Investigator
Tohoku University
Clinical and prognostic insights into Trousseau’s syndrome in gynecologic malignancies: a multicenter study
Breast cancer surveillance for epithelial ovarian cancer patients with BRCA1 and BRCA2 pathogenic variants: a single-center retrospective study
Abstract Objectives To identify a method for breast cancer (BC) surveillance in patients with epithelial ovarian cancer (EOC) with germline BRCA1/2 pathogenic variants (gBRCA1/2m) and the incidence of BC after EOC in the era of broad PARP inhibitors use. Methods We retrospectively analyzed the data on EOC patients who had gBRCA1/2m by genetic testing between January 2017 and August 2023 in our single center. Results Of 125 patients with EOC, 33 had gBRCA1/2m. Of these, 27 (81.8%) underwent BC surveillance, 20 ultrasound and/or mammography, and seven magnetic resonance imaging (MRI). The median time from EOC diagnosis to the initiation of BC surveillance was 8 months. EOC recurrence was significantly lower in the group with MRI than in the group without MRI (no case vs. 10 cases, P = .0261). The duration from EOC diagnosis to the start of BC surveillance was longer in the group with MRI than in the group without MRI (21 vs. 7 months, P = .1033). Two (6.1%) patients developed BC after EOC. Both cases were early stage, triple-negative BCs that occurred more than 3 years after the diagnosis of stage III EOC. Conclusions With the advent of PARP inhibitors, long-term survival is expected to increase, and a certain number of patients with EOC after initial treatment may benefit from BC surveillance using MRI. In particular, BC surveillance with MRI may be considered for patients who have not experienced EOC recurrence for more than 2 years.
Rethinking the significance of surgery for uterine cervical cancer
AbstractBackgroundTreatment strategies based on histological subtypes are unestablished.AimsRethinking the significance of surgery for uterine cervical cancer.MethodsUsing the database of cervical cancer stages IB–IIB with extensive hysterectomy (Federation of Gynecology and Obstetrics [FIGO] 2008) established by the Japanese Gynecologic Oncology Group network, we conducted a clinicopathological study of cervical cancer cases reclassified according to the FIGO 2018 staging. In stage IB (FIGO 2018) cervical cancer patients, there was no significant difference in treatment outcome according to histological type, but in stages IIA, IIB, and IIIC1 (FIGO 2018), the treatment outcome of nonsquamous cell carcinoma was significantly worse than that of squamous cell carcinoma. Considering post‐treatment health care, it is important to consider ovarian preservation in young patients with cervical cancer, up to stage IIA (FIGO 2018) for squamous cell carcinoma and stage IB1 (FIGO 2018) for nonsquamous cell carcinoma, after careful evaluation of clinicopathological factors before surgery.DiscussionLocally advanced adenocarcinoma of the cervix is a rare and refractory cancer that has been shown to have low radiosensitivity, and its treatment outcome is still unsatisfactory. A new therapeutic strategy involving multidisciplinary treatment in combination with perioperative chemotherapy at a facility that can provide highly curative surgical treatment is desired.ConclusionMinimally invasive surgery is being introduced for the treatment of early‐stage cervical cancer. However, the number of eligible cases should be expanded in a phased manner, based on an objective evaluation of surgical outcomes at the facilities. Omics analysis may be useful to develop a new treatment for human papillomavirus nonrelated cervical cancer, represented by gastric mucinous carcinoma.
The trend and outcome of postsurgical therapy for high-risk early-stage cervical cancer with lymph node metastasis in Japan: a report from the Japan Society of Gynecologic Oncology (JSGO) guidelines evaluation committee
The Japan Society of Gynecologic Oncology published the first guidelines for the treatment of cervical cancer in 2007. The aim of this research was to evaluate the influence of the introduction of the first guideline on clinical trends and outcomes of patients with early-stage cervical cancer who underwent surgery. This analysis included 9,756 patients who were diagnosed based on the pathological Tumor-Node-Metastasis (pTNM) classification (i.e., pT1b1, pT1b2, pT2b and pN0, pN1, pNX) and received surgery as a primary treatment between 2004 and 2009. Data of these patients were retrospectively reviewed, and clinicopathological trends were assessed. The influence of the introduction of the guideline on survival was determined by using a competing risk model. For surgery cases, the estimated subdistribution hazard ratio (HR) by the competing risk model for the influence of the guideline adjusted for age, year of registration, pT classification, pN classification, histological type, and treatment methods was 1.024 (p=0.864). Following the introduction of the first guideline in 2007, for patients with lymph node metastasis, the use of chemotherapy (CT) as a postsurgical therapy increased, whereas that of concurrent chemoradiotherapy (CCRT)/radiotherapy (RT) decreased (p<0.010). For pN1 cases, the estimated subdistribution HR by the competing risk model for the influence of the guideline was 1.094 (p=0.634). There was no significance in the postsurgical therapy between CT and CCRT/RT (p=0.078). Survival of surgical cases was not improved by the introduction of the guidelines. It is necessary to consider more effective postsurgical therapy for high-risk early-stage cervical cancer.
Identification of predictive biomarkers for diagnosis and radiation sensitivity of uterine cervical cancer using wide‐targeted metabolomics
AbstractAimUterine cervical cancer (UCC) is the fourth most common cancer in women, responsible for more than 300 000 deaths worldwide. Its early detection, by cervical cytology, and prevention, by vaccinating against human papilloma virus, greatly contribute to reducing cervical cancer mortality in women. However, penetration of the effective prevention of UCC in Japan remains low. Plasma metabolome analysis is widely used for biomarker discovery and the identification of cancer‐specific metabolic pathways. Here, we aimed to identify predictive biomarkers for the diagnosis and radiation sensitivity of UCC using wide‐targeted plasma metabolomics.MethodsWe analyzed 628 metabolites in plasma samples obtained from 45 patients with UCC using ultra‐high‐performance liquid chromatography with tandem mass spectrometry.ResultsThe levels of 47 metabolites were significantly increased and those of 75 metabolites were significantly decreased in patients with UCC relative to healthy controls. Increased levels of arginine and ceramides, and decreased levels of tryptophan, ornithine, glycosylceramides, lysophosphatidylcholine, and phosphatidylcholine were characteristic of patients with UCC. Comparison of metabolite profiles in groups susceptible and non‐susceptible to radiation therapy, a treatment for UCC, revealed marked variations in polyunsaturated fatty acid, nucleic acid, and arginine metabolism in the group not susceptible to treatment.ConclusionsOur findings suggest that the metabolite profile of patients with UCC may be an important indicator for distinguishing these patients from healthy cohorts, and may also be useful for predicting sensitivity to radiotherapy.