Kiyoko Kato

Current Status of Fertility‐Sparing Treatment for Gynecological Cancers in Japan: A Nationwide Survey

ABSTRACT Aim There is an increasing demand for fertility‐sparing treatment (FST) among young women with gynecological cancer. This study aimed to clarify the current status of FST implementation across Japan by focusing on institutional practice patterns and clinical protocols for cervical, endometrial, and ovarian cancers. Methods A nationwide cross‐sectional survey was conducted between August and September 2024. An online questionnaire was distributed to 481 gynecologic tumor registry institutions through the Japan Society of Obstetrics and Gynecology mailing list. Data on institutional characteristics, specific FST eligibility criteria, treatment methods, and post‐treatment management were collected. Results Responses were received from 226 institutions (response rate: 47.0%), and all respondent institutions (100%) performed FST for at least one gynecological cancer. Although FST is widely available, significant heterogeneity in clinical protocols was observed across all three cancers. Key variations among respondent institutions included a low implementation rate of radical trachelectomy for cervical cancer (20.8%), a high rate of post‐FST hysterectomy for endometrial cancer (63.6%) compared to cervical cancer and ovarian cancer, and exclusion criteria for patients with hereditary cancer syndromes. Conclusion FST is an established practice in Japan; however, there is a lack of consensus regarding its clinical application. These findings provide a critical benchmark for future efforts to standardize care and develop collaborative networks to optimize this essential treatment modality for young patients with gynecological cancer.

Olaparib maintenance therapy for recurrent adult granulosa cell tumors: A case report

Abstract Poly (ADP‐ribose) polymerase inhibitors (PARPi) are now available for advanced or recurrent epithelial ovarian cancer after platinum‐based chemotherapy; however, there is little known concerning the use of PARPi for adult granulosa cell tumors (AGCT). A 49‐year‐old woman, who previously had primary debulking surgery and a second surgery for a first intraperitoneal recurrence, received a surgery for a second intraperitoneal recurrence of AGCT. Although she received paclitaxel–carboplatin combination chemotherapy and a combination of bleomycin, etoposide, and cisplatin after the surgeries for the first and the second recurrences, respectively, the risk of a third recurrence was considered very high due to microscopic peritoneal dissemination. Olaparib administration was initiated based on a FANCA mutation, which results in homologous recombination deficiency. The patient has been recurrence‐free for over 4 years since the initiation of olaparib. This case highlights the possibility of using olaparib for AGCT with a homologous recombination gene mutation.

Claudin‐18 expression in gastric type adenocarcinoma and HPV ‐associated adenocarcinoma of the uterine cervix

Aims Claudin‐18 (CLDN18) is both a marker for the gastric phenotype and a therapeutic target. However, little is known about its immunoexpression in endocervical adenocarcinomas (ECAs), particularly as detected using the clone 43‐14A antibody, or about the gene expression of its isoforms in ECAs. Methods and results We examined CLDN18, HIK1083, p16 and Rb expression by immunohistochemistry and high‐risk human papillomavirus (HR‐HPV) mRNA by in situ hybridization (ISH) in 121 ECAs, including 35 HPV‐independent adenocarcinomas (gastric type [GAS], n  = 24; non‐GAS, n  = 11) and 86 HPV‐associated ECAs. We also analysed mRNA expression of the CLDN18.1 (lung type) and CLDN18.2 (gastric type) isoforms by quantitative polymerase chain reaction (qPCR) in selected cases. CLDN18 positivity was detected in 8/24 (33%) GASs, 0/11 (0%) non‐GASs and 2/86 (2%) HPV‐associated ECAs, with positivity defined as staining in ≥75% of tumour cells, as in gastric cancer. When a 5% cut‐off was used, CLDN18 positivity was detected in 22/24 (92%) GASs, 0/11 (0%) non‐GASs and 6/86 (7%) HPV‐associated ECAs; CLDN18 expression was thus significantly associated with GAS histology ( P  < 0.0001). Among the 6 cases of HPV‐associated ECAs with CLDN18 expression (ranging from 5% to 80%), the histological patterns included a mix of usual and mucinous features in 4 cases, pure usual type in 1 and villoglandular variant in 1. Otherwise features such as p16 overexpression and the Rb partial loss pattern were consistent with those of HPV‐associated ECAs. Six of 22 (27%) CLDN18‐positive GASs were also positive for p16, but their other features—such as CLDN18 expression and the Rb preserved pattern—were the same as in p16 negative GASs. Expression of CLDN18.2 mRNA but not CLDN18.1 mRNA was confirmed in both GASs and HPV‐associated ECAs. Conclusions CLDN18 (43‐14A) emerged as a potential diagnostic and therapeutic marker for GAS. A minor subset of HPV‐associated ECAs also can be immunoreactive for CLDN18 and express CLDN18.2 mRNA, suggesting divergent gastric phenotypic differentiation. The caution is that GAS and HPV‐associated ECAs can share overlapping histological features and similar expression of CLDN18 and p16.

Obstetric Outcome After Trachelectomy for Cervical Cancer Without Uterine Artery Preservation

ABSTRACT Aim A trachelectomy is a fertility‐preserving surgery that is performed for cervical cancer. Transecting the uterine arteries (UAs) during abdominal radical trachelectomy (ART) or abdominal modified radical trachelectomy (AmRT) has the advantage of simplifying other surgical procedures. However, the effect of UA transection on subsequent pregnancy outcome is unknown. The purpose of this study was to clarify the pregnancy outcomes in post‐RT pregnancies in which the UAs were not preserved. Methods This was a retrospective cohort study of electronic case records involving pregnant women after ART and AmRT, which were managed at Kyushu University Hospital from January 2008 to July 2024. Results Complications that often occur in pregnancies after ART and AmRT, such as antepartum bleeding, premature birth, and preterm premature rupture of membranes, were noted to the same degree after UA‐sparing ART. In contrast, abnormalities related to placental attachment, such as placenta previa and adherent placenta, occurred at a high rate after UA transection. Furthermore, compared to pregnancies with normal placentation, pregnancies with abnormal placentation had more blood loss during cesarean section (1150 g vs. 2289 g; p  = 0.0004) and required blood transfusion more frequently (5.7% vs. 64.2%; p  < 0.0001). Conclusions Although ART and AmRT with UA transection may increase the risk of abnormal placentation and bleeding‐related complications during cesarean section, UA transection may not increase the risk of major obstetric complications after ART and AmRT. Therefore, UA transection should be considered during ART and AmRT due technical advantages.

Retrospective analysis of treatment and prognosis for clear cell carcinoma of the uterine cervix: 15‐year experience at a single institution

AbstractAimClear cell carcinoma of the uterine cervix (CCCUC) is a rare disease, accounting for 4% to 9% of cervical adenocarcinomas. Because it is so rare, its pathogenesis is largely unknown, and the standard treatment is unclear due to a lack of prospective studies. Our aim is to investigate the clinical features, treatment, and prognosis of CCCUC.MethodsWe retrospectively evaluated the clinical characteristics, treatment choices, and outcomes of 12 patients with CCCUC treated at our institution between January 2009 and July 2024.ResultsThe median patient age was 62.5 years (range, 14–90 years). The most common stage was IB (IA, n = 3; IB, n = 4; IIB, n = 1; IIIC, n = 2; IVB, n = 2). Ten patients underwent surgery as initial treatment: 6 underwent radical hysterectomy plus pelvic lymphadenectomy (PLD) or sentinel lymph node biopsy (SLNB), with or without para‐aortic lymphadenectomy (PALD); 3 underwent modified radical hysterectomy plus PLD with or without PALD; and 1 underwent radical trachelectomy with SLNB as fertility‐preserving surgery. All patients underwent bilateral salpingo‐oophorectomy except for the patient who opted for radical trachelectomy. Five patients received adjuvant treatment: 3 received platinum‐based systemic chemotherapy (2 of whom had combination therapy with bevacizumab), and 2 received concurrent chemoradiotherapy. The median follow‐up was 43.5 months (range, 1–123 months). The 5‐year progression‐free survival rate was 64.5%.ConclusionSystemic platinum‐based chemotherapy with bevacizumab may be more effective than concurrent chemoradiotherapy as adjuvant therapy for CCCUC.

Safety evaluation of abdominal trachelectomy in patients with cervical tumors ≥2 cm: a single-institution, retrospective analysis

For oncologic safety, vaginal radical trachelectomy is generally performed only in patients with cervical cancers smaller than 2 cm. However, because inclusion criteria for abdominal trachelectomy are controversial, we evaluated the safety of abdominal trachelectomy for cervical cancers ≥2 cm. We began performing abdominal trachelectomies at our institution in 2005, primarily for squamous cell carcinoma ≤3 cm or adenocarcinoma/adenosquamous carcinoma ≤2 cm. If a positive sentinel lymph node or cervical margin was diagnosed intraoperatively by frozen section, the trachelectomy was converted to a hysterectomy. Medical records of these patients were reviewed retrospectively. Patients who had undergone simple abdominal trachelectomy were excluded from this study. We attempted trachelectomy in 212 patients. Among the 135 patients with tumors <2 cm, trachelectomy was successful in 120, one of whom developed recurrence and none of whom died of their disease. Among 77 patients with tumors ≥2 cm, trachelectomy was successful in 62, 2 of whom developed recurrence and 1 of whom died of her disease. The overall relapse rate after trachelectomy was 1.6% (0.8% in <2 cm group and 3.2% in ≥2 cm group), and the mortality rate was 0.5% (0% in <2 cm group and 1.6% in ≥2 cm group). Recurrence-free survival (p=0.303) and overall survival (p=0.193) did not differ significantly between the <2 cm and ≥2 cm groups. Abdominal trachelectomy with intraoperative frozen sections of sentinel lymph nodes and cervical margins is oncologically safe, even in patients with tumors ≥2 cm.

Gut microbiome associated with PARP inhibitor efficacy in patients with ovarian cancer

To investigate an association between the gut microbiome and efficacy of poly(ADP-ribose) polymerase inhibitors (PARPi) in ovarian cancer. This study conducted fecal microbiome analysis (16S rRNA gene sequencing) and circulating tumor DNA (ctDNA) profiling for ovarian cancer patients who underwent PARPi maintenance therapy. Fecal and blood samples were collected at the baseline and the progressive disease (PD) or last follow-up. The relative abundance of gut microbes and progression-free survival (PFS) were analyzed using linear discriminant analysis of effect size and the Cox proportional hazard model according to Baseline samples were available from 23 High fecal composition of