Effect of a web-based fertility preservation training program for medical professionals in Japan.

BACKGROUND: Our web-based training program called "Educating Medical Professionals about Reproductive Issues in Cancer Healthcare" aims to help healthcare professionals communicate promptly with patients and survivors who are adolescents and young adults, with information pertinent to reproductive health issues such as the risk of infertility and fertility preservation. METHODS: The study participants were professional healthcare providers, including physicians, nurses, pharmacists, social workers, midwives, psychologists, laboratory technicians, genetic counselors, and dieticians. Pre- and post- and 3-month follow-up tests consisting of 41 questions were administered to measure changes in knowledge and confidence. The participants also received a follow-up survey that covered confidence, communication techniques, and practice habits. A total of 820 healthcare providers participated in this program. RESULTS: The mean total score from the pre-test to the post-test grew significantly (p < 0.01), and participants' self-confidence increased. In addition, there was a change in the behavior of healthcare providers, who began asking about patients' marital status and parity. CONCLUSION: Our web-based fertility preservation training program improved knowledge and self-confidence regarding fertility preservation issues among healthcare providers caring for adolescents and young adult cancer patients and survivors.

Cancer risk and genotype-phenotype correlation in Japanese patients with Cowden syndrome.

BACKGROUND: Cowden syndrome (CS) is an autosomal-dominant hereditary disorder caused by a germline PTEN variant and characterized by multiple hamartomas and a high risk of cancers. However, no detailed data on CS in Asian patients nor genotype-phenotype correlation have been reported. METHODS: We performed the first Japanese nationwide questionnaire survey on CS and obtained questionnaire response data on 49 CS patients. RESULTS: Patients included 26 females (median age 48 years). The incidence of breast, thyroid, endometrium, and colorectal cancer was 32.7%, 12.2%, 19.2% (among females), and 6.1%, respectively. The incidence of any cancers was relatively high among all patients (46.9%, 23/49), and particularly female patients (73.1%, 19/26), compared with previous reports from Western countries. Gastrointestinal (GI) polyps were more frequently found throughout the GI tract compared with previous studies. PTEN variants were detected in 95.6% (22/23) of patients; 12 in the N-terminal region (11 in phosphatase domain) and 10 in the C-terminal (C2 domain) region. The incidence of cancer in the C2 domain group was significantly higher than in the N-terminal region (phosphatase) group. All female patients with C2 domain variant had breast cancer. CONCLUSION: Our data suggest that Japanese patients with CS, particularly female patients and patients with C2 domain variant may have a high risk of cancers.

[The Role of Genetic Counselors in Comprehensive Genomic Profiling].

Genome information has been utilized for the determination of cancer therapy, where some of the hereditary cancer chance to be diagnosed by the analysis of germline variants. The more genomic technology has advanced, the more interpretation of genomic information has been complicated. It is required to enhance the medical network to provide strong support and to determine the appropriate medicine for patients. In this paper, we will discuss the essential roles of genomic counselors in the age of genomic medicine.

Clinical practice guidance for next-generation sequencing in cancer diagnosis and treatment (edition 2.1).

BACKGROUND: To promote precision oncology in clinical practice, the Japanese Society of Medical Oncology, the Japanese Society of Clinical Oncology, and the Japanese Cancer Association, jointly published "Clinical practice guidance for next-generation sequencing in cancer diagnosis and treatment" in 2017. Since new information on cancer genomic medicine has emerged since the 1st edition of the guidance was released, including reimbursement for NGS-based multiplex gene panel tests in 2019, the guidance revision was made. METHODS: A working group was organized with 33 researchers from cancer genomic medicine designated core hospitals and other academic institutions. For an impartial evaluation of the draft version, eight committee members from each society conducted an external evaluation. Public comments were also made on the draft. The finalized Japanese version was published on the websites of the three societies in March 2020. RESULTS: The revised edition consists of two parts: an explanation of the cancer genomic profiling test (General Discussion) and clinical questions (CQs) that are of concern in clinical practice. Particularly, patient selection should be based on the expectation that the patient's post-test general condition and organ function will be able to tolerate drug therapy, and the optimal timing of test should be considered in consideration of subsequent treatment plans, not limited to treatment lines. CONCLUSION: We expect that the revised version will be used by healthcare professionals and will also need to be continually reviewed in line with future developments in cancer genome medicine.

[Diagnosis of pancreatic neuroendocrine tumor led to diagnosis of multiple endocrine neoplasia type 1:a report of two cases].

Two cases of multiple endocrine neoplasia type 1 are reported. In both cases, computed tomography (CT) showed hypervascular lesions of the pancreas. Endoscopic ultrasound showed multiple lesions in the pancreas, and each case was diagnosed as pancreatic neuroendocrine tumor by EUS-FNA. In addition to a pancreatic neuroendocrine tumor, case 1 had hyperparathyroidism and case 2 had a history of parathyroid tumor. Furthermore, case 1 had a family history of pancreatic tumor and case 2 had a family history of pancreatic tumor and parathyroid resection. From these indications, multiple endocrine neoplasia type 1 was diagnosed by genetic testing. As demonstrated in these two cases, it is important to consider multiple endocrine neoplasia type 1 when diagnosing pancreatic neuroendocrine tumor.

Comprehensive assay for the molecular profiling of cancer by target enrichment from formalin-fixed paraffin-embedded specimens.

Tumor molecular profiling is becoming a standard of care for patients with cancer, but the optimal platform for cancer sequencing remains undetermined. We established a comprehensive assay, the Todai OncoPanel (TOP), which consists of DNA and RNA hybridization capture-based next-generation sequencing panels. A novel method for target enrichment, named the junction capture method, was developed for the RNA panel to accurately and cost-effectively detect 365 fusion genes as well as aberrantly spliced transcripts. The TOP RNA panel can also measure the expression profiles of an additional 109 genes. The TOP DNA panel was developed to detect single nucleotide variants and insertions/deletions for 464 genes, to calculate tumor mutation burden and microsatellite instability status, and to infer chromosomal copy number. Clinically relevant somatic mutations were identified in 32.2% (59/183) of patients by prospective TOP testing, signifying the clinical utility of TOP for providing personalized medicine to cancer patients.

Experience with Bilateral Risk-Reducing Mastectomy for an Unaffected BRCA Mutation Carrier.

Women with BRCA1/2 mutations have a high risk of breast cancer and may opt for risk-reducing mastectomy (RRM). We report a 38-year-old Japanese woman who was diagnosed as a BRCA2 mutation carrier. She underwent prophylactic bilateral skin-sparing mastectomy (SSM) with excision of the nipple and preservation of the areola skin. It is unclear whether a bilateral RRM leads to better survival compared with intensive surveillance. The oncological risk associated with the presence of remnant breast glandular tissue after SSM or nipple-sparing mastectomy has been obscure. We report the first case of RRM for a Japanese BRCA mutation carrier and provide a literature review on risk management for BRCA mutation carriers with a focus on the concepts and procedures of RRM.

Mutational analysis of FOXL2 p.C134W and expression of bone morphogenetic protein 2 in Japanese patients with granulosa cell tumor of ovary.

AIM: To assess whether FOXL2 p.C134W mutation may play a role in the development of human ovarian tumors in the Japanese, we investigated the FOXL2 codon 134 mutation and protein expression of inhibin-α, bone morphogenetic protein 2 (BMP2) and follistatin (FST) in Japanese patients with granulosa cell tumor (GCT) of the ovary and other ovarian tumors. METHODS: We analyzed 114 tumor tissues from ovarian tumors, including 44 adult-type and two juvenile-type GCT of the ovary and 68 ovarian tumors by DNA sequencing. Immunohistochemistry was also performed in the adult and juvenile GCT tissues by immunostaining inhibin-α, BMP2 and FST. RESULTS: We found the FOXL2 p.C134W mutation in 27 out of 44 (61.4%) adult-type GCT of the ovary, but none in other ovarian tumors. Histologically, all of the adult-type GCT sections were positive for inhibin-α, and the expression of BMP2 and FST was detected in 14 of 44 (31.8%) and zero of 47 (0%), respectively. No significant differences regarding the diagnosed age, preoperative serum carbohydrate antigen 125 levels, or BMP2 immunopositivity between the FOXL2 p.C134W mutation-positive and mutation-negative were found in the adult-type GCT patients. CONCLUSION: Our findings suggest that FOXL2 p.C134W mutation-positive adult-type GCT of the ovary may not be common in the Japanese as compared to the previous data.