MR Imaging Findings of Carcinoma Ex Pleomorphic Adenoma Related to Extracapsular Invasion and Prognosis.

BACKGROUND AND PURPOSE: MR imaging can reflect the pathologic progression of carcinoma ex pleomorphic adenoma (CXPA). This study aimed to identify the imaging findings related to extracapsular invasion of CXPA. Additionally, the pathologic background of these findings was investigated. MATERIALS AND METHODS: This retrospective study included 37 patients with histologically confirmed CXPA. Three radiologists independently evaluated whether the CXPA showed the following characteristic MR imaging findings: border, capsule, the corona sign on fat-saturated T2WI and contrast-enhanced fat-saturated T1WI, and the black ring sign. The corona sign appeared larger on fat-saturated and/or contrast-enhanced fat-saturated T1WI than on T1WI. The black ring sign was defined as an intratumoral nodule with a thick low-intensity rim on T2WI. Interreader agreement of the visual assessment was performed using κ analysis, and MR imaging and histopathologic findings were also correlated. Kaplan-Meier survival and the log-rank test were used to estimate the 3-year disease-free survival. RESULTS: MR imaging findings, especially peritumoral findings, showed a significant difference between invasive and noninvasive CXPA. The reliability was poor for the border and capsule. In contrast, it was good for the corona sign on fat-saturated and contrast-enhanced fat-saturated T1WI and the black ring sign. Pathologically, the corona sign reflected the invasiveness of the tumor and inflammatory cells, while the black ring sign reflected hyalinization or fibrosis. The corona sign also showed a significant difference in the 3-year disease-free survival. CONCLUSIONS: MR imaging findings, including the corona and black ring signs, reliably differentiated invasive and noninvasive CXPA. The corona sign can be used as a prognostic factor for CXPA.

Enhanced miR-210 expression promotes the pathogenesis of endometriosis through activation of signal transducer and activator of transcription 3.

STUDY QUESTION: What are the roles of the microRNA miR-210-an miRNA that is up-regulated in endometriotic cyst stromal cells (ECSCs)-in the pathogenesis of endometriosis? SUMMARY ANSWER: Up-regulated miR-210 expression in ECSCs is involved in their proliferation, resistance to apoptosis and angiogenesis through signal transducer and activator of transcription (STAT) 3. WHAT IS KNOWN ALREADY: In the pathogenesis of endometriosis, a number of roles for microRNAs (miRNAs) are becoming apparent. STUDY DESIGN, SIZE, DURATION: ECSCs and normal endometrial stromal cells (NESCs) were isolated from ovarian endometriotic tissues (patients aged 24-40 years undergoing salpingo-oophorectomy or evisceration for the treatment of ovarian endometriotic cysts, n = 10) and the eutopic endometrial tissues without endometriosis (premenopausal patients aged 35-45 years undergoing hysterectomies for subserousal leiomyoma, n = 13), respectively. PARTICIPANTS/MATERIALS, SETTING, METHODS: We used a global gene expression microarray technique to identify downstream targets of miR-210, and we assessed the functions of miR-210 in the pathogenesis of endometriosis by using the miR-210-transfected NESCs. MAIN RESULTS AND THE ROLE OF CHANCE: Gene expression microarray analysis revealed that one of the key target molecules of miR-210 is STAT3. In the NESCs, in comparison to the control, miR-210 transfection resulted in the induction of cell proliferation (P < 0.0005), the production of vascular endothelial cell growth factor (VEGF) (P < 0.0005) and the inhibition of apoptosis (P < 0.05) through STAT3 activation [increased levels of mRNA (P < 0.0005), and protein (P < 0.005)]. In the ECSCs, inhibitors of STAT3 inhibited the cell proliferation and VEGF production (P < 0.05), and induced the apoptosis of these cells (P < 0.05). LIMITATIONS, REASONS FOR CAUTION: The roles of aberrant miR-210 expression were investigated only in the stromal component of ectopic and eutopic endometrium. Control endometrial tissues were obtained from premenopausal patients who had subserosal leiomyoma and NESC gene expression patterns may be altered in these women. Furthermore, the effects of STAT3 inhibitors were evaluated only in ECSCs and not in NESCs. WIDER IMPLICATIONS OF THE FINDINGS: The present findings indicate that miR-210 induces NESCs to differentiate into the endometriotic phenotype and we speculate that up-regulated miR-210 expression in ECSCs is involved in the creation of the endometriosis-specific cellular dysfunctions through epigenetic mechanisms. The data indicate that STAT3 inhibitors may be promising candidates for the treatment of endometriosis. STUDY FUNDING/COMPETING INTERESTS: This work was supported in part by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (no. 13237327 to K.N., no. 25861500 to Y.K. and no. 23592407 to H.N.). There are no conflicts of interest to declare.

A case of maxillary sarcoma in a chimpanzee (Pan troglodytes).

Oral malignancy is rare in chimpanzees. A 34-year-old female chimpanzee (Pan troglodytes) at Kumamoto Sanctuary, Japan, had developed it. Treatment is technically difficult for chimpanzees while malignant neoplasm is seemingly rising in captive populations. Widespread expert discussion, guidelines for treatment, especially for great apes in terminal stages is urgently needed.

Malignant lymphoma of the vagina successfully treated with rituximab, adryamicin, cyclophosphamide, vincristine sulfate, and prednisolone.

PURPOSE: Primary malignant lymphoma of the vagina is extremely rare. The most common histologic subtype is diffuse large B-cell lymphoma (DLBCL). We report a case of vaginal DLBCL successfully treated with chemotherapy consisting of rituximab, adryamicin, cyclophosphamide, vincristine sulfate, and prednisolone (R-CHOP), followed by pelvic irradiation. CASE: A 44-year-old Japanese woman was admitted complaining of atypical genital bleeding and puruloid vaginal discharge. Gynecological examination showed an ulceration of the vaginal wall and a hard mass the size of a goose egg beneath the left vaginal wall, which had infiltrated to the left pelvic wall. The pathological diagnosis based on a punch biopsy taken from the vaginal tumor was non-Hodgkin's lymphoma. Based on immunohistochemical study, the tumor was subclassified as activated B-cell type DLBCL. The patient was diagnosed with Ann Arbor Stage IEA DLBCL and Stage III vaginal cancer, according to the International Federation of Gynecologists and Obstetricians (FIGO) classification system. She was successfully treated by six courses of R-CHOP, followed by radiation therapy. The patient is well without evidence of disease 13 months following the initial treatment. CONCLUSION: Little attention has been paid to the use of rituximab in addition to conventional chemotherapy and the importance of clinical and morphological subgrouping of DLBCL arising in the vagina. The present case indicates that the effects of rituximab on the prognosis of vaginal DLBCL must be evaluated, and that clinical use of immunophenotypic subgrouping should be considered for vaginal DLBCL.

Depression and pregnancy-associated death by suicide after spinal cord injury: a case report.

PURPOSE OF INVESTIGATION: To report a case of a pregnant woman with traumatic spinal cord injury complicated with a psychiatric disorder. CASE REPORT: A 24-year-old woman at 18 weeks of gestation was transferred to our hospital with a history of having jumped from a third-floor apartment patio. RESULT: A trauma survey showed no life-threatening hemorrhage, and fetal wellbeing was confirmed. Neurological examination showed complete loss of motor and sensory function in her lower extremities. Termination of pregnancy was advised and was achieved medically. Surgical intervention was performed to achieve stabilization of the spine and decompression of neural elements. After the operation, she was referred to a psychiatrist, and the administration of paroxetine, etizolam and flunitrazepam was begun. Four months after undergoing the abortion, she choked herself to death on her ward bed. CONCLUSION: Although it is rare, we should pay special attention to the substantial suicide risk of women who face severe spinal cord injury.

Primary mucinous adenocarcinoma of the vagina.

PURPOSE: Primary mucinous adenocarcinoma of the vagina is a rare disease which is characterized by aggressiveness and poor prognosis because of its rapid growth and recurrence, its frequent distant metastases, and its relative resistance to conventional treatment modalities including surgery, radiotherapy, and chemotherapy. We report a case of advanced stage primary mucinous adenocarcinoma of the vagina that showed a highly aggressive course and resistance to combination chemotherapy with paclitaxel and carboplatin. CASE: A 46-year-old multigravid Japanese woman was admitted to our hospital to be treated for Stage IVb primary mucinous adenocarcinoma of the vagina. She had no history of in utero exposure to diethylstilbestrol. She was treated by two courses of neoadjuvant chemotherapy with tri-weekly paclitaxel and carboplatin, which were not effective. Subsequently, total pelvic exenteration with pelvic lymphadenectomy was performed. However, the disease progressed rapidly and the patient died five months after the initial treatment. CONCLUSION: Because of its rarity, little is known about the behavior of primary mucinous adenocarcinoma of the vagina. Additional data about patients with this rare tumor should be collected and analyzed in an attempt to elucidate its prognostic factors, characteristics, optimal treatment, and outcome.

Involvement of resistance to apoptosis in the pathogenesis of endometriosis.

Endometriosis, a disease affecting 3-10% of women of reproductive age, is characterized by the ectopic growth of endometrial tissue. Increasingly, endometriosis is also becoming recognized as a condition in which ectopic endometrial cells exhibit abnormal proliferative and apoptotic regulation in response to appropriate stimuli. Apoptosis plays a critical role in maintaining tissue homeostasis and represents a normal function to eliminate excess or dysfunctional cells. Accumulated evidence suggests that, in healthy women, endometrial cells expelled during menstruation do not survive in ectopic locations because of programmed cell death, while decreased apoptosis may lead to the ectopic survival and implantation of these cells, resulting in the development of endometriosis. Both the inability of endometrial cells to transmit a 'death' signal and the ability of endometrial cells to avoid cell death have been associated with increased expression of anti-apoptotic factors and decreased expression of pre-apoptotic factors. This paper is a review of the recent literature focused on the differential expression of apoptosis-associated molecules in the normal endometria of women without endometriosis, and in the eutopic and ectopic endometria of women with endometriosis. The role of apoptosis in the pathogenesis of endometriosis and the basic and clinical research on the current medical treatment for endometriosis from the view of apoptosis will be discussed.

Formation of sp3-bonded carbon nanostructures by femtosecond laser excitation of graphite.

A scanning tunneling microscopy study and ab initio total energy calculations have identified the atomic-level structure of novel sp;{3}-bonded carbon nanoscale domains formed dynamically from graphite by femtosecond-laser excitation. The structure is characterized by a pseudo sp;{3}-bonding configuration that results in inward displacement of surface carbon atoms by 0.5 A in every third row along the [11[over ]00] orientation. This structural periodicity is unique and differs from conventional phases of diamond.

Direct observation of the critical relaxation of polarization clusters in BaTiO3 using a pulsed x-ray laser technique.

We have developed a new method to investigate the relaxation time of the dipole moment in polarization clusters in BaTiO3. Time correlation of speckle intensities was measured by the use of a double pulsed soft x-ray laser. The evolution of the relaxation time of the dipole moment near the Curie temperature (T(C)) was investigated. The maximum relaxation time (approximately 90 ps) is shown to appear at a temperature of 4.5 K above the T(C), being coincident with the one where the maximum polarization takes place. This method is widely applicable to any other critical decay processes at phase transitions.

Bowel obstruction due to endometriosis in the rectovaginal septum.

It is very rare that endometriotic lesions in the rectovaginal septum cause ileus. We report a case of bowel obstruction due to endometriotic lesions in the rectovaginal septum in a 22-year-old woman whose barium enema presented with apple-core-like findings. Diagnostic and treatment modalities were discussed. Preoperative and postoperative gonadotropin-releasing hormone analog and aromatase inhibitor therapy promote relief of clinical symptoms, a reduction of tumor volume and a better approach to radical surgery.

Plaque characterisation by Virtual Histology intravascular ultrasound analysis in patients with type 2 diabetes.

OBJECTIVES: To evaluate the in-vivo plaque composition and characteristics in patients with type 2 diabetes mellitus (DM) using Virtual Histology intravascular ultrasound (VH IVUS). METHODS: In 90 patients with stable angina pectoris, de novo target vessels were studied and plaque components were analysed. Patients were divided into two groups: a diabetic group (36 vessels) and a non-diabetic group (54 vessels). RESULTS: The percentage area of necrotic core and dense calcium were significantly larger in the DM group than the non-DM group (necrotic core: 11.0% (interquartile range (IQR): 7.2-15.2%) vs 7.6% (IQR 5.6-13.2%), p = 0.03; dense calcium: 5.6% (IQR: 2.3-7.3%) vs 2.9% (IQR: 1.7-4.9%), p = 0.01). The DM group presented with a significantly higher presence of at least one VH IVUS-derived thin-cap fibroatheroma (VHD-TCFA) (75% vs 41%, p = 0.001) and VH IVUS-derived fibrocalcific atheroma (VHD-FCA) (75% vs 40%, p = 0.001). In the DM group, 53% of the vessels had both VHD-TCFA and VHD-FCA, which was significantly higher than non-DM group (17%, p = 0.0004). CONCLUSIONS: Coronary plaque characteristics in DM patients showed an increased amount of dense calcium and necrotic core, as well as a higher frequency of VHD-TCFA and VHD-FCA. Atherosclerosis of the target vessel was more advanced in diabetic patients.

Clinical and prognostic significance of cytokine receptor expression in adult acute lymphoblastic leukemia: interleukin-2 receptor alpha-chain predicts a poor prognosis.

We quantitatively assessed the expression of cytokine receptors (interleukin-2 receptor (IL-2R), IL-3R, IL-4R, IL-5R, IL-6R, IL-7R, granulocyte-macrophage colony-stimulating factor R (GM-CSFR), G-CSFR, c-fms, c-mpl, c-kit and FLT3) in cells from 211 adults with acute lymphoblastic leukemia (ALL) by flow cytometry and determined their prevalence and clinical significance. Although all cytokine receptors were expressed to various degrees, the levels of IL-3R alpha-chain (IL-3Ralpha), IL-2Ralpha, IL-2Rbeta, IL-7Ralpha, common-Rgamma(gammac), c-mpl, c-kit and FLT3 exhibited a wide spectrum > or =2000 sites/cell. Among them, IL-3Ralpha, IL-2Ralpha and FLT3 were highly expressed in B-lineage ALL, whereas IL-7Ralpha, gammac and c-kit predominated in T-lineage ALL. Higher levels of IL-3Ralpha, IL-2Ralpha, c-kit and FLT3 correlated with the expression of CD13/33. Increased IL-2Ralpha levels related to the presence of Philadelphia chromosome (Ph), leukocytosis and shorter event-free survival (EFS). C-kit preferred in male. Elevated FLT3 levels correlated with age > or =60 years. Multivariate analysis in B-lineage ALL revealed only IL-2Ralpha (P=0.028) and Ph (P=0.020) as independent factors for EFS. These findings suggest that several cytokine receptors associated with certain cellular and clinical features, but IL-2Ralpha solely had a prognostic value and should be considered as a major prognostic factor for adult ALL that is comparable with Ph.

Human oviductal epithelial cells express Toll-like receptor 3 and respond to double-stranded RNA: Fallopian tube-specific mucosal immunity against viral infection.

BACKGROUND: The aim of this study was to evaluate the site-specific immunoregulatory mechanisms against viral infection in human Fallopian tubes. METHODS: We therefore investigated the effects of double-stranded RNA (dsRNA) on the production of interleukin (IL)-6, IL-8 and granulocyte chemotactic protein-2 (GCP-2) by cultured oviductal epithelial cells (OECs) using enzyme-linked immunosorbent assays. Phosphorylation of inhibitor kappaB-alpha (IkappaB-alpha) protein after dsRNA stimulation and the expression of Toll-like receptor (TLR) 3 in these cells were also evaluated by western blot analysis. RESULTS: Polyriboinosinic:polyribocytidylic acid (poly I:C), a synthetic dsRNA that antagonizes TLR3, stimulated the secretion of IL-6, IL-8 and GCP-2 by OECs. Poly I:C-induced production of these cytokines by OECs was inhibited by the pretreatment of these cells with anti-TLR3 antibody. The phosphorylation of IkappaB-alpha protein was detected in OECs after stimulation by poly I:C. The expression of TLR3 was also detected in OECs. CONCLUSION: These results suggest that the epithelial cells of the human Fallopian tube have evolved a unique, site-specific mechanism for recognizing viral infection. TLR3-mediated production of proinflammatory cytokines and chemokines in OECs in response to viral dsRNA may be important for antiviral immunity in the human female reproductive tract.

Beta-hydroxyisovalerylshikonin induces apoptosis and G0/G1 cell-cycle arrest of endometriotic stromal cells: a preliminary in vitro study.

BACKGROUND: Most of the current medical treatments for endometriosis aim to down-regulate the estrogen activity. However, a high recurrence rate after medical treatments has been the most significant problem. Beta-hydroxyisovalerylshikonin (beta-HIVS) is an ATP non-competitive inhibitor of protein-tyrosine kinases and is considered an apoptosis-inducing agent. The aim of this study is to evaluate the effects of beta-HIVS on the proliferation, cell cycle and apoptosis of endometriotic stromal cells. METHODS: We investigated the effects of beta-HIVS on cultured ovarian endometriotic cyst stromal cells (ECSC) by a modified methylthiazoletetrazolium (MTT) assay, a 5-bromo-2'-deoxyuridine (BrdU) incorporation assay and internucleosomal DNA fragmentation assays. The effect of beta-HIVS on the cell cycle of ECSC was determined by flow cytometry. The expression of apoptosis-related molecules was examined in ECSC using western blot analysis. RESULTS: Beta-HIVS significantly inhibited the proliferation and DNA synthesis of ECSC and induced apoptosis and G0/G1 phase cell-cycle arrest of these cells. Down-regulation of the B-cell lymphoma/leukaemia-2 (Bcl-2) expression with the activation of caspase-3, caspase-8 and caspase-9 was observed in ECSC after beta-HIVS treatment. CONCLUSIONS: These results suggest that beta-HIVS induces apoptosis of ECSC by suppressing anti-apoptotic proteins. Although our present findings are preliminary, beta-HIVS could potentially be a therapeutic agent for the treatment of endometriosis.

EXpression of ErbB proteins in human prostate.

ErbB proteins are widely expressed in human and animal tissues, notably in cells of epithelial or neuroendocrine origin. Protein expression and interactions of ErbBs were examined in prostate cancer specimens. Expression of ErbB1-4 proteins was determined with immunohistochemical methods using each monoclonal antibody in 20 prostatic adenocarcinomas. The 4 ErbB proteins were widely expressed in normal, hyperplastic and cancerous tissues of the prostate. ErbBs may contribute to normal development or tumor growth and progression in human prostate.

Gastrointestinal stromal tumor arising in the rectovaginal septum.

We report herein a rare case of malignant gastrointestinal stromal tumor (GIST) originated from the rectal wall, which presented as a tumor on the rectovaginal septum. A 54-year-old Japanese woman, gravida 4, para 3, was admitted complaining of anuresis and severe constipation. She had a history of hysterectomy and right salpingo-oophorectomy for uterine leiomyoma 11 years previously. Pelvic examination revealed an 8.5 x 7.5 x 7.5 cm hard mass in the rectovaginal space. The inferior border of the tumor was 2 cm from the vaginal introitus and 2 cm from the anus. Computed tomography and magnetic resonance imaging showed a well-circumscribed soft-tissue mass filling the rectovaginal space. Urinary bladder and rectum were markedly compressed and displaced. Colon fiberscopy revealed invasion of the tumor into the rectal mucosa. An abdominoperineal resection of the rectum with posterior vaginal wall resection and pelvic lymphadenectomy was performed. The resected specimen showed a rectal submucosal tumor that was 8 x 8 x 7 cm in size. The tumor was diagnosed as a malignant GIST. Immunohistochemical analysis confirmed this diagnosis. The patient is now healthy without evidence of recurrence at 13 months after surgery. Gynecologists should be aware of rectal GIST arising in the rectovaginal space as a differential diagnosis of vaginal submucosal tumor.