Naoyuki Iwahashi

Downregulation of indoleamine 2, 3-dioxygenase expression in the villous stromal endothelial cells of placentas with preeclampsia

INTRODUCTION Previous studies have shown that indoleamine 2, 3-dioxygenase (IDO), an immunosuppressive enzyme that converts tryptophan to kynurenine, is expressed in the placenta and might play a role in the maintenance of pregnancy, although its associations with the pathogeneses of preeclampsia (PE) and fetal growth restriction (FGR) remain unclear. The objective of this study was to investigate the differences in IDO expression among normal, PE, and FGR placentas, and the associations between IDO expression and clinical symptoms, or the expression of fms-like tyrosine kinase receptor-1 (Flt-1). METHODS Immunohistochemical studies of IDO and Flt-1 expression were performed in human placentas that were complicated with FGR alone (n=19), PE alone (n=20), or both PE and FGR (n=39), and gestational age-matched controls (n=23). RESULTS It was found that IDO was expressed on endothelial cells in the villous stroma, while Flt-1 was located on trophoblast cells. The IDO expression level of the PE alone group was significantly lower than those of the FGR alone and control groups. The IDO expression of the PE+FGR group was significantly lower than that of the FGR alone group. Lower IDO expression was significantly correlated with more severe maternal hypertension or proteinuria in PE patients, who exhibited higher Flt-1 expression. The late onset PE patients exhibited significantly lower IDO expression than the early onset PE patients. CONCLUSION This study demonstrated that the downregulation of IDO expression on the endothelial cells of the villous stroma was associated with PE, but not FGR, suggesting that IDO might be involved in the pathophysiology of PE.

Large uterine pyomyoma in a perimenopausal female: A case report and review of 50 reported cases in the literature

Pyomyoma is a rare complication, which withoug antibiotics or surgical intervention, may cause sepsis and mortality. The present study reported a case of large uterine pyomyoma in a perimenopausal female. A 53-year-old multigravida woman was referred to the Department of Obstetrics and Gynecology (Wakayama Medical University, Wakayama, Japan) due to progressive abdominal distension. The patient presented with anemia gravis, severe inflammatory reaction and cachexia. Computed tomography revealed a large unilocular mass, 50 cm in size, with an irregular surface and thickened wall, occupying the entire abdomen. Following antibiotic medication, the patient underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy. Intraoperative findings demonstrated a solid tumor arising from the back of the uterine body. A total of 12 liters of purulent, malodorous fluid was drained from the tumor. The resected mass was 50 cm in size and 13.5 kg in weight. Cultures of the pus revealed the presence of Streptococcus agalactiae. Pathological findings revealed suppurative leiomyoma with no malignancy. Large pyomyoma is difficult to distinguish from a gynecological malignant tumor types, particularly in perimenopausal women with non-specific clinical presentation. Although pyomyoma is a benign tumor, care must be taken to discriminate these from large abdominal tumors.

Vasa previa evaluated by noncontrast time-of-flight magnetic resonance angiography

OBJECTIVE Vasa previa is a rare complication, and rupture of vasa previa during pregnancy may lead to significant perinatal mortality. Here, we report a case of vasa previa evaluated prenatally using noncontrast time-of-flight magnetic resonance angiography (TOF MRA). CASE REPORT A 22-year-old primiparous woman was referred to our hospital due to suspicion of vasa previa. Transvaginal ultrasonography showed two vessels running over the internal os. To obtain further information, magnetic resonance imaging (MRI) and TOF MRA were performed. Caesarean section was carried out, and macroscopic findings of the vascular distribution on the fetal membrane were consistent with those identified by TOF MRA. CONCLUSION TOF MRA in addition to MRI may be an option for prenatal identification of the precise three-dimensional vascular distribution in patients with vasa previa.

A comprehensive gene mutation analysis of liquid biopsy samples from patients with metastatic colorectal cancer to the ovary: A case report

Liquid biopsies of circulating tumor DNA (ctDNA) can detect molecular alterations, including tumor-specific mutations, and have recently been used as a non-invasive diagnostic, prognostic, and predictive tool. However, this technique is not commonly used in the gynecological field. Gene mutation profiling of liquid biopsy samples was performed using CAncer Personalized Profiling by deep Sequencing (CAPP-Seq), a novel next-generation sequencing-based approach to ultrasensitive ctDNA detection, in order to make it possible to molecularly diagnose metastatic colorectal cancer to the ovary. Liquid biopsy (plasma) samples and formalin-fixed paraffin-embedded tumor samples were obtained from two patients with ovarian tumors, who had a history of surgery for colorectal cancer, and comprehensive gene mutation profiling was conducted using CAPP-Seq. In patient 1, mutations were identified in the same three regions in both the ovarian tumor and preoperative plasma sample (in the KRAS G13D, APC E1306*, and TP53 H193Y genes). In patient 2, mutation was identified in the same one region in all the primary colorectal tumor, the ovarian tumor, and preoperative plasma sample (in APC R216* gene). These mutations are well-known genetic signatures of colorectal cancer, suggesting that the ovarian tumor was metastatic. Tthe gene mutation patterns of colorectal cancer were examined by subjecting liquid biopsy samples from patients with suspected metastatic ovarian tumors to CAPP-Seq. Gene mutation profiling of liquid biopsy samples can contribute to the preoperative differential diagnosis of metastatic ovarian cancer and its subsequent personalized treatment.

Live birth following laparoscopic fertility‑sparing surgery for papillary thyroid carcinoma arising from mature ovarian cystic teratoma: A case report

Papillary thyroid carcinoma arising from ovarian mature cystic teratoma is clinically rare. We herein present a case of live birth following two laparoscopic surgeries for papillary thyroid carcinoma arising in a mature ovarian cystic teratoma. A 30-year-old female patient, gravida 1 para 1, was treated by laparoscopic bilateral ovarian cystectomy for suspicion of bilateral mature cystic teratoma. The diagnosis of papillary thyroid carcinoma arising from right ovarian mature cystic teratoma was established based on postoperative pathological examination of the tumor. Such rare neoplasms may be difficult to diagnose preoperatively based on radiological examinations alone. The patient underwent laparoscopic fertility-preserving unilateral (right) salpingo-oophorectomy. Following an extensive discussion with the patient and her family, appropriate informed consent was obtained for the treatment option and the patient and her family chose to preserve her fertility. She could have a baby following the treatment and no evidence of disease for 6 years. Gynecologists should be aware of the possibility of such rare cases, and the available surgical interventions should be fully discussed with patients who wish to preserve their fertility. Laparoscopic fertility-sparing surgery may be a feasible option when encountering such a rare condition.

Postpartum Methicillin-Resistant Staphylococcus aureus Toxic Shock Syndrome Caused by a Perineal Infection

Although toxic shock syndrome (TSS) is rare, multiorgan failure can occur without early identification and appropriate therapy. In particular, a few cases of postpartum TSS due to methicillin-resistant Staphylococcus aureus (MRSA) have been reported. Here, we describe a rare case in which a 32-year-old Japanese woman had TSS due to MRSA that was caused by a perineal infection after a normal vaginal delivery. Twelve days after giving birth to a healthy child, she was readmitted to our hospital due to a 2-day fever and perineal pain without uterine tenderness. She developed emesis and watery diarrhea on the night of admission. On the second day, a diffuse cutaneous macular rash appeared over her trunk. Laboratory data revealed deteriorated renal function and thrombocytopenia. Her history and clinical results were compatible with a typical course of TSS. Administration of ceftriaxone and clindamycin was started immediately after admission and was effective. The patient recuperated steadily over the next week with desquamation of the skin. MRSA was isolated from her vaginal discharge and was found to produce TSS toxin 1 (TSST-1). Furthermore, since MRSA was not detected in the nasal and vaginal cavity during pregnancy, it suggests that vaginal colonization can also occur postpartum and be the disease source in mothers. Therefore, MRSA infections should be considered when treating for postpartum TSS.

Omental synovial sarcoma mimicking an ovarian malignancy: A case report

Synovial sarcoma is clinically rare, and cases of synovial sarcoma arising in the omentum are particularly rare. Only 3 cases have been reported in the literature to dtae, and they were associated with a poor prognosis. We herein report a rare case of aggressive primary omental synovial sarcoma presenting as an ovarian malignancy. A 53-year-old multigravida woman was referred to our hospital due to progressive abdominal distension. Magnetic resonance imaging revealed a large heterogeneous mass with an irregular component occupying the lower abdominal cavity, with an intact uterus. Intraoperative examination revealed a solid mass arising from the lower omentum. The diagnosis of omental synovial sarcoma was established based on postoperative pathological and immunohistochemical examination of the tumor. The patient underwent multiple surgical resection procedures due to the development of metastases in the liver, lungs and abdominal cavity and received adjuvant chemotherapy including doxorubicin-ifosfamide, pazopanib and trabectedin. Such rare neoplasms may be difficult to diagnose preoperatively based on radiological examinations alone. Thus, gynecologists should be aware of the possibility of omental synovial sarcoma, and combined surgical and chemotherapeutic interventions are required to control such aggressive tumors.

Non‑neural granular cell tumor of the uterine corpus mimicking uterine leiomyoma: A case report

Non-neural granular cell tumors (GCTs) are clinically rare, whereas cases arising in the uterine corpus are exceedingly rare. Only three uterine cervical cases of GCTs have been reported to date and, to the best of our knowledge, there are no reports of GCT of the uterine corpus in the literature. We herein describe the first case of non-neural GCT arising from the uterine corpus reported to date. A 55-year-old premenopausal woman was referred to the Department of Obstetrics and Gynecology of Hashimoto Municipal Hospital (Wakayama, Japan) with a suspected uterine tumor. The tumor presented as a uterine leiomyoma-like mass on radiological examinations, but the diagnosis of non-neural GCT was established based on pathological and immunohistochemical examinations. Microscopically, histological examination of the entire surgical specimen revealed large polygonal cells with abundant eosinophilic granular cytoplasm and round to oval nuclei. Immunohistochemistry revealed positive periodic acid-Schiff staining of the cytoplasmic granules, which was resistant to diastase. In addition, the tumor cells stained positive for CD68, but negative for S-100, neuron-specific enolase, cytokeratin, CD34, α-smooth muscle actin, desmin, estrogen receptor and progesterone receptor. It is important for gynecologists to be aware of the possibility of non-neural GCT of the uterine corpus, for which accurate diagnosis, complete resection and long-term follow-up are crucial, as it may be easily misdiagnosed as uterine leiomyoma.

Calreticulin Is Involved in Invasion of Human Extravillous Trophoblasts Through Functional Regulation of Integrin β1

Calreticulin (CRT), a molecular chaperone in the endoplasmic reticulum (ER), plays a variety of roles in cell growth, differentiation, apoptosis, immunity, and cancer biology. It has been reported that CRT is expressed in the human placenta, although its function in placental development is poorly understood. Appropriate invasion of extravillous trophoblasts (EVTs) into the maternal decidua is necessary for successful pregnancy. The objective of the present study was to investigate the expression and functional role of CRT in EVTs using the human EVT cell line HTR8/SVneo, in which CRT gene expression was knocked down. We found that CRT was highly expressed in the human placenta in the early stage of pregnancy and localized to the EVTs. CRT knockdown markedly suppressed the invasion ability of HTR8/SVneo cells. Furthermore, the adhesion to fibronectin was suppressed in the CRT-knockdown cells via the dysfunction of integrin α5β1. In the CRT-knockdown cells, terminal sialylation and fucosylation were decreased, and the core galactose-containing structure was increased in the N-glycans of integrin β1. In addition, the expression levels of several critical glycosyltransferases were changed in the CRT-knockdown cells, consistent with the changes in the N-glycans. These results showed that CRT regulates the function of integrin β1 by affecting the synthesis of N-glycans in HTR8/SVneo cells. Collectively, the results of the present study demonstrate that the ER chaperone CRT plays a regulatory role in the invasion of EVTs, suggesting the importance of CRT expression in placental development during early pregnancy.

A Third Surgically Managed Ectopic Pregnancy after Two Salpingectomies Involving the Opposite Tube

Recurrent ectopic pregnancy in a remnant fallopian tube after ipsilateral salpingectomy is clinically rare. We report the extremely rare case of a third recurrent ectopic pregnancy after two previous salpingectomy procedures involving the opposite tube. A 26-year-old woman, gravida 3 para 0, experienced three ectopic pregnancies brought about by natural conception, all of which were treated surgically (right partial salpingectomy, right remnant tube resection, and left total salpingectomy). During the two salpingectomy procedures involving the right tube, the patency of the intact left tube was intraoperatively confirmed with indigo carmine. The most appropriate surgical intervention should be discussed when managing recurrent ectopic pregnancies. It might be necessary to perform total salpingectomy to reduce the risk of future recurrence on the remaining tube.