Carcinosarcoma of the uterus, derived from subserous cystic adenomyosis, presenting as an acute abdomen: A case report and review of the literature.

When a woman presents with an acute abdomen with cystic lesions in the abdominal cavity, the differential diagnosis includes torsion or rupture of an ovarian tumor. We report our experience with a 54-year-old nulliparous woman who underwent emergency surgery for a suspected ruptured ovarian tumor. Intraoperative examination revealed disruption of a cystic tumor that had developed externally from the fundus of the uterus. The patient, who was taking aspirin because of a history of medullary infarction, reported lower abdominal discomfort for several days. When she sought care, she was referred to the gynecology department where transvaginal ultrasonography and contrast-enhanced computed tomography showed a poorly toned mass with a maximum diameter of 20 cm posterior to the uterus. She also had a large amount of ascites reaching around the liver and the spleen. She underwent an emergency laparotomy for a presumed diagnosis of acute abdomen caused by a ruptured ovarian tumor with intra-abdominal bleeding. Intraoperative examination revealed normal adnexae bilaterally, but there was a cystic tumor in the pouch of Douglas that was strongly adherent to the surrounding intestines. This mass was connected to the posterior uterus by a stalk and appeared to be continuous with the uterine tissue. The postoperative pathological diagnosis was carcinosarcoma derived from subserous cystic adenomyosis. This is the first case report of carcinosarcoma developing from subserous cystic adenomyosis in the English literature as far as we know.

Efficacy and Adverse Events of Carboplatin Desensitisation Therapy for Gynaecological Cancer: A Retrospective Study.

BACKGROUND: Carboplatin, the key drug used in treating gynaecological cancer, has an approximately 12-16% risk of hypersensitivity reactions. We aimed to investigate the efficacy and adverse effects of carboplatin desensitisation therapy for gynaecological cancer. METHODS: The desensitisation protocol was standardised as a four-step, 4-h, carboplatin administration in the hospital. A retrospective medical record review was conducted on 15 patients who underwent carboplatin desensitisation for gynaecological malignancies at our hospital. Patients' data were analysed to evaluate the treatment success rate, therapeutic effect of desensitisation, adverse events, and treatment. RESULTS: Of 91 carboplatin desensitisation cycles scheduled; the completion rate was 93.4% (85/91). Adverse events occurred in 23 of these 91 (25.3%). In four (4.4%) of the 23 cycles, hypersensitivity reactions could be treated only by discontinuing the infusion and slowing the administration, while in the remaining 19 (20.9%), medication was administered intravenously after discontinuing the infusion to manage hypersensitivity reactions. No treatment-related deaths occurred. Overall, 23 series of anti-cancer agent regimens, including carboplatin desensitisation, were administered to the 15 patients. The therapeutic response rate was 82.6% and the disease control rate was 95.7%. CONCLUSIONS: Carboplatin desensitisation was beneficial in patients with a history of carboplatin-induced hypersensitivity reactions.

Ovarian dysgerminoma with a metastasis to para-aortic lymph node.

We present a case of dysgerminoma of the right adnexa with an infiltration to the right wall of the uterus and a metastasis of para-aortic lymph node.

Goblet cell carcinoma of appendix detected during surgery for ovarian tumors.

An appendectomy with a thorough examination of the gastrointestinal tract should be performed in women with a mucinous ovarian tumor.

Uterine leiomyosarcomas with osteoclast-like giant cells associated with high expression of RUNX2 and RANKL.

Uterine leiomyosarcoma (ULMS) with osteoclast-like giant cells (OLGCs) has been reported as a rare phenomenon in ULMS, and its clinico-pathological features and tumorigenesis remain unclear. We recently reported high expression of receptor activator of nuclear factor κB ligand (RANKL) in ULMS with OLGCs. As osteoblasts produce RANKL, in this study, we analyzed the expression of Runt-related transcription factor 2 (RUNX2), a critical transcription factor for osteoblasts, and osteoclast-related proteins in three cases of ULMS with OLGCs as well as five conventional ULMSs and nine leiomyomas. Immunohistochemistry and real-time reverse transcription quantitative polymerase chain reaction analyses showed high expression of RUNX2 and RANKL in ULMS with OLGCs. In these cases, macrophages expressed receptor activator of nuclear factor κB (RANK), and OLGCs expressed osteoclast-related proteins (nuclear factor of activated T cells, cytoplasmic 1 (NFATc1), and cathepsin K). Accumulation sites of cathepsin K-positive OLGCs showed hemorrhagic appearance and degraded type IV collagen. We reviewed reported cases of ULMS with OLGCs, including ours, and found that they presented an aggressive course even at stage I. Furthermore, metastatic lesions showed similar histological features to those of OLGC association in ULMS. Here, we show that tumor cells in ULMS with OLGCs highly express RUNX2 and RANKL and that osteoclastic differentiation of macrophages occurs in the tumor tissue.

Serum CA 125 Level after Neoadjuvant Chemotherapy is Predictive of Prognosis and Debulking Surgery Outcomes in Advanced Epithelial Ovarian Cancer.

Recently, neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) has been recommended for selected patients with International Federation of Gynecology and Obstetrics (FIGO) stage III or IV disease and bulky tumors. The aim of this study was to evaluate associations between post-NACT serum CA 125 levels, surgical outcomes, and clinical outcomes in patients with advanced epithelial ovarian cancer. We retrospectively analyzed 107 patients with FIGO stage III or IV ovarian cancer who were treated with NACT-IDS at the Gynecology Department of Kanagawa Cancer Center between January 2001 and December 2012. Serum CA 125 levels after NACT were significantly lower in the complete/optimal IDS group compared to the suboptimal IDS group (mean±standard deviation: 48.1±27.6 vs. 346.5±295.2 U/mL, p<0.01). Patients with low preoperative CA 125 levels (<35 U/mL) had a higher probability of optimal IDS (78.1±41.9% vs. 33.3±19.2%, p<0.01) and longer progression-free survival (mean±standard deviation: 30.4±14.3 months vs. 21.3±7.3 months, p<0.05) than patients with high CA 125 levels (>100 U/mL). Patients with low CA 125 levels (<35 U/mL) had a higher probability of complete/optimal IDS and longer progression-free survival compared to patients with high CA 125 levels (>100 U/mL).

Pregnancy-associated Deaths: 31-year Experience.

AIM: The aim of the present study was to elucidate the clinical characteristics of pregnancy-associated maternal deaths. METHODS: We performed a retrospective analysis with medical records and autopsy reports of cases of pregnancy-associated deaths. We collected information on all maternal deaths related to pregnancy that occurred in 3 hospitals affiliated with Nippon Medical School in Japan from January 1, 1984, to December 31, 2014. Data analyzed were maternal age, past medical history, parity, gestational age, clinical signs and symptoms, cause of death, and maternal autopsy findings. RESULTS: A total of 26 maternal deaths occurred during the 31-year study period. Autopsies were performed for 16 patients (61.5%). The 26 deaths included 19 (73.1%) classified as direct maternal deaths and 7 (26.9%) classified as indirect maternal deaths. The mean maternal age at death was 33.1±4.3 years (range, 26-41 years). The highest percentage of women was aged 35 to 39 years (38.5%). Of the 26 maternal deaths, 69% occurred at 32 to 41 weeks of gestation. In cases of direct maternal death, the leading causes were amniotic fluid embolism (7 cases, 27.0% of all deaths) and hemorrhage (6 cases, 23.1% of all deaths). In cases of indirect obstetric deaths, the causes included cardiovascular disorders, cerebrovascular disorders, sepsis due to group A streptococcal infection, and hepatic failure of unknown etiology. CONCLUSIONS: Amniotic fluid embolism was the leading cause of maternal deaths and was followed by obstetric hemorrhage. To prevent and reduce the number of maternal deaths in Japan, further basic and clinical research on amniotic fluid embolism is required.

miR-200a, miR-200b and miR-429 are onco-miRs that target the PTEN gene in endometrioid endometrial carcinoma.

Endometrioid endometrial carcinoma (EEC) is a common malignancy of the female genital tract. However, no adequate biomarker is currently available for predicting the prognosis of this cancer. Recent studies have revealed dysregulated expression of several microRNAs (miRNAs) in various cancer tissues, and therefore, these cancer-associated miRNAs (also called onco-miRs) could be promising prognostic biomarkers of cancer progression or metastasis. In this study, in order to identify onco-miRs and their possible targets involved in EEC, we performed microarray-based integrative analyses of miRNA and mRNA expression in specimens excised from EEC lesions and adjacent normal endometrial tissues. Using integrated statistical analyses, we identified miR-200a, miR-200b and miR-429 as highly up-regulated onco-miRs in EECs. Conversely, we detected expression of a tumor-suppressor gene, phosphatase and tensin homolog (PTEN), which was predicted in silico using a miRNA-targeting mRNA prediction algorithm, as a target of the three miRNAs and which was down-regulated in EECs. Furthermore, these miRNAs were validated to target PTEN experimentally using luciferase assays and real-time polymerase chain reaction. These results suggest that the occurrence of EEC is, at least in part, mediated by miRNA-induced suppression of PTEN expression.

Proteomic identification of autoantibodies in sera from patients with ovarian cancer as possible diagnostic biomarkers.

BACKGROUND/AIM: Accumulating evidence shows that various types of cancers induce a specific immune response resulting in the production of antibodies against self-components (autoantibodies). The aim of the present study was to identify antigens for autoantibodies in sera from patients with ovarian cancer, especially clear cell carcinoma (CCC), as novel diagnostic markers for the disease. MATERIALS AND METHODS: The reactivity of individual sera from patients was examined by two-dimensional (2-D) immunoblotting using lysates of CCC cell lines, ES-2 and RMG-1, as antigens to identify autoantigens. ELISA was established to quantitatively measure autoantibody titer of patients' sera. RESULTS: Autoantibodies against RhoGDI were induced in sera of ovarian cancer patients. Elevated levels of autoantibodies against heterogeneous nuclear ribonucleoprotein L (hnRNPL) and a mitochondrial protein, dihydrolipoamide dehydrogenase (DLD), were detected in patients with CCC. CONCLUSION: Autoantibodies against RhoGDI and hnRNPL and DLD may serve as novel diagnostic markers for ovarian cancer and CCC, respectively.

Proteomic identification of dihydrolipoamide dehydrogenase as a target of autoantibodies in patients with endometrial cancer.

BACKGROUND/AIM: Accumulating evidence shows that various types of cancers induce a specific immune response, resulting in the production of antibodies against self-components (autoantibodies). The aim of the present study was to identify antigens for autoantibodies in sera from endometrial cancer patients as novel diagnostic markers for the disease. MATERIALS AND METHODS: The reactivity of individual sera from patients was examined by 2-dimensional (2-D) immunoblotting using HeLa cell lysates as antigens to identify autoantigens. ELISA was established to quantitatively measure autoantibody titer of patients' sera. RESULTS: A mitochondrial protein, dihydrolipoamide dehydrogenase (DLD), was identified as an autoantigen specific to endometrial cancer patients. The levels of immunoglobulin (Ig)A but not IgG autoantibody to DLD were significantly increased in the sera of endometrial cancer patients. CONCLUSION: IgA autoantibody against DLD could be a novel diagnostic marker for endometrial cancer.

Clinical characteristics of amniotic fluid embolism: an experience of 29 years.

AIM: The aim of this study was to elucidate the clinical characteristics and risk factors for amniotic fluid embolism (AFE). METHODS: We performed a retrospective case study analysis of patients using medical records and autopsy records. The diagnosis of AFE was based on the presence of clinical symptoms using Clark's criteria and autopsy results. We analyzed patient records from a 29-year period in three hospitals affiliated with the Nippon Medical School in Japan. RESULTS: Ten diagnoses of AFE were found in the records. First, we classified AFE patients into two types based on the initial presenting symptoms: post-partum hemorrhage and cardiopulmonary collapse. Fifty percent of the patients initially presented with post-partum hemorrhage and disseminated intravascular coagulation. Most were diagnosed with post-partum hemorrhage or uterine atony at AFE onset. Similarly, 50% presented with cardiopulmonary arrest or pulmonary arrest as initial symptoms, and most were diagnosed with eclampsia. Second, risk factors for AFE included advanced maternal age, multiparity, increased intrauterine pressure and disruptions of the uterine vasculature. Third, the case fatality rate was 70%. Fourth, squamous cells were observed in maternal central venous blood of five patients. CONCLUSION: AFE patients were classified into two types based on presenting signs and symptoms. Knowledge of the various initial symptoms of AFE enables a correct diagnosis.

Expression of fibroblast growth factor receptor 2 IIIc in human uterine cervical intraepithelial neoplasia and cervical cancer.

Fibroblast growth factor receptors (FGFRs) 1-3 have IIIb and IIIc isoforms, and we reported that FGFR2 IIIb is highly expressed in cervical keratinizing squamous cell carcinoma (SCC). In this study, we determined the expression and roles of FGFR2 IIIc in cervical intraepithelial neoplasia (CIN) and cervical cancer. In CINs 1 and 2, FGFR2 IIIc was found to be localized at the basal to lower two-thirds of the squamous epithelium, whereas it was localized in most of the squamous epithelium, except for the superficial layer in CIN 3. In situ hybridization (ISH) analysis showed that the expression patterns of FGFR2 IIIc mRNA are similar to those of FGFR2 IIIc protein in CINs. The FGFR2 IIIc protein was detected in all invasive cervical cancer patients (29 cases) and its mRNA was found to be strongly expressed in the invasive front of cancer cell nests. FGFR2 IIIc cDNA was stably transfected into CaSki cells, which are derived from a cervical SCC. The growth rates of the CaSki cells were higher than those of Mock cells in vitro, and the CaSki cells tended to form larger subcutaneous tumors in nude mice. These findings suggest that FGFR2 IIIc plays important roles in carcinogenesis and growth of cervical cancer cells. Anti-FGFR2 IIIc therapies may represent therapeutic strategies for inhibiting the growth of CIN and cervical cancer.

Effect of insulin resistance improvement due to lifestyle intervention on overweight perimenopausal Japanese women: a preliminary study.

OBJECTIVE: We hypothesized that body composition and biomarkers of menopausal obesity would be affected by administration of a nutrition and exercise regimen. To test this hypothesis, an interventional study was performed in which perimenopausal subjects increased their daily level of physical activity and decreased their daily caloric intake for a period of 12 weeks. METHOD: Nine patients with a chief complaint of obesity and menopausal disorders were enrolled in this study. We prescribed that the subjects engage in the daily physical activity of walking more than 10,000 steps, which is equivalent to 150 to 400 kcal per day, and reduce their daily nutritional intake by 200 kcal. Daily physical activity was measured with a computerized accelerometer, and nutrition intake was measured using food frequency questionnaires. Body composition was measured via biophysical impedance analysis. Biochemical examinations were performed before and after the study. As an assessment of glucose tolerance, homeostasis model assessment-insulin resistance (HOMA-IR) values were measured. RESULTS: There were no significant changes in weight, body mass index, or body composition after 12 weeks. However, daily physical activity related to energy consumption was slightly but not significantly increased. Six of the nine subjects (66.7%) had abnormal baseline HOMA-IR values (mean 7.0 +/- 2.6; normal upper limit = 1.5) and demonstrated decreases in HOMA-IR values, with an average of 5.2 +/- 2.3 (P <0.05), after 12 weeks of study. CONCLUSION: Our mild intervention on daily physical activity and nutrition changed HOMA-IR values, an assessment of impaired glucose tolerance. These results suggest that longitudinal mild intervention on daily physical activity and nutrition could change insulin sensitivity even without weight reduction.

Simultaneous supraventricular tachycardias in both fetuses of a twin gestation.

BACKGROUND: Fetal supraventricular tachycardia confers an increased risk of cardiac failure, hydrops, and eventual intrauterine death. Although protocols for prenatal anti-arrhythmic treatment are now well established, few published reports discuss this condition in the setting of multiple pregnancies. CASE REPORT: A 20-year-old primigravida woman with a twin pregnancy presented at 31 weeks of gestation for routine obstetrical check-up which revealed simultaneous supraventricular tachycardia in both fetuses. She was treated with oral digoxin, resulting in successful cardioversion in both of the fetuses, which was maintained until they were delivered by caesarian section at 38 weeks gestation. However, several hours after birth, tachyarrhythmias recurred in each of the infants. Combined disopyramide therapy with digoxin was necessary to control their heart rates. CONCLUSION: The treatment of arrhythmia in fetuses of a multiple gestation presents unique issues, particularly when diagnosed prior to fetal lung maturity.