Tertiary prevention strategies for micrometastatic lymph node cervical cancer: A systematic review and a prototype of an adapted model of care.

PURPOSE: We found a need for balancing the application of clinical guidelines and tailored approaches to follow-up of cervical cancer (CC) patients in the lymph node micrometastatic (MICs) setting. This review aimed to determine the current knowledge of management of MIC-positive CC cases. METHODOLOGY: We addressed prognostic and risk of recurrence monitoring impacts associated with MIC+ cases. The electronic databases for literature and relevant articles were analysed. RESULTS: Fifteen studies, (4882 patients), were included in our systematic review. While the results show that MICs significantly worsen prognosis in early CC. A tertiary prevention algorithm for low volume lymph node disease may stratify follow-up according to the burden of nodal disease and provide data that helps improve follow-up performance. CONCLUSION: MICs worsen prognosis and should be managed as suggested by the algorithm. However, this algorithm must be externally validated. The clinical impact of isolated tumor cells (ITC) remains unclear.

Protocol of Breast Cancer Prevention Model with Addition of Breast Ultrasound to Routine Gynecological Visits as a Chance for an Early Diagnosis and Treatment in 25 to 49-Year-Old Polish Females.

The low attendance rate for cancer screening tests in Poland is a major healthcare concern that requires specific analysis and the development of implementation recommendations for prevention, and both actions are likely to benefit culturally similar countries. Four female cancers account for approximately 20% of all cancer cases-breast cancer, cervical cancer, endometrial cancer, and ovarian cancer-suggesting that gynecologists have a significant preventative role. Of the four, breast cancer and cervical cancer are among the 10 most common malignant neoplasms globally, regardless of gender, occur only in women and are known to have effective screening measures. Our research aims to create a screening model that combines cervical cancer and breast cancer to maximize health outcomes for women at risk of both cancers. In the study protocol, we have created a model that maximizes benefits for patients with minimal additional costs to the health care system. To achieve the set goal, instead of regular clinical breast exams as recommended by the gynecological societies, we proposed an ultrasound examination, during which palpation may also be performed (in the absence of elastography). We present a scheme for such a protocol that takes into consideration all types of prevention in both cancers, and that emphasizes breast ultrasound as the most frequently missing element. Our study includes a discussion of the strengths and weaknesses of our strategy, and the crucial need for infrastructure and education for the successful implementation of the program. We conclude that our model merits consideration and discussion among health-care decision makers, as the screening changes we propose have significant potential benefits for the female population.

Breastfeeding vs. Formula Feeding and Maternal Sexuality among Polish Women: A Preliminary Report.

Although postpartum sexual problems are common, there is a poor understanding of the underlying influencing factors and the impact of the infant feeding method on the mother's sexual life. A cross-sectional control study was conducted with a group of 253 women during their postpartum period. This study aimed to investigate the effects of different infant feeding methods on female sexual life after childbirth. The study followed the STROBE guidelines for cross-sectional control analysis. The study design included a questionnaire characterizing sociodemographic, obstetric and breastfeeding variables and the PL-FSFI (Female Sexual Function Index). The authors collected the data in compliance with the CAWI (Computer-Assisted Web Interview) research methodology-an interview conducted via an Internet channel. Each respondent received and completed the survey provided to them via the same online link. This study included women in the postpartum period: 170 breastfeeding women (study group) and 83 formula-feeding women (control group). There were statistically significant difference between the groups that practiced different types of breastfeeding. Out of all the PL-FSFI-assessing domains, the highest average score for the whole group correlated with satisfaction and the lowest score correlated with lubrication use. Our findings indicate that women practicing only breastfeeding are more likely to develop sexual problems. In order to maintain sexual health and promote long-term breastfeeding, extensive and professional counseling is needed for couples about postpartum sexuality and the factors that affect it, such as breastfeeding.

Incorporation of Tumor-Free Distance and Other Alternative Ultrasound Biomarkers into a Myometrial Invasion-Based Model Better Predicts Lymph Node Metastasis in Endometrial Cancer: Evidence and Future Prospects.

Myometrial invasion (MI) is a parameter currently used in transvaginal ultrasound (TVS) in endometrial cancer (EC) to determine local staging; however, without molecular diagnostics, it is insufficient for the selection of high-risk cases, i.e., those with a high risk of lymph node metastases (LNM). The study's objective was to answer the question of which TVS markers, or their combination, reflecting the molecular changes in EC, can improve the prediction of LNM. Methods: The TVS examination was performed on 116 consecutive EC patients included in this prospective study. The results from the final histopathology were a reference standard. Univariate and multivariate logistic models of analyzed TVS biomarkers (tumor [T] size, T area [AREA], T volume [SPE-VOL], MI, T-free distance to serosa [TFD], endo-myometrial irregularity, [EMIR], cervical stromal involvement, CSI) were evaluated to assess the relative accuracy of the possible LNM predictors., Spline functions were applied to avoid a potential bias in assuming linear relations between LNM and continuous predictors. Calculations were made in R using libraries splines, glmulti, and pROC. Results: LNM was found in 20 out of the 116 (17%) patients. In univariate analysis, only uMI, EMIR, uCSI and uTFD were significant predictors of LNM. The accuracy was 0.707 (AUC 0.684, 95% CI 0.568−0.801) for uMI (p < 0.01), 0.672 (AUC 0.664, 95% CI 0.547−0.781) for EMIR (p < 0.01), 0.776 (AUC 0.647, 95% CI 0.529−0.765) for uCSI (p < 0.01), and 0.638 (AUC 0.683, 95% CI 0.563−0.803) for uTFD (p < 0.05). The cut-off value for uTFD was 5.2 mm. However, AREA and VOL revealed a significant relationship by nonlinear analysis as well. Among all possible multivariate models, the one comprising interactions of splines of uTFD with uMI and splines of SPE-VOL with uCSI showed the most usefulness. Accuracy was 0.802 (AUC 0.791, 95% CI 0.673−0.91) Conclusions: A combination of uTFD for patients with uMI > 50%, and SPE-VOL for patients with uCSI, allows for the most accurate prediction of LNM in EC, rather than uMI alone.

A shared fate: adapting and personalising medical care from the perspective of a refugee reception country.

The article outlines socio-medical challenges faced by a country hosting refugees. Since the full-scale Russian invasion, more than 3.6 million Ukrainians have fled to Poland. Among these, a 9-year-old post-transplant patient, Tetiana. The story of the girl and her family reveals the refugees', the authors', and other doctors' varied attitudes towards the war. Considering differences between the Polish and Ukrainian health care systems, and the need for well-coordinated and effective assistance, a professional, and realistically financed system needs to be established. The presence of Ukrainian doctors is potentially advantageous because of the shared language with Ukrainian refugees. Notwithstanding the medical community's demonstrable solidarity, the months of effort and the awareness that many people may not be helped may result in burnout. Supporting others starts with us, so that neither poor management, nor cultural differences or simple fatigue, undermine the community cohesion that Poles and Ukrainians can build together.

Thousands of Women's Lives Depend on the Improvement of Poland's Cervical Cancer Screening and Prevention Education as Well as Better Networking Strategies Amongst Cervical Cancer Facilities.

Proper targeted cancer prophylaxis reduces the incidence of cancer in all forms; this includes cancers with significant progression potential and poor prognosis. Based on the assumption that one of the risk factors of cervical cancer is the avoidance of screening tests, we analyzed the current scenario of cervical cancer (CC) screening and recommendations in Poland (country with a well-off socioeconomic status). Based on the comprehensive literature review concerning documents of guidelines and recommendations of various bodies, including national ones, data on the implementation of CC screening in Poland, and different models for medium-to-high-income countries, we proposed how the CC screening strategy could be improved. Finally, the new strategy was further developed for those who are prone to not being screened. The proposal on how to improve the Polish CC screening program is the following: refinement of the public education on CC risk factors, popularization of CC screening incentives amongst the public, and improvement of networking strategies between CC screening facilities ("cervical screening clinical"), allowing screenings to be more efficient and rapid. We believe that, to enhance the future quality of life of those with rapid CC progression by catching the disease preemptively and limiting the sequelae of the disease, we have to improve education and access to medical services.

Clinical impact of low-volume lymph node metastases in early-stage cervical cancer: A comprehensive meta-analysis.

OBJECTIVE: In order to define the clinical significance of low-volume metastasis, a comprehensive meta-analysis of published data and individual data obtained from articles mentioning micrometastases (MIC) and isolated tumor cells (ITC) in cervical cancer was performed, with a follow up of at least 3 years. METHODS: We performed a systematic literature review and meta-analysis, following Cochrane's review methods guide and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The primary outcome was the disease-free survival (DFS), and the secondary outcome was the overall survival (OS). The hazard ratio (HR) was taken as the measure of the association between the low-volume metastases (MIC+ITC and MIC alone) and DFS or OS; it quantified the hazard of an event in the MIC (+/- ITC) group compared to the hazard in node-negative (N0) patients. A random-effect meta-analysis model using the inverse variance method was selected for pooling. Forest plots were used to display the HRs and risk differences within individual trials and overall. RESULTS: Eleven articles were finally retained for the meta-analysis. In the analysis of DFS in patients with low-volume metastasis (MIC + ITC), the HR was increased to 2.60 (1.55-4.34) in the case of low-volume metastasis vs. N0. The presence of MICs had a negative prognostic impact, with an HR of 4.10 (2.71-6.20) compared to N0. Moreover, this impact was worse than that of MIC pooled with ITCs. Concerning OS, the meta-analysis shows an HR of 5.65 (2.81-11.39) in the case of low-volume metastases vs. N0. The presence of MICs alone had a negative effect, with an HR of 6.94 (2.56-18.81). CONCLUSIONS: In conclusion, the presence of MIC seems to be associated with a negative impact on both the DFS and OS and should be treated as MAC.

Ultrasound Measurement of Tumor-Free Distance from the Serosal Surface as the Alternative to Measuring the Depth of Myometrial Invasion in Predicting Lymph Node Metastases in Endometrial Cancer.

BACKGROUND: Ultrasonography's usefulness in endometrial cancer (EC) diagnosis consists in its roles in staging and prediction of metastasis. Ultrasound-measured tumor-free distance from the tumor to the uterine serosa (uTFD) is a promising marker for these diagnostic and prognostic variables. The aim of the study was to determine the usefulness of this biomarker in locoregional staging, and thus in the prediction of lymph node metastasis (LNM). METHODS: We conducted a single-institutional, prospective study on 116 consecutive patients with EC who underwent 2D transvaginal ultrasound examination. The uTFD marker was compared with the depth of ultrasound-measured myometrial invasion (uMI). Univariable and multivariable logit models were evaluated to assess the predictive power of the uTFD and uMI in regard to LNM. The reference standard was a final histopathology result. Survival was assessed by the Kaplan-Meier method. RESULTS: LNM was found in 17% of the patients (20/116). In the univariable analysis, uMI and uTFD were significant predictors of LNM. The accuracy was 70.7%, and the NPV was 92.68% (OR 4.746, 95% CI 1.710-13.174) for uMI (p = 0.002), and they were 63.8% and 89.02% (OR 0.842, 95% CI 0.736-0.963), respectively, for uTFD (p = 0.01). The cutoff value for uTFD in the prediction of LNM was 5.2 mm. The association between absence of LNM and biomarker values of uMI < 1/2 and uTFD ≥ 5.2 mm was greater than that between the presence of metastases and uMI > 1/2 and uTFD values <5.2 mm. In the multivariable analysis, the accuracy of the uMI-uTFD model was 74%, and its NPV was 90.24% (p = non-significant). Neither uMI nor uTFD were surrogates for overall and recurrence-free survivals in endometrial cancer. CONCLUSIONS: Both uMI and uTFD, either alone or in combination, were valuable tools for gaining additional preoperative information on expected lymph node status. Negative lymph nodes status was better described by ultrasound biomarkers than a positive status. It was easier to use the uTFD rather than the uMI measurement as a biomarker of EC invasion, and the former still maintained a similar predictive value for lymph node metastases to the latter at diagnosis.

Factors limiting the detection of sentinel lymph nodes in early-stage cervical cancer.

OBJECTIVES: Sentinel lymph node detection (SLND) has not yet displaced lymphadenectomy, but it is a desired supplementary technique in cervical cancer surgery. The aim of our study was to identify the sources of SLND failure while performing the procedure by injecting blue dye (BD) into the cervix in cases of early-stage cervical cancer (ECC). MATERIAL AND METHODS: We analyzed 27 consecutive ECC patients (FIGO IA2-IB1) who underwent hysterectomy with SLND and systematic lymphadenectomy between October 2011 and June 2014. The main inclusion criterion was at least unilateral SLND by BD. Predictors of either unilateral or bilateral staining were identified using multinomial logit models and a decision tree. RESULTS: Overall, bilateral staining was achieved in nine patients (33%). Among the factors analyzed, BMI > 23.5 kg/m2 was the only factor negatively affecting the quality of SLND using BD (p < 0.02) in the univariable multinomial logit model. All patients with BMI < 23.5 kg/m2 and depth of invasion ≥ 15 mm had unilateral mapping. CONCLUSIONS: Both obese and overweight patients are unlikely to achieve optimal SLN staining with BD alone. Although some possible reasons are discussed, we believe that further studies are needed to clarify the specific limitations of other dyes currently in use.

Diabetic Mastopathy. Review of Diagnostic Methods and Therapeutic Options.

Diabetic mastopathy is a rare breast condition that may occur in insulin-treated men and women of any age. The etiology is still unclear; however, the autoimmunological background of the disease is highly suspected. The changes in diabetic mastopathy may mimic breast cancer; therefore, its diagnostic process is demanding, and treatment options are not clear and limited. Lesions in DM are usually multiple; therefore, surgical removal is not fully effective. A well-done anamnesis with core-needle biopsy is essential and definitive in most cases. In this review, we summarize up-to-date knowledge of diagnostic methods and therapeutic options for diabetic mastopathy treatment and present three cases of diabetic mastopathy-type lesions in ultrasound and radiological examinations.

BARD1 and Breast Cancer: The Possibility of Creating Screening Tests and New Preventive and Therapeutic Pathways for Predisposed Women.

Current oncological developments are based on improved understanding of genetics, and especially the discovery of genes whose alterations affect cell functions with consequences for the whole body. Our work is focused on the one of these genes, BRCA1-associated RING domain protein 1 (BARD1), and its oncogenic role in breast cancer. Most importantly, the study points to new avenues in the treatment and prevention of the most frequent female cancer based on BARD1 research. The BARD1 and BRCA1 (BReast CAncer type 1) proteins have similar structures and functions, and they combine to form the new molecule BARD1-BRCA1 heterodimer. The BARD1-BRCA1 complex is involved in genetic stabilization at the cellular level. It allows to mark abnormal DNA fragments by attaching ubiquitin to them. In addition, it blocks (by ubiquitination of RNA polymerase II) the transcription of damaged DNA. Ubiquitination, as well as stabilizing chromatin, or regulating the number of centrosomes, confirms the protective cooperation of BARD1 and BRCA1 in the stabilization of the genome. The overexpression of the oncogenic isoforms BARD1ß and BARD1δ permit cancer development. The introduction of routine tests, for instance, to identify the presence of the BARD1ß isoform, would make it possible to detect patients at high risk of developing cancer. On the other hand, introducing BARD1δ isoform blocking therapy, which would reduce estrogen sensitivity, may be a new line of cancer therapy with potential to modulate responses to existing treatments. It is possible that the BARD 1 gene offers new hope for improving breast cancer therapy.

New therapeutic approaches in the treatment of node-positive cervical cancer patients based on molecular targets: a systematic review.

Cervical uterine cancer is the second most frequent female cancer worldwide and a substantial burden for low-income societies and the patients themselves. Understanding the molecular mechanisms of metastasis permits the development of therapies that limit tumor progression, as well as providing health and social benefits. Pathomorphology is still the basis of research and a reference standard for molecular analysis. The aim of our study was to research and critically evaluate clinical trials that use new oncological approaches for node-positive cervical cancer to gain an insight into the molecular mechanisms of tumor metastasis. INCLUSION CRITERIA: node-positive disease at baseline; at least a first phase clinical study comprising adult female patients; novel clinical approach (e.g., radiotherapy, immunotherapy, targeted therapy, vaccines, radiosurgery); histologic measurement of treatment efficacy (preferably lymph node ultrastaging); and publications in English language only. INFORMATION SOURCES: US Clinical trials registry, EU Clinical trials register, ISRCTN registry, and Ovid, EBSCO and Cochrane Collaboration databases. Access dates: from January 2010 to April 2018. EXCLUSIONS: Abstracts that did not meet the inclusion criteria or with unreliable data. We collected complete data (e.g., the entire publication associated with included abstracts, heterogeneity examination of individual studies, and validity measurement of the statistical methods used). Results were analyzed in relation to the most recent understanding of the pathogenesis of cervical cancer metastasis. We proposed a possible direction for drug treatment of epithelial tumors based on the mechanisms of metastasis.

The impact of low volume lymph node metastases and stage migration after pathologic ultrastaging of non-sentinel lymph nodes in early-stage cervical cancer: a study of 54 patients with 4.2 years of follow up.

OBJECTIVES: To assess the significance of pathologic ultrastaging (PU) of sentinel (SLN) and non-sentinel (nSLN) lymph nodes (LNs) and the influence on cancer staging in patients with International Federation of Gynecology and Obstetrics (FIGO) stage IA2-IB1 cervical cancer. MATERIAL AND METHODS: A retrospective study was conducted with 54 patients divided into two equal-sized groups. In test group (n1), at least one SLN/patient was detected with blue dye. All excised LNs in this group were subjected to PU (4 µm slices/150 µm intervals) with hematoxylin-eosin staining and immunohistochemistry (AE1-AE3 antibodies). In none of the control group (n2) was PU performed, but in 2 patients SLN concept was performed. Patients in both groups underwent radical hysterectomy and lymphadenectomy. The effect of PU was expressed in puTNM and compared with both standard pTNM and FIGO systems. The influence of PU on patients' disease-free survival (DFS) and overall survival (OS) was assessed using Kaplan-Meier curves. RESULTS: In total, 516 LNs were extracted (66 SLNs, 36% bilaterally). Micrometastases (MIC) or isolated tumor cells (ITC) were detected in 34 of the 482 LNs (7.1%), including 16 MICs and 9 ITC in non-SLNs. False negative rates were: 3.7%/side-specific, and 7.4%/both sides. The use of PU resulted in stage change in 2 cases (N and M status change), FIGO stage did not changed. No PU impact on DFS or OS was observed. CONCLUSIONS: The risk of TNM stage migration in early cervical cancer is low, is more likely in inattentively evaluated patients, and has indeterminate prognostic and predictive value. Selection of cases with cT ≤ 2 cm and cN0 is sufficient to avoid the risk of improper staging.

Spectrum and Prevalence of Pathogenic Variants in Ovarian Cancer Susceptibility Genes in a Group of 333 Patients.

Constitutional loss-of-function pathogenic variants in the tumor suppressor genes BRCA1 and BRCA2 are widely associated with an elevated risk of ovarian cancer (OC). As only ~15% of OC individuals carry the BRCA1/2 pathogenic variants, the identification of other potential OC-susceptibility genes is of great clinical importance. Here, we established the prevalence and spectrum of the germline pathogenic variants in the BRCA1/2 and 23 other cancer-related genes in a large Polish population of 333 unselected OC cases. Approximately 21% of cases (71/333) carried the BRCA1/2 pathogenic or likely pathogenic variants, with c.5266dup (p.Gln1756Profs*74) and c.3700_3704del (p.Val1234Glnfs*8) being the most prevalent. Additionally, ~6% of women (20/333) were carriers of the pathogenic or likely pathogenic variants in other cancer-related genes, with NBN and CHEK2 reported as the most frequently mutated, accounting for 1.8% (6/333) and 1.2% (4/333) of cases, respectively. We also found ten pathogenic or likely pathogenic variants in other genes: 1/333 in APC, 1/333 in ATM, 2/333 in BLM, 1/333 in BRIP1, 1/333 in MRE11A, 2/333 in PALB2, 1/333 in RAD50, and 1/333 in RAD51C, accounting for 50% of all detected variants in moderate- and low-penetrant genes. Our findings confirmed the presence of the additional OC-associated genes in the Polish population that may improve the personalized risk assessment of these individuals.

Mucinous borderline ovarian tumor: a case report with diagnostic insights on ultrasound findings.

Borderline ovarian tumors represent about 10% of all epithelial ovarian cancers, but in contrast to epithelial ovarian cancers, they constitute a group of tumors with a much better prognosis. An assessment of clinical presentation, physical examination, radiological and biochemical findings is necessary to tailor management strategies for patients with ovarian tumors. The article, which is based on a case report, describes different approaches for preoperative diagnosis as well as discusses approaches that might bring some insights on tumor histology. Furthermore, it raises a question about which imaging techniques should be proposed for a reliable diagnosis of borderline ovarian tumors to ensure safe surgery planning.