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The Hatter Cardiovascular Institute biennial workshop, originally scheduled for April 2020 but postponed for 2 years due to the Covid pandemic, was organised to debate and discuss the future of Remote Ischaemic Conditioning (RIC). This evolved from the large multicentre CONDI-2–ERIC–PPCI outcome study which demonstrated no additional benefit when using RIC in the setting of ST-elevation myocardial infarction (STEMI). The workshop discussed how conditioning has led to a significant and fundamental understanding of the mechanisms preventing cell death following ischaemia and reperfusion, and the key target cyto-protective pathways recruited by protective interventions, such as RIC. However, the obvious need to translate this protection to the clinical setting has not materialised largely due to the disconnect between preclinical and clinical studies. Discussion points included how to adapt preclinical animal studies to mirror the patient presenting with an acute myocardial infarction, as well as how to refine patient selection in clinical studies to account for co-morbidities and ongoing therapy. These latter scenarios can modify cytoprotective signalling and need to be taken into account to allow for a more robust outcome when powered appropriately. The workshop also discussed the potential for RIC in other disease settings including ischaemic stroke, cardio-oncology and COVID-19. The workshop, therefore, put forward specific classifications which could help identify so-called responders vs. non-responders in both the preclinical and clinical settings.

Inflammatory cell infiltration is central to healing after acute myocardial infarction (AMI). The relation of regional inflammation to edema, infarct size (IS), microvascular obstruction (MVO), intramyocardial hemorrhage (IMH), and regional and global LV function is not clear. Here we noninvasively characterized regional inflammation and contractile function in reperfused AMI in pigs using fluorine (19F) cardiovascular magnetic resonance (CMR). Adult anesthetized pigs underwent left anterior descending coronary artery instrumentation with either 90 min occlusion (n = 17) or without occlusion (sham, n = 5). After 3 days, in surviving animals a perfluorooctyl bromide nanoemulsion was infused intravenously to label monocytes/macrophages. At day 6, in vivo 1H-CMR was performed with cine, T2 and T2* weighted imaging, T2 and T1 mapping, perfusion and late gadolinium enhancement followed by 19F-CMR. Pigs were sacrificed for subsequent ex vivo scans and histology. Edema extent was 35 ± 8% and IS was 22 ± 6% of LV mass. Six of ten surviving AMI animals displayed both MVO and IMH (3.3 ± 1.6% and 1.9 ± 0.8% of LV mass). The 19F signal, reflecting the presence and density of monocytes/macrophages, was consistently smaller than edema volume or IS and not apparent in remote areas. The 19F signal-to-noise ratio (SNR) > 8 in the infarct border zone was associated with impaired remote systolic wall thickening. A whole heart value of 19F integral (19F SNR × milliliter) > 200 was related to initial LV remodeling independently of edema, IS, MVO, and IMH. Thus, 19F-CMR quantitatively characterizes regional inflammation after AMI and its relation to edema, IS, MVO, IMH and regional and global LV function and remodeling.

A long-standing aim in the setting of various pathologies including acute myocardial infarction, chronic kidney disease (CKD), and ischaemic stroke, has been to identify successful approaches to augment cellular and organ protection. Although the continual evolution and refinement of ideas over the past few decades has allowed the field to progress, we are yet to realise successful clinical translation of this concept. The 12th Hatter Cardiovascular Workshop identified a number of important points and key questions for future research relating to cardio- and neuro-protection and interorgan communication. Specific topics that were discussed include the ‘cardio-metabolic-renal’ axis of organ protection, the parasympathetic signalling hypothesis, the role of the coronary microvasculature in myocardial infarction, the RISK pathway of cardioprotection, extracellular vesicles and the way forward, the future for clinical studies of remote ischaemic conditioning, and new experimental models for cardio-oncology investigations.

Introduction/Background*The aim of this study was to correlate the serum concentrations of tumor markers HE4 and CA125 with the tumor burden evaluated through the volumetric parameters of FDG-PET/CT FDG in patients with advanced epithelial ovarian cancer (EOC) before primary treatment.MethodologySixty-six patients with advanced stage high grade serous ovarian carcinoma (HGSOC) or undifferentiated carcinoma (UOC) were included. Serum HE4, serum CA125 and FDG PET/CT were performed before primary treatment. Volumes of interest (VOIs) were delimited on every pathological uptake in PET images. Whole-body metabolic tumor volume (wbMTV) and total lesion glycolysis (wbTLG) were calculated as the sum of every single VOI value. SUVmax thresholds were set at 40% and 50%. Four VOIs subgroups were defined for analysis: carcinomatosis, retroperitoneal, supradiaphragmatic and metastases. MTV and TLG values were calculated for each of them. The associations between these parameters and serum tumor markers were assessed through Pearson and Spearman tests.Result(s)*When correlating wbMTV and wbTLG with both CA125 and HE4, significant associations were found. The strongest correlation was observed between HE4 and wbMTV40% (r=0.61, p<0.001). Peritoneal carcinomatosis MTV exhibited a statistically significant correlation with both tumor markers. Pearson’s correlation coefficient was 0.61 (p<0.0001) between HE4 and MTV40% and 0,29 (p=0.02) between CA125 and MTV40%. Neither the retroperitoneal nor the supradiaphragmatic or metastatic disease assessed by MTV and TLG showed any correlation with these tumor markers.Conclusion*Peritoneal tumor burden measured by FDG PET/CT volumetric parameters correlates better with HE4 than with CA125 in patients with advanced epithelial ovarian cancer. These results support the increasing utility of HE4 to improve the stratification of these patients in clinical practice

Introduction/Background*The combination of improved survival and delaying child bearing increases the trend of early cervical cancer diagnosis in women without a fulfilled gestational wish. Fertility preservation surgery (FSS) becomes a necessary treatment option for young women.The aim of this study is to analyze the impact of tumor size on surgical and oncological outcomes of FSS in early cervical cancer in Spain.MethodologyA multicenter, retrospective cohort study of early cervical cancer (IA2- IB1, FIGO 2009) patients with gestational desire who underwent FSS was carried out at the departments of gynecology of 12 tertiary care hospitals between 01/2005 and 01/2019 throughout Spain. The data were registered in an on-line database. All analyses were performed using STATA 15 statistical softwareResult(s)*A total of 111 patients who underwent trachelectomy were included, 82 (73.9%) of them with tumors < 2 cm and 29 (26.1%) of them ≥ 2 cm. Patients’ characteristics were balanced except linfovascular space infiltration (LVSI). All patients were intraoperative node negative. There were no significant differences between groups regarding surgical approach, performance of a posterior cerclage, intraoperative complications or need of posterior hysterectomy.Median follow-up was 55.7 months in patients group <2 cm tumor and 30.7 months in group ≥2 cm. Eleven recurrences were diagnosed (9.9%), 5 (6.0%) in the <2cms tumor group and 6 (21.4%) in the ≥ 2cms tumor group (p<0.05).Cox regression was performed to identify different predictor factor for recurrence. Only tumor size (<2cm vs. ≥2cms) was found to be significant among histology, LVSI, previous conization or surgical approach. After adjusting for the rest of the variables, tumor size ≥2cm has a Hazard Ratio of 5.99 (CI 95% 1.01-35.41, p=0.036)Conclusion*This study shows a real world data of a large number of trachelectomies performed in patients with early cervical cancer after negative lymphnode assessment. Selection criteria should be rigorous especially for patients with tumor ≥ 2 cm due to its worse oncological outcomes. Options may be discussed with the patient to reach a balance between the risk of recurrence and the best fertility results

Introduction/Background*Ovarian cancer is the eighth most frequent cancer worldwide. Although the vast majority of ovarian cancers are diagnosed in postmenopausal women and at advanced stage, a significant subset occurs in younger women. Our objective is to describe the diagnosis and treatment of ovarian cancer in young women in a tertiary Spanish hospital during a 7-year period.MethodologyRetrospective descriptive cohort study of patients aged between 18 and 45 years old diagnosed with ovarian cancer between 01/2012 and 12/2019 at University Hospital 12 de Octubre, Madrid, Spain.Result(s)*A total of 34 women were included. The mean age at diagnosis was 35.9 years old and the mean body mass index (BMI) was 23.7 kg/m2. 22/34 (64.7%) women were nulligesta; 6/34 (17.6%) had a family history of breast/ovarian cancer; 7/34 (19.6%) were smokers and 3/34 (7.8%) were BRCA mutated.The mean tumor’s size in presurgical imaging workup (ultrasound, CT or MRI scan) was 110.1 ± 68.5mm. The mean Ca-125 serum concentration was 128.4 U/mL in FIGO stages I-II and 393.7 U/mL in FIGO stages III-IV.The diagnostic method was adnexectomy in 79.4% of the patients; 55.9% performed by laparotomy. 29/34 (85.3%) patients presented epithelial tumours (20.6% low-grade serous, 14.7% high-grade serous, 17.6% mucinous, 14.7% clear cells, 14.7% endometrioid) and 5/34 non epithelial (5.9% dysgerminoma and 11.8% other non epithelial histology). 23/34 (67.6%) patients were diagnosed at FIGO stages I-II.In patients with FIGO stage III-IV, 4/11 (36.4%) of patients underwent primary cytoreductive surgery and 6/11 (54.5%) of patients underwent surgery after neoadjuvant chemotherapy. Complete tumor resection was obtained in 90.9% of all surgeries. Fertility preservation was possible in 7/34 patients (20.6%).Mean follow up time was 48.4 ± 24.7 months. Five patients (14.7%) relapsed, one patient (3.4%) died because of disease and one patient (3.4%) died because other disease.At the time of last follow up, 28/34 (82.4%) women were tumor free, 2/34 (5.8%) were alive with disease, 2/34 (5.8%) were lost in the follow up.Conclusion*As reported in literature, women under 45 years old are often diagnosed with early stage ovarian cancer and present optimal survival results with low recurrence rate.

A critical step in the metastatic cascade is the survival of circulating tumor cells (CTCs) within the bloodstream. Although interactions between CTCs and various hematopoietic cells have been described, the role of red blood cells (RBCs) remains underexplored. This study investigated the interactions between tumor cells and RBCs from breast and lung cancer patients, revealing significant phenotypic and functional changes in tumor cells, unlike interactions with RBCs from healthy donors. Tumor cell and patient-derived RBC co-cultures increased tumor cell attachment and induced morphological changes. RBC-primed tumor cells showed increased adhesion, disruption of the endothelial barrier, and invasiveness, both in vitro and in vivo. Global proteome changes, including actin remodeling and VASP accumulation at cell edges, promote directional migration. RBCs from patients with metastatic breast cancer also upregulate PAK4, enhancing migration and epithelial-mesenchymal transition, whereas PAK4 inhibition reduces these effects. Clinically, a higher red blood cell distribution width (RDW) in patients with metastasis is associated with increased CTC counts and poor outcomes. This study highlights the previously unrecognized role of RBCs in promoting metastatic behavior in cancer cells and suggests potential therapeutic targets, such as PAK4, to counteract these effects.

Introduction/Background*The goal of this study is to review the sentinel lymph node (SLN) in endometrial cancer in the University Hospital 12 de Octubre in Madrid from June 2016 to October 2020. The aim is to know the demographic and clinical features of the patients and to assess the outcomes of SLN in our population with technetium99 (Tc99), indocyanine green (ICG) or blue dye.MethodologyResult(s)*From June 2016 to October 2020, 166 patients diagnosed with endometrial cancer underwent surgery in our hospital. In 34.4% (n= 57) of them SLN was performed and included in this review.Demographic and clinical features are shown in table 1. 80.7% (n=46) were classified as low risk endometrial cancer and 19,3% (n=11) as intermediate risk.Laparoscopy was the most frequent approach (96.4%). Median operative time was 203 minutes (IQR, 173 to 249).A combined tracer technique was used in 75.4% cases. Most of them combining Tc99 and ICG (64.9%). Tc99 and blue dye were used in 10.5%. Only one tracer was used in 24.6% (Tc99 5.3%; ICG 17.5%; blue dye 1.8%). Cervix was the only injection site into submucosa and stroma.In 89.5% of the patients, tracer migration was observed. Only 6 patients (10.5%) had no migration. In table 2, detection and migration data of the tracers are shown.One hundred forty-four SLNs were detected. Right side (52.8%) was slightly more frequent than left side (47.2%). Most SLNs were located in external iliac area (40.5%), followed by iliac bifurcation (25.3%), obturator fossa (17.7%) and common iliac (13.9%).In three patients isolated tumor cells were detected (5.2%) and one patient had macrometastases (1.8%). 93% of the patients had no pathological findings in SLNs.Age was significantly higher in the no migration/no detection group in both Tc99 (70 vs 58.5 years; p= 0.01) and ICG/blue dye (72.5 vs 59.4 years; p=0.034). No migration/detection differences were detected for other patient´s features.Abstract 680 Table 1Demographic and clinical features of the 57 included patientsAbstract 680 Table 2Tracer detection and migration for Tc99 and ICG/Blue dyeConclusion*A combined tracer technique is an effective method to detect SLNs in low-risk endometrial cancer to check lymphatic spread. Older women in our series have lower tracer migration/detection.

Introduction/Background*Lower limb lymphoedema (LLL) is the most disabling adverse effect of surgical staging of pelvic lymph nodes. In studies, LLL is often assessed by calculation of limb volumes based on five circumference measurements. However, the lack of standardisation of this method hinders direct comparison between the studies and makes LLL reporting unreliable. The aim of our study is to report outcomes from a prospective SENTIX trial that have implications for the standardisation of LLL assessment.MethodologyIn the prospective international multicentre trial SENTIX (ENGOT-cx2/CEEGOG CX-01), a group of 150 patients with stage IA1–IB2 cervical cancer treated by uterine surgery with bilateral SLN biopsy was prospectively evaluated by objective LLL assessment, based on limb volume change (LVC) using circumferrential limb measurements and subjective patient-reported swelling. The assessments were conducted in six-month periods over 24 months post-surgery.Result(s)*Patient LVC substantially fluctuated in both positive and negative directions (figure 1), which were comparable in frequency up to 14% +/- LVC increments. Thirty-eight patients experienced persistent LVC increase and >10% classified as LLL, for whom median time to onset was nine months (95% CI: 7.0-11.0). Some 34.2% of cases experienced onset later than one year after the surgery. Thirty-three patients (22%) experienced transient oedema characterised as LVC >10%, which resolved without intervention between two consequent follow-up visits (figure 2). No significant correlation between LVC >10% and a patient-reported swelling was observed.Abstract 959 Figure 1Distribution of the limb volume change (from preoperative assesment; LVC) of right and left lower limb during the folloe-up-period. Each dot on the violin plot represents the LVC of one patient’s limb. 6M: six months post-surgery; 12M months post-surgery; 18M months post-surgery; 24M: 24 months post-surgery.Abstract 959 Figure 2Incidence of transient oedema. Each dot marks the transient oedema (>10% LVC increase from preoperative measurement) of one patient. Boxplots depict the median value of respective transient oedema LVI (%); the percentile range was set at 25% and 50%; the whisker is between minimal and maximal calculated value. FU; follow-up; LVC: limb volume change.Conclusion*Our study showed that lower-limb volumes after surgical treatment of cervical cancer significantly fluctuate in positive and negative directions. A diagnostic threshold for LLL should be increased to >15% LVC. Transient oedema occurs frequently, and its distinction from persistent LLL requires repeated measurements. One-third of new LLL cases were diagnosed in the second year of follow-up, highlighting the importance of a sufficient follow-up period duration. Finally, patient-reported limb swelling correlated poorly with LVC and should only be used as an adjunct to objective LLL assessment.