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PURPOSE This phase III, multicenter, randomized, open-label study investigated the efficacy and safety of nivolumab versus chemotherapy (gemcitabine [GEM] or pegylated liposomal doxorubicin [PLD]) in patients with platinum-resistant ovarian cancer. MATERIALS AND METHODS Eligible patients had platinum-resistant epithelial ovarian cancer, received ≤ 1 regimen after diagnosis of resistance, and had an Eastern Cooperative Oncology Group performance score of ≤ 1. Patients were randomly assigned 1:1 to nivolumab (240 mg once every 2 weeks [as one cycle]) or chemotherapy (GEM 1000 mg/m2 for 30 minutes [once on days 1, 8, and 15] followed by a week's rest [as one cycle], or PLD 50 mg/m2 once every 4 weeks [as one cycle]). The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), overall response rate, duration of response, and safety. RESULTS Patients (n = 316) were randomly assigned to nivolumab (n = 157) or GEM or PLD (n = 159) between October 2015 and December 2017. Median OS was 10.1 (95% CI, 8.3 to 14.1) and 12.1 (95% CI, 9.3 to 15.3) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.0; 95% CI, 0.8 to 1.3; P = .808). Median PFS was 2.0 (95% CI, 1.9 to 2.2) and 3.8 (95% CI, 3.6 to 4.2) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.5; 95% CI, 1.2 to 1.9; P = .002). There was no statistical difference in overall response rate between groups (7.6% v 13.2%; odds ratio, 0.6; 95% CI, 0.2 to 1.3; P = .191). Median duration of response was numerically longer with nivolumab than GEM or PLD (18.7 v 7.4 months). Fewer treatment-related adverse events were observed with nivolumab versus GEM or PLD (61.5% v 98.1%), with no additional or new safety risks. CONCLUSION Although well-tolerated, nivolumab did not improve OS and showed worse PFS compared with GEM or PLD in patients with platinum-resistant ovarian cancer.

Objective This retrospective analysis of a real-world database of open radical hysterectomy in Japan aimed to reveal the clinicopathological findings and clinical outcomes of low-risk patients with stage IB-IIA cervical cancer. Methods A total of 1143 stage IB1, IB2 and IIA1 (reclassified by FIGO 2018 staging system) patients with cervical cancer who underwent radical hysterectomy between January 2004 and December 2008 from the Japanese Gynecologic Oncology Group database were analyzed. Low-risk patients were defined as those without a tumor size exceeding 4 cm, parametrial tumor involvement, deep (outer half) stromal invasion, lymphovascular space invasion or lymph nodal metastasis. Results 61.2% (772/1262) patients with stage IB1, 32.1% (229/932) with stage IB2 and 16.9% (72/294) of stage IIA1 were classified into the low-risk group. The 5-year overall survival and disease-free survival rates were 98.4 and 93.7%, respectively. Histological classification did not affect the survival rates, but stage IIA cases had significantly lower overall survival and disease-free survival (83.5 and 93.8%, respectively) than stage IB cases. The independent prognostic factors for disease-free survival were older age (≧50), histology, clinical stage and clinical stage as independent prognostic factors for overall survival. Regarding recurrence, older age, non-SCC and stage IIA1 were independent risk factors for local recurrence, but stage IIA1 was the only independent risk factor for distant metastasis. Conclusion We found that stage IIA1 was the strongest risk factor for survival and recurrence of low-risk uterine cervical cancer (FIGO, 2018). In low-risk cases, stage IIA1 should be considered separately from stage IB.

Contains fulltext : 241226.pdf (Publisher’s version ) (Closed access) BACKGROUND: Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, has previously been shown to extend progression-free survival versus placebo when given to patients with relapsed high-grade serous or endometrioid ovarian cancer who were platinum sensitive and who had a BRCA1 or BRCA2 (BRCA1/2) mutation, as part of the SOLO2/ENGOT-Ov21 trial. The aim of this final analysis is to investigate the effect of olaparib on overall survival. METHODS: This double-blind, randomised, placebo-controlled, phase 3 trial was done across 123 medical centres in 16 countries. Eligible patients were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status at baseline of 0-1, had histologically confirmed, relapsed, high-grade serous or high-grade endometrioid ovarian cancer, including primary peritoneal or fallopian tube cancer, and had received two or more previous platinum regimens. Patients were randomly assigned (2:1) to receive olaparib tablets (300 mg in two 150 mg tablets twice daily) or matching placebo tablets using an interactive web or voice-response system. Stratification was by response to previous chemotherapy and length of platinum-free interval. Treatment assignment was masked to patients, treatment providers, and data assessors. The primary endpoint of progression-free survival has been reported previously. Overall survival was a key secondary endpoint and was analysed in all patients as randomly allocated. Safety was assessed in all patients who received at least one treatment dose. This trial is registered with ClinicalTrials.gov, NCT01874353, and is no longer recruiting patients. FINDINGS: Between Sept 3, 2013 and Nov 21, 2014, 295 patients were enrolled. Patients were randomly assigned to receive either olaparib (n=196 [66%]) or placebo (n=99 [34%]). One patient, randomised in error, did not receive olaparib. Median follow-up was 65·7 months (IQR 63·6-69·3) with olaparib and 64·5 months (63·4-68·7) with placebo. Median overall survival was 51·7 months (95% CI 41·5-59·1) with olaparib and 38·8 months (31·4-48·6) with placebo (hazard ratio 0·74 [95% CI 0·54-1·00]; p=0·054), unadjusted for the 38% of patients in the placebo group who received subsequent PARP inhibitor therapy. The most common grade 3 or worse treatment-emergent adverse event was anaemia (which occurred in 41 [21%] of 195 patients in the olaparib group and two [2%] of 99 patients in the placebo group). Serious treatment-emergent adverse events were reported in 50 (26%) of 195 patients receiving olaparib and eight (8%) of 99 patients receiving placebo. Treatment-emergent adverse events with a fatal outcome occurred in eight (4%) of the 195 patients receiving olaparib, six of which were judged to be treatment-related (attributed to myelodysplastic syndrome [n=3] and acute myeloid leukaemia [n=3]). INTERPRETATION: Olaparib provided a median overall survival benefit of 12·9 months compared with placebo in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation. Although statistical significance was not reached, these findings are arguably clinically meaningful and support the use of maintenance olaparib in these patients. FUNDING: AstraZeneca and Merck.

Aim: We present the study protocol of a multicenter, retrospective observational study that aims to investigate the efficacy of the actual treatment (the efficacy of conventional and Kampo medicines) of patients with mild to moderate or suspected coronavirus disease (COVID-19) Methods: This study is designed as a multicenter, retrospective observational study Outpatients and inpatients will be recruited from Japanese hospitals The inclusion criteria are as follows: having or suspected to have COVID-19, mild to moderate COVID-19, symptomatic, ≥20 years of age, male or female, able to communicate in Japanese, and treated with conventional and Kampo medicine The exclusion criteria are: unable to provide informed consent due to dementia, psychosis, or psychiatric symptoms, severe COVID-19, or determined unsuitable for this study The sample size is set at 1000, as this number of people can be treated at the collaborating medical institutions during the study period Results: The main outcome is the number of days without fever, with a body temperature of less than 37°C The secondary outcome is set at common cold-like symptoms other than fever (fatigue, cough, shortness of breath, sputum, diarrhea) and severity of illness and hospitalization up to 14 days after the visit Trial registration: The trial was registered in the University Hospital Medical Information Network (Reservation No UMIN000041301) on August 4, 2020 Conclusion: Our study will explore the contribution of conventional and Kampo medicine in the treatment of patients with mild and moderate COVID-19

Objective To investigate whether radical hysterectomy (RAH) can effectively treat true Stage IIB (pTIIB) cervical adenocarcinoma (AC) because FIGO (clinical) Stage IIB cervical cancer is rarely treated with RAH and radiotherapy has unfavorable effects on AC. Methods We retrospectively analyzed data for 82 patients with Stage pTIIB cervical cancer who underwent RAH at our institution between January 1997 and December 2017. The end points were disease‐free survival (DFS) and overall survival (OS) among squamous cell carcinoma (SCC) (n = 60) and AC (n = 22) patients. Kaplan–Meier survival analysis with and without propensity score matching was conducted to identify the impact of RAH. Results Para‐aortic lymph node metastasis and tumor diameter were significant factors for recurrence, and adjuvant chemotherapy prevented recurrence on multivariate analysis. After propensity score matching, there was no significant difference in DFS and OS between the groups. Five‐year DFS and OS of the SCC group were 0.505 (95% confidence interval [CI] 0.268–0.702) and 0.619 (95% CI 0.351–0.803), respectively, and those of the AC group were 0.444 (95% CI 0.232–0.638) and 0.602 (95% CI 0.351–0.782), respectively. Conclusion Bulky Stage pTIIB cervical cancer is hard to cure, but RAH plus adjuvant therapy might be an option for radio‐resistant pTIIB cervical AC., Radical hysterectomy plus radiotherapy or concurrent chemoradiotherapy and/or adjuvant chemotherapy could be an alternative treatment option for bulky pTIIB cervical adenocarcinoma with a radio‐unfavorable nature.

Purpose Computed tomography of the abdomen and pelvis is a useful imaging modality for identifying origin and extent of ovarian cancer before primary debulking surgery. However, the International Federation of Gynecology and Obstetrics staging for ovarian cancer is determined based on surgico-pathological findings. The purpose of this study is to determine whether computed tomography staging can be the surrogate for surgico-pathological International Federation of Gynecology and Obstetrics staging in advanced ovarian cancer undergoing neoadjuvant chemotherapy. Methods Computed tomography staging was compared with surgico-pathological International Federation of Gynecology and Obstetrics staging in primary debulking surgery arm patients in a randomized controlled trial comparing primary debulking surgery and neoadjuvant chemotherapy (JCOG0602). The cancer of primary debulking surgery arm was identically diagnosed regarding the origin and extent with the cancer of neoadjuvant chemotherapy arm before accrual, using imaging studies (computed tomography and/or magnetic resonance imaging), cytological examination (ascites, pleural effusion or tumor contents fluid) and tumor marker (CA125 > 200 U/mL and CEA < 20 ng/mL). Institutional computed tomography staging was also compared with computed tomography staging by central review. Results Among 149 primary debulking surgery arm patients, 147 patients who underwent primary debulking surgery immediately were analyzed. Positive predictive values and sensitivity of computed tomography staging for surgical stage III disease (extra-pelvic peritoneal disease and/or retroperitoneal lymph node metastasis) were 99%. Meanwhile, positive predictive values for the presence of small (≤2 cm) extra-pelvic peritoneal disease were low; Conclusions Preoperative computed tomography staging in each institution can be the surrogate for surgico-pathological diagnosis in stage III disease of ovarian cancer patients undergoing neoadjuvant chemotherapy without diagnostic surgery, but reliability of diagnosis of stage IIIB disease is inadequate. Clinical trial registration: UMIN000000523(UMIN-CTR).

Objective: Malignant transformation of a mature cystic teratoma (MTMCT) of the ovary is extremely rare; the occurrence rate is ∼1%–3% of all mature cystic teratomas. Because of the rarity of MTMCT,...

Regarding the comparison between primary debulking surgery (PDS) and neoadjuvant chemotherapy (NACT) for stage III/IV ovarian, tubal and peritoneal cancers, EORTC55971 and CHORUS studies demonstrated noninferiority of NACT. Previously, we reported reduced invasiveness of NACT in JCOG0602. This is a final analysis including the primary endpoint of overall survival (OS).Patients were randomised to PDS (PDS followed by 8x paclitaxel and carboplatin, i.e. TC regimen) or NACT (4x TC, interval debulking surgery [IDS], 4x TC). The primary endpoint was OS. The noninferiority hazard ratio (HR) margin for NACT compared with PDS was 1·161. The planned sample size was 300.Between 2006 and 2011, 301 patients were randomised, 149 to PDS and 152 to NACT. The median OS was 49·0 and 44·3 months in the PDS and NACT. HR for NACT was 1·052 [90·8% confidence interval (CI) 0·835-1·326], and one-sided noninferiority p-value was 0·24. Median progression-free survival was 15·1 and 16·4 months in the PDS and NACT (HR: 0·96 [95%CI 0·75-1·23]). In the PDS arm, 147/149 underwent PDS and 49/147 underwent IDS. In the NACT arm 130/152 underwent IDS. Complete resection was achieved in 12% (17/147) of PDS and 31% (45/147) of PDS ± IDS in the PDS arm and in 64% (83/130) of IDS in the NACT arm. Optimal surgery (residual tumour1 cm) was achieved in 37% (55/147), 63% (92/147), and 82% (107/130 respectively. In the NACT, PS 2/3, serum albumin ≤2·5, CA125 2000 an institution with low study activity was advantageous, whereas clear/mucinous histology was disadvantageous for OS.The noninferiority of NACT was not confirmed. NACT may not always be a substitute for PDS. However, as our study had smaller numbers, the noninferiority of the previous studies cannot be denied.Ministry of Health, Labour and Welfare, Japan and the National Cancer Center, Japan.UMIN000000523.

Objective Uterine leiomyosarcoma (uLMS) is a rare gynecologic malignancy for which the currently available treatments do not consistently provide long-term disease control. This study aimed to reveal the current clinical status of uLMS to support future clinical trials. Methods This study enrolled patients with uLMS treated at 53 Japanese institutions from 2000 to 2012. Central pathological review (CPR) was performed. All cases were confirmed by CPR, and epidemiological features, treatment, and prognosis were analyzed statistically. Results A total of 307 patients were enrolled. A diagnosis of uLMS was confirmed in 266 patients (86.6%) of patients after CPR, of whom data for 259 were analyzed. Of these, 186 (71.8%) patients underwent complete gross resection as primary therapy. Ninety-eight patients received no additional adjuvant therapy, while docetaxel and gemcitabine was the most frequent regimen among 155 patients treated with adjuvant chemotherapy. In all cases, the median overall survival (OS) was 44.2 months. Multivariate analyses of prognostic factors in all cases identified stage III and IV disease, high serum lactate dehydrogenase level, and menopausal status as poor prognostic factors. However, in stage I cases, high serum lactate dehydrogenase level and no adjuvant treatment were identified as poor prognostic factors. The 5-year OS of patients with stage I uLMS treated with adjuvant chemotherapy was significantly better than that of those without adjuvant treatment (67.8% vs 46.7%, P = 0.0461). Conclusions Despite complete removal of the primary lesion, the clinical course of patients with uLMS was poor due to recurrence of distant metastasis. The application of a suitable biomarker and effective adjuvant chemotherapy are required to improve the prognosis of patients with uLMS.

Sulfate is currently not regulated by Japanese water quality standards but could pose adverse health effects to dialysis patients if it remains in high concentration (more than 100 mg/L) in dialysis water and dialysis fluid prepared at healthcare facilities (HCFs). In this study, we obtained sulfate levels in raw water and finished water at Japanese drinking water purification plants (DWPPs) from “Statistics on Water Supply (Water Quality)” in FY2012-2014, and then estimated increases in sulfate by water purification processes. Impact of water treatment chemicals containing sulfate (e.g., alum for coagulation and sulfuric acid for pH adjustment) was also evaluated by water sampling at selected three DWPPs. In FY2012-14, sulfate levels in finished water were mostly less than 50 mg/L; however, sulfate at 18 out of 1,497 DWPPs exceeded 100 mg/L. Increases in sulfate level by dosing of the water treatment chemicals were typically less than 10 mg/L, and other part of the sulfate in finished water came from raw water. These information on water quality should be shared with medical professionals conducting the dialysis therapies, and it would be worthwhile to collaborate with them in water quality management at HCFs.

To clarify the frequency of deficient mismatch repair (dMMR) in Japanese ovarian cancer patients, we examined microsatellite instability (MSI) status and immunohistochemistry (IHC) subtypes, including endometrioid carcinoma (EMC), clear cell carcinoma (CCC), or a mixture of both (Mix).We registered 390 patients who were diagnosed with EMC/CCC/Mix between 2006 and 2015 and treated at seven participating facilities. For 339 patients confirmed eligible by the Central Pathological Review Board, MSI, IHC, and MutL homolog 1 methylation analyses were conducted. The tissues of patients with Lynch syndrome (LS)-related cancer histories, such as colorectal and endometrial cancer, were also investigated.MSI-high (MSI-H) status was observed in 2/217 CCC (0.9%), 10/115 EMC (8.7%), and 1/4 Mix (25%). Additionally, loss of MMR protein expression (LoE-MMR) was observed in 5/219 (2.3%), 16/115 (14.0%), and 1/4 (25%) patients with CCC, EMC, and Mix, respectively. Both MSI-H and LoE-MMR were found significantly more often in EMC (p0.001). The median (range) ages of patients with MMR expression and LoE-MMR were 54 (30-90) and 46 (22-76) (p=0.002), respectively. In the multivariate analysis, advanced stage and histological type were identified as prognostic factors.The dMMR rate for EMC/CCC was similar to that reported in Western countries. In Japan, it is assumed that the dMMR frequency is higher because of the increased proportion of CCC.

Aim Serous carcinoma of the uterine cervix (USCC) is a very rare malignant tumor, while this histological subtype is common in the ovary, fallopian tube, uterine corpus and peritoneum. Because of its rarity, details of the clinicopathological features of USCC are largely unknown. We retrospectively analyzed the clinicopathological characteristics of five cases of pure USCC. Methods We reviewed the medical records and pathological specimens of five USCC cases who were treated at the Gynecology Service of the National Hospital Organization Kyushu Cancer Center, Japan, between 2000 and 2017. The clinicopathological features were also compared with those of serous carcinomas of the endometrium and ovary who were treated during the same period. Results Five patients were treated at our hospital between 2000 and 2017. Three tumors were stage IB1, one was stage IIB, and one was stage IVB. The median follow‐up time was 104 months (range 26–210). Four patients other than stage IVB were treated with radical hysterectomy and have been free of relapse. One patient with stage IVB tumor was treated with platinum‐based combination chemotherapy and is currently on maintenance therapy with bevacizumab and remains free of relapse. Conclusion USCC has a distinctive clinicopathological feature that differentiates it from serous carcinomas of other female organs. USCC had been thought to be a poor prognostic disease; however, it could be curable if it is not accompanied by lymph node metastasis or peritoneal dissemination. We might conquer USCC even if it is accompanied by lymph node metastasis with the use of multimodal therapy.

The aim of this study was to evaluate the effects of treatment with both three-dimensional radiotherapy (3DRT) and weekly 40-mg/m2 cisplatin on postoperative uterine cervical cancer patients with high-risk prognostic factors. We conducted a retrospective multi-institutional chart review of postoperative uterine cervical cancer patients with high-risk prognostic factors who had been treated with both 3DRT and weekly 40-mg/m2 cisplatin from 2007 to 2012. Each participating hospital provided detailed information regarding patient characteristics, treatment outcomes, and treatment complications. The eligible 96 patients were analyzed. The median follow-up period was 61 months. The 3-year relapse-free survival, overall survival (OS), and locoregional relapse-free survival (LRFS) rates were 76%, 90%, and 88%, respectively. In multivariate analysis, the histological finding of either adenocarcinoma or adenosquamous carcinoma was a significant risk factor for both OS and LRFS. The percentage of patients with grade ≥ 3 acute hematologic toxicity, acute lower gastrointestinal toxicity (GIT), and late lower GIT were 45%, 19%, and 17%, respectively. The outcomes of concurrent chemoradiotherapy (CCRT) using weekly 40-mg/m2 cisplatin are similar to those in the previous studies that used several chemotherapy regimens. However, postoperative CCRT using 3DRT had a high level of late GIT.

Lanthanide complexes were prepared with 2,6-diacetylpyridinebis(benzoylhydrazone) (DAPBH2) and 7,7,8,8-tetracyano-p-quinodimethanide (TCNQ•−). The complexes adopted one of two structure types depending on the reaction solvent. The complexes were categorized as Type I (i.e. bis{[2,6-diacetylpyridinebis(benzoylhydrazone)] methanollanthanide(III)}bis(µ2- 7,7,8,8-tetracyanoquinodimethanide(1−))bis(7,7,8,8-tetracyanoquinodimethanide(1−))bis(7,7,8,8-tetracyanoquinodimethanide(1−)) methanol disolvate, [Ln2(DAPBH2)2 (µ2-TCNQ•−)2(TCNQ•−)2(MeOH)2](TCNQ•−)2·2MeOH (Ln = Gd, Tb, or Dy) or Type-II (i.e. [Ln2(DAPBH2)2(µ2-TCNQ•−)2(TCNQ•−)2(EtOH)2] (TCNQ•−)2·solvent (Ln = Tb and Dy, solvent =4EtOH for the Tb and 2EtOH·2CH2Cl2 for the Dy complexes). These two complexes exhibit dramatically different molecular structures and packings. In all complexes, the strong intra- and intermolecular stacking interactions of the TCNQ•− radicals lead to the formation of 1D TCNQ chains. Magnetic susceptibility measurements for Type I and Type II complexes reveal that they exhibit paramagnetic behavior and that their magnetic properties originate from the lanthanide ions alone, owing to the diamagnetic nature of the TCNQ•− stacks.

The purpose of our study was to conduct a detailed survey of radical hysterectomy in Japanese patients with early-stage cervical cancer, and to compare oncologic outcomes between open and minimally invasive radical hysterectomy. In Japan during 2015, the medical records of 929 patients with FIGO stage IB1 and IIA disease treated with radical hysterectomy were retrospectively reviewed. We assessed patients’ characteristics, disease-free survival (DFS), overall survival (OS) and prognostic factors for survival. The median patient age was 44 (20–80) years. Most patients (94.4%) had stage IB1 disease. Of the patients who underwent radical hysterectomy, 91.2% underwent open surgery and 8.8% underwent minimally invasive surgery (MIS). The median follow-up period was 40.8 months (range, 0.49–51.1 months). The rate of DFS and OS at 4 years in all patients was 88.3% and 96.4%, respectively. Multivariate analysis identified age (≥ 47), adenocarcinoma histology, tumor size (≥ 2 cm), parametrial invasion, positive lymph node metastasis and institutional accreditation as independent predictors of recurrence, and adenocarcinoma, other cell types, and positive lymph node metastasis as independent predictors of death. Oncologic outcomes in all patients were similar between open and MIS, including DFS and OS. The survival rate of the Japanese patients underwent radical hysterectomy for early-stage cervical cancer was favorable. No significant differences were observed for DFS and OS between open and MIS performed by a limited number of surgeons at a limited number of facilities in Japan. Further investigations are required to identify the appropriate patients might benefit from MIS.

Highlights • LG-ESS is a rare and indolent uterine tumor which has remarkable sensitivity to hormonal agents. • We presented the case of recurrent LG-ESS that was effectively and safely treated with Dienogest. • Dienogest may be useful for the treatment of LG-ESS that is resistant to other progestins., Low-grade endometrial stromal sarcoma (LG-ESS) is a rare uterine tumor that sometimes recurs and advances. Hormonal treatment, especially high-dose progestins and aromatase inhibitors (AIs), has demonstrated efficacy against these tumors. Because the standard treatment period is uncertain and hormonal treatment is effective, hormonal agents are likely to be used long-term, especially when a residual tumor is present. However, the long-term use of high-dose progestins and AIs may cause thromboembolism, as well as musculoskeletal stiffness and pain. Dienogest, a relatively new progestin, has demonstrated safety after long-term administration; it also appears to have a more favorable long-term safety profile compared with other progestins and AIs. We encountered a young patient with recurrent LG-ESS that metastasized to the liver and exhibited resistance to high-dose medroxyprogesterone acetate (MPA). The patient was successfully treated with dienogest monotherapy. This is the first report describing the efficacy of dienogest against recurrent and metastatic LG-ESS that is resistant to MPA and other agents.

Spin ice is an exotic type of magnetism displayed by bulk rare-earth pyrochlore oxides. We discovered a spin ice-like magnetic relaxation of [{Mn(saltmen)}4 {Mn(CN)6 }](ClO4 )⋅13 H2 O (saltmen2- =N,N'-(1,1,2,2-tetramethylethylene)bis(salicylideneiminate)). This magnetic system can be considered as a two-dimensional network of MnIII salen-type single-molecule magnets (SMMs) in which each SMM unit (ST =4) has two orthogonally oriented axial anisotropies and is connected ferromagnetically through the [Mn(CN)6 ]3- unit (S=1). This work illustrates that a two-dimensional SMM network with competition between the ferromagnetic interaction and local noncollinear magnetic anisotropies on SMMs is a new type of magnetic system exhibiting slow relaxation of magnetization with a Davidson-Cole-type broad distribution of the relaxation time.

This is the first case report of a vaginal squamous cell carcinoma that metastasized to the duodenum. Cytological and histopathological examinations are useful for the diagnosis of a duodenal metastasis.

This study examined the association between peritoneal cytology and survival in early-stage cervical cancer. This is a nationwide multicenter retrospective study, examining consecutive women with clinical stage IB1-IIB cervical cancer who underwent radical hysterectomy with available peritoneal cytology results from 2004&ndash, 2008. Propensity score inverse probability of treatment weighting was used to assess the impact of malignant peritoneal cytology on survival. Among 1409 analyzed cases, 88 (6.2%) had malignant peritoneal cytology. On weighted models, malignant peritoneal cytology was associated with decreased disease-free survival (hazard ratio (HR) 1.78, 95% confidence interval (CI) 1.36&ndash, 2.32) and overall survival (OS, HR 1.93, 95% CI 1.44&ndash, 2.59). On sensitivity analyses, malignant peritoneal cytology was associated with decreased OS in adenocarcinoma/adenosquamous carcinoma, high-risk early-stage disease and those who received concurrent chemo-radiotherapy. However, among women who received postoperative systemic chemotherapy, malignant peritoneal cytology was not associated with OS (HR 1.21, 95% CI 0.72&ndash, 2.04). A systematic review, including our results, showed that malignant peritoneal cytology was associated with decreased OS (HR 4.03, 95% CI 1.81&ndash, 8.99) and increased recurrence in squamous carcinoma (odds ratio 1.89, 95% CI 1.05&ndash, 3.39) and adenocarcinoma (odds ratio 4.30, 95% CI 2.30&ndash, 8.02). In conclusion, the presence of malignant cells in peritoneal cytology is associated with decreased survival in early-stage cervical cancer. The possible benefit of systemic chemotherapy in this subgroup merits further investigation.

Aim In concordance with population aging, the number of patients living in long-term care facilities or who require nursing care has been increasing in Japan. However, little is known about the characteristics of urinary tract infection in these patients. The present study aimed to clarify the background or risk factors for multidrug-resistant urinary tract infection in this patient population. Methods A retrospective study was carried out of patients aged ≥65 years who presented to Kesennuma City Municipal Motoyoshi Hospital from April 2014 to July 2017 with suspected urinary tract infection and a positive urine culture. Results Among a total of 76 patients, 20 (26%) had multidrug-resistant bacteriuria. The prevalence of multidrug-resistant bacteriuria was 40% among the long-term care facility residents, 34% among the patients who were certified as requiring care under the long-term care system in Japan and 47% among those with antibiotic prescription within 90 days. By multivariate analysis, long-term care facility residency was an independent risk factor for multidrug-resistant bacteriuria (odds ratio 4.1, 95% confidence interval 1.2-14.3). Conclusions Long-term care facility residency was found to be a significant predictor of multidrug-resistant bacteriuria. Nursing- and healthcare-associated urinary tract infection, which has different characteristics from those of community- or hospital-acquired infections, should be considered when deciding treatment in this population. Geriatr Gerontol Int 2018; 18: 1183-1188.

Purpose: A growing number of treatment options and active compounds in treatments have led to better outcomes for patients with advanced or recurrent epithelial ovarian cancer. We examined the association between progression-free survival (PFS), post-progression survival (PPS) and overall survival (OS) in phase III trials of second- and third-line chemotherapy for advanced or recurrent epithelial ovarian cancer. We aim to determine whether PFS or PPS is a surrogate of OS so that we can decide progress of disease is optimal endpoint for ovarian cancer. Methods: We identified 22 trials conducted between January 1, 2000 through December 31, 2014 by literature search. We divided OS into PFS and PPS, and assessed the association between OS and PFS/PPS. We also examined whether the year of trial enrollment completion was associated with any variables. Results: The median PPS was slightly longer in recent trials compared to older trials (10.0 vs. 8.8 months). While PPS was strongly associated with OS (r = 0.88) in all trials, PFS was moderately correlated with OS (r = 0.72). The correlation between OS and PPS in recent trials (r = 0.93) was stronger than in older trials (r = 0.84). Conclusions: Our findings indicate that PPS is highly associated with OS in second/third-line chemotherapy for advanced or recurrent epithelial ovarian cancer, while the association between PFS and OS is moderate. We recommend using OS as primary endpoint for clinical trial of ovarian cancer, however PFS is still an optional endpoint.

We investigated the magnetic properties of Ba1−xLaxTbO3 with x ​= ​0, 0.1, and 0.2. The parent compound BaTbO3, which has single valent Tb4+ ions, undergoes an antiferromagnetic transition at the Neel temperature TN ​= ​33 ​K. Substitution of Ba2+ with La3+ reduces Tb4+ into Tb3+ and significantly enhances the magnetization (M) below around 25 ​K. The enhancement of the M can be explained by the formation of ferrimagnetic (FIM) or ferromagnetic (FM) clusters caused by a magnetic interaction between Tb4+ and Tb3+. At x ​= ​0.2, the TN merges into the onset temperature of the formation of the FIM or FM clusters.

This study seeks to identify risk factors associated with ovarian metastasis and to characterize a population with minimum risk of ovarian metastasis in young women with stage IB-IIB cervical cancer. This was a nation-wide multicenter retrospective study in Japan examining consecutive cases of surgically-treated women with clinical stage IB-IIB cervical cancer who had oophorectomy at radical hysterectomy (n = 5,697). Multivariable analysis was performed to identify independent risk factors for ovarian metastasis. Ovarian metastasis was seen in 70 (1.2%, 95% confidence interval 0.9-1.5) cases. In the entire cohort, adenocarcinoma, lympho-vascular space invasion, uterine corpus tumor invasion, and pelvic/para-aortic nodal metastases remained independent risk factors for ovarian metastasis (all, adjusted-p

The Japan Society of Obstetrics and Gynecology collects and analyzes annual data on gynecologic cancers from member institutions. We present the Patient Annual Report for 2014 and the Treatment Annual Report for 2009. Data on 7436 patients with cervical cancer, 9673 with endometrial cancer, 5924 with ovarian cancer, and 1909 with ovarian borderline tumor for whom treatment was initiated in 2014 were summarized in the Patient Annual Report. Stage I accounted for 55.6%, stage II for 22.9%, stage III for 10.2%, and stage IV for 11.2% of all patients with cervical cancer. Stage I accounted for 72.3%, stage II for 6.0%, stage III for 14.1%, and stage IV for 7.7% of all patients with endometrial cancer. Stage I accounted for 43.3%, stage II for 9.1%, stage III for 27.6%, and stage IV for 7.2% of all patients with ovarian cancer. Data on the prognosis of 4126 patients with cervical cancer, 4613 with endometrial cancer, and 3205 with ovarian cancer for whom treatment was initiated in 2009 were analyzed in the Treatment Annual Report. Survival was analyzed by using the Kaplan-Meier method, the log-rank test and the Wilcoxon test. The 5-year overall survival rates for patients with cervical cancer were 92.4% for stage I, 76.7% for stage II, 54.3% for stage III, and 25.2% for stage IV. The equivalent rates for patients with endometrial cancer were 94.6%, 89.4%, 78.3%, and 25.0%, respectively; and those for patients with ovarian cancer (surface epithelial-stromal tumors) were 90.5%, 78.8%, 46.0%, and 25.1%, respectively.

Background Little is known about clinical factors associated with undetectable pneumonic shadows on chest radiographs (CRs) for diagnosing pneumonia in the primary care setting. Methods A retrospective assessment of CRs was conducted to compare chest computed tomography (CT) images of patients admitted to Kesennuma City Motoyoshi Municipal Hospital who were diagnosed with pneumonia from April 2014 to June 2016. Results Eighty‐three patients were included, and their average age was 83.8 years. Sixty‐eight patients (81.9%) were officially certified as requiring long‐term care or support. Twenty‐nine of the 83 patients (34.9%) had either negative or normal findings on CRs, and positive findings consistent with pneumonia on CT. There were no significant differences in gender, age, cardiothoracic ratio on CR, or severity between the CR‐negative and CR‐positive groups. The proportion of negative CRs was significantly higher in patients with certified care level 5 under the long‐term care system in Japan and tube feeding. Conclusion The failure rate of CRs for detecting pneumonic shadows was significantly higher in patients with certified care level 5 and tube feeding.

Objective The prognosis of ovarian cancer has improved because of platinum- and taxane-containing chemotherapy. We investigated the 5-year disease-specific overall survival and prognostic factors of patients with advanced ovarian cancer to elucidate the change in clinical course of ovarian cancer with the advance of chemotherapy for patients who developed relapse in the era before the addition of molecular targeting therapy. Methods We reviewed the clinical course of 134 patients with advanced ovarian cancer (FIGO Stage III and IV) treated in the past 11 years (1999-2010). We classified the patients into two groups: those who had been diagnosed with ovarian cancer from 1999 to 2005 (Group A) and those who had been diagnosed from 2006 to 2010 (Group B). We compared the 5-year disease-specific overall survival and median survival rates between these two groups. We also investigated the prognostic factors of 104 patients who developed relapse. Results The 5-year disease-specific overall survival rate was significantly higher in Group B than A (67.0% vs. 38.6%; P = 0.032). Chemotherapy containing pegylated liposomal doxorubicin hydrochloride, non-clear cell adenocarcinoma and intestinal resection were independent prognostic factors. Conclusions The induction of new chemotherapeutic drugs and the increased variation of second- or third-line chemotherapy affected the improvement in overall survival of patients with advanced epithelial ovarian cancer.

The Water and Environment Technology Conference 2019 (WET 2019)；2019.7.13-14；Osaka, Japan

BACKGROUND: Angiopoietin 1 and 2 regulate angiogenesis and vascular remodelling by interacting with the tyrosine kinase receptor Tie2, and inhibition of angiogenesis has shown promise in the treatment of ovarian cancer. We aimed to assess whether trebananib, a peptibody that inhibits binding of angiopoietin 1 and 2 to Tie2, improved progression-free survival when added to carboplatin and paclitaxel as first-line therapy in advanced epithelial ovarian, primary fallopian tube, or peritoneal cancer in a phase 3 clinical trial. METHODS: TRINOVA-3, a multicentre, multinational, phase 3, double-blind study, was done at 206 investigational sites (hospitals and cancer centres) in 14 countries. Eligible patients were aged 18 years or older with biopsy-confirmed International Federation of Gynecology and Obstetrics (FIGO) stage III to IV epithelial ovarian, primary peritoneal, or fallopian tube cancers, and an ECOG performance status of 0 or 1. Eligible patients were randomly assigned (2:1) using a permuted block method (block size of six patients) to receive six cycles of paclitaxel (175 mg/m2) and carboplatin (area under the serum concentration-time curve 5 or 6) every 3 weeks, plus weekly intravenous trebananib 15 mg/kg or placebo. Maintenance therapy with trebananib or placebo continued for up to 18 additional months. The primary endpoint was progression-free survival, as assessed by the investigators, in the intention-to-treat population. Safety analyses included patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01493505, and is complete. FINDINGS: Between Jan 30, 2012, and Feb 25, 2014, 1164 patients were screened and 1015 eligible patients were randomly allocated to treatment (678 to trebananib and 337 to placebo). After a median follow-up of 27·4 months (IQR 17·7-34·2), 626 patients had progression-free survival events (405 [60%] of 678 in the trebananib group and 221 [66%] of 337 in the placebo group). Median progression-free survival did not differ between the trebananib group (15·9 months [15·0-17·6]) and the placebo group (15·0 months [12·6-16·1]) groups (hazard ratio 0·93 [95% CI 0·79-1·09]; p=0·36). 512 (76%) of 675 patients in the trebananib group and 237 (71%) of 336 in the placebo group had grade 3 or worse treatment-emergent adverse events; of which the most common events were neutropenia (trebananib 238 [35%] vs placebo 126 [38%]) anaemia (76 [11%] vs 40 [12%]), and leucopenia (81 [12%] vs 35 [10%]). 269 (40%) patients in the trebananib group and 104 (31%) in the placebo group had serious adverse events. Two fatal adverse events in the trebananib group were considered related to trebananib, paclitaxel, and carboplatin (lung infection and neutropenic colitis); two were considered to be related to paclitaxel and carboplatin (general physical health deterioration and platelet count decreased). No treatment-related fatal adverse events occurred in the placebo group. INTERPRETATION: Trebananib plus carboplatin and paclitaxel did not improve progression-free survival as first-line treatment for advanced ovarian cancer. The combination of trebananib plus carboplatin and paclitaxel did not produce new safety signals. These results show that trebananib in combination with carboplatin and paclitaxel is minimally effective in this patient population. FUNDING: Amgen. ispartof: LANCET ONCOLOGY vol:20 issue:6 pages:862-876 ispartof: location:England status: published

Importance The efficacy of taxane plus platinum regimens has been demonstrated for advanced or recurrent endometrial cancer; however, it has not been assessed in postoperative adjuvant chemotherapy for endometrial cancer. Objective To evaluate the clinical benefit of taxane plus platinum compared with standard doxorubicin plus cisplatin as postoperative adjuvant chemotherapy in endometrial cancer. Design, Setting, and Participants In this multicenter, open-label, phase 3 randomized clinical trial, patients with endometrial cancer at high-risk stage I or II or stage III or IV that did not extend beyond the abdominal cavity and had 2 cm or greater residual tumor were included from 118 institutions in Japan from November 24, 2006, to January 7, 2011. Data was analyzed from March 15, 2017, to June 30, 2017. Interventions Eligible patients were randomly assigned (1:1:1) to receive 6 cycles of doxorubicin, 60 mg/m2, plus cisplatin, 50 mg/m2, on day 1; docetaxel, 70 mg/m2, plus cisplatin, 60 mg/m2, on day 1; or paclitaxel, 180 mg/m2, plus carboplatin (area under the curve, 6.0 mg/mL × min) on day 1 every 3 weeks. Main Outcomes and Measures The primary end point was progression-free survival. Secondary end points were overall survival, occurrence of adverse events, tolerability, and status of lymph node dissection. Results Among 788 eligible patients, the median (SD) age was 59 (22-74) years; 263 patients were assigned to doxorubicin plus cisplatin treatment, 263 patients to docetaxel plus cisplatin treatment, and 262 patients to paclitaxel plus carboplatin treatment. The number of patients who did not complete 6 cycles was 53 (20.1%) for the doxorubicin plus cisplatin group, 45 (17.1%) for the docetaxel plus cisplatin group, and 63 (24.0%) for the paclitaxel plus carboplatin group. Tolerability of these regimens were not statistically different. After a median follow-up period of 7 years, there was no statistical difference of progression-free survival (doxorubicin plus cisplatin, 191; docetaxel plus cisplatin, 208; paclitaxel plus carboplatin, 187;P = .12) or overall survival (doxorubicin plus cisplatin, 217; docetaxel plus cisplatin, 223; paclitaxel plus carboplatin, 215;P = .67) among the 3 groups. The 5-year progression-free survival rate was 73.3% for the doxorubicin plus cisplatin group, 79.0% for the docetaxel plus cisplatin group, and 73.9% for the paclitaxel plus carboplatin group, while the 5-year overall survival rates were 82.7%, 88.1%, and 86.1%, respectively. Conclusions and Relevance There was no significant difference of survival among patients receiving doxorubicin plus cisplatin, docetaxel plus cisplatin, or paclitaxel plus carboplatin as postoperative adjuvant chemotherapy for endometrial cancer. Because each regimen showed adequate tolerability but different toxic effects, taxane plus platinum regimens may be a reasonable alternative to treatment with doxorubicin plus cisplatin. Trial Registration UMIN-CTR identifier:UMIN000000522

Vulvar cancer and vaginal cancer are relatively rare cancer in the field of gynecologic oncology. Nevertheless, several advancements have been achieved in the surgical treatment for these cancers in the past two or three decades, especially in vulvar cancer. Individualization and minimization is the modern trend in the surgical treatment of vulvar cancer. However, the skills and techniques of the surgery for vulvar cancer are derived from the traditional surgery. Especially, the inguinal lymph node dissection is an essential part of the surgery but is not common as a daily practice. It is important for a surgeon to be well acquainted before surgery with the anatomy of the femoral triangle and the skills of the dissection before surgery. Reconstruction surgery is also important to close the wound adequately and safely reducing the postoperative wound breakdown, but is not familiar to most of the gynecologists. In the present chapter, these basic surgical methods in vulvar cancer are mainly described showing examples of the surgery.

Two spin crossover (SCO) coordination polymers assembled by combining FeII octahedral ion, 4-cyanopyridine (4-CNpy) and [Au(CN)2]&minus, liner unit are described. These compounds, Fe(4-CNpy)2[Au(CN)2]2&middot, 1/2(4-CNpy) (1a) and {Fe(4-CNpy)2[Au(CN)2]2}-{Fe(H2O)2[Au(CN)2]2} (1b), present quite different supramolecular networks that show different magnetic behaviors. Compound 1a crystallizes in the centrosymmetric space group Pbcn. The asymmetric unit contains two 4-CNpy, one type of Fe2+, and two types of crystallographically distinct [Au(CN)2]&minus, units which form Hofmann-like two dimensional layer structures with guest spaces. The layers are combined with another layer by strong gold-gold intermetalic interactions. Compound 1b crystallizes in the centrosymmetric space group Pnma. The bent bismonodentate [AuI(CN)2] units and FeII ions form a complicated interpenetrated three dimensional structure. In addition, 1b exhibits ferromagnetic interaction.

The Japan Society of Obstetrics and Gynecology collects and analyzes annual data on gynecologic cancers from member institutions. We present the Patient Annual Report for 2013 and the Treatment Annual Report for 2008. Data on 7280 patients with cervical cancer, 8952 with endometrial cancer, 5792 with ovarian cancer and 1903 with ovarian borderline tumor for whom treatment was initiated in 2013 were summarized in the Patient Annual Report. Stage I accounted for 56.7%, stage II for 23.4%, stage III for 9.8% and stage IV for 10.2% of all patients with cervical cancer. Stage I accounted for 71.7%, stage II for 6.5%, stage III for 14.5% and stage IV for 7.3% of all patients with endometrial cancer. Stage I accounted for 42.2%, stage II for 9.8%, stage III for 28.2% and stage IV for 8.3% of all patients with ovarian cancer. Data on the prognosis of 3658 patients with cervical cancer, 4159 with endometrial cancer and 2866 with ovarian cancer for whom treatment was initiated in 2008 were analyzed in the Treatment Annual Report. Survival was analyzed by using the Kaplan–Meier method, the log–rank test and the Wilcoxon test. The 5-year overall survival rates for patients with cervical cancer were 93.0% for stage I, 73.1% for stage II, 55.2% for stage III and 24.2% for stage IV. The equivalent rates for patients with endometrial cancer were 94.5%, 90.3%, 74.2% and 24.0%, respectively; and those for patients with ovarian cancer (surface epithelial–stromal tumors) were 90.5%, 73.5%, 48.1% and 29.4%, respectively.