Nowoczesna ultrasonografia i modele prognostyczne w przedoperacyjnym różnicowaniu nowotworów jajnika

Wybór prawidłowej metody leczenia chorych z guzami jajnika zależy od rodzaju guza, przy czym zmiany niezłośliwe mogą być obserwowane lub usuwane za pomocą metod o minimalnej inwazyjności, takich jak laparoskopia lub minilaparotomia. Zabiegi chirurgiczne u kobiet z guzami granicznymi mogą być mniej agresywne, szczególnie jeżeli ze względu na wiek chorej istotne jest zachowanie płodności. Podobna sytuacja występuje u pacjentek z rakiem jajnika w I stopniu zaawansowania klinicznego. Decyzja o rozszerzeniu procedur diagnostycznych jest z kolei istotna, gdy wykryty guz może być zmianą zaawansowaną klinicznie albo guzem przerzutowym do jajnika. Nowoczesne sposoby wstępnego przedoperacyjnego różnicowania różnych typów zmian przydatków macicy u kobiet oraz metody oceny prawdopodobieństwa istnienia zmiany złośliwej w badanym guzie opierają się obecnie przede wszystkim na badaniu ultrasonograficznym i na ocenie ekspresji wybranych markerów nowotworowych. W pracy omówiono „klasyczne” i najnowsze zastosowanie metody „prostych reguł” zaproponowanej przez Międzynarodową Grupę Analizy Guzów Jajnika (IOTA) w 2008 roku oraz sposoby wykorzystania w diagnostyce ultrasonograficznej guzów jajnika pierwszego politomicznego modelu prognostycznego ADNEX grupy IOTA. Model ten pozwala na ocenę prawdopodobieństwa, że w badanym guzie przydatkowym wystąpi jedna z 5 kategorii: guzy niezłośliwe, raki graniczne, raki w I stopniu oraz w II–IV stopniu zaawansowania klinicznego, a także guzy przerzutowe do jajnika. W pracy przedstawiono praktyczne sposoby wykorzystania metody „prostych” reguł i modelu ADNEX w diagnostyce ambulatoryjnej i klinicznej

Proliferation and maturation of intratumoral blood vessels in women with malignant ovarian tumors assessed with cancer stem cells marker nestin and platelet derived growth factor PDGF-B

Objectives: Platelet-derived growth factor B (PDGF-B) and nestin have been suggested to be useful in the assessment of neoangiogenesis in malignant ovarian masses. We aimed to investigate a possible association of these markers with newly formed microcapillaries and perivascular cells in ovarian tumors. Material and methods: Microvessel density (MVD) and pericytes were studied in 82 women with ovarian neoplasms, including 7 benign cysts, 7 borderline masses, 64 epithelial ovarian cancers and 4 other malignant ovarian tumors. Immunohistochemical staining included antibodies to CD34, PDGF-B and nestin. Results: Median values of CD34-positive and nestin-positive MVD were: 24,5 (range:17-32) and 21 (range: 12–31), respectively. No significant correlation between intratumoral CD-34 positive MVD and nestin-positive MVD was found. Benign and borderline lesions more frequently than malignant tumors displayed low or medium values of nestin-positive MVD (p = 0.01). Histological grading of malignant tumors was associated with nestin-positive MVD (p = 0.01). Nestin expression in tumor cells was not correlated with tumor grade or histological subtype. PDGF-B expression was found in tumor microves­sels in 72% of cases (59/82). High expression of PDGF in pericapillary cells was strongly associated with high expression of this marker in cancer cells (p = 0.007). Significant correlations between PDGF-B and nestin expression in malignant tumor microvessels were also found (p = 0.04). Nestin and PDGF-B expressions were strongly associated with high grade tumors when compared to low grade or benign masses. Conclusions: We conclude that the assessment of PDGF-B and nestin-positive MVD could be used to identify only highly active, angiogenic malignant ovarian masses, where tumor vasculature is formed

Predicting the risk of malignancy in adnexal masses based on the Simple Rules from the International Ovarian Tumor Analysis group

BACKGROUND: Accurate methods to preoperatively characterize adnexal tumors are pivotal for optimal patient management. A recent metaanalysis concluded that the International Ovarian Tumor Analysis algorithms such as the Simple Rules are the best approaches to preoperatively classify adnexal masses as benign or malignant. OBJECTIVE: We sought to develop and validate a model to predict the risk of malignancy in adnexal masses using the ultrasound features in the Simple Rules. STUDY DESIGN: This was an international cross-sectional cohort study involving 22 oncology centers, referral centers for ultrasonography, and general hospitals. We included consecutive patients with an adnexal tumor who underwent a standardized transvaginal ultrasound examination and were selected for surgery. Data on 5020 patients were recorded in 3 phases from 2002 through 2012. The 5 Simple Rules features indicative of a benign tumor (B-features) and the 5 features indicative of malignancy (M-features) are based on the presence of ascites, tumor morphology, and degree of vascularity at ultrasonography. Gold standard was the histopathologic diagnosis of the adnexal mass (pathologist blinded to ultrasound findings). Logistic regression analysis was used to estimate the risk of malignancy based on the 10 ultrasound features and type of center. The diagnostic performance was evaluated by area under the receiver operating characteristic curve, sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), positive predictive value (PPV), negative predictive value (NPV), and calibration curves. RESULTS: Data on 4848 patients were analyzed. The malignancy rate was 43% (1402/3263) in oncology centers and 17% (263/1585) in other centers. The area under the receiver operating characteristic curve on validation data was very similar in oncology centers (0.917; 95% confidence interval, 0.901-0.931) and other centers (0.916; 95% confidence interval, 0.873-0.945). Risk estimates showed good calibration. In all, 23% of patients in the validation data set had a very low estimated risk (<1%) and 48% had a high estimated risk (≥30%). For the 1% risk cutoff, sensitivity was 99.7%, specificity 33.7%, LR+ 1.5, LR- 0.010, PPV 44.8%, and NPV 98.9%. For the 30% risk cutoff, sensitivity was 89.0%, specificity 84.7%, LR+ 5.8, LR- 0.13, PPV 75.4%, and NPV 93.9%. CONCLUSION: Quantification of the risk of malignancy based on the Simple Rules has good diagnostic performance both in oncology centers and other centers. A simple classification based on these risk estimates may form the basis of a clinical management system. Patients with a high risk may benefit from surgery by a gynecological oncologist, while patients with a lower risk may be managed locally

Evaluating the risk of ovarian cancer before surgery using the ADNEX model to differentiate between benign, borderline, early and advanced stage invasive, and secondary metastatic tumours: prospective multicentre diagnostic study

Objectives To develop a risk prediction model to preoperatively discriminate between benign, borderline, stage I invasive, stage II-IV invasive, and secondary metastatic ovarian tumours. Design Observational diagnostic study using prospectively collected clinical and ultrasound data. Setting 24 ultrasound centres in 10 countries. Participants Women with an ovarian (including para-ovarian and tubal) mass and who underwent a standardised ultrasound examination before surgery. The model was developed on 3506 patients recruited between 1999 and 2007, temporally validated on 2403 patients recruited between 2009 and 2012, and then updated on all 5909 patients. Main outcome measures Histological classification and surgical staging of the mass. Results The Assessment of Different NEoplasias in the adneXa (ADNEX) model contains three clinical and six ultrasound predictors: age, serum CA-125 level, type of centre (oncology centres v other hospitals), maximum diameter of lesion, proportion of solid tissue, more than 10 cyst locules, number of papillary projections, acoustic shadows, and ascites. The area under the receiver operating characteristic curve (AUC) for the classic discrimination between benign and malignant tumours was 0.94 (0.93 to 0.95) on temporal validation. The AUC was 0.85 for benign versus borderline, 0.92 for benign versus stage I cancer, 0.99 for benign versus stage II-IV cancer, and 0.95 for benign versus secondary metastatic. AUCs between malignant subtypes varied between 0.71 and 0.95, with an AUC of 0.75 for borderline versus stage I cancer and 0.82 for stage II-IV versus secondary metastatic. Calibration curves showed that the estimated risks were accurate. Conclusions The ADNEX model discriminates well between benign and malignant tumours and offers fair to excellent discrimination between four types of ovarian malignancy. The use of ADNEX has the potential to improve triage and management decisions and so reduce morbidity and mortality associated with adnexal pathology

Diagnostic hysteroscopy and the risk of malignant cells intraabdominal spread in women with endometrial cancer

Although hysteroscopy is currently the undisputed gold standard for the examination of the uterine cavity in women with suspected endometrial cancer, it remains controversial as a procedure that can enhance metastasis spread. Endometrial cancer cells may shed during hysteroscopy and be passively transported with fluid flow into the peritoneal cavity. The paper presents the review of current knowledge regarding the risk of neoplasm metastases in women who had diagnostic hysteroscopy and the conditions that have to be met for the procedure to be safe. We searched PubMed, Ovid, Medline and Scopus databases for data published in the years 1985–2017. The following browsing criteria, the “MeSH headings”: hysteroscopy, endometrial cancer, intraperitoneal or metastatic spread were used to find relevant papers. Based on the current data analysis we conclude that (1.) diagnostic hysteroscopy performed in women with endometrial cancer, especially in its early stages, is a very useful, efficient and safe diagnostic method and (2.) the distension media used for endoscopic procedures in the uterine cavity must be strictly controlled for relatively low pressures to prevent the increase in risk of endometrial cancer intraperitoneal spread

Non-invasive therapeutic use of High-Intensity Focused Ultrasound (HIFU) with 3 Tesla Magnetic Resonance Imaging in women with symptomatic uterine fibroids

Benign uterine fibroids are common female genital tract tumors and if symptomatic often require extensive surgery. When tumors are multiple and large or unusually located, the operative treatment may lead to significant morbidity and compromise quality of life. Recovery period after surgical treatment may be complicated by patient’s medical condition and wound healing problems. Currently used other non-surgical treatment modalities usually provide only a temporal symptoms relief and may not be efficient in all affected women. In the last decade, minimally invasive treatment of uterine fibroids called Magnetic Resonance guided High-Intensity Focused Ultrasound (MRI HIFU) was introduced. This technique uses thermal ablation simultaneously with MRI imaging of the mass and tissue temperature measurements during the procedure where a focused ultrasound beam is applied externally to destroy tumors located in the human body. Successful application of MRI HIFU has been recently described in patients with various malignancies, such as breast, prostate and hepatocellular cancers as well as soft tissue and bone tumors. This technique is innovative and has been proven to be safe and effective but there are several limitations for treatment. The article highlights the relative advantages and disadvantages of MRI guided HIFU in women with uterine fibroids. The authors also describe high-resolution MRI technique on 3T MRI, along with the approach to interpretation of HIFU results applied to uterine fibroids that has been experienced at one institution

Mig-7 expression and vasculogenic mimicry in malignant ovarian tumors

Objectives: To investigate the possible association of vasculogenic mimicry (VM), VE-cadherin and MIG-7 expression with clinicopathological features of women with malignant ovarian masses. Material and methods: VM was studied with the PAS reaction and VE-cadherin was assessed with immunohistochemistry in 108 women with malignant ovarian tumors. Additionally, quantitative expression of MIG-7 mRNA was performed in 52 ovarian cancers with qRT-PCR. Results: VM was found in 48/108 cases (44%), more often in higher FIGO stage tumors (83% cases; 40 vs. 8; p = 0.01). High expression of VE-cadherin was present in 37% of all ovarian masses. Ovarian tumors without VM more often expressed low levels of VE-cadherin than tumors where VM was found (37.6% vs.14.6%). No expression or very low expression of MIG-7 mRNA was found in all normal ovarian tissues and in 32 cancer samples. Median RQ of MIG-7 mRNA in tumor samples was higher than in normal ovarian tissue (RQ = 0.29 vs. RQ = 0.05, respectively; p &lt; 0.005) and higher than in non-malignant ovarian masses (0.98 vs. 0.05 respectively; p = 0.03). Expression of MIG-7 mRNA was significantly correlated with VM (p = 0.039). In tumors with PAS-positive structures median RQ MIG-7 mRNA was higher than in tumors with PAS-negative findings (1.89 vs. 0.13 respectively). VE-cadherin expression was more frequently found in tumors where MIG-7 mRNA was present (p = 0.004). Conclusions: Vasculogenic mimicry exists in malignant ovarian tumors and advanced clinical stages of malignancy are accompanied by a high incidence of VM formation. MIG-7 mRNA and VE-cadherin expression may serve as additional molecular markers of VM in ovarian malignancies

SNCG (synuclein, gamma (breast cancer-specific protein 1))

Review on SNCG (synuclein, gamma (breast cancer-specific protein 1)), with data on DNA, on the protein encoded, and where the gene is implicated

The use of sonographic subjective tumor assessment, IOTA logistic regression model 1, IOTA Simple Rules and GI-RADS system in the preoperative prediction of malignancy in women with adnexal masses

Background: Sonography based methods with various tumor markers are currently used to discriminate the type of adnexal masses. Objective: To compare the predictive value of selected sonography-based models along with subjective assessment in ovarian cancer prediction. Material and methods: We analyzed data of 271 women operated because of adnexal masses. All masses were verified by histological examination. Preoperative sonography was performed in all patients and various predictive models includ¬ing IOTA group logistic regression model LR1 (LR1), IOTA simple ultrasound-based rules by IOTA (SR), GI-RADS and risk of malignancy index (RMI3) were used. ROC curves were constructed and respective AUC’s with 95% CI’s were compared. Results: Of 271 masses 78 proved to be malignant including 6 borderline tumors. LR1 had sensitivity of 91.0%, specificity of 91.2%, AUC = 0.95 (95% CI: 0.92–0.98). Sensitivity for GI-RADS for 271 patients was 88.5% with specificity of 85% and AUC = 0.91 (95% CI: 0.88–0.95). Subjective assessment yielded sensitivity and specificity of 85.9% and 96.9%, respectively with AUC = 0.97 (95% CI: 0.94–0.99). SR were applicable in 236 masses and had sensitivity of 90.6% with specificity of 95.3% and AUC = 0.93 (95% CI 0.89–0.97). RMI3 was calculated only in 104 women who had CA125 available and had sensitivity of 55.3%, specificity of 94% and AUC = 0.85 (95% CI: 0.77–0.93). Conclusions: Although subjective assessment by the ultrasound expert remains the best current method of adnexal tumors preoperative discrimination, the simplicity and high predictive value favor the IOTA SR method, and when not applicable, the IOTA LR1 or GI-RADS models to be primarily and effectively used

Prognostic significance of TEM7 and nestin expression in women with advanced high grade serous ovarian cancer

Objectives: Tumor endothelial marker 7 (TEM7) and nestin have been proposed to be new candidates for neoangiogenesis assessment. Nestin is also cancer stem cells marker in various malignant tumors. AIMS. To investigate the expression of TEM7, nestin and nestin-related microvessel density (MVD) in high-grade serous ovarian cancer samples and to study their correlation with overall survival (OS) and disease-free survival (DFS) times. Material and methods: Tumor samples obtained from 70 women with FIGO IIIc/IV ovarian serous cancer were studied with immunohistochemistry. Results: Patients median age was 54 yrs (range: 29–72 years), 86% died of the disease with median OS = 28.5 months and median DFS = 10 months (3 years DFS = 19%; 5 years. DFS = 13.8%). High nestin expression was found in 16 (23%) patients with 3 years and 5 years OS of 14% and 0%. In low-nestin expression group OS and DFS were 42% and 25%, respectively. Median nestin-MVD (16, range:12–23) was not correlated with cancer cells nestin expression and with both DFS and OS. High TEM7 expression was found in 29 women (41%) of whom 21 (72%) died of the disease. A 5-year OS in these women was 27% as compared to 8% in low TEM7 expression group, but TEM7 presence had no association with nestin, nestin-MVD and both OS and DFS. Conclusions: Nestin as a marker of cancer stem cells may assist in the prediction of OS and DFS in women with high grade serous ovarian cancer. Nestin may also be considered a novel therapeutic target for antiangiogenic agents