Sentinel lymph node biopsy for breast cancer during pregnancy: A comprehensive update.

BACKGROUND: Pregnant patients diagnosed with breast cancer (PrBC) may receive substantially different treatments compared to general population, considering that certain treatment options cannot be applied during pregnancy due to their potential harmful effects to the foetus. Regarding the use of sentinel lymph node biopsy (SLNB) in pregnant patients, potential concerns include foetal harm from radiation exposure, possible teratogenic effects of blue dyes and maternal anaphylaxis to isosulfan. OBJECTIVE: The main objective of the present systematic review is to summarize and present current knowledge and up-to-date evidence about the safety and efficacy of SLNB in PABC. METHODS: MEDLINE, Google Scholar and UpToDate databases were searched up to 22 January 2023. Articles studying the safety and effectiveness of SLNB in patients for PrBC were eligible for inclusion in the present review. RESULTS: In total, 63 articles that met the inclusion criteria were included in this study. Forty-seven articles were strongly in favour of performing SLNB in PABC, 4 articles were partially in favour, 10 articles were strongly against and 2 articles were partially against performing SLNB in PABC. Sub-categorization based on type of study showed that the majority of studies in favour were of higher level of evidence than those against. Furthermore, there were overall 12 studies reporting on outcomes. There were overall 382 women with PrBC that underwent SLNB. Full data were reported for 237 cases. Overall live birth rate was 95.8%, while overall neonatal complication rate was 3.4%. No case of maternal side effects or anaphylactic reaction, maternal death, stillbirth and neonatal death was reported (0%). CONCLUSIONS: Sentinel lymph node biopsy seems to be safe and effective technique for breast cancer during pregnancy.

Breast Carcinogenesis during Pregnancy: Molecular Mechanisms, Maternal and Fetal Adverse Outcomes.

Breast cancer is a common type of cancer diagnosed during pregnancy, with increasing incidence over the last years, as more women choose to delay childbearing. Compared to breast cancer in general population, pregnancy-associated breast cancer (PABC) is significantly different in its terms of epidemiology, diagnostic and therapeutic management, while it exhibits particularly aggressive behavior, deriving from its unique molecular and biological profile. Although not fully elucidated, the pathophysiological basis of PABC can be traced back to a combination of hormonal and immune changes during pregnancy, breast involution and altered gene expression. There is considerable controversy in the existing literature about the influence of PABC on pregnancy outcomes, regarding both short- and long-term effects on maternal and fetal/neonatal health. The majority of PABC patients have advanced-stage disease at initial diagnosis and face a significantly poorer prognosis, with decreased survival rates. The most commonly reported adverse obstetrical-fetal events are preterm delivery and prematurity-associated neonatal morbidity, while other neonatal treatment-associated complications might also occur, even when safe therapeutic options are applied during pregnancy. The objective of the present comprehensive review was to summarize current knowledge and up-to-date evidence about the pathophysiological, molecular and biological basis of PABC, as well as its association with adverse maternal, obstetrical, fetal and neonatal outcomes.

Therapeutic Management and Prognostic Factors for Ovarian Malignant Tumours in Adolescents: A Comprehensive Review of Current Guidelines.

Background: Ovarian malignant tumours are rarely diagnosed in adolescents but may have a significant impact on their survival, future fertility and quality of life. The management of such cases is rather complex and requires expertise and careful planning according to scarce existing evidence and recommendations. Objective: The aim of this study was to review and compare recommendations from published guidelines regarding the diagnosis, prognosis and treatment of malignant ovarian tumours in adolescents. Evidence acquisition: A comparative descriptive/narrative review of guidelines issued by L'Observatoire des Tumeurs Malignes Rares Gynécologiques, the British Society for Paediatric & Adolescent Gynaecology, the European Society for Medical Oncology, the European Society of Gynecological Oncology-European Society for Paediatric Oncology and the European Cooperative Study Group for Pediatric Rare Tumors was conducted. Results: All guidelines recommend a thorough diagnostic work-up, consisting of both imaging tests and serum tumour marker measurement, as well as the use of immunohistochemical methods to confirm the diagnosis and complete surgical staging prior to constructing the treatment plan. There is a lack of recommendations regarding the assessment of prognostic factors, with only one guideline providing detailed information. Treatment strategies, as suggested by the majority of guidelines and with only a few discrepancies between them, should include both surgery and adjuvant therapies, mainly chemotherapy, with great emphasis on fertility preservation when it is considered oncologically safe and on the significance of regular and long-term follow-up. Conclusions: There is a significant degree of agreement among recommendations of existing guidelines. The reported differences, although limited, highlight the need for the adoption of an international consensus in order to further improve the management of adolescent ovarian cancer.

Sarcoma Botryoides: Optimal Therapeutic Management and Prognosis of an Unfavorable Malignant Neoplasm of Female Children.

Embryonal rhabdomyosarcoma (ERMS) is a rare malignancy and occurs primarily in the first two decades of life. Botryoid rhabdomyosarcoma is an aggressive subtype of ERMS that often manifests in the genital tract of female infants and children. Due to its rarity, the optimal treatment approach has been a matter of debate. We conducted a search in the PubMed database and supplemented it with a manual search to retrieve additional papers eligible for inclusion. We retrieved 13 case reports and case series, from which we summarized that the current trend is to approach each patient with a personalized treatment plan. This consists of a combination of local debulking surgery and adjuvant or neoadjuvant chemotherapy (NACT). Effort is made in every approach to avoid radiation for the sake of preserving fertility. Radical surgeries and radiation still have a role to play in extensive disease and in cases of relapse. Despite the rarity and aggressiveness of this tumor, disease-free survival and overall prognosis is excellent, especially when it is diagnosed early, compared with other subtypes of rhabdomyosarcoma (RMS). We conclude that the practice of a multidisciplinary approach is appropriate, with favorable outcomes; however, larger-scale studies need to be organized to have a definite consensus on optimal management.

Contraceptive methods in adolescence: a narrative review of guidelines.

PURPOSE: Adolescent pregnancy, while recently in decline, remains a matter in need of addressing. Education and counselling are deemed crucial and this review aims at comparing published contraceptive guidelines, thus resolving any surrounding misconceptions. MATERIALS AND METHODS: Recently published contraception guidelines regarding adolescent pregnancy were retrieved. In particular, guidelines and recommendations from ACOG, RCOG, SOCG, AAP, CPS, NICE, CDC, and WHO were compared and reviewed based on each guideline's method of reporting. RESULTS: Three categories of contraceptive methods are available for adolescents and recommendations on their initiation should be made based on their efficacy, according to all guidelines. Therefore, long acting reversible contraceptives (LARCs) should be highly recommended as the most effective method (typical use failure rate: 0.05%), followed by short-acting hormonal contraceptives (typical use failure rate: 3-9%). The third contraceptive option includes contraceptives used in the moment of intercourse and displays the lowest effectiveness (typical use failure rate: 12-25%), mostly due to its dependence on personal consistency, however offers protection against STI transmission. CONCLUSION: Adolescents should be encouraged to initiate contraception, with LARCs being the primary choice followed by short-acting hormonal contraception. However, regardless of the chosen effective contraceptive method, the use of condom is necessary for STI prevention.

Adolescent pregnancy, while recently in decline, remains a matter in need of addressing. The use of contraceptive methods such as LARCs and short-acting hormonal contraceptives should be encouraged and suggested based on effectiveness with the addition of condom for STI prevention.

Sentinel Lymph Node Staging in Early-Stage Cervical Cancer: A Comprehensive Review.

Cervical cancer (CC) continues to be a significant global public health concern, even with preventive measures in place. In women with early-stage CC, the status of lymph nodes is of paramount importance, not only for the final prognosis but also for determining the best therapeutic strategy. According to main international guidelines, pelvic full lymphadenectomy (PLND) is recommended for lymph node staging. However, in these early stages of CC, sentinel lymph node biopsy (SLNB) has emerged as a precise technique for evaluating lymph node involvement, improving its morbidity profile. We performed a literature review through PubMed articles about progress on the application of SLNB in women with early-stage CC focusing on the comparison with PET/CT and PLND in terms of oncological outcomes and diagnostic accuracy. While the superiority of SLNB is clear compared to radiologic modalities, it demonstrates no clear oncologic inferiority over PLND, given the higher detection rate of positive lymph nodes and predominance of no lymph node recurrences. However, due to a lack of prospective evidence, particularly concerning long-term oncological safety, SLNB is not the current gold standard. With careful patient selection and adherence to straightforward protocols, a low false-negative rate can be ensured. The aim of the ongoing prospective trials is to address these issues.

Sentinel lymph node mapping in endometrial cancer to reduce surgical morbidity: always, sometimes, or never.

Introduction: Surgical staging of nodal status is of utmost significance to determine the stage of endometrial cancer and construct a targeted treatment plan. Systematic lymphadenectomy has for years been the procedure of choice for staging purposes, enabling thorough assessment of lymph nodes. Nevertheless, it is associated with increased morbidity and severe postoperative complications. In an attempt to avoid the disadvantages of lymphadenectomy, the use of sentinel lymph node (SLN) biopsy has been examined as an alternative staging procedure.The purpose of the present review is to summarize and provide up-to-date evidence about the role of SLN biopsy in the staging and management of endometrial cancer cases in the terms of optimal technique, efficacy, safety, and postoperative morbidity, as an alternative approach to regional lymphadenectomy. Material and methods: A thorough literature search was conducted in MEDLINE and SCOPUS to identify recent primary research and previous review articles that explore the use of SLN mapping as a staging procedure in patients with endometrial cancer. Results: There is increasing evidence that SLN mapping is efficient in identifying metastatic nodal disease without compromising oncological safety, achieving comparable or even superior detection rates to those of lymphadenectomy, when optimal technique and careful intraoperative nodal assessment are applied. Conclusions: Sentinel lymph node mapping can safely replace lymphadenectomy as an acceptable alternative staging method for endometrial cancer; however, future research might further strengthen this suggestion by resolving potential areas of doubt and debate, especially for high-risk endometrial cancer cases.

Axillary lymph node dissection vs. sentinel node biopsy for early-stage clinically node-negative breast cancer: a systematic review and meta-analysis.

ΟBJECTIVE: This study aimed at comparing survival outcomes between systematic axillary lymph node dissection (ALND) vs sentinel lymph node and axillary lymph node dissection only if sentinel positive (SLN ± ALND) in early-stage, clinically node-negative breast cancer patients. ΜETHODS: A systematic review and meta-analysis adhered to PRISMA guidelines was performed. Included studies were prospective randomized controlled trials (RCTs) comparing survival outcomes of ALND vs. SLN ± ALND in early-stage, node-negative breast cancer patients. Patients enrolled were only those with tumor size lower than 4 cm, clinically negative nodes and treated with breast-conservative surgery. Primary endpoints were locoregional recurrence, overall death and cancer-related death. RESULTS: There were four studies included in the analysis, enrolling overall 2982 patients, of which 1494 in ALND arm and 1488 in the SLN ± ALND arm. No statistically significant difference was observed in locoregional recurrence, breast cancer-related death and overall death. Locoregional recurrence was observed in 2.8% (ALND) vs. 4.1% (SLND ± ALND), (RR 0.69, 95% CI 0.20-2.30). Overall death rate was 7.0% vs. 6.8% respectively, (RR 1.00, 95% CI 0.73-1.39, I2 = 28.7%). Breast cancer-related death was 3.6% vs. 3.5%, respectively (SLN ± ALND), (RR 1.11, 95% CI 0.70-1.78, I2 = 0%). No statistically significant difference was observed in any of secondary study outcomes. CONCLUSIONS: Systematic axillary axillary lymph node dissection provides no survival benefit compared with sentinel lymph node dissection for early-stage clinically node-negative breast cancer patients.

The role of endoglin and its soluble form in pathogenesis of preeclampsia.

Preeclampsia remains till today a leading cause of maternal and fetal morbidity and mortality. Pathophysiology of the disease is not yet fully elucidated, though it is evident that it revolves around placenta. Cellular ischemia in the preeclamptic placenta creates an imbalance between angiogenic and anti-angiogenic factors in maternal circulation. Endoglin, a transmembrane co-receptor of transforming growth factor ß (TGF-ß) demonstrating angiogenic effects, is involved in a variety of angiogenesis-dependent diseases with endothelial dysfunction, including preeclampsia. Endoglin expression is up-regulated in preeclamptic placentas, through mechanisms mainly induced by hypoxia, oxidative stress and oxysterol-mediated activation of liver X receptors. Overexpression of endoglin results in an increase of its soluble form in maternal circulation. Soluble endoglin represents the extracellular domain of membrane endoglin, cleaved by the action of metalloproteinases, predominantly matrix metalloproteinase-14. Released in circulation, soluble endoglin interferes in TGF-ß1 and activin receptor-like kinase 1 signaling pathways and inhibits endothelial nitric oxide synthase activation, consequently deranging angiogenesis and promoting vasoconstriction. Due to these properties, soluble endoglin actively contributes to the impaired placentation observed in preeclampsia, as well as to the pathogenesis and manifestation of its clinical signs and symptoms, especially hypertension and proteinuria. The significant role of endoglin and soluble endoglin in pathophysiology of preeclampsia could have prognostic, diagnostic and therapeutic perspectives. Further research is essential to extensively explore the potential use of these molecules in the management of preeclampsia in clinical settings.

Neoadjuvant chemotherapy in advanced-stage ovarian cancer - state of the art.

Ovarian cancer represents the fifth cause of cancer death among women, carrying one of the worst prognoses among gynaecological malignancies. The need to achieve no residual disease after surgery in order to optimize prognosis of advanced-stage ovarian cancer introduced the idea of neoadjuvant chemotherapy. The present review aims to summarize current state-of-the-art evidence regarding the efficacy and safety of neoadjuvant chemotherapy as well as novel insights regarding the usage of modern therapeutic regimens in the context of neoadjuvant chemotherapy. The last decade has been characterized by the breakthrough scientific evidence that neoadjuvant chemotherapy followed by interval debulking surgery for advanced-stage ovarian cancer may be comparable to primary debulking surgery. Neoadjuvant chemotherapy followed by interval debulking surgery is an acceptable - if not preferable - therapeutic approach in advanced-staged ovarian cancer patients because it is associated with higher optimal debulking surgery, fewer complications, and non-inferior survival outcomes. The addition of bevacizumab to chemotherapy contributes significantly to survival outcomes without causing side effects that outbalance the benefits. Patients with recurrent high-grade serous ovarian cancer and a germline or breast cancer mutation should be offered maintenance olaparib after a response to platinum-based chemotherapy. Finally, the role of hyperthermic intraperitoneal chemotherapy in the context of neoadjuvant chemotherapy remains unjustified.

Micro-RNA Implications in Type-1 Diabetes Mellitus: A Review of Literature.

Type-1 diabetes mellitus (T1DM) is one of the most well-defined and complex metabolic disorders, characterized by hyperglycemia, with a constantly increasing incidence in children and adolescents. While current knowledge regarding the molecules related to the pathogenesis and diagnosis of T1DM is vast, the discovery of new molecules, such as micro ribonucleic acids (micro-RNAs, miRNAs), as well as their interactions with T1DM, has spurred novel prospects in the diagnosis of the disease. This review aims at summarizing current knowledge regarding miRNAs' biosynthesis and action pathways and their role as gene expression regulators in T1DM. MiRNAs follow a complex biosynthesis pathway, including cleaving and transport from nucleus to cytoplasm. After assembly of their final form, they inhibit translation or cause messenger RNA (mRNA) degradation, resulting in the obstruction of protein synthesis. Many studies have reported miRNA involvement in T1DM pathogenesis, mainly through interference with pancreatic b-cell function, insulin production and secretion. They are also found to contribute to ß-cell destruction, as they aid in the production of autoreactive agents. Due to their elevated accumulation in various biological specimens, as well as their involvement in T1DM pathogenesis, their role as biomarkers in early preclinical T1DM diagnosis is widely hypothesized, with future studies concerning their diagnostic value deemed a necessity.

Soluble endoglin concentration in maternal blood as a diagnostic biomarker of preeclampsia: A systematic review and meta-analysis.

OBJECTIVE: Preeclampsia is a main cause of maternal and fetal morbidity and mortality. Research about maternal circulating diagnostic biomarkers is continuously performed, often with conflicting results that necessitate quantitative synthesis. Objective of this meta-analysis is to examine the value of soluble endoglin as predictor of preeclampsia separately at each pregnancy trimester, therefore exploring its potential usage as diagnostic biomarker in preeclampsia. STUDY DESIGN: This systematic review and meta-analysis adhered to PRISMA and MOOSE guidelines. MEDLINE, SCOPUS, Cochrane CENTRAL and ClinicalTrials.gov were searched up to April 20, 2020. Included studies were those comparing soluble endoglin levels in maternal serum or plasma at any pregnancy trimester, between women who subsequently developed preeclampsia and normotensive pregnant women being low-risk for preeclampsia development. Primary outcome was development of preeclampsia, while soluble endoglin levels in 1 st, 2nd and 3rd trimester of pregnancy were examined as possible predictors of preeclampsia. Subgroup analysis was performed regarding time of preeclampsia onset (early, late). Methodological quality of included studies was assessed using Newcastle-Ottawa scale. Overall quality of evidence for primary and secondary outcomes was evaluated using GRADEpro GD tool. RESULTS: There were overall 20 studies included in meta-analysis, enrolling 1146 preeclamptic and 1675 normotensive pregnant women. Soluble endoglin concentration (ng/mL) was significantly higher in preeclamptic women during 2nd (8 studies, MD:5.554, 95 %CI:2.671-8.436, P < .001, I2 = 97 %) and 3rd trimester (12 studies, MD:31.006, 95 %CI:24.734-37.278, P < .001, I2 = 98 %). Levels were also higher during 1st trimester; however, the difference was marginally not significant (MD:1.105, 95 %CI: -0.071 to 2.282, P = .06, I2 = 64 %). Furthermore, levels were significantly higher both in early-onset and late-onset preeclamptic vs normotensive pregnancies, (4 studies, MD:51.611, 95 %CI:2.250-100.972, P = .04, I2 = 97 %), (5 studies, MD:12.426, 95 %CI:7.863-16.989, P < .001, I2 = 98 %) respectively. However, when comparing directly early and late-onset preeclamptic women, no significant difference was detected (3 studies, MD:20.725, 95 %CI: -11.601 to 53.052, P = .209, I2 = 93 %). CONCLUSIONS: Soluble endoglin levels were consistently higher in preeclamptic compared to normotensive pregnant women almost throughout pregnancy. Our results firmly indicate soluble endoglin's potential use as predictor of preeclampsia. Further studies are required to support the use of soluble endoglin as a diagnostic tool for preeclampsia in clinical settings.

Circulating serum and plasma levels of micro-RNA in type-1 diabetes in children and adolescents: A systematic review and meta-analysis.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is a complex metabolic disorder characterized by hyperglycaemia, with constantly increasing incidence in paediatric population. The discovery of new molecules, such as microRNAs, and their possible interactions with T1DM create novel aspects in the diagnosis of the disease. METHODS: This systematic review and meta-analysis adhered to PRISMA guidelines. MEDLINE, SCOPUS, Cochrane CENTRAL and Clinicaltrials.gov. were searched up to 20 April 2020. Inclusion criteria for individual studies were quantification of microRNAs in serum/plasma samples and study groups consisting of children and adolescents with T1DM and healthy controls. Primary outcome of the study was the qualitative expression of microRNAs between the two groups. Statistical analysis was performed with Comprehensive Meta-Analysis Software v3.0. Methodological quality of included studies was assessed using Newcastle-Ottawa scale. RESULTS: A total of 484 studies were retrieved from the initial search of the databases. These were subsequently limited to seven included studies. Seven microRNAs demonstrated contrasting expression between the two groups, with two of them showing significant overexpression in T1DM group (miR-181:95% CI: 0.429 to 1.341 P < .001, miR-210:95% CI: 0.381 to 0.852, P < .001) and one micro-RNA being significantly overexpressed in control group (miR-375:95% CI: 0.293 to 1.459, P = .003). CONCLUSION: A total of three micro-RNA molecules appeared to have a significantly different expression in T1DM patients, serving as a possible diagnostic panel of biomarkers. These findings may contribute as reference for future research to further support the use of microRNAs as a novel diagnostic tool in T1DM.