Essentiality of Trace Elements in Pregnancy, Fertility, and Gynecologic Cancers—A State-of-the-Art Review

Gynecological neoplasms pose a serious threat to women’s health. It is estimated that in 2020, there were nearly 1.3 million new cases worldwide, from which almost 50% ended in death. The most commonly diagnosed are cervical and endometrial cancers; when it comes to infertility, it affects ~48.5 million couples worldwide and the number is continually rising. Ageing of the population, environmental factors such as dietary habits, environmental pollutants and increasing prevalence of risk factors may affect the reproductive potential in women. Therefore, in order to identify potential risk factors for these issues, attention has been drawn to trace elements. Trace mineral imbalances can be caused by a variety of causes, starting with hereditary diseases, finishing with an incorrect diet or exposure to polluted air or water. In this review, we aimed to summarize the current knowledge regarding trace elements imbalances in the case of gynecologic cancers as well as female fertility and during pregnancy.

Understanding the Role and Clinical Applications of Exosomes in Gynecologic Malignancies: A Review of the Current Literature

Background: Gynecologic malignancies are those which arise in the female reproductive organs of the ovaries, cervix, and uterus. They carry a great deal of morbidity and mortality for patients, largely due to challenges in diagnosis and treatment of these cancers. Although advances in technology and understanding of these diseases have greatly improved diagnosis, treatment, and ultimately survival for patients with gynecologic malignancies over the last few decades, there is still room for improvements in diagnosis and treatment, for which exosomes may be the key. This paper reviews the current knowledge regarding gynecologic tumor derived-exosomal genetic material and proteins, their role in cancer progression, and their potential for advancing the clinical care of patients with gynecologic cancers through novel diagnostics and therapeutics. Literature Review: Ovarian tumor derived exosome specific proteins are reviewed in detail, discussing their role in ovarian cancer metastasis. The key microRNAs in cervical cancer and their implications in future clinical use are discussed. Additionally, uterine cancer-associated fibroblast (CAF)-derived exosomes which may promote endometrial cancer cell migration and invasion through a specific miR-148b are reviewed. The various laboratory techniques and commercial kits for the isolation of exosomes to allow for their clinical utilization are described as well. Conclusion: Exosomes may be the key to solving many unanswered questions, and closing the gaps so as to improve the outcomes of patients with gynecologic cancers around the world. The potential utilization of the current knowledge of exosomes, as they relate to gynecologic cancers, to advance the field and bridge the gaps in diagnostics and therapeutics highlight the promising future of exosomes in gynecologic malignancies.

Surgical Outcomes of Transperitoneal Para-Aortic Lymphadenectomy Compared With Extraperitoneal Approach in Gynecologic Cancers: A Systematic Review and Meta-Analysis

Purpose: The optimal surgical approach for para-aortic lymphadenectomy (PALND) in gynecologic cancers using minimally invasive surgery (laparoscopy or robotic-assisted) is controversial. This study summarizes the current evidence on the extraperitoneal (EP) approach and compares its perioperative, surgical outcomes, and complications to the transperitoneal (TP) approach in an updated meta-analysis.Methods: We performed a systematic search in PubMed, Embase, Web of Science, Cochrane Library database for randomized controlled trials (RCTs) and non-RCTs that compare EP to TP for PALND. The main outcomes included surgical, perioperative outcomes, and complications. The weighted mean difference (WMD) and odds ratio (OR) were applied for the comparison of continuous and dichotomous variables with 95% CIs. Three RCTs and 10 non-RCTs trials, including 2,354 patients were identified and enrolled in the meta-analysis.Results: A total of three RCTs and ten non-RCTs trials, including 2,354 patients were identified and enrolled in the meta-analysis. We reported similar results for EP and TP in terms of the hospital stay, estimated blood loss, blood transfusion, conversion to laparotomy, total operative time, and postoperative complications (Clavien grade ≥ 1 and Clavien grade ≥ 3). However, the PALND operative time (WMD −10.46 min, 95% CI −19.04, −1.88; p = 0.02) and intraoperative complications (OR 0.40, 95% CI 0.23, 0.69; p = 0.001) were less with EP. Also, more nodes were removed in EP compared with the TP (WMD 1.45, 95% CI 0.05, 2.86; p = 0.04).Conclusions: The EP approach did not show differences regarding surgical and perioperative parameters compared with the TP approach. However, the number of aortic nodes retrieved was higher. Furthermore, The PALND operative time and intraoperative complications were less in EP.

Indocyanine Green to Assess Vascularity of Ileal Conduit Anastomosis During Pelvic Exenteration for Recurrent/Persistent Gynecological Cancer: A Pilot Study

IntroductionPelvic exenteration performed for recurrent/persistent gynecological malignancies has been associated with urological short- and long-term morbidity due to altered vascularization of tissues for previous radiotherapy. The aims of the present study were to describe the use of intravenous indocyanine green (ICG) to assess vascularity of urinary diversion (UD) after pelvic exenteration for gynecologic cancers, to evaluate the feasibility and safety of this technique, and to assess the postoperative complications.MethodsProspective, observational, single-center, pilot study including consecutive patients undergoing anterior or total pelvic exenteration due to persistent/recurrent gynecologic cancers between August 2020 and March 2021 at Fondazione Policlinico Gemelli IRCCS, Rome, Italy. All patients underwent intravenous injection of 3–6 ml of ICG (1.25 mg/ml) once the UD was completed. A near-infrared camera was used to evaluate ICG perfusion of anastomoses (ileum–ileum, right and left ureter with small bowel, and colostomy or colorectal sides of anastomosis) a few seconds after ICG injection.ResultsFifteen patients were included in the study. No patient reported adverse reactions to ICG injection. Only 3/15 patients (20.0%) had an optimal ICG perfusion in all anastomoses. The remaining 12 (80.0%) patients had at least one ICG deficit; the most common ICG deficit was on the left ureter: 3 (20.0%) vs. 1 (6.7%) patient had no ICG perfusion on the left vs. right ureter, respectively (p = 0.598). 8/15 (53.3%) and 6/15 (40.0%) patients experienced grade ≥3 30-day early and late postoperative complications, respectively. Of these, two patients had early and one had late postoperative complications directly related to poor perfusion of anastomosis (UD leak, ileum–ileum leak, and benign ureteric stricture); all these cases had a suboptimal intraoperative ICG perfusion.ConclusionThe use of ICG to intraoperatively assess the anastomosis perfusion at time of pelvic exenteration for gynecologic malignancy is a feasible and safe technique. The different vascularization of anastomotic stumps may be related to anatomical sites and to previous radiation treatment. This approach could be in support of selecting patients at higher risk of complications who may need personalized follow-up.