Elastography in the Urological Practice: Urinary and Male Genital Tract, Prostate Excluded-Review.

The aim of this article is to review the utility of elastography in the day-to-day clinical practice of the urologist. An electronic database search was performed on PubMed and Cochrane Library with a date range between January 2000 and December 2021. The search yielded 94 articles that passed the inclusion and exclusion criteria. The articles were reviewed and discussed by organ, pathology and according to the physical principle underlying the elastographic method. Elastography was used in the study of normal organs, tumoral masses, chronic upper and lower urinary tract obstructive diseases, dysfunctions of the lower urinary tract and the male reproductive system, and as a pre- and post-treatment monitoring tool. Elastography has numerous applications in urology, but due to a lack of standardization in the methodology and equipment, further studies are required.

Alteration of Gene and miRNA Expression in Cervical Intraepithelial Neoplasia and Cervical Cancer.

Background: Cervical cancer is one of the most common malignancies in women in terms of prevalence and mortality. Cervical cancer has some particularities that distinguish it from any other oncologic pathology: first, it is completely preventable by prompt detection of its precursor, cervical intraepithelial neoplasia (CIN); second, the Human Papillomavirus (HPV) infection is a known etiological agent; third, the mean age at diagnosis is much lower than in other oncologic conditions, as a consequence of the sexually-transmitted HPV. Methods: We evaluated the expression level of several long noncoding RNAs and a microRNA in samples from 30 patients with CIN, 9 with cervical cancer and 38 normal samples using qRT-PCR technology. Results: We observed higher expression levels for MEG3, DAPK1, MLH1 and MALAT1 in CIN samples than in normal samples, whereas TIMP3 and SOX1 had lower expression levels. For cancer samples, DAPK1, MLH1 and MALAT1 had higher expression, and MEG3, TIMP3 and SOX1 had lower expression when compared to normal samples. In the case of CIN versus cancer samples, only MEG3 gene showed a statistically significant difference. The expression of miR-205-5p was lower in both CIN and cancer samples compared to normal samples. Conclusion: Decreased MEG3 expression could be considered an alarm signal in the transition from a premalignant cervical lesion to invasive cancer, while altered expression levels of TIMP3, SOX1, MLH1, MALAT1 and miR-205-5p could serve as early biomarkers in the diagnosis of premalignant cervical lesions. Future studies, including a larger number of patients with CIN, will be of particular importance in validating these observations.

Inter- and intraobserver reproducibility of Strain and 2D Shear Wave Elastography - a phantom study.

AIMS: To analyse the intra- and interobserver variability of two elastographic methods of quantification available on the same machine, the technical factors that may influence variability as well as the intra- and interobserver variability for the same indices between two different ultrasound machines in an in vitro experimental setting. MATERIAL AND METHODS: Three different types of silicone experimental devices (ED) were conceived for the purpose of this study. Two observers performed repeated measurements on two ultrasound machines. Strain elastography, with strain ratio determination between the ED was performed on both machines. Shear wave ratio was also assessed. The data obtained were used to calculate intra- and interobservervariability. Reproducibility was assessed in relation to the size of the elastographic region of interest (ROI) and to the difference in stiffness between the ED, through the value of the ICCs (Intraclass Correlation Coefficient). RESULTS: Strain ratio had high inter- and intraobserver reproducibility, regardless of the machine used, on a large number of determinations.The choice of a small ROI diameter (5 mm) over a large ROI diameter (15mm) increased reproducibility (ICC = 0.87 vs 0.78, p=0.000). It is observed that, by Shear Wave Elastography, only when analysing structures with a large difference in hardness, significance is obtained in terms of interobserver reproducibility (ICC = 0.75, p=0.000). CONCLUSIONS: On a large number of determinations, both techniques are inter- and intraobserver reproducible. It is preferable to opt for a smaller ROI diameter in order to increase interobserver reproducibility. SWE Ratio provides significant reproducibility only when analysing structureswith large difference in hardness.

Elastography of the uterine cervix in gynecology: normal appearance, cervical intraepithelial neoplasia and cancer. A systematic review.

AIMS: To revise the current literature about the usefulness of elastography in cervical cancer (CC) and cervical intraepithelial neoplasia (CIN), from methods and technical limitations, to diagnosis, staging and the ability of predicting the response to oncologic treatment. METHODS: An electronic database search was performed (PubMed, EMBASE, Web of Science) with the data range from January 2000 until May 2020. All studies, fully-available in English, assessing elastography of the uterine cervix in CC and CIN were selected. Studies were reviewed and discussed according to the elastographic technique and to the purpose of the research. RESULTS: Twenty-three articles were found: 11 articles regarding strain elastography, 4 articles assessing shear wave elastography and 8 papers with matter-related information. Elastography was used in the study of normal variants of the uterine cervix as well as: the positive diagnosis of CC and CIN, clinical staging and the prediction of therapeutic response in CC. Comparison of the elastographic techniques was also performed. CONCLUSIONS: Elastography has multiple applications in the gynecological pathology of the cervix. The methods used to assess the cervix are diverse, and none have become universally accepted. With regard to CC and CIN, elastography is still an ongoing research field.

Identification of Core Genes Involved in the Progression of Cervical Cancer Using an Integrative mRNA Analysis.

In spite of being a preventable disease, cervical cancer (CC) remains at high incidence, and it has a significant mortality rate. Although hijacking of the host cellular pathway is fundamental for developing a better understanding of the human papillomavirus (HPV) pathogenesis, a major obstacle is identifying the central molecular targets involved in HPV-driven CC. The aim of this study is to investigate transcriptomic patterns of HPV-infected and normal tissues to identify novel prognostic markers. Analyses of functional enrichment and interaction networks reveal that altered genes are mainly involved in cell cycle, DNA damage, and regulated cell-to-cell signaling. Analysis of The Cancer Genome Atlas (TCGA) data has suggested that patients with unfavorable prognostics are more likely to have DNA repair defects attributed, in most cases, to the presence of HPV. However, further studies are needed to fully unravel the molecular mechanisms of such genes involved in CC.

Usefulness of real time elastography strain ratio in the assessment of cervical intraepithelial neoplasia and cervical cancer using a reference material.

AIMS: To assess the usefulness of real time elastography (RTE) strain ratio (SR) in diagnosing cervical cancer (CC) and cervical intraepithelial neoplasia (CIN), using a synthetic experimental device (ED) as reference material. MATERIAL AND METHODS: Seventy-nine participants were enrolled, divided in three groups: Group 1 - benign cervix (n=39); Group 2 - CIN (n=32); Group 3 - CC (n=8). Transvaginal RTE was performed, with SR determination, as the ratio between the ED and the cervical tissue. Mean SR values of the groups were compared; diagnostic performance was assessed by tracing the receiver operating characteristic (ROC) curve. Area under the curve (AUC) was analyzed. Cut-off values were established. Pathological results were considered as reference for data interpretation. RESULTS: SR means significantly differed in Group 1 as compared to Groups 2 and 3 (p=0.001). Excluding 2 aberrant values in Group 3, assigned to cases complicated by hemorrhagic necrosis, statistical difference was also noted between Groups 2 and 3 (p=0.02). For Groups 1 and 3, AUC was 0.966 with a 95%CI (0.914-1.000); the cut-off point of SR was 1.42, with a sensitivity of 100% and a specificity of 94.9%. AUC was 0.752 with a 95%CI (0.629-0.876) for Groups 1 and 2. For the cut-off value of 1.03, sensitivity and specificity were 75% and 74%, respectively. CONCLUSION: RTE SR, performed with a synthetic reference material, seems a reliable method for distinguishing between benign uterine cervix and malignancy, with promising results as a complementary investigation in diagnosing CIN. However, SR becomes inoperant in cases of cancer complicated with hemorrhagic necrosis.

Ultrasound Probe Pressure on the Maternal Abdominal Wall and the Effect on Fetal Middle Cerebral Artery Doppler Indices.

Background and objectives: Doppler ultrasound of umbilical and fetal vessels is useful for monitoring fetal well-being, fetal anemia, intrauterine growth retardation, and other perinatal outcomes. The adverse perinatal outcome and circulatory changes can be reflected in fetal Doppler studies. The aim of this study was to evaluate the effect of increased pressure exerted on the maternal abdominal wall during routine ultrasound on the middle cerebral artery (MCA), resistance index (RI), pulsatility index (PI), and peak systolic velocity (PSV). Materials and Methods: A prospective study was conducted, in which we included 40 pregnant women between 24 + 0 and 41 + 3 gestational weeks (GW), with singleton pregnancies, without any associated pathologies, undergoing routine US examination. We recorded the flow velocity waveforms in the MCA, and we measured the RI, PI, PSV, and the applied pressure on to the maternal abdominal wall-needed for a proper evaluation of MCA. We then repeated the same measurements at two different higher pressure levels, at the same time having a proper image of the targeted vessel. Results: We found significant differences for the PI and RI levels with an increase in abdominal pressure (median PI 1.46, 1.58, and 1.92, respectively; median RI 0.74, 0.78, and 0.85, respectively; p < 0.05), for both PI and RI. At the same time, we found no significant differences for PSV in the studied group in relationship with increase in abdominal pressure (median PSV 39.56, 40.10, and 39.70, respectively; p > 0.05). Conclusions: The applied abdominal pressure by the examiner's hand, during routine US scan in pregnancy, can modify the MCA parameters of blood flow resistance (PI and RI) when measured by Doppler US, thus influencing the diagnostic accuracy in a series of pregnancy associated pathologies, such as chronic fetal distress (CFD) or intrauterine growth restriction (IUGR).