Investigator
Kyushu University
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.
The BHLHE40‒PPM1F‒AMPK pathway regulates energy metabolism and is associated with the aggressiveness of endometrial cancer
BHLHE40 is a basic helix-loop-helix transcription factor that is involved in multiple cell activities including differentiation, cell cycle, and epithelial-to-mesenchymal transition. While there is growing evidence to support the functions of BHLHE40 in energy metabolism, little is known about the mechanism. In this study, we found that BHLHE40 expression was downregulated in cases of endometrial cancer of higher grade and advanced disease. Knockdown of BHLHE40 in endometrial cancer cells resulted in suppressed oxygen consumption and enhanced extracellular acidification. Suppressed pyruvate dehydrogenase (PDH) activity and enhanced lactated dehydrogenase (LDH) activity were observed in the knockdown cells. Knockdown of BHLHE40 also led to dephosphorylation of AMPKα Thr172 and enhanced phosphorylation of pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1) Ser293 and lactate dehydrogenase A (LDHA) Tyr10. These results suggested that BHLHE40 modulates PDH and LDH activity by regulating the phosphorylation status of PDHA1 and LDHA. We found that BHLHE40 enhanced AMPKα phosphorylation by directly suppressing the transcription of an AMPKα-specific phosphatase, PPM1F. Our immunohistochemical study showed that the expression of BHLHE40, PPM1F, and phosphorylated AMPKα correlated with the prognosis of endometrial cancer patients. Because AMPK is a central regulator of energy metabolism in cancer cells, targeting the BHLHE40‒PPM1F‒AMPK axis may represent a strategy to control cancer development.
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.
