Hirokazu Usui

Therapy‐related myeloid neoplasms after treatment for ovarian cancer: A retrospective single‐center case series

Abstract Objective Therapy‐related myeloid neoplasms (t‐MNs) are often fatal and arise as late complications of previous anticancer drug treatment. No single‐center case series has examined t‐MNs in epithelial ovarian cancer (EOC). Methods All patients with EOC treated at Chiba University Hospital between 2000 and 2021 were included. We retrospectively analyzed the characteristics, clinical course, and outcomes of patients who developed t‐MNs. Results Among 895 cases with EOC, 814 cases were treated with anticancer drugs. The median follow‐up period was 45 months (interquartile range, 27–81) months. Ten patients (1.2%) developed t‐MNs (FIGO IIIA in one case, IIIC in three, IVA in one, and IVB in five). Nine patients were diagnosed with myelodysplastic syndrome and one with acute leukemia. One patient with myelodysplastic syndrome developed acute leukemia. The median time from the first chemotherapy administration to t‐MN onset was 42 months (range, 21–94 months), with t‐MN diagnoses resulting from pancytopenia in four cases, thrombocytopenia in three, and blast or abnormal cell morphology in four. The median number of previous treatment regimens was four (range, 1–7). Paclitaxel + carboplatin therapy was administered to all patients, gemcitabine and irinotecan combination therapy to nine, bevacizumab to eight, and olaparib to four. Six patients received chemotherapy for t‐MN. All patients died (eight cancer‐related deaths and two t‐MN‐related deaths). None of the patients was able to restart cancer treatment. The median survival time from t‐MN onset was 4 months. Conclusions Patients with EOC who developed t‐MN were unable to restart cancer treatment and had a significantly worse prognosis.

Evaluation of the usefulness of sentinel lymph node mapping using indocyanine green in patients with cervical and endometrial cancers: A single‐center prospective exploratory study

AbstractAimSentinel lymph node (SLN) mapping using indocyanine green (ICG) is an alternative for reducing comprehensive lymph node dissection and its associated morbidity. This trial aimed to assess the efficacy and safety of ICG for SLN detection in patients with cervical and endometrial cancers at a single academic teaching hospital.MethodsThis single‐arm, open‐label trial conducted at Chiba University Hospital included patients with endometrial or cervical cancer, aged 20–70 years, with an Eastern Cooperative Oncology Group performance status of 0 or 1. ICG was injected into the uterine cervix after anesthesia induction. For patients with endometrial cancer, ICG was additionally injected into the uterine myometrium after laparotomy. Imaging‐assisted surgery was then performed to locate and remove the SLNs. Systematic pelvic lymph node dissection was performed as the standard procedure, with additional para‐aortic lymph node dissection in selected cases.ResultsThe overall and bilateral SLN detection rates were 80.4% (37/46) and 50.0% (23/46), respectively. SLN identification was successful in 37 patients. Of these, 34 had pathologically negative SLNs, and all of them showed no lymph node metastasis in the backup dissection (negative predictive value: 100%). The remaining three cases had pathologically positive SLNs. No adverse events were observed in a total of 49 enrolled patients.ConclusionsICG injection was found to be safe. SLN mapping using ICG has demonstrated significant potential in reducing surgical interventions and associated complications in the treatment of early‐stage gynecological cancers.

High prevalence of pulmonary embolism prior to cancer therapies in patients with ovarian and endometrial cancers detected by contrast‐enhanced CT using D‐dimer as an index

AbstractObjectiveWe aimed to evaluate the prevalence of pulmonary embolism (PE) before cancer therapies in patients with ovarian and endometrial cancers with enhanced computed tomography (CT) using D‐dimer (DD), and determine the optimal cut‐off level of DD.MethodsSince 2009, we have performed preoperative venous thromboembolism (VTE) screening of patients with ovarian and endometrial cancer. For patients with DD levels of more than 1.0 μg/ml, enhanced CT images were obtained from the pulmonary apex to the foot to detect PE and deep venous thrombosis (DVT) simultaneously.ResultsAmong patients with ovarian cancer, 84 of 413 (20.3%) had VTEs (DVT alone, n = 31 [7.5%]; PE with or without DVT, n = 53 [12.8%]; PE alone, n = 12 [2.9%]). Among patients with endometrial cancer, 50 of 455 (11.0%) had VTEs (DVT alone, n = 19 [4.2%]; PE with or without DVT, n = 31 [6.8%], PE alone, n = 14 [3.1%]). The optimal cut‐off level of DD was estimated to be ≥1.5 and ≥1.2 μg/ml in ovarian and endometrial cancers, respectively.ConclusionOur study revealed a high prevalence of PE before cancer therapies in patients with ovarian and endometrial cancers by enhanced CT using DD.

Resolution of pelvic postoperative spindle cell nodule with sarcomatous onset after 9 years of follow‐up

AbstractIntroductionPostoperative spindle cell nodules are benign and reactive lesions that occur at the previous surgical site. It often develops like a sarcoma and is resected via highly invasive procedures. To date, there have been no published reports on the natural progression of postoperative spindle cell nodules without surgical intervention.CaseA 45‐year‐old woman underwent a total abdominal hysterectomy for leiomyoma. A 5‐cm pelvic mass exposed in the vaginal stump developed 7 weeks later, causing genital bleeding. Positron emission tomography–computed tomography revealed a pelvic mass and an enlarged pelvic lymph node with high uptake. We suspected an invasive sarcoma in the pelvis. However, through a transvaginal needle biopsy, the mass was diagnosed as a postoperative spindle cell nodule posthysterectomy. The nodule slowly reduced in size and completely disappeared 9 years posthysterectomy.ConclusionsCorrect diagnosis of this nodule with sarcomatous onset based on biopsy was important to avoid unnecessary surgeries. The lesion completely disappeared spontaneously after long‐term follow‐up.

Single‐nucleotide polymorphism array and fluorescence in situ hybridization analysis to decode the cytogenetic profile of atypical partial hydatidiform moles diagnosed by short tandem repeat polymorphism analysis

AbstractAccurate diagnosis of partial hydatidiform moles (PHMs) is crucial for improving outcomes of gestational trophoblastic neoplasia. The use of short tandem repeat (STR) polymorphism analysis to distinguish between PHM and hydropic abortuses is instrumental; however, its diagnostic power has not been comprehensively assessed. Herein, we evaluated the diagnostic efficacy of STR in differentiating between PHM and hydropic abortus, thus providing an opportunity for early measurement of human chorionic gonadotropin for PHMs. We reviewed charts of STR polymorphism analysis performed on fresh villous specimens and patient blood samples using a commercial kit for 16 loci. The genetic classification of 79 PHMs was confirmed. STR was reliable in differentiating PHMs when at least 15 loci were available. Typically, PHMs are characterized by their triploidy, including two paternal and one maternal haploid contribution. In our sample, seven PHMs lacked the three‐allelic loci, requiring fluorescence in situ hybridization (FISH) analysis to investigate imbalanced biparental conceptus and single‐nucleotide polymorphism array analysis to reveal cytogenetic details. Of these PHMs, two, three, and one were identified as androgenetic/biparental mosaics (diploids), monospermic diandric monogynic triploids, and a typical dispermic diandric monogynic triploid, respectively. The remaining case was monospermic origin, but its ploidy details could not be available. Therefore, STR differentiated PHM from a biparental diploid abortus in most cases. However, PHM diagnosis may be compromised when STR is used as the sole method for cases displaying distinct cytogenetic patterns lacking the three‐allelic loci, including androgenetic/biparental mosaicism. Therefore, FISH should be considered to confirm the diagnosis.

A Phase Ib Study of Durvalumab (MEDI4736) in Combination with Carbon-Ion Radiotherapy and Weekly Cisplatin for Patients with Locally Advanced Cervical Cancer (DECISION Study): The Early Safety and Efficacy Results

We conducted a phase Ib study to examine the safety of a combination of carbon-ion RT (CIRT) with durvalumab (MEDI4736; AstraZeneca) in patients with locally advanced cervical cancer. This was an open-label, single-arm study with a modified 3 + 3 design. Patients with newly diagnosed histologically proven locally advanced cervical cancer were enrolled. All patients received 74.4 Gy of CIRT in 20 fractions and concurrent weekly cisplatin (chemo-CIRT) at a dose of 40 mg/m2. Durvalumab was administered (1500 mg/body) at weeks two and six. The primary endpoint was the incidence of adverse events (AEs) and serious AEs (SAEs), including dose-limiting toxicity (DLT). All three enrolled patients completed the treatment without interruption. One patient developed hypothyroidism after treatment and was determined to be an SAE. No other SAEs were observed. The patient recovered after levothyroxine sodium hydrate treatment. None of the AEs, including hypothyroidism, were associated with DLT in the present study. All three patients achieved complete responses within the CIRT region concerning treatment efficacy. This phase 1b trial demonstrates the safety of combining chemo-CIRT and durvalumab for locally advanced cervical cancer in the early phase. Further research is required as only three patients were included in this study.

Comparison of the efficacy and safety of five-day methotrexate versus pulse actinomycin D for low-risk gestational trophoblastic neoplasia: a single-center historical cohort study☆

In 2019, our institution changed the first-line regimen for low-risk gestational trophoblastic neoplasia from 5-day methotrexate (MTX) (20 mg × 5 days, intramuscular injection) to pulse actinomycin D (1.25 mg/m Between 2007 and 2022, 105 low-risk gestational trophoblastic neoplasia cases were identified. The patients' background, outcomes, and adverse effects were analyzed retrospectively using the Mann-Whitney U test, Fisher's exact test, and propensity score-matching analyses. Among the patients, 83 were treated before 2019 (MTX group), and 22 were treated after 2019 (actinomycin D group). Age and pre-treatment human chorionic gonadotropin levels were comparable between the groups. However, the International Federation of Gynecology and Obstetrics score was significantly greater in the MTX group (p < .05). The primary remission rate was significantly greater in the actinomycin D group (81.8%, 18/22) than in the MTX group (38.6%, 32/83, p < .01). Drug resistance was observed in 24.1% (20/83) and 18.2% (4/22) of patients in the MTX and actinomycin D groups, respectively (p = .78). The superior effects of actinomycin D were also observed in the analysis of matched patient backgrounds, including age, human chorionic gonadotropin levels, and International Federation of Gynecology and Obstetrics scores (p < .05). Severe adverse effects requiring a change in chemotherapy were reported in 37.3% (31/83) of the patients in the MTX group but none in the actinomycin D group. Pulse actinomycin D was more effective and safer than 5-day MTX. Considering the convenience of fewer hospital visits, the pulse actinomycin D regimen is a better option for low-risk gestational trophoblastic neoplasia in the Japanese population.