The use of CA125, human epididymis protein 4 (HE4), risk of ovarian malignancy algorithm (ROMA), risk of malignancy index (RMI) and subjective assessment (SA) in preoperative diagnosing of ovarian tumors.

OBJECTIVES: To compare utility of CA125, human epididymis protein 4 (HE4), risk of ovarian malignancy algorithm (ROMA), risk of malignancy index (RMI) and subjective assessment (SA) in preoperative diagnosis of ovarian tumors. MATERIAL AND METHODS: Research was conducted among 456 patients qualified for surgery due to ovarian tumor. Preoperatively, CA125 and HE4 serum levels were estimated, and transvaginal ultrasound was performed. ROMA and RMI values and SA qualifications were obtained. Results were compared with pathomorphological findings. RESULTS: Receiver Operating Characteristic (ROC)-Area Under Curve (AUC) values for CA125, HE4, ROMA, RMI and SA in preoperative diagnosis of malignant lesions were 0.819, 0.909, 0.911, 0.895 and 0.895, respectively. Combinations of biochemical and sonographic methods increased sensitivity in diagnosis of ovarian tumors. Combinations utilizing serum HE4 concentrations were most useful. CONCLUSIONS: CA125, HE4, ROMA, RMI and SA proved to be useful in preoperative diagnosis of ovarian tumors. HE4 and ROMA occurred to be the most useful. Ultrasonographic methods are considerably useful in diagnosis of ovarian tumors. RMI and SA present similar overall diagnostic value.

Chemokine expression in patients with ovarian cancer or benign ovarian tumors.

Introduction: Chemokines play a crucial role in tumor growth and progression according to proangiogenic and immunosuppressive action. The aim of this study was to investigate the serum levels of selected chemokines in patients with ovarian cancer or benign ovarian tumors to assess their role in tumorigenesis and their potential use in preoperative diagnosis of an adnexal mass. Material and methods: The study group consisted of 59 women with ovarian cancer: 17 epithelial ovarian cancer (EOC) patients and 42 women with benign ovarian tumors. We measured in sera obtained preoperatively the level of CA125 and a panel of 5 chemokines - CX3CL1/fractalkine, CXCL1/GRO-α, CXCL12/SDF-1, CCL20/MIP-3α and IL-17F - using the chemiluminescence method with multiplexed bead based immunoassay. Results: CX3CL1 was significantly elevated in sera of advanced ovarian cancer patients compared to women with benign ovarian tumors. The significant elevation of CXCL1 was also observed (both early and advanced stages). A similar pattern was present with the standard ovarian cancer marker CA125. In our patients with endometriotic cysts CA125 levels were significantly higher than in women with other benign tumors, whereas all analyzed chemokines had similar serum titers in patients with endometriotic vs. other benign ovarian cysts. Conclusions: CX3CL1 and CXCL1 are elevated in sera of EOC patients, which indicates their role in cancer development. Moreover, they might be useful in preoperative differential diagnosis of ovarian tumors, especially as they were not elevated in cases of endometriosis.

A body shape index (ABSI) and endometrial pathology.

A body shape index (ABSI) is an anthropometric measure that allows evaluating abdominal adiposity. Obesity is considered a risk factor for endometrial cancer (EC). Due to the increase in EC's incidence, identifying risk factors for endometrial pathology is essential in women's health. The study aimed to identify an association between EC/endometrial pathology and ABSI. We identified well-known risk factors for endometrial cancer and calculated ABSI in 408 women who were admitted to the Polish Mother's Memorial Hospital Research Institute between January 2016 and December 2017. Patients were divided into four subgroups: no endometrial pathology, endometrial polyps, hyperplasia without atypia, and hyperplasia with atypia/cancer. Statistical analysis showed a correlation between ABSI and the presence of cancer/atypical hyperplasia (Kruskal-Wallis test, p = .042). Additional multivariate analysis revealed that both ABSI and body mass index (BMI) z scores might potentially be associated with EC presence (ABSI z score quintiles Q1, Q2, Q3 vs. Q4, Q5: p = .039; BMI z score quintiles Q1, Q2, Q3 vs. Q4, Q5: p = .038). We found an association between cancer/atypical hyperplasia and ABSI. Further studies on ABSI are needed to establish ABSI as a risk factor for EC fully.

Current clinical application of serum biomarkers to detect and monitor ovarian cancer - update.

In recent decades many potential serum biomarkers have been assessed in the diagnosis of ovarian cancer. Except cancer antigen 125 (CA125) and human epididymis protein 4 (HE4), none of them have been applied to everyday clinical practice. Based on extensive scientific evidence, CA125 combined with HE4 to form the risk of ovarian malignancy algorithm (ROMA), have become widespread in clinical practice in the evaluation of adnexal masses. Early ovarian cancer is often asymptomatic, so it remains challenging to develop even more effective methods for early diagnosis and screening. Among others, OVA1 is tested as a potential tool to improve the stratification of the risk of ovarian cancer. Also, a lot of effort is being made to develop suitable methods to monitor ovarian cancer patients. Serum CA125 already plays an established role in monitoring the treatment (except targeted therapies) and relapse setting in ovarian cancer patients, with a more limited role in subtypes other than in high-grade serous carcinoma, and always in correlation with imaging and clinical assessment. Human epididymis protein 4 (as well as circulating tumour DNA - ctDNA) is not recommended for monitoring at that timepoint, although encouraging newly published studies might influence their role in the future.

Analysis of the results of invasive diagnostic procedures in patients referred to gynecologic department due to abnormal uterine bleeding.

INTRODUCTION: Abnormal uterine bleeding (AUB) is one of the most common reason for visits to gynecologists. Endometrial biopsy is a routine procedure in gynecological practice to detect the etiology of AUB and to exclude precancerous and cancerous lesions of the endometrium. The aim of this study was to assess the causes of AUB among women, who had undergone invasive diagnostics due to AUB. MATERIAL AND METHODS: This study was carried among 531 women, who had undergone invasive diagnostics due to AUB between January 2018 and December 2018. Women were divided into premenopausal (with perimenopausal) and postmenopausal groups. Transvaginal ultrasound was performed. Endometrial thickness was compared with histopathological results in each subgroup and statistically analyzed. The incidence of histopathological findings and rate of anemia were also analyzed. RESULTS: In our series of patients the most common cause of AUB based on histopathological results was endometrial polyp, both before and after menopause. The most frequent pathologies at ultrasound findings were leiomyomas and endometrial polyps. The incidence of taken together: atypical hyperplasia and endometrial cancer was significantly higher in postmenopausal group (8.58%) than in pre- and perimenopausal (1.35%, p = 0.0001). The median endometrial thickness, both before and after menopause, was significantly greater in patients with pathological than with nonpathological endometrium. 31% of women with abnormal uterine bleeding before menopause and 10% after menopause had anemia. CONCLUSIONS: Measurements of endometrial thickness seems to be acceptable initial diagnostic tool to distinguish between benign and pathological endometrial changes both before and after menopause.

[Evaluation of applicability of HE4 and ROMA in the preoperative diagnosis of adnexal masses]. / Ocena uzytecznosci oznaczen bialka HE4 i algorytmnu ROMA w przedoperacyjnej diagnostyce guzow przydatków.

OBJECTIVE: The aim of the study was to evaluate the effectiveness of HE4 alone and in combination with CA 125 (ROMA) in selecting patients at high risk of adnexal malignancy. MATERIAL AND METHODS: Serum CA 125 and HE4 levels were determined and the ROMA value was calculated in 259 women qualified for surgery due to adnexal mass. The results were compared with histopathological findings. RESULTS: Sensitivity and specificity in preoperative diagnosis of primary ovarian cancer were 93.2% and 71.5% for CA 125 and 95.4% and 81.3% for HE4, respectively ROMA algorithm achieved sensitivity of 95.4% and specificity of 79.8%. All methods reached sensitivity of 100% at specificity of 65.6% for CA125, 93.4% for HE4 and 82.0% for ROMA in premenopausal women, whereas in postmenopausal women sensitivity and specificity achieved levels of 92.1% and 81.7% for CA 125, 94.7% and 60.6% for HE4 and 94.7% and 76.1% for ROMA, respectively Serum levels of both CA 125 and HE4 were significantly higher in women with primary ovarian cancer as compared to benign disease. Concentrations of CA 125 in patients with endometriosis were significantly elevated as compared to women with other benign tumors. Such relation was not observed when HE4 levels were concerned. CONCLUSIONS: CA 125, HE4 and ROMA are useful in preoperative diagnosis of ovarian malignancy HE4 improves the diagnostic accuracy in cases of endometriosis, verifying false positive results of CA 125.

Current clinical application of serum biomarkers to detect ovarian cancer.

For the last decades, hundreds of potential serum biomarkers have been assessed in diagnosing of ovarian cancer including the wide spectrum of cytokines, growth factors, adhesion molecules, proteases, hormones, coagulation factors, acute phase reactants, and apoptosis factors but except CA125 none of them have been applied to everyday clinical practice. Nowadays, the growing number of evidence suggests that the classic marker CA125 should be accompanied by HE4 and in fact, Risk of Ovarian Malignancy Algorithm (ROMA) is becoming more and more widespread in clinical practice for the evaluation of adnexal masses. Early ovarian cancer is often asymptomatic, so the challenge still exists to develop serum markers suitable for early diagnosis and screening. Current knowledge strongly points to different mechanisms of pathogenesis, genetic disturbances and clinical course of major histological subtypes of ovarian cancer. Thus, future biomarker/multimarker panels should take into consideration the implications of different molecular patterns and biological behavior of various subtypes of ovarian cancer. Very promising are studies on miRNAs - small non-protein coding gene-regulatory RNA molecules functionally involved in the pathogenesis of cancers acting as oncogenes (oncomirs) or tumor suppressors. The studies devoted to ovarian cancer tissue miRNA profiling have shown that miRNAs could be useful in diagnosing and predicting the OC outcome. They also confirmed that OC is a highly heterogeneous disease, gathering four distinct histological tumor subtypes characterized not only by distinct origin, behavior and response to chemotherapy but also by different patterns of miRNA expression.

Microvesicles as a potential biomarker of neoplastic diseases and their role in development and progression of neoplasm.

Neoplastic diseases together with cardiovascular diseases are the most frequent causes of death in the Polish population. Cancers of reproductive organs with breast cancer are responsible for the highest morbidity and mortality in women suffering from neoplasm diseases. Asymptomatic dynamics of the development of a neoplasm and no deviations from the normal level of laboratory results contribute to the fact that malignant diseases are diagnosed too late. The aim of modern medicine is to diagnose cancer at the earliest stage, however, there is no sufficiently sensitive and specific biomarker which can be used for diagnostic, prognostic and therapeutic purposes. Cellular interactions play the main role in the development, angiogenesis and invasiveness of a tumor. Recent research suggests the possibility of microvesicles (MVs) involvement in communication between cells. The MVs ability to fuse with various cells is used in cell-to-cell contact. Microvesicles cargo may include growth factors, their receptors, protease, adhesion molecules, signaling molecules and the sequence of DNA, mRNA, and micro-RNA. Larger quantities of MVs released from neoplastic cells affect both the local environment and systematic range causing metastases and progression. The research on molecular mechanisms of MVs' release and the presence of characteristic oncogenes in blood of patients with neoplasms is being carried out. Confirmation of MVs presence in patients' serum can potentially serve as useful information for therapeutic purposes and as the biomarker of a neoplastic disease.

Classical radical hysterectomy and nerve-sparing radical hysterectomy in the treatment of cervical cancer.

AIM OF THE STUDY: To compare Piver III radical hysterectomy (RH) with nerve-sparing radical hysterectomy (NSRH) for cervical cancer patients in terms of postoperative physiology of pelvic autonomic nerves and perioperative complications. MATERIAL AND METHODS: Seventy-three consecutive patients with invasive cervical cancer underwent RH (53 cases) or NSRH (20 cases) from 2001 to 2012 at the Department of Gynecology and Gynecologic Oncology of Polish Mother's Memorial Hospital - Research Institute in Lódz. RESULTS: Compared with patients treated with RH, patients who underwent NSRH presented no significant difference in terms of operative time (146 vs. 143 minutes, p > 0.05), blood loss and hospital stay (9.2 vs. 7.5 days, p > 0.05). A positive surgical margin was found in 6 cases of RH. No serious surgical complications were found in the NSRH group, while there were 4 cases in the RH group. CONCLUSIONS: Nerve-sparing radical hysterectomy is safe and feasible surgical management for cervical cancer patients, which should improve the physiology of the pelvic autonomic nerve system postoperatively. The technique is relatively new and its oncologic efficiency has not been fully established yet, moreover it requires sophisticated anatomical knowledge and high operative skills.