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Background/purpose: To compare the clinical outcomes of Taiwanese patients with ovarian clear cell carcinomas (CCCs) and serous carcinomas (SCs).Methods: We retrieved the clinical records of women with epithelial ovarian cancer (Stage I-IV) who received primary surgeries between 2000 and 2013. Cancer-specific survival (CSS), progression-free survival, and survival after recurrence (SAR) of CCC and SC patients were retrospectively compared. Multivariate analysis was used to identify the independent predictors of survival.Results: Of 891 women diagnosed with epithelial ovarian cancer, 169 CCCs and 351 high-grade SCs were analyzed. The 5-year CSS rates of CCC patients were significantly lower than those of SC for both Stage III (22.3% vs. 47.3%, p = 0.001) and Stage IV (0% vs. 24.4%, p = 0.001) disease. In the absence of gross residual malignancies, the 5-year CSS rate was better for CCC (82.3%) than SC (75.2%, p = 0.010). The 5-year SAR rate was significantly lower for CCC than SC (14.3% vs. 24.4%, p = 0.002). Old age and residual malignancies were independent prognostic factors for CSS in the entire cohort of CCC patients. In the subgroup of Stage I CCC, positive cytology was identified as the only adverse prognostic factor for CSS.Conclusion: The clinical outcomes of CCC are generally poorer than SC. Complete cytoreduction to no gross residual disease should be ideally achieved in CCC patients. A greater understanding of the molecular pathogenesis of CCC may lead to tailored therapies, ultimately optimizing outcomes. [ABSTRACT FROM AUTHOR]

Objectives: To compare the diagnostic accuracy of diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) magnetic resonance (MR) imaging for detecting cervical stromal invasion in endometrial cancer.Methods: Eighty-three consecutive women with endometrial cancer underwent preoperative evaluation in a 3-T unit, including T2-weighted, DW (b = 0 and 1000 s/mm2), and DCE MR imaging. Two radiologists independently assessed presence of cervical stromal invasion, with histopathological reference as gold standard.Results: For assessing cervical stromal invasion, the diagnostic accuracy, sensitivity, and specificity, respectively for Reader 1/Reader 2, were as follows: DW MR imaging- 95.2 %/91.6 %, 91.7 %/100 %, and 95.8 %/90.1 %; DCE MR imaging- 91.6 %/88 %, 58.3 %/50 %, and 97.2 %/94.4 %. The diagnostic performance of DW MR imaging (Reader 1: areas under the receiver operating characteristic curve (AUC) = 0.98; Reader 2: AUC = 0.97) was significantly higher than that of DCE MR imaging (p = 0.009 for Reader 2) or T2-weighted MR imaging (Reader 1: p = 0.006; Reader 2: p = 0.013). Patients with cervical stromal invasion showed a significantly greater canal width (p < 0.0001) and myometrial invasion extent (p = 0.006).Conclusions: DW MR imaging has superior diagnostic performance compared with DCE MR imaging in the detection of cervical stromal invasion.Key Points: • DWI demonstrates a higher accuracy than DCE in detecting cervical stromal invasion. • Tumour ADC values are similar between patients without or with cervical invasion. • Canal widening causes false-negativity on DCE and T2W but not on DWI. [ABSTRACT FROM AUTHOR]

Objectives: We prospectively investigated the roles of pretreatment dynamic contrast-enhanced MR imaging (DCE-MRI), diffusion-weighted MR imaging (DWI) and 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG PET)/CT for predicting survival of oropharyngeal or hypopharyngeal squamous cell carcinoma (OHSCC) patients treated with chemoradiation.Methods: Patients with histologically proven OHSCC and neck nodal metastases scheduled for chemoradiation were eligible. Clinical variables as well as DCE-MRI-, DWI- and 18F-FDG PET/CT-derived parameters of the primary tumours and metastatic neck nodes were analysed in relation to 3-year progression-free survival (PFS) and overall survival (OS) rates.Results: Eighty-six patients were available for analysis. Multivariate analysis identified the efflux rate constant (K ep)-tumour < 3.79 min-1 (P = 0.001), relative volume of extracellular extravascular space (V e)-node < 0.23 (P = 0.004) and SUVmax-tumour > 19.44 (P = 0.025) as independent risk factors for both PFS and OS. A scoring system based upon the sum of each of the three imaging parameters allowed stratification of our patients into three groups (patients with 0/1 factor, patients with 2 factors and patients with 3 factors, respectively) with distinct PFS (3-year rates = 72 %, 38 % and 0 %, P < 0.0001) and OS (3-year rates = 81 %, 46 % and 20 %, P < 0.0001).Conclusions: K ep-tumour, V e-node and SUVmax-tumour were independent prognosticators for OHSCC treated with chemoradiation. Their combination helped survival stratification.Key Points: • K ep -tumour, V e -node and SUV max -tumour are independent predictors of survival rates. • The combination of these three prognosticators may help stratification of survival. • MRI and FDG-PET/CT play complementary roles in prognostication of head and neck cancer. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to evaluate the safety and efficacy of adding bevacizumab to dose-dense adjuvant chemotherapy with bevacizumab maintenance after neoadjuvant chemotherapy (NAC) and interval debulking surgery (IDS) for stage III/IV ovarian, tubal, and primary peritoneal cancer.Study Design: This phase II clinical trial using Simon's minimax two-stage design was conducted. At the first stage, 13 subjects were enrolled, and the trial would proceed to second stage if ≤3 subjects discontinued treatment for study-defined significant adverse events (AEs). Patients with stage III/IV ovarian, tubal, and primary peritoneal cancer deemed not feasible for primary cytoreductive surgery were enrolled after 3-4 cycles of NAC and IDS without disease progression. NAC could be either weekly paclitaxel (80 mg/m2) (dose-dense) plus 3-weekly carboplatin (AUC5-6) or 3-weekly conventional schedule. After IDS, postoperative dose-dense adjuvant chemotherapy for 3 cycles at least (best to 6 cycles), and 3-weekly bevacizumab 15 mg/kg was given since postoperative cycle 2. Further 3-weekly maintenance bevacizumab 15 mg/kg was given intravenously for 17 cycles.Results: Of the 22 enrolled subjects, 13 (59.1 %) had no gross lesion after IDS. Of the 13 subjects enrolled on the 1 st stage, one study-defined significant AE occurred, therefore the trial proceeded to the 2nd stage (n = 9). The median progression-free survival (PFS) was 22.1 months (95 % confidence interval [CI], 13.7-30.5), and the median overall survival (OS) was 49.2 months (95 % CI, 33.8-64.6). Peritoneal Cancer Index score at entering abdomen during IDS was significant for PFS (>12 vs ≤ 12: p = 0.003). One of the 22 subjects did not receive any study treatment. In the safety analysis (n = 21), grade 3/4 AEs included thrombocytopenia of 38.1 %, neutropenia 71.4 %, and anemia 28.6 %. Study-defined significant AEs of bowel perforation, poor-healing wound, and hypertension were found in 1 case each, respectively.Conclusion: This phase II trial demonstrated adding bevacizumab to dose-dense adjuvant chemotherapy with bevacizumab maintenance after NAC was feasible with tolerable toxicity and comparable PFS/OS as compared to other studies using bevacizumab in the NAC phase or dose-dense scheduling throughout. [ABSTRACT FROM AUTHOR]

Objectives: Although patients with buccal squamous cell carcinoma (SCC) usually show acceptable outcomes, local control and survival rates are generally lower than those observed for tongue SCC. This study was designed to compare the clinical outcomes of Taiwanese patients with these two common oral cavity malignancies.Methods: Patients with first primary buccal or tongue SCC who were included in the Taiwanese Cancer Registry Database between 2004 and 2012 were eligible. The study sample consisted of 16,379 patients (7870 buccal SCC and 8509 tongue SCC) who received surgery with or without adjuvant therapy. The 5-year disease-specific survival (DSS) and overall survival (OS) rates served as the outcome measures.Results: Compared with tongue SCC, patients with buccal SCC had a higher prevalence of males (95.7% vs. 86.4%, p<0.0001), pT4 disease (21.4% vs. 12.7%, p<0.0001), and p-Stage IV (30.4% vs. 24.8%, p<0.0001) but a lower frequency of pN2 disease (15.2% vs. 18.5%, p<0.0001). The 5-year DSS and OS rates of buccal SCC patients were slightly higher than those of tongue SCC (78% vs. 77%, p=0.0297; and 71% vs. 69%, p=0.0231, respectively). Multivariate analysis identified tumor site (tongue vs. buccal SCC), sex (male vs. female), age (≥65 vs. <65years), pT classification (T4/T3/T2 vs. T1), and pN classification (N3/N2/N1vs. N0) as independent prognostic factors in the entire study cohort.Conclusions: The survival advantage of buccal SCC over tongue SCC appears significant in large clinical samples, despite a higher prevalence of p-Stage IV disease in the former. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Urtica dentata Hand (UDH), the root of Laportea bulbifera (Sieb. et. Zucc.) Wedd, has been traditionally used in traditional Chinese medicine as an anti-inflammatory and immuno-regulatory agent for rheumatoid arthritis and some other autoimmune diseases treatment. And the coumarins are the major components of UDH. Aim of the study: To investigate the effect of total coumarins (TC) isolated from UDH on the development of autoimmune diabetes. Materials and methods: Eight-week-old non-obese diabetic (NOD) mice were randomly divided into four groups: control group, low-dose (37.5mg/kg), middle-dose (75mg/kg), and high-dose (150mg/kg) TC-treatment groups. NOD mice were then given with a suspension of TC or saline by intragastric (i.g.) administration every other day. After 4 weeks of treatment, 8 mice at 12-weeks of age per group were randomly selected to be sacrificed to perform intraperitoneal glucose tolerance test, examine histopathological insulitis, spleen T lymphocyte proliferation, the percentage of CD4+CD25+Foxp3+ T regulatory cell (Treg), dendritic cell (DC) surface molecules, toll-like receptor (TLR)4 expression and signal pathways involved. The remaining 10 mice per group were kept until 26 weeks of age to assess the incidence of diabetes. We also studied the direct effect of TC on DC and CD4+CD25+ Tregs in vitro. Results: Treatment with TC for 4 weeks significantly inhibited insulitis, increased pancreatic islet number, delayed the onset and decreased the development of diabetes by 26 weeks of age in NOD mice, compared with the untreated control mice. TC suppressed spleen T lymphocyte proliferation, induced Th2-biased cytokine response, the generation of CD4+CD25+Foxp3+ Tregs and Foxp3 mRNA expression. And TC-treated DCs were characterized as low expression of MHC class II and CD86 molecules. TLR4 gene and protein expressions in the spleen, thymus and pancreas were down-regulated in TC-treated groups. The key molecules in the downstream signaling cascades of TLR4, including myeloid differentiation factor (MyD)88, nuclear factor (NF)-κB, IL-1β, Toll–IL-1 receptor domain-containing adaptor inducing interferon-β(TRIF), TRIF-related adaptor molecule (TRAM), interferon regulatory factor (IRF)-3 and IFN-β, all decreased significantly in TC groups, suggesting that TC inhibits both MyD88-dependent and -independent pathways of TLR4. At the cellular level, however, TLR4 protein expression in DCs, but not in Tregs, was downregulated by TC. And TC strengthened the role of DC, not Treg, in negative immune regulation in vitro. In contrast, anti-TLR4 antibody could block the effect of TC on DCs immune function. Conclusion: These results suggest that TC extracted from UDH prevent the development of autoimmune diabetes in NOD mice via suppression of the TLR4-signaling pathways. TC maintain the DCs in an immature tolerogenic state, at least in part, mediated by down-regulating TLR4-signaling pathways in DCs, then enhance Treg differentiation, shift toward Th2 and suppress T lymphocyte proliferation. [Copyright &y& Elsevier]

Objective: Previous studies have shown that excess weight (including obesity and overweight) can increase the risk of cardiovascular, cerebrovascular and other diseases, but there is no study on the incidence of post-stroke depression (PSD) and related factors in patients with excessive weight. The main purpose of this study was to find related factors of PSD at 3 months after stroke in patients with excessive weight and construct artificial neural network (ANN) and decision tree (DT) models.Methods: This is a prospective multicenter cohort study (Registration number: ChiCTR-ROC-17013993). Five hundred and three stroke patients with Body Mass Index(BMI) ≥ 24 were included in this study. The diagnostic criteria of PSD is according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-V) diagnostic criteria for depression due to other medical conditions and the HAMD-17 scores > 7 at 3 months after stroke was used as the primary endpoint. The χ2 test, Mann-Whitney U test or t-test were used to check for statistical significance.Results: Our study found that sleeping time < 5 h, CHD, physical exercise, BI score, N dimension(EPQ) and subjective support(SSRS) were associated with PSD in patients with excessive weight. Physical exercise(odd ratio [OR] = 0.49, p = 0.001, 95%CI [confidence interval]: 0.32-0.75) and BI score(OR = 0.99, p < 0.001, 95%CI: 0.98-0.99) were protective factors; sleeping time < 5 h(OR = 2.86, p < 0.001, 95%CI: 1.62-5.04), CHD(OR = 2.18, p = 0.018, 95%CI: 1.14-4.15), N dimension(OR = 1.08, p = 0.001, 95%CI: 1.03-1.13) and subjective support(OR = 1.04, p = 0.022, 95%CI: 1.01-1.07) were risk factors.Conclusion: This study found several factors related to the occurrence of PSD at 3 months in patients with excessive weight. Meanwhile, ANN and DT models were constructed for clinicians to use. [ABSTRACT FROM AUTHOR]

Purpose: The evidence for adjuvant therapy of oral cavity squamous cell carcinoma (OCSCC) in National Comprehensive Cancer Network (NCCN) guidelines is derived from patients with head and neck cancer. Here, we examined whether adjuvant therapy should be guided by a detailed analysis of pathologic risk factors in patients with pure OCSCC.Methods and Materials: Between 2004 and 2016, we retrospectively reviewed 1200 consecutive patients with OCSCC who underwent radical surgery and neck dissection in the Chang-Gung Memorial Hospital (CGMH). Patients were divided into 3 prognostic groups. High-risk patients were those with extranodal extension (ENE) and/or positive margins (ENE/margins+, n = 267). Intermediate-risk patients were further divided into 3 subgroups: (1) patients in whom adjuvant therapy was indicated according to the CGMH but not the NCCN guidelines (NCCN[-]/CGMH[+], n = 14); (2) patients in whom adjuvant therapy was indicated by the NCCN but not the CGMH guidelines (NCCN[+]/CGMH[-], n = 160); and (3) patients in whom adjuvant therapy was indicated according to both guidelines (NCCN[+]/CGMH[+], n = 411). Low-risk patients were those for whom adjuvant therapy was not suggested in light of either guideline (NCCN[-]/CGMH[-], n = 348).Results: According to NCCN guidelines, postoperative adjuvant therapy was indicated in 69.8% of the participants. However, only 57.7% of patients were in need of adjuvant therapy by CGMH guidelines. The following 5-year outcomes were observed in the NCCN(-)/CGMH(-), NCCN(-)/CGMH(+), NCCN(+)/CGMH(-), NCCN(+)/CGMH(+), and ENE/margins+ subgroups: locoregional control, 88%/70%/83%/79%/68%, P < .001 (NCCN[+]/CGMH[-] vs NCCN[+]/CGMH[+], P = .576); distant metastases, 2%/7%/2%/9%/36%, P < .001 (NCCN[+]/CGMH[-] vs NCCN[+]/CGMH[+], P = .003); disease-specific survival, 97%/86%/94%/84%/56%, P < .001 (NCCN[+]/CGMH[-] vs NCCN[+]/CGMH[+], P < .001); and overall survival, 92%/86%/87%/68%/42%, P < .001 (NCCN[+]/CGMH[-] vs NCCN[+]/CGMH[+], P < .001), respectively.Conclusions: Patients in the NCCN(+)/CGMH(-) subgroup, 28% (160/571[160 + 411]) of NCCN intermediate-risk patients, had more favorable 5-year disease-specific and overall survival (94% and 87%) than the NCCN(+)/CGMH(+) subgroup. The former are unlikely to derive clinical benefits from NCCN guidelines. The 70% adjuvant therapy rate required by NCCN guidelines after radical surgery might be too high, ultimately leaving room for improvement. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Polygonum capitatum is a well-known Miao medicinal plant that has been used for many years for its unique therapeutic effects on various urological disorders, including urinary calculus and urinary tract infections. To investigate the effect of Polygonum capitatum on cytochrome P450 (CYP) isoforms (CYP1A2, CYP2C9, CYP2C19, CYP2E1, and CYP3A4) in vivo using a “cocktail” approach by administering five probe drugs to rats. This study assessed the potential of Polygonum capitatum to interact with co-administered drugs. Materials and methods An aqueous extract of dried whole Polygonum capitatum was prepared and administered orally to rats at a dose of 0.58 g/kg or 1.74 g/kg twice daily for 7 or 14 consecutive days. A cocktail of caffeine (1.0 mg/kg), tolbutamide (1.0 mg/kg), omeprazole (2.0 mg/kg), chlorzoxazone (4.0 mg/kg) and midazolam (4.0 mg/kg) was then administered on the eighth or fifteenth day to evaluate the effects of Polygonum capitatum on CYP1A2, 2C9, 2C19, 2E1, and 3A4, respectively. Blood samples were collected at a range of time-points and the plasma concentrations of the probe drugs were simultaneously quantified using ultra high-performance liquid chromatography–tandem mass spectrometry. Pharmacokinetic parameters were calculated to evaluate the effects of Polygonum capitatum on the activities of these CYP enzymes in rats. Results Polygonum capitatum pre-treatment had no significant effect on the pharmacokinetic parameters of caffeine, omeprazole or chlorzoxazone. However, the pharmacokinetics of tolbutamide and midazolam were affected significantly ( P <0.05) by Polygonum capitatum , which induced more rapid metabolism of these probe compounds. Conclusions These results suggested that Polygonum capitatum could induce CYP2C9 and CYP3A4, and did not influence CYP1A2, CYP2C19 or CYP2E1. Therefore, the clinical dose of drugs metabolized by human CYP2C9 or CYP3A4 may need to be adjusted in patients taking Polygonum capitatum , as this herbal medication may result in reduced effective concentrations of these drugs. [ABSTRACT FROM AUTHOR]

Abstract: Aim of the study: This study was designed to investigate the antibacterial and anti-inflammatory activities of the extracts and the structure-based fractions from P. capitatum so as to provide the evidence for the traditional use of this plant in the treatment of urinary tract infections and to clarify the structural types that were responsible for the clinical use of the plant. Materials and methods: The dry whole plant of P. capitatum was extracted with water and 70% aqueous ethanol and then separated, respectively, into a fraction enriched in polysaccharides and proteins (PP) and four other fractions enriched in gallic acid and its analogues (GAA), flavonoids (FV), tannins (TN), and triterpenoids and steroids (TS). UV spectral or chemical methods were used for the confirmation of the five fractions. The in vitro antibacterial activities of the aqueous (AE) and 70% aqueous ethanol (70EE) extracts as well as the fractions against gram-positive and gram-negative bacteria were initially evaluated by a disc diffusion test. The anti-bacterial potencies of the active extracts or fractions were then assessed in vitro by determining the MICs and MBCs. The anti-inflammatory activity was evaluated employing the xylene-induced mouse ear edema model. Results: Except for fraction PP, AE, 70EE, and the four fractions (GAA, FV, TN, and TS) exhibited varying degrees of antibacterial and anti-inflammatory activities. The results of the minimal inhibition concentration (MIC) and minimal bactericidal concentration (MBC) indicated that the crude extracts or fractions FV and TN all possess bacteriostatic and bactericidal properties. Fractions FV and TS showed significantly anti-inflammatory activity (P <0.01) with the inhibition rates of 86.15 and 73.71% at 0.6g/kg, respectively, as compared to 76.93% of the positive control dexamethasone. Conclusions: The overall results suggested that the traditional use of this plant for the treatment of urinary tract infections were attributed to the presence of antibacterial and anti-inflammatory agents. The results also provided evidence that the studied plant extracts, as well as some of the fractions obtained from this plant might be potential sources for antimicrobial and anti-inflammatory drug development. [Copyright &y& Elsevier]

Purpose: The aim of the present study was to evaluate whether texture features extracted from 18F-FDG PET/CT images may provide additional prognostic information in patients with metastatic nasopharyngeal carcinoma (NPC).Materials and Method: We retrospectively examined 52 patients with metastatic NPC who underwent assessment of EBV DNA titers and pretreatment 18F-FDG PET/CT imaging. All participants were followed up for at least two years. The following 18F-FDG PET parameters were analyzed: standardized uptake value (SUV), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and texture parameters. Independent predictors of outcomes were identified using receiver operating characteristic curve analysis and multivariate Cox proportional hazards models.Results: On multivariate analysis, EBV DNA titers > 3500 copies/mL and TLG of metastatic lesions > 138 mL were identified as independent predictors of overall survival (OS) (P = 0.036 and P = 0.047, respectively). Patients were divided into two subgroups based on their EBV DNA titers (high versus low). In the high EBV DNA titer group, a lower homogeneity of distant metastatic lesions and higher TLG values of distant metastatic lesions were independent risk factors for OS (P = 0.033 and P < 0.001, respectively). In the low EBV DNA titer group, a reduced uniformity of distant metastatic lesions and a higher SUVmax of distant metastatic lesions were unfavorable risk factors for OS (P = 0.004 and P = 0.005, respectively). Based on these results, we devised two prognostic scoring systems for the prediction of 2-year OS in each EBV DNA titer group.Conclusion: Some of the PET-derived texture parameters are independent predictors of outcomes in patients with metastatic NPC and provide complementary information to EBV DNA titers. [ABSTRACT FROM AUTHOR]