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Aberrant DNA methylation is associated with oncogenesis of various human cancers, including pancreatic cancer (PC). PC is the seventh most common cancer, and obesity is a known high-risk factor. However, whether obesity influences DNA methylation in pancreatic exocrine cells and if this influences PC development remain unclear. Here, we performed an epigenome-wide analysis of isolated pancreatic exocrine cells obtained from mice with high-fat-diet-induced obesity (DIO). Using the Illumina Mouse Methylation BeadChip array (280K), we identified 316 differentially methylated regions (DMRs) that were enriched for cellular processes, such as DNA repair, transcription regulation, and cell proliferation, which confirmed obesity-related dysregulation of certain metabolic processes in the pancreatic cells in DIO mice. Comparing the DMRs with those in stage IB PC helped identify 82 overlapping DMRs. Three pathways including the cell hypertrophy pathway involving PLC, PKC, SMAD2/3, and TRKA; the metabolic control pathway involving CREB and AMPK; and the potassium regulation pathway involving K

Uterine artery pseudoaneurysm (UAP) is a rare disease that causes genital bleeding during the postpartum period after cesarean section. Uterine artery embolization (UAE) is an effective procedure for UAP. UAP was unexpectedly encountered in a patient with gestational trophoblastic disease; however, this patient was conservatively managed without UAE. UAP can occur during treatment for gestational trophoblastic disease. Since asymptomatic UAP may spontaneously disappear, in the selection of conservative treatment, it is important to carefully monitor patients using transvaginal ultrasonography focusing on the size of the UAP and the speed of internal blood flow.

Background In patients with epithelial ovarian cancer, whether metastasis to para-aortic lymph nodes located cephalad to the renal veins (supra-renal PAN) should be classified as regional lymph node metastasis or distant metastasis remains controversial. This study was a preliminary retrospective evaluation of the pattern of supra-renal PAN metastasis in patients with epithelial ovarian cancer. Methods The subjects were 25 patients with epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer who underwent systematic dissection of the para-aortic nodes, including the supra-renal PAN, and pelvic lymph nodes (PLN). Patient factors, perioperative factors, the number of dissected lymph nodes, and pathological lymph node metastasis were investigated. Results Supra-renal PAN metastasis was found in 4/25 patients (16.0%). None of the 14 patients with pT1 or pT2 disease had supra-renal PAN metastasis, while 4/11 patients (36.4%) with pT3 or ypT3 disease had such metastases. None of the patients had isolated supra-renal PAN metastasis, while patients with supra-renal PAN metastasis also had multiple metastases to the infra-renal PAN and PLN. Conclusions In patients with epithelial ovarian cancer, supra-renal PAN metastases might be considered to be distant rather than regional metastases. Further studies are needed to better define the clinical significance of supra-renal PAN metastasis.

Aberrant DNA methylation is associated with the oncogenesis of a variety of human cancers, including endometrial cancer (EC), the seventh most common cancer among women. Obesity is known to be a high-risk factor for EC; however, whether obesity influences DNA methylation in the presymptomatic uterus and if this influences EC development remain unclear. Here, we performed genome-wide DNA methylation analysis of isolated endometrial epithelial cells obtained from obese presymptomatic participants. Using the Illumina MethylationEPIC array (850 K), we identified 592 differentially methylated regions (DMRs), most of which undergo hypomethylated changes. These DMRs were enriched for pyrimidine metabolism, Epstein-Barr virus infection, and B cell signaling pathways, indicating obesity-related dysregulation of certain metabolic processes in the presymptomatic uterus. Comparison of the DMRs with those in stage I EC revealed that 54 DMRs overlapped; additionally, B cell signaling and Epstein-Barr virus infection pathways were shared between the presymptomatic uterus of obese women and stage I EC with greater hypomethylation in women with EC than in presymptomatic obese women. These findings indicated that obesity influences DNA methylation in presymptomatic endometrial epithelial cells, and persistent dysregulation of DNA methylation in obese women may result in EC development.

Administration of bevacizumab to ovarian cancer patients with distal deep vein thrombosis (DVT) is problematic because of lack of evidence about the likely outcomes. We conducted a preliminary study in ovarian cancer patients with DVT who received bevacizumab combined with a direct oral anticoagulant (DOAC). We retrospectively investigated patients with advanced or recurrent epithelial ovarian cancer and distal DVT diagnosed by ultrasonography who underwent chemotherapy containing bevacizumab (15 mg/kg every 3 weeks) combined with DOAC therapy. Bevacizumab was administered to 88 patients, including 7 patients (7.9%) receiving concomitant DOAC therapy for distal DVT. In these 7 patients, the median body mass index was 21.3 kg/m2, median D-dimer level at diagnosis of DVT was 4.3 µg/mL, and median duration of DOAC therapy was 8 months. Adverse events during DOAC therapy were grade 1 epistaxis and grade 1 hemorrhoidal bleeding in one patient each. DVT resolved in four patients and was unchanged in three patients, with no central progression or secondary thromboembolism. In ovarian cancer patients who have distal DVT, bevacizumab can possibly be administered safely when combined with a DOAC. To confirm this finding, further investigation on a larger scale will be required.

Ovarian endometriotic cysts have been identified as the possible origin of ovarian clear cell carcinoma (OCCC), so predicting or preventing future transformation is important. Early detection of clear cell carcinoma is important because it shows low sensitivity to chemotherapy and the prognosis is worse than for other histologic types. We recently treated 2 patients with OCCC. They were both young women with no family history of cancer who received long-term oral contraceptive therapy for endometriotic cysts, and the histologic diagnosis was typical clear cell carcinoma in both patients. However, in Case 1, the tumor was detected by periodic examination, tumor expression of WT1 was positive, and the stage was IA. On the other hand, Case 2 presented with fever of unknown origin, her tumor showed expression of p53, and the stage was IVB. Case 1 is alive with no evidence of disease at 38 months after surgery, while Case 2 died after 19 months despite intensive treatment. These contrasting cases suggest that we need to be aware of the risk of cancer in young women receiving long-term hormone therapy for endometriotic cysts and that OCCC may show greater heterogeneity than what has been reported previously.

Introduction: It has been suggested the relationship between infertility treatment and ovarian cancer. Furthermore, endometriosis that is one of the causes of the infertility tends to develop into endometrioid adenocarcinoma and clear cell carcinoma in many studies. Case: A 38-year-old woman underwent laparoscopic enucleation of bilateral ovarian endometrial cysts at 29 and 33 years old. She then received 11 sessions of artificial insemination and 7 cycles of ovarian stimulation, egg collection, in vitro fertilization, and embryo transfer at multiple medical institutions before conceiving and giving birth to her first child. After naturally conceiving her second child, she presented at our hospital for pregnancy/delivery management with a right ovarian tumor. She underwent abdominal right adnexectomy for a mucinous cystic tumor of borderline malignancy at 36 years old (17 weeks of pregnancy with the second child). After vaginal delivery at 38 weeks, a 1-month postpartum checkup revealed a left adnexal mass and ascites. Further workup led to a diagnosis of left ovarian cancer. The cancer was diagnosed by ovarian biopsy as unresectable stage-IIIc endometrioid carcinoma. Despite chemotherapy, the patient developed liver metastasis during treatment and died due to worsened general condition 9 months after childbirth. In addition to ovarian endometrial cyst, repeated cycles of injury and repair of the ovarian surface epithelium are also suggested to mediate the development of epithelial ovarian cancer. Conclusion: Evaluation of long-term outcome and follow-up of patients who have undergone fertility treatment should be addressed.

• In three familial cases and one sporadic case of late-onset distal myopathy, muscle wasting started in the distal portions of the lower extremities. The most striking change seen by light microscopy was the appearance of rimmed vacuoles. These were presumed to be autophagic, because they were found by electron microscopy to contain membranous lamellar structures and other heterogenous materials enclosed by a limiting membrane. On the other hand, lysosomal activity was markedly increased in skeletal muscle. In 6% to 22% of affected muscle fibers there were acid phosphatase-positive granules deep in the sarcoplasm, whereas control muscles had no such granules. The degenerative process in distal myopathy may be different from that in other muscular dystrophies.