Graft Failure after Uterus Transplantation in 16 Recipients: A Review.

Uterus transplantation (UTx) is now an alternative to surrogacy and adoption for women with uterine factor infertility to have children; however, there are still unresolved clinical and technical issues. One of these is that the graft failure rate after transplantation is somewhat higher than that of other life-saving organ transplants, which is a critical concern. Herein, we summarize the details of 16 graft failures after UTx with living or deceased donors using the published literature in order to learn from these negative outcomes. To date, the main causes of graft failure are vascular factors (arterial and/or venous thrombosis, atherosclerosis, and poor perfusion). Many recipients with thrombosis develop graft failure within one month of surgery. Therefore, it is necessary to devise a safe and stable surgical technique with higher success rates for further development in the UTx field.

Registry of the International Society of Uterus Transplantation: First Report.

BACKGROUND: Uterus transplantation (UTx) is a novel type of transplantation to treat infertility in women with an absent or nonfunctioning uterus. The International Society of Uterus Transplantation (ISUTx) has developed a registry to monitor worldwide UTx activities while serving as a repository for specific research questions. METHODS: The web-based registry has separate data fields for donor, recipient, surgeries, immunosuppression, rejections, pregnancies with live birth(s), and transplant hysterectomies. Data are prospectively registered. RESULTS: A total of 45 UTx procedures have been registered; the majority (78%) of those procedures were live donor (LD) transplants. Median age of the LDs, deceased donors, and recipients were 50 y (range 32-62), 38.5 y (19-57), and 29 y (22-38), respectively. The duration of LD surgery was approximately twice as long as the recipient surgery. Postoperative complications of any Clavien-Dindo grade were registered in 20% of LDs and 24% of recipients. Rejection episodes were more frequent (33%) early after transplantation (months 1-5) compared with later time points (months 6-10; 21%). Healthy neonates were delivered by 16 recipients, with 3 women giving birth twice. The total live birth rate per embryo transfer was 35.8%. Median length of pregnancy was 35 gestational weeks. Twelve uteri were removed without childbirth, with 9 transplant hysterectomies occurring during the initial 7 mo post-UTx. CONCLUSIONS: A mandatory registry is critical to determine quality and process improvement for any novel transplantation. This registry provides a detailed analysis of 45 UTx procedures performed worldwide with a thorough analysis of outcomes and complications.

A New Horizon in Reproductive Research with Pluripotent Stem Cells: Successful In Vitro Gametogenesis in Rodents, Its Application to Large Animals, and Future In Vitro Reconstitution of Reproductive Organs Such as "Uteroid" and "Oviductoid".

Recent success in derivation of functional gametes (oocytes and spermatozoa) from pluripotent stem cells (PSCs) of rodents has made it feasible for future application to large animals including endangered species and to ultimately humans. Here, we summarize backgrounds and recent studies on in vitro gametogenesis from rodent PSCs, and similar approaches using PSCs from large animals, including livestock, nonhuman primates (NHPs), and humans. We also describe additional developing approaches for in vitro reconstitution of reproductive organs, such as the ovary (ovarioid), testis (testisoid), and future challenges in the uterus (uteroid) and oviduct (oviductoid), all of which may be derived from PSCs. Once established, these in vitro systems may serve as a robust platform for elucidating the pathology of infertility-related disorders and ectopic pregnancy, principle of reproduction, and artificial biogenesis. Therefore, these possibilities, especially when using human cells, require consideration of ethical issues, and international agreements and guidelines need to be raised before opening "Pandora's Box".

Uterus Transplantation: From a Deceased Donor or Living Donor?

Uterus transplantation (UTx) is a new alternative to surrogacy or adaption for women with uterine factor infertility to have a child [...].

Novel vaginoplasty technique involving the use of peritoneal flaps during laparoscopic radical hysterectomy for early-stage cervical cancer.

Radical hysterectomy is often performed to treat early-stage cervical cancer in women of reproductive age, and sexual dysfunction due to postoperative vaginal shortening is a major concern [1,2]. Vaginoplasty using various techniques is commonly performed in patients with congenital vaginal agenesis [3]. However, there are few reports of vaginoplasty being performed for vaginal shortening after radical hysterectomy in a patient with cervical cancer [4,5]. We demonstrate a novel vaginoplasty technique in which peritoneal flaps are used during laparoscopic radical hysterectomy to prevent postoperative vaginal shortening and consequent sexual dysfunction in patients with early-stage cervical cancer. A 37-year-old woman with early-stage cervical cancer who wished to perform sexual activity postoperatively underwent laparoscopic radical hysterectomy and vaginoplasty. After radical hysterectomy, the residual vaginal length was 4 cm. The dissected peritoneum of pouch of Douglas (posterior peritoneal flap) was sutured to the posterior vaginal stump. The supravesical peritoneum was dissected from the ventral to the dorsal side to create an anterior peritoneal flap, which was inverted, pulled down, and sutured to the anterior vaginal stump. The anterior peritoneal flap and suprarectal peritoneum were sutured to create a 10-cm neovaginal vault. Subsequently, a methacrylic resin mold was inserted into the neovagina to prevent postoperative neovaginal stenosis. The patient had sexual intercourse 3 months postoperatively. She was satisfied with the sexual activity and experienced no vaginal shortening or stenosis. Our novel vaginoplasty technique is feasible and effective for preventing sexual dysfunction by lengthening the vagina during laparoscopic radical hysterectomy for early-stage cervical cancer. Trial Registration: Japan Registry of Clinical Trials Identifier: jRCT1030210227.

Keio Uterus Transplantation Research: From Basic Research toward Future Clinical Application.

Uterus transplantation (UTx) is now a potential option to allow women with uterine factor infertility to give birth. However, UTx is still at an experimental stage, and basic animal studies, including in non-human primates, are needed for the accumulation of data prior to clinical application. Considering that UTx may provide new hope to Japanese women, we launched UTx research in 2009 and have since accumulated a large archive of results in the UTx research field. Furthermore, we have carried out various activities aimed at the implementation of clinical applications of UTx in Japan while clarifying the ethical and social issues involved. Currently, the clinical application of UTx in Japan is just around the corner, and it is expected that UTx research will develop further in the future. Herein, we summarize our basic experiences using non-human primates and our activities with the goal of future clinical applications.

Technique for transvaginal removal of large specimen using an Alexis Contained Extraction System during laparoscopic hysterectomy.

OBJECTIVE: Transvaginal removal of large specimens during laparoscopic hysterectomy can be a complex surgical procedure that poses a risk of organ injury and tissue spillage into the abdominal cavity and is associated with extraction of the specimen and manual morcellation. Our objective was to demonstrate a technique for transvaginal removal of large specimens using the Alexis Contained Extraction System (CES) in laparoscopic hysterectomy. METHODS: The technique used for transvaginal removal of large specimens using the Alexis CES was presented in this video. Surgery was performed at a tertiary hospital. RESULTS: Following resection of the specimen during laparoscopic hysterectomy, the Alexis CES was inserted into the abdominal cavity through the umbilical trocar wound. The specimen was placed in a bag to prevent tissue spillage. The ring retractor was guided to the vagina and pulled out transvaginally. By repeatedly turning the ring retractor, tension was applied to the specimen bag, and the vaginal wall was unfolded all around to enable a secure surgical field. During manual morcellation of the specimen in the bag, the retractor was pulled and additionally turned to roll and re-tension the specimen bag when the bag was loosened. The specimen was pushed out of the vagina and safely and effectively extracted without concerns about tissue spillage in the abdominal cavity or related organ injuries. CONCLUSION: The technique for transvaginal removal of large specimens using the Alexis CES enables simple, effective, and safe tissue extraction with contained manual morcellation during laparoscopic hysterectomy.

Laparoscopic Vaginoplasty Procedure Using a Modified Peritoneal Pull-Down Technique with Uterine Strand Incision in Patients with Mayer-Rokitansky-Küster-Hauser Syndrome: Kisu Modification.

Various vaginoplasty procedures have been developed for patients with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. Here, we describe a novel laparoscopic vaginoplasty procedure, known as the Kisu modification, using a pull-down technique of the peritoneal flaps with additional structural support to the neovaginal apex using the incised uterine strand in patients with MRKH syndrome. Ten patients with MRKH syndrome (mean age at surgery: 23.9 ± 6.5 years, mean postoperative follow-up period: 17.3 ± 3.7 months) underwent construction of a neovagina via laparoscopic vaginoplasty. All surgeries were performed successfully without complications. The mean neovaginal length at discharge was 10.3 ± 0.5 cm. Anatomical success was achieved in all patients, as two fingers were easily introduced, the neovagina was epithelialized, and the mean neovaginal length was 10.1 ± 1.0 cm 1 year postoperatively. No obliteration, granulation tissue formation at the neovaginal apex, or neovaginal prolapse was recorded. Five of the 10 patients attempted sexual intercourse and all five patients were satisfied with the sexual activity, indicating functional success. Although the number of cases in this case series is few, our favorable experience suggests that the Kisu modification of laparoscopic vaginoplasty procedure is an effective, feasible, and safe approach for neovaginal creation in patients with MRKH syndrome.

Hysteroscopic treatment assisted by photodynamic diagnosis for atypical polypoid adenomyoma: A report of two cases.

Atypical polypoid adenomyoma (APA) is an intrauterine tumor for which hysteroscopic tumor resection allows for fertility preservation. Complete resection is important because of the high recurrence rate of APA, but is difficult due to the lack of characteristic hysteroscopic findings. We previously reported a case in which photodynamic diagnosis (PDD) was useful for detection of APA. Here, we report two additional cases of APA treated by hysteroscopic resection with PDD. The procedure was approved by the ethical committee. Case 1: A 35-year-old female who underwent hysteroscopic surgery for a submucosal tumor suspected to be APA with hypermenorrhea. Case 2: A 37-year-old female in whom hysteroscopic surgery was performed for a residual APA lesion after hormone therapy. In Case 1, PDD identified the tumor borders and this enabled as complete resection as possible. In Case 2, lesions could not be identified clearly under white light, but some areas were PDD-positive and were excised. Among 19 specimens from these two cases and the previously reported case, all PDD-positive specimens were pathologically diagnosed as APA. The sensitivity and specificity of PDD for APA were 76.9% and 100%, respectively. These results suggest that PDD can contribute to identification of APA.

Real-time intraoperative ureter visualization with a novel Near-Infrared Ray Catheter during laparoscopic hysterectomy for gynecological cancer.

Ureteral injuries are well-known complications of gynecologic surgery, with a higher prevalence in laparoscopic surgery than in laparotomy [1]. The use of near-infrared fluorescent imaging navigation is currently being considered a novel method to identify the ureters intraoperatively and prevent ureteral injuries [2]. The Near-Infrared Ray Catheter (NIRC) fluorescent ureteral catheter is a newly developed device, containing a fluorescent resin that can be recognized by near-infrared irradiation. We found few reports on the use of this catheter in laparoscopic surgery for colon and rectal cancer [3, 4], but no reports in gynecologic surgery. We demonstrate the feasibility, safety, and potential usefulness of the real-time intraoperative visualization of the ureters using a novel NIRC fluorescent ureteral catheter in laparoscopic hysterectomy for endometrial cancer. A 30-year-old woman with early grade 1 endometrioid carcinoma was treated with medroxyprogesterone acetate for fertility preservation. After achieving complete response, she got pregnant and underwent cesarean section. The recurrence of atypical endometrial hyperplasia one year post-delivery prompted a total laparoscopic hysterectomy. Before the laparoscopic surgery began, the NIRC fluorescent ureteral catheters were placed in the ureters under the obtainment of informed consent from the patient. During the surgery, the catheters were successfully visualized by near-infrared fluorescence observation, which helped identify the ureters clearly and prevent ureteral injuries. This novel ureteral imaging navigation is expected to be an effective tool in cases of obesity, severe pelvic adhesion, deep infiltrating endometriosis, and malignancy in gynecologic laparoscopic surgery to clearly identify the ureter and to reduce the risk of ureteral injury.

A Rare Urothelial Malignant Transformation in a Mature Cystic Teratoma of the Ovary.

Approximately 0.17-2% of mature cystic teratomas undergo malignant transformation, of which squamous cell carcinoma (SCC) is the most common, accounting for 80% of these cases. Urothelial malignant transformation is extremely rare. The present study involves a 58-year-old patient who visited the hospital with discomfort in the lower abdomen. USG and pelvic MRI showed a left ovarian mature cystic teratoma. Left salpingo-oophorectomy was performed, and pathological examination revealed urothelial carcinoma transformation of the mature cystic teratoma morphologically and immunohistochemically. No metastasis to other organs was identified by CT after the surgery. Additional surgery, including total hysterectomy, right salpingo-oophorectomy, omentectomy, and dissection of pelvic and para-aortic lymph nodes, was performed without complications. No tumors were identified elsewhere, and the patient's stage was confirmed as IA. She had an uneventful postoperative course and was discharged 10 days later. CT showed no metastasis or recurrence six months later.

Rectal mobilization for laparoscopic pelvic lymphadenectomy of the lower paracervical pathway in patients with uterine cancer.

OBJECTIVE: The pelvic lymphatic drainage system comprises the upper and lower paracervical pathways (LPPs). Lymph node dissection of the LPP, including the cardinal ligament, internal iliac, internal common iliac, and presacral lymph nodes, requires higher surgical skills because of the anatomical limitations of the pelvic cavity and the dissection of vessels while preserving the nerves in the pelvic floor. In this video, we demonstrate rectal mobilization for laparoscopic complete pelvic lymph node dissection of the LPP in patients with uterine cancer. METHODS: Rectal mobilization was performed before complete pelvic lymph node dissection of the LPP. The pararectal space was opened widely and the connective tissue between the presacral fascia and prehypogastric nerve fascia was dissected bilaterally, allowing the rectum to be pulled. RESULTS: This procedure created a wide-open space in the pelvic floor, allowing clear visualization of the nerves and lymph nodes of the LPP. Laparoscopic complete lymph node dissection of the LPP was performed in the open space while preserving the hypogastric and pelvic splanchnic nerves and isolating the extensive network of blood vessels in the pelvic cavity. CONCLUSION: Rectal mobilization enabled the safe execution of laparoscopic complete pelvic lymph node dissection of the LPP in patients with uterine cancer.

Bilateral adrenal metastases of endometrial cancer with adrenal insufficiency.

Adrenal metastasis from endometrial cancer is extremely rare and has a poor prognosis, especially for bilateral adrenal metastases. It is usually asymptomatic without any adrenal hormonal abnormalities. A 50-year-old postmenopausal woman presented with acute right-sided back pain and history of occasional abnormal uterine bleeding. She was diagnosed with endometrial cancer with ruptured bilateral adrenal metastases. She underwent total hysterectomy and bilateral salpingo-oophorectomy, and the pathological findings revealed dedifferentiated carcinoma. After three courses of adjuvant chemotherapy, the bilateral adrenal metastases had increased in size, with worsening back pain and adrenal hormone insufficiency. The patient died 6 months after the identification of adrenal tumors. Acute back pain may lead to the identification of a ruptured adrenal metastasis. The possibility of gradual adrenal insufficiency should be considered in bilateral adrenal metastases. Although the prognosis is poor, tumor debulking surgery followed by adjuvant chemotherapy could be suggested to improve the prognosis.

Inappropriate surgery in a patient with misdiagnosed Robert's uterus.

BACKGROUND: Robert's uterus is a rare Mullerian anomaly, which can be described as an asymmetric, septate uterus with a non-communicating hemicavity. Herein, we present the case of a misdiagnosed Robert's uterus, resulting in an invasive and disadvantageous surgery. CASE PRESENTATION: A 16-year-old woman was referred to our department because of dysmenorrhea and suspicion of uterine malformation. We misdiagnosed Robert's uterus as a unicornuate uterus with a non-communicating rudimentary horn and hematometra, and performed laparoscopic hemi-hysterectomy. Although the patient's symptoms were relieved, our surgical procedure left the lateral uterine wall weak, making the patient's uterus susceptible to uterine rupture in any future pregnancy. CONCLUSIONS: Although the early diagnosis of Robert's uterus is challenging, it is important in order to determine appropriate surgical interventions and management for maintaining the quality of life and ensuring safety in future pregnancies.