Optimizing patient selection for secondary cytoreductive surgery in recurrent endometrial cancer.

OBJECTIVE: This retrospective, multicenter, observational study aimed to refine patient selection criteria for secondary cytoreductive surgery in recurrent endometrial cancer. The objective was to identify preoperative predictors of complete cytoreduction, assess surgical complexity, and propose a preoperative predictive scoring system to identify suitable candidates for secondary cytoreductive surgery. METHODS: Data from 331 women with recurrent endometrial cancer were analyzed across three Italian centers from January 2010 to December 2021. Patients were categorized based on treatment received (medical treatment, diagnostic laparoscopy/examination under anesthesia, or secondary cytoreductive surgery). Preoperative predictors, surgical complexity, complications, and a predictive scoring system were assessed. Logistic regression and receiver operating characteristic analysis were used for statistical evaluation. RESULTS: Of the cohort, 56.2% underwent debulking surgery, 17.2% had diagnostic laparoscopy, and 26.6% received medical treatment. Patients undergoing secondary cytoreductive surgery were younger, with a lower body mass index, better performance status, and fewer comorbidities. Single site locoregional relapse was common in secondary cytoreductive surgery patients. Age <65 years, single site relapse, lymph node, and hematogenous relapse were independent predictors of complete cytoreduction. A predictive scoring system demonstrated a clear relationship between the score and the likelihood of complete cytoreduction. CONCLUSION: This study identified age <65 years, single site recurrence, as well as nodal and hematogenous recurrence, as predictive factors for achieving optimal cytoreduction. A predictive scoring system incorporating these factors has been proposed to identify optimal candidates for secondary cytoreductive surgery in recurrent endometrial cancer. The scoring system showed promising predictive accuracy and could aid in refining the decision making process, ensuring appropriate patient selection for secondary cytoreductive surgery. Further prospective studies are warranted to validate and enhance the predictive model.

Sentinel node mapping, sentinel node mapping plus back-up lymphadenectomy, and lymphadenectomy in Early-sTage cERvical caNcer scheduled for fertilItY-sparing approach: The ETERNITY project.

OBJECTIVE: To investigate the safety of sentinel node mapping for patients with early-stage cervical cancer undergoing cervical conization plus nodal evaluation. METHODS: The ETERNITY project is a retrospective, multi-institutional study collecting data of patients with early-stage cervical cancer undergoing fertility-sparing treatment. Here, we compared outcomes related to three methods of nodal assessment: sentinel node mapping (SNM), SNM plus backup lymphadenectomy (SNM + LND); pelvic lymphadenectomy (LND). RESULTS: Charts of 123 patients (with stage IA1-IB1 cervical cancer) were evaluated. Median patients' age was 34 (range, 22-44) years. SNM, SNM + LND, and LND were performed in 32 (26 %), 31 (25.2 %), and 60 (48.8 %) patients, respectively. Overall, eight (6.5 %) patients were diagnosed with positive nodes. Two (3.3 %), three (9.7 %), and three (9.4 %) patients were detected in patients who had LND, SNM + LND, and SNM respectively. Considering the 63 patients undergoing SNM (31 SNM + LND and 32 SNM alone), macrometastases, micrometastases, and isolated tumor cells were detected in four (3.2 %), three (2.4 %), and one (0.8 %) patients, respectively. All patients with positive nodes discontinued the fertility sparing treatment. Other two patients (one (1.7 %) in the LND group and one (3.1 %) in the SNM group) required hysterectomy even after negative nodal evaluation. After a median follow-up of 53.6 (range, 1.3, 158.0) months, nine (7.3 %) and two (1.6 %) patients developed cervical and pelvic nodes recurrences, respectively. Disease-free (p = 0.332, log-rank test) and overall survival (p = 0.769, log-rank test) were similar among groups. CONCLUSIONS: In this retrospective experience, SNM upholds long-term oncologic effectiveness of LND, reducing morbidity.

Where Morphological and Molecular Classifications Meet: The Role of p53 Immunohistochemistry in the Prognosis of Low-Risk Endometrial Carcinoma (GLAMOUR Study).

No prospective study has validated molecular classification to guide adjuvant treatment in endometrial cancer (EC), and not even retrospective data are present for patients with morphological low-risk EC. We conducted a retrospective, multicenter, observational study including 370 patients with low-risk endometrioid EC to evaluate the incidence and prognostic role of p53 abnormal expression (p53abn) in this specific subgroup. Among 370 patients, 18 had abnormal expressions of p53 (4.9%). In 13 out of 370 patients (3.6%), recurrences were observed and two were p53abn. When adjusting for median follow-up time, the odds ratio (OR) for recurrence among those with p53abn versus p53 wild type (p53wt) was 5.23-CI 95% 0.98-27.95, p = 0.053. The most common site of recurrence was the vaginal cuff (46.2%). One recurrence occurred within the first year of follow-up, and the patient exhibited p53abn. Both 1-year and 2-year DFS rates were 94.4% and 100% in the p53abn and p53wt groups, respectively. One patient died from the disease and comprised p53wt. No difference in OS was registered between the two groups; the median OS was 21.9 months (16.4-30.1). Larger multicenter studies are needed to tailor the treatment of low-risk EC patients with p53abn. Performing molecular classification on all EC patients might be cost-effective, and despite the limits of our relatively small sample, p53abn patients seem to be at greater risk of recurrence, especially locally and after two years since diagnosis.

Concurrent endometrial cancer in atypical endometrial hyperplasia and the role of sentinel lymph nodes: clinical insights from a multicenter experience.

OBJECTIVE: This study aimed to evaluate the prevalence of concurrent endometrial cancer in patients pre-operatively diagnosed with atypical endometrial hyperplasia undergoing hysterectomy. Additionally, we assessed the occurrence of high to intermediate-risk and high-risk tumors according to the ESGO-ESTRO-ESP classification. The study also compared surgical outcomes and complications between patients undergoing simple hysterectomy and those undergoing hysterectomy with sentinel lymph node biopsy. METHODS: In this multicenter retrospective study, patients with a pre-operative diagnosis of atypical endometrial hyperplasia were identified and divided into two groups: Group 1, which included patients treated with total hysterectomy with or without bilateral salpingo-oophorectomy, and Group 2, where sentinel lymph node biopsy was incorporated into the standard surgical treatment. RESULTS: Among 460 patients with atypical endometrial hyperplasia, 192 received standard surgical management (Group 1) and 268 underwent sentinel lymph node biopsy (Group 2). A total of 47.2% (95% CI 42.6% to 51.7%) of patients were upgraded to endometrial cancer on final histopathological examination. High to intermediate-risk and high-risk tumors constituted 12.3% and 9.2% in Group 2 and 7.4% and 3.7% in Group 1. Lymph node metastases were identified in 7.6% of patients with concurrent endometrial cancer who underwent nodal assessment with at least unilateral mapping. Of the 12 sentinel lymph node metastases, 75.0% were micrometastases, 16.7% macrometastases, and 8.3% isolated tumor cells. No significant differences were found in estimated blood loss, operative time, and intra-operative and post-operative complications between the two groups. The rate of patients undergoing sentinel lymph node biopsy doubled every 2 years (OR 2.010, p<0.001), reaching 79.1% in the last 2 years. CONCLUSION: This study found a prevalence of concurrent endometrial cancer of 47.2%, and sentinel lymph node biopsy provided prognostic and therapeutic information in 60.8% of cases. It also allowed for the adjustment of adjuvant therapy in 12.3% of high to intermediate-risk patients without increasing operative time or complication rates.

Pattern of recurrence in endometrial cancer. The murderer always returns to the scene of the crime.

BACKGROUND: Endometrial cancer recurrence occurs in about 18 % of patients. This study aims to analyze the pattern recurrence of endometrial cancer and the relationship between the initial site of primary disease and the relapse site in patients undergoing surgical treatment. METHODS: We retrospectively reviewed all surgically treated patients with endometrial cancer selecting those with recurrence. We defined primary site disease as uterus, lymph nodes, or peritoneum according to pathology analysis of the surgical specimen. The site of recurrence was defined as vaginal cuff, lymph nodes, peritoneum, and parenchymatous organs. Our primary endpoint was to correlate the site of initial disease with the site of recurrence. RESULTS: The study enrolled 1416 patients. The overall recurrence rate was 17,5 % with 248 relapses included in the study. An increase of 9.9, 5.7, and 5.7 times in the odds of relapse on the lymph node, peritoneum, and abdominal parenchymatous sites respectively was observed in case of nodal initial disease (p < 0.001). A not significant difference in odds was observed in terms of vaginal cuff relapse (OR 0.9) between lymph node ad uterine primary disease (p = 0.78). An increasing OR of 8.7 times for nodal recurrences, 46.6 times for peritoneum, and 23.3 times for parenchymatous abdominal recurrences were found in the case of primary peritoneal disease (p < 0.001). CONCLUSION: Endometrial cancer tends to recur at the initial site of the disease. Intraoperative inspection of the adjacent sites of primary disease and targeted instrumental examination of the initial sites of disease during follow-up are strongly recommended.

Restoration of blood vessel regeneration in the era of combination SGLT2i and GLP-1RA therapy for diabetes and obesity.

Ischaemic cardiovascular diseases, including peripheral and coronary artery disease, myocardial infarction, and stroke, remain major comorbidities for individuals with type 2 diabetes (T2D) and obesity. During cardiometabolic chronic disease (CMCD), hyperglycaemia and excess adiposity elevate oxidative stress and promote endothelial damage, alongside an imbalance in circulating pro-vascular progenitor cells that mediate vascular repair. Individuals with CMCD demonstrate pro-vascular 'regenerative cell exhaustion' (RCE) characterized by excess pro-inflammatory granulocyte precursor mobilization into the circulation, monocyte polarization towards pro-inflammatory vs. anti-inflammatory phenotype, and decreased pro-vascular progenitor cell content, impairing the capacity for vessel repair. Remarkably, targeted treatment with the sodium-glucose cotransporter-2 inhibitor (SGLT2i) empagliflozin in subjects with T2D and coronary artery disease, and gastric bypass surgery in subjects with severe obesity, has been shown to partially reverse these RCE phenotypes. SGLT2is and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have reshaped the management of individuals with T2D and comorbid obesity. In addition to glucose-lowering action, both drug classes have been shown to induce weight loss and reduce mortality and adverse cardiovascular outcomes in landmark clinical trials. Furthermore, both drug families also act to reduce systemic oxidative stress through altered activity of overlapping oxidase and antioxidant pathways, providing a putative mechanism to augment circulating pro-vascular progenitor cell content. As SGLT2i and GLP-1RA combination therapies are emerging as a novel therapeutic opportunity for individuals with poorly controlled hyperglycaemia, potential additive effects in the reduction of oxidative stress may also enhance vascular repair and further reduce the ischaemic cardiovascular comorbidities associated with T2D and obesity.

Horizontal versus vertical direction of posterior vaginal wall suture after eradication of rectovaginal endometriosis: A multicenter study.

OBJECTIVE: To compare safety and effectiveness of two-different directions of suturing the posterior vaginal breach (horizontal [Ho] vs vertical [Ve]) in women undergoing recto-vaginal endometriosis (RVE) nodule resection. METHODS: A multicenter, retrospective, observational, cohort study was performed including all women of reproductive age undergoing RVE nodule resection between March 2013 and December 2018 at our tertiary centers. Patients included in the present study were divided into two groups based on the direction in suturing the posterior vaginal fornix defect, for comparisons in terms of rate of postoperative complications, pain relief, pain and anatomical recurrence, and length of hospital stay. Univariate comparisons were performed adopting the t test or the Mann-Whitney test for continuous data and the chi-square test or the Fisher exact test for categorical data, with a significant P value set to <0.05. RESULTS: A total of 101 women were included: 67 in the Ho-group and 34 in the Ve-group. The two groups did not significantly differ in length of hospital stay (6.7 ± 6.9 vs 6.6 ± 3.3 days; P = 0.95), overall postoperative complications (32.8% vs 14.7%; P = 0.05), pain recurrence (35.8% vs 26.5%; P = 0.34) and anatomical recurrence rate (19.4% vs 23.5%; P = 0.62). Conversely, grade III complications were significantly more common in the Ho-group than in the Ve-group (22.7% vs 20%, P = 0.009), while pain relief in terms of deep dyspareunia, dyschezia, dysuria and chronic pelvic pain was more consistent in the Ve-group patients (P = 0.04, 0.04, 0.05, 0.004, respectively). CONCLUSION: In symptomatic women undergoing RVE nodule resection, Ho suturing of the vaginal breach appears more commonly associated with severe postoperative complications and a worse pain control.

Sentinel-node biopsy in apparent early stage ovarian cancer: final results of a prospective multicentre study (SELLY).

AIM: To evaluate the sensitivity and specificity of sentinel-lymph-node mapping compared with the gold standard of systematic lymphadenectomy in detecting lymph node metastasis in apparent early stage ovarian cancer. METHODS: Multicenter, prospective, phase II trial, conducted in seven centers from March 2018 to July 2022. Patients with presumed stage I-II epithelial ovarian cancer planned for surgical staging were eligible. Patients received injection of indocyanine green in the infundibulo-pelvic and, when feasible, utero-ovarian ligaments and sentinel lymph node biopsy followed by pelvic and para-aortic lymphadenectomy was performed. Histopathological examination of all nodes was performed including ultra-staging protocol for the sentinel lymph node. RESULTS: 174 patients were enrolled and 169 (97.1 %) received study interventions. 99 (58.6 %) patients had successful mapping of at least one sentinel lymph node and 15 (15.1 %) of them had positive nodes. Of these, 11 of 15 (73.3 %) had a correct identification of the disease in the sentinel lymph node; 7 of 11 (63.6 %) required ultra-staging protocol to detect nodal metastasis. Four (26.7 %) patients with node-positive disease had a negative sentinel-lymph-node (sensitivity 73.3 % and specificity 100.0 %). CONCLUSIONS: In a multicenter setting, identifying sentinel-lymph nodes in apparent early stage epithelial ovarian cancer did not reach the expected sensitivity: 1 of 4 patients might have metastatic lymphatic disease unrecognized by sentinel-lymph-node biopsy. Nevertheless, 35.0 % of node positive patients was identified only thanks to ultra-staging protocol on sentinel-lymph-nodes.

Patterns of recurrence in FIGO stage IB1-IB2 cervical cancer: Comparison between minimally invasive and abdominal radical hysterectomy.

OBJECTIVE: Aim of our study was to evaluate whether the different laparotomic (ARH) or minimally invasive (laparoscopic and robotic) approaches (MIS) in FIGO stage IB1-IB2 cervical cancer, present different patterns of recurrence of the disease. The secondary endpoint of the study was the evaluation of the variables most involved with the risk of relapse and therefore lower DFS and OS. MATERIAL AND METHODS: The study enrolled patients with definitive histological diagnosis of squamous or adenocarcinoma stage IB1-IB2 cervical cancer who underwent minimally invasive or abdominal radical hysterectomy from 2001 to 2018. RESULTS: The study enrolled 360 patients and 59 patients (16.4 %) reported a disease relapse. The data showed that ARH group was not associated with different recurrence patterns than MIS group (p = 0.14). Moreover, there was no statistically significant difference regarding DFS (p = 0.52) and OS (p = 0.29) between the ARH group and the MIS group. CONCLUSIONS: MIS, in FIGO stage IB1-IB2 cervical cancer, is not associated with different relapse patterns compared to ARH, nor with a higher risk of distance metastasis and finally, without significant difference in term of DFS and OS. More studies are needed to determine the factors that modify the site of relapse.

Data from network meta-analyses can inform clinical practice guidelines and decision-making in diabetes management: perspectives of the taskforce of the guideline workshop.

In recent years, several novel agents have become available to treat individuals with type 2 diabetes (T2D), such as sodium-glucose cotransporter-2 inhibitors (SGLT-2i), tirzepatide, which is a dual glucose-dependent insulinotropic polypeptide receptor agonist (GIP RA)/glucagon-like peptide-1 receptor agonist (GLP-1 RA), and finerenone, a non-steroidal mineralocorticoid receptor antagonist (MRA) that confers significant renal and cardiovascular benefits in individuals with (CKD). New medications have the potential to improve the lives of individuals with diabetes. However, clinicians are challenged to understand the benefits and potential risks associated with these new and emerging treatment options. In this article, we discuss how use of network meta-analyses (NMA) can fill this need.

Major determinants of survival in recurrent endometrial cancer-the role of secondary cytoreductive surgery: a multicenter study.

OBJECTIVE: The main objective of the study was to assess the influence of different clinical and therapeutic variables on the oncological outcomes of patients with endometrial cancer relapse. In particular, we evaluated the impact of cytoreductive surgery with the achievement of complete gross resection. METHODS: This is a multicenter retrospective cohort study conducted in three centers in Italy and including all patients with first relapse of endometrial cancer from January 2010 to December 2021. RESULTS: Data from 331 women with recurrent endometrial cancer were analyzed. Secondary cytoreductive surgery was performed in 56.2% of cases (186 patients). Complete gross resection was achieved in 178 patients (95.7%). Complete gross resection conferred a statistically significant survival benefit both for post-relapse survival and post-relapse free survival (3 years post-relapse survival: 75.4% vs 56.4%, p<0.001; 3 years post-relapse free survival: 32.6% vs 26.5%, p=0.027). At multivariate Cox regression analysis, age ≥75 years, Eastern Cooperative Oncology Group Performance Status ≥2, the advanced-metastatic risk group, complete gross resection, and multiple site relapses were identified as independent significant predictors for post-relapse survival; regarding post-relapse free survival, only age ≥75, the high and advanced-metastatic risk groups, and complete gross resection confirmed their statistical significance. CONCLUSIONS: Secondary cytoreductive surgery with achievement of complete gross resection was confirmed to be an independent positive predictor for survival in patients with recurrent endometrial cancer and should be considered a valid primary treatment in the therapeutic decision-making process.

Prevalence of sonographic signs in women with uterine sarcoma: a systematic review and meta-analysis.

OBJECTIVE: To assess the prevalence of sonographic signs in women with uterine sarcoma. MATERIALS AND METHODS: A systematic review and meta-analysis were performed. Five electronic databases were searched from inception to June 2022 for all studies allowing calculation of the prevalence of sonographic signs in women with uterine sarcoma. Pooled prevalence with 95% confidence intervals was calculated for each sonographic sign and was a priori defined as "very high" when it was ≥ 80%, "high" when it ranged from 80% to 70%, and less relevant when it was ≤ 70%. RESULTS: 6 studies with 317 sarcoma patients were included. The pooled prevalence was: · 25.0% (95%CI:15.4-37.9%) for absence of visibility of the myometrium. · 80.5% (95%CI:74.8-85.2%) for solid component. · 78.3% (95%CI:59.3-89.9%) for inhomogeneous echogenicity of solid component. · 47.9% (95%CI:41.1-54.8%) for cystic areas. · 80.7% (95%CI:68.3-89.0%) for irregular walls of cystic areas. · 72.3% (95%CI:16.7-97.2%) for anechoic cystic areas. · 54.8% (95%CI:34.0-74.1%) for absence of shadowing. · 73.5% (95%CI:43.3-90.9%) for absence of calcifications. · 48.7% (95%CI:18.6-79.8%) for color score 3 or 4. · 47.3% (95%CI:37.0-57.8%) for irregular tumor borders. · 45.4% (95%CI:27.6-64.3%) for endometrial cavity not visualizable. · 10.9% (95%CI:3.5-29.1%) for free pelvic fluid. · 6.4% (95%CI:1.1-30.2%) for ascites. · 21.2% (95%CI:2.1-76.8%) for intracavitary process. · 81.5% (95%CI:56.1-93.8%) for singular lesion.. CONCLUSION: Solid component, irregular walls of cystic areas, and singular lesions are signs with very high prevalence, while inhomogeneous echogenicity of solid component, anechoic cystic areas, and absence of calcifications are signs with high prevalence. The remaining signs were less relevant.

Cardiometabolic risk management: insights from a European Society of Cardiology Cardiovascular Round Table.

Metabolic comorbidities are common in patients with cardiorenal disease; they can cause atherosclerotic cardiovascular disease (ASCVD), speed progression, and adversely affect prognosis. Common comorbidities are Type 2 diabetes mellitus (T2DM), obesity/overweight, chronic kidney disease (CKD), and chronic liver disease. The cardiovascular system, kidneys, and liver are linked to many of the same risk factors (e.g. dyslipidaemia, hypertension, tobacco use, diabetes, and central/truncal obesity), and shared metabolic and functional abnormalities lead to damage throughout these organs via overlapping pathophysiological pathways. The COVID-19 pandemic has further complicated the management of cardiometabolic diseases. Obesity, T2DM, CKD, and liver disease are associated with increased risk of poor outcomes of COVID-19 infection, and conversely, COVID-19 can lead to worsening of pre-existing ASCVD. The high rates of these comorbidities highlight the need to improve recognition and treatment of ASCVD in patients with obesity, insulin resistance or T2DM, chronic liver diseases, and CKD and equally, to improve recognition and treatment of these diseases in patients with ASCVD. Strategies to prevent and manage cardiometabolic diseases include lifestyle modification, pharmacotherapy, and surgery. There is a need for more programmes at the societal level to encourage a healthy diet and physical activity. Many pharmacotherapies offer mechanism-based approaches that can target multiple pathophysiological pathways across diseases. These include sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists, selective mineralocorticoid receptor antagonists, and combined glucose-dependent insulinotropic peptide/glucagon-like peptide-1 receptor agonist. Non-surgical and surgical weight loss strategies can improve cardiometabolic disorders in individuals living with obesity. New biomarkers under investigation may help in the early identification of individuals at risk and reveal new treatment targets.

Patient phenotype profiling in heart failure with preserved ejection fraction to guide therapeutic decision making. A scientific statement of the Heart Failure Association, the European Heart Rhythm Association of the European Society of Cardiology, and the European Society of Hypertension.

Heart failure with preserved ejection fraction (HFpEF) represents a highly heterogeneous clinical syndrome affected in its development and progression by many comorbidities. The left ventricular diastolic dysfunction may be a manifestation of various combinations of cardiovascular, metabolic, pulmonary, renal, and geriatric conditions. Thus, in addition to treatment with sodium-glucose cotransporter 2 inhibitors in all patients, the most effective method of improving clinical outcomes may be therapy tailored to each patient's clinical profile. To better outline a phenotype-based approach for the treatment of HFpEF, in this joint position paper, the Heart Failure Association of the European Society of Cardiology, the European Heart Rhythm Association and the European Hypertension Society, have developed an algorithm to identify the most common HFpEF phenotypes and identify the evidence-based treatment strategy for each, while taking into account the complexities of multiple comorbidities and polypharmacy.

Hysteroscopic endometrial tumor localization and sentinel lymph node mapping. An upgrade of the hysteroscopic role in endometrial cancer patients.

INTRODUCTION: Given the growing interest in sentinel node mapping (SLN) biopsy in Endometrial Cancer (EC) patients, many efforts have been made to maximize the SLN bilateral detection rate. However, at present, no previous research assessed the potential correlation between primary EC location in the uterine cavity and SLN mapping. In this context, this study aims to investigate the possible role of intrauterine EC hysteroscopic localization in predicting SLN nodal placement. MATERIALS AND METHODS: EC patients surgically treated from January 2017 to December 2021 were retrospectively analyzed. All patients underwent hysterectomy, bilateral salpingo-oophorectomy, and SLN mapping. During hysteroscopy, the location of the neoplastic lesion was described as follows: uterine fundus (comprising the most cranial portion of the uterine cavity up to the tubal ostium including the cornual areas), corpus uteri (from the tubal ostium to the inner uterine orifice), and diffuse (when the tumor invades more than 50% of the uterine cavity). RESULTS: Three hundred ninety patients met the inclusion criteria. The tumor pattern diffused to the whole uterine cavity was statistically associated with SLN uptake on common iliac lymph nodes (OR 2.4, 95%CI 1-5.8, p = 0.05). Patients'age is an independent factor associated with SLN failure (OR: 0.95, 95%CI 0.93-0.98, p < 0.001). CONCLUSIONS: The study showed a statistically significant association between EC hysteroscopically spread throughout the whole uterine cavity and SLN uptake at the common iliac lymph nodes. Furthermore, patient age negatively affected the SLN detection rate.

Long-term survival outcomes in high-risk endometrial cancer patients undergoing sentinel lymph node biopsy alone versus lymphadenectomy.

OBJECTIVE: Endometrial cancer is the most common gynecologic neoplasm. To date, international guidelines recommend sentinel lymph node biopsy for low-risk neoplasms, while systematic lymphadenectomy is still considered for high-risk cases. This study aimed to compare the long-term survival of high-risk patients who were submitted to sentinel lymph node biopsy alone versus systematic pelvic lymphadenectomy. METHODS: Patients with high-risk endometrial cancer according to the 2021 European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology risk classification were retrospectively analyzed. The primary aim of the study was to compare the long-term overall survival and disease-free survival of high-risk endometrial cancer patients undergoing sentinel lymph node biopsy versus systematic lymphadenectomy. A supplementary post-hoc survival analysis of cases with nodal metastasis was performed to compare sentinel lymph node and lymphadenectomy survival outcomes in this subset of patients. RESULTS: The study enrolled 237 patients with histologically proven high-risk endometrial cancer. Patients were followed up for a median of 31 months (IQR 18-40). During the follow-up, 38 (16.0%) patients had a recurrence, and 19 (8.0%) patients died. Disease-free survival (85.2% vs 82.8%; p=0.74) and overall survival (91.3% vs 92.6%; p=0.62) were not different between the sentinel lymph node alone and lymphadenectomy groups. Furthermore, neither overall survival (96.1% vs 91.4%; p=0.43) nor disease-free survival (83.7% vs 76.4%; p=0.46) were different among sentinel lymph node alone and lymphadenectomy groups in patients with nodal metastasis. CONCLUSIONS: Sentinel lymph node mapping alone in high-risk endometrial cancer appears to be an oncologically safe technique over a long observational time. Systematic lymphadenectomy in this population does not offer a survival advantage.

Human papillomavirus independent status on pathologic response and outcomes in locally advanced cervical cancer managed with chemoradiotherapy followed by surgery.

OBJECTIVE: While human papillomavirus (HPV) has been shown to play a significant role in cervical cancer carcinogenesis (HPV associated cases), a considerable percentage of cervical cancers occur independently of HPV status (HPV independent). METHODS: In this retrospective study of 254 locally advanced cervical cancer patients treated with chemoradiotherapy and radical surgery, HPV genotypes were determined using the Anyplex II HPV28 kit that uses multiplex, real time polymerase chain reaction technology. The primary endpoints of this study were to evaluate the complete response to chemoradiotherapy (pathologic complete response), the presence of microscopic (<3 mm, pathologic micro partial response, group 1) and macroscopic (>3 mm, pathologic macro partial response, group 2) residual carcinoma in the cervix, and the persistence of metastatic lymph nodes (group 3) in HPV independent cervical cancers. Secondary endpoints were evaluation of disease-free survival and overall survival. RESULTS: Of 254 patients studied, 21 cases (8.3%) of cervical cancer were determined to be HPV independent. The percentage of pathologic complete response was found to be higher in the HPV associated group compared with the HPV independent group (p<0.001). In the HPV associated cervical cancer group, 5 year disease free survival was found to be 80.8% versus 59.9% in the HPV independent group (p=0.014). Overall survival was also higher in the HPV associated group (87.9%) compared with the HPV independent patients (69.4%) (p=0.023). In the multivariate analysis, the International Federation of Gynecology and Obstetrics (FIGO) stage and HPV genotypes maintained their relevant impact on pathologic complete response to chemoradiotherapy: FIGO stages IIIC1 and IIIC2 were associated with a 13-fold increased risk for the presence of metastatic lymph nodes compared with group 1 (p<0.001). HPV independent cervical cancers showed the highest risk for the development of macroscopic/stable disease (p=0.007), and persistence of metastatic lymph nodes (p=0.004) versus group 1, respectively. CONCLUSIONS: This study showed that HPV status at diagnosis could be a relevant factor for clinical outcomes in locally advanced cervical cancer patients.

Preoperative Tumor Texture Analysis on MRI for High-Risk Disease Prediction in Endometrial Cancer: A Hypothesis-Generating Study.

OBJECTIVE: To develop and validate magnetic resonance (MR) imaging-based radiomics models for high-risk endometrial cancer (EC) prediction preoperatively, to be able to estimate deep myometrial invasion (DMI) and lymphovascular space invasion (LVSI), and to discriminate between low-risk and other categories of risk as proposed by ESGO/ESTRO/ESP (European Society of Gynaecological Oncology-European Society for Radiotherapy & Oncology and European Society of Pathology) guidelines. METHODS: This retrospective study included 96 women with EC who underwent 1.5-T MR imaging before surgical staging between April 2009 and May 2019 in two referral centers divided into training (T = 73) and validation cohorts (V = 23). Radiomics features were extracted using the MODDICOM library with manual delineation of whole-tumor volume on MR images (axial T2-weighted). Diagnostic performances of radiomic models were evaluated by area under the receiver operating characteristic (ROC) curve in training (AUCT) and validation (AUCV) cohorts by using a subset of the most relevant texture features tested individually in univariate analysis using Wilcoxon-Mann-Whitney. RESULTS: A total of 228 radiomics features were extracted and ultimately limited to 38 for DMI, 29 for LVSI, and 15 for risk-classes prediction for logistic radiomic modeling. Whole-tumor radiomic models yielded an AUCT/AUCV of 0.85/0.68 in DMI estimation, 0.92/0.81 in LVSI prediction, and 0.84/0.76 for differentiating low-risk vs other risk classes (intermediate/high-intermediate/high). CONCLUSION: MRI-based radiomics has great potential in developing advanced prognostication in EC.

Molecular and pro-inflammatory aspects of COVID-19: The impact on cardiometabolic health.

Obesity, type 2 diabetes (T2DM), hypertension (HTN), and Cardiovascular Disease (CVD) often cluster together as "Cardiometabolic Disease" (CMD). Just under 50% of patients with CMD increased the risk of morbidity and mortality right from the beginning of the COVID-19 pandemic as it has been reported in most countries affected by the SARS-CoV2 virus. One of the pathophysiological hallmarks of COVID-19 is the overactivation of the immune system with a prominent IL-6 response, resulting in severe and systemic damage involving also cytokines such as IL2, IL4, IL8, IL10, and interferon-gamma were considered strong predictors of COVID-19 severity. Thus, in this mini-review, we try to describe the inflammatory state, the alteration of the adipokine profile, and cytokine production in the obese state of infected and not infected patients by SARS-CoV2 with the final aim to find possible influences of COVID-19 on CMD and CVD. The immunological-based discussion of the molecular processes could inspire the study of promising targets for managing CMD patients and its complications during COVID-19.

Different Surgical Approaches for Early-Stage Ovarian Cancer Staging. A Large Monocentric Experience.

Introduction: Ovarian cancer is the third most frequent gynecological cancer. In early stage ovarian cancer (ESOC) comprehensive surgical staging is recommended. Surgical staging is traditionally approached by laparotomy, although minimally invasive surgery can be a valid alternative in selected patients. This study aims to analyze the surgical and oncological outcomes of three different surgical approaches in a large series of patients. Methods: We retrospectively included all histologically proven ESOC cases treated between January 2014 and December 2017. ESOC was defined as stage IA to IIB according to the 2018 FIGO staging system. Subjects were divided into groups 1, 2, and 3, based on the surgical approach (open abdominal, laparoscopic, or robotic, respectively). Results: Within patients enrolled during the study period, 455 met the inclusion criteria. No difference in intraoperative complications was recorded in the three groups (p = 0.709). Conversely, a significant difference occurred in postoperative complications (16.2 vs. 3.8 vs. 11.1%, in groups 1, 2, and 3 respectively, p = 0.004). No difference was found in overall survival (OS) (32 vs. 31 vs. 25 months, p = 0.481) and disease-free survival (DFS) (26 vs. 29 vs. 24 months, p = 0.178) in groups 1, 2, and 3, respectively. At univariate analysis FIGO stage I (p = 0.004) showed a lower recurrence rate compared to FIGO stage II. Conclusion: No significant difference was found in OS and DFS among the three groups (open, laparoscopic, and robotic). The minimally invasive approach showed lower rate of complications than the laparotomic approach.