Hideaki Tsuyoshi

18F-fluorothymidine PET is a potential predictive imaging biomarker of the response to gemcitabine-based chemotherapeutic treatment for recurrent ovarian cancer: preliminary results in three patients.

In order to establish early and precise methods for evaluating the effect of secondary chemotherapy in patients with recurrent ovarian cancer, both the clinical course of 3 women treated with gemcitabine-based secondary chemotherapy and the potential for early and accurate evaluation of the secondary chemotherapeutic effect of 18F-fluorothymidine (FLT) PET are reported. Standard uptake value with FLT PET decreased earlier than with 18F-fluorodeoxyglucose PET and was better correlated with a reduction in size as measured by CT. FLT PET could become a new standard for monitoring response to gemcitabine-based secondary chemotherapy treatment for recurrent ovarian cancer.

Massive Subchorionic Hematoma: Peculiar Prenatal Images and Review of the Literature

Massive subchorionic hematoma is a localized collection of blood or hematoma in the placenta, and can result in serious obstetrical complications. The condition can be diagnosed antenatally by ultrasound. However, no reports have previously described the same condition featuring an intraplacental fluid–fluid level on imaging studies. We report a case of massive subchorionic hematoma diagnosed prenatally, and propose an additional peculiar finding detectable on both the ultrasound and magnetic resonance images: the intraplacental fluid–fluid level. We also review previously reported cases that were detected by ultrasonography.

Diagnosis and management of leiomyosarcoma arising from ovarian vein: case report and literature review.

Primary leiomyosarcomas arising from the ovarian vein are extremely rare and are associated with high morbidity. A 49‐year‐old nulliparous woman presented with a left lower abdominal mass. Although extremely rare, the radiological appearance is able to preoperatively identify malignant retroperitoneal masses, such as leiomyosarcomas originating from the ovarian vein; thus, the patient underwent a simple total excision of the mass‐adjacent organs, as well as complete resection of the uterus, bilateral adnexae and the left ovarian vein. Adjuvant postoperative combination chemotherapy with gemcitabine and docetaxel was administered. At 22 months, she had no recurrence or metastasis. Delayed diagnosis and high metastatic potentiality are associated with the high morbidity of vascular leiomyosarcomas. The preoperative radiological appearance is useful for early diagnosis, and radical treatment with adjuvant chemotherapy consisting of gemcitabine and docetaxel may improve the poor prognosis of patients with leiomyosarcoma arising from the ovarian vein.

Transient elevation of international normalized ratio during cisplatin-based chemotherapy in patients who are taking warfarin.

Objective: To report 2 cases of a probable interaction between cisplatin and warfarin. Case Summary: Two cases of transient elevation of international normalized ratio (INR) during Irinotecan (60 mg/m2 on days 1, 8, and 15) plus cisplatin (60 mg/m2 on day 1) chemotherapy with concomitant warfarin are presented. In both cases, warfarin dosages were stable at the therapeutic target range prior to initiation of chemotherapy. Granisetron hydrochloride (3 mg on days 1, 6, and 15) and dexamethasone (13.2 mg on day 1 and 6.6 mg on days 2, 3, 8, and 15) were used prior to irinotecan administration in both patients. In addition, aprepitant was administered to both patients for 3–5 days with cisplatin. One of these patients also received aprepitant with irinotecan on days 8 and 15. During chemotherapy, INR was transiently elevated almost 1.5-fold over baseline level on day 3. This variation did not occur in subsequent irinotecan cycles on days 8 and 15. The timing of these increases was similar in each of the cycles. Discussion: Cisplatin was the common drug in the cases presented and therefore could be related to the INR elevations. To our knowledge, these are the first reports of an Interaction between warfarin and irinotecan-cisplatin chemotherapy, but reports of a similar interaction with chemotherapy including platinum derivatives exist. Use of the Horn Drug Interaction Probability Scale indicated a probable interaction between warfarin and cisplatin. Conclusions: Cisplatin might affect the anticoagulation function of warfarin. Careful INR monitoring is necessary during antineoplastic chemotherapy with cisplatin in patients taking warfarin.

Protective effect of dienogest on chemotherapy-induced reduced fertility in female rats.

Reduced fertility is one of the main long-term consequences of chemotherapy given for lymphoma, leukemia, and other malignancies in young women. We examined with a female rat model whether and how dienogest, a fourth-generation progestin, modulates reduced fertility following exposure to gonadotoxic chemotherapy. Female rats were administered cyclophosphamide with or without GnRH agonist and different concentrations of dienogest for 20 days. Animals were sacrificed on Day 29, and the numbers of follicle at primordial, preantral and antral stage in the ovaries were counted histologically. Rats treated with sterile saline solution (as control), cyclophosphamide, cyclophosphamide plus GnRH agonist, and cyclophosphamide plus dienogest were also mated with male rats to evaluate their fertility and pregnancy outcomes. Cyclophosphamide significantly reduced the number of primordial follicles, whereas dienogest suppressed depletion of primordial follicle pool induced by chemotherapy. Although the rats exposed to cyclophosphamide alone failed to deliver live births, co-treatment with dienogest improved the pregnancy outcomes of treated rats. The protective effect of dienogest on chemotherapy-induced ovarian damage and reduced fertility was comparable to that of GnRH agonist. The present results suggest that the co-administration of dienogest and chemotherapy may be a useful strategy in preserving ovarian function and fertility in premenopausal women facing gonadotoxic chemotherapy.

Molecular biomarkers for uterine leiomyosarcoma and endometrial stromal sarcoma

Uterine leiomyosarcoma (u‐LMS) and endometrial stromal sarcoma (ESS) are among the most frequent soft tissue sarcomas, which, in adults, lead to fatal lung metastases and patients have an extremely poor prognosis. Due to their rarity and heterogeneity, there are no suitable biomarkers for diagnosis and prognosis, although some biomarker candidates have appeared. In 2017, The Cancer Genome Atlas (TCGA) Research Networks work on u‐LMS has confirmed mutations and deletions in RB1, TP53 and PTEN. In addition, whole‐exome sequencing of u‐LMS has confirmed and demonstrated frequent alterations in TP53, RB1, α‐thalassemia/mental retardation syndrome X‐linked (ATRX) and mediator complex subunit 12 (MED12). MED12 is a useful biomarker to diagnose uterine‐derived LMS and tumors arising from (LM) with a relatively favorable prognosis. TP53 and ATRX mutations can be important mechanisms in the pathogenesis of u‐LMS and are correlated with a poor prognosis. In an update based on the 2014 WHO classification, low‐grade ESS is often associated with gene rearrangement bringing about the JAZF 1‐SUZ12 (formerly JAZF1‐JJAZ1) fusion gene, whereas high‐grade ESS is associated with the YWHAE‐NUTM fusion gene. Low‐grade ESS with JAZF1 rearrangement may correlate with metastasis. However, high‐grade ESS with metastasis with YWHAE rearrangement shows a relatively favorable prognosis. The genetic/molecular genetic aberrations in u‐LMS and ESS are reviewed, focusing on molecular biomarkers for these primary and metastatic tumors.

Saikosaponin-d, a calcium mobilizing agent, sensitizes chemoresistant ovarian cancer cells to cisplatin-induced apoptosis by facilitating mitochondrial fission and G2/M arrest

Cisplatin (CDDP) and its derivatives are first line anti-cancer drugs for ovarian cancer (OVCA). However, chemoresistance due to high incidence of p53 mutations leads to poor clinical prognosis. Saikosaponin-d (Ssd), a saponin from a herbal plant extract, has been shown to induce cell death and sensitize chemoresistant cells to chemotherapeutic agents. Here, we demonstrated that Ssd sensitized chemoresistant OVCA cells with either p53-wt, -mutant and -null to CDDP. The action of Ssd appears to be through induction of mitochondrial fragmentation and G2/M arrest. Ssd is mediated via calcium signaling, up-regulation of the mitochondrial fission proteins Dynamin-related protein 1 (Drp1) and optic atrophy 1 (Opa1), and loss in mitochondrial membrane potential (MMP). Moreover, in the presence of CDDP, Ssd also down-regulates protein phosphatase magnesium-dependent 1 D (PPM1D) and increases the phosphorylation of checkpoint protein kinases (Chk) 1, cell division cycle 25c (Cdc25c) and Cyclin dependent kinase 1 (Cdk1). Our findings suggest that Ssd could sensitize OVCA to CDDP independent of the p53 status through multiple signaling pathways. They support the notion that Ssd may be a novel adjuvant for the treatment of chemoresistant OVCA.

Diagnostic imaging using positron emission tomography for gynecological malignancy

Imaging has played a pivotal role in the management of gynecological malignancy. Positron emission tomography (PET), particularly 18F‐fluorodeoxyglucose (18F‐FDG) PET to reflect cellular glycolytic metabolism, is being increasingly used and has proven superior to conventional imaging including ultrasonography, computed tomography (CT), and magnetic resonance imaging. Studies of and evidence for the utility of 18F‐FDG PET/CT for the detection of local or metastatic disease, treatment planning, response assessment, restaging of recurrent disease, and prognostic assessment are growing. We review the latest evidence for and limitations of 18F‐FDG PET/CT in the diagnosis of gynecological malignancy. Moreover, we also describe the benefits of and evidence for other tracers.

Selected PET radiomic features remain the same

Purpose We investigated whether PET radiomic features are affected by differences in the scanner, scan protocol, and lesion location using 18F-FDG PET/CT and PET/MR scans. Results SUV, TMR, skewness, kurtosis, entropy, and homogeneity strongly correlated between PET/CT and PET/MR images. SUVs were significantly higher on PET/MR0-2 min and PET/MR0-10 min than on PET/CT in gynecological cancer (p = 0.008 and 0.008, respectively), whereas no significant difference was observed between PET/CT, PET/MR0–2 min, and PET/MR0–10 min images in oral cavity/oropharyngeal cancer. TMRs on PET/CT, PET/MR0–2 min, and PET/MR0–10 min increased in this order in gynecological cancer and oral cavity/oropharyngeal cancer. In contrast to conventional and histogram indices, 4 textural features (entropy, homogeneity, SRE, and LRE) were not significantly different between PET/CT, PET/MR0–2 min, and PET/MR0–10 min images. Conclusions 18F-FDG PET radiomic features strongly correlated between PET/CT and PET/MR images. Dixon-based attenuation correction on PET/MR images underestimated tumor tracer uptake more significantly in oral cavity/oropharyngeal cancer than in gynecological cancer. 18F-FDG PET textural features were affected less by differences in the scanner and scan protocol than conventional and histogram features, possibly due to the resampling process using a medium bin width. Methods Eight patients with gynecological cancer and 7 with oral cavity/oropharyngeal cancer underwent a whole-body 18F-FDG PET/CT scan and regional PET/MR scan in one day. PET/MR scans were performed for 10 minutes in the list mode, and PET/CT and 0–2 min and 0–10 min PET/MR images were reconstructed. The standardized uptake value (SUV), tumor-to-muscle SUV ratio (TMR), skewness, kurtosis, entropy, homogeneity, short-run emphasis (SRE), and long-run emphasis (LRE) were compared between PET/CT, PET/MR0-2 min, and PET/MR0-10 min images.

Amniotic Fluid Embolism Triggered By Hypertensive Crisis Due to Undiagnosed Pheochromocytoma in a Pregnant Subject With Neurofibromatosis Type 1

ABSTRACT Objective: To report an unusual case of amniotic fluid embolism (AFE) caused by undiagnosed pheochromocytoma in a pregnant subject with neurofibromatosis type 1 (NF-1). Methods: We describe the clinical course and discuss the management of AFE in a patient with pheochromocytoma complicating NF-1 and present a review of relevant literature. Results: A 29-year-old female with a history of NF-1 presented with hypertension but no neurologic abnormalities. Pre-eclampsia and fetal dysfunction were diagnosed, and a cesarean section was performed. After it was completed, her oxygen saturation suddenly dropped, and an endotracheal intubation was performed. A watery discharge gushed out of the endotracheal tube. Whole-body computed tomography showed a left adrenal tumor (5-cm diameter). Two hours after admission to the intensive care unit, she developed ventricular fibrillation with cardiac shock. Direct current cardioversion, percutaneous cardiopulmonary support, and intra-aortic balloon pumping were imme...