Multiple Somatic Mutations of SMARCA4 in Small Cell Carcinoma of the Ovary, Hypercalcemic Type: A Case Report.

Small-cell carcinoma of the ovary, the hypercalcemic type (SCCOHT) is a rare, aggressive tumor that primarily affects young females. It is a monogenic disorder caused by germline and/or somatic SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4 (SMARCA4) mutations. Here, we report a case of SCCOHT harboring multiple previously unreported somatic mutations in SMARCA4 (c.2866_2867delC>T; c.3543del). A 28-year-old breastfeeding Japanese female presented to a previous hospital with nausea and vomiting. She had no family history of relevant malignancies, including ovarian cancer. Based on an evaluation performed at another institution, she was referred to a gynecologist for suspected ovarian cancer. Imaging studies revealed a 16×15 cm heterogenous enhancing mass within the right ovary without lymph node or distant metastasis. She had mild ascites without peritoneal dissemination, but there was an elevation in the serum calcium level (15.1 mg/dL). The patient underwent cytoreductive surgery and was pathologically diagnosed with SCCOHT. Auxiliary immunohistochemical staining confirmed the loss of SMARCA4 protein expression. The patient was diagnosed with the International Federation of Gynecology and Obstetrics (FIGO) 2014 stage IA (pT1a pN0 M0). The serum calcium levels returned to normal post-surgery. Matched-pair analysis using tumor tissue and peripheral blood revealed multiple somatic mutations in SMARCA4, but no deleterious germline mutations were present. Microsatellite instability was not significant, and the patients had a heterozygous mutation of uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1)*6. She underwent six cycles of irinotecan hydrochloride plus cisplatin chemotherapy and achieved complete remission. The patient was finally examined and evaluated 45 months postoperatively; there was no evidence of the disease. Overall, the genetic findings will not aid in the SCCOHT diagnosis and relevant genetic counseling; however, they may have implications for the treatment of this disease in the future.

Hydrothermal synthesis of layered zirconium phosphates and their intercalation properties.

Layered inorganic materials are widely used as fillers in nanocomposites due to their unique properties such as mechanical performance, thermal properties, flame resistance, barrier properties, corrosion resistance, catalytic activity, and multifunctionality. Among them, layered α-zirconium phosphate (α-ZrP: Zr(HPO4)2H2O) is one of the representative inorganic materials and unique properties with P-O-H groups that can exchange inorganic and organic cations and intercalate basic molecules. This paper deals with the use of this compound as an adsorbent for heavy metal cations in wastewater. Samples were prepared by hydrothermal treatment at various Zr/P ratio, water amounts, and temperatures. Furthermore, an attempt was made to widen the interlayer distance of the sample using n-butylamine. The α- zirconium phosphate prepared at 160°C for 20 h with Zr/P = 1/2 adsorbed the most amount of metal ions. Furthermore, interlayer amine modification was effective. Then, the behaviour of the adsorption process was observed by varying the time of adsorption from 1 h to 50 h, in order to clarify the change in adsorption of the samples over time.

Synthesis of Cobalt-Substituted Manganese Phosphate Purple Pigments.

Some manganese phosphates are known as violet pigments. In this study, pigments in which manganese was partially replaced with cobalt and aluminum was replaced with lanthanum and cerium were synthesized with a heating method to obtain pigments with a more reddish color. The obtained samples were evaluated in terms of chemical composition, hue, acid and base resistances, and hiding power. Among the samples examined, the samples obtained in the Co/Mn/La/P system were the most vivid. The brighter and redder samples were obtained by prolonged heating. Furthermore, prolonged heating improved the acid and base resistance of the samples. Finally, the substitution of manganese for cobalt improved the hiding power.

Coexistence of Ovarian Endometrioma and Ovarian Pregnancy: A Case Report.

Both ovarian pregnancy and endometrioma can rupture and cause life-threatening hemoperitoneum. However, little is known about their coexistence. We report the case of a 34-year-old Japanese woman with a life-threatening hemoperitoneum in the first trimester coexisting with ovarian endometrioma and ovarian pregnancy. The patient was hospitalized in our department for acute hypogastric pain and massive hemoperitoneum during pregnancy. She had a history of miscarriage at eight weeks of gestation one year prior. Her serum beta-human chorionic gonadotropin (hCG) level was >2,000 mIU/mL. Also, a transvaginal ultrasound showed an empty uterus, an intact right ovary, an inhomogeneous left ovary, and a massive hemoperitoneum. An exploratory laparoscopy revealed a rupture of the left ovarian endometrioma, a left corpus luteal cyst, and intraperitoneal bleeding of approximately 1,200 mL. However, no ectopic lesions were observed. Microscopic examination revealed an endometriotic cyst with decidual changes in the stroma, a corpus luteal cyst, and chorionic villi with hemorrhage. Serum beta-hCG levels became negative on the 27th postoperative day. The postoperative course was uneventful. This case shows that, in addition to the differential diagnosis of ovarian pregnancy from ovarian endometrioma, clinicians should consider the coexistence of both conditions.

Evaluation of thumbnail clipping as a specimen for retrospectively assessing average production of testosterone.

BACKGROUND: The chronic abnormal production of testosterone (T) is associated with many disorders in men. Fingernail clippings might be more suited for the diagnosis and medium-to-long term therapeutic monitoring for the T-related chronic disorders than the blood-derived specimens. The objective of this study was to characterize a thumbnail clipping as the specimen for assessing the several months-old T status. METHODS: Thumbnail clippings from various subjects were analyzed by liquid chromatography/electrospray ionization-tandem mass spectrometry to evaluate the gender difference, and changes caused by aging and androgen deprivation therapy (ADT) in the thumbnail T concentration. RESULTS: There was an evident gender difference in the thumbnail T concentrations [male; 2.55 ± 0.85 ng/g and female; 0.48 ± 0.29 ng/g, mean ± SD (n = 25 each), Welch t-test]. The thumbnail T concentrations significantly decreased with age in men (n = 268, Scheffé F-test), which was similar to those of the free or bioavailable T in serum/plasma. The thumbnail T concentrations sharply decreased by a 6-months ADT (especially the effect of the luteinizing hormone-releasing hormone agonist/antagonist) for patients with prostate cancer (n = 10). CONCLUSIONS: The thumbnail clipping can be a specimen to retrospectively assess the average T production.

Demons syndrome with pericardial effusion followed by intensive care unit-acquired weakness: A case report and literature review.

Demons syndrome is defined by hydrothorax and ascites associated with a benign genital tumor that resolves after resection of the tumor. However, Demons syndrome with pericardial effusion has never been reported. Intensive care unit-acquired weakness is a neurological sequela to sepsis/systemic inflammatory response syndrome, or multi-organ failure. A 47-year-old, nulligravid, Japanese woman, was transferred to our hospital for refractory heart failure and a ruptured ovarian tumor. She had an 11-cm left ovarian tumor with ascites, hydrothorax, and pericardial effusion; she was intubated for pulmonary hypertension and admitted to the intensive care unit for septic shock. Four days later, a left salpingo-oophorectomy was performed for Demons syndrome with pericardial effusion. The histological diagnosis indicated a serous cystadenoma with fibrotic changes. Following surgery, ventilator weaning was delayed due to intensive care unit-acquired weakness. The association between Demons syndrome and pericardial effusion should be recognized to ensure early treatment and for preventing sequalae from the disease.

Derivatization-based quadruplex LC/ESI-MS/MS method for high throughput quantification of serum dehydroepiandrosterone sulfate.

The quantification of the circulating dehydroepiandrosterone sulfate (DHEAS) might be of diagnostic help for several diseases. For the DHEAS quantification, LC/ESI-MS/MS has the advantage of a high specificity compared with immunoassay, whereas LC/ESI-MS/MS has room to improve the analysis throughput. One of the promising solutions to enhance the analysis throughput is sample-multiplexing in the same injection, which can reduce the total LC/ESI-MS/MS run time. In this study, a quadruplex LC/ESI-MS/MS method was developed to quantify DHEAS in four different serum samples in a single run. After the four samples were separately deproteinized and derivatized with one of four Girard reagents (Girard reagent T, P and their isotopologs), the resulting samples were mixed, then injected into the LC/ESI-MS/MS. The applicability and advantage of the developed method were evaluated based on the analysis of nine batches of serum samples from healthy subjects (total 36 samples). The limit of quantitation was 0.050 µg/ml, which was sensitive enough for clinical laboratory use. The method was precise (intra- and inter-assay RSDs ≤ 3.6%), accurate (94.4-108.1%) and robust for the matrix effects. The analysis time was also shortened by about 60% for 36 samples by the introduced method compared with the conventional method.

Pembrolizumab and Radiotherapy for Platinum-refractory Recurrent Uterine Carcinosarcoma With an Abscopal Effect: A Case Report.

BACKGROUND: Immune responses due to radiotherapy and immune checkpoint inhibitors potentially have synergistic effects. CASE REPORT: Here, we report a 65-year-old Japanese woman presenting with high-grade endometrial cancer. She was diagnosed with carcinosarcoma, stage IB. A month post-surgery, lung, and mediastinal lymph node metastasis/recurrence was detected. Progressive disease (with high microsatellite instability) with local recurrence and bone metastasis was detected after six chemotherapy cycles with paclitaxel and carboplatin. After combination therapy with pembrolizumab (2 mg/kg, tri-weekly, 10 cycles) and pelvic radiotherapy (30 Gy/10 fractions), enhanced computed tomography revealed a complete response. The patient survived for 14 months with the residual tumour post-relapse. This is the first case of a complete response of recurrent endometrial carcinosarcoma upon combinatorial pembrolizumab and radiotherapy. CONCLUSION: Combinatorial immune checkpoint inhibitors and local radiotherapy cause the abscopal effect and may be a promising treatment strategy for advanced or recurrent carcinosarcomas refractory to traditional chemotherapy.

Uterine tumor resembling ovarian sex-cord tumor (UTROSCT) with sarcomatous features without recurrence after extended radical surgery: A case report.

RATIONALE: The malignant potential and the appropriate treatment of uterine tumor resembling ovarian sex-cord tumor (UTROSCT) is controversial. Although these tumors generally have benign outcomes, several reports have described recurrences, metastases, and deaths associated with this disease. PATIENT CONCERNS: A 57-year-old Japanese woman (gravida 2, para 2) was referred to our hospital for the evaluation and treatment of uterine fibroids. Magnetic resonance imaging revealed a right ovarian mass and multiple fibroids in the uterine myometrium. DIAGNOSES: The patient was diagnosed with UTROSCT with sarcomatous features. INTERVENTIONS: She initially underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy, followed by second-stage surgery comprising pelvic and para-aortic lymphadenectomy and subtotal omentectomy. OUTCOMES: No postoperative recurrence was observed in the patient in 36 months. LESSONS: In this case, extended radical surgery prevented the development of recurrent disease in a patient with UTROSCT with sarcomatous features. These clinicopathological findings suggest that UTROSCT is associated with several risk factors, including older age, presence of necrosis, lymphovascular invasion, significant nuclear atypia, and significant mitotic activity. This lesion type should be considered malignant and treated with curative intent.

Effect of interfacial serum proteins on the cell membrane disruption induced by amorphous silica nanoparticles in erythrocytes, lymphocytes, malignant melanocytes, and macrophages.

It is very important to examine carefully the potential adverse effects of engineered nanoparticles (NPs) on human health and environments. In the present study, we have investigated the impact of interfacial serum proteins on the cell membrane disruption induced by silica NPs of primary diameter of 55-68 nm in four types of cells (erythrocytes, Jurkat, B16F10, and J774.1). The silica-induced membranolysis was repressed by addition of 1-2% serum into culture media, where the adhesion amount of the FBS-coated silica NPs onto a cell surface seemed comparable with that of the bare silica NPs. The nonspecific attraction between the bare silica and J774.1 cell membrane surfaces was masked by pretreatment of the silica surface with serum albumin, whereas the serum proteins-coated silica surface exhibited the attractive interactions with the cell membrane due to specific binding between some of adsorbed proteins thereon and the membrane receptors. The difference in silica-cell interaction between the nonspecific and specific attractions would explain the reason why interfacial serum proteins reduced the membranolysis without prevention of silica NPs adhering to cell surfaces.