CD25+FOXP3+CD45RA- regulatory T-cell infiltration as a prognostic biomarker for endometrial carcinoma.

BACKGROUND: Regulatory T (Treg) cells reportedly play crucial roles in tumor angiogenesis as well as antitumor immunity. In order to explore their therapeutic potential, we investigated the precise prognostic impact of Treg markers in endometrial carcinoma. METHODS: We performed multiplexed immunofluorescence and quantitative image analyses of CD25, FOXP3, CTLA4, and CD45RA in tumor specimens from 176 consecutive patients treated at our institution for primary endometrial carcinomas. Bioinformatics analyses were further conducted to corroborate the findings. RESULTS: High CD25+, FOXP3+, and CD25+FOXP3+CD45RA- stromal cell counts correlated with better overall survival (OS) (p = 0.00019, 0.028 and 0.0012) and MSI-high (p = 0.015, 0.016 and 0.047). High CD45RA+ stromal cell count was associated with superficial myometrial invasion (p = 0.0038). Bioinformatics survival analysis by Kaplan-Meier plotter showed that high CD25, FOXP3, CTLA4, and CD45RA mRNA expressions correlated with better OS (p = 0.046, 0.00042, 0.000044, and 0.0022). Univariate and multivariate analyses with various clinicopathologic prognostic factors indicated that high CD25+ or CD25+FOXP3+CD45RA- stromal cell count was significant and independent for favorable OS (p = 0.0053 and 0.0015). We subsequently analyzed the correlations between the multiplexed immunofluorescence results and treatment-free interval (TFI) after primary chemotherapy in recurrent cases, finding no significant associations. Further analysis revealed that high ratio of CD25+ : CD8+ cell count or CD25+FOXP3+CD45RA- : CD8+ cell count correlated with longer TFI (p = 0.021 and 0.021). CONCLUSION: The current observations suggest that the balance between CD25+ or CD25+FOXP3+CD45RA- cells and CD8+ cells, corresponding to promoting or inhibiting effect on tumor angiogenesis, affect tumor chemosensitivity leading to prognostic significance. CD25+FOXP3+CD45RA- effector Treg tumor infiltration may serve as a useful prognostic biomarker and a potential target for immunotherapeutic manipulation of tumor chemosensitivity by novel management for advanced/recurrent endometrial carcinomas.

Pharmacokinetic study of erlotinib in a pregnant woman with advanced non-small cell lung cancer and observation of the effects on the child growth.

AIMS: The aim of the study is to report the clinical and pharmacological observations from a pregnant patient treated with erlotinib in the second and third trimesters of pregnancy. METHODS: Maternal and neonatal blood levels and safety of erlotinib and its metabolites were evaluated. Child development was monitored for 6 years. RESULTS: A 31-year-old woman with stage IV lung adenocarcinoma with EGFR exon19 deletion began treatment with erlotinib 150 mg/day at 17 weeks of gestation. Although foetal growth retardation and oligohydramnios were observed at several times during the pregnancy, treatment was continued due to the severity of the maternal presentation, with ongoing foetal monitoring. The foetus seemed to tolerate and recover well without specific interventions. A healthy baby boy was delivered at 37 weeks gestation. The child grew and developed without any obvious issues. At last follow-up, at age 6 years, he was attending school at a grade appropriate for his age without health or developmental problems. Blood levels of erlotinib were 397-856 ng/mL at 18-37 weeks of gestation and 1190 ng/mL at 8 weeks postpartum. The blood concentration ratios of OSI-413-to-erlotinib ranged from 0.167 to 0.253 at 18-37 weeks of gestation, excluding 24 weeks, and 0.131 at 8 weeks postpartum. The maternal-to-foetal transfer rate of erlotinib, OSI-420 and OSI-413 were 24.5, 34.8 and 20.3%, respectively. CONCLUSION: Erlotinib use during the second and third trimester of pregnancy did not seem to cause any untoward effects on the developing foetus, or any long-lasting effects that could be detected during 6 years of follow-up of the child.

Updated progression-free survival and final overall survival with maintenance olaparib plus bevacizumab according to clinical risk in patients with newly diagnosed advanced ovarian cancer in the phase III PAOLA-1/ENGOT-ov25 trial.

OBJECTIVE: In the PAOLA-1/ENGOT-ov25 trial (NCT02477644), adding maintenance olaparib to bevacizumab provided a substantial progression-free survival benefit in patients with newly diagnosed advanced ovarian cancer and homologous recombination deficiency (HRD)-positive tumors, irrespective of clinical risk. Subsequently, a clinically meaningful improvement in overall survival was reported with olaparib plus bevacizumab in the HRD-positive subgroup. We report updated progression-free survival and overall survival by clinical risk and HRD status. METHODS: Patients in clinical response after first-line platinum-based chemotherapy plus bevacizumab received maintenance olaparib (up to 24 months) plus bevacizumab (up to 15 months in total) or placebo plus bevacizumab. This post hoc analysis evaluated 5-year progression-free survival and mature overall survival in patients classified by clinical risk and HRD status. RESULTS: Of 806 randomized patients, 74% were higher-risk and 26% were lower-risk. In higher-risk HRD-positive patients, the hazard ratio (HR) for progression-free survival was 0.46 (95% confidence interval (95% CI) 0.34 to 0.61), with 5-year progression-free survival of 35% with olaparib plus bevacizumab versus 15% with bevacizumab alone; and the HR for overall survival was 0.70 (95% CI 0.50 to 1.00), with 5-year overall survival of 55% versus 42%, respectively. In lower-risk HRD-positive patients, the HR for progression-free survival was 0.26 (95% CI 0.15 to 0.45), with 5-year progression-free survival of 72% with olaparib plus bevacizumab versus 28% with bevacizumab alone; and the HR for overall survival was 0.31 (95% CI 0.14 to 0.66), with 5-year overall survival of 88% versus 61%, respectively. No benefit was seen in HRD-negative patients regardless of clinical risk. CONCLUSION: This post hoc analysis indicates that in patients with newly diagnosed advanced HRD-positive ovarian cancer, maintenance olaparib plus bevacizumab should not be limited to those considered at higher risk of disease progression. Five-year progression-free survival rates support long-term remission and suggest an increased potential for cure with particular benefit suggested in lower-risk HRD-positive patients.

Re-administration of platinum-based chemotherapy for recurrent endometrial cancer: an ancillary analysis of the SGSG-012/GOTIC-004/Intergroup study.

BACKGROUND: We previously demonstrated the applicability of the concept of "platinum sensitivity" in recurrent endometrial cancer. Although immune checkpoint inhibitors have been widely incorporated into endometrial cancer treatment, the debate continues regarding treatment options in patients with recurrent endometrial cancer who have previously received platinum-based chemotherapy. In this study, we assessed the duration of response to secondary platinum-based treatment using pooled data from the SGSG-012/GOTIC-004/Intergroup study. METHODS: Among the 279 participants in the SGSG-012/GOTIC-004/Intergroup study wherein platinum-based chemotherapy was re-administered for managing recurrent endometrial cancer between January 2005 and December 2009, 130 (47%) responded to chemotherapy. We compared the relationship between platinum-free interval and duration of secondary platinum-based treatment using pooled data. RESULTS: In 40 patients (31%), the duration of response to secondary platinum-based treatment exceeded the platinum-free interval. The duration of response to secondary platinum-based treatment exceeded 12 months in 51 patients (39%) [platinum-free interval: < 12 months, 14/48 (29%); 12-23 months, 18/43 (42%); 24-35 months, 8/19 (42%); ≥ 36 months, 11/20 (55%)]. In particular, in eight patients (6%), the duration of response to secondary platinum-based treatment exceeded 36 months [platinum-free interval: < 12 months, 3/48 (6%); 12-23 months, 0/19 (0%); 24-35 months, 2/19 (11%); ≥ 36 months, 3/20 (15%)]. CONCLUSIONS: Re-administration of platinum-based chemotherapy for recurrent endometrial cancer may result in a long-term response exceeding the platinum-free interval in some patients. Even in the current situation, where immune checkpoint inhibitors have been introduced, re-administration of platinum-based chemotherapy is worth considering.

Quality of care measurement for patients with ovarian cancer in Japan.

AIM: Quality of care is important to reduce disease progression, and improve both survival and quality of life. The Japan Society of Gynecologic Oncology has published treatment guidelines to promote standardized high-quality care for ovarian cancer in Japan. We developed quality indicators based on the guideline recommendations and used them on large datasets of health service use to examine the quality of ovarian cancer care. METHODS: A panel of experts developed the indicators using a modified Delphi method. Adherence to each indicator was evaluated using data from a hospital-based cancer registry of patients diagnosed in 2018. All patients receiving first-line treatment at participating facilities were included. The adherence rates were returned to participating hospitals, and reasons for nonadherence were collected. A total of 580 hospitals participated, and the study examined the care received by 6611 patients with ovarian cancer and 1879 with borderline tumors using 11 measurable quality indicators. RESULTS: The adherence rate ranged from 22.6% for "Estrogen replacement within 6 months of operation" to 93.5% for "Bleomycin, etoposide, and cisplatin for germ cell tumor more than Stage II." Of 580 hospitals, 184 submitted the reasons for nonadherence. CONCLUSIONS: The quality of ovarian cancer care should be continuously assessed to encourage the use of best practices. These indicators may be a useful tool for this purpose.

Clinical characteristics and prognostic factors of endometrial stromal sarcoma and undifferentiated uterine sarcoma confirmed by central pathologic review: A multi-institutional retrospective study from the Japanese Clinical Oncology Group.

OBJECTIVES: Low-grade and high-grade endometrial stromal sarcomas (LGESS and HGESS) and undifferentiated uterine sarcomas (UUS) are rare tumors whose pathological classification and staging system have changed recently. These tumors are reported to contain fusion genes. We aimed to clarify the genetic background, clinical features, prognostic factors, and optimal therapy of these tumors using a new classification and staging system. METHODS: We analyzed the clinical features and prognostic information of 72 patients with LGESS, 25 with HGESS, and 16 with UUS using central pathological review. Estrogen and progesterone receptors (PgRs) were examined by immunohistochemistry. JAZF1-SUZ12 and YWHAE-NUTM2A/B gene fusions were tested using real-time polymerase chain reaction. RESULTS: The 5-year overall survival (OS) rates of LGESS, HGESS, and UUS were 94%, 53%, and 25%, respectively. In LGESS, stage IV, incomplete surgery, and absence of PgR were associated with poor OS. The presence of JAZF1-SUZ12 fusion gene was not associated with OS. In HGESS, the relationship between stage and prognosis was unclear. None of the 3 patients with YWHAE-NUTM2A/B fusion gene died during follow-up. Adjuvant chemotherapy was associated with a favorable OS. Incomplete resection of UUS was associated with poor OS; however, residual tumors frequently occurred. Although most patients underwent adjuvant chemotherapy, their prognosis was extremely poor even in stage I disease. CONCLUSIONS: Prognosis of LGESS is generally good; however, stage IV, incomplete surgery, and PgR-negative tumors are associated with poor prognosis. Adjuvant chemotherapy may be useful for HGESS. Prognosis of UUS is extremely poor, even with adjuvant chemotherapy.

Final analysis of a randomized phase II/III trial of conventional paclitaxel and carboplatin with or without bevacizumab versus dose-dense paclitaxel and carboplatin with or without bevacizumab, in stage IVB, recurrent, or persistent cervical carcinoma (JCOG1311).

OBJECTIVE: To assess the efficacy of dose-dense weekly paclitaxel plus carboplatin in metastatic or recurrent cervical carcinoma, we conducted a phase II/III randomized controlled study comparing dose-dense paclitaxel and carboplatin with or without bevacizumab to conventional paclitaxel and carboplatin with or without bevacizumab. However, at the primary analysis of the phase II part, the response rate in the dose-dense arm was not higher than in the conventional arm and the study was terminated early before starting phase III. After a further 2 years of follow-up, we conducted this final analysis. METHODS: 122 patients were enrolled and randomly assigned to either the conventional or dose-dense arm. After bevacizumab was approved in Japan, patients in both arms received bevacizumab if not contraindicated. In the final analysis, overall survival, progression-free survival, and adverse events were updated. RESULTS: The median follow-up of surviving patients was 34.8 months (range 19.2-64.8). Median overall survival in the conventional arm was 17.7 months and in the dose-dense arm 18.5 months (p=0.71). Median progression-free survival in the conventional arm was 7.9 months and in the dose-dense arm 7.2 months (p=0.64). A platinum-free interval within 24 weeks and treatment without bevacizumab were identified as prognostic factors for overall and progression-free survival. Grade 3 to 4 non-hematologic toxicity occurred in 46.7% of patients who received the conventional regimen and in 43.3% of patients who received the dose-dense regimen. Adverse events related to bevacizumab in 82 patients included fistula in five (6.1%) and gastrointestinal perforation in three (3.7%). CONCLUSIONS: It was confirmed that dose-dense paclitaxel plus carboplatin for metastatic or recurrent cervical carcinoma is not superior to conventional paclitaxel and carboplatin. Patients who had early refractory disease after prior chemoradiotherapy had the poorest prognosis. The development of treatments that improve the prognosis of such patients remains an important issue. CLINICAL TRIAL INFORMATION: jRCTs031180007.

Cellular angiofibroma in the retroperitoneal space during pregnancy: A case report.

BACKGROUND: Cellular angiofibroma (CA) is a rare, benign mesenchymal tumor first described by Nucci et al. (Am J Surg Pathol 21:636-644, 1997. 10.1097/00000478-199706000-00002). It affects both men and women, although it is more common in middle-aged women. CA is well circumscribed and usually observed on the body surface, primarily in distal genital regions. Aggressive angiomyxoma and angiomyofibroblastoma are clinically and histologically similar; therefore, it may be necessary to distinguish between CA and these similar tumors. We present a rare case of CA, with atypical features, in the retroperitoneal space during pregnancy. CASE PRESENTATION: The presence of a 130 mm tumor was detected in a 19-year-old woman. The tumor, located in the retroperitoneal space, was found during first pregnancy examination. At 16 weeks of gestation, the woman developed nausea and fever, and it was diagnosed with acute pyelonephritis. After a few days, the amniotic membranes prematurely ruptured, leading to a miscarriage. The woman underwent a tumor resection, after miscarriage. This case presented with atypical features of CA. This included the young age of the patient, and presence of a tumor in the retroperitoneal space. CONCLUSION: In this case, the diagnosis of CA was difficult due to the rarity of the disease and its atypical clinical features. From this experience, we recommend that the discussion on the efficacy of surgical treatment and pregnancy outcomes should be done based on individual case, and not generalized.

Ovarian serous borderline tumors with recurrent or extraovarian lesions: a Japanese, retrospective, multi-institutional, population-based study.

BACKGROUND: Ovarian serous borderline tumors (SBT) are typically unilateral and are primarily treated using hysterectomy and bilateral salpingooophorectomy (SO). However, most young patients prefer fertility-sparing surgeries (FSS) with tumorectomy or unilateral SO. Micropapillary morphology and invasive implants have been designated as histopathological risk indicators for recurrence or metastasis, but their clinical impact remains controversial because of limitations like diagnostic inconsistency and incomplete surgical staging. METHODS: A nationwide multi-institutional population-based retrospective surveillance was conducted with a thorough central pathology review to reveal the clinical features of SBT. Of 313 SBT patients enrolled in the Japanese Society of Clinical Oncology's Surveillance of Gynecologic Rare Tumors, 289 patient records were reviewed for clinical outcomes. The glass slides of patients at stage II-IV or with recurrence or death were re-evaluated by three gynecological pathologists. RESULT: The 10-year overall and progression-free survival (PFS) rates were 98.6% and 92.3%. The median recurrence period was 40 months and 77.0% was observed in the contralateral ovary within 60 months. Patients aged ≤ 35 years underwent FSS more frequently and relapsed more (p < .001). A clinic-pathological analysis revealed diagnosis during pregnancy, FSS, and treatment at non-university institutes as well as advanced stage and large diameter were independent risk factors of recurrence. Among patients having pathologically confirmed SBTs, PFS was not influenced by the presence of micropapillary pattern or invasive implants. CONCLUSION: The recurrence rate was lower in this cohort than previous reports, but the clinical impacts of incomplete resection and misclassification of the tumor were still significant on the treatment of SBT.

The Prevalence of COVID-19 Vaccination and Vaccine Hesitancy in Pregnant Women: An Internet-based Cross-sectional Study in Japan.

BACKGROUND: Reluctance of people to receive recommended vaccines is a growing concern, as distribution of vaccines is considered critical to ending the COVID-19 pandemic. There is little information regarding pregnant women's views toward coronavirus vaccination in Japan. Therefore, we investigated the vaccination rate and reasons for vaccination and vaccine hesitancy among pregnant women in Japan. METHODS: We conducted a cross-sectional study involving 1,791 pregnant women using data from the Japan "COVID-19 and Society" Internet Survey, conducted from July to August 2021, and valid response from 1,621 respondents were analyzed. We defined participants with vaccine hesitancy as those who identified with the statement "I do not want to be vaccinated" or "I want to 'wait and see' before getting vaccinated." Multivariate Poisson regression analysis was used to investigate the factors contributing to vaccine hesitancy. RESULTS: The prevalence of vaccination and vaccine hesitancy among pregnant women was 13.4% (n = 217) and 50.9% (n = 825), respectively. The main reasons for hesitancy were concerns about adverse reactions and negative effects on the fetus and breastfeeding. Vaccine hesitancy was significantly associated with the lack of trust in the government (adjusted prevalence ratio, 1.26; 95% confidence interval, 1.03-1.54). Other factors, such as age, educational attainment, and state of emergency declaration, were not associated with vaccine hesitancy. CONCLUSIONS: COVID-19 vaccination is not widespread among pregnant women in Japan, although many vaccines have been shown to be safe in pregnancy. Accurate information dissemination and boosting trust in the government may be important to address vaccine hesitancy among pregnant women.

The efficacy of deep learning models in the diagnosis of endometrial cancer using MRI: a comparison with radiologists.

PURPOSE: To compare the diagnostic performance of deep learning models using convolutional neural networks (CNN) with that of radiologists in diagnosing endometrial cancer and to verify suitable imaging conditions. METHODS: This retrospective study included patients with endometrial cancer or non-cancerous lesions who underwent MRI between 2015 and 2020. In Experiment 1, single and combined image sets of several sequences from 204 patients with cancer and 184 patients with non-cancerous lesions were used to train CNNs. Subsequently, testing was performed using 97 images from 51 patients with cancer and 46 patients with non-cancerous lesions. The test image sets were independently interpreted by three blinded radiologists. Experiment 2 investigated whether the addition of different types of images for training using the single image sets improved the diagnostic performance of CNNs. RESULTS: The AUC of the CNNs pertaining to the single and combined image sets were 0.88-0.95 and 0.87-0.93, respectively, indicating non-inferior diagnostic performance than the radiologists. The AUC of the CNNs trained with the addition of other types of single images to the single image sets was 0.88-0.95. CONCLUSION: CNNs demonstrated high diagnostic performance for the diagnosis of endometrial cancer using MRI. Although there were no significant differences, adding other types of images improved the diagnostic performance for some single image sets.

Japan Society of Clinical Oncology Clinical Practice Guidelines 2017 for fertility preservation in childhood, adolescent, and young adult cancer patients: part 2.

The Japan Society of Clinical Oncology (JSCO) published the "JSCO Clinical Practice Guidelines 2017 for Fertility Preservation in Childhood, Adolescent, and Young Adult Cancer Patients" in 2017. This was the first guideline in cancer reproductive medicine in Japan. In the field of cancer reproductive medicine, close cooperation between an oncologist and a physician for reproductive medicine is important from before treatment initiation until long after treatment. The guideline takes into consideration disease specificity and provides opinions from the perspective of oncologists and specialists in reproductive medicine that are in line with the current state of the Japanese medical system. It is intended to serve as a reference for medical staff in both fields regarding the availability of fertility preservation therapy before the start of cancer treatment. Appropriate use of this guideline makes it easier to determine whether fertility preservation therapy is feasible and, ultimately, to improve survivorship in childhood, adolescent, and young adult cancer patients. In this article (Part 2), we describe details by organ/system and also for pediatric cancer.

Japan Society of Clinical Oncology Clinical Practice Guidelines 2017 for fertility preservation in childhood, adolescent, and young adult cancer patients: part 1.

In 2017, the Japan Society of Clinical Oncology (JSCO) published the JSCO Clinical Practice Guidelines 2017 for Fertility Preservation in Childhood, Adolescent, and Young Adult Cancer Patients. These were the first Japanese guidelines to address issues of oncofertility. In this field of medicine, sustained close cooperation between oncologists and reproductive specialists is essential from the diagnosis of cancer until many years after completion of cancer treatment. These JSCO guidelines were intended to guide multidisciplinary medical staff in considering the availability of fertility preservation options and to help them decide whether to provide fertility preservation to childhood, adolescent, and young adult cancer patients before treatment starts, with the ultimate goal of improving patient survivorship. The guidelines are presented as Parts 1 and 2. This article (Part 1) summarizes the goals of the guidelines and the methods used to develop them and provides an overview of fertility preservation across all oncology areas. It includes general remarks on the basic concepts surrounding fertility preservation and explanations of the impacts of cancer treatment on gonadal function by sex and treatment modality and of the options for protecting/preserving gonadal function and makes recommendations based on 4 clinical questions. Part 2 of these guidelines provides specific recommendations on fertility preservation in 8 types of cancer (gynecologic, breast, urologic, pediatric, hematologic, bone and soft tissue, brain, and digestive).

Differential roles of the Wip1-p38-p53 DNA damage response pathway in early/advanced-stage ovarian clear cell carcinomas.

BACKGROUND: Ovarian clear cell carcinoma (OCCC) is one of the most lethal types of ovarian cancer. Early-stage OCCC can be cured by surgery; however, advanced-stage disease shows poor prognosis due to chemoresistance unlike the more common high-grade serous carcinoma. METHODS: We explored the differential roles of the Wip1-p38-p53 DNA damage response pathway in respective early- or advanced-stage OCCC by immunohistochemistry of Wip1, phospho-p38, p53, and phospho-p53 from consecutive 143 patients. RESULTS: High Wip1 expression correlated with positive p53 (p=0.011), which in turn correlated with low nuclear phospho-p38 expression (p=0.0094). In the early stages, positive p53 showed trends toward worse overall survival (OS) (p=0.062), whereas in the advanced stages, high Wip1 correlated with worse OS (p=0.0012). The univariate and multivariate analyses of prognostic factors indicated that high Wip1 was significant and independent for worse OS (p=0.011) in the advanced stages, but not in the early stages. Additionally, high Wip1 showed trends toward shorter treatment-free interval (TFI) in the advanced stages, but not in the early stages (p=0.083 vs. 0.93). Furthermore, high Wip1 was significantly associated with positive p53 only in the patients with shorter TFI (<6 months), but not in those with longer TFI (≥6 months) (p=0.036 vs. 0.34). CONCLUSIONS: Wip1 appears to play a crucial role for the prognosis of OCCC through chemoresistance specifically in the advanced stages, implicating that Wip1 possibly serves as a reasonable therapeutic target for improving chemoresistance and poor prognosis of advanced-stage OCCC.

Obstetric venous thromboembolism: Evaluation of prophylactic approach based on risk scores, D-dimer levels, and ultrasonography findings in a tertiary hospital in Japan.

AIM: Pulmonary embolism remains a leading cause of maternal mortality in developed countries despite developments in venous thromboembolism prophylaxis strategies. This study aimed to evaluate the effectiveness of our approach involving risk-scoring, D-dimer level assessment, and ultrasonography for obstetric venous thromboembolism. METHODS: This retrospective cohort study included women who delivered at 22-41 weeks of gestation in The University of Tsukuba Hospital, Japan between January and December 2020. Venous thromboembolism risk (determined according to Japanese guidelines) and D-dimer levels were evaluated within 20 weeks of gestation, 30-34 weeks of gestation, and during the pre-delivery period (36 weeks of gestation or any time before preterm delivery). Compression and color Doppler ultrasonography for lower extremity deep vein thrombosis were performed if D-dimer levels were ≥3.2 µg/mL (for those undergoing cesarean delivery, 1.0 µg/mL). RESULTS: Of 1026 women, 6 women had deep vein thrombosis during pregnancy and 1 during the puerperium period. Pulmonary embolism was not observed. The D-dimer screening result was positive for 8 women (2%) within 20 weeks of gestation (deep vein thrombosis was confirmed in 3 of them), 87 women (10%) (no deep vein thrombosis) at 30-34 weeks of gestation, and 367 women (36%) during the pre-delivery period (asymptomatic deep vein thrombosis in one). Based on the Japanese guidelines, 1%, 11%, 33%, and 55% of women had high, intermediate, low, and no postpartum risk factors, respectively. CONCLUSIONS: Our approach appears useful for antenatal venous thromboembolism screening in the first trimester. For postpartum prophylaxis, more cost-effective strategies are needed.

Survival and reproductive outcomes after fertility-sparing surgery performed for borderline epithelial ovarian tumor in Japanese adolescents and young adults: Results of a retrospective nationwide study.

OBJECTIVE: Epithelial borderline ovarian tumor (BOT) frequently occurs in young women. Because progression-free survival, overall survival, and reproductive function are important outcomes, BOT is often treated by fertility-sparing surgery (FSS). We conducted a Japan-wide study to understand post-FSS prognosis in relation to clinical characteristics and types of FSS performed. METHODS: We analyzed clinical and outcome data pertaining to 531 adolescent and young adult (AYA) patients (aged 15-39 years) who underwent FSS for BOT between 2009 and 2013. RESULTS: Median (range) age was 30 (15-39) years, and median observation time was 70 (2-120) months. The disease was of FIGO stage I in 492 (93%) patients. Histopathologically, tumors were of the mucinous (n = 372, 70%), serous (n = 120, 23%), seromucinous (n = 23, 4%), and other (n = 16, 3%) types. Five-year overall survival was 99.5% among patients with stage I and 100% among those with stage II-IV. Five-year progression-free survival was 96.7% and 69.3%, respectively. Multivariate analysis in cases of stage I showed a positive peritoneal cytology to be a significant risk factor for recurrence (HR, 5.199; p = 0.0188). The post-FSS pregnancy rate was relatively low for patients aged ≥30 years (OR, 0.868; 95% CI, 1.16-3.00; p = 0.0090). CONCLUSION: Post-FFS outcomes in terms of overall and progression-free survival are favorable, especially for AYA patients with stage I BOT. However, the relapse rate is high for patients with FIGO stage II-IV and for those with stage I but a positive peritoneal cytology. A long-term prospective observation is needed before reproductive outcomes can be fully established.

Relationship between the serum cancer antigen 125 level and the weight of surgically enucleated adenomyosis.

Elevated serum levels of cancer antigen 125 (CA125) are known to occur in adenomyosis. However, the relationship between the severity of adenomyosis and serum CA125 levels has not yet been elucidated. The present study aimed to examine the correlation between the weight of adenomyosis and the serum CA125 level. This retrospective study, after applying exclusion criteria, investigated 308 patients who underwent conservative surgery for adenomyosis. Serum CA125 levels were measured before surgery and weights of surgically enucleated adenomyosis were measured in the operating room. Both serum CA125 and surgically enucleated adenomyosis weight showed log-normal distributions. Pearson's product-moment correlation coefficient for the logarithmically converted values was 0.617 (95% confidence interval, 0.54-0.68).The serum CA125 level correlated positively with the weight of adenomyosis. Although the qualitative characteristics and clinical significance of adenomyosis lesions remain unclear, it seems that the investigation of the relative relationship between the serum CA125 level and the size of the affected lesion is useful to observe one of the qualitative features of adenomyosis. Furthermore, the present study supports the use of postoperative serum CA125 levels as an important indicator for determining the therapeutic effects of conservative surgical treatment for adenomyosis and detecting early signs of recurrence. Impact StatementWhat is already known on this subject? Elevated serum cancer antigen 125 (CA125) levels are known to occur in adenomyosis and are widely recognised as helpful in the diagnosis of adenomyosis.What do the results of this study add? There is a positive correlation between the serum CA125 level and the weight of adenomyosis.What are the implications of these findings for clinical practice and/or further research? The postoperative serum CA125 level is an important indicator for evaluating the extent of the affected lesion remaining after conservative surgical treatment for adenomyosis and also helpful for detecting early signs of recurrence. Further study is required to examine whether it is possible to clarify the qualitative characteristics of adenomyosis in each different case based on the CA125-producing ability of the lesion.

Differentiation of carcinosarcoma from endometrial carcinoma on magnetic resonance imaging using deep learning.

Purpose: To verify whether deep learning can be used to differentiate between carcinosarcomas (CSs) and endometrial carcinomas (ECs) using several magnetic resonance imaging (MRI) sequences. Material and methods: This retrospective study included 52 patients with CS and 279 patients with EC. A deep-learning model that uses convolutional neural networks (CNN) was trained with 572 T2-weighted images (T2WI) from 42 patients, 488 apparent diffusion coefficient of water maps from 33 patients, and 539 fat-saturated contrast-enhanced T1-weighted images from 40 patients with CS, as well as 1612 images from 223 patients with EC for each sequence. These were tested with 9-10 images of 9-10 patients with CS and 56 images of 56 patients with EC for each sequence, respectively. Three experienced radiologists independently interpreted these test images. The sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUC) for each sequence were compared between the CNN models and the radiologists. Results: The CNN model of each sequence had sensitivity 0.89-0.93, specificity 0.44-0.70, accuracy 0.83-0.89, and AUC 0.80-0.94. It also showed an equivalent or better diagnostic performance than the 3 readers (sensitivity 0.43-0.91, specificity 0.30-0.78, accuracy 0.45-0.88, and AUC 0.49-0.92). The CNN model displayed the highest diagnostic performance on T2WI (sensitivity 0.93, specificity 0.70, accuracy 0.89, and AUC 0.94). Conclusions: Deep learning provided diagnostic performance comparable to or better than experienced radiologists when distinguishing between CS and EC on MRI.

Malignant tumor is the greatest risk factor for pulmonary embolism in hospitalized patients: a single-center study.

BACKGROUND: This study aimed to investigate the background of patients who presented with pulmonary embolism (PE) on contrast-enhanced chest computed tomography (CT) and to explore the risk factors for PE. METHODS: This study included a review of the medical records of all 50,621 patients who were admitted to one community hospital between January 1, 2013 and December 31, 2017. Data on sex, age, risk factors related to blood flow stagnation (obesity, long-term bed rest, cardiopulmonary disease, cast fixation, long-term sitting), risk factors related to vascular endothelial disorder (surgery, trauma/fracture, central venous catheterization, catheter tests/treatments, vasculitis, antiphospholipid antibody syndrome, history of venous thromboembolism (VTE)), and risk factors related to hypercoagulability (malignant tumor, use of oral contraceptives/low-dose estrogen progestin/steroids, infection, inflammatory enteric disease, polycythemia, protein C or protein S deficiency, dehydration) were evaluated. RESULTS: Of all inpatients, 179(0.35%) out of 50,621 were diagnosed with PE after contrast-enhanced chest CT examination, in which 74 patients were symptomatic and 105 patients had no symptom. Among asymptomatic 105 patients, 71 patients got CT scans for other reasons including cancer screening and searching infection focus, and 34 patients got CT scans for searching PE due to either apparent or suspicious DVT. The rate of discovering PE was significantly greater in women (0.46%, 90/19,409) than men (0.29%, 89/31,212) (P = 0.008). Of the 179 patients with PE, 164 (92%) had some type of risk factor. For both men and women, the most frequent risk factor was a malignant tumor, followed by obesity, long-term bed rest and infection for men and long-term bed rest, obesity and infection for women. The most common malignant tumor was lung cancer. Although taking antipsychotic agent is not advocated as a risk factor, there is a possibility of involvement. CONCLUSIONS: The risk factors for PE were identified in this single-center, retrospective study.

Stage III disease of ovarian, tubal and peritoneal cancers can be accurately diagnosed with pre-operative CT. Japan Clinical Oncology Group Study JCOG0602.

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; <20% in omentum. Accuracy of institutional computed tomography staging was comparable with computed tomography staging by central review. 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).