Current Status and Issues of the Japan Oncofertility Registry.

Purpose: Fertility preservation (FP) is becoming increasingly common among child, adolescent, and young-adult (CAYA) patients with cancer. However, Japan has long lacked definite estimates of utilization rates for FP services among CAYA patients with cancer, and little is known about disease/FP outcomes among users. Therefore, the Japan Society for Fertility Preservation (JSFP) launched the Japan Oncofertility Registry (JOFR) in 2018 and started the online registration of information regarding primary disease, FP, and data on prognosis and pregnancy outcomes. This study reports the analytical results of FP data registered in the JOFR as of 2021. Methods: Data about patients' primary disease(s), treatment courses, cancer and pregnancy outcomes, and specific procedures were extracted from the JOFR and analyzed. Results: In 2021, 1244 patients received counseling or treatment related to FP (540 males, 704 females). While the numbers of males in each age group were approximately equal, most females were aged between 31 and 40 years. In total, 490 male and 540 female patients underwent FP procedures. Leukemia, testicular cancer, and malignant lymphoma accounted for the majority of male cases seeking treatment, whereas breast cancer was the primary disease in two-thirds of the females. Since 1999, 395 patients have accumulatively experienced subsequent pregnancy. Conclusions: As of January 2022, >7000 cases from >100 fertility facilities have been registered in the JOFR. In the future, maintaining JOFR to disseminate information on cancer prognoses, pregnancy rates, and other oncofertility outcomes is expected to drive further expansion of oncofertility services in Japan.

Vaginal cancer diagnosed during pregnancy presenting a therapeutic dilemma: A case report.

BACKGROUND: Vaginal cancer is rare, accounting for only about 2% of all cancers of the female reproductive organs, and it is a disease that is rarely encountered in routine clinical practice. Vaginal cancer is mainly treated with radiation therapy or concurrent chemoradiotherapy (CCRT). However, in stage I-II cases, when the lesion is confined to the upper third of the vagina, surgical treatment may include total hysterectomy and vaginal resection with an adequate resection margin. We report a case of stage I vaginal cancer diagnosed at 13 weeks of gestation. There are very few reports on the diagnosis and treatment of vaginal cancer during pregnancy, and it was difficult to decide on a treatment plan; therefore, we report on the course of treatment followed for this patient. CASE PRESENTATION: The patient was a 38-year-old woman with a history of two pregnancies and zero births. The patient had thrombocytopenia and was diagnosed highly suspicious of myelodysplastic syndrome by bone marrow biopsy, and her platelet count remained at approximately 50,000/µL. At the time of the 11-week gestational checkup, a 4-cm pedunculated tumor was found in the right posterior vaginal fornix. Transvaginal tumor resection was performed at 13 weeks of gestation, and the patient was diagnosed with stage I vaginal cancer (squamous cell carcinoma). Because vaginal cancer was confined to the posterior vaginal wall fornix, radical surgery after abortion was suggested as a treatment plan. However, the patient strongly desired to continue the pregnancy, so the policy was to continue the pregnancy and follow-up. However, at 22 weeks of gestation, a recurrent tumor was found in the posterior fornix of the vagina. The lesion had invaded the paravaginal tissue, making radical surgery impossible. At 26 weeks of gestation, an elective cesarean section was performed because of giving priority to early therapeutic intervention to her recurrent vaginal cancer, and it was decided that CCRT with cisplatin would be administered from postpartum day 1. However, because of thrombocytopenia, chemotherapy could not be co-administered, and the treatment was completed with radiation alone. The therapeutic effect was partial response, but 13 weeks after the end of radiation therapy, we observed regrowth of the recurrent tumor and emergence of pelvic lymph node metastasis. The patient received palliative treatment but died 8 months after delivery due to a generally deteriorating condition, sepsis, and disseminated intravascular coagulation. CONCLUSIONS: In cases of malignant tumors associated with pregnancy, treatment policies should consider the perinatal prognosis at the same time as treatment for malignant tumors, and gynecologic oncologists, obstetricians, and neonatologists, from the standpoint of their respective specialties, should thoroughly discuss the "curative effect of treatment for malignant tumors" and the "prognosis of the child after birth" and consider the treatment plan for each case.

Undifferentiated Carcinoma After Laparoscopic Surgery for a Cystic Ovarian Tumour: A Case Study.

Background: Laparoscopic surgery for malignant tumours occasionally results in recurrence at the trocar insertion site or port-site metastasis (PSM). We report on a patient requiring emergency laparoscopic surgery for an ovarian tumour with a review of the relevant literature. Case Report: A 42-year-old woman developed sudden abdominal pain and underwent laparoscopic right adnexectomy because of a suspected ovarian cystic tumour rupture. The postoperative histological diagnosis was a mucinous borderline ovarian tumour; however, an undifferentiated carcinoma was detected at the port site eight months after the initial surgery. The histopathological diagnosis of the abdominal wall tumour at the port site differed from intraoperative pathological findings, which was contradictory to PSM definition. Postoperatively, she received three systemic chemotherapy courses but died consequent to tumour metastasis. Conclusion: This is an atypical PSM case with histopathological differences from the initial tumour. Careful preoperative diagnosis and intraoperative attention are essential in such cases.

Differences in laboratory reporting standards leading to a difficult prenatal diagnosis for a patient with suspected 4p duplication.

Not all obstetric care facilities offer sufficient genetic counseling in Japan. When necessary, patients are referred to tertiary perinatal care centers for genetic counseling and further testing. Because each facility typically has an exclusive contract with a laboratory, the additional testing required may be performed at a different laboratory. With no reporting standards for normal chromosomal variants, differences between laboratories impede result interpretation, and clinical errors may occur. We present a case of a patient diagnosed with 46,XX,?dup (4)(p12p12) variant over two pregnancies. During the first pregnancy, the variant was determined to be a de novo, leading the parents to terminate the pregnancy. During the second pregnancy, further analysis revealed no 4p duplication, and we diagnosed as a normal variant, 4cenh+, inherited from the mother. Differences in reporting standards for a normal variant made evaluation of this patient difficult. Medical staff should be aware of this issue, and reporting standards should be standardized.

[Promotion of Equal Access to Medical Services for Children, Adolescent and Young Adult(CAYA)Cancer Patients with Reproductive Problems-A Nationwide Expansion of the Regional Oncofertility Network in Japan].

OBJECTIVES: Fertility preservation is important for Children, Adolescent and Young Adult(CAYA)cancer patients. Although a regional oncofertility network was established in Japan in 2012, regional inequality persists. This study was aimed at expanding the oncofertility network throughout Japan. METHODS: Oncologists, reproductive medicine specialists, and administrative officials from 24 regions, currently without a regional oncofertility network, conferred to discuss problems and strategies for network expansion. RESULTS: Regional oncofertility networks had already been established in 4 of 24 regions. Consultation and support and a collaboration system between facilities and individual doctors were found in 13 and 14 regions, respectively. Regarding which organization should lead the network operation, the regions(number)chose the prefecture (10), prefectural cancer centers(10), and OB/GYN department of hospitals specializing in cancer treatment(9). Obstacles to establishing a regional oncofertility network were the lack of manpower(21), budget(19), know-how(16), and specialists( 12). DISCUSSION: CAYA cancer patients need equal access to oncofertility networks, and a public support system is essential for preserving the fertility of cancer patients. We should organize a oncofertility network in association with prefectural administration. Medical staff training and supply of materials using the Oncofertility Consortium Japan system are required to promote the oncofertility network throughout Japan.

Kagami-Ogata syndrome in a fetus presenting with polyhydramnios, malformations, and preterm delivery: a case report.

BACKGROUND: Kagami-Ogata syndrome is also known as paternal uniparental disomy 14 and related disorders and is caused by abnormal genomic imprinting in the long arm of the chromosome 14q32.2 region. Its clinical manifestations include polyhydramnios in the fetal stage, respiratory insufficiency because of a small thorax, abdominal wall abnormalities, and peculiar facial features after birth. CASE PRESENTATION: A 38-year-old Japanese primigravida woman was referred to our hospital in the 19th week of pregnancy for suspected omphalocele. She had a history of hypothyroidism but was prescribed orally administered levothyroxine (50 µg/day) prior to conception and was euthyroid. Her ultrasound scan prior to visiting our hospital revealed fetal omphalocele, heavy for date, and polyhydramnios. The mother was advised to be admitted for observation from 28 weeks of gestation for threatened premature delivery. She required amniodrainage at 29 and 32 weeks of gestation. At 35 weeks of gestation, the fetal membrane prematurely ruptured and she gave birth after an emergency Cesarean section. The infant was a male child with a birth weight of 3188 g, and was suspected to have Kagami-Ogata syndrome after birth based on thoracic hypoplasia, swallowing function abnormalities, and peculiar facial features. A definitive diagnosis was established by performing genetic testing of the infant after obtaining informed written consent from both the parents; the results of the genetic testing revealed hypermethylated intergenic-differentially methylated region and maternally expressed gene 3-differentially methylated region in the corresponding chromosome 14 region. Both the parents were genetically tested after adequate genetic counseling, which revealed a de novo microdeletion in a differentially methylated region. CONCLUSION: Kagami-Ogata syndrome should have been suspected because of the presence of polyhydramnios and omphalocele during pregnancy. Respiratory insufficiency soon after birth, because of a small thorax, is expected in this disease and a diagnosis during pregnancy may have enabled appropriate care after birth.

Diagnosis of female 17α-hydroxylase deficiency after gonadectomy: a case report.

BACKGROUND: 17α-Hydroxylase deficiency is a recessively inherited autosomal disease caused by mutations in the CYP17A1 gene. It is a rare disease and accounts for approximately 1% of congenital adrenal cortex hyperplasias. Inhibition of 17α-hydroxylase causes low levels of cortisol and high levels of adrenocorticotropic hormone in the blood as well as excessive levels of mineralocorticoids that lead to hypertension and hypokalemia. Usually, the female patients are diagnosed with abnormality of the genitalia or extra genitalia, primary amenorrhea, or hypertension in puberty. We report a case of a 29-year-old woman who had undergone gonadectomy in her childhood due to complete androgen insensitivity syndrome and was diagnosed with 17α-hydroxylase deficiency in adulthood. CASE PRESENTATION: Our patient was a Japanese female diagnosed with androgen insensitivity syndrome, and both gonadectomy and episioplasty were performed at the age of 11 years at the University of Tsukuba Hospital. Thereafter, she was transferred to our hospital at the age of 21 years for vaginoplasty. At the age of 25 years, she presented with hypertension followed by complicated hypokalemia at the age of 28 years. The captopril loading test and adrenocorticotropic hormone loading test of her adrenal steroidogenesis revealed primary aldosteronism. After sufficient genetic counseling, a genetic test was performed that identified her as having CYP17A1 gene mutation. CONCLUSIONS: The differential diagnosis of disorders of sex development can be difficult at a young age without complete expression of the phenotype. However, diagnosis at a later age would change the treatment and prognosis of the disease; therefore, a genetic examination should be considered.