It is time to implement molecular classification in endometrial cancer.

A huge effort has been done in redefining endometrial cancer (EC) risk classes in the last decade. However, known prognostic factors (FIGO staging and grading, biomolecular classification and ESMO-ESGO-ESTRO risk classes stratification) are not able to predict outcomes and especially recurrences. Biomolecular classification has helped in re-classifying patients for a more appropriate adjuvant treatment and clinical studies suggest that currently used molecular classification improves the risk assessment of women with EC, however, it does not clearly explain differences in recurrence profiles. Furthermore, a lack of evidence appears in EC guidelines. Here, we summarize the main concepts why molecular classification is not enough in the management of endometrial cancer, by highlighting some promising innovative examples in scientific literature studies with a clinical potential significant impact.

Urological Complications in Radical Surgery for Cervical Cancer: A Comparative Meta-Analysis before and after LACC Trial.

BACKGROUND: After the LACC trial publication in 2018, the minimally invasive approach (MIS) has severely decreased in favor of open surgery: MIS radical hysterectomy was associated with worse oncological outcomes than open surgery, but urological complications were never extensively explored in pre- versus post-LACC eras, even if they had a great impact on post-operative QoL. The purpose of this meta-analysis is to compare functional and organic urological complication rates before and after LACC trial. METHODS: An independent search of the literature was conducted 4 years before and after the LACC trial and 50 studies were included. RESULTS: The overall rate of urologic complications was higher in pre-LACC studies while no differences were found for organic urological complications. Conversely, the overall risk of dysfunctional urological complications showed a higher rate in the pre-LACC era. This is probably related to a sudden shift to open surgery, with potential lower thermal damage to the urinary tract autonomic nervous fibers. CONCLUSIONS: This meta-analysis showed that the incidence of urological complications in radical cervical cancer surgery was higher before the LACC trial, potentially due to the shift to open surgery. Nevertheless, further studies are needed to shed light on the connection between minimally invasive surgery and urological damage.

Potential Protective Role of Pregnancy and Breastfeeding in Delaying Onset Symptoms Related to Multiple Sclerosis.

The impact of pregnancy and breastfeeding on the development and outcomes of Multiple sclerosis (MS) has been debated for decades. Since several factors can influence the evolution of the disease, the protective role of multiparity and breastfeeding remains uncertain, as well the role of hormone replacement therapy in the perimenopausal period. We report two cases of relatively late-onset MS in two parous women, who developed their first neurological symptoms after six and nine pregnancies, respectively. Both women breastfed each of their children for 3 to 12 months. One of them underwent surgical menopause and received hormone replacement therapy for 7 years before MS onset. We performed a systematic literature review to highlight the characteristics shared by women who develop the disease in similar conditions, after unique hormonal imbalances, and to collect promising evidence on this controversial issue. Several studies suggest that the beneficial effects of pregnancy and breastfeeding on MS onset and disability accumulation may only be realized when several pregnancies occur. However, these data on pregnancy and breastfeeding and their long-term benefits on MS outcomes suffer from the possibility of reverse causality, as women with milder impairment might choose to become pregnant more readily than those with a higher level of disability. Thus, the hypothesis that multiparity might have a protective role on MS outcomes needs to be tested in larger prospective cohort studies of neo-diagnosed women, evaluating both clinical and radiological features at presentation.

A randomized trial of goal directed vs. standard fluid therapy in cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.

The use of adequate fluid therapy during cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) remains controversial. The aim of the study was to assess whether the use of fluid therapy protocol combined with goal-directed therapy (GDT) is associated with a significant change in morbidity, length of hospital stay, and mortality compared to standard fluid therapy. Patients American Society of Anesthesiologists (ASA) II-III undergoing CRS and HIPEC were randomized into two groups. The GDT group (N = 38) received fluid therapy according to a protocol guided by monitored hemodynamic parameters. The control group (N = 42) received standard fluid therapy. We evaluated incidence of major complications, total length of hospital stay, total amount of fluids administered, and mortality rate. The incidence of major abdominal complications was 10.5% in GDT group and 38.1% in the control group (P = 0.005). The median duration of hospitalization was 19 days in GDT group and 29 days in the control group (P < 0.0001). The mortality rate was zero in GDT group vs. 9.5% in the control group (P = 0.12). GDT group received a significantly (P < 0.0001) lower amount of fluid (5812 ± 1244 ml) than the control group (8269 ± 1452 ml), with a significantly (P < 0.0001) lower volume of crystalloids (3884 ± 1003 vs. 68,528 ± 1413 ml). In CRS and HIPEC, the use of a GDT improves outcome in terms of incidence of major abdominal and systemic postoperative complications and length of hospital stay, compared to standard fluid therapy protocol.

Robotic single-site hysterectomy in low risk endometrial cancer: a pilot study.

BACKGROUND: To evaluate the feasibility and the safety of robotic single-site hysterectomy (RSSH) in low risk early endometrial cancer. METHODS: Patients with clinical low risk early endometrial cancer were enrolled onto a prospective cohort trial. All surgical procedures were performed through a single 2-2.5 cm umbilical incision, with a multichannel system consisting of a five-lumen port providing access for two single-site instruments (da Vinci Si Surgical System, Intuitive Surgical, Sunnyvale, CA), the 8.5 mm 3D HD endoscope, a 5/10 mm accessory port, and an insufflation adaptor. RESULTS: Between December 2011 and June 2012, a total of 17 patients were included in our pilot study. The median age of the patients was 64 years (range, 42-84 years), and median body mass index was 26.6 kg/m(2) (range, 18-52 kg/m(2)). One patient was excluded from the study as a result of pelvic metastasis during inspection of abdominal cavity, and another patient was converted to vaginal surgery as a result of problems of hypercapnia. The median docking time, console time, and total operative time was 8 min (range, 5-14 min), 48 min (range, 45-51 min), and 90 min (range, 70-147 min), respectively. The median blood loss was 75 mL (range, 50-150 mL). No laparoscopy/laparotomy conversion was registered. The median time to discharge was 2 days (range, 1-3 days). Neither intraoperative nor postoperative complications occurred. At a median of 7.5 months' follow-up, all patients were disease-free. CONCLUSIONS: RSSH is technically feasible in patients affected by low risk early endometrial cancer. Additional studies with gynecologic oncologic cases should be performed to explore the possible benefits of RSSH.

Immunomodulatory effects of total intravenous and balanced inhalation anesthesia in patients with bladder cancer undergoing elective radical cystectomy: preliminary results.

BACKGROUND: Although surgery and anesthesia induce immunesuppression, remains largely unknown whether various anesthetic techniques have different immunosuppressive effects on cancer patients. Therefore, the aim of this study was to investigate the influence of total intravenous anesthesia with target-controlled infusion (TIVA-TCI) and balanced inhalation anesthesia (BAL) on the peri-operative levels of inflammatory cytokines and regulatory T cells (Tregs) in patients with bladder cancer undergoing surgery. METHODS: Twenty eight consecutive patients with bladder cancer who underwent radical cystectomy were prospectively randomized into two groups to receive TIVA-TCI (n = 14) or BAL (n = 14). Before the induction of anesthesia (T0), 6-8 hours (T1) post-surgery, and 5 days post-surgery (T2), Tregs and serum levels of interleukin -1beta (IL-1ß), interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukin -2 (IL-2), interleukin -6 (IL-6), and interleukin -10 (IL-10) were measured. RESULTS: In the peri-operative period all cancer patients showed a marked and significant increase in IL-6. Moreover, TIVA-TCI patients also showed a higher increase in IFN-γ, whereas in BAL patients Tregs were reduced by approximately 30% during surgery. The incidence of infections, metastases, and death was similar in both groups. CONCLUSIONS: The increase in the Th1 response in the TIVA-TCI group and the reduction in Tregs in the BAL group seem to balance the immunosuppressive effect induced by IL-6. Therefore TIVA-TCI and BAL can be both used in major surgery in patients with bladder cancer without worsening the outcome.

The AtMYB11 gene from Arabidopsis is expressed in meristematic cells and modulates growth in planta and organogenesis in vitro.

In plants, MYB transcription factors play important roles in many developmental processes including cell cycle progression, cell differentiation, and lateral organ polarity. It is shown here that the R2R3-MYB AtMYB11 gene is expressed in root and shoot meristems and also in young still meristematic leaf and flower primordia of Arabidopsis. Knock-out atmyb11-I mutants and RNAi plants germinate faster, show a faster hypocotyl and primary root elongation, develop more lateral and adventitious roots, show faster development of the inflorescence, and initiate more lateral inflorescences and fruits than wild-type plants. The opposite phenotype was displayed by plants overexpressing AtMYB11. De novo formation of root meristemoids and, consequently, macroscopic roots, from thin cell layers cultured in vitro was enhanced in explants from atmyb11-I and reduced in those from lines overexpressing AtMYB11. These findings indicate that AtMYB11 modulates overall growth in plants by reducing the proliferation activity of meristematic cells and delaying plant development.