Recurrent Endometrial Cancer: Which Is the Best Treatment? Systematic Review of the Literature

Background: Endometrial cancer is the most common gynaecological tumour in developed countries. The overall rate of relapse has remained unchanged in recent decades. Recurrences occur in approximately 20% of endometrioid and 50% of non-endometrioid cases. The aim of this systematic review is to compare different therapeutic strategies in the treatment of endometrial cancer recurrence to evaluate their prognostic and curative effects based on site and type of recurrence. Methods: This systematic review of literature was conducted in accordance with the PRISMA guidelines. The study protocol was registered on PROSPERO (CRD42020154042). PubMed, Embase, Chocrane and Cinahl databases were searched from January 1995 to September 2021. Five retrospective studies were selected. Results: A total of 3571 studies were included in the initial search. Applying the screening criteria, 299 articles were considered eligible for full-text reading, of which, after applying the exclusion criteria, 4 studies were selected for the final analysis and included in the systematic review. No studies were included for a quantitative analysis. We divided the results according to the location of the recurrence: locoregional recurrence, abdominal recurrence and extra abdominal recurrence. Conclusion: the treatment of choice should be assessed according to the relapse location and to the presence of single or multiple lesions. A crucial role in the decision-making algorithm is also the type of adjuvant treatment received at the time of the first diagnosis

Leptin Administration Favors Muscle Mass Accretion by Decreasing FoxO3a and Increasing PGC-1α in ob/ob Mice

Absence of leptin has been associated with reduced skeletal muscle mass in leptin-deficient ob/ob mice. The aim of our study was to examine the effect of leptin on the catabolic and anabolic pathways regulating muscle mass. Gastrocnemius, extensor digitorum longus and soleus muscle mass as well as fiber size were significantly lower in ob/ob mice compared to wild type littermates, being significantly increased by leptin administration (P<0.001). This effect was associated with an inactivation of the muscle atrophy-related transcription factor forkhead box class O3 (FoxO3a) (P<0.05), and with a decrease in the protein expression levels of the E3 ubiquitin-ligases muscle atrophy F-box (MAFbx) (P<0.05) and muscle RING finger 1 (MuRF1) (P<0.05). Moreover, leptin increased (P<0.01) protein expression levels of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), a regulator of muscle fiber type, and decreased (P<0.05) myostatin protein, a negative regulator of muscle growth. Leptin administration also activated (P<0.01) the regulators of cell cycle progression proliferating cell nuclear antigen (PCNA) and cyclin D1, and increased (P<0.01) myofibrillar protein troponin T. The present study provides evidence that leptin treatment may increase muscle mass of ob/ob mice by inhibiting myofibrillar protein degradation as well as enhancing muscle cell proliferation

Comparative effectiveness and safety of non-vitamin K antagonists for atrial fibrillation in clinical practice: GLORIA-AF Registry

Background and purpose: Prospectively collected data comparing the safety and effectiveness of individual non-vitamin K antagonists (NOACs) are lacking. Our objective was to directly compare the effectiveness and safety of NOACs in patients with newly diagnosed atrial fibrillation (AF). Methods: In GLORIA-AF, a large, prospective, global registry program, consecutive patients with newly diagnosed AF were followed for 3&nbsp;years. The comparative analyses for (1) dabigatran vs rivaroxaban or apixaban and (2) rivaroxaban vs apixaban were performed on propensity score (PS)-matched patient sets. Proportional hazards regression was used to estimate hazard ratios (HRs) for outcomes of interest. Results: The GLORIA-AF Phase III registry enrolled 21,300 patients between January 2014 and December 2016. Of these, 3839 were prescribed dabigatran, 4015 rivaroxaban and 4505 apixaban, with median ages of 71.0, 71.0, and 73.0&nbsp;years, respectively. In the PS-matched set, the adjusted HRs and 95% confidence intervals (CIs) for dabigatran vs rivaroxaban were, for stroke: 1.27 (0.79–2.03), major bleeding 0.59 (0.40–0.88), myocardial infarction 0.68 (0.40–1.16), and all-cause death 0.86 (0.67–1.10). For the comparison of dabigatran vs apixaban, in the PS-matched set, the adjusted HRs were, for stroke 1.16 (0.76–1.78), myocardial infarction 0.84 (0.48–1.46), major bleeding 0.98 (0.63–1.52) and all-cause death 1.01 (0.79–1.29). For the comparison of rivaroxaban vs apixaban, in the PS-matched set, the adjusted HRs were, for stroke 0.78 (0.52–1.19), myocardial infarction 0.96 (0.63–1.45), major bleeding 1.54 (1.14–2.08), and all-cause death 0.97 (0.80–1.19). Conclusions: Patients treated with dabigatran had a 41% lower risk of major bleeding compared with rivaroxaban, but similar risks of stroke, MI, and death. Relative to apixaban, patients treated with dabigatran had similar risks of stroke, major bleeding, MI, and death. Rivaroxaban relative to apixaban had increased risk for major bleeding, but similar risks for stroke, MI, and death. Registration: URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01468701, NCT01671007. Date of registration: September 2013

Anticoagulant selection in relation to the SAMe-TT2R2 score in patients with atrial fibrillation. the GLORIA-AF registry

Aim: The SAMe-TT2R2 score helps identify patients with atrial fibrillation (AF) likely to have poor anticoagulation control during anticoagulation with vitamin K antagonists (VKA) and those with scores &gt;2 might be better managed with a target-specific oral anticoagulant (NOAC). We hypothesized that in clinical practice, VKAs may be prescribed less frequently to patients with AF and SAMe-TT2R2 scores &gt;2 than to patients with lower scores. Methods and results: We analyzed the Phase III dataset of the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF), a large, global, prospective global registry of patients with newly diagnosed AF and ≥1 stroke risk factor. We compared baseline clinical characteristics and antithrombotic prescriptions to determine the probability of the VKA prescription among anticoagulated patients with the baseline SAMe-TT2R2 score &gt;2 and ≤ 2. Among 17,465 anticoagulated patients with AF, 4,828 (27.6%) patients were prescribed VKA and 12,637 (72.4%) patients an NOAC: 11,884 (68.0%) patients had SAMe-TT2R2 scores 0-2 and 5,581 (32.0%) patients had scores &gt;2. The proportion of patients prescribed VKA was 28.0% among patients with SAMe-TT2R2 scores &gt;2 and 27.5% in those with scores ≤2. Conclusions: The lack of a clear association between the SAMe-TT2R2 score and anticoagulant selection may be attributed to the relative efficacy and safety profiles between NOACs and VKAs as well as to the absence of trial evidence that an SAMe-TT2R2-guided strategy for the selection of the type of anticoagulation in NVAF patients has an impact on clinical outcomes of efficacy and safety. The latter hypothesis is currently being tested in a randomized controlled trial. Clinical trial registration: URL: https://www.clinicaltrials.gov//Unique identifier: NCT01937377, NCT01468701, and NCT01671007

Detection of Arcobacter spp. in the Coastal Environment of the Mediterranean Sea

The occurrence of Arcobacter spp. was studied in seawater and plankton samples collected from the Straits of Messina, Italy, during an annual period of observation by using cultural and molecular techniques. A PCR assay with three pairs of primers targeting the 16S and 23S rRNA genes was used for detection and identification of Arcobacter butzleri, Arcobacter cryaerophilus, and Arcobacter skirrowii in cultures and environmental samples. Only one of the Arcobacter species, A. butzleri, was isolated from seawater and plankton samples. With some samples the A. butzleri PCR assay gave amplified products when cultures were negative. A. cryaerophilus and A. skirrowii were never detected by culture on selective agar plates; they were detected only by PCR performed directly with environmental samples. Collectively, our data suggest that culturable and nonculturable forms of Arcobacter are present in marine environments. The assay was useful for detecting Arcobacter spp. both as free forms and intimately associated with plankton. This is the first report showing both direct isolation of A. butzleri and the presence of nonculturable Arcobacter spp. in the coastal environment of the Mediterranean Sea

Induction and Resuscitation of Viable Nonculturable Arcobacter butzleri Cells▿

Two strains of Arcobacter butzleri, ATCC 49616 and an environmental isolate, became nonculturable in seawater microcosms at 4°C by 20 days and at room temperature by 14 days. Nonculturable cells were viable for up to 270 days of incubation in microcosms. Resuscitation of A. butzleri cells from microcosms at both temperatures was achieved 9 days after nutrient addition

Intra-operative assessment of sentinel lymph node status by one-step nucleic acid amplification assay (OSNA) in early endometrial cancer: A prospective study

Background Sentinel node mapping has been proposed to reduce surgical side effects, maintaining the accuracy in nodal status assessment for endometrial cancer. Objective To investigate the role of one-step nucleic acid amplification assay (OSNA) analysis, in the intra-operative tailoring of full nodal dissection, and to analyze the correlation between the type of sentinel node metastasis and the risk of non-sentinel node metastasis. Methods Surgical and pathological data were collected from 141 consecutive, clinical stage I patients with endometrial cancer undergoing surgical staging. Patients were excluded if they had previous pelvic or abdominal radiotherapy, chemotherapy, abdominal cancer, pelvic or abdominal lymphadenectomy, or contraindications to indocyanine green. All sentinel nodes were analyzed by OSNA, and full lymphadenectomy was performed in positive cases. Statistical analysis was performed using \uce\ua7 2 and Fisher's exact test to determine whether any of these characteristics could accurately predict the non-sentinel nodes status in positive sentinel node patients. Results A total of 141 patients were included in the analysis. Bilateral sentinel nodes were identified in 104 (73.8%) patients, with a median number of 2 (range 2-6) sentinel nodes per patient. In the remaining 37 patients (26.2%), a unilateral sentinel node was obtained, with a median of 1 (range 1-3) sentinel node per patient. Thirty-three (12.0%) positive nodes were found in 24 (17.0%) patients: micro-metastases and macro-metastases were detected in 22 and 2 patients, respectively. At final pathology, all patients with positive non-sentinel nodes had macro-metastases in the sentinel node, whereas in micro-metastatic sentinel nodes no other positive nodes were found at full lymphadenectomy (p&lt;0.001). Conclusions Our results showed a correlation between the type of metastasis in the sentinel lymph node (SLN) and the incidence of positive non-SLNs. These data suggest a potential role of OSNA analysis in the surgical tailoring of patients with early endometrial cancer, with the goal of definitive risk stratification and a better individualization of adjuvant therapy

Sentinel lymph node detection in endometrial cancer with indocyanine green: laparoscopic versus robotic approach

Background: The aims of the present study were to assess bilateral sentinel lymph node (SLN) mapping with laparoscopic versus robotic approach, to assess variables affecting bilateral detection rates and to assess survival difference in patients with no/unilateral, compared to bilateral SLN detection.Methods: This is a retrospective, single-centre, observational cohort study, including patients with endometrial cancer FIGO stage IA-IVB, treated with minimally invasive primary surgery and undergoing indocyanine green (ICG) injection to detect SLN, between January 2015 and December 2019.Results: Of the 549 included patients, 286 (52.1%) and 263 (47.9%) underwent the laparoscopic and robotic approach respectively. 387 (70.5%) patients had bilateral SLN mapping, 102 ( 18.6%) and 60 (10.9%) had unilateral and no mapping, respectively. Patients who underwent the robotic approach were older (median 61 versus 64 years, p=0.046) and had a higher BMI (median 26.0 versus 34.8 kg/m(2), p&lt;0.001). No difference in any SLN mapping or in SLN bilateral detection was evident between the laparoscopic or robotic approach (p=0.892 and p=0.507 respectively). Patients with bilateral SLN detection in the entire cohort were younger (p&lt;0.001) and had a better 3-year disease- free survival (DFS) compared to patients with no/unilateral SLN mapping (77.0% versus 66.3%, respectively, p=0.036). No 3-year overall survival (OS) difference was reported (p=0.491).Conclusion: SLN mapping and bilateral SLN detection with ICG in endometrial cancer was not different in the laparoscopic and robotic approach, even though patients undergoing the robotic approach were older and more obese. Bilateral SLN detection was associated with improved 3-year DFS, but not with 3-year OS, compared to no and unilateral SLN detection