High-intermediate Risk Group Research Articles

Genetic risk stratification and risk factors of early menopause in women: a multi-center study utilizing polygenic risk scores

ObjectiveThis study aims to evaluate the utility of polygenic risk scores (PRS) in women with early menopause (EM) and to investigate the clinical characteristics and risk factors associated with EM based on genetic risk.Study designGenotyping data and clinical data from women with EM and women with normal age of menopause retrieved from UK Biobank were used for early menopause risk prediction model establishment. Subsequently, 99 women diagnosed with EM and 1027 control women underwent PGT-M were recruited for model validation from across eight hospitals in China. According to PRS percentiles, these participants were further classified into high risk and intermediate risk groups. Characteristics among women at different risk levels were compared, and risk factors with early menopause were also statistical analyzed.Main outcome measuresThe proportion of women at high risk in EM and control groups; Characteristics with significant difference among women at different risk levels; risk factors associated with EM.ResultsThe proportion of high-risk women in the EM group was significantly higher than that in control women underwent PGT-M (Group PGT-M) (OR = 3.78), and that in women with normal age menopause from UK Biobank (Group UKB) (OR = 5.11). Notably, the women with high risk of EM exhibited distinct characteristics compared to women with the intermediate-risk of EM, and identified several risk factors associated with EM.ConclusionsWe established a PRS model to serves as a valuable instrument for EM risk prediction. The exploratory analysis revealed that women with high risk of EM exhibited a higher height, suggesting EM related genetic loci may also influence growth and development level. Several risk factors were found to be potentially associated with EM, such as excessive familial contentment, COVID-19 vaccination, staying up late, and the husband’s engagement in smoking and alcohol abuse.

Whole gland versus partial gland ablation in patients with localized prostate cancer treated by high-intensity focused ultrasound ablation

BackgroundFocal therapy is considered one of the treatment options for localized prostate cancer (PCa), particularly for low or very-low-risk patients. In this study, we compared the mid-term oncological outcomes in localized PCa patients treated with high-intensity focused ultrasound (HIFU). MethodsWe retrospectively analyzed 237 patients who underwent HIFU for localized PCa. Patients were divided into two groups based on ablation type: whole gland ablation (WGA) and partial gland ablation (PGA). Follow-up biopsies were performed after one year postoperatively, and the oncological outcomes were compared between the groups. ResultsAmong the total of 237 patients, 54 subjects were treated by WGA and 183 subjects by PGA. After one year postoperatively, follow-up biopsies were conducted on 199 patients, revealing residual cancer in 21.4% of WGA group and 15.3% of PGA group. Additionally, clinically significant (CS) cancer was observed in 14.3% of WGA group and 8.3% of PGA group. Survival analyses revealed significantly longer failure-free (P < 0.001) and salvage-free survival (P < 0.001) in WGA group than in PGA group. Similarly, in the intermediate—high risk group, WGA group exhibited longer failure-free (P = 0.005) and salvage-free survival (P < 0.001). ConclusionHIFU was performed with acceptable oncological outcomes in localized PCa. Despite higher proportion of high-risk patients in WGA group, WGA was associated with significantly better failure-free survival and salvage-free survival. Further prospective and multi-center studies are warranted.

Morphomolecular Correlation and Clinicopathologic Analysis in Endometrial Carcinoma.

Research groups have identified 4 groups [polymerase epsilon (POLE) mutant, mismatch repair-deficient, p53-abnormal, and no specific molecular profile)] reflecting the Tumor Cancer Genomic Atlas Research Network subgroups in endometrial carcinomas, improving the clinical applicability of molecular classification. We have analyzed the histopathologic and prognostic characteristics of our cases based on the ProMisE classification, supported by growing data on recommended treatment regimens. The study included 118 cases of endometrial carcinoma diagnosed between 2016 and 2020, which underwent mismatch repair and p53 immunohistochemistry. Next-generation sequencing was performed for POLE mutation analysis, dividing the cases into 4 subgroups. The histopathologic and clinical characteristics of these groups were then analyzed statistically. Four cases(3.4%) were classified as POLE mutant, 31 (26.3%) as mismatch repair-deficient, 22 (18.6%) as p53 mutant, and 61 (51.7%) as no specific molecular profile. We categorized 118 patients with endometrial carcinoma into low (n=43), intermediate (n=28), high-intermediate (n=21), high (n=22), and advanced metastatic (n=4) risk groups regardless of the molecular subtypes of their disease. When we reclassified all cases according to the molecular subtypes of endometrial carcinoma only the risk group of 3 (2.5%) cases changed. Using the new algorithm we designed, after narrowing down the number of patients, the microcystic, elongated, and fragmented pattern of invasion was revealed as an independent prognostic factor that reduces overall survival time (hazard ratio: 16.395, 95% CI: 2.140-125.606, P =0.007). In conclusion, using the new algorithm we have designed, and by identifying patients for whom molecular classification could alter risk groups, we observed that molecular tests can be utilized more efficiently in populations with limited economic resources and, in doing so, we discovered a new morphologic marker with prognostic significance.

Prognostic significance of adjuvant chemotherapy in stage I-II endometrial carcinoma patients who underwent lymphadenectomy.

Endometrial carcinoma, the most common gynecologic carcinoma, has an excellent prognosis post-surgery when diagnosed early. The role of postoperative adjuvant chemotherapy in stages I-II endometrial carcinoma remains controversial. This study assesses the efficacy of adjuvant chemotherapy in improving prognosis for these patients. A retrospective analysis was conducted on 1223 stage I-II endometrial carcinoma patients who underwent surgical treatment including total hysterectomy, bilateral salpingo-oophorectomy, and lymph-node biopsy or dissection across four Jikei University School of Medicine-affiliated facilities between 2001 and 2018. Patients were divided into low intermediate risk (LIR) and high intermediate risk (HIR) groups based on recurrence risk. Propensity score matching adjusted for various covariates was used to compare progression-free survival (PFS) and overall survival (OS) between patients who received adjuvant chemotherapy and those who did not. The study included 443 eligible patients, with 288 in the LIR group and 155 in the HIR group. Post propensity score matching, no significant difference in PFS or OS was observed between the observation and adjuvant chemotherapy groups within both risk categories. Notably, the 5-year OS for LIR was 97.6% in the observation group and 96.7% in the chemotherapy group; for HIR, the 5-year OS was similarly high with no significant difference. The findings suggest that postoperative adjuvant chemotherapy does not significantly contribute to the improvement of recurrence or prognosis in patients with stage I-II endometrial carcinoma who are categorized outside the low-risk group and have no lymph-node metastasis.

Application of REVEAL Lite 2 and COMPERA 2.0 risk scores to patients with pulmonary arterial hypertension switching to riociguat in the REPLACE study

In REPLACE (NCT02891850), improvements in risk status were observed in patients with pulmonary arterial hypertension (PAH) at intermediate risk switching to riociguat vs continuing phosphodiesterase-5 inhibitors (PDE5i). This post hoc study applied the REVEAL Lite 2 and COMPERA 2.0 risk-assessment tools to REPLACE to investigate the impact of baseline risk status on clinical improvement. The proportions of riociguat- and PDE5i-treated patients achieving the primary endpoint at REVEAL Lite 2 low, intermediate, and high baseline risk reflected the overall population. Proportions of riociguat-treated patients achieving the primary endpoint were comparable between the COMPERA 2.0 intermediate-low risk (39%) and intermediate-high risk (43%) groups. Our findings show that patients in REPLACE achieved clinical improvement by switching from PDE5i to riociguat across all COMPERA 2.0 and most REVEAL Lite 2 baseline risk strata.

Treatment of high- and intermediate-high-risk pulmonary embolism by the Pulmonary Embolism Response Team: Focus on catheter-directed therapies.

Multidisciplinary Pulmonary Embolism Response Teams (PERTs) were established to individualize the treatment of high-risk (HR) and intermediate-high-risk (IHR) pulmonary embolism (PE) patients, which pose a challenge in clinical practice. We retrospectively collected the data of all HR and IHR acute PE patients consulted by PERT CELZAT between September 2017 and October 2022. The patient population was divided into four different treatment methods: anticoagulation alone (AC), systemic thrombolysis (ST), surgical embolectomy (SE), and catheter-directed therapies (CDTx). Baseline clinical characteristics, risk stratification, PE severity parameters, and treatment outcomes were compared between the four groups. Of the 110 patients with HR and IHR PE, 67 (61%) patients were treated with AC only, 11 (10%) with ST, 15 (14%) underwent SE, and 17 (15%) were treated with CTDx. The most common treatment option in the HR group was reperfusion therapy, used in 20/24 (83%) cases, including ST in 7 (29%) patients, SE in 5 (21%) patients, and CTDx in 8 (33%) patients. In contrast, IHR patients were treated with AC alone in 63/86 (73%) cases. The in-hospital mortality rate was 9/24 (37.5%) in the HR group and 4/86 (4.7%) in the IHR group. The number of advanced procedures aimed at reperfusion was substantially higher in the HR group than in the IHR PE group. Despite the common use of advanced reperfusion techniques in the HR group, patient mortality remained high. There is a need further to optimize the treatment of patients with HR PE to improve outcomes.

Contribution of plasma MicroRNA-21, MicroRNA-155 and circulating monocytes plasticity to childhood neuroblastoma development and induction treatment outcome

Neuroblastoma (NB) accounts for 15% of all pediatric cancer fatalities (NB). Biomarkers that facilitate early NB detection are needed because by the time of diagnosis, over half of NBs had spread. MicroRNA-21(miR-21) and miR-155 are involved in cancer biology due to their immune modulation functions. Altered monocyte subset distribution is thought to be involved in a number of solid tumors due to its immunological role. We aimed to investigate the expression levels of miR-21 and miR-155 and their association with circulating monocytes subsets in NB and to evaluate if they correlate to the disease pathogenesis and outcome. Patients and methodsThis case control study involved 79 children classified into 39 newly diagnosed NB children and 40 age and sex matched healthy children. Real-time PCR was used to assess the expression of plasma miR-21 and miR-155. The frequency of circulating monocytes subsets was assessed by flow cytometry. ResultsNB group showed significant up-regulation in expression of miR-21(20.9 folds) and miR-155 (1.8 folds) when compared to the control group (p < 0.001) and (p = 0.02) respectively. Also, frequency of circulating intermediate monocytes revealed significant up regulation in children with NB. In NB patients, there was a positive correlation between miR-21 and frequency of total and intermediate monocytes (r = 0.5 p < 0.001 and r = 0.7, p < 0.001, respectively). We found no discernible differences when we compared study markers between the high risk and intermediate risk groups. In addition, no significant difference was seen in study markers when patients were sub-grouped according to their induction treatment response. ROC curve analysis revealed that miR-21 up-regulation distinguished NB in childhood at an AUC of 0.94 (82% sensitivity and 100% specificity) while miR-155 up-regulation had less capacity to distinguish NB in childhood at an AUC of 0.65 (38% sensitivity and 93% specificity). ConclusionmiR-21 can be utilized as a sensitive biomarker for childhood NB development. In pediatric NB, miR-21 was linked to intermediate monocyte plasticity. Both, miR-21 and miR-155 had no impact on NB outcome.

Outcome differences in HPV-driven head and neck squamous cell carcinoma attributable to altered human leukocyte antigen frequencies.

Effective immune surveillance requires a functioning immune system and natural killer (NK) and T cells for adequate innate and antigen-specific immune responses critically depending on human leukocyte antigens (HLAs) and haplotypes representing advantageous combinations of HLA antigens. Recently, we reported a link between altered frequencies of HLA alleles and haplotypes and developing head and neck squamous cell carcinoma (HNSCC). Whereas the majority of HNSCCs seem to be related to classical risk factors alcohol and tobacco, a subset of HNSCC and especially oropharyngeal squamous cell carcinoma (OPSCC) were etiologically linked to human papillomavirus (HPV) recently. Here, we demonstrate in HPV-driven (p16-positive high risk-HPV DNA-positive) HNSCC a deviating distribution of HLA antigens and haplotypes and their relevance to outcome. Leukocyte DNA of n = 94 HPV-driven HNSCC patients (n = 57 OPSCC, n = 37 outside oropharynx) underwent HLA SSO typing, allowing allele, antigen (allele group), and haplo-typing. Besides comparing these frequencies with those of German blood donors, we analyzed their impact on outcome using Kaplan-Meier plots and Cox proportional hazard regression. Antigen and haplotype frequencies demonstrate enrichment of rare antigens and haplotypes. The HLA score for unselected HNSCC patients was not predictive for outcome here. However, together with alcohol consumption, tobacco smoking, T category, and extranodal extension of locoregional metastases and treatment applied, eight HLA traits allow for predicting progression-free and tumor-specific survival. Patients can be categorized into low, intermediate-low, intermediate-high, and high risk groups. Using a new PFS risk score for HPV-driven HNSCC may allow to improve prognostication.

Prognosis of Patients with Diffuse Large B Cell Lymphoma with Central Nervous System Relapse: USC Experience

Introduction: Diffuse large B cell lymphoma (DLBCL) is the most common form of lymphoma and a potentially curable disease with systemic immunochemotherapy regimens. Involvement of the central nervous system (CNS) in patients with DLBCL is a relatively rare event which occurs in approximately 2-5% of patients overall, but the CNS relapse rate can be as high as 10-12% in high-risk patients. Unfortunately, CNS relapse confers poor prognosis with some studies estimating median survival of 2.5 months from relapse. Our study evaluates prognostic factors and outcomes in this patient population. Methods: This study is a retrospective review of patients diagnosed with DLBCL who then developed CNS relapse and were treated at Los Angeles General Medical Center (LAGMC) and Norris Comprehensive Cancer Center (NCCC) from 2016-2023. Information regarding patient demographics, prognostic factors to calculate NCCN-IPI scores, pathologic characterization, therapy, clinical course, and survival were collected. CNS relapse was defined as pathologic or imaging diagnosis of CNS involvement after initial treatment was received. Results: A total of 29 patients with CNS relapse of DLBCL were identified with a median age of 60 (range 43-86). The median time from initial diagnosis to CNS relapse was 9 months. The patients were 72.4% male (N=21), 79.3% Hispanic (N=23), and 17.2% (N=5) HIV positive. NCCN-IPI scores were calculated for all patients and divided into NCCN-IPI risk groups. The low-risk group (NCCN-IPI 0-1) made up 10.3% (N=3), low-intermediate risk group (NCCN-IPI 2-3) 48.3% (N=14), high-intermediate risk group (NCCN-IPI 4-5) 34.5% (N=10), and high-risk group (6-8) 6.90% (N=2). Pathologic analysis revealed 41.4% (N=12) of patients had germinal center type lymphoma, 44.8% (N=13) were BCL-2/c-myc double expressors, 13.8% (N=4) were BCL-2/c-myc double hit, and 13.8% (N=4) were BCL-6/c-myc double hit (Table 1). Overall survival (OS) for the entire cohort was 18.5% at five years after CNS relapse of DLBCL with a median survival of 12 months. Patients with a low or low-intermediate NCCN-IPI score (0-3) had an OS of 57.4% at 12 months and 29.1% at five years. Patients with a high-intermediate or high NCCN-IPI score had an OS of 35.7% at 12 months and 0% by 33 months. OS at 12 months for the HIV negative group was 70.4% compared to 40.0% in the HIV positive group, but OS at 5 years was similar in both groups at 19.4% and 20.0%, respectively (Figure 1). Conclusions: CNS relapse in patients with DLBCL is a rare but devastating complication. In our largely male and Hispanic patient population, prognosis at five years was very poor for those with CNS relapse, but higher NCCN-IPI scores demonstrated a trend that conferred a higher likelihood of death at both the one year and five year time points compared to those with lower scores. Survival after CNS relapse in our cohort is longer compared to prior studies, indicating possible improvements in the prognosis of patients with CNS relapse of DLBCL. Given the overall poor prognosis of CNS relapse of DLBCL, improved prognostic stratification is of the utmost importance in this highly curable disease.

Abstract 14319: Riociguat in Pulmonary Arterial Hypertension: Application of the 4-strata COMPERA 2.0 Risk Assessment Tool in the PATENT Studies

Background: The 2022 ESC/ERS treatment guidelines for pulmonary arterial hypertension (PAH) recommend using a four-strata risk assessment strategy at follow-up. COMPERA 2.0 is a refined four-strata risk assessment tool that subdivides patients at intermediate risk of mortality at 1 year into intermediate-low and intermediate-high risk groups for a more granular approach to risk prediction. Aim: This post-hoc analysis applied COMPERA 2.0 to the PATENT studies of riociguat in patients with PAH. Methods: COMPERA 2.0 was applied to patients who were pretreated with PAH therapy at PATENT-1 entry. Patients with missing data for COMPERA 2.0 variables were excluded. In PATENT-1, risk strata were assessed at baseline and Week 12; and 6-minute walking distance (6MWD) at Week 12 was analyzed by risk strata at baseline. All pretreated patients entering the PATENT-2 open-label extension were included in Kaplan-Meier analyses to assess association of risk strata at PATENT-1 baseline and Week 12 with clinical worsening and survival. Results: At PATENT-1 baseline (riociguat 2.5 mg n=102, placebo n=49), more patients were at intermediate-low risk than intermediate-high risk (Figure 1). At PATENT-1 Week 12, a higher proportion of patients were at low risk with riociguat vs placebo (Figure 1). At PATENT-1 Week 12, the following mean [SD] changes in 6MWD were seen in patients at intermediate-low risk (riociguat 24 m [57 m], placebo 10 m [60 m]) and intermediate-high risk (riociguat 34 m [56 m], placebo –2 m [70 m]) by COMPERA 2.0 at baseline. COMPERA 2.0 assessed at PATENT-1 baseline and Week 12 was able to discriminate between risk strata for clinical worsening and survival in PATENT-2 (n=167, log-rank tests: p≤0.001 for all analyses). Conclusion: This analysis confirmed the risk-reduction benefits of riociguat in patients with PAH and validated the utility of COMPERA 2.0 in the long-term risk assessment of patients from a clinical trial population.

Practical lessons learned from real-world implementation of the molecular classification for endometrial carcinoma

ObjectivesThis study aimed to explore the practical organisational aspects and difficulties in the implementation of the molecular classification of endometrial carcinoma (EC), and to demonstrate its potential impact in prognostic risk group classification. MethodsWe conducted a multicentre, retrospective cohort study of 230 patients with EC diagnosed between 2019 and 2022. Sample processing, clinicopathological, treatment and follow-up data were collected. Molecular classification was obtained by p53 and mismatch repair proteins immunohistochemistry, and POLE next-generation sequencing. ResultsImplementation was achieved through centralization of molecular analysis. In practice, it was possible to optimise turnaround times of complete integrative reports for hysterectomy specimens to a median time of 18 workdays. If genetic study was started in endometrial biopsies before surgery, 82.0% were available at the time of multidisciplinary tumour board, compared to 8.4% if performed in hysterectomy. ECs were classified as follows: 37.8% no specific molecular profile, 31.7% p53 abnormal, 24.3% mismatch repair deficient, and 6.1% POLE mutant. Integration of these results with traditional clinicopathologic factors led to a change in prognostic risk group in 15 (6.5%) patients, most being initially allocated to high-intermediate (n = 8) and low (n = 5) risk groups. Eight patients changed to a higher risk, and 7 to a lower risk group, whereas 2 remained in the same group. ConclusionsCentralization of EC molecular classification is a feasible option for countries with limited resources. Optimization of workflows may be achieved by earlier analysis in biopsies and prioritisation of patients whose results imply changes in risk group classification.

Image-guided radiation therapy (IGRT) in prostate cancer in México, survey of SOMERA (Sociedad Mexicana de Radioterapeutas/Mexican Society of Radiation Oncologists) with recommendations on its implementation and process.

Prostate cancer is one of the main tumors worldwide, its treatment is multidisciplinary, includes radiotherapy in all stages: curative, radical, adjuvant, salvage and palliative. Technological advances in planning systems, image acquisition and treatment equipment have allowed the delivery of higher doses limiting toxicity in healthy tissues, distributing radiation optimally and ensuring reproducibility of conditions. Image-guided radiotherapy (IGRT) is not standard in guidelines, only recommended with heterogeneity in its own process. A survey was conducted to members of the Mexican Society of Radiation Oncologists (SOMERA), to know the current status and make recommendations about its implementation and use, taking into account existing resources. Responses of 541 patients were evaluated, 85% belonged to the intermediate-high risk group, 65% received adjuvant or salvage radiotherapy (RT), 80% received intensity-modulated radiation therapy (IMRT) using doses up to 80 Gy/2 Gy. Cone beam computed tomography (CBCT) was performed on 506 (93.5%), (100% IMRT) and 90% at a periodicity of 3-5/week. 3D treatment with 42% portal images 1/week. Online correction strategies (36% changes before treatment), following a diet and bladder and rectal control. Evidence and recommendations are reviewed. IGRT should be performed in patients with prostate cancer. In Mexico, despite limitations in the distribution of human and technological resources, it is routinely applied. More information is still needed on clinical evidence of its benefits and the process should be implemented according to infrastructure, following institutional guidelines, recommending to report the initial experience that helps to standardize national conduct.

Echocardiographic parameters analysis in acute pulmonary embolism: what is the prognostic value in the real-world setting?

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Transthoracic echocardiogram performed after the diagnosis of acute pulmonary embolism is used for risk stratification. The individual prognostic value of the echocardiographic parameters and its association with the clinical data is still being studied. Objective To determine the impact of echocardiographic parameters (TAPSE, PSAP e TAPSE/PSAP), as well as its association with the clinical evaluation in the patient’s prognosis. Methods Single centre retrospective study, evaluating 131 patients admitted by acute pulmonary embolism between January 2017 and December 2020. Mean age was 67.6 ± 15.3 years, 38 patients were male (29.0%). The patients were stratified according to the European Cardiology Association (ESC) early mortality risk classification in high or intermediate-high risk (group A) and low or intermediate low risk (group B). The correlation with echocardiographic parameters was evaluated. In-hospital mortality at 30 days and 1 year was determined. Results Group A included 27 patients (20.6%) and group B 104 patients (79.4%), with no difference regarding demographic and clinic characteristics between both groups. In group A the mean PSAP was 49.4 ± 22.8 mmHg, TAPSE 14.7 ± 5.2 mm and TAPSE/PSAP 0.3. In group B the mean PSAP was 34.6 ± 16.8 mmHg, TAPSE 20.9 ± 4.5 mm and TAPSE/PSAP 0.7. The ROC analysis shows PSAP has good discriminative power for risk stratification (AUC 0.716; p = 0.017 95% CI 0.56 – 0.87), with a cut-off point at 35 mmHg. The TAPSE/PSAP ratio has an excellent discriminative power (AUC 0.873, p value 0.001, CI 95% 0.767 – 0.978), with a cut-off point of 0.3. In-hospital mortality was 8.4% (11 patients), 30-day mortality was 12.2% (16 patients) and 1-year mortality was 19.8% (26 patients). There was no difference regarding mortality between groups A and B. Comparing PSAP and TAPSE/PSAP ≤ 0.3, only the latter was correlated with mortality at 1 year (p = 0.021). The addition of TAPSE/PSAP ≤ 0.3 to ESC classification for each group had a significant impact on mortality at 1 year (p = 0.004). Conclusion The addition of TAPSE/PSAP ≤ 0.3 to risk scores in groups A and B confers relevant prognostic information on long-term mortality. When available, the addition of echocardiographic parameters to the clinical data could add relevant prognostic value.

Anatomical and anastomotic viability indexes for stratifying the risk of anastomotic leakage in esophagectomy with retrosternal reconstruction.

Risk prediction of anastomotic leakage using anatomical and vascular factors has not been well established. This study aimed to assess the anatomical and vascular factors affecting the hemodynamics of the gastric conduit and develop a novel risk stratification system in patients undergoing esophagectomy with retrosternal reconstruction. This retrospective cohort study analyzed 202 patients with esophageal cancer who underwent subtotal esophagectomy with gastric tube retrosternal reconstruction between January 2008 and December 2020. Risk factors for anastomotic leakage (AL), including the anatomical index (AI) and anastomotic viability index (AVI), were evaluated using a logistic regression model. According to the logistic regression model, the independent risk factors for AL were preoperative body mass index ≥23.6 kg/m2 (odds ratio [OR], 7.97; 95% confidence interval [CI], 2.44-26.00; P < 0.01), AI <1.4 (OR, 23.90; 95% CI, 5.02-114.00; P < 0.01), and AVI <0.62 (OR, 8.02; 95% CI, 2.57-25.00; P < 0.01). The patients were stratified into four AL risk groups using AI and AVI as follows: low-risk group (AI ≥1.4, AVI ≥0.62 [2/99, 2.0%]), intermediate low-risk group (AI ≥1.4, AVI <0.62 [2/29, 6.9%]), intermediate high-risk group (AI <1.4, AVI ≥0.62 [8/53, 15.1%]), and high-risk group (AI <1.4, AVI <0.62 [11/21, 52.4%]). The combination of AI and AVI strongly predicted AL. Additionally, the use of AI and AVI enabled the stratification of the risk of AL in patients who underwent esophagectomy with retrosternal reconstruction.

Evolving paradigm of thrombolysis in pulmonary embolism: Comprehensive review of clinical manifestations, indications, recent advances and guideline.

Thrombolytic therapy has been the mainstay for patients with pulmonary embolism (PE). Despite being linked to a higher risk of significant bleeding, clinical trials demonstrate that thrombolytic therapy should be used in patients with moderate to high-risk PE, in addition to hemodynamic instability symptoms. This prevents the progression of right heart failure and impending hemodynamic collapse. Diagnosing PE can be challenging due to the variety of presentations; therefore, guidelines and scoring systems have been established to guide physicians to correctly identify and manage the condition. Traditionally, systemic thrombolysis has been utilized to lyse the emboli in PE. However, newer techniques for thrombolysis have been developed, such as endovascular ultrasound-assisted catheter-directed thrombolysis for massive and intermediate-high submassive risk groups. Additional newer techniques explored are the use of extracorporeal membrane oxygenation, direct aspiration, or fragmentation with aspiration. Because of the constantly changing therapeutic options and the scarcity of randomized controlled trials, choosing the best course of treatment for a given patient may be difficult. To help, the Pulmonary Embolism Reaction Team is a multidisciplinary, rapid response team that has been developed and is used at many institutions. Hence to bridge the knowledge gap, our review highlights various indications of thrombolysis in addition to the recent advances and management guidelines.

Pulmonary embolism: options for interventional treatment in the intermediate-high risk group

Pulmonary embolism: options for interventional treatment in the intermediate-high risk group

It is not the time to abandon intraoperative frozen section in endometrioid adenocarcinoma: A large-scale, multi-center, and retrospective study.

Stage IB (deep myometrial invasion) high-grade endometrioid adenocarcinoma (EA), regardless of LVSI status, is classified into high-intermediate risk groups, requiring surgical lymph node staging. Intraoperative frozen section (IFS) is commonly used, but its adequacy and reliability vary between reports. Hence, we determined the utility of IFS in identification of high-risk factors, including deep myometrial invasion and high-grade. We retrospectively analyzed 9,985 cases operated with hysterectomy and diagnosed with FIGO stage I/II EA in postoperative paraffin section (PS) results at 30 Chinese hospitals from 2000 to 2019. We determined diagnostic performance of IFS and investigated whether the addition of IFS to preoperative biopsy and imaging could improve identification of high-risk factors. IFS and postoperative PS presented the highest concordance in assessing deep myometrial invasion (Kappa: 0.834), followed by intraoperative gross examination (IGE Kappa: 0.643), MRI (Kappa: 0.395), and CT (Kappa: 0.207). IFS and postoperative PS presented the highest concordance for high-grade EA (Kappa: 0.585) compared to diagnostic curettage (D&C 0.226) and hysteroscope (Hys 0.180). Sensitivity and specificity for detecting deep myometrial invasion were 86.21 and 97.20% for IFS versus 51.72 and 88.81% for MRI, 68.97 and 94.41% for IGE. These figures for detecting high-grade EA were 58.21 and 96.50% for IFS versus 16.42 and 98.83% for D&C, 13.43 and 98.64% for Hys. Parallel strategies, including MRI-IFS (Kappa: 0.626), D&C-IFS (Kappa: 0.595), and Hys-IFS (Kappa: 0.578) improved the diagnostic efficiencies of individual preoperative examinations. Based on the high sensitivity of IFS, parallel strategies improved the sensitivities of preoperative examinations to 89.66% (MRI), 64.18% (D&C), 62.69% (Hys), respectively, and these differences were statistically significant (p=0.000). IFS presented reasonable agreement rates predicting postoperative PS results, including deep myometrial invasion and high-grade. IFS helps identify high-intermediate risk patients in preoperative biopsy and MRI and guides intraoperative lymphadenectomy decisions in EA.

The relationship between tumor mean standard uptake value (SUVmax) in preoperative PET/computed tomography and prognostic risk groups in endometrial cancer.

Our aim in this study wasto determine the relationship between tumor mean standard uptake value (SUVmax) value in preoperative PET/computed tomography (CT) and prognostic risk groups in cases with endometrial cancer. A total of 368 patients operated on for endometrial cancer were evaluated in the study. The SUVmax value of endometrial primary tumor of the patients screened within 30 days of operation, was compared with prognostic parametersand risk groups. P value <0.05 was considered significant for all tests. A statistically significant relationship was found between the mean SUVmax value and risk groups (P < 0.001), grade (P < 0.001), stage (P < 0.001), myometrial invasion of the tumor (P < 0.001), cervical involvement (P = 0.002), lymphovascular space invasion (LVSI) (P < 0.001), lymph node metastasis (P < 0.001), tumor size (P < 0.001), lymph node involvement in PET/CT (P < 0.001). There was no significant relationship found between the histologic type of tumor and the mean SUVmax value (P = 0.113). Cutoff SUVmax value for endometrial cancer tumor tissue, which will be used to determine the possible lymph node metastasis, was accepted as 19 as a result of the ROC analysis. The risk of lymph node metastasis was found 4.74 times (confidence interval, 2.510-8.977) higher in patients with SUVmax value above cutoff 19 (P < 0.001). Considering risk groups, it was observed that patients with mean SUVmax value above 19 were in medium/high-high risk group, 2.3 times more than those in low-intermediate risk group (P < 0.001). As a result of logistic regression analysis, in determining intermediate-high and high-risk groups, histological type (P < 0.001), myometrial invasion (P = 0.003), cervical invasion (CI) (P < 0.001), grade (P = 0.018) and SUVmax value (P = 0.028) had statistically significant importance. The higher the mean SUVmax value in the endometrial cancer tumor tissue in preoperative PET/CT in patients with endometrial cancer, the higher the risk group of the patients.

Evaluation of vaginal brachytherapy for treating early-stage endometrial cancer according to the European Society of Medical Oncology 2020 risk stratification.

The aim was to evaluate vaginal brachytherapy (VB) after surgery in early-stage endometrial cancer. The patients with Stage I-II endometrial adeno-cancer operated between 1998 and 2018 and whose adjuvant therapies had been arranged were evaluated retrospectively. A total of 618 patients were enrolled. In 409 patients in the low-risk group, the vaginal, pelvic recurrence, and distant metastasis rates were found to be higher in the VB group. When the results of 112 patients in the intermediate-risk group were evaluated, there was no statistically significant difference between the vaginal, pelvic recurrence, and distance metastasis rates. In 89 patients in the intermediate-high risk group, vaginal recurrence rates were 0%, 4.8%, 0%, and 25% for VB, external beam radiotherapy, combination radiotherapy, and the follow-up groups, respectively (p=0.010), and pelvic recurrence rates were found to be 18.2%, 0%, 1.9% and 0% (p=0.036). Distant metastasis rates were 0%, 0%, 9.6% and 0% (p=0.229). When the overall survival in all groups was examined, no significant difference was found between the groups. In conclusion, no adjuvant treatment is a proper approach for low-risk patients. Brachytherapy can be considered a suitable option for the intermediate risk group. Combined treatments instead of VB in the high-intermediate risk group would be preferred in terms of local control.

Endometrial cancer risk factors, treatment, and survival outcomes as per the European Society for Medical Oncology (ESMO) - European Society of Gynaecological Oncology (ESGO) - European Society for Radiotherapy and Oncology (ESTRO) risk groups and International Federation of Gynecology and Obstetrics (FIGO) staging: An experience from developing world.

There is limited data on endometrial cancer from developing countries. The risk groups as defined by the ESMO-ESGO-ESTRO and their recommendations for adjuvant treatment have redefined the management protocols. In this retrospective analysis, the outcomes are assessed in the light of the new risk groups and FIGO staging. One hundred and two patients of endometrial cancer reporting to the Department of Radiation Oncology from 2015 to 2019 were analysed retrospectively. Patients were stratified as per the ESMO-ESGO-ESTRO risk groups and FIGO staging. Patients were analysed for demographic profile, histopathology details, FIGO stage, treatment modalities received as per the ESMO-ESGO-ESTRO risk groups and the outcomes in terms of disease free survival and overall survival. A total of 102 patients were analysed. The mean age at presentation was 57.7 years. Seventy four percent (74.41%) were stage I patients, 14.7 % were stage II, 8.8% were stage III and remaining 2% were stage IV. The mean disease free survival for the patients in FIGO stage I, II, III and IV were found to be 63.5 (59.9 - 67) months, 60.5 (54.2 - 66.9) months, 30.9 (21.5 - 40.2) months and 15.4 (7.8 - 23.0) months respectively. The 5-year overall survival of patients in Stage I was 90.3%. The 3-year mortality of Stage III patients was 58.3%. While there was no mortality observed among Stage II patients, none of the Stage IV patient survived beyond 20 months. The 5-year disease-free survival for patients in Low Risk (LR) group, Intermediate Risk (IR) group and High Risk (HR) group was found to be 91.3%, 90% and 87% respectively. None of the patient in High Intermediate Risk (HIR) group experienced progression of disease and 33.3% patients in advanced group were disease free at 2 years follow-up. The multivariate analysis showed that lymph node involvement is significantly associated with disease-free (p=0.03) and overall survival (p=0.04). Even in the developing world, majority of patients present in early stage with survival outcomes comparable to the West. FIGO stage and lymph node involvement continue to be the most important prognostic markers for disease outcomes.