Tumor cachexia is an important prognostic parameter in epithelial ovarian cancer (EOC). Tumor cachexia is characterized by metabolic and inflammatory disturbances. These conditions might be reflected ...by body composition measurements (BCMs) ascertained by pre-operative computed tomography (CT). Thus, we aimed to identify the prognostically most relevant BCMs assessed by pre-operative CT in EOC patients.
We evaluated muscle BCMs and well established markers of nutritional and inflammatory status, as well as clinical-pathological parameters in 140 consecutive patients with EOC. Furthermore, a multiplexed inflammatory marker panel of 25 cytokines was used to determine the relationship of BCMs with inflammatory markers and patient's outcome. All relevant parameters were evaluated in uni- and multivariate survival analysis.
Muscle attenuation (MA)-a well established BCM parameter-is an independent prognostic factor for survival in multivariate analysis (HR 2.25; p = 0.028). Low MA-reflecting a state of cachexia-is also associated with residual tumor after cytoreductive surgery (p = 0.046) and with an unfavorable performance status (p = 0.015). Moreover, MA is associated with Eotaxin and IL-10 out of the 25 cytokine multiplex marker panel in multivariate linear regression analysis (p = 0.021 and p = 0.047, respectively).
MA-ascertained by routine pre-operative CT-is an independent prognostic parameter in EOC patients. Low MA is associated with the inflammatory, as well as the nutritional component of cachexia. Therefore, the clinical value of pre-operative CT could be enhanced by the assessment of MA.
Gamma-glutamyltransferase (GGT) is a known marker for apoptotic balance and cell detoxification. Recently, an association of baseline GGT levels and breast cancer incidence, tumor progression and ...chemotherapy resistance was shown. The purpose of this study was to evaluate the association of pre-therapeutic GGT levels, clinical-pathological parameters and survival in patients with primary metastatic breast cancer (PMBC).
In this multicenter analysis, pre-therapeutic GGT levels and clinical-pathological parameters of 114 patients diagnosed with PMBC between 1996 and 2012 were evaluated. The association between GGT levels and clinical-pathological parameters were analysed. Patients were stratified into four GGT risk-groups (GGT < 18.00 U/L: normal low, 18.00 to 35.99 U/L: normal high, 36.00 to 71.99 U/L: elevated and ≥ 72.00 U/L: highly elevated) and survival analyses were performed.
Patients in the high risk GGT group had a poorer overall survival, when compared to the low risk group with five-year overall survival rates of 39.5% and 53.7% (p = 0.04), respectively. Patients with larger breast tumors had a trend towards higher GGT levels (p = 0.053). Pre-therapeutic GGT levels were not associated with indicators of aggressive tumor biology such as HER2-status, triple negative histology, or poorly differentiated cancers.
Pre-therapeutic GGT serum level might serve as a novel prognostic factor for overall-survival in patients with PMBC.
Since it is known that bitter taste receptors (TAS2Rs) are expressed and functionally active in various extra-oral cells, their genetic variability and functional response initiated by their ...activation have become of broader interest, including in the context of cancer.
A systematic research was performed in PubMed and Google Scholar to identify relevant publications concerning the role of TAS2Rs in cancer.
While the findings on variations of TAS2R genotypes and phenotypes and their association to the risk of developing cancer are still inconclusive, gene expression analyses revealed that TAS2Rs are expressed and some of them are predominately downregulated in cancerous compared to non-cancerous cell lines and tissue samples. Additionally, receptor-specific, agonist-mediated activation induced various anti-cancer effects, such as decreased cell proliferation, migration, and invasion, as well as increased apoptosis. Furthermore, the overexpression of TAS2Rs resulted in a decreased tumour incidence in an in vivo study and TAS2R activation could even enhance the therapeutic effect of chemotherapeutics in vitro. Finally, higher expression levels of TAS2Rs in primary cancerous cells and tissues were associated with an improved prognosis in humans.
Since current evidence demonstrates a functional role of TAS2Rs in carcinogenesis, further studies should exploit their potential as (co-)targets of chemotherapeutics.
Knowledge base construction (KBC) using AI has been one of the key goals of this highly popular technology since its emergence, as it helps to comprehend everything, including relations, around us. ...The construction of knowledge bases can summarize a piece of text in a machine-processable and understandable way. This can prove to be valuable and assistive to knowledge engineers. In this paper, we present the application of natural language processing in the construction of knowledge bases. We demonstrate how a trained bidirectional long short-term memory or bi-LSTM neural network model can be used to construct knowledge bases in accordance with the exact ISO26262 definitions as defined in the GENIAL! Basic Ontology. We provide the system with an electronic text document from the microelectronics domain and the system attempts to create a knowledge base from the available information in textual format. This information is then expressed in the form of graphs when queried by the user. This method of information retrieval presents the user with a much more technical and comprehensive understanding of an expert piece of text. This is achieved by applying the process of named entity recognition (NER) for knowledge extraction. This paper provides a result report of the current status of our knowledge construction process and knowledge base content, as well as describes our challenges and experiences.
Discrimination between benign and malignant adnexal masses is essential for optimal treatment planning, but still remains challenging in a routine clinical setting. In this retrospective study, we ...aimed to compare albumin as a single parameter to calculate models by analyzing laboratory parameters of 1552 patients with an adnexal mass (epithelial ovarian cancer (EOC): n= 294; borderline tumor of the ovary (BTO): n = 66; benign adnexal mass: n = 1192) undergoing surgery. Models comprising classical laboratory parameters show better accuracies (AUCs 0.92–0.93; 95% CI 0.90–0.95) compared to the use of single markers, and could easily be implemented in clinical practice by containing only readily available markers. This has been incorporated into a nomogram.
To investigate fused multiparametric positron emission tomography/magnetic resonance imaging (MP PET/MRI) at 3T in patients with locally advanced cervical cancer, using high-resolution T2-weighted, ...contrast-enhanced MRI (CE-MRI), diffusion-weighted imaging (DWI), and the radiotracers 18Ffluorodeoxyglucose (18FFDG) and 18Ffluoromisonidazol (18FFMISO) for the non-invasive detection of tumor heterogeneity for an improved planning of chemo-radiation therapy (CRT).
Sixteen patients with locally advanced cervix were enrolled in this IRB approved and were examined with fused MP 18FFDG/ 18FFMISO PET/MRI and in eleven patients complete data sets were acquired. MP PET/MRI was assessed for tumor volume, enhancement (EH)-kinetics, diffusivity, and 18FFDG/ 18FFMISO-avidity. Descriptive statistics and voxel-by-voxel analysis of MRI and PET parameters were performed. Correlations were assessed using multiple correlation analysis.
All tumors displayed imaging parameters concordant with cervix cancer, i.e. type II/III EH-kinetics, restricted diffusivity (median ADC 0.80x10-3mm2/sec), 18FFDG- (median SUVmax16.2) and 18FFMISO-avidity (median SUVmax3.1). In all patients, 18FFMISO PET identified the hypoxic tumor subvolume, which was independent of tumor volume. A voxel-by-voxel analysis revealed only weak correlations between the MRI and PET parameters (0.05-0.22), indicating that each individual parameter yields independent information and the presence of tumor heterogeneity.
MP 18FFDG/ 18FFMISO PET/MRI in patients with cervical cancer facilitates the acquisition of independent predictive and prognostic imaging parameters. MP 18FFDG/ 18FFMISO PET/MRI enables insights into tumor biology on multiple levels and provides information on tumor heterogeneity, which has the potential to improve the planning of CRT.
To study the natural history of cervical intraepithelial neoplasia (CIN) during pregnancy and to compare the rates of persistence, progression and regression of CIN by colposcopically guided biopsy ...(CGB) during pregnancy with outcome in non-pregnant-women.
A retrospective analysis of all pregnant women diagnosed with CIN at our outpatient clinic between 2005 and 2010 was performed. A CGB for histo-pathological analysis was obtained in all participants and observational management was performed. The histo-pathologic findings of initial and postpartum visits were collected. Rates of persistence, progression and regression of CIN were assessed. Results were compared to a matched control group of non-pregnant women where observational management was performed for at least three months. In addition a review of the literature and pooled analysis of published data was performed.
A total of 51 pregnant women with CIN were included into analysis. CIN 1, 2, and 3 was diagnosed by CGB in 33.3, 13.7 and 52.9% of all pregnant women, respectively. The postpartum histo-pathologic evaluation of the pregnant cohort revealed a significantly higher tendency to spontaneous regression (56.9 versus 31.4%, p = 0.010) and a considerably, but not significantly higher complete remission rate (41.2 versus 27.5%, p = 0.144) when compared to the non-pregnant cohort. In addition, we observed a significantly lower CIN persistence rate than in the non-pregnant cohort (39.2 versus 58.8%, p = 0.048). The progression rate was notably low in the pregnant cohort (3.9%) and no progression to invasive cancer was observed.
CIN lesions show considerably high spontaneous regression rates postpartum. Once presence of invasive cancer is ruled out definitive treatment can be deferred to the postpartum period.
Radical trachelectomy allows for fertility preservation in patients with early cervical cancer not qualifying as “low-risk” as defined by ConCerv. This study reports on the 10-year surgical, ...oncological, and obstetrical experience of patients treated by radical abdominal trachelectomy at an Austrian tertiary care center. A retrospective chart analysis and telephone survey of all patients with FIGO stage IA2-IB2 (2018) cervical cancer treated by radical abdominal trachelectomy and pelvic lymphadenectomy between 2013 and 2022 were performed. Radical abdominal trachelectomy was attempted in 29 patients, of whom 3 patients underwent neoadjuvant chemotherapy. Three cases, including one after neoadjuvant therapy, required conversion to radical hysterectomy due to positive margins; four cases had positive lymph nodes following surgical staging and were referred to primary chemo-radiotherapy. Twenty-two (75.9%) successful abdominal radical trachelectomies preserving fertility were performed. According to final histopathology, 79.3% of tumors would not have met the “low-risk”-criteria. At a median follow-up of 64.5 (25.5–104.0) months, no recurrence was observed. Eight (36.4%) patients attempted to conceive, with a live birth rate of 62.5%. Radical abdominal trachelectomy appears oncologically safe in early-stage cervical cancers that do not fulfill the “low-risk”-criteria. Strict preoperative selection of patients who might qualify for more conservative surgical approaches is strongly recommended.
To evaluate serum C-reactive protein (CRP) as prognostic variable in patients with epithelial ovarian cancer (EOC).
In a multicenter study, preoperative serum CRP was evaluated in 623 patients with ...EOC. Results were correlated with clinical data.
Mean (SD) preoperative serum CRP was 3.6 (4.8) mg/dL. Serum CRP was significantly associated with International Federation of Gynecologists and Obstetricians stage (P < 0.001) and postoperative residual tumor mass (P < 0.001) but not with histologic grade (P = 0.1) and type (P = 0.7), patients' age (Pearson's correlation coefficient = 0.05; P = 0.2), and serum CA 125 (Pearson's correlation coefficient = 0.02; P = 0.6). Patients with platinum-resistant EOC had significantly higher CRP serum levels compared with patients with platinum-sensitive EOC 6.0 (6.6) mg/dL versus 2.8 (3.8) mg/dL; P < 0.001. Higher International Federation of Gynecologists and Obstetricians stage (P < 0.001), presence of postoperative residual tumor mass (P < 0.001), tumor grade (P = 0.001), serum CA 125 (P = 0.03), and serum CRP (P = 0.001) were independently associated with overall survival. Patients with serum CRP < or =1 mg/dL versus >1 mg/dL had an overall 5-year survival of 82% versus 58.5% (P < 0.001).
Serum CRP can be seen as a novel, widely available independent prognostic variable of ovarian cancer.
This study aimed to assess the predictive value of tumor growth rate estimates based on serial cancer antigen-125 (CA-125) levels on therapy response and survival of patients with recurrent ...high-grade serous ovarian cancer (HGSOC). In total, 301 consecutive patients with advanced HGSOC (exploratory cohort:
= 155, treated at the Medical University of Vienna; external validation cohort:
= 146, from the Ovarian Cancer Therapy-Innovative Models Prolong Survival (OCTIPS) consortium) were enrolled. Tumor growth estimates were obtained using a validated two-phase equation model involving serial CA-125 levels, and their predictive value with respect to treatment response to the next chemotherapy and the prognostic value with respect to disease-specific survival and overall survival were assessed. Tumor growth estimates were an independent predictor for response to second-line chemotherapy and an independent prognostic factor for second-line chemotherapy use in both univariate and multivariable analyses, outperforming both the predictive (second line:
= 0.003, HR 5.19 1.73-15.58 vs.
= 0.453, HR 1.95 0.34-11.17) and prognostic values (second line:
= 0.042, HR 1.53 1.02-2.31 vs.
= 0.331, HR 1.39 0.71-2.27) of a therapy-free interval (TFI) < 6 months. Tumor growth estimates were a predictive factor for response to third- and fourth-line chemotherapy and a prognostic factor for third- and fourth-line chemotherapy use in the univariate analysis. The CA-125-derived tumor growth rate estimate may be a quantifiable and easily assessable surrogate to TFI in treatment decision making for patients with recurrent HGSOC.
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