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Background: Whether smokers and former smokers have worse lipid profiles or glucose levels than non-smokers remains unclear. Methods: The subjects were 1152 Japanese males aged 42 to 81 years. The subjects were divided according to their smoking habits (nonsmokers, former smokers, and current smokers) and their visceral fat area (VFA) (

Ovarian hemorrhage during antithrombotic therapy is sometimes difficult to manage. A 38-year-old woman, diagnosed with Marfan syndrome and implanted with a left ventricular assist device (LVAD) and taking aspirin and warfarin potassium, had a history of right adnexal oophorectomy via open surgery for a right ovarian hemorrhage at the age of 35 years. Thereafer, she had been treated with dienogest to suppress ovulation as much as possible. The patient was admitted to a local hospital with lower abdominal pain, and computed tomography showed a 10 cm left adnexal mass with suspected ovarian hemorrhage. Two days after the initiation of careful conservative treatment, with the cessation of antithrombotic therapy and monitoring of hemostasis, the patient was referred to a tertiary hospital. As the left ovarian hemorrhage continued 3 days after the transfer, emergency laparoscopic left salpingo-oophorectomy was performed due to the difficulty in conserving the left normal ovary. Although coagulopathy caused continuous oozing of blood from the pelvis after the removal of the left ovarian mass, hemostasis was successfully achieved laparoscopically. No postoperative bleeding was noted, and anticoagulant therapy was resumed on postoperative day 1 to prevent life-threatening thrombotic events associated with the LVAD. Postoperative pathological examination of the left ovary revealed an endometriotic cyst. To manage surgical menopause, complementary therapy using Japanese traditional herbal medicine was administered, as hormone replacement therapy was not recommended, to avoid the risk of fatal LVAD-associated thrombosis. Less invasive laparoscopic surgery for ovarian hemorrhage during anticoagulant therapy can be considered for reducing bleeding during and after surgery.

Pancreatic fistulas are rare after gynecologic surgeries but are sometimes difficult to manage. A 62-year-old woman was admitted to a local hospital with acute abdominal pain. Computed tomography (CT) images showed subileus and an obstruction site in the transverse/descending colon, with invasion of peritoneal metastasis. A metal stent was placed in the bowel through colonoscopy. Suspecting advanced-stage ovarian cancer, the patient was referred to a tertiary hospital. Diagnostic laparoscopy was performed prior to neoadjuvant chemotherapy. Due to concerns raised by gastrointestinal surgeons regarding the high risk of stent perforation during chemotherapy, an abdominal colectomy of the transverse/descending colon was performed along with the removal of the disseminated tumor and the stent. Post-surgery, the patient was histologically diagnosed with stage IVB left fallopian tube carcinosarcoma. On postoperative day 3, the patient developed a fever, and CT images showed an abscess around the pancreas/spleen, prompting the placement of a drainage tube. The amylase level in the drained fluid was 258,111 U/L, leading to a diagnosis of a pancreatic fistula. Conservative management was undertaken, with drainage, fasting, and octreotide administration. After two months, the drainage tube was removed as the volume of drained fluid had decreased. After four cycles of carboplatin/paclitaxel chemotherapy, CT images showed partial response to chemotherapy, and interval debulking surgery was performed. The necessity of metallic stent placement should be carefully considered as the subileus caused by peritoneal metastasis might be alleviated by the induction of chemotherapy for gynecologic cancer.

Abstract Background Gynecological cancer is one of the highest risk factors for cancer-associated thrombosis (CAT). Although low-molecular-weight heparin (LMWH) is recommended as an anticoagulant for treating CAT, recent studies have shown that direct oral anticoagulants (DOACs) are an acceptable alternative. Patients with cancer require a series of chemotherapies concomitantly with DOAC administration; however, the extent to which these drugs influence DOAC blood concentrations is unknown. In this study, we measured the plasma concentration of edoxaban during chemotherapy for gynecological cancers to determine its safety. Methods Patients histologically diagnosed with ovarian or uterine corpus cancer and CAT were recruited after primary surgery and before the initiation of postoperative adjuvant chemotherapy, including paclitaxel. Patients were administered edoxaban (30 or 60 mg) orally for CAT. The plasma concentrations of edoxaban and active factor Xa were determined and their percentage change before and after chemotherapy was calculated. Additionally, blood coagulation tests were analyzed. Results Sixteen patients with gynecological cancer (12 with ovarian cancer and 4 with uterine corpus cancer) were enrolled. Among these, 15 samples were collected one day after chemotherapy initiation. During chemotherapy, the trough concentration of edoxaban changed from 17.6 ± 10.6 to 20.0 ± 15.6 ng/ml, and the mean percentage change in edoxaban concentration was 14.5%. Therefore, the trough concentrations of edoxaban, which represent excretion capacity, were not significantly increased by chemotherapy with paclitaxel. The area under the plasma edoxaban concentration–time curve and the active factor Xa concentration were also unaffected. Conclusion Patients with CAT and ovarian or uterine corpus cancer administered edoxaban orally showed no significant increase in the trough concentration of edoxaban while undergoing chemotherapy. This suggests the safety of edoxaban use during the treatment of gynecological cancers. Trial registration EGCAT study; Japan Registry of Clinical Trials, jRCTs051190024.

We retrospectively investigated the significance of metastatic lymph nodes in patients with locally recurrent or persistent cervical cancer in a previously irradiated field and subsequently had salvage hysterectomy. Clinical data were obtained from a chart review, and the prognostic impact of the presence, number (1–2 versus ≥3), and location (pelvic versus pelvic plus para-aortic) of lymph node metastasis was investigated by comparing recurrence and survival. In total, 50 patients were included in this study, of which 21 (42.0%) showed pathological evidence of lymph node metastasis (node-positive group). Both the univariate and multivariate analyses showed that lymph node metastasis was an independent prognostic factor for postoperative recurrence (hazard ratio (HR) 5.36; 95% CI 1.41–6.66; p = 0.0020). The predominant sites of recurrence after salvage surgery were the visceral organs and lymph nodes in the node-negative and node-positive groups, respectively. Patients with ≥3 node metastases showed similar survival to those with 1–2 node metastases. Patients with pelvic node metastasis showed similar survival to those with pelvic and para-aortic node metastases. The presence, not number or location, of lymph node metastasis was an independent poor prognostic factor for post-operative recurrence in patients who developed locally recurrent or persistent cervical cancer treated with salvage hysterectomy plus lymphadenectomy.

Abstract Background Preoperative anemia affects perioperative outcomes and often causes fatigue and psychological disorders. Therefore, anemia should be treated before a patient undergoes surgery. Ninjin’yoeito (NYT), a Japanese Kampo medicine composed of ginseng and Japanese angelica root with the other 10 herbs, is administered for anemia, fatigue and anxiety; however, there are a few reports that have prospectively examined the effects of NYT before surgery for gynecological diseases. Hence, we tended to investigate its efficacy and safety. Methods In this open-label randomized trial, women with gynecological diseases accompanied by preoperative anemia (defined as

Hemorrhagic ovarian cysts (HOCs), a common gynecological disease causing intraabdominal bleeding, can be life threatening in patients undergoing antithrombotic therapy, especially those with left ventricular assist device (LVAD) implantation under strong antithrombotic therapy. We encountered three postLVAD implantation cases with intraabdominal bleeding due to suspected HOCs, which required surgery for hemostasis. Such patients are not only at a higher risk of bleeding but also have restrictions in available surgical incision sites to avoid damaging the LVAD driveline located underneath the abdominal wall. Laparoscopic surgery, which can be performed through minute incisions with flexible site selection, may benefit intraabdominal hemorrhage patients with LVADs.

Abstract We investigated the prognostic significance and the underlying mechanism of increased bone marrow (BM) 2-(18F) fluoro-2-deoxy-D-glucose as a tracer (FDG)-uptake in patients with gynecological cancer. A list of patients diagnosed with cervical, endometrial, and ovarian cancer from January 2008 to December 2014 were identified. Then, through chart reviews, 559 patients who underwent staging by FDG-positron emission tomography (PET)/computed tomography (CT) and subsequent surgical resection were identified, and their clinical data were reviewed retrospectively. BM FDG-uptake was evaluated using maximum standardized uptake value (SUVmax) and BM-to-aorta uptake ratio (BAR). As a result, we have found that increased BAR was observed in 20 (8.7%), 21 (13.0%), 21 (12.6%) of cervical, endometrial, and ovarian cancer, respectively, and was associated with significantly shorter survival. Increased BAR was also closely associated with increased granulopoiesis. In vitro and in vivo experiments revealed that tumor-derived granulocyte colony-stimulating factor (G-CSF) was involved in the underlying causative mechanism of increased BM FDG-uptake, and that immune suppression mediated by G-CSF-induced myeloid-derived suppressor cells (MDSCs) is responsible for the poor prognosis of this type of cancer. In conclusion, increased BM FDG-uptake, as represented by increased BAR, is an indicator of poor prognosis in patients with gynecological cancer.

Abstract Background microRNAs (miRNAs) stably exist in circulating blood and are encapsulated in extracellular vesicles such as exosomes. The aims of this study were to identify which exosomal miRNAs are highly produced from epithelial ovarian cancer (EOC) cells, to analyze whether serum miRNA can be used to discriminate patients with EOC from healthy volunteers, and to investigate the functional role of exosomal miRNAs in ovarian cancer progression. Methods Exosomes were collected from the culture media of serous ovarian cancer cell lines, namely TYK-nu and HeyA8 cells. An exosomal miRNA microarray revealed that several miRNAs including miR-99a-5p were specifically elevated in EOC-derived exosomes. Expression levels of serum miR-99a-5p in 62 patients with EOC, 26 patients with benign ovarian tumors, and 20 healthy volunteers were determined by miRNA quantitative reverse transcription-polymerase chain reaction. To investigate the role of exosomal miR-99a-5p in peritoneal dissemination, neighboring human peritoneal mesothelial cells (HPMCs) were treated with EOC-derived exosomes and then expression levels of miR-99a-5p were examined. Furthermore, mimics of miR-99a-5p were transfected into HPMCs and the effect of miR-99a-5p on cancer invasion was analyzed using a 3D culture model. Proteomic analysis with the tandem mass tag method was performed on HPMCs transfected with miR-99a-5p and then potential target genes of miR-99a-5p were examined. Results The serum miR-99a-5p levels were significantly increased in patients with EOC, compared with those in benign tumor patients and healthy volunteers (1.7-fold and 2.8-fold, respectively). A receiver operating characteristic curve analysis showed with a cut-off of 1.41 showed sensitivity and specificity of 0.85 and 0.75, respectively, for detecting EOC (area under the curve = 0.88). Serum miR-99a-5p expression levels were significantly decreased after EOC surgeries (1.8 to 1.3, p = 0.002), indicating that miR-99a-5p reflects tumor burden. Treatment with EOC-derived exosomes significantly increased miR-99a-5p expression in HPMCs. HPMCs transfected with miR-99a-5p promoted ovarian cancer invasion and exhibited increased expression levels of fibronectin and vitronectin. Conclusions Serum miR-99a-5p is significantly elevated in ovarian cancer patients. Exosomal miR-99a-5p from EOC cells promotes cell invasion by affecting HPMCs through fibronectin and vitronectin upregulation and may serve as a target for inhibiting ovarian cancer progression.

Abstract Background microRNAs (miRNAs) stably exist in circulating blood encapsulated in extracellular vesicles such as exosomes; therefore, serum miRNAs have the potential to serve as novel cancer biomarkers. New diagnostic markers to detect high grade serous ovarian cancer (HGSOC) are urgently needed. The aim of this study was to identify miRNAs specific to HGSOC and analyze whether serum miRNA can discriminate HGSOC patients from healthy controls or patients with ovarian malignancies of other histological types. Methods Exosomes from ovarian cancer cell lines were collected and exosomal miRNAs extracted. miRNA microarray analysis revealed several elevated miRNAs specific to HGSOC. Among these, we focused on miR-1290. Sera from 70 ovarian cancer patients and 13 healthy controls were gathered and its expression levels detected by quantitative real-time polymerase chain reaction. Results In HGSOC patients, serum miR-1290 was significantly overexpressed compared to in healthy controls (3.52 fold; P = 0.03), unlike in patients with ovarian cancers of other histological types. The relative expression of miR-1290 was higher in advanced stages of HGSOC than in early stages (4.23 vs. 1.58; P = 0.23). Its expression significantly decreased after operation (5.87 to 1.17; P

Systemic inflammatory responses including thrombocytosis, leukocytosis, or neutrophilia have gained attention as prognostic indicators in patients with various solid malignancies.current study, we aimed to investigate the clinical implications and underlying biological mechanism of the systemic inflammatory response in endometrial cancer. Clinical data from 900 patients with endometrial cancer were analyzed to investigate the association between pretreatment leukocytosis, thrombocytosis, and treatment outcome. Clinical samples, endometrial cancer cell lines, and a mouse model of endometrial cancer were used to examine the mechanisms responsible for systemic inflammatory response in endometrial cancer, focusing on the role of tumor-derived granulocyte colony-stimulating factor (G-CSF) and MDSCs. Then, we showed that pretreatment concurrent leukocytosis and thrombocytosis is associated with significantly shorter survival and decreased chemosensitivity among patients with endometrial cancer. In vitro and in vivo experiments revealed that tumor-derived G-CSF and G-CSF-mediated IL-6 production from the tumor microenvironment are involved in the development of leukocytosis and thrombocytosis in patients with endometrial cancer. Moreover, increased tumor-infiltrating MDSCs induced by tumor-derived G-CSF, MDSC-mediated T cell suppression, and MDSC-mediated cancer stem cell induction are responsible for progression and chemoresistance in this type of endometrial cancer. MDSC depletion using an anti-Gr-1 neutralizing antibody or inhibition of MDSC activity by celecoxib inhibited tumor growth and enhanced chemosensitivity in endometrial cancer displaying concurrent leukocytosis and thrombocytosis. In conclusion, Pretreatment concurrent leukocytosis and thrombocytosis are associated with significantly shorter survival and decreased chemosensitivity among patients with endometrial cancer. Combining MDSC-targeting treatments with current standard chemotherapies might have therapeutic efficacy for these patients.

Pelvic organ prolapse (POP) can occur if the support tissues or the pelvic floor muscles are weakened and damaged. There is increased probability for POP occurrence after childbirth, menopause, or in overweight women. Because the natural history and progression of POP is still unknown, the approaches used to prevent it have not been clear. POP is an uncomfortable condition that affects one every three women. However, most people feel uncomfortable to discuss it. Herein, we conducted a feasibility evaluation study for self-assessment approaches with a vaginal endoscope based on three-dimensional (3D) printing. The proposed endoscope has two parts: (a) rubber material used to cover it for its intended insertion, to avoid direct contact with the walls of the vagina, and (b) two types of sensors at the tip for measurements. The condition inside the vagina was observed with a camera and depth sensors based on the regulation of the amount of air. Arbitrary temporary prolapses from the testbed’s generator enabled us to perceive the location of the problem and symptoms that were regarded as the early stage. As discussed, the low-cost design of the 3D-printed-based vaginal endoscope provides a self-check capability and allows continuous observations that help prevent POP.