Vaginal stenosis in women with cervical or endometrial cancer after pelvic radiotherapy: a cross-sectional study of vaginal measurements, risk for sexual dysfunction and quality of life.

INTRODUCTION AND HYPOTHESIS: Radiotherapy (RT) for cervical (CC) and endometrial cancer (EC) is known to lead to vaginal stenosis (VS), but the comparison between vaginal anatomical measurements and the risk of sexual dysfunction presents a wide variety of results among the literature. Thus, we sought to assess the prevalence of VS, vaginal measurements, sexual dysfunction and QOL in women with CC and EC submitted to pelvic RT with or without previous surgery. METHODS: Cross-sectional study that included 61 women with CC and 69 with EC. VS was classified by the Common Terminology Criteria for Adverse Effects version 5.0 (CTCAE v5.0), sexual function by the validated Female Sexual Function Index (FSFI) and QOL by the validated World Health Organization questionnaire (WHOQOL-BREF). Acrylic cylinders were used for vaginal measurements. Uni-/multivariate analyses to address factors associated with VC in both groups were performed. RESULTS: The prevalence of VS was 79% and 67% within patients with CC and EC, respectively. Vagina length was decreased in both groups without statistical difference (7.2 ± 1.7 vs. 6.6 ± 1.8;p = 0.072). Vaginal diameter was significantly higher (p = 0.047) in women with EC (25.4 ± 6.3) than in those with CC (23.1 ± 5.7). Sexual dysfunction was highly prevalent for both CC and EC (88% vs. 91%; p = 0.598). There was no difference in all WHOQOL-BREF domains between women with CC and EC. CONCLUSIONS: VS is highly prevalent in CC and EC patients, with vaginal length decreased in both groups but with a higher vaginal diameter in those with EC. Nevertheless, sexual dysfunction is highly prevalent in both groups.

The value of the endocervical margin status in LEEP: analysis of 610 cases.

PURPOSE: To describe the results of 610 patients who underwent LEEP and evaluate factors related to a negative margin. METHODS: A retrospective study of patients treated by LEEP at a colposcopy referral service in Campinas, Brazil, 2017-2019. Patients were referred to treat high-grade squamous intraepithelial lesion or adenocarcinoma in situ suspected by cytology and colposcopy (screen-and-treat) or by biopsy. Descriptive analysis was performed by frequencies as a function of the status of the margins (negative or positive). Factors associated with margin status were assessed by regression. RESULTS: The endocervical, ectocervical or both margins were negative in 82.4%, 75.7% and 65.9%, respectively. Age, sexual debut, parity, menopause status, smoking and hormonal contraception showed no difference in the proportion of negative margins. Both margins were negative in 66.1% of patients with transformation zone type(TZ) 1, 73.1% of TZ 2, and 54.7% of TZ 3 (p = 0.015). The endocervical negative margin was obtained in 78.0% of patients submitted to excision I (loop 10 mm) and 82.5% to excision II (loop 15 mm) (p = 0.016). Having the sexual debut at 18 years or older or being submitted to an excision type II doubled the chance of negative endocervical margin (1.98;1.04-3.77 and 1.95; 1.18-3.21, respectively). CONCLUSION: The proportion of negative endocervical margin was 78% in excision I and 86% in excision II. Sexual onset and excision type II increased the chance of obtaining a negative endocervical margin.

Endocervical Margins Status in Excision for Preventing Cervical Cancer According to the Transformation Zone Type.

OBJECTIVE: The aim of this study is to assess the outcomes of 610 excision types I and II in a referral facility as a function of transformation zone (TZ) types. METHODS: This is a retrospective cohort study of women with cervical precursor lesions who underwent loop electrocautery excision procedure from 2017 to 2019 at the University of Campinas. The primary outcome was endocervical margin status, negative or positive. Other variables were excision type (I/II), TZ (1/2/3), age, menopausal status, hormonal contraceptives, smoking, and sexual debut. Tests used were chi-square or Fisher exact, Mann-Whitney, and simple and multiple logistic regression. RESULTS: The most frequent was TZ 1 (62.5%). Excision II was the most frequent: 54.1% in TZ 1, 67.2% in TZ 2, and 82.1% in TZ 3. A negative margin was observed in TZ 1, 76.0% when excision I and 86.4% when excision II ( p = .009); TZ 2, 86.4% when excision I and 88.9% when excision II ( p = .672); and TZ 3, 76.5% when excision I and 78.9% when excision II ( p = .672). Multivariate analysis revealed in TZ 1 a 2.12 (1.23-3.65) higher risk of obtaining a negative margin in excision type II. In TZ 2 and 3, none of the variables predicted the chance of a negative margin. CONCLUSIONS: The endocervical margin was negative in 3 in every 4 women who underwent loop electrocautery excision procedure, regardless of excision type. Age, menopausal status, smoking, and hormonal contraception did not predict margin status.

Longitudinal, Long-Term Comparison of Single- versus Multipoint Upper Limb Circumference Periodical Measurements as a Tool to Predict Persistent Lymphedema in Women Treated Surgically for Breast Cancer: An Optimized Strategy to Early Diagnose Lymphedema and Avoid Permanent Sequelae in Breast Cancer Survivors.

PURPOSE: We aim to evaluate whether upper limb (UL) circumference (ULC) and UL swelling sensation (ULSS) performed shortly after surgery or later on during follow-up can predict long-term/persistent forms of lymphedema in women who underwent surgery for breast cancer. PATIENTS AND METHODS: Eighty-five women completed at least 24 months of follow-up. At each follow-up visit (1, 3, 6, 12, and 24 months after surgery), patients were tested for lymphedema using ULC and ULSS. Two different approaches to ULC were compared: (1) a "positive" lymphedema diagnosis if a difference ≥ 2 cm between the affected and contralateral UL was detected in at least two contiguous measurement points (MPs) and (2) a "positive" result if just one MP ≥ 2 cm. Patients were also questioned about their perception of weight, swelling, and/or tension (ULSS). The gold standard for long-term lymphedema was a water displacement difference between the UL ≥ 200 mL 24 months after surgery (ULWD). RESULTS: Twenty-four months after surgery, 19 (22.4%) women were diagnosed with long-term lymphedema. Using 24-month data, comparison of log-likelihoods denoted a clear superiority of the ULC approach 1 compared with 2 for the diagnosis of long-term lymphedema (p < 0.001). Using approach 1, the best prediction of a woman developing long-term lymphedema if she had a positive ULC in the follow-up was obtained at 6 months after surgery (posterior probability of 60%). CONCLUSIONS: Our study reveals that performing ULC 6 months after surgery, regarding as "positive" only women with a difference ≥ 2 cm at two contiguous MPs, is the best strategy to identify women at increased risk of later developing permanent forms of lymphedema.

Physical and functional well-being and symptoms of ovarian cancer in women undergoing first-line of chemotherapy: a one-year follow-up.

PURPOSE: Clinicopathological features and chemotherapy can influence the quality of life (QOL), women with ovarian cancer. This study aimed to evaluate the physical and functional well-being, and ovarian cancer-specific effects scores reported from QOL questionnaire among women with ovarian cancer at the time of in their initial diagnosis and access the scores trajectory of women receiving neoadjuvant and adjuvant chemotherapy. METHODS: This prospective study used cross-sectional analysis at baseline and longitudinal analysis from baseline to 12-month post-chemotherapy. QOL was evaluated at the baseline, at sixth cycle and 12-month post-chemotherapy using FACT-O questionnaire. Clinicopathological features and chemotherapy regime were evaluated and tested for associations with QOL measures. RESULTS: Of the 38 women enrolled in this study, 27 (80.1%) completed the questionnaire for 12 months. The multivariate linear regression results suggest, at the baseline, women with advance stage and presence of post-surgery residual disease showed lower scores in physical and functional well-being, ovarian cancer-specific effects, and FACT-O TOI domains (p < 0.05). Longitudinal analysis spanning over 12 months showed an improvement in mean physical well-being, functional well-being, and ovarian cancer-specific effects scores, independent of chemotherapy received (p < 0.05). CONCLUSIONS: At the baseline, the clinicopathological features such as stage, presence of post-surgery residual disease, and type of chemotherapy correlated with on QOL scores. At one-year follow-up, women who underwent chemotherapy showed improvement in QOL regardless of the type of chemotherapy they received. Future prospective study with a larger group is recommended.

Pelvic floor muscle assessment by digital palpation and translabial ultrasound of women with cervical or endometrial cancer after pelvic radiotherapy: a cross-sectional study.

INTRODUCTION AND HYPOTHESIS: We hypothesized that anatomical changes in the pelvic floor muscles (PFM) could be detected using four-dimensional translabial ultrasound (4D TLUS) in patients with cervical (CC) or endometrial cancer (EC) who underwent pelvic radiotherapy (RT) as digital palpation may present sensitivity limitations. METHODS: This was a cross-sectional study that included 64 women (26 with CC and 38 with EC). PFM function was assessed by digital palpation, grading muscle strength according to the Modified Oxford Scale and by 4D TLUS. Ultrasonographic variables were: levator plate angle, hiatal area, puborectalis muscle thickness, puborectalis strain and levator ani muscle integrity. These variables were also correlated with clinical and sociodemographic data from all these patients. A 5% significance level was adopted. RESULTS: When assessed by digital palpation, no significant difference was found in PFM strength between women with CC and those with EC (p = 0.747). However, when assessed by 4D TLUS, women with CC presented greater thickening of the left (p = 0.039) and right (p = 0.014) lower portion of the puborectalis muscle during PFM contraction compared to those with EC. After pooling the groups, higher cancer staging (p = 0.028) was associated with smaller narrowing in the symphysis-levator distance, and shorter RT finishing duration (< 60 months) was associated with higher thickening in the left (p = 0.029) and right (p = 0.013) upper portion of the puborectalis muscle during PFM contraction as well as a shorter menopause duration (p = 0.007 and p = 0.002, respectively). CONCLUSIONS: Anatomical changes in the puborectalis muscle during PFM contraction were detected by 4D TLUS within gynecological cancer patients after pelvic RT.

Levonorgestrel-releasing intrauterine system and breast cancer risk: A systematic review and meta-analysis.

INTRODUCTION: Epidemiological studies have shown that some hormonal contraceptive methods are associated with increased breast cancer risk, especially if used over long periods. Our objective was to conduct a systematic review and meta-analysis of the literature on the risk of breast cancer development in women using the 52-mg levonorgestrel-releasing intrauterine system (LNG-IUS). MATERIAL AND METHODS: We performed a thorough review of peer-reviewed publications from 10 January 1999, through 31 July 2019, using combinations of search terms for breast cancer risk and LNG-IUS in the Medline, EMBASE, LILACS (Latin American and Caribbean Health Sciences Literature), and Scielo databases. This review was registered in PROSPERO (CRD42017059076). Studies reporting breast cancer risk estimates among healthy users of LNG-IUS were included according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analysis) criteria. Two authors performed data extraction, and a third author resolved disagreements. The quality of evidence was evaluated using the Downs and Black instrument. A funnel plot was generated, and a linear regression test of funnel plot asymmetry was used to assess publication bias. Finally, we performed a random-effects model (owing to high study heterogeneity) meta-analysis of seven suitable studies, stratified by the age distribution of patients (<50 years, ≥50 years, and mixed). RESULTS: We identified 96 studies and manually cross-referenced and excluded duplicate articles. Seventy articles were excluded on the basis of the inclusion and exclusion criteria, resulting in the assessment of 26 full-text articles. Eight articles were considered adequate for inclusion in this systematic review, and seven studies were included in the meta-analysis. Three publications were case-control studies and five were cohort studies. According to the Downs and Black instrument, 5 studies were rated as "good" and 3 studies were deemed "fair". Our meta-analysis results indicated increased breast cancer risk in LNG-IUS users: for all women, odds ratio (OR) = 1.16 (95% CI 1.06-1.28, I2  = 78%, P < .01); for women aged <50 years, OR = 1.12 (95% CI 1.02-1.22, I2  = 66%, P = .02); and for women aged ≥50 years, OR = 1.52 (95% CI 1.34-1.72, I2  = 0%, P = .84). CONCLUSIONS: Current evidence suggests that LNG-IUS users have an increased breast cancer risk regardless of age and indication. The effect of LNG-IUS on breast cancer risk seems to be larger in older users. However, our systematic review detected methodological issues across the available studies, and confounding factors may be responsible for at least a fraction of the risk effects associated with LNG-IUS use. Nevertheless, users of LNG-IUS should be aware of these trends. We believe that caution is needed, and risks should be balanced against proven health benefits (eg effective treatment of heavy menstrual bleeding and avoidance of surgical interventions), when prescribing LNG-IUS for long periods of use, especially in women with other known breast cancer risk factors such as old age, obesity, and familial predisposition.

Multiplatform Investigation of Plasma and Tissue Lipid Signatures of Breast Cancer Using Mass Spectrometry Tools.

Plasma and tissue from breast cancer patients are valuable for diagnostic/prognostic purposes and are accessible by multiple mass spectrometry (MS) tools. Liquid chromatography-mass spectrometry (LC-MS) and ambient mass spectrometry imaging (MSI) were shown to be robust and reproducible technologies for breast cancer diagnosis. Here, we investigated whether there is a correspondence between lipid cancer features observed by desorption electrospray ionization (DESI)-MSI in tissue and those detected by LC-MS in plasma samples. The study included 28 tissues and 20 plasma samples from 24 women with ductal breast carcinomas of both special and no special type (NST) along with 22 plasma samples from healthy women. The comparison of plasma and tissue lipid signatures revealed that each one of the studied matrices (i.e., blood or tumor) has its own specific molecular signature and the full interposition of their discriminant ions is not possible. This comparison also revealed that the molecular indicators of tissue injury, characteristic of the breast cancer tissue profile obtained by DESI-MSI, do not persist as cancer discriminators in peripheral blood even though some of them could be found in plasma samples.

Role of discoidin domain receptor 2 (DDR2) and microRNA-182 in survival of women with high-grade serous ovarian cancer.

The objective of this study is to evaluate the relationship between discoidin domain receptor 2 (DDR2) and miR-182 expression with response to platinum-based chemotherapy and survival in women with high-grade serous ovarian cancer (HGSOC). We evaluated 78 women with HGSOC stages I-IV, diagnosed between 1996 and 2013, and followed up until 2016. DDR2 expression was assessed using immunohistochemistry on tissue microarray slides. The microRNAs were evaluated by qRT-PCR. DDR2 expression was high in 11 (14.1%) women. PFS was significantly lower in women with FIGO stage I/II - versus III/IV, post-surgery residual disease and high expression of DDR2. Women with postsurgery residual disease, FIGO stage I/II - versus III/IV and DDR2 expression had worse OS, but only post-surgery residual disease remained an independent prognostic factor for worse OS in multivariable analysis. miR-182 expression levels were significantly lower in patients harboring tumors with higher expression of DDR2 (p < 0.001). In this relatively large cohort of women with HSGOC, higher DDR2 expression was associated with lower miR-182 levels and worse PFS, suggesting that these molecules may be associated with mechanisms of HGSOC progression.

Perinodal fibrosis developed after ultrasonography-guided core-needle biopsy of a contrast-enhanced ultrasound-detected sentinel axillary node interferes with subsequent surgical sentinel node dissection.

OBJECTIVE: To evaluate perinodal fibrosis after 14-gauge staging core-needle biopsy (CNB) of the axillary sentinel lymph node (SLN) identified using contrast-enhanced ultrasonography (CEUS) and its interference with subsequent surgical SLN dissection in breast cancer patients. METHODS: Frequencies or means of main clinical, sonographic, pathological, and surgical characteristics were calculated. We also compared patient groups with and without perinodal pathological fibrosis. RESULTS: Forty-eight patients who underwent CEUS + CNB and axillary surgery were eligible for this cross-sectional study. Axillary surgical specimens showed perinodal fibrosis in 9/48 (18.7%) patients. Interference with SLN dissection was reported in 4/48 (8.3%) patients (two hematomas, three abnormal palpation findings, and four difficult dissections). The overall surgical detection rate of SLN was 43/48 (89.6%). In the majority of cases, perinodal fibrosis was described as moderate (4/9 [44.4%]) or severe (4/9 [44.4%]). The mean time elapsed between CEUS + CNB and axillary dissection was shorter in patients with perinodal fibrosis (P = .04). Interference with SLN dissection was only reported in patients with perinodal fibrosis (P < .001). Surgical SLN detection was successful in all nine cases in which perinodal pathological fibrosis or interference with SLN dissection was reported. CONCLUSION: Perinodal fibrosis may impair the surgical SLN dissection in early stage breast cancer patients who were staged using CEUS + CNB using a14-gauge needle.

Collagen analysis by second-harmonic generation microscopy predicts outcome of luminal breast cancer.

Second-harmonic generation microscopy represents an important tool to evaluate extracellular matrix collagen structure, which undergoes changes during cancer progression. Thus, it is potentially relevant to assess breast cancer development. We propose the use of second-harmonic generation images of tumor stroma selected on hematoxylin and eosin-stained slides to evaluate the prognostic value of collagen fibers analyses in peri and intratumoral areas in patients diagnosed with invasive ductal breast carcinoma. Quantitative analyses of collagen parameters were performed using ImageJ software. These parameters presented significantly higher values in peri than in intratumoral areas. Higher intratumoral collagen uniformity was associated with high pathological stages and with the presence of axillary lymph node metastasis. In patients with immunohistochemistry-based luminal subtype, higher intratumoral collagen uniformity and quantity were independently associated with poorer relapse-free and overall survival, respectively. A multivariate response recursive partitioning model determined 12.857 and 11.894 as the best cut-offs for intratumoral collagen quantity and uniformity, respectively. These values have shown high sensitivity and specificity to differentiate distinct outcomes. Values of intratumoral collagen quantity and uniformity exceeding the cut-offs were strongly associated with poorer relapse-free and overall survival. Our findings support a promising prognostic value of quantitative evaluation of intratumoral collagen by second-harmonic generation imaging mainly in the luminal subtype breast cancer.

Endometriosis-Associated Ovarian Cancer: Population Characteristics and Prognosis.

OBJECTIVE: The aim of this study was to analyze and compare the clinicopathologic features and prognosis of clear cell ovarian carcinoma (CCOC) and endometrioid ovarian carcinoma (EOC) associated or not with endometriosis. METHODS: This was a reconstituted cohort study from a single-institution Brazilian cancer center approved under review board no. 68150617.7.0000.5404 with 50 patients with CCOC and EOC diagnosed between 1995 and 2016, followed up until 2017. Clinicopathologic characteristics and survival outcomes were analyzed. RESULT(S): There were 23 women (46%) with CCOC and 27 with EOC (54%); 80% of those women had histologic confirmation of endometriosis; 42% were nulliparous, and 42% were premenopausal; and cancer antigen 125 was elevated in both International Federation of Gynecology and Obstetrics stages I-II disease (mean, 614.7 Ui/mL; range, 3-6030 Ui/mL) or International Federation of Gynecology and Obstetrics stages III-IV disease (mean, 2361.2 Ui/mL; range, 8-12771 Ui/mL). Women with EOC were 7 years younger than those with CCOC. When associated with endometriosis, CCOCs were more likely diagnosed at earlier stages. Endometrioid ovarian carcinoma and CCOC at initial stage and EOC at advanced stage share similar good prognosis. Univariate analysis showed that CCOC not associated with endometriosis has worse overall survival (OS). However, multivariate analysis showed that only abnormally elevated levels of cancer antigen 125 and advanced stage at diagnosis were significantly associated with reduced progression-free survival. Tumor stage remains the only prognostic factor for OS. CONCLUSIONS: The presence of coexisting endometriosis did not change the prognosis of EOC but was associated with better OS in patients with CCOC. Patients with CCOC and EOC at initial stages and EOC at advanced stages have a good prognosis; however, CCOC at advanced stages had a sooner recurrence and shorter OS.

BRCA1, Ki67, and ß-Catenin Immunoexpression Is Not Related to Differentiation, Platinum Response, or Prognosis in Women With Low- and High-Grade Serous Ovarian Carcinoma.

OBJECTIVE: The purpose of this study was to compare the immunohistochemical expression of BRCA1, Ki67, and ß-catenin in women with low-grade (LGSOC) and high-grade serous ovarian carcinomas (HGSOC) and their relationship with clinicopathological features, response to platinum-based chemotherapy, and survival. METHODS: For this study, 21 LGSOC and 85 HGSOC stage I to IV cases, diagnosed and treated from 1996 to 2013 and followed-up until December 2016, were included. BRCA1, Ki67, and ß-catenin expression was assessed using tissue microarray-based immunohistochemistry. RESULTS: Women with HGSOC were significantly more likely to have advanced-stage disease (P < 0.001), higher CA125 levels (P < 0.001), postsurgery residual disease (P < 0.01), and higher rates of disease progression and recurrence (P = 0.001). The percentage of women with HGSOC whose tumors expressed Ki67 was significantly higher compared with women with LGSOC (P < 0.001). The expression of BRCA1 and ß-catenin did not differ between LGSOC and HGSOC (P = 0.12 and P = 1.00, respectively). The clinicopathological features and the response to platinum-based chemotherapy did not differ according to the BRCA1, Ki67, and ß-catenin expression in either group. In HGSOC, only International Federation of Gynecology and Obstetrics stage was independently associated with poor survival (PFS and OS). CONCLUSIONS: Ki67 expression was significantly higher in HGSOC. BRCA1 and ß-catenin expression did not differ between LGSOC and HGSOC samples. BRCA1, Ki67, and ß-catenin expression was neither related to clinicopathological features, response to platinum-based chemotherapy, nor survival. Only International Federation of Gynecology and Obstetrics stage remained associated with poor survival in women with HGSOC.

A Metabolomic Approach to Predict Breast Cancer Behavior and Chemotherapy Response.

Although the classification of breast carcinomas into molecular or immunohistochemical subtypes has contributed to a better categorization of women into different therapeutic regimens, breast cancer nevertheless still progresses or recurs in a remarkable number of patients. Identifying women who would benefit from chemotherapy could potentially increase treatment effectiveness, which has important implications for long-term survival. Metabolomic analyses of fluids and tissues from cancer patients improve our knowledge of the reprogramming of metabolic pathways involved in resistance to chemotherapy. This review evaluates how recent metabolomic approaches have contributed to understanding the relationship between breast cancer and the acquisition of resistance. We focus on the advantages and challenges of cancer treatment and the use of new strategies in clinical care, which helps us comprehend drug resistance and predict responses to treatment.

CAISMOV24, a new human low-grade serous ovarian carcinoma cell line.

BACKGROUND: The spontaneous immortalization of primary malignant cells is frequently assigned to their genetic instability during in vitro culturing. In this study, the new epithelial ovarian cancer cell line CAISMOV24 was described and compared with its original low-grade serous ovarian carcinoma. METHODS: The in vitro culture was established with cells isolated from ascites of a 60-year-old female patient with recurrent ovarian cancer. The CAISMOV24 line was assessed for cell growth, production of soluble biomarkers, expression of surface molecules and screened for typical mutations found in serous ovarian carcinoma. Additionally, comparative genomic hybridization was employed to compare genomic alterations between the CAISMOV24 cell line and its primary malignant cells. RESULTS: CAISMOV24 has been in continuous culture for more than 30 months and more than 100 in vitro passages. The cell surface molecules EpCAM, PVR and CD73 are overexpressed on CAISMOV24 cells compared to the primary malignant cells. CAISMOV24 continues to produce CA125 and HE4 in vitro. Although the cell line had developed alongside the accumulation of genomic alterations (28 CNV in primary cells and 37 CNV in CAISMOV24), most of them were related to CNVs already present in primary malignant cells. CAISMOV24 cell line harbored KRAS mutation with wild type TP53, therefore it is characterized as low-grade serous carcinoma. CONCLUSION: Our results corroborate with the idea that genomic alterations, depicted by CNVs, can be used for subtyping epithelial ovarian carcinomas. Additionally, CAISMOV24 cell line was characterized as a low-grade serous ovarian carcinoma, which still resembles its primary malignant cells.

VEGF gene polymorphisms and outcome of epithelial ovarian cancer patients.

AIM: Since VEGF polymorphisms were associated with variable protein production, we analyzed herein their roles in outcome of epithelial ovarian cancer (EOC) patients. METHODS: Genotypes of 85 patients with primary EOC were identified in DNA by real-time PCR. Progression-free survival and overall survival were analyzed using Kaplan-Meier method, univariate Cox model and bootstrap resampling study. RESULTS: At 60 months of follow-up, progression-free survival was shorter in patients with VEGF c.-2578 CC genotype compared with others (52.7 vs 82.2%; p = 0.04). Those patients had 2.15 more chance of presenting disease progression than others (p = 0.04); bootstrap study validated the result (p = 0.03). CONCLUSION: Our data suggest that VEGF c.-2578C>A polymorphism acts as a prognostic factor in EOC.

Variations in the sonographic measurement techniques of BI-RADS 3 breast masses.

OBJECTIVE: To evaluate the differences in sonographic (US) distance and volume measurements from different sonologists and identify the optimal parameters to avoid clinically relevant variations in the measurement of BI-RADS 3 breast masses. METHODS: For this cross-sectional study with prospectively collected data, four physicians with various levels of experience in US, herein called sonologists, performed distance and volume US measurements of 80 masses classified as BI-RADS 3. The Cochran Q test was used to compare the matched sets of rates of clinically relevant variability between all pairs of sonologists' measurements. RESULTS: There were clinically relevant differences between sonologists in the measurements of the longest diameter (range, 17.5-43.7%, p = 0.003), the longest diameter perpendicular to the previous one (anteroposterior diameter) (17.5-33.7%, p = 0.06), the third diameter orthogonal to the plane defined by the previous two (transverse diameter) (28.7-55%, p = 0.001), and at least two of those three diameters (18.7-38.7%, p = 0.015). The smallest clinically relevant differences were observed with volume measurements (range of differences, 6.2-13.7%, p = 0.51). CONCLUSIONS: Volume measurement technique was associated with the least variations, whereas distance measurements, which are used routinely, were associated with unacceptable rates of clinically relevant variations. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:252-260, 2017.

Natural Killer Cells Response to IL-2 Stimulation Is Distinct between Ascites with the Presence or Absence of Malignant Cells in Ovarian Cancer Patients.

Peritoneal ascites are a distinguishable feature of patients with advanced epithelial ovarian cancer (EOC). The presence of different lymphocyte subsets has been reported in EOC-associated ascites, which also can or not contain malignant cells. The goal of this study was to analyze the functional characteristics of natural killer (NK) cells from EOC-associated ascites in terms of their expression of activating receptors and ascites' contents of lymphocyte subtypes, cytokine profile and presence of EOC cells. NK cell function was evaluated by the expression of the degranulation marker CD107a in resting and interleukin (IL)-2 stimulated NK cells from ascites and blood. Degranulation of NK cells from EOC cell-free ascites was significantly (p < 0.05) higher than all the other groups, either in their resting state or after IL-2 stimulation, suggesting a previous local stimulation. In contrast, treatment with IL-2 had no effect on NK cells from ascites with EOC cells. The amount of regulatory T cells was significantly higher in ascites with EOC cells compared to EOC cell-free ascites. Ascites with EOC cells also had higher levels of tumor necrosis factor (TNF)-α, suggesting inflammation related to the malignancy. In conclusion, the functional performance of NK cells was distinct between EOC cell-free ascites and ascites with EOC cells. The impairment of NK cell response to IL-2 in ascites with EOC cells was consistent with an immunosuppressive tumor microenvironment.

Comparing the Copenhagen Index (CPH-I) and Risk of Ovarian Malignancy Algorithm (ROMA): Two equivalent ways to differentiate malignant from benign ovarian tumors before surgery?

AIM: To evaluate the prediction of malignancy in women with pelvic masses using the Copenhagen Index (CPH-I) and Risk of Ovarian Malignancy Algorithm (ROMA). PATIENTS AND METHODS: Three hundred eighty four women operated due to an ovarian mass were enrolled between January 2010 and June 2015. All patients had histopathological diagnosis, HE4 and CA125 measurement. CPH-I and ROMA were calculated and their performances compared in two distinct scenarios: 1) for the discrimination of benign ovarian disease from epithelial ovarian cancer (EOC), non-epithelial ovarian cancer, borderline ovarian tumors (BOT) and ovarian metastases, and 2) for the discrimination of benign disease from EOC. Receiver Operator Characteristics' Areas Under the Curves (AUC) were calculated for CPH-I and ROMA and compared. RESULTS: Of the 384 women, 224 presented a benign ovarian tumor, 32 BOT, 87 EOC, 26 non-epithelial ovarian cancer, and 15 had ovarian metastases. The best AUCs were obtained for the discrimination of EOC from benign tumors. CPH-I performed slightly better than ROMA, and both approached 89% sensitivity and 85% specificity. When all malignant tumors (EOC, BOT, ovarian metastases and non-epithelial ovarian cancer - entire cohort) were included, the performance of CPH-I and ROMA declined to nearly 72%, although the specificity remained close to 85%. CONCLUSION: CPH-I and ROMA performed similarly well for the discrimination of EOC from benign ovarian tumors. However, caution is necessary since, in practical situations, where all the histological possibilities for malignant ovarian tumors must be considered, the sensitivity of CPH-I and ROMA may not surpass 70%.