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Background: Japan's health insurance covers multigene panel testing. This study aimed to determine the potential availability and utility of gene panel testing clinically in gynecologic oncology. Methods: We analyzed the characteristics of patients with gynecologic cancer who underwent gene panel testing using FoundationOne® CDx or OncoGuide™ NCC Oncopanel between November 2019 and October 2022. Results: Out of 102 patients analyzed, 32, 18, 43, 8, and 1 had cervical, endometrial, ovarian cancers, sarcoma, and vaginal cancer, respectively. Druggable gene alteration was found in 70 patients (68.6%; 21 with cervical cancer, 15 with endometrial cancer, 28 with ovarian cancer, 5 with sarcoma, and 1 with other). The most common druggable gene alteration was PIK3CA mutation (n = 21), followed by PTEN mutation (n = 12) and high tumor mutation burden (TMB-H) (n = 11). TMB-H was detected in 5 patients with cervical cancer, 5 with endometrial cancer, and 1 with endometrial stromal sarcoma. Eleven patients (10.8%) received molecularly targeted therapy according to their gene aberrations. Gene panel testing was mostly performed when the second-line treatment was ineffective. Of all 102 patients, 60 did not have recommended treatment, and 15 died or had worsened conditions before obtaining the test results. Conclusion: Through multigene panel testing, although many patients had druggable gene alterations, 10.8% of them received the recommended treatment. TMB-H was mainly observed in cervical/endometrial cancer, suggesting its potential as a therapeutic biomarker of immune checkpoint inhibitors. Furthermore, patients' prognosis and performance status should be considered before performing the test. [ABSTRACT FROM AUTHOR]

Purpose: Uterine blood flow is required for the maintenance of uterine viability in pregnancy and delivery, but it is unknown how many vessels are necessary for maintenance of uterine viability. The objective of this study was to examine whether unilateral uterine vessels provide sufficient nutrition in pregnancy in a cynomolgus macaque and to evaluate hemodynamics of pregnant uterus by indocyanine green (ICG) fluorescence imaging. Methods: A cynomolgus macaque with uterine blood flow maintained by the right uterine artery and vein alone was made pregnant. Hemodynamics of the uterus in the third trimester was evaluated by ICG fluorescence imaging. Results: Pregnancy was maintained with the right uterine artery and vein. An appropriate-for-date infant was delivered by Cesarean section. ICG fluorescence imaging showed that the uterine body was imaged from the right side to the center; furthermore, collateral circulation was present from the right uterine artery toward the left uterine artery, with expanded blood flow to the left uterine body. Conclusion: Pregnancy and delivery were achieved in a cynomolgus macaque with a unilateral right uterine artery and vein. Blood flow to the side without the artery was complemented by vascularization of collateral circulation to the uterine artery. [ABSTRACT FROM AUTHOR]

Uterus transplantation (UTx) is an alternative to gestational surrogacy and adoption for patients with absolute uterine infertility. Studies have been conducted in animals, and UTx is now within the reach of clinical application in humans. Procedures in humans have been published, but many medical, ethical, and social problems and risks of UTx require discussion prior to widespread clinical application, from the perspectives of donors, recipients, families, and newborns. In this article, we summarize the burdens and risks of UTx, with a focus on donors who provide the uterus. [ABSTRACT FROM PUBLISHER]

MicroRNAs (miRNAs) are small non-coding ribonucleic acids (RNAs) of approximately 22 bp that induce RNA interference with a complementary messenger RNA (mRNA) and act in silencing of mRNA. miRNAs are strongly associated with cancer development and those involved in carcinogenesis are classified into oncogenic miRNAs and tumor suppressor miRNAs (tumor suppressor miRs). Specific miRNAs are expressed in various tissues and changes in regulation of gene expression are thought to cause carcinogenesis. Thus, tissue-specific miRNAs may be biomarkers for cancer diagnosis and prognosis. Approaches to application of miRNAs as cancer therapy are also ongoing, based on the involvement of miRNAs in carcinogenesis. In endometrial cancer, miRNAs are associated with regulation of gene expression, epigenetic dysfunction and carcinogenesis. Thus, miRNAs are likely to have key roles in diagnosis, prognostic prediction, and therapy in endometrial cancer. [ABSTRACT FROM AUTHOR]

Objective: Uterine transplantation experiments have been performed in various animal species for future clinical applications of uterine transplantation for permanent uterine factor infertility in humans. The aim of this study was to confirm the feasibility of uterine auto-transplantation in cynomolgus monkeys by developing new surgical techniques. Methods: Two female cynomolgus monkeys underwent surgery under general anesthesia. The uterus with vascular grafts and the vaginal wall was removed, and back-table preparation was performed using heparinized saline. The uterus with vascular grafts and the vaginal wall was anastomosed with the vaginal stump and blood vessels in the pelvis, respectively. The auto-transplant uterine function was evaluated by confirming engraftment of the uterus by laparotomy, endometrial proliferation by transabdominal ultrasonography and periodical menstruation. Results: The first animal died due to acute renal failure 2 days after the operation. Second-look laparotomy in the second animal at 40 days after the operation indicated there was no congestion in the uterus, and the uterus showed the typical red color of a normal uterus. Thereafter, endometrial proliferation was observed by transabdominal ultrasonography and periodical menstruation was confirmed, indicating re-established uterine function. Conclusion: This is the preliminary report of uterine auto-transplantation in cynomolgus monkeys. This study demonstrates the feasibility of uterine auto-transplantation by using new surgical technique in cynomolgus monkeys. Accumulation of basic experimental data in non-human primates is required prior to performing the procedure in humans. [ABSTRACT FROM AUTHOR]

Hereditary nonpolyposis colorectal cancer (HNPCC) is among the representative familial cancers that are autosomally dominant inherited disorders. Because endometrial cancers develop at high rates in women with HNPCC, it is suggested that some endometrial cancers are familial cancers that are induced by mutations of the DNA mismatch repair (MMR) genes, as in HNPCC. To understand the clinical pathology of familial endometrial cancers that are associated with HNPCC, we surveyed the family histories of 385 patients with endometrial cancer and found that 0.5% of endometrial cancers met the new diagnostic criteria of HNPCC. From molecular and biological analyses, we found microsatellite instability in 30.8% of endometrial cancers and germline mutations of MMR genes in 8.3%. These results suggest a close relationship of MMR gene mutations to the development of endometrial cancers. For a better understanding of the clinical pathology of HNPCC-associated familial endometrial cancers, it is critical for gynecologists to perform a large multicenter study, including detailed family histories. [ABSTRACT FROM AUTHOR]

Uterus transplantation (UTx) is a potential option for women with uterine factor infertility to have a child. The clinical features indicating irreversible rejection of the uterus are unknown. In our experimental series of allogeneic UTx in cynomolgus macaques, six female macaques were retrospectively examined, which were unresponsive to treatment with immunosuppressants (i.e. irreversible rejection). Clinical features including general condition, hematology, uterine size, indocyanine green (ICG) fluorescence imaging by laparotomy, and histopathological findings of the removed uterus were evaluated. In all cases, general condition was good at the time of diagnosis of irreversible rejection and thereafter. Laboratory evaluation showed temporary increases in white blood cells, lactate dehydrogenase and C-reactive protein, then these levels tended to decrease gradually. In transabdominal ultrasonography, the uterus showed time-dependent shrinkage after transient swelling at the time of diagnosis of irreversible rejection. In laparotomy, a whitish transplanted uterus was observed and enhancement of the transplanted uterus was absent in ICG fluorescence imaging. Histopathological findings in each removed uterus showed hyalinized fibrosis, endometrial deficit, lymphocytic infiltration and vasculitis. These findings suggest that uterine transplantation rejection is not fatal, in contrast to rejection of life-supporting organs. Since the transplanted uterus with irreversible rejection atrophies naturally, hysterectomy may be unnecessary. [ABSTRACT FROM AUTHOR]