High-temperature sputter-deposited IrO x (1 < x < 2) or HT-IrO x was employed as a top electrode (TE) instead of room-temperature (RT) deposited IrO x or RT-IrO x over two PLZT stacked layers. We observed that polarization characteristics drastically improved even at −45 °C by employing HT-IrO x and thinning PLZT, even though leakage current was increased by about one order of magnitude. Transmission electron microscopy observations showed that HT-IrO x has a columnar-like crystalline structure while RT-IrO x has a granular-like crystalline structure. Secondary ion mass spectroscopy indicated that Pb diffusion from PLZT into TE was suppressed by HT-IrO x , which is considered to cause the improvement of polarization characteristics.

We developed 16 Mb 1T1R NRAM integrating CNTs resistor elements into the intermediate wirings of 55 nm CMOS. Excellent reliabilities were proven by the retention test at 150 °C extrapolated for 100 kh and the endurance test of 1E6 cycles. The switching speed was realized for cell array at 200 ns. In addition, we successfully fabricated CNTs resistor elements with 49% shrunk small via pitch cell area and realized advantageous high switching speed with 0.5 ns single pulse even omitting verify operation.

Background: Within the claudin (CLDN) family, CLDN12 mRNA expression is altered in various types of cancer, but its clinicopathological relevance has yet to be established due to the absence of specific antibodies (Abs) with broad applications. Methods: We generated a monoclonal Ab (mAb) against human/mouse CLDN12 and verified its specificity. By performing immunohistochemical staining and semiquantification, we evaluated the relationship between CLDN12 expression and clinicopathological parameters in tissues from 138 cases of cervical cancer. Results: Western blot and immunohistochemical analyses revealed that the established mAb selectively recognized the CLDN12 protein. Twenty six of the 138 cases (18.8%) showed low CLDN12 expression, and the disease-specific survival (DSS) and recurrence-free survival rates were significantly decreased compared with those in the high CLDN12 expression group. We also demonstrated, via univariable and multivariable analyses, that the low CLDN12 expression represents a significant prognostic factor for the DSS of cervical cancer patients (HR 3.412, p = 0.002 and HR 2.615, p = 0.029, respectively). Conclusions: It can be concluded that a reduced CLDN12 expression predicts a poor outcome for cervical cancer. The novel anti-CLDN12 mAb could be a valuable tool to evaluate the biological relevance of the CLDN12 expression in diverse cancer types and other diseases.

We developed a lanthanum-doped Pb(Zr0.4,Ti0.6)O3 (PLZT)-based ferroelectric capacitor for low-voltage operation of ferroelectric memory for use in edge devices in the internet of things. The structure, consisting of PLZT stacked layers 30 and 90 nm thick, showed drastically improved performance in three main measures: low leakage current, high saturation polarization, and low saturation voltage. Secondary ion mass spectroscopy indicated that atomic interdiffusion between PLZT and IrOx in the top electrode (TE) was suppressed by the 30 nm thick PLZT, which plays the role of a diffusion barrier, producing a low leakage current and high saturation polarization. The higher oxygen atomic density of the PLZT near the TE interface lowers the oxygen vacancy, which should also suppress the leakage current and the P–V hysteresis shift (imprint). The large grain size and high crystalline quality of PLZT near the TE interface in the PLZT structure provide a high saturation polarization with low leakage current.

It is well known that tumour initiation and progression are primarily an accumulation of genetic mutations. The mutation status of a tumour may predict prognosis and enable better selection of targeted therapies. In the current study, we analysed a total of 55 surgical tumours from stage IB-IIB cervical cancer (CC) patients who had undergone radical hysterectomy including pelvic lymphadenectomy, using a cancer panel covering 50 highly mutated tumorigenesis-related genes. In 35 patients (63.6%), a total 52 mutations were detected (58.3% in squamous cell carcinoma, 73.7% in adenocarcinoma), mostly in PIK3CA (34.5%) and KRAS and TP53 (9.1%). Being mutation-positive was significantly correlated with pelvic lymph node (PLN) metastasis (P = 0.035) and tended to have a worse overall survival (P = 0.076). In particular, in the patients with squamous cell carcinoma, there was a significant association between being mutation-positive and relapse-free survival (P = 0.041). The patients with PLN metastasis had a significantly worse overall survival than those without (P = 0.006). These results indicate that somatic mutation status is a predictive biomarker for PLN metastasis in early-stage CC, and is consequently related to poor prognosis. Therefore, comprehensive genetic mutations, rather than a single genetic mutation, should be examined widely in order to identify novel genetic indicators with clinical usefulness.

Simple Summary The claudin (CLDN) family, the backbone of tight junctions, consists of more than 20 members in humans, and exhibits distinct expression patterns in tissue- and cell-type-specific manners. Among the CLDN members, CLDN6 is primarily expressed in diverse embryonic epithelial cells. It is also aberrantly expressed in various types of cancers, but its significance remains obscure. In the present study, we generated a highly specific anti-human CLDN6 monoclonal antibody, and assessed the prognostic significance of aberrant CLDN6 expression in endometrial cancer tissues. This study indicates that high CLDN6 expression in endometrial cancer relates to several clinicopathological factors and is an independent prognostic factor. The established monoclonal antibody could be a valuable tool to evaluate CLDN6-expressing tumors. Abstract Background: Among the claudin (CLDN) family, CLDN6 exhibits aberrant expression in various cancers, but its biological relevance has not yet been established. We generated a monoclonal antibody (mAb) against human CLDN6 and verified its specificity. By immunohistochemical staining and semi-quantification, we evaluated the relationship between CLDN6 expression and clinicopathological parameters in tissues from 173 cases of endometrial cancer. Results: The established mAb selectively recognized CLDN6 protein. Ten of the 173 cases (5.8%) showed high CLDN6 expression (score 3+), whereas 19 (11.0%), 18 (10.4%) and 126 (72.4%) cases revealed low CLDN6 expression (score 2+, 1+ and 0, respectively). In addition, intratumor heterogeneity of CLDN6 expression was observed even in the cases with high CLDN6 expression. The 5-year survival rates in the high and low CLDN6 groups was approximately 30% and 90%, respectively. Among the clinicopathological factors, the high CLDN6 expression was significantly associated with surgical stage III/IV, histological type, histological grade 3, lymphovascular space involvement, lymph node metastasis and distant metastasis. Furthermore, the high CLDN6 expression was an independent prognostic marker for overall survival of endometrial cancer patients (hazard ratio 3.50, p = 0.014). Conclusions: It can be concluded that aberrant CLDN6 expression is useful to predict poor outcome for endometrial cancer and might be a promising therapeutic target.

Cell adhesion proteins not only maintain tissue integrity but also possess signaling abilities to organize diverse cellular events in physiological and pathological processes; however, the underlying mechanism remains obscure. Among cell adhesion molecules, the claudin (CLDN) family often possesses aberrant expression in various cancers, but the biological relevance and molecular basis have not yet been established. Here, we show that high CLDN6 expression promotes endometrial cancer progression and represents the poor prognostic marker. The second extracellular domain and Y196/200 of CLDN6 were required to recruit and activate Src-family kinases (SFKs) and to stimulate malignant phenotypes. Importantly, we demonstrate that the CLDN6/SFK/PI3K-dependent AKT and SGK (serum- and glucocorticoid-regulated kinase) signalings target Ser518 in the human estrogen receptor α and ligand-independently activate target genes in endometrial cancer cells, resulting in cancer development. The identification of this machinery highlights regulation of the transcription factors by cell adhesion to advance tumor progression.

Study Objective To evaluate a unique learning system for uterine artery embolization (UAE) and examine its feasibility and clinical outcomes for the treatment of symptomatic uterine leiomyomas and adenomyosis when performed by obstetrician-gynecologists in cooperation with interventional radiologists (IVRs). Design Retrospective study (Canadian Task Force classification II-2). Setting University hospital. Patients One hundred seventy-three patients who underwent UAE for symptomatic leiomyomas and adenomyosis. Interventions We examined the medical records of patients who underwent UAE for symptomatic uterine leiomyomas and adenomyosis at our department between 2003 and 2012 using our learning system for UAE for obstetrician-gynecologists in cooperation with IVRs. The charts of all patients were reviewed, and data on etiologic factors, past medical history of leiomyomas and adenomyosis, symptoms, details of UAE, and clinical outcomes after UAE were extracted. Measurements and Main Results A total of 173 patients who underwent 177 UAEs were identified, including 4 patients who underwent embolization twice because of primary treatment failure or symptom recurrence. During the study period, 2 gynecologists successfully acquired endovascular skills. The technical success rate was 97.7% (174 of 177). The duration of fluoroscopy in procedures performed by obstetrician-gynecologists who acquired endovascular skills was not significantly different from that in procedures performed by IVRs at our institution; however, this duration was significantly longer in procedures performed by obstetrician-gynecologists who did not have sufficient experience with our learning protocol for UAE because of inadequate live observation of UAEs performed by skilled IVRs. Complications that necessitated discontinuation of the procedure occurred in 2.3% of cases (4 of 177). The clinical outcomes were similar to those reported in previous studies. Adverse events after UAE included myeloid passages in 7.0% (11 of 158), infections in 2.5% (4 of 158), vaginal discharge in 2.5% of patients with leiomyomas (4 of 158), and vaginal discharge in 7.1% of patients with adenomyosis (1 of 14). All the adverse events were adequately treated by the obstetrician-gynecologists themselves. The timing of hysterectomy due to complications or recurrence of symptoms after UAE varied widely. Conclusion UAE performed by obstetrician-gynecologists in cooperation with radiologists can be achieved safely and successfully with acceptable clinical outcomes. Live observation of the procedure performed by skilled IVRs is essential to improving the skills and reducing the fluoroscopic time of obstetrician-gynecologists.

Highlights • Comprehensive somatic mutations profiling in endometrial carcinoma. • Relationships between somatic mutations and clinicopathological characteristics. • Relatiohship between FBXW7 mutation and vascular invasion in endometrial carcinoma. • FGFR2 mutations are related with deep myometrial invasion in endometrial carcinoma., Purpose Endometrial carcinoma (EC) is a clinically heterogeneous disease characterized by a number of different histological subtypes, and its heterogeneity may be involved in the accumulation of multiple genetic alterations. The aim of this work was to investigate the comprehensive mutational profile of EC tumors, and examine the associations between somatic mutations and clinicopathological features or survival in EC patients. Methods A total of 100 surgical tumors were obtained from EC patients who had previously undergone surgery. Genomic DNA samples extracted from fresh-frozen tissues were analyzed using the Ion AmpliSeq Cancer Hotspot Panel v2 Kit, covering 50 tumor-related genes. Results Validated mutations were detected in 91 of the 100 tumors (91%) and identified in eight of the most frequently mutated genes, namely PTEN (57%), PIK3CA (51%), TP53 (30%), KRAS (23%), CTNNB1 (21%), FBFR2 (13%), FBXW7(10%) and RB1 (9%). PTEN mutations were found to associated with young age (< 60), early-stage, endometrioid histology, non-recurrence and better overall survival (OS). CTNNB1 mutations were associated with young age, endometrioid histology and better OS. On the other hands, TP53 mutations were associated with late-stage, non-endometrioid histology, high-grade, recurrence and worse OS. FBWX7 mutations were associated with late-stage, vascular invasion and lymph node metastasis. FGFR2 mutations correlated with deep (≥ 1/2) myometrial invasion. Conclusion Our comprehensive mutational profile will be useful for understanding and evaluating the molecular characteristics of EC tumors, and may lead to the establishment of novel treatment strategies that improve the survival of patients with EC in the future.

The authors wish to make the following correction to this paper [...]

Lymphovascular space invasion (LVSI) is considered to be the beginning of lymphogenous and hematogenous metastases. It is strongly related to dissemination, and therefore could be a valuable predictive sign of lymph node metastases and distant spread. Recently, the presence of LVSI in endometrial cancer (EC) has been shown to be an independent prognostic factor. The preoperative diagnosis of LVSI by pathological examination is difficult and LVSI is detected after surgery. The aim of the current study was to explore candidate genes as potential diagnostic biomarkers and determine whether they are predictors of LVSI in patients with EC. A total of 88 surgical specimens obtained from EC patients who had undergone surgical resection at Fukushima Medical University Hospital between 2010 and 2015 were analyzed using DNA microarray. LVSI was significantly associated with poor prognostic factors in EC such as higher tumor grade, lymph node metastasis, deep myometrium invasion, advanced stage and recurrence. Fifty-five candidate genes were significantly differentially expressed between 26 LVSI-positive and 62 LVSI-negative samples. All 88 samples were divided into two groups according to hierarchical clustering of 55 genes. Regarding diagnostic accuracy, sensitivity and negative predictive value were both high (92% and 95%, respectively); further, specificity and positive predictive value were both moderate (63% and 71%, respectively). Our data suggests that the 55-gene signature could contribute to predicting LVSI in EC, and provide clinically important information for better management. The molecular signatures of 55 genes may be also useful for understanding the underlying mechanism of LVSI.

We reconstruct the interface between ferroelectric (FE) lanthanum-doped lead zirconate titanate (PLZT) and an iridium oxide (IrOx) top electrode (TE), taking advantage of the interdiffusion of Ir and Pb during postdeposition annealing. The tetragonal perovskite phase with a low c/a axis ratio at the IrOx/PLZT interface is observed by X-ray diffraction. It is suggested that the low c/a axis ratio in the interfacial layer is due to the effect of diffusion of Ir from the TE-IrOx. It is also considered that the low c/a axis ratio interfacial layer functions as a nucleation layer for reversal of polarization, thereby achieving a low coercive electric field. The formation of the interfacial layer is very sensitive to the O2 content of the Ar/O2 atmosphere during TE-IrOx deposition. Although an optimized Ar/O2 ratio achieves excellent polarization characteristics (high polarization value and low coercive field), the optimum Ar/O2 region is very narrow at around 36% O2. In other Ar/O2 regions, a pyrochlore phase is formed at the interface owing to interdiffusion of the TE and FE films, and polarization characteristics deteriorate.

Highlights • Sclerosing stromal tumor (SST) is an extremely rare benign tumor of the ovary and preoperative diagnosis of SST is difficult as it often mimics a malignant tumor. • SST occurs in young women. • Many cases of SST were treated by abdominal oophorectomy and laparoscopic surgery is seldom performed in SST cases. • We report a case of SST of the ovary in an 18-year-old girl who was diagnosed by preoperative imaging and underwent laparoscopic cystectomy., Sclerosing stromal tumor (SST) is an extremely rare benign tumor of the ovary that is derived from the sex cord stroma [1,2] and occurs in young women [3–11]. Preoperative diagnosis of the tumor is difficult as it often mimics a malignant tumor. Oophorectomy is usually performed in many cases of young women [3], and diagnosis of SST is made based on post-operative pathological examination. Laparoscopic surgery is seldom performed in SST cases. Here, we report a case of SST of the ovary in an 18-year-old girl who was diagnosed by preoperative imaging and underwent laparoscopic cystectomy. Accurate preoperative imaging helped to perform minimally invasive surgery for SST.

Study Objective To describe the incidence of uterine vascular malformations (UVMs) including uterine arteriovenous malformations (AVMs) in patients after abortion or delivery and in outpatients. Design Prospective study (Canadian Task Force classification II-3). Setting Fukushima Red Cross Hospital. Patients Six patients with a UVM including 1 with an AVM. Interventions Clinical screening of patients using transvaginal color Doppler ultrasonography between April 2010 and March 2012. Measurements and Main Results The incidence of UVM developing after abortion or delivery or in outpatients was prospectively evaluated using transvaginal color Doppler ultrasonography. From 959 patients, we identified 6 (0.63%) with UVMs, including 1 (0.10%) with a uterine AVM. Specifically, we detected UVMs in 4 of 77 patients (5.2%) after abortion, 1 of 458 patients (0.22%) after delivery, and 1 of 424 outpatients (0.24%). Four patients after abortion and 1 after delivery reported mild symptoms, which were treated conservatively; however, the outpatient had a severe uterine AVM, which was confirmed via 3-dimensional computed tomography angiography. Conclusion The incidence of UVMs was relatively higher, in particular in the patients after abortion, and was significantly higher than that in postpartum or outpatient groups. Therefore, it is important to consider the possibility of UVMs in any patient with episodes of unexplained uterine bleeding and to perform follow-up analysis using color Doppler ultrasonography. Such an approach will facilitate accurate diagnosis and lead to appropriate clinical management to prevent unnecessary dangerous repeat curettage, which might induce profuse uterine bleeding.

Although ferroelectric random access memory (FRAM) has superior electric properties, its downside is that it has a relatively larger cell area in comparison other non-volatile memories. We tried to apply TiOx, and AlOx to an underlying layer (TiOx-UL, AlOx-UL) instead of our previously used Ti underlying layer (Ti-UL) for the La-doped lead zirconate titanate (PLZT) capacitor to obtain a high polarization value aiming to a lowering cell area. The failed bit ratio of the FRAM with TiOx-UL was found to be higher than that with AlOx-UL even though polarization values of the PLZT capacitor with both underlying layers are almost the same and much higher than that with Ti-UL. It is strongly suggested that the imprint induced in PLZT by charged defect is a main cause of bit failure by fail-bit analysis. X-ray diffraction and atomic force microscopy observations shows that charged defect density in PLZT over TiOx-UL is possibly higher than that in PLZT over AlOx-UL due to surface roughness of underlying layers.

Ferroelectric random access memory (FRAM) has been commercialized for about 20 years and its reliability has been well proven all over the world. In the recent Internet of Things (IoT) era, it also plays important roles to particularly in edge computing because of its high writing speed, high rewriting endurance, and low writing energy consumption. We review the history of semiconductor memories using ferroelectrics and overview the progresses of the new ferroelectrics and promising ferroelectric applications in the future.

In our previous works on La-doped Pb(Zr,Ti)O3 (PLZT) growth on a Pt/Ti bottom electrode, the O2 content in postdeposition annealing (PDA) was found to play an important role in obtaining good electrical characteristics and high manufacturing yield of ferroelectric random access memory (FeRAM). The optimal O2 content of around 2% inhibits the growth of randomly oriented La-doped Pb(Zr,Ti)O3 (PLZT) grains near the PLZT surface, resulting in the growth of highly {111}-oriented PLZT. We found that the Pt bottom electrode grown on an AlO x layer can further suppress the formation of randomly oriented PLZT grains near the PLZT surface and increases the optimal O2 content range from 2 to 50%, which can enlarge the manufacturing process margin of PDA. It is proven that the AlO x layer blocks the diffusion of lead oxides (PbO x ) from PLZT to SiO2 interlayers through Pt and promotes pyrochlore-perovskite transformation near the bottom electrode during PDA.

Advanced input/output (I/O) technology is reported for leading-edge system on a chip (SoC) applications, including high-speed I/O and RF circuits. Our device having a laterally modulated channel shows sufficient reliability even at 3.3 V operation with the same size as a conventional 2.5 V device. Since this technology also improves current drivability, the layout area of an I/O circuit block can be reduced down to 55% because of a reduced total gate width. Moreover, a metal-on-gate (MOG) option has been developed for RF applications, and an fmax of 55 GHz was achieved.

A polymetal dual gate dynamic random access memory (DRAM) for application specific memory (ASM) with dual nitrogen concentrated oxynitrides was developed for the first time. This technology uses selective nitrogen implantation performed just after gate oxidation. The nitrogen concentration of p-type metal oxide semiconductor (PMOS) in gate dielectric combined with nitrogen implantation and NO (nitric oxide) annealing is sufficiently high to suppress boron penetration, whereas that of the cell array transistor (cell-Tr) and n-type metal oxide semiconductor (NMOS) is sufficiently low to maintain the threshold voltage (Vth) without increasing the channel dosage by using only NO annealing.

An exact solution procedure is presented for solving axisymmetric free vibrations of laminated composite conical shells with varying thickness. Based on the classical lamination theory neglecting shear deformation and rotary inertia, equations of motion and boundary conditions are obtained from the stationary conditions of the Lagrangian. The equations of motion are solved exactly by using a power series expansion for symmetrically laminated, cross-ply conical shells. Numerical studies are made for conical shells having both ends clamped to show the effects of the number of laminae, stacking sequences and other parameters upon the frequencies.

A drive-current enhancement in NMOS with a compressively strained SiGe structure, which had been a difficult challenge for CMOS integration with strained SiGe high-hole-mobility PMOS, was successfully achieved using a Si-SiGe heterostructure low electric field channel of optimum thickness. A 4-nm-thick Si low-field-channel NMOS with a 4-nm-thick Si/sub 0.8/Ge/sub 0.2/ layer improved drive current by 10% with a 20% reduction in gate leakage current compared with Si-control, while suppressing threshold-voltage rolloff characteristic degradation, and demonstrated excellent I/sub on/--I/sub off/ characteristics of I/sub on/ = 1 mA//spl mu/m for I/sub off/ = 100 nA//spl mu/m. These results are the best in ever reported NMOS with a compressively strained SiGe structure and indicate that a Si-SiGe heterostructure low-field-channel NMOS integrated with a compressively strained SiGe channel PMOS is a promising candidate for high-speed CMOS in 65-nm node logic technology.

Silicon-on-insulator devices have problems with both performance and cost. We developed three advanced devices on bonded SOI produced using pulse-field-assisted bonding and selective polishing in an attempt to solve these problems. We tightly bonded highly implanted wafers, epitaxial wafers, and wafers covered with smoothed CVD oxide at temperatures below 1000 o C. We uniformly thinned bonded wafers by grinding, polishing, resistivity-sensitive etching, or selective polishing. We formed buried layers and buried electrodes by bonding and polishing techniques. Our high speed epitaxial-base transistor on 1-μm thick SOI has a cutoff frequency of 32 GHz

Silicon-on-insulator devices have problems with both performance and cost. We developed three advanced devices on bonded SOI produced using pulse-field-assisted bonding and selective polishing in an attempt to solve these problems. We tightly bonded highly implanted wafers, epitaxial wafers, and wafers covered with smoothed CVD oxide at temperatures below 1000 o C. We uniformly thinned bonded wafers by grinding, polishing, resistivity-sensitive etching, or selective polishing. We formed buried layers and buried electrodes by bonding and polishing techniques. Our high speed epitaxial-base transistor on 1-μm thick SOI has a cutoff frequency of 32 GHz