Background: Since malignant struma ovarii is a very rare disease, its carcinogenic mechanism has not been elucidated. Here, we sought to identify the genetic lesions that may have led to the carcinogenesis of a rare case of malignant struma ovarii (follicular carcinoma) with peritoneal dissemination. Methods: DNA was extracted from the paraffin-embedded sections of normal uterine tissues and malignant struma ovarii for genetic analysis. Whole-exome sequencing and DNA methylation analysis were then performed. Results: Germline variants of RECQL4, CNTNAP2, and PRDM2, which are tumor-suppressor genes, were detected by whole-exome sequencing. Somatic uniparental disomy (UPD) was also observed in these three genes. Additionally, the methylation of FRMD6-AS2, SESN3, CYTL1, MIR4429, HIF3A, and ATP1B2, which are associated with tumor growth suppression, was detected by DNA methylation analysis. Conclusions: Somatic UPD and DNA methylation in tumor suppressor genes may be associated with the pathogenesis of malignant struma ovarii. To our knowledge, this is the first report of whole-exome sequencing and DNA methylation analysis in malignant struma ovarii. Genetic and DNA methylation analysis may help elucidate the mechanism of carcinogenesis in rare diseases and guide treatment decisions.

Recent studies reported the presence of oncogenic mutations in normal endometrial glands, but the biological significance remains unclear. The present study investigated the status of KRAS/PIK3CA driver mutations in normal endometrial glands as well as spheroids derived from single glands. The normal endometria of surgically removed uteri (n = 3) were divided into nine regions, and 40 endometrial single glands were isolated from each region. The DNAs of 10 glands in each region were extracted and subjected to Sanger sequencing for KRAS or PIK3CA driver mutations, while the remaining 30 glands were conferred to a long-term spheroid culture, followed by Sanger sequencing. Immunohistochemical analyses of stem cell (Axin2, ALDH1A1, SOX9) markers were undertaken for spheroids. Sanger sequencing successfully detected oncogenic mutations of KRAS or PIK3CA in a single gland. Twenty-five of the 270 glands (9.3%) had mutations in either KRAS or PIK3CA, and the mutation frequency in each endometrial region varied from 0% to 50%. The droplet digital PCR showed high mutation allele frequency (MAF) of PIK3CA mutation, suggestive of clonal expansion of mutated cells within a gland. Over 60% of the collected spheroids had PIK3CA mutations, but no KRAS mutations were detected. Immunohistochemically, spheroids were mainly composed of cells with stem cell marker expressions. High MAF of PIK3CA mutation in a single gland as well as frequent PIK3CA mutation in stem cell-rich spheroids that originated from a single gland suggest the role of PIK3CA mutation in stem cell propagation. This information could improve our understanding of endometrial physiology as well as stem cell-oriented endometrial regeneration and carcinogenesis.

Background Laparoscopic myomectomy (LM) is one of the techniques feasible for the treatment of intramural myoma. This technique is reported to be difficult when large fibroids are involved because of excessive blood loss during surgery. Skillful and fast suturing appears to be associated with reduced blood loss during LM. Barbed sutures have been recently introduced to facilitate laparoscopic suturing. A suture with bidirectional barbs offers several advantages over conventional sutures. Although the efficacy and safety of barbed sutures have been demonstrated in various gynecologic surgeries in many countries, no comparable studies have been conducted in Japan. Therefore, in this study, we compared surgical outcomes of using bidirectional Stratafix barbed sutures versus conventional sutures during LM. Methods This retrospective study included all patients who underwent LM for the treatment of intramural myoma in our institution between 2015 and 2017. Patients were divided into two groups according to the technique of suturing during LM: group 1 comprised patients in whom Stratafix barbed suture was used (n = 29), and group 2 comprised those in whom conventional sutures was used (n = 10). Data of patient age, myoma size, hemoglobin levels, total operation time, and blood loss during surgery were compared between the two groups. Results No significant differences in age (P = 0.443) or myoma size (P = 0.343) were observed between the two groups. Operation time (P = 0.0134) and blood loss (P = 0.0395) during surgery was significantly less with Stratafix barbed suture than with conventional suture. No patient required intraoperative transfusion or conversion to laparotomy. Conclusions The use of bidirectional barbed suture reduces operation time and blood loss. As these new sutures have barbs, no knot-tying is required; thus, continuous suturing becomes very simple, and maintaining hemostasis is easy. Inexperienced gynecological surgeons who apply this suture technique can also perform LM easily. As a bidirectional barbed suture has multiple points of fixation, this suture technique can reapproximate tissue securely, which reduces chances of reoperation because of proper suture knotting. Therefore, bidirectional Stratafix barbed sutures could be an optimal and efficient alternative to conventional sutures for use by gynecological surgeons in Japan.