Chemotherapy for end-of-life ovarian cancer patients is a complex and delicate problem. We evaluated whether active palliative chemotherapy is beneficial for such patients using inflammatory parameters, nutritional indicators, and the PPI (Palliative Prognostic Index), which predicts short-term prognosis. Thirty-six patients among 49 patients who died from ovarian cancer from 2014 to 2019 at our hospital were enrolled, whom clinical and laboratory data just before starting their final chemotherapy regimen could be obtained. Associations between the time from last chemotherapy to death and the following parameters were investigated: age, performance status, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio, Modified Glasgow Prognostic Score (mGPS), Prognostic Nutritional Index (PNI) score, and PPI score. The median age was 57 (range 19–80) years. The median time from last chemotherapy to death was 45.5 (range 11–110) days. Eight patients (22%) died within 30 days of their last chemotherapy regimen. In univariate analysis, median survival time was significantly shorter in patients with higher NLR, mGPS 2, and higher PPI values; NLR (≥ median vs. < median): 32 (range 11–80) days vs. 54 (range 35–110) days, p = 0.008; mGPS (2 vs. 0–1): 42 (range 11–80) days vs. 96 (range 49–110) days, p = 0.012; and PPI score (≥ median vs. < median): 38 (range 11–74) days vs. 60 (range 18–110) days, p = 0.005. However, in multivariate analysis, no factors were identified as independent prognostic factors for survival. Parameters, such as NLR, mGPS, and PPI score, may be indicators for discontinuation of palliative chemotherapy, and may be useful for maximizing end-of-life care for ovarian cancer patients.

A 27‐year‐old woman, gravida 1, para 0, was transferred to our hospital with acute abdominal pain. Her serum human chorionic gonadotropin level was 60 231 mIU/mL. Transabdominal ultrasound revealed an echo‐free space, and emergency laparoscopy‐assisted surgery was performed with a preoperative diagnosis of ruptured ectopic pregnancy. The pelvic cavity was filled with clots, and the peritoneal surface of the uterine fundus was swollen and showed continuous bleeding. The lesion was located on peritoneum and not connected with the uterine cavity. Histological examination of the conceptus showed features of a complete hydatidiform mole. After a mild decrease, hCG levels adversely increased 3 weeks later with multiple lung nodules. With a diagnosis of invasive moles, the patient was administered chemotherapy. This case demonstrates that it is important to recognize the potential of ectopic hydatidiform moles through abdominal pregnancy. This is the first report of an invasive abdominal hydatidiform mole, and hCG monitoring seemed to be essential for gestational trophoblastic neoplasia detection.

The association of gestational hypertension (GH) with future hypertension in Japanese women is unclear. Hence, this study aimed to examine the association between GH and the risk of future hypertension in middle-aged-to-older Japanese women. A case-control study was performed, including 62 hypertensive women (case) and 75 nonhypertensive women (control). GH during the first pregnancy was diagnosed on the basis of the Maternal and Child Health Handbook record. Hypertensive women were recruited from outpatients in the hospital and residents who completed an annual health check-up in a community. Hypertension was defined as blood pressure with systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg, or taking antihypertensive medications. The average age (SD) of the cases and controls at the time of recruitment was 63.1 (8.4) and 57.7 (9.4), respectively. The multivariable-adjusted odds ratio of GH for hypertension in middle-aged-to-older women was 4.2 (95% confidence interval, 1.0–17.5) after adjustment for potential confounding factors such as age and body-mass index (BMI) upon recruitment, prepregnancy BMI, and age at first delivery. In conclusion, GH can be an independent risk factor for future hypertension among Japanese women.

Background Postpartum hemorrhage (PPH) is a major cause of maternal mortality. Even seemingly low-risk women may suddenly develop postpartum hemorrhage, and these cases are often unpredictable and threatens maternal life. We hypothesized that innate poor uterine contractility may be a risk factor of PPH. In this study, we examined the association between the innate poor uterine contractility, suggested by the characteristics of labor and PPH in obstetrically low-risk women.Methods We used the Japan Perinatal Registry database of the Japan Society of Obstetrics and Gynecology registered in 2013–2016. With exclusion of women with well-known risk factors for PPH (maternal basal disease of hematologic disease, uterine leiomyoma, pregnancy by assisted reproductive technology, placenta abruption, placenta accrete, low-lying placenta, hypertensive disorders of pregnancy, macrosomia, polyhydramnios, or epidural analgesia), we analyzed 174,082 primiparous women who had one live singleton birth via vaginal delivery in cephalic presentation at 37 weeks’ gestation. Information about abnormal labor patterns (hypotonic uterine dysfunction, prolonged labor, and arrest of labor) diagnosed by obstetricians were also used in this study. In order to focus on innate maternal poor uterine contractility, we classified subjects into four classes according to whether they were diagnosed with abnormal labor patterns and whether they had used uterotonics, and Odds ratios and their 95% CI were calculated as well.Results Among the enrolled women, 10,508 (6.0%) had PPH. Abnormal labor patterns, including hypotonic uterine dysfunction (adjusted OR 1.28, 95% CI 1.22 to 1.34), prolonged labor (adjusted OR 1.41, 95% CI 1.30 to 1.52) and arrest of labor (adjusted OR 2.02, 95% CI 1.78 to 2.29) were significantly associated with an increased risk of PPH. Compared to women who were not diagnosed any abnormal labor patterns and did not use any uterotonics, women who were diagnosed with abnormal labor patterns were at a significantly increased risk for PPH regardless of whether they had used uterotonics(adjusted OR 1.23, 95% CI 1.10 to 1.37) or not (adjusted OR 1.30, 95% CI 1.23 to 1.37).Conclusion Our study suggests that innate poor uterine contractility is a significant predisposing risk factor in otherwise low-risk women.Trial Registration: This study is retrospectively registered.

We conducted a nationwide retrospective study in Japan to evaluate the effectiveness of oral amoxicillin or ampicillin as alternatives to injectable benzathine penicillin G for treating pregnant women with syphilis and preventing congenital syphilis (CS). We investigated 80 pregnant women with active syphilis treated with amoxicillin or ampicillin during 2010-2018. Overall, 21% (15/71) had pregnancies resulting in CS cases, and 3.8% (3/80) changed therapies because of side effects. Among 26 patients with early syphilis, no CS cases occurred, but among 45 with late syphilis, 15 (33%) CS cases occurred. Among 57 patients who started treatment >60 days before delivery, 8 (14%) had CS pregnancy outcomes. We found oral amoxicillin potentially ineffective for preventing CS cases among pregnant women with late syphilis but potentially effective in those with early syphilis. Prospective studies are needed to definitively evaluate the efficacy of amoxicillin for the treatment of pregnant women with syphilis to prevent CS.

To examine the association between the risk of postpartum hemorrhage (PPH) and poor uterine contractility, which is suggested by the characteristics of labor.

Ovarian gonadoblastoma coexisting with a dysgerminoma is extremely rare in patients with Turner syndrome (TS) and a Y chromosome. The cytological findings, including imprint cytology, of these unusual ovarian tumors have rarely been reported. We report a rare patient with a gonadoblastoma with dysgerminoma, 3.0 × 2.0 cm in size; she was a 19-year-old woman with TS and a Y chromosome. She underwent laparoscopic bilateral gonadectomy, and the tumor was classified as stage IA (pT1aNxM0) according to the International Federation of Gynecology and Obstetrics classification system. Intraoperative imprint cytology revealed two types of neoplastic cells: small tumor cells surrounding light green-stained or eosinophilic hyaline globules with marked calcification, suspicious for gonadoblastoma; and large, round, atypical cells with abundant cytoplasm, macronucleoli, and marked lymphocytic infiltration (two-cell pattern), suspicious for dysgerminoma. The cytology results in our patient may represent the second reported results of imprint cytology describing a gonadoblastoma with dysgerminoma. They are the first reported results in a patient with TS and a Y chromosome.

Recently, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) or prognostic nutritional index (PNI) have been investigated as prognostic parameters in various malignancies. Herein, we detail how we have investigated the prognostic significance of NLR, PLR and PNI together with the other clinicopathological factors for International Federation of Gynaecology and Obstetrics stage IVB endometrial carcinoma. Thirty-two patients with clinical stage IVB disease were enrolled. The relationship between clinicopathological factors, NLR, PLR or PNI and overall survival (OS) rates was investigated. The 5-year OS rate was 9.7%, and the median survival time was 9 months. In univariate analysis, PS 0-1, G1-2 endometrioid carcinoma, occurrence of surgery, NLR (below median) and PNI (≥median) were identified as favourable prognostic factors. In multivariate analysis, only a histology (G1-2 endometrioid carcinoma) was identified as an independent favourable prognostic factor. Additional large-scale studies are required to confirm the prognostic significance of NLR, PLR and PNI in clinical stage IVB endometrial carcinoma. Impact Statement What is already known on this subject? Several parameters representing the systemic inflammatory response (e.g. neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR)) or the nutritional condition (e.g. prognostic nutritional index (PNI)) have been investigated as prognostic parameters in various malignancies, whereas they have not been thoroughly investigated in endometrial carcinoma. What the results of this study add? In univariate analysis of various factors for overall survival, the performance status (PS) 0-1, grade 1-2 endometrioid carcinoma, occurrence of surgery, NLR (below median) and PNI (≥median) were identified as favourable prognostic factors. However, in a multivariate analysis, only the histology (grade 1-2 endometrioid carcinoma) was identified as an independent favourable prognostic factor. What the implications are of these findings for clinical practice and/or further research? This retrospective study identified that neither inflammatory parameters nor the nutritional index were revealed to be independent prognostic factors by multivariate analyses. Additional large-scale studies are required to confirm the prognostic significance of NLR, PLR and PNI in clinical stage IVB endometrial carcinoma to improve the poor prognosis of this disease.

Liposarcoma of the uterine corpus is extremely rare. We performed a laparotomy on a 55-year-old woman with the complaints of abdominal distension and genital bleeding who was found to have a uterine tumor, 17 × 16 cm in diameter. The preoperative diagnosis was a lipoma or lipoleiomyoma of the uterine corpus. However, pathological examination revealed proliferation of mature adipocytes and lipoblast-like atypical cells with small, weakly pleomorphic nuclei and foamy or vacuolated cytoplasm present within a fibrous septum. Immunohistochemistry showed that the tumor cells were focally positive for mouse double minute 2 homolog (MDM2). The final pathological diagnosis was a well-differentiated liposarcoma of International Federation of Gynecology and Obstetrics (FIGO) stage IB (pT1bNxM0). On magnetic resonance imaging (MRI), T1 -weighted and fat-saturated images showed high and low intensity in the tumor, respectively, suggesting that this tumor contained a fat component. The septum inside the tumor had a contrast enhancement on T1-weighted, gadolinium-enhanced imaging. The septum was nonuniformly thickened and partially nodular. In hindsight, these findings may have suggested a well-differentiated liposarcoma in the uterine corpus rather than a lipoma or lipoleiomyoma. Clinicians should be aware of the possibility of a liposarcoma of the uterine corpus when a neoplasm contains adipose tissue and a nonuniformly thickened or partially nodular septum on MRI.

Aim Leiomyosarcoma is the most common type of uterine sarcoma. In some leiomyosarcoma cases, preoperative diagnosis might be difficult, and they might be treated as benign lesions. We evaluated diagnostic values of preoperative serum lactate dehydrogenase (LDH), D-dimer and C-reactive protein for differentiating leiomyosarcoma. Methods From 2008 to 2013, leiomyosarcoma cases in three university hospitals were enrolled. Preoperative serum LDH, D-dimer and C-reactive protein were analyzed if tested. These markers of pathologically diagnosed leiomyoma cases presumed benign (group B) and presumed malignant (group PM) were compared with those of leiomyosarcoma cases (group S). Results Groups S, PM and B had 36, 28 and 69 cases, respectively. Positive rates of LDH were 66.7%, 14.3% and 0% in groups S, PM and B, respectively. Positive rates of D-dimer and C-reactive protein were 83.3% and 64.5%, 17.9% and 10.7% and 5% and 2.9% in groups S, PM and B, respectively. Positive rates of all three markers were high in the order of leiomyosarcoma, atypical leiomyoma and typical leiomyoma. In group PM, 12 (63.2%) cases were negative for all three markers, whereas 1 (3.3%) case was negative in group S. No case was positive for all markers in group PM, whereas 41.2% leiomyosarcoma cases were positive for all markers. When all parameters were positive, specificity and positive predictive value were 100% in differentiating leiomyosarcoma from group PM. Conclusion Combination of LDH, D-dimer and C-reactive protein could be useful for distinguishing leiomyosarcoma from especially degenerated or atypical leiomyoma.

BACKGROUND:Ovarian steroid cell tumors (SCTs) are rare and usually benign, although 25-43% are reportedly malignant. The cytologic findings of these rare ovarian tumors have almost never been reported.CASE:We report a rare case of a malignant ovarian SCT with peritoneal dissemination and malignant ascites in a 40-year-old woman. Her tumor was classified as stage IIB (pT2bNoM0) according to the FIGO (International Federation of Gynecology and Obstetrics) classification system, and she was treated with adjuvant chemotherapy following staging laparotomy. Cytology of the ascitic fluid revealed large, polygonal-to-round cells and multinucleated cells with atypia, appearing in clusters with slight overlapping or as isolated tumor cells. Numerous tumor cells had small central round or eccentric nuclei with conspicuous nucleoli, and a moderate-to-abundant amount of cytoplasm, varying from granular and eosinophilic to pale and multivacuolated (foamy), with cannibalism formations. The nuclear chromatin was fine and granular, with irregular distribution and nuclear-membrane thickening.CONCLUSION:These may be the first reported cytology results for ascites with a malignant SCT. Our patient's cytological ascitic findings, rather than the histopathologic features of the original and disseminated tumors, represent the malignant features of the tumor.

Objective: This study was conducted to retrospectively evaluate the effectiveness of salvage chemotherapy in patients with recurrent or persistent clear cell carcinomas (CCC). Methods: Fifteen patients who received chemotherapy for recurrent or persistent CCC were enrolled. Primary outcomes were response rate (RR; CR+PR), and disease control rate (DCR; CR+PR+SD). Clinical response was evaluated every two or three cycles using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Results: The median age was 59 (range, 48 to 76) years. The median time to recurrence was 10(range, 1 to 36) months. Eight regimens were used more than two cycles as salvage chemotherapy. The median number of chemotherapy regimens after recurrence were 3 (range, 0-6), and the median cycles of each regimen was 6 (0∼23). The RR and DCR in eight regimens were as follows; CPT-11+CDDP, 0% and 16.7% (1 SD and 5 PD); PTX+CBDCA, 20% and 40% (1 PR, 1 SD and 1 PD); gemcitabine, 20% and 60% (1 CR, 2 SD and 2 PD); PLD, 0% and 25% (1 SD and 4 PD); CPT-11+DTX, 0% and 25% (1 SD and 3 PD); PTX, 0% and 50% (2 SD and 2 PD); DTX, 3 PD; topotecan, 3 PD. Conclusion: The treatment effects was more favorable in the patients treated with gemcitabine. The combination treatment with gemcitabine and molecular target therapy, such as bevacizumab is required to clarify the efficacy in the future.

The mechanism for the chemoresistance of cancer cells is quite complicated. Most of the anti-cancer drugs are known to induce apoptosis in cancer cells, as well as in normal cells, in part by the activation of the p53 pathway. p53 is often referred to as the 'guardian of the genome' and is one of the most investigated tumor suppressor genes. A majority of human tumors harbor p53 mutations which can influence the effect of chemotherapy. Thus pre-therapeutic evaluation of the p53 gene can be extremely informative for patients with diverse malignancies. In this mini review, we introduce a p53 functional analysis system in mammalian cells, which can identify different types of p53 abnormalities, such as loss of function, dominant negative function, or gain of oncogenic function. The kinetic analysis of mutated-p53 may help to determine the therapeutic strategy in the individual patients with several malignancies. Furthermore, detailed information on the mutated p53 gene in cancer cells might provide useful suggestions for developing new anti-cancer drugs. Keywords: Chemoresistance, head and neck cancer, oncogenic mutation, p53, p53-target genes, tumor suppressor gene.

BACKGROUND:Several approaches for treating severe uterine cervical stenosis after conization for cervical intraepithelial neoplasia have been reported; yet, the condition can still be difficult to treat successfully.CASE PRESENTATION:We performed uterine cervical dilation surgery in two patients with severe stenosis, followed by insertion of the levonorgestrel-releasing intrauterine system, which is used for dysmenorrhea or endometriosis-related pain because of its strong progesterone activity. Patient 1 was a 34-year-old Japanese woman who was diagnosed with dysmenorrhea caused by recurrent uterine cervical stenosis and hematometra after laser conization. Patient 2 was a 44-year-old Japanese woman who developed dysmenorrhea and prolonged menstruation caused by uterine cervical stenosis without hematometra. After providing informed consent, they underwent cervical dilation surgery followed by insertion of the levonorgestrel-releasing intrauterine system. After treatment, their symptoms immediately improved, and after removal of their devices, they remained asymptomatic.CONCLUSIONS:To the best of our knowledge, this is the first report to confirm the usefulness and easy applicability of the levonorgestrel-releasing intrauterine system for uterine cervical stenosis. Although we had success with the method, this study of two patients is preliminary. Further study with larger numbers of patients is necessary to confirm the usefulness of our technique.