Evaluation of the holding-up uterus technique for placenta accreta spectrum cesarean hysterectomy in shocked patients with a high shock index: a case series study.

BACKGROUND: Placenta accreta spectrum (PAS) cesarean hysterectomy is performed under conditions of shock and can result in serious complications. This study aimed to evaluate the usefulness of the "Holding-up uterus" surgical technique with a shock index (S.I.) > 1.5. METHODS: Twelve patients who underwent PAS cesarean hysterectomy were included in the study. RESULTS: Group I had S.I. > 1.5, and group II had S.I. ≤ 1.5. Group I had more complications, but none were above Grade 3 or fatal. Preoperative scheduled uterine artery embolization did not result in serious complications, but three patients who had emergency common iliac artery balloon occlusion (CIABO) and a primary total hysterectomy with S.I. > 1.5 had postoperative Grade 2 thrombosis. Two patients underwent manual ablation of the placenta under CIABO to preserve the uterus, both with S.I. > 1.5. CONCLUSIONS: The study found that the "Holding-up uterus" technique was safe, even in critical situations with S.I. > 1.5. CIABO had no intervention effect. The study also identified assisted reproductive technology pregnancies with a uterine cavity length of less than 5 cm before conception as a critical factor.

Attitudes toward cancer screening in regional Japan during the COVID-19 pandemic: An anonymous survey.

The coronavirus disease (COVID-19) pandemic has raised concerns about the impact of delayed health check-ups and cancer screenings on cancer diagnosis and treatment. This study aimed to investigate the awareness of cancer patients on future screening measures during the pandemic in rural Japan. An anonymized open-data survey was undertaken in Fukui Prefecture, a rural region of Japan, in 2021. Participants were asked about their cancer screening history, screening frequency during the pandemic, and reasons for not undergoing screening. Among the 1262 respondents, the proportion of patients who underwent cancer screening in 2020 during the pandemic was similar to the proportion who underwent regular (annual or biannual) screening in 2019 before the pandemic. Of those who underwent regular screening, 82% still underwent screening in 2020, while only 21% of those who had irregular screenings. The number of respondents who believed they were healthy and did not require screening increased over time, possibly due to restrictions on going out and refraining from activities during the pandemic. This study in rural Japan found that regular cancer screening prior to the pandemic was associated with a more positive attitude toward screening during the pandemic. Raising awareness about the importance of cancer screening and encouraging participation is crucial for promoting positive attitudes in the future. The findings highlight the need for continued efforts to ensure access to screening services during the pandemic and future public health emergencies.

Impact of maternal late hospital arrival on adverse outcome of offspring affected by placental abruption: A regional multicenter nested case-control study in Japan.

AIMS: To elucidate the influence of the time-intervals between the onset and arrival (TIME 1), onset and delivery (TIME 2), and the decision to deliver and delivery (TIME 3) on severe adverse outcomes of offspring born to mothers complicated by placental abruption outside the hospital. METHODS: This is a multicenter nested case-control study about placental abruption at Fukui Prefecture, a regional area in Japan, through 2013 to 2017. Multiple pregnancy, fetal or neonatal congenital abnormality, and unknown detailed information at onset of placental abruption were excluded. A composite of perinatal death and cerebral palsy or death at 18-36 months of corrected age was defined as the adverse outcome. The relationship between time-intervals and the adverse outcome was analyzed. RESULTS: The 45 subjects for analysis were divided into two groups, including a group with and without adverse outcome (poor, n = 8; and good, n = 37). TIME 1 was longer in the poor group (150 vs. 45 min, p < 0.001). A subgroup analysis targeted to 29 cases with preterm birth at the third trimester indicates that TIME 1 and TIME 2 were longer in the poor group (185 vs. 55 min, p = 0.02; and 211 vs. 125 min, p = 0.03), while TIME 3 was shorter in the poor group (21 vs. 53 min, p = 0.01). CONCLUSIONS: Long time-intervals between onset and arrival or onset and delivery may be correlated with perinatal death or cerebral palsy in surviving infants affected by placental abruption.

The role of pituitary gonadotropins and intraovarian regulators in follicle development: A mini-review.

BACKGROUND: The process of follicle development is tightly regulated by pituitary gonadotropins (follicle-stimulating hormone [FSH] and luteinizing hormone [LH]) and intraovarian regulators (eg, steroids, growth factors, and cytokines). METHODS: This review outlines recent findings on the mechanisms of human follicle development, based on the research on animal models such as mice, rats, cows, and sheep. MAIN FINDINGS: Phosphatidylinositol 3-kinase/protein kinase B signaling pathway and anti-Müllerian hormone are involved in primordial follicle activation during the gonadotropin-independent phase. The intraovarian regulators, such as androgen, insulin-like growth factor system, activin, oocyte-derived factors (growth differentiation factor-9 and bone morphogenetic protein 15), and gap junction membrane channel protein (connexin), play a central role in the acquisition of FSH dependence in preantral follicles during the gonadotropin-responsive phase. Antral follicle development can be divided into FSH-dependent growth and LH-dependent maturation. The indispensable tetralogy for follicle selection and final maturation of antral follicles involves (a) acquisition of LH dependence, (b) greater capacity for E2 production, (c) activation of the IGF system, and (d) an antiapoptotic follicular microenvironment. CONCLUSION: We reproductive endocrinologists should accumulate further knowledge from animal model studies to develop methods that promote early folliculogenesis and connect to subsequent gonadotropin therapy in infertile women.

The study protocol of the evaluation for the preventive efficacy of the HPV vaccine for persistent HPV16/18 infection in Japanese adult women: the HAKUOH study.

BACKGROUND: In general, human papillomavirus (HPV) vaccines have demonstrated efficacy in young women worldwide, but there is limited evidence on the efficacy of the quadrivalent HPV6/11/16/18 vaccine in adult women and no evidence of its effectiveness in Japanese adult women in particular. This study aims to evaluate the efficacy of the quadrivalent HPV6/11/16/18 vaccine for persistent HPV16/18 infection in Japanese women aged 27-45 years. METHODS: This is an interventional, nonrandomized, non-double-blind prospective cohort study designed to compare the rates of persistent HPV16/18 infection between the vaccinated arm and unvaccinated arm. The subjects will consist of all women aged 27-45 years who have normal cytology results confirmed by cervical cancer screening from May 2019 to March 2021. The follow-up time is two years. The subjects will be divided into two groups: the vaccinated group and the unvaccinated group. The study will need to enroll 600 vaccinated participants (experimental arm) and 2200 unvaccinated participants (control arm). DISCUSSION: The findings of this trial (HAKUOH study) might provide the first local evidence on the subject and be significantly useful not only to medical academia but also to the Japanese Ministry of Health, Labour and Welfare. The findings could contribute to public health improvement by providing local supportive knowledge on the prevention of HPV infection through HPV vaccination in young adult women in Japan, where active recommendations have been suspended for a long time due to adverse effects. TRIAL REGISTRATION: Trial registration number: NCT04022148 . Registration began on December 1, 2019.

Prognostic impact of Dynamin related protein 1 (Drp1) in epithelial ovarian cancer.

BACKGROUND: The mitochondrial fission protein, Dynamin related protein 1 (Drp1), and its upstream protein calcium/calmodulin-dependent protein kinase I (CaMKI) play a critical role in chemoresistance in ovarian cancer (OVCA). Thus, we examined the expression of Drp1, CaMKI and their phosphorylated forms and their prognostic impact in epithelial OVCA patients. METHODS: Expression analysis was performed by immunohistochemistry (IHC) of paraffin-embedded tumor samples from 49 patients with epithelial OVCA. Staining intensity and the percentage of positively stained tumor cells were used to calculate an immunoreactive score (IRS) of 0-12. The expression scores calculated were correlated with clinicopathological parameters and patient survival. RESULTS: High immunoreactivity of phospho-Drp1Ser637 was significantly correlated with high-grade serous carcinoma (HGSC) (p = 0.034), residual postoperative tumor of > 1 cm (p = 0.006), and non-responders to adjuvant chemotherapy (p = 0.007), whereas high expression of CaMKI was significantly correlated with stage III/IV [International Federation of Gynecologists and Obstetricians (FIGO)] (p = 0.011) and platinum-resistant recurrence (p = 0.030). ROC curve analysis showed that Drp1, phospho-Drp1Ser637 and CaMKI could significantly detect tumor progression with 0.710, 0.779, and 0.686 of area under the curve (AUC), respectively. The Kaplan-Meier survival curve showed that patients with high Drp1, phospho-Drp1Ser637 and CaMKI levels had significantly poorer progression free survival (PFS) (p = 0.003, p < 0.001 and p = 0.017, respectively). Using multivariate analyses, phospho-Drp1Ser637 was significantly associated with PFS [p = 0.043, hazard ratio (HR) 3.151, 95% confidence interval (CI) 1.039-9.561]. CONCLUSIONS: Drp1 and CaMKI are novel potential candidates for the detection and prognosis of epithelial OVCA and as such further studies should be performed to exploit their therapeutic significance.

Development of a novel and rapid measurement system for growth differentiation factor-15, progranulin, and osteopontin in uterine sarcoma.

Uterine sarcomas are rare and aggressive gynecologic tumors with poor prognosis; therefore, early diagnosis is crucial for therapy. However, it is very difficult to distinguish uterine sarcomas from leiomyomas which are common benign uterine tumors. Therefore, the development of a diagnostic method that utilizes reliable biomarkers to distinguish uterine sarcomas from leiomyomas is important so as to identify the rare tumors. The candidate factors as novel biomarkers were searched for in public databases and a pilot study was performed for confirmation. Growth differentiation factor-15 (GDF15), progranulin, and osteopontin were identified as candidate biomarkers for diagnosing uterine sarcoma. Thus, developing a rapid and easy method to measure these factors could help establish a screening system for uterine sarcomas. In this study, we developed a novel measurement system for these factors using a compact chemical luminescence immunological automatic analyzer POCubeTM. This assay system, which is based on the flow-through membrane immunoassay, completes the whole process and generates results within 15 min. Serum concentrations of these factors measured via POCubeTM correlated well with those measured using enzyme-linked immunosorbent assay (r = 0.994 for GDF15, r = 0.992 for progranulin, and r = 0.976 for osteopontin). The POCubeTM system provides rapid and easy measurement of these factors, thereby facilitating uterine sarcoma diagnosis.

Hyperthermic intraperitoneal chemotherapy (HIPEC) for gynecological cancer.

AIM: Hyperthermic intraperitoneal chemotherapy (HIPEC) is a method of administering anticancer agents directly while heating the abdominal cavity. The aim of this review is to know the current position of HIPEC in ovarian cancer and uterine sarcoma and its future prospects. METHODS: This article reviews the current literature and evidence for the clinical trial of HIPEC in ovarian cancer and uterine sarcoma with consideration of the cases treated in our department. RESULTS: In January 2018, van Driel et al. reported the results of their phase 3, randomized, controlled trial and the usefulness of neoadjuvant chemotherapy followed by interval debulking surgery. With respect to greater than grade 3 complications, such as suture failure, intestinal perforation, postoperative bleeding, wound issues and death, there were no significant differences between the HIPEC group and the no-HIPEC group. In a meta-analysis including two randomized, controlled studies and 11 observational studies in 2019, the addition of HIPEC to cytoreductive surgery significantly improved overall survival of ovarian cancer patients. Moreover, growing evidence of the efficacy of cytoreductive surgery with HIPEC has also been reported in uterine sarcoma with peritoneal sarcomatosis in a multi-institutional study. HIPEC could be one of the new therapeutic strategies for such disseminated peritoneal lesions. CONCLUSION: Since the usage regimen and temperature setting of HIPEC are not standardized, and its effectiveness and adverse events are greatly affected by the time of administration, it is necessary to consider clinical trials for the optimization and establishment of HIPEC in Japan in the future.

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 Network's 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.

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 18 F-fluorodeoxyglucose (18 F-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 18 F-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 18 F-FDG PET/CT in the diagnosis of gynecological malignancy. Moreover, we also describe the benefits of and evidence for other tracers.

Color Doppler sonography as an adjunct to repeat uterine evacuation for gestational trophoblastic disease: case report.

Repeat uterine evacuation is a therapeutic option for preserving fertility in patients with gestational trophoblastic neoplasms and chemoresistance, but remains controversial due to the risks of hemorrhage and perforation. A 25-year-old patient with low-risk gestational trophoblastic neoplasm became chemoresistant; however, chemotherapy reduced intrauterine tumor vascularity as observed by color Doppler sonography, suggesting that patients could undergo uterine evacuation without major risk of bleeding. After 18 months, she achieved a normal pregnancy. Serial assessment of tumor vascularity with color Doppler sonography may provide information regarding the appropriate time to perform a repeat uterine evacuation without significant bleeding.

Evaluation of calcification distribution by CT-based textural analysis for discrimination of immature teratoma.

BACKGROUND: Mature and immature teratomas are differentiated based on tumor markers and calcification or fat distribution. However, no study has objectively quantified the differences in calcification and fat distributions between these tumors. This study aimed to evaluate the diagnostic potential of CT-based textural analysis in differentiating between mature and immature teratomas in patients aged < 20 years. MATERIALS AND METHODS: Thirty-two patients with pathologically proven mature cystic (n = 28) and immature teratomas (n = 4) underwent transabdominal ultrasound and/or abdominal and pelvic CT before surgery. The diagnostic performance of CT for assessing imaging features, including subjective manual measurement and objective textural analysis of fat and calcification distributions in the tumors, was evaluated by two experienced readers. The histopathological results were used as the gold standard. The Mann-Whitney U test was used for statistical analysis. RESULTS: We evaluated 32 patients (mean age, 14.5 years; age range, 6-19 years). The mean maximum diameter and number of calcifications of immature teratomas were significantly larger than those of mature cystic teratomas (p < 0.01). The mean number of fats of immature teratomas was significantly larger than that of mature cystic teratomas (p < 0.01); however, no significant difference in the maximum diameter of fats was observed. CT textural features for calcification distribution in the tumors showed that mature cystic teratomas had higher homogeneity and energy than immature teratomas. However, immature teratomas showed higher correlation, entropy, and dissimilarity than mature cystic teratomas among features derived from the gray-level co-occurrence matrix (GLCM) (p < 0.05). No significant differences were observed in the CT features of fats derived from GLCM. CONCLUSION: Our results demonstrate that calcification distribution on CT is a potential diagnostic biomarker to discriminate mature from immature teratomas, thus enabling optimal therapeutic selection for patients aged < 20 years.

Prognostic value of 18F-FDG PET in uterine cervical cancer patients with stage IIICr allocated by imaging.

The effect on survival of radiographic lymph node metastasis in uterine cervical cancer patients is more important than before, even though its prognostic value not been well investigated. The aim of our study is to evaluate the prognostic potential of 18F-fluorodeoxyglucose Positron Emission Tomography (18F-FDG PET) compared with Computed Tomography (CT) in uterine cervical cancer patients with stage IIICr allocated by imaging. Fifty-five patients with biopsy-proven primary cervical cancer underwent definitive radiation therapy for stages IIB-IVB of The International Federation of Gynecology and Obstetrics (FIGO) 2018 classifications. The prognostic performance of pretreatment 18F-FDG PET and CT for assessing lymph node metastasis was evaluated by two experienced readers. The PET and CT findings were correlated with the risk of progression-free survival (PFS) and overall survival (OS). Kaplan-Meier survival curves showed that PFS was significantly worse in patients with positive lymph nodes on 18F-FDG PET than in those patients with negative lymph nodes on 18F-FDG PET (p = 0.003), whereas there was no significant difference in PFS between patients with lymph nodes sized ≥ 1 cm and those sized < 1 cm (p = 0.140). Univariate analysis showed that positive lymph nodes on 18F-FDG PET was significantly associated with poor PFS (p = 0.006), whereas lymph node size was not significantly associated with poor PFS (p = 0.145). In multivariate analysis, positive lymph nodes on 18F-FDG PET was significantly associated with poor PFS (p = 0.006) and was an independent prognostic factor for PFS. 18F-FDG PET offers high prognostic value for patients with stage IIICr allocated by imaging compared with CT, suggesting that 18F-FDG PET might be useful in clinical staging decisions and thus promote optimal diagnostic and therapeutic strategies.

Chronic low-grade inflammation and ovarian dysfunction in women with polycystic ovarian syndrome, endometriosis, and aging.

The ovarian microenvironment is critical for follicular development and oocyte maturation. Maternal conditions, including polycystic ovary syndrome (PCOS), endometriosis, and aging, may compromise the ovarian microenvironment, follicular development, and oocyte quality. Chronic low-grade inflammation can induce oxidative stress and tissue fibrosis in the ovary. In PCOS, endometriosis, and aging, pro-inflammatory cytokine levels are often elevated in follicular fluids. In women with obesity and PCOS, hyperandrogenemia and insulin resistance induce ovarian chronic low-grade inflammation, thereby disrupting follicular development by increasing oxidative stress. In endometriosis, ovarian endometrioma-derived iron overload can induce chronic inflammation and oxidative stress, leading to ovarian ferroptosis and fibrosis. In inflammatory aging (inflammaging), senescent cells may secrete senescence-associated secretory phenotype factors, causing chronic inflammation and oxidative stress in the ovary. Therefore, controlling chronic low-grade inflammation and fibrosis in the ovary would present a novel therapeutic strategy for improving the follicular microenvironment and minimizing ovarian dysfunction.

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.

PET Imaging of Estrogen Receptors for Gynecological Tumors.

ABSTRACT: In the past few decades, PET with 18F-FDG has been used for the diagnosis of gynecological malignancies and is considered to be superior to conventional imaging methods in diagnostic accuracy for detecting metastatic lesions and local recurrence and in evaluating the treatment response. On the other hand, several gynecological tumors, such as endometrial cancer and leiomyoma, and breast cancer are estrogen-dependent, in which estrogen is essential for their development and progression. 18F-FES is an 18F-labeled compound of estradiol, the most bioactive type of estrogen, and 18F-FES PET has been well-established for diagnosis, staging, and posttherapeutic follow-up in patients with estrogen receptor-positive breast cancer. Compared with in vitro assessment of tumor biopsy material, PET imaging has the advantages of being able to measure in vivo tumor behavior, characterize the entire tumor burden, and capture the heterogeneity of the tumor phenotype. In this article, we review the phenotyping of estrogen-related gynecological tumors other than breast cancer using 18F-FES PET and demonstrate the additional value of 18F-FES PET to 18F-FDG PET in their diagnosis and prognostication. Moreover, promising PET tracers other than 18F-FES and 18F-FDG for the evaluation of estrogen-related gynecological tumors are introduced.

Laparoscopic surgery-associated massive subcutaneous emphysema requiring mechanical ventilation in a patient with endometriosis: a case report.

Although subcutaneous emphysema is a common benign complication of laparoscopic surgery, airway obstruction can occur due to pharyngeal emphysema when it extends to the neck. Here, we report a case of subcutaneous emphysema extending to the neck that required mechanical ventilation in a 51-year-old patient with endometriosis and severe adhesions during total laparoscopic hysterectomy and bilateral salpingo-oophorectomy. Although surgical or disease-specific risk stratification has not yet been established, the severe adhesions due to endometriosis and massive peritoneal defect due to the procedure might lead to the fragility of the subcutaneous tissue, resulting in a massive subcutaneous emphysema. This study highlights the importance of preoperative risk assessment in addition to intraoperative and postoperative monitoring for ventilation disorders and subcutaneous emphysema.

COVID-19 pneumonia detected by [18F]FDG PET/MRI: a case with negative antigen test and chest X-ray results.

Since the outbreak of pneumonia caused by a novel coronavirus (SARS-CoV-2) named Coronavirus disease 2019 (COVID-19) in China, researchers have reported the fluorodeoxyglucose positron emission tomography/CT (FDG PET/CT) manifestations of COVID-19 infection. We present a 37-year-old female with early-stage cervical cancer and fever without a focus who had negative SARS-CoV-2 antigen test and chest X-ray results. FDG PET/MRI performed for preoperative evaluation incidentally detected pneumonia showing high FDG uptake and diffusion-weighted imaging signals in right lung base. She retested positive for SARS-CoV-2 and was diagnosed as having COVID-19 pneumonia. Whole-body PET/MRI can provide multi functional images and could be useful for evaluating the pathophysiology of COVID-19.

Plasma Gelsolin Confers Chemoresistance in Ovarian Cancer by Resetting the Relative Abundance and Function of Macrophage Subtypes.

Ovarian cancer (OVCA) is the most lethal gynaecological cancer with a 5-year survival rate less than 50%. Despite new therapeutic strategies, such as immune checkpoint blockers (ICBs), tumor recurrence and drug resistance remain key obstacles in achieving long-term therapeutic success. Therefore, there is an urgent need to understand the cellular mechanisms of immune dysregulation in chemoresistant OVCA in order to harness the host's immune system to improve survival. The over-expression of plasma gelsolin (pGSN) mRNA is associated with a poorer prognosis in OVCA patients; however, its immuno-modulatory role has not been elucidated. In this study, for the first time, we report pGSN as an inhibitor of M1 macrophage anti-tumor functions in OVCA chemoresistance. Increased epithelial pGSN expression was associated with the loss of chemoresponsiveness and poor survival. While patients with increased M1 macrophage infiltration exhibited better survival due to nitric-oxide-induced ROS accumulation in OVCA cells, cohorts with poor survival had a higher infiltration of M2 macrophages. Interestingly, increased epithelial pGSN expression was significantly associated with the reduced survival benefits of infiltrated M1 macrophages, through apoptosis via increased caspase-3 activation and reduced production of iNOS and TNFα. Additionally, epithelial pGSN expression was an independent prognostic marker in predicting progression-free survival. These findings support our hypothesis that pGSN is a modulator of inflammation and confers chemoresistance in OVCA, in part by resetting the relative abundance and function of macrophage subtypes in the ovarian tumor microenvironment. Our findings raise the possibility that pGSN may be a potential therapeutic target for immune-mediated chemoresistance in OVCA.

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, 8, 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.