Trends in incidence and hormonal management of endometrial cancer during potentially reproductive age in Japan: a population-based study.

BACKGROUND: We aimed to investigate the trends in the incidence and treatment of endometrial cancer (EC) during potentially reproductive age in Japan, with a special focus on the relative oncologic safety of hormonal therapy (HT) over surgery. METHODS: This population-based retrospective cohort study was conducted using data from the Osaka Cancer Registry from 2004 to 2018. Women with EC were first identified and then distributions of age, stage, histology, and initial treatment were examined. Then, the relative oncologic safety of HT over surgery in patients under the age of 50 years was evaluated. RESULTS: Among the 9417 patients with EC, 1937 were diagnosed during their potentially reproductive age (< 50 years). The incidence of EC during potentially reproductive age has increased from 18.5% in 2004-2011 to 21.9% in 2012-2018. ECs during potentially reproductive age more frequently displayed favorable characteristics, such as endometrioid histology, and lower histological grade than those in non-potentially reproductive age. Among the 1223 patients diagnosed with localized endometrioid EC, 74 cases (6.0%) received HT as an initial treatment, while 1100 cases (90.0%) underwent surgery as their initial treatment. When the two treatment groups were compared, there was no significant difference in overall survival (p = 0.3713). The estimated 5-year survival rates were 100 and 98.8% in the HT and surgery groups, respectively. CONCLUSION: EC is increasingly diagnosed during potentially reproductive age in Japan. The use of HT as an initial treatment is increasing, and achieved comparable survival outcomes to urgery against localized endometrioid EC during the potentially reproductive age.

Evaluation of survival outcomes between minimally invasive and open surgery in the treatment of early-stage endometrial cancer: a population-based study in Osaka Japan.

OBJECTIVE: To compare the oncological outcomes between Japanese women who underwent minimally invasive surgery and those who underwent open surgery for early-stage endometrial cancer. METHODS: This population-based retrospective cohort study was conducted using data from the Osaka Cancer Registry from 2011 to 2018. Surgically treated patients for localized (uterine-confined) endometrial cancer were identified. Patients were classified into two groups according to the type of surgery (minimally invasive surgery group and open-surgery group), pathological risk factors (low-risk and high-risk), and year of diagnosis (Group 1, 2011-14; Group 2, 2015-18). Overall survival was compared between the minimally invasive surgery and open-surgery groups. RESULTS: In the analyses including all patients, there was no difference in overall survival between the minimally invasive surgery and open-surgery groups (P = 0.0797). The 4-year overall survival rate was 97.1 and 95.7% in the minimally invasive surgery and open-surgery groups, respectively. When investigated according to pathological risks, there were no differences in overall survival between the minimally invasive surgery and open-surgery groups in both the low- and high-risk groups. In the low-risk group, the 4-year overall survival rates in the minimally invasive surgery and open-surgery groups were 97.7 and 96.5%, respectively. In the high-risk group, the 4-year overall survival rates in the minimally invasive surgery and open-surgery groups were 91.2 and 93.2%, respectively. Similarly, there were no differences in overall survival between the minimally invasive surgery and open-surgery groups in both Group 1 (P = 0.4479 in low-risk and P = 0.1826 in high-risk groups) and Group 2 (P = 0.1750 in low-risk and P = 0.0799 in high-risk groups). CONCLUSION: Our study provides epidemiological evidence that minimally invasive surgery is an effective alternative to open surgery in Japanese patients with early-stage endometrial cancer.

The role of myeloid-derived suppressor cells in increasing cancer stem-like cells and promoting PD-L1 expression in epithelial ovarian cancer.

The aim of this study was to investigate the role of myeloid-derived suppressor cells (MDSC) in the induction of cancer stem-like cells (CSC) and programmed death ligand 1 (PD-L1) expression in ovarian cancer. CSC were defined as tumor cells expressing high levels of aldehyde dehydrogenase 1 (ALDH 1). We inoculated G-CSF-expressing or Mock-expressing ovarian cancer cells into mice, and the frequencies of MDSC and CSC in tumors of these models were compared by flow cytometry. To directly demonstrate the role of MDSC in the induction of CSC and the increase in PD-L1 expression, we performed in vitro co-culture. MDSC and CSC (ALDH-high cells) were more frequently observed in G-CSF-expressing cell-derived tumors than in Mock-expressing cell-derived tumors. Co-culture experiments revealed that MDSC increased the number of CSC via the production of PGE2. Moreover, PGE2 produced by MDSC increased tumor PD-L1 expression via the mammalian target of rapamycin (mTOR) pathway in ovarian cancer cells. In an in vitro experiment in which ovarian cancer cells were co-cultured with MDSC, higher expression of PD-L1 was observed in CSC than in non-CSC (ALDH-low cells). Furthermore, by immunofluorescence staining, we found that PD-L1 was co-expressed with ALDH1 in in vivo mouse models. In conclusion, PGE2 produced by MDSC increases the stem cell-like properties and tumor PD-L1 expression in epithelial ovarian cancer. Depleting MDSC may be therapeutically effective against ovarian cancer by reducing the number of CSC and tumor PD-L1 expression.

Lurbinectedin (PM01183), a selective inhibitor of active transcription, effectively eliminates both cancer cells and cancer stem cells in preclinical models of uterine cervical cancer.

Objective The objective of this study was to evaluate the antitumor effects of lurbinectedin on cervical cancer with a special focus on its effects on cancer stem cells (CSCs). Methods Using two cervical cell lines (ME180 and CaSki cells), the antitumor effects of lurbinectedin were assessed in vitro using the MTS assay and colony formation assay. The growth inhibitory effects of paclitaxel and cisplatin were also evaluated as controls. By employing ALDH1 activity as a marker of CSCs, the antitumor effects of lurbinectedin on cervical CSCs and non-CSCs were individually evaluated. Finally, we investigated the mechanisms by which lurbinectedin eliminated cervical CSCs. Results Lurbinectedin had significant antitumor activity toward cervical cancer cells at low nanomolar concentrations in vitro. Mouse xenografts of cervical cancer revealed that lurbinectedin significantly inhibits tumor growth. The growth-inhibitory effect of lurbinectedin was greater than that of cisplatin and paclitaxel. ALDH-high CSCs were observed in both cervical cancer cell lines (4.4% and 2.4% in ME180 and CaSki cells, respectively). Lurbinectedin downregulated stem cell-related gene expression (Oct4, Nanog, and SOX2), inhibited HDAC1 activity, and effectively eliminated ALDH-high CSCs. Conclusions Lurbinectedin is highly effective on uterine cervical cancer because it eliminates CSCs, and lurbinectedin is a promising agent to overcome platinum resistance in cervical cancer.

Comparison of clinical utility between neutrophil count and neutrophil-lymphocyte ratio in patients with ovarian cancer: a single institutional experience and a literature review.

OBJECTIVE: We retrospectively investigated the prognostic significance and clinical utility of pretreatment neutrophilia and elevated neutrophil-lymphocyte ratio (NLR) in patients with epithelial ovarian cancer. METHODS: Clinical data were collected from 344 surgically staged ovarian cancer patients between April 2007 and March 2016 and retrospectively reviewed. Neutrophilia and elevated NLR were defined as a neutrophil count ≥ 8,000/µl and an NLR ≥ 4.0, respectively. Univariate or multivariate analysis was conducted to evaluate the association between pretreatment neutrophilia or elevated NLR and clinicopathological characteristics, optimal surgery rate, progression-free survival (PFS) and disease-specific survival (DSS). Finally, we compared the clinical utility between neutrophil count and NLR by receiver operating characteristic (ROC) analysis. RESULTS: Pretreatment neutrophilia and elevated NLR were observed in 24 (7.0%) and 142 (41.3%) patients, respectively. In univariate analysis, both neutrophilia and elevated NLR were found to be associated with short PFS and DSS (p < 0.005). Multivariate analysis showed that neutrophilia and elevated NLR were predictors for shorter survival. In ROC analysis, the NLR tended to have a greater area under the ROC curve (AUC) value than the neutrophil count in predicting recurrence (0.7011 vs 0.6516, p = 0.0546) and had a significantly greater AUC value in predicting DSS (0.7249 vs 0.6379, p = 0.0182). Finally, based on the neutrophil count and NLR, we divided the patients into 3 prognostic groups-high-risk group (elevated NLR with neutrophilia), intermediate-risk group (elevated NLR without neutrophilia), and low-risk group (normal NLR), which allows for individualized and accurate survival estimates. CONCLUSIONS: Pretreatment neutrophilia and elevated NLR are independent poor prognostic factors in epithelial ovarian cancer patients. The NLR was superior to neutrophil count in predicting the survival of epithelial ovarian cancer patients.

The significance of tumor-associated neutrophil density in uterine cervical cancer treated with definitive radiotherapy.

OBJECTIVE: The aim of this study was to investigate the prognostic significance of tumor-associated neutrophil (TAN) density in cervical cancer patients that were treated with definitive radiotherapy. METHODS: The baseline characteristics and outcome data of FIGO stages IB-IVA cervical cancer patients who were treated with definitive radiotherapy between January 1996 and December 2011 were collected. Using biopsy samples obtained at the time of the initial diagnosis, the expression levels of CD66b in the patients' cervical tumors were evaluated by immunohistochemistry. Univariate and multivariate analyses were performed to evaluate the relationships between intratumoral TAN density and various clinicopathological features as well as progression-free survival (PFS) in these patients. RESULTS: The CD66b-positive cells (TAN) were observed in 209 (83.6%) of 250 cervical cancer specimens. The TAN density was significantly associated with shorter PFS. Multivariate analysis identified an increased number of TAN (hazard ratio [HR]: 4.95; 95% confidence interval [CI]: 2.51-10.7; p<0.0001), FIGO stage IVB disease (HR: 2.64; 95% CI: 1.38-5.01; p=0.01), non-squamous cell carcinoma (SCC) histology (HR: 2.50; 95% CI: 1.23-4.64; p=0.01), larger tumors (HR: 1.58; 95% CI: 1.03-2.40; p=0.04), and pelvic lymph node metastasis (HR: 2.24; 95% CI: 1.48-3.38; p=0.0001) as independent prognostic factors for short PFS. CONCLUSION: Intratumoral TAN density is an independent prognostic factor for short PFS in cervical cancer patients treated with definitive radiotherapy.

Predictors of Survival in Patients With FIGO Stage IVB Cervical Cancer.

OBJECTIVE: The aim of this study was to identify prognostic factors and establish a model for predicting life expectancy in International Federation of Gynecology and Obstetrics stage IVB cervical cancer patients. METHODS: The baseline characteristics and outcome data of patients with stage IVB cervical cancer between May 1994 and October 2014 were collected and retrospectively reviewed. A Cox proportional hazards regression model was used to identify independent predictors of survival in stage IVB cervical cancer patients. RESULTS: A total of 107 patients were included in our database. The median overall survival (OS) period was 16 months. Multivariate analysis revealed that the metastatic site (hazards ratio, 3.09; 95% confidence interval, 1.94-4.88; P < 0.0001) and a white blood cell (WBC) count exceeding 10,000/µL (hazards ratio, 2.02; 95% confidence interval, 1.19-3.30; P = 0.0102) were significant prognostic factors in terms of OS. Patient survival was inversely correlated with the number of these prognostic factors possessed. When the patients were divided into 3 prognostic groups, the median OS of the patients with 0, 1, or 2 poor prognostic factors was 26, 12, and 7 months, respectively. Among the patients with WBC counts of less than 10,000/µL, treatment with radiotherapy resulted in improved survival compared with chemotherapy or palliative care alone. In contrast, radiotherapy had minimal effects on survival in patients with WBC counts of greater than 10,000/µL. CONCLUSIONS: The metastatic site and an elevated WBC count are significant prognostic factors in patients with stage IVB cervical cancer. Our prognostic model composed of these 2 clinical variables might enable physicians to predict survival more accurately.

The PI3K/AKT/mTOR pathway as a therapeutic target in ovarian cancer.

The phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway plays a critical role in the malignant transformation of human tumors and their subsequent growth, proliferation, and metastasis. Preclinical investigations have suggested that the PI3K/AKT/mTOR pathway is frequently activated in ovarian cancer, especially in clear cell carcinoma and endometrioid adenocarcinoma. Thus, this pathway is regarded as an attractive candidate for therapeutic interventions, and inhibitors targeting different components of this pathway are in various stages of clinical development. Here, we highlight the recent progress that has been made in our understanding of the PI3K/AKT/mTOR pathway and discuss the potential of therapeutic agents that target this pathway as treatments for ovarian cancer and the obstacles to their development.

Prognostic significance of systemic neutrophil and leukocyte alterations in surgically treated endometrial cancer patients: a monoinstitutional study.

OBJECTIVE: The aim of this study was to investigate the prognostic significance of an elevated neutrophil count at the time of the initial diagnosis in patients with surgically treated endometrial cancer. METHODS: The baseline characteristics and outcome data of patients who were diagnosed with endometrial cancer between January 2000 and December 2010 were collected and retrospectively reviewed. The patients were separated into two groups according to their neutrophil counts. The clinicopathological characteristics and overall survival rates of the two groups were compared. A Cox proportional hazard regression model was used to investigate the prognostic significance of an elevated neutrophil count among patients with surgically treated endometrial cancer. RESULTS: An elevated neutrophil count was found to be associated with an advanced clinical stage (P<0.0001), lymphovascular space involvement (P=0.0003), cervical involvement (P=0.0049), the proportion of patients that received adjuvant therapy (P=0.0020), elevated NLR (P<0.0001), and treatment failure (P<0.0001). Multivariate analyses demonstrated that age (hazard ratio (HR)=2.23, 95% confidence interval (95% CI)=1.30 to 3.91; P=0.0035), clinical stage (HR=4.72, 95% CI=2.61 to 8.90; P<0.0001), lymphovascular space involvement (HR=3.15, 95% CI=1.60 to 6.68; P=0.0007), an elevated neutrophil count (HR=2.76, 95% CI=1.43 to 5.03; P=0.0033), and an elevated white blood cell count (HR=2.79, 95% CI=1.50 to 4.96; P=0.0017) were significant predictors of survival. CONCLUSION: The elevated neutrophil or leukocyte counts at the time of the initial diagnosis are independent prognostic factors in patients with surgically treated endometrial cancer.

Prognostic Significance of Pretreatment Thrombocytosis in Cervical Cancer Patients Treated With Definitive Radiotherapy.

OBJECTIVE: The aim of this study was to investigate the prevalence and prognostic significance of an elevated platelet count at the time of the initial diagnosis in patients with cervical cancer who are treated with definitive radiotherapy. METHODS: The baseline characteristics and outcome data of cervical cancer patients who were treated with definitive radiotherapy between November 1993 and December 2011 were collected and retrospectively reviewed. The patients were separated into 2 groups according to their platelet counts. The clinicopathological characteristics and overall survival rates of the 2 groups were compared. A Cox proportional hazards regression model was used to investigate the prognostic significance of an elevated platelet count. RESULTS: An elevated platelet count was found to be associated with younger age (P = 0.0003), an advanced clinical stage (P < 0.0001), larger tumors (P = 0.0025), lower hemoglobin levels (P < 0.0001), and more frequent treatment failure (P = 0.0015). Multivariate analysis demonstrated that an advanced clinical stage (hazards ratio [HR], 2.93; 95% confidence interval [CI], 1.47-6.70; P = 0.0015), nonsquamous cell carcinoma histology (HR, 2.67; 95% CI, 1.52-4.42; P = 0.0011), larger tumors (HR, 3.86; 95% CI, 2.18-7.03; P < 0.0001), lower hemoglobin levels (HR, 1.99; 95% CI, 1.34-2.93; P = 0.0008), and an elevated platelet count (HR, 1.65; 95% CI, 1.03-2.56; P = 0.0395) were significant predictors of survival. CONCLUSIONS: An elevated platelet count at the time of the initial diagnosis is an independent prognostic factor in cervical cancer patients who are treated with definitive radiotherapy.

First two cases of primary carcinoma of the vagina successfully treated with concurrent weekly carboplatin plus paclitaxel, external beam radiotherapy and high-dose-rate interstitial brachytherapy: a case report and published work review.

Vaginal carcinoma is rare, accounting for only 2% of all gynecological malignancies. Due to a lack of prospective randomized studies, the role of concurrent chemoradiotherapy in the treatment of primary vaginal carcinoma remains unclear. We report the first two cases of primary vaginal carcinoma successfully treated with a regimen involving concurrent weekly carboplatin plus paclitaxel, external beam radiotherapy and high-dose-rate interstitial brachytherapy. These cases strongly indicate that definitive chemoradiation involving carboplatin plus paclitaxel may be a reasonable treatment for primary vaginal carcinoma.

Reirradiation using high-dose-rate interstitial brachytherapy for locally recurrent cervical cancer: a single institutional experience.

OBJECTIVES: This study aimed to evaluate the effectiveness and feasibility of reirradiation using high-dose-rate interstitial brachytherapy (HDR-ISBT) in patients with recurrent cervical cancer. METHODS: The records of 52 consecutive women with central pelvic recurrence who were salvaged with HDR-ISBT-based reirradiation were retrospectively reviewed. Data regarding the primary disease, follow-up findings, recurrence, the treatment outcome, and toxicities were collected. Multivariate analysis was performed using the Cox proportional hazards regression model to identify predictors of the response to HDR-ISBT. Survival rate was calculated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: A total of 52 patients who had been treated with HDR-ISBT-based reirradiation were included in our database. The local control rate was 76.9% (40/52), and the median postrecurrence survival period was 32 months. Grade 3 or 4 late toxicities were observed in 13 patients (25%). Multivariate analysis revealed that tumor size and the treatment-free interval were significant poor prognostic factors of postrecurrence survival. In a comparison between the patients who were salvaged with HDR-ISBT-based reirradiation (ISBT group) and those who were treated with palliative therapy alone (palliative group), we found that among the patients who displayed 0 or 1 poor prognostic factors, the patients in the ISBT group survived significantly longer than those in the palliative group. In contrast, similar survival rates were seen in both groups among the patients with 2 or more poor prognostic factors. CONCLUSIONS: Reirradiation using HDR-ISBT is effective and feasible in patients with recurrent cervical cancer. Our 2-clinical variable prognostic model might enable physicians to identify patients who would not derive clinical benefit from HDR-ISBT and offer them the opportunity to receive other types of treatment.

Combination treatment with trabectedin and irinotecan or topotecan has synergistic effects against ovarian clear cell carcinoma cells.

OBJECTIVES: The objective of this study was to investigate the chemotherapeutic agents that produce the strongest synergistic effects when combined with trabectedin against ovarian clear cell carcinoma (CCC), which is regarded as an aggressive chemoresistant histological subtype. METHODS: Using 4 human CCC cell lines (RMG1, RMG2, KOC7C, and HAC2), the cytotoxicities of trabectedin, SN-38, topotecan, doxorubicin, cisplatin, and paclitaxel as single agents were first assessed using the MTS assay. Then, the cytotoxicities of combination treatments involving trabectedin and 1 of the other 4 agents were evaluated by isobologram analysis to examine whether these combinations displayed synergistic, additive, or antagonistic effects. The antitumor activities of the combination treatments were also examined using cisplatin-resistant and paclitaxel-resistant CCC sublines, which were derived from the parental CCC cells by continuously exposing them to cisplatin or paclitaxel. Finally, we determined the effect of everolimus on the antitumor efficacy of trabectedin-based combination chemotherapy. RESULTS: Concurrent exposure to trabectedin and SN-38 or topotecan resulted in synergistic interactions in all 4 CCC cell lines. Among the tested combinations, trabectedin plus SN-38 was the most effective cytotoxic regimen. The combination of trabectedin plus SN-38 also had strong synergistic effects on both the cisplatin-resistant and paclitaxel-resistant CCC cell lines. Treatment with everolimus significantly enhanced the antitumor activity of trabectedin plus SN-38 or topotecan. CONCLUSIONS: Combination treatment with trabectedin and SN-38 displays the greatest cytotoxic effect against ovarian CCC. Our in vitro study provides the rationale for future clinical trials of trabectedin plus irinotecan with or without everolimus in patients with ovarian CCC in both the front-line chemotherapy setting and as a second-line treatment of recurrent CCC that had previously been treated with cisplatin or paclitaxel.

Impact of the addition of concurrent chemotherapy to pelvic radiotherapy in surgically treated stage IB1-IIB cervical cancer patients with intermediate-risk or high-risk factors: a 13-year experience.

OBJECTIVES: To identify groups of patients who derive clinical benefit from postoperative adjuvant concurrent chemoradiotherapy (CCRT), we retrospectively investigated the survival outcomes of surgically treated early-stage cervical cancer patients. METHODS: We reviewed the medical records of 316 patients with FIGO stage IB1-IIB cervical cancer who had been treated with adjuvant radiotherapy (RT) (n = 124, RT group) or adjuvant CCRT (n = 192, CCRT group) after radical hysterectomy between January 1996 and December 2009. Of these, 187 patients displayed high-risk prognostic factors (high-risk group), and 129 displayed intermediate-risk prognostic factors (intermediate-risk group). Sixty patients with 1 intermediate-risk prognostic factor who received no adjuvant therapy were also identified and used as controls (NFT group). Survival was calculated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: In the high-risk group, adjuvant CCRT was significantly superior to RT alone with regard to recurrence rate, progression-free survival (PFS), and overall survival. In the intermediate-risk group, CCRT was superior to RT with regard to recurrence rate and PFS in patents with 2 or more risk factors. Among the patients with only 1 intermediate-risk factor, although no survival benefit of CCRT over RT was observed, addition of adjuvant treatment resulted in significantly improved PFS compared with the NFT group in patients with deep stromal invasion (log-rank, P = 0.012). CONCLUSIONS: Postoperative CCRT improved the prognosis of FIGO stage IB1-IIB cervical cancer patients in the high-risk group and patients who displayed 2 or more intermediate-risk factors. Patients who displayed deep stromal invasion alone also derived clinical benefit from adjuvant treatment.

Laboratory Findings of Benign Convulsions With Mild Gastroenteritis: A Meta-Analysis.

Investigating factors associated with benign convulsions with mild gastroenteritis (CwG) is important for early detection and treatment. In previous studies, uric acid (UA) has been reported to be associated with CwG. However, the association between CwG and abnormal laboratory values remains inconclusive. We performed a meta-analysis of recent reports to determine the association between CwG and laboratory findings, including UA, in patients with acute gastroenteritis without convulsions. We conducted electronic searches of three databases (PubMed, EMBASE, and Cochrane Library) and one scholarly search engine (Google Scholar (Google, Inc., Mountain View, CA, USA)) up to February 2023 for studies on CwG. Eligible studies were observational studies that assessed patients with CwG, reported laboratory data, and stated the presence or absence of convulsions during illness episodes. Patients were children with mild gastroenteritis, with the exposure group developing convulsions and the control group not. The outcome was a comparison of laboratory data between the two groups. The effect size was calculated using the standardized mean difference (SMD), and random-effects models were used for the analysis because of high heterogeneity. In total, 148 articles were included in this study. After the screening, nine studies, including 8,367 patients, were selected for the meta-analysis. The most prevalent laboratory finding was an increased serum UA level, with an SMD of 1.42 (N = 6,411; 95% confidence interval (CI): (1.12, 1.72); Z = 9.242, p< 0.001; I 2 = 81.68%, p= 0.002). The optimal serum UA cutoff value was 7.21 mg/dL, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.827 (95% CI: (0.807, 0.846)). This meta-analysis suggests that CwG is strongly associated with increased serum UA levels. These results demonstrate that more attention should be paid when interpreting laboratory findings in pediatric patients with acute gastroenteritis.

Twenty-five-year mortality trends of four major histological subtypes of cervical cancer: a population-based study using the Osaka cancer registry data.

Objective: To assess the mortality trends of four major histological subtypes of cervical cancer diagnosed between 1994 and 2018. Methods: This population-based retrospective cohort study was conducted using the Osaka Cancer Registry data from 1994 to 2018. A total of 12,003 patients with cervical cancer, squamous cell carcinoma (SCC), adenocarcinoma (A), adenosquamous cell carcinoma (AS), or small cell neuroendocrine carcinoma (SCNEC) were identified. Patients were classified into groups according to the extent of disease (localized, regional, or distant), year of diagnosis (1994-2002, 2003-2010, or 2011-2018), and histological subtype (SCC, A/AS, or SCNEC). Then, their survival rates were assessed using univariate and multivariate analyses. Results: Overall, improved survival rates were observed according to the year of diagnosis in patients with local, regional, and distant cervical cancers. When examined according to the histological subtypes, improved survival rates according to the year of diagnosis were observed in patients with local, regional, and distant SCCs and in those with local and regional A/AS. In patients with distant A/AS, the survival rates did not improve since 2003. In patients with cervical cancer with SCNEC, the survival rates did not improve since 1994 irrespective of the extent of the disease. In the multivariate analysis, non-SCC histology was found to be an independent prognostic factor for OS. Conclusion: In contrast to SCC histology associated with improved survival between 1994 and 2018, SCNEC histology and advanced (stage IVB) A/AS remain to be the unmet medical needs for the management of cervical cancer.

Comparison of the Survival Outcomes of Minimally Invasive Surgery with Open Surgery in Patients with Uterine-Confined and Node-Negative Cervical Cancer: A Population-Based Study.

We aimed to compare the oncological outcomes between Japanese women with uterine-confined and node-negative cervical cancer who underwent open surgery and those who underwent minimally invasive surgery (MIS). A population-based retrospective cohort study was conducted using data from the Osaka Cancer Registry that ranged from 2011 to 2018. A total of 2279 patients who underwent surgical treatment for uterine-confined and node-negative cervical cancer were identified. The patients were classified into groups according to surgery type (open and MIS groups) and year of diagnosis (group one, 2011-2014; group two, 2015-2018). The oncologic outcomes were compared between the MIS and open groups. When the MIS group (n = 225) was compared with open group (n = 2054), overall, there was no significant between-group difference in terms of overall survival. Based on Kaplan-Meier estimates, the probability of overall survival at four years was 99.5% in the MIS group and 97.2% in the open group (p = 0.1110). When examined according to the year of diagnosis, there were no significant between-group differences in the overall survival in both groups one and two. In this population-based cohort study, MIS did not compromise survival outcomes when compared with conventional open surgery in Japanese patients with uterine-confined and node-negative (FIGO 2018 stage I) cervical cancer.

Population-Based Survival Analysis of Stage IVB Small-Cell Neuroendocrine Carcinoma in Comparison to Major Histological Subtypes of Cervical Cancer.

The aim of the current study is to investigate the survival outcome of stage IVB SCNEC of the uterine cervix in comparison to major histological subtypes of cervical cancer. A population-based retrospective cohort study was conducted using the Osaka Cancer Registry data from 1994 to 2018. All FIGO 2009 stage IVB cervical cancer patients who displayed squamous cell carcinoma (SCC), adenocarcinoma (A), adenosquamous cell carcinoma (AS), or small-cell neuroendocrine carcinoma (SCNEC) were first identified. The patients were classified into groups according to the types of primary treatment. Then, their survival rates were examined using the Kaplan-Meier method. Overall, in a total of 1158 patients, clearly differential survival rates were observed according to the histological subtypes, and SCNEC was associated with shortest survival. When examined according to the types of primary treatments, SCNEC was associated with significantly decreased survival when compared to SCC or A/AS, except for those treated with surgery. In patients with FIGO 2009 stage IVB cervical cancer, SCNEC was associated with decreased survival when compared to SCC or A/AS. Although current treatments with either surgery, chemotherapy or radiotherapy have some therapeutic efficacies, to improve the prognosis, novel effective treatments specifically targeting cervical SCNEC need to be developed.

Hyponatremia and Recurrent Febrile Seizures During Febrile Episodes: A Meta-Analysis.

Several studies have investigated the potential effects of hyponatremia on recurrent febrile seizures (RFS) during febrile illness. Because findings were inconsistent across studies, we aimed to evaluate the serum sodium levels in febrile seizures (FS) of children with or without RFS during the same episode. We conducted electronic searches in three databases (PubMed, EMBASE, Cochrane Library) and one scholarly search engine (Google Scholar) up to June 2021 for studies on FS. Screening was done based on the titles and abstracts of primary studies. Then, eligibility was reviewed based on the abstracts. Finally, in order to match the inclusion and exclusion criteria, full-text articles were evaluated by two authors and inconsistencies were discussed. Data extraction was carried out by two independent authors. The extracted variables were author's name, article title, journal name, year of publication, study location, study design, sample size, and mean and standard deviation of blood Na concentration in FS. We performed a risk of bias assessment of included studies using the Newcastle-Ottawa Scale (NOS). The effect size was calculated using the standardized mean difference (SMD), and random-effects models were used for the analysis. A total of 12 articles were included with a single outlier. This analysis suggested that serum sodium level was lower in patients with RFS during the same febrile episode than in those with single FS, with SMD of -0.70, (n=1784; 95% CI: -1.03, -0.36; Z=-4.10, p<0.01; I 2 86.67%, p<0.01). In the sensitivity analysis, no significant change was observed in pooled SMD. The optimal cutoff value of serum sodium level was 134.72 mmol/L with an area under the receiver operating characteristic curve of 0.81 (95% CI: 0.61, 1.00), with sensitivity of 80.0% and specificity of 70.0%. This result indicated a significant association between hyponatremia and RFS during the same febrile episode. Decreased serum sodium levels may be involved in seizure recurrence and may play a role in FS pathogenesis.