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Objectives: To externally and prospectively validate the International Ovarian Tumor Analysis (IOTA) Simple Rules (SRs), Logistic Regression model 2 (LR2) and Assessment of Different NEoplasias in the adneXa (ADNEX) model in a Portuguese population, comparing these approaches with subjective assessment and the risk‐of‐malignancy index (RMI), as well as with each other. This study also aimed to retrospectively validate the IOTA two‐step strategy, using modified benign simple descriptors (MBDs) followed by the ADNEX model in cases in which MBDs were not applicable. Methods: This was a prospective multicenter diagnostic accuracy study conducted between January 2016 and December 2021 of consecutive patients with an ultrasound diagnosis of at least one adnexal tumor, who underwent surgery at one of three tertiary referral centers in Lisbon, Portugal. All ultrasound assessments were performed by Level‐II or ‐III sonologists with IOTA certification. Patient clinical data and serum CA 125 levels were collected from hospital databases. Each adnexal mass was classified as benign or malignant using subjective assessment, RMI, IOTA SRs, LR2 and the ADNEX model (with and without CA 125). The reference standard was histopathological diagnosis. In the second phase, all adnexal tumors were classified retrospectively using the two‐step strategy (MBDs + ADNEX). Sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios and overall accuracy were determined for all methods. Receiver‐operating‐characteristics curves were constructed and corresponding areas under the curve (AUC) were determined for RMI, LR2, the ADNEX model and the two‐step strategy. The ADNEX model calibration plots were constructed using locally estimated scatterplot smoothing (LOESS). Results: Of the 571 patients included in the study, 428 had benign disease and 143 had malignant disease (prevalence of malignancy, 25.0%), of which 42 had borderline ovarian tumor, 93 had primary invasive adnexal cancer and eight had metastatic tumors in the adnexa. Subjective assessment had an overall sensitivity of 97.9% and a specificity of 83.6% for distinguishing between benign and malignant lesions. RMI showed high specificity (95.6%) but very low sensitivity (58.7%), with an AUC of 0.913. The IOTA SRs were applicable in 80.0% of patients, with a sensitivity of 94.8% and specificity of 98.6%. The IOTA LR2 had a sensitivity of 84.6%, specificity of 86.9% and an AUC of 0.939, at a malignancy risk cut‐off of 10%. At the same cut‐off, the sensitivity, specificity and AUC for the ADNEX model with vs without CA 125 were 95.8% vs 98.6%, 82.5% vs 79.7% and 0.962 vs 0.960, respectively. The ADNEX model gave heterogeneous results for distinguishing between benign masses and different subtypes of malignancy, with the highest AUC (0.991) for discriminating benign masses from primary invasive adnexal cancer Stages II–IV, and the lowest AUC (0.696) for discriminating primary invasive adnexal cancer Stage I from metastatic lesion in the adnexa. The calibration plot suggested underestimation of the risk by the ADNEX model compared with the observed proportion of malignancy. The MBDs were applicable in 26.3% (150/571) of cases, of which none was malignant. The two‐step strategy using the ADNEX model in the second step only, with and without CA 125, had AUCs of 0.964 and 0.961, respectively, which was similar to applying the ADNEX model in all patients. Conclusions: The IOTA methods showed good‐to‐excellent performance in the Portuguese population, outperforming RMI. The ADNEX model was superior to other methods in terms of accuracy, but interpretation of its ability to distinguish between malignant subtypes was limited by sample size and large differences in the prevalence of tumor subtypes. The IOTA MBDs are reliable in identifying benign disease. The two‐step strategy comprising application of MBDs followed by the ADNEX model if MBDs are not applicable, is suitable for daily clinical practice, circumventing the need to calculate the risk of malignancy in all patients. © 2024 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Background: The optimal primary debulking surgery outcome of serous ovarian carcinoma (SOC) is greatly affected by primary ovarian neoplasm or metastatic lesion close to the rectum. Purpose: To study the risk factors affecting postoperative residual primary ovarian neoplasm or metastatic lesion close to the rectum of SOC. Material and Methods: The clinical and MRI data of 164 patients with SOC eligible from institution A (training and test groups) and 36 patients with SOC eligible from institution B (external validation group) were collected and retrospectively analyzed. The clinical data included age, serum carbohydrate antigen 125 (CA-125), human epididymis protein 4, and neutrophil-to-lymphocyte ratio (NLR). Magnetic resonance imaging (MRI) data included ovarian mass distribution, maximum diameter of ovarian mass, ovarian mass features, degree of rectal invasion of the primary ovarian neoplasm or metastatic lesion, and amount of ascites. A model was established using multivariate logistic regression. Results: By univariate and multivariate logistic regressions, CA-125 (P = 0.024, odds ratio [OR] = 3.798, 95% confidence interval [CI] = 1.24–13.32), NLR (P = 0.037, OR = 3.543, 95% CI = 1.13–12.72), and degree of rectal invasion of the primary ovarian neoplasm or metastatic lesion (P < 0.001, OR = 37.723, 95% CI = 7.46–266.88) were screened as independent predictors. The area under the curve values of the model in the training, test, and external validation groups were 0.860, 0.764, and 0.778, respectively. Conclusion: The clinical-radiological model based on T1-weighted dual-echo MRI can be used non-invasively to predict postoperative residual ovarian neoplasm or metastasis close to SOC in the rectum. [ABSTRACT FROM AUTHOR]

Background: endometrial cancer (EC) has a high latency, making prognosis difficult to predict. cancer antigen 125 (CA125) is not specific as a tumour marker for EC; however, complete blood count (CBC) inflammatory markers are associated with prognosis in various malignancies. Thus, this study investigated the value of CBC inflammatory markers combined with CA125 levels in predicting the prognosis of patients with EC. Methods: In this study, 517 patients with EC were recruited between January 2015 and January 2022, and clinical characteristics, CBC inflammatory markers, and CA125 levels were assessed. Differences in each index at different EC stages and the correlation between the index and EC stage were analysed, and the influence of the index on EC prognosis was evaluated. Results: Platelet distribution width (PDW) levels were significantly lower in patients with advanced EC than in those with early EC, whereas the systemic immune-inflammation index (SU), neutrophil-to- lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and CA125 levels were significantly higher in patients with advanced EC (all P < 0.05). ROC curve and multivariate logistic regression analyses indicated that decreased PDW and increased CA125 levels were independent risk factors for EC staging progression. in addition, multivariate Cox regression analysis showed that the combination of low PDW and high CA125 (PDW + CA125 = 2) was an independent prognostic factor of survival in EC patients. Kaplan-Meier survival analysis indicated that patients with low PDW and high CA125 had worse overall survival. Conclusions: The PDW and CA125 score may be an independent prognostic factor for postoperative overall survival in patients with EC and a useful marker for predicting the prognosis of these patients. [ABSTRACT FROM AUTHOR]

This article discusses a case of eosinophilic cholecystitis with polyserositis that mimicked malignancy in a 36-year-old man. The patient presented with symptoms of abdominal fullness and poor appetite, and laboratory findings showed elevated inflammatory markers and peripheral eosinophils. Imaging tests indicated peritonitis, pleural and pericardial effusions, and a thickened gallbladder wall. Despite initial suspicions of gallbladder malignancy, cholecystectomy revealed eosinophilic cholecystitis. The patient's condition improved after surgery, with reduced eosinophil count and resolution of symptoms. The article highlights the misleading clinical picture created by the multisystemic manifestations of eosinophilic cholecystitis. [Extracted from the article]

This study aimed to analyze the relationship between human epididymal protein 4 (HE4) and infiltration depth, postoperative recurrence, and metastasis of epithelial ovarian cancer (OVCA). Immunohistochemistry was used to detect the expression level of HE4 in cancer tissues and adjacent tissues of 90 patients with epithelial OVCA admitted to our hospital from May 2017 to January 2018. Cox regression was used to analyze the factors affecting the prognosis of epithelial OVCA. The relationship between HE4 and the prognosis of epithelial OVCA was analyzed by the receiver operating characteristic curve and Kaplan‐Meier survival curve. The positive expression rate of HE4 in epithelial OVCA was 85.56%, which was higher than 34.44% in adjacent tissues (p < 0.01). The International Federation of Gynecology and Obstetrics stage, infiltration depth, lymph node metastasis, postoperative recurrence and metastasis, and HE4 positivity were independent risk factors for the prognosis, and platinum‐based chemotherapy sensitivity was an independent protective factor for the prognosis of patients with epithelial OVCA (p < 0.05). The area under the curve of HE4 in diagnosing epithelial OVCA and predicting recurrence was 0.863 and 0.700, the sensitivity was 91.60% and 85.60%, and the specificity was 90.20% and 65.60%. The median progression‐free survival and overall survival were 26.1 and 30.2 months in HE4‐positive epithelial OVCA patients, while these were 31.4 and 35.6 months in HE4‐negative epithelial OVCA patients (p < 0.05). In conclusion, HE4 was highly expressed in epithelial OVCA tissues. Its expression level was related to the depth of tumor invasion, postoperative recurrence and metastasis, and other clinicopathological characteristics of patients with epithelial OVCA. [ABSTRACT FROM AUTHOR]

Background: Carbohydrate antigen 125 (CA125) is a proteolytic fragment of MUC-16 that is increased in heart failure (HF) and associated with inflammation, fluid overload, and worse adverse events. Our main objective was to study the expression of CA125 on epicardium and its association with inflammation, adipogenesis, and fibrosis. Methods: Epicardial fat biopsies and blood were obtained from 151 non-selected patients undergoing open heart surgery. Immunohistochemistry, ELISA, or real-time PCR were used for analyzing protein or mRNA expression levels of CA125 and markers of inflammatory cells, fibroblasts, and adipocytes. Epithelial or stromal cells from epicardium were isolated and cultured to identify CA125 and its association with the adipogenesis and fibrosis pathways, respectively. Results: The median age was 71 (63–74) years, 106 patients (70%) were male, and 62 (41%) had an established diagnosis of HF before surgery. The slice of epicardial fat biopsy determined a positive and colorimetric staining on the epithelial layer after incubating with the CA125 M11 antibody, providing the first description of CA125 expression in the human epicardium. Epicardial CA125 showed a strong and positive correlation with markers of inflammation and fibrosis in the epicardial fat tissue while exhibiting a negative correlation with markers of the adipogenesis pathway. This relationship remained significant after adjusting for potential confounders such as a prior HF diagnosis and plasma CA125 levels. Conclusion: Epicardial cells express CA125, which is positively associated with inflammatory and fibroblast markers in epicardial adipose tissue. These results suggest that CA125 may be biologically involved in HF progression (transition from adipogenesis to fibrosis). Highlights: This is the first time that CA125 was identified on human epicardium biopsies and primary culture of epithelial cells was performed. This is a promising tool for understanding the pathophysiological mechanisms association between CA-125 and HF progression. [ABSTRACT FROM AUTHOR]

Elevated allostatic load (AL), an integrated, cumulative marker of physiologic damage due to socioenvironmental stress, is associated with increased mortality in patients with breast, lung, and other cancers. The relationship between allostatic load and mortality in ovarian cancer patients remains unknown. We examined the relationship between allostatic load and overall survival in ovarian cancer patients. This cross-sectional study used data from 201 patients enrolled in a prospective observational ovarian cancer cohort study at a National Cancer Institute-designated Comprehensive Cancer Center from October 2012 through June 2022. All patients underwent debulking surgery and completed a full course of standard-of-care platinum-based chemotherapy. Follow-up was completed through January 2024. Allostatic load was calculated as a summary score by assigning one point to the worst sample quartile for each of ten biomarkers measured within 45 days before the ovarian cancer diagnosis. High allostatic load was defined as having an allostatic load in the top quartile of the summary score. A Cox proportional hazard model with robust variance tested the association between allostatic load and overall survival. There were no associations between allostatic load and ovarian cancer clinical characteristics. After accounting for demographic, clinical, and treatment factors, high allostatic load was associated with a significant increase in mortality (hazard ratio 2.17 [95%CI, 1.13–4.15]; P = 0.02). Higher allostatic load is associated with worse survival among ovarian cancer patients. Allostatic load could help identify patients at risk for poorer outcomes who may benefit from greater socioenvironmental support during treatment. • Allostatic load (AL) is an integrated, cumulative marker of physiologic damage due to socioenvironmental stress. • AL is calculated using 10 clinical markers across 4 physiologic systems routinely measured before ovarian cancer treatment. • Greater AL is associated with poorer survival in patients with ovarian cancer. • AL may identify patients at risk for poorer outcomes who may benefit from greater socioenvironmental support during care. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer has the highest mortality among gynecologic cancers, primarily because it typically is diagnosed at a late stage and because of the development of chemoresistance in recurrent disease. Improving outcomes in women with platinumresistant ovarian cancer is a substantial unmet need. Activation of the glucocorticoid receptor (GR) by cortisol has been shown to suppress the apoptotic pathways used by cytotoxic agents, limiting their efficacy. Selective GR modulation may be able to counteract cortisol's antiapoptotic effects, enhancing chemotherapy's efficacy. A previous phase 2 study has shown that adding intermittently dosed relacorilant, a selective GR modulator, to nab-paclitaxel improved outcomes, including progression-free survival (PFS) and overall survival (OS), with minimal added toxicity, in women with recurrent platinum-resistant ovarian cancer. The ROSELLA study aims to confirm and expand on these findings in a larger population. Methods: ROSELLA is a phase 3, randomized, 2-arm, open-label, global multicenter study in women with recurrent, platinum-resistant, high-grade serous epithelial ovarian, primary peritoneal, or fallopian tube cancer. Eligible participants have received 1 to 3 lines of prior systemic anticancer therapy, including ≥1 prior line of platinum therapy and prior treatment with bevacizumab, with documented progressive disease or intolerance to the most recent therapy. There is no biomarker-based requirement for participant selection. Participants are randomized 1:1 to receive intermittently dosed relacorilant in combination with nabpaclitaxel or nab-paclitaxel monotherapy. The study's primary efficacy endpoint is PFS as assessed by blinded independent central review. Secondary efficacy endpoints include OS, investigator-assessed PFS, objective response rate, best overall response, duration of response, clinical benefit rate at 24 weeks, and cancer antigen 125 response. The study is also evaluating safety and patient-reported outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Serum levels of procalcitonin and C‐reactive protein (CRP) have been used to predict anastomotic leakage after colorectal surgery, but information is scarce in advanced ovarian cancer (AOC) surgery with bowel resection. This study aimed to assess the predictive value of procalcitonin and CRP in detecting anastomotic leakage after AOC surgery with bowel resection. The study also aimed to determine the optimal postoperative reference values and the best day for evaluating these markers. Material and methods: This prospective, observational and multicentric trial included 92 patients with AOC undergoing debulking surgery with bowel resection between 2017 and 2020 in 10 reference hospitals in Spain. Procalcitonin and CRP levels were measured at baseline and on postoperative days 1–6. Receiver operating characteristic analysis was performed to evaluate the predictive value of procalcitonin and CRP at each postoperative day. Sensitivity, specificity, positive and negative predictive values were calculated. Results: Anastomotic leakage was detected in six patients (6.5%). Procalcitonin and CRP values were consistently higher in patients with anastomotic leakage at all postoperative days. The maximum area under the curve (AUC) for procalcitonin was observed at postoperative day 1 (AUC = 0.823) with a cutoff value of 3.8 ng/mL (83.3% sensitivity, 81.3% specificity). For CRP, the maximum AUC was found at postoperative day 3 (AUC = 0.833) with a cutoff level of 30.5 mg/dL (100% sensitivity, 80.4% specificity). Conclusions: Procalcitonin and C‐reactive protein are potential biomarkers for early detection of anastomotic leakage after ovarian cancer surgery with bowel resection. Further prospective studies with a larger sample size are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to assess the clinical importance of various biomarkers, including NLR, CEA, CA199, CA125, CA153, and HE4, through dynamic testing to evaluate the effectiveness of neoadjuvant chemotherapy (NACT) for individuals facing advanced ovarian cancer. This provides valuable information for tailoring treatment plans to individual patients, thereby leading to a more personalized and effective management of individuals facing ovarian cancer. Methods: The levels of NLR, CA125, CA199, CEA, CA153, and HE4 were detected before chemotherapy and after 3 courses of chemotherapy. Patients were categorized into ineffective and effective groups according to the effectiveness of NACT. To evaluate the factors influencing NACT’s effectiveness in individuals facing advanced ovarian cancer, receiver operating characteristic (ROC) curves, predictive modeling, and multifactorial regression analysis were employed. Results: In the effective group, the patients’ age, maximum tumor diameter, and CEA and HE4 levels of the patients were significantly higher compared to those in the ineffective group (P <.05). Additionally, the difference in HE4 levels before and after treatment between the effective and ineffective groups was statistically significant (P<.05). Multifactorial analysis showed that age and maximum tumor diameter were independent risk factors impacting the effectiveness of NACT in individuals facing advanced ovarian cancer (P<.05). The ROC curve for predicting the effectiveness of NACT in individuals facing advanced ovarian cancer showed a sensitivity of 93.3% for NLR and a specificity of 92.3% for CA199. HE4 emerged as the most reliable predictor, demonstrating a specificity of 84.6% and a sensitivity of 75.3%. The area under the curve of the combined CA125 and HE4 assays for predicting the ineffectiveness of NACT in individuals facing advanced ovarian cancer was 0.825, showcasing a specificity of 74.2% and a sensitivity of 84.6%. Conclusion: The predictive capacity for the effectiveness of NACT in individuals facing advanced ovarian cancer is notably high when considering the sensitivity of NLR and the specificity of CA199. Additionally, the combination of CA125 and HE4 assays can obtain a better predictive effect, which can accurately select patients suitable for NACT, determine the appropriate timing of the interval debulking surgery (IDS) surgery, and achieve a satisfactory tumor reduction effect. [ABSTRACT FROM AUTHOR]

Objective: To describe the characteristics of pregnant women diagnosed with adnexal masses and review our experience with diagnosis, management and treatment modalities in this area for which there are no definitive treatment guidelines. Methods: All women with adnexal masses during pregnancy whose management and follow-up was completed at a large tertiary referral center between January 2018 and September 2023 were retrospectively evaluated. After applying the exclusion criteria, a total of 19 women who underwent antepartum laparoscopic adnexal surgery (group 1) and 34 women who underwent expectant management (group 2) were included. Results: Gestational age at birth, cesarean section rates, birthweight and APGAR-5 scores were similar, while the largest mass diameter and CA-125 levels were significantly higher in group 1 (p<0.001 and p=0.014, respectively). Of the patients in group 1, 15 (78.9%) had unilateral complex cysts and 4 (21.1%) had unilateral simple cysts, while there were no bilateral masses. Emergency laparoscopy was performed in 6 (31.6%) of patients for adnexal torsion and in 7 (36.8%) for cyst rupture, while elective laparoscopy was performed in 6 (31.6%) asymptomatic patients with suspected malignancy. While functional cyst was the most common histopathologic finding, malignancy was found in 2 cases (granulosa cell tumor and endometrioid adenocarcinoma). Preterm births occurred in 8 (41.1%) women, of whom 5 (26.3%) gave birth before 34 weeks' gestation and 3 (15.7%) between 34-36 weeks and 6 days. Conclusion: Parallel to the increase in ultrasound examinations in early pregnancy, both the overdiagnosis and early detection of adnexal masses during pregnancy have increased. Given the high rate of spontaneous regression in most lesions and the fact that bleeding in ruptured cases is usually self-limiting, an expectant approach would be appropriate in cases without hemodynamic instability, acute abdomen and/or suspected malignancy. Laparoscopy is a safe and efficient surgical approach for surgery. [ABSTRACT FROM AUTHOR]

Background: Tumor immunotherapy has become an important adjuvant therapy after surgery, radiotherapy, and chemotherapy. In recent years, the role of tumor‐associated antigen (TAA) in tumor immunotherapy has become increasingly prominent. Cancer‐testis antigen (CTA) is a kind of TAA that is highly restricted in a variety of tumors and can induce an immune response. Aims: This review article aimed to evaluate the role of CTA on the progression of ovarian cancer, its diagnostic efficacy, and the potential for immunotherapy. Methods: We analyzed publications and outlined a comprehensive of overview the regulatory mechanism, immunogenicity, clinical expression significance, tumorigenesis, and application prospects of CTA in ovarian cancer, with a particular focus on recent progress in CTA‐based immunotherapy. Results: The expression of CTA affects the occurrence, development, and prognosis of ovarian cancer and is closely related to tumor immunity. Conclusion: CTA can be used as a biomarker for the diagnosis and prognosis evaluation of ovarian cancer and is an ideal target for antitumor immunotherapy. These findings provide novel insights on CTA in the improvement of diagnosis and treatment for ovarian cancer. The successes, current challenges and future prospects were also discussed to portray its significant potential. [ABSTRACT FROM AUTHOR]

• For patients with EMs-related infertility undergoing laparoscopic surgery, factors such as age > 35 years, infertility duration > 3 years, concurrent adenomyosis, severe EMs, surgery duration ≥ 2 h, intraoperative blood loss ≥ 50 ml, and low AMH before surgery are detrimental for the pregnancy rate within the first postoperative year. • However, BMI, dysmenorrhea, past history of pelvic surgery, EMs pathology types (ovarian, peritoneal, deep infiltrating),and preoperative result of serum CA125 barely show any statistical difference in their effect on postoperative pregnancy rates. • In terms of postoperative live birth rate, age > 35 years, severe EMs, intraoperative blood loss ≥ 50 ml, and adenomyosis were adverse factors. To analyze the factors that might influence the pregnancy rate in patients with infertility related to endometriosis (EMs) after undergoing laparoscopic surgery, providing guidance for our clinical diagnostic and therapeutic decision-making. A retrospective analysis was conducted on clinical records and 1-year postoperative pregnancy outcomes of 335 patients diagnosed with endometriosis-related infertility via laparoscopic surgery, admitted to our department from January 2018 to December 2020. The overall pregnancy rate for patients with endometriosis (EMs) related infertility 1-year post-surgery was 57.3 %, with the highest pregnancy rate observed between 3 to 6 months after surgery. Factors such as Body Mass Index (BMI) (P = 0.515), presence of dysmenorrhea (P = 0.515), previous pelvic surgery (P = 0.247), type of EMs pathology (P = 0.893), and preoperative result of serum carbohydrate antigen 125 (CA125)（ P = 0.615）had no statistically significant effect on postoperative pregnancy rates. The duration of infertility (P = 0.029), coexistence of adenomyosis (P = 0.042), surgery duration (P = 0.015), intraoperative blood loss (P = 0.050), preoperative result of serum anti-Müllerian hormone (AMH) (P = 0.002) and age greater than 35 (P = 0.000) significantly impacted postoperative pregnancy rates. The post-surgery pregnancy rate in patients with mild (Stage I-II) EMs was notably higher than those with moderate to severe (Stage III-IV) EMs (P = 0.009). Age (P = 0.002), EMs stage (P = 0.018), intraoperative blood loss (P = 0.010) and adenomyosis (P = 0.022) were the factors that affected the postoperative live birth rate. For patients with EMs-related infertility undergoing laparoscopic surgery, factors such as age > 35 years, infertility duration > 3 years, concurrent adenomyosis, severe EMs, surgery duration ≥ 2 h, intraoperative blood loss ≥ 50 ml, and low AMH before surgery are detrimental for the pregnancy rate within the first postoperative year. However, BMI, dysmenorrhea, past history of pelvic surgery, EMs pathology types (ovarian, peritoneal, deep infiltrating),and preoperative result of serum CA125 barely show any statistical difference in their effect on postoperative pregnancy rates. In terms of postoperative live birth rate, age > 35 years, severe EMs, intraoperative blood loss ≥ 50 ml, and adenomyosis were adverse factors. [ABSTRACT FROM AUTHOR]

Introduction: Despite the remarkable progress in minimally invasive surgery, the potential association between laparoscopic gastrectomy and the risk of peritoneal metastasis remains uncertain. Aim: To investigate variations in tumour markers in intraperitoneal drainage fluid between laparoscopic radical gastrectomy and open radical gastrectomy for gastric cancer. Material and methods: A total of 106 patients diagnosed with gastric cancer between July 2018 and November 2020 were included in this study, 45 of whom underwent laparoscopic radical gastrectomy (laparoscopic group) and 61 underwent open radical gastrectomy (open group). Variations in the levels of carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), cancer antigen 199 (CA199), and a-fetoprotein (AFP) in the intraperitoneal drainage fluid were compared and analysed on postoperative days (PODs) 1, 2, 3, and 5 between the two groups. Additionally, the postoperative 3-year survival rates between the two groups were compared and analysed. Results: No significant differences in CEA, CA199, and AFP levels in the intraperitoneal drainage fluid were observed between the two groups on postoperative days (PODs) 1, 2, 3, and 5 (p > 0.05). However, the level of CA125 in the intraperitoneal drainage fluid of the laparoscopic group was notably higher than that of the open group on POD 2 (p < 0.05); however, there were no significant differences between the two groups on PODs 1, 3, and 5 (p > 0.05). There was no significant difference in the 3-year postoperative survival rates between the two groups. Conclusions: There were no significant differences in CEA, CA125, CA199, and AFP levels in the intraperitoneal drainage fluid between laparoscopic radical gastrectomy and open radical gastrectomy for gastric cancer, confirming from another perspective that laparoscopic radical gastrectomy does not increase the risk of intraperitoneal metastasis. [ABSTRACT FROM AUTHOR]

This article discusses the topic of acute abdominal pain caused by ovarian endometriosis, a common gynecologic disease. The study examined the characteristics and outcomes of patients who underwent surgical intervention for this condition. The findings suggest that certain symptoms, such as sudden onset of pain, enlargement of the adnexal mass with tenderness, and a history of dysmenorrhea requiring painkillers, are important indicators of ovarian endometriosis manifesting as acute abdominal pain. Patients with progressive ovarian endometriosis are more likely to experience severe pain, fever, and leukocytosis. The study recommends early intervention and elective surgery for stable patients, but acknowledges the limitations of its retrospective design and single-center data. Further research is needed to improve treatment and explore long-term outcomes. [Extracted from the article]

Background: Distant metastases of ovarian cancer are rarely detected alone. The effectiveness of surgical intervention for pulmonary metastases from ovarian cancer remains uncertain. This study aimed to investigate the clinicopathologic characteristics and outcomes of patients undergoing resection for pulmonary metastasis from ovarian cancer. Case presentation: The clinicopathologic characteristics and outcomes of radical surgery for pulmonary metastasis from ovarian cancer were investigated. Out of 537 patients who underwent pulmonary metastasis resection at two affiliated hospitals between 2010 and 2021, four (0.74%) patients who underwent radical surgery for pulmonary metastasis from ovarian cancer were included. The patients were aged 67, 47, 21, and 59 years; the intervals from primary surgery to detection of pulmonary metastasis from ovarian cancer were 94, 21, 36, and 50 months; and the overall survival times after pulmonary metastasectomy were 53, 50, 94, and 34 months, respectively. Three of the four patients experienced recurrence after pulmonary metastasectomy. Further, preoperative carbohydrate antigen (CA) 125 levels were normal in two surviving patients and elevated in the two deceased patients. Conclusion: In this study, three of the four patients experienced recurrence after pulmonary metastasectomy, but all patients survived for > 30 months after surgery. Patients with ovarian cancer and elevated CA125 levels may not be optimal candidates for pulmonary metastasectomy. To establish appropriate criteria for pulmonary metastasectomy in patients with ovarian cancer, further research on a larger patient cohort is warranted. [ABSTRACT FROM AUTHOR]

Background: The modeled CA-125 elimination constant K (KELIM) is a potential marker of tumor chemosensitivity in ovarian cancer patients treated with neoadjuvant chemotherapy (NACT) before interval surgery. The objective of this study was to externally validate the KELIM (rate of elimination of CA-125) score in patients with high-grade serous ovarian cancer (HGSC) undergoing NACT and explore its relation to the completeness of IDS and survival. Methods: The study was based on a retrospective cohort of 133 patients treated for advanced HGSC, International Federation of Gynecology and Obstetrics (FIGO) stages III–IV, with neoadjuvant chemotherapy, folllowed by interval surgery, in two centres in China. CA-125 concentrations at baseline and during neoadjuvant chemotherapy were collected. We used standardized (std) KELIM for subsequent analysis. Clinicopathologic parameters were collected, and Kaplan‒Meier survival analyses were performed for PFS and OS. Results: KELIM was an independent predictor of the probability of complete surgery and survival in our cohort. The median std KELIM score of patients with complete surgery was significantly higher than that of patients with incomplete IDS (1.20 vs. 0.71, P < 0.001). Multivariate analysis showed that a std KELIM score 0.925 was an independent predictive factor for achieving complete resection (OR = 5.480; 95% CI, 2.409–12.466, P < 0.001) and better PFS (HR = 0.544; 95% CI: 0.349–0.849, P = 0.007) and OS (HR = 0.484; 95% CI: 0.251–0.930, P = 0.030). Conclusions: The tumor-primary tumor chemosensitivity, assessed by the modeled CA-125 KELIM, calculated during NACT, is a major parameter to consider for decision-making regarding IDS attempts and predicting patient survival. [ABSTRACT FROM AUTHOR]

Objective: To determine whether proactive molecular risk classifier for endometrial cancer (ProMisE) could be used to assess the prognosis of patients with atypical endometrial hyperplasia (AEH) or early-stage endometrial cancer (EC) treated with levonorgestrelreleasing intrauterine system (LNG-IUS). Methods: A retrospective cohort study was conducted among 93 AEH or early-stage EC patients who received LNG-IUS to preserve fertility. By immunohistochemistry and gene sequencing, 4 subtypes of ProMisE were identified (p53 wild type [p53 wt], mismatch repairdeficient [MMRd], p53-abnormal, and POLE-mutated). The primary outcome was the time to complete response (CR) after LNG-IUS therapy. Secondary outcomes included the recurrence rate after CR and success rate of conception. Results: Among the 93 patients, 15 (16.1%) were classified as MMRd, 6 (6.5%) as POLEmutated, 5 (5.4%) as p53-abnormal, and 67 (72.0%) as p53 wt. Comparison of serum cancer antigen 125, family history of tumor, and positive rates of programmed cell death 1 ligand 1 protein and Ki67 protein in 4 groups showed statistically significant differences (p<0.05). Patients with the p53-abnormal subtype had the lowest overall CR rate (40%) and the highest recurrence rate (2/2). Patients with POLE-mutated subtype had the best prognosis, and all 6 patients achieved CR. When patients achieved complete remission, assisted reproductive technology was more likely to help them conceive than natural conception (p<0.05). Conclusion: Patients with early-stage EC or AEH who are more likely to benefit from fertilitysparing treatment can be identified using ProMisE classifier. Patients with POLE-mutated are suitable for fertility-sparing treatment with LNG-IUS. [ABSTRACT FROM AUTHOR]

PURPOSE: The multicenter, open-label, randomized phase 2 NCI-9944 study (NCT02595892) demonstrated that addition of ATR inhibitor (ATRi) berzosertib to gemcitabine increased progression-free survival (PFS) compared to gemcitabine alone (hazard ratio [HR]=0.57, one-sided log-rank P =.044, which met the one-sided significance level of 0.1 used for sample size calculation). METHODS: We report here the final overall survival (OS) analysis and biomarker correlations (ATM expression by immunohistochemistry, mutational signature 3 and a genomic biomarker of replication stress) along with post-hoc exploratory analyses to adjust for crossover from gemcitabine to gemcitabine/berzosertib. RESULTS: At the data cutoff of January 27, 2023 (>30 months of additional follow-up from the primary analysis), median OS was 59.4 weeks with gemcitabine/berzosertib versus 43.0 weeks with gemcitabine alone (HR 0.79, 90% CI 0.52 to 1.2, one-sided log-rank P =.18). An OS benefit with addition of berzosertib to gemcitabine was suggested in patients stratified into the platinum-free interval ≤3 months (N = 26) subgroup (HR, 0.48, 90% CI 0.22 to 1.01, one-sided log-rank P =.04) and in patients with ATM-negative/low (N = 24) tumors (HR, 0.50, 90% CI 0.23 to 1.08, one-sided log-rank P =.06). CONCLUSION: The results of this follow-up analysis continue to support the promise of combined gemcitabine/ATRi therapy in platinum resistant ovarian cancer, an active area of investigation with several ongoing clinical trials. Final OS and biomarker analysis support the promise of gemcitabine with ATR inhibitor therapy in platinum resistant ovarian cancer [ABSTRACT FROM AUTHOR]

Background: Single‐agent immune checkpoint inhibitors (ICIs) have demonstrated limited responses in recurrent ovarian cancer; however, 30%–40% of patients achieve stable disease. The primary objective was to estimate progression‐free survival (PFS) after sequential versus combination cytotoxic T‐lymphocyte antigen 4 and programmed death ligand 1 ICIs in patients with platinum‐resistant high‐grade serous ovarian cancer (HGSOC). Methods: Patients were randomized to a sequential arm (tremelimumab followed by durvalumab on progression) or a combination arm (tremelimumab plus durvalumab, followed by durvalumab) via a Bayesian adaptive design that made it more likely for patients to be randomized to the more effective arm. The primary end point was immune‐related PFS (irPFS). Results: Sixty‐one subjects were randomized to sequential (n = 38) or combination therapy (n = 23). Thirteen patients (34.2%) in the sequential arm received durvalumab. There was no difference in PFS in the sequential arm (1.84 months; 95% CI, 1.77–2.17 months) compared with the combination arm (1.87 months; 95% CI, 1.77–2.43 months) (p =.402). In the sequential arm, no responses were observed, although 12 patients (31.6%) demonstrated stable disease. In the combination arm, two patients (8.7%) had partial response, whereas one patient (4.4%) had stable disease. Adverse events were consistent with those previously reported for ICIs. Patient‐reported outcomes were similar in both arms. Conclusions: There was no difference in irPFS for combination tremelimumab plus durvalumab compared to tremelimumab alone (administered as part of a sequential treatment strategy) in a heavily pretreated population of patients with platinum‐resistant HGSOC. Response rates were comparable to prior reports, although the combination regimen did not add significant benefit, as has been previously described. There was no difference in the median progression‐free survival for combination tremelimumab plus durvalumab compared to tremelimumab alone (administered as part of a sequential treatment strategy) in a heavily pretreated population of patients with platinum‐resistant high‐grade serous ovarian cancer. The adverse event profile was consistent with that previously reported for immune checkpoint blockade, and patient‐reported outcomes were similar in both arms. [ABSTRACT FROM AUTHOR]

This article explores the relationship between tumor vessel heterogeneity and the response to neoadjuvant chemotherapy in ovarian cancer patients. The study utilized human intravital microscopy to directly observe tumor vessel characteristics. The findings revealed that tumor vessels in patients had smaller diameters, lower velocities, and a higher proportion of non-functional vessels compared to normal tissues. Patients who had a poorer response to chemotherapy had a lower number and density of functional blood vessels and a higher number of non-functional vessels. The study suggests that tumor vessel heterogeneity may play a role in determining treatment outcomes in ovarian cancer. Additionally, the article discusses the correlation between pathologic tumor vessel measurements and human intravital microscopy measurements. The study found a significant correlation between pathologic vessel density and HIVM vessel density, as well as between pathologic vessel diameter and HIVM-measured diameters. The researchers also observed that patients who had a complete or partial response to neoadjuvant chemotherapy had higher vessel density and larger blood vessels compared to those with stable or progressive disease. The study suggests that human intravital microscopy can be utilized to monitor drug delivery and investigate tumor vessel heterogeneity. [Extracted from the article]

Background: Ovarian clear cell carcinoma (OCCC) is one of the special histologic subtypes of ovarian cancer. This study aimed to construct and validate log odds of positive lymph nodes (LODDS)-based nomograms for predicting the overall survival (OS) and cancer-specific survival (CSS) in patients with OCCC. Methods: Patients who underwent surgical treatment between 2010 and 2016 were extracted from the Surveillance Epidemiology and End Results (SEER) database and the data of OCCC patients from the First Affiliated Hospital of Dalian Medical University were used as the external validation group to test the validity of the prognostic model. The best-fitting models were selected by stepwise Cox regression analysis. Survival probability was calculated by the Kaplan-Meier method, and the differences in survival time between subgroups were compared using the log-rank test. Each nomogram's performance was assessed by the calibration plots, decision curve analysis (DCA), and receiver operating characteristics (ROC) curves. Results: T stage, distant metastasis, marital status, and LODDS were identified as significant risk factors for OS. A model with four risk factors (age, T stage, stage, and LODDS value) was obtained for CSS. Nomograms were constructed by incorporating the prognostic factors to predict 1-, 3- and 5-year OS and CSS for OCCC patients, respectively. The area under the curve (AUC) range of our nomogram model for OS and CSS prediction ranged from 0.738-0.771 and 0.769-0.794, respectively, in the training cohort. The performance of this model was verified in the internal and external validation cohorts. Calibration plots illustrated nomograms have good prognostic reliability. Conclusion: Predictive nomograms were constructed and validated to evaluate the OS and CSS of OCCC patients. These nomograms may provide valuable prognostic information and guide postoperative personalized care in OCCC. [ABSTRACT FROM AUTHOR]

Background: Residual disease following cytoreductive surgery in patients with ovarian cancer has been associated with poorer survival outcomes compared with no residual disease. We performed a meta-analysis to assess the impact of varying levels of residual disease status on survival outcomes in patients with ovarian cancer who have undergone primary cytoreductive surgery or interval cytoreductive surgery in the setting of new therapies for this disease. Methods: Medline, Embase, and Cochrane databases (January 2011 – July 2020) and grey literature, bibliographic and key conference proceedings, were searched for eligible studies. Fixed and random-effects meta-analyses compared progression and survival by residual disease level across studies. Heterogeneity between comparisons was explored via type of surgery, disease stage, and type of adjuvant chemotherapy. Results: Of 2832 database and 16 supplementary search articles screened, 50 studies were selected; most were observational studies. The meta-analysis showed that median progression-free survival and overall survival decreased progressively with increasing residual disease (residual disease categories of 0 cm, > 0–1 cm and > 1 cm). Compared with no residual disease, hazard ratios (HR) for disease progression increased with increasing residual disease category (1.75 [95% confidence interval: 1.42, 2.16] for residual disease > 0–1 cm and 2.14 [1.34, 3.39] for residual disease > 1 cm), and also for reduced survival (HR versus no residual disease, 1.75 [ 1.62, 1.90] for residual disease > 0–1 cm and 2.32 [1.97, 2.72] for residual disease > 1 cm). All comparisons were significant (p < 0.05). Subgroup analyses showed an association between residual disease and disease progression/reduced survival irrespective of type of surgery, disease stage, or type of adjuvant chemotherapy. Conclusions: This meta-analysis provided an update on the impact of residual disease following primary or interval cytoreductive surgery, and demonstrated that residual disease was still highly predictive of progression-free survival and overall survival in adults with ovarian cancer despite changes in ovarian cancer therapy over the last decade. Higher numerical categories of residual disease were associated with reduced survival than lower categories. [ABSTRACT FROM AUTHOR]

The genome-wide profiling of 5-hydroxymethylcytosines (5hmC) on circulating cell-free DNA (cfDNA) has revealed promising biomarkers for various diseases. The purpose of this study was to investigate 5hmC signals in serum cfDNA and identify novel predictive biomarkers for the development of chemoresistance in high-grade serous ovarian cancer (HGSOC). We hypothesized that 5hmC profiles in cfDNA reflect the development of chemoresistance and elucidate pathways that may drive chemoresistance in HGSOC. Moreover, we sought to identify predictors that would better stratify outcomes for women with intermediate-sensitive HGSOC. Women diagnosed with HGSOC and known platinum sensitivity status were selected for this study. Nano-hmC-Seal was performed on cfDNA isolated from archived serum samples, and differential 5hmC features were identified using DESeq2 to establish a model predictive of chemoresistance. A multivariate model consisting of three features (preoperative CA-125, largest residual implant after surgery, 5hmC level of OSGEPL) , stratified samples from intermediate sensitive, chemo-naive women diagnosed with HGSOC into chemotherapy-resistant- and sensitive-like strata with a significant difference in overall survival (OS). Independent analysis of The Cancer Genome Atlas data further confirmed that high OSGEPL1 expression is a favorable prognostic factor for HGSOC. We have developed a novel multivariate model based on clinico-pathologic data and a cfDNA-derived 5hmC modified gene, OSGEPL1 , that predicted response to platinum-based chemotherapy in intermediate-sensitive HGSOC. Our multivariate model applies to chemo-naïve samples regardless if the patint was treated with adjuvant or neoadjuvant chemotherapy. These results merit further investigation of the predictive capability of our model in larger cohorts. • Chemotherapy does not alter global 5hmC deposition patterns on genomic features. • Neoadjuvant-treated platinum resistant disease is enriched in pathways associated with cellular responses to stress. • Adjuvant-treated platinum resistant disease is enriched in pathways associated with drug- and metabolism pathways. • An adjuvant chemotherapy-specific model stratifies intermediate sensitive disease into resistant- and sensitive-like groups. [ABSTRACT FROM AUTHOR]

Objective: To study clinical characters and outcomes in patients of malignant ovarian germ cell tumor (MOGCT) undergoing surgery following neoadjuvant chemotherapy (NACT). Methods: Retrospective study of patients undergoing surgery following NACT for MOGCT at our institute. Platinum based chemotherapy was given in all patients in NACT. Results: Between March 2013 and February 2023, 30 patients had surgery after NACT. Patient's median age was 22 years (range, 12 to 35 years) and median follow up 42months (range, 6 to 132 months). Majority had endodermal sinus tumor (n=12), dysgerminoma (n=9) and mixed GCT (n=7). All had either International Federation of Gynecology and Obstetrics (FIGO) stage 3 (n=19) or FIGO stage 4 disease (n=11). Complete response to NACT seen in 5 patients and 23 patients had partial response. Fertility sparing surgery in 18 patients and complete surgery in 12 patients. Suboptimal surgery was seen in 4 patients. Currently, 20 of 30 patients are alive and disease free, 3 lost for follow up and 7 patients had progression after adjuvant therapy. Five patients had mortality--4 with progression and 1 with bleomycin toxicity. Fifteen of 17 eligible patients have resumed menstruation and one had successful pregnancy. Prognostic factors noted in study are stage, optimal surgery and viable tumor in histopathology. Dysgerminoma had better outcome than other histology. Conclusion: NACT may be a reasonable option in patients with extensive unresectable disease or in whom fertility sparing is not possible or in the poor general condition. Fertility sparing surgery can be attempted post neoadjuvant chemotherapy without adversely affecting prognosis. [ABSTRACT FROM AUTHOR]

Purpose: Few studies have focused on the management of inoperable ampullary carcinoma (AC), and patients with jaundice suffer from biliary stents replacement frequently. Iodine-125 (125I) brachytherapy has been used in the treatment of malignant tumors owing to its curative effect, minimal surgical trauma, and tolerable complications. The aim of the study was to investigate the role of 125I seed implantation in patients with unresectable ampullary carcinoma after relief of obstructive jaundice. Material and methods: A total of 44 patients with obstructive jaundice resulting from unresectable ampullary carcinoma from January 1, 2010 to October 31, 2020 were enrolled in the study. Eleven patients underwent implantation of 125I seeds under endoscopic ultrasound (EUS) after receiving biliary stent placement via endoscopic retrograde cholangiopancreatography (ERCP) (treatment group), and 33 patients received a stent alone via ERCP (control group). Cox regression model was applied in this single-center retrospective comparison study. Results: The median maximum intervention interval for biliary obstruction was 381 days (interquartile range [IQR]: 204-419 days) in the treatment group and 175 days (IQR: 126-274 days) in the control group (p < 0.05). Stent occlusion rates at 90 and 180 days in the control group were 12.9% and 51.6%, respectively. No stent occlusion occurred in the treatment group. Patients in the treatment group obtained longer survival time (median, 26 vs. 13 months; p < 0.01) and prolonged duodenal obstruction (median, 20.5 vs. 11 months; p < 0.05). No brachytherapy-related grade 3 or 4 adverse events were observed. Conclusions: Longer intervention interval for biliary obstruction and survival as well as better stent patency and prolonged time to duodenal obstruction could be achieved by implanting 125I seeds combined with biliary stent in patients with unresectable ampullary cancer. [ABSTRACT FROM AUTHOR]

Background: Most patients with epithelial ovarian cancers (EOC) present with advanced-stage disease because of non-specific symptoms and lack of reliable strategies for early diagnosis. Cancer antigen 125 (CA-125) is suggested as a useful prognostic biomarker, its serum level is raised in over 80.0% of patients with EOC. Primary debulking surgery (PDS) followed by chemotherapy is the conventional treatment, but neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) is offered to patients with unresectable disease. There are inconsistencies regarding the role of preoperative CA-125 serum levels to adopt in stratifying patients for treatment choice that offers the most benefit. This review aimed to determine the role of preoperative CA-125 levels in predicting optimal cytoreduction and the association between optimal cytoreduction and survival outcome in patients with EOC. Methodology: Three electronic databases CINAHL, Cochrane library and PubMed were searched for potentially relevant articles from 2016 to 2021 on the role of preoperative CA-125 levels in predicting optimal cytoreduction and survival in patients with epithelial ovarian carcinomas. Conclusion: In patients who underwent NACT-IDS, a lower preoperative CA-125 value is a predictor of optimal cytoreduction and an increase in preoperative CA-125 value is consistently associated with a decrease in optimal cytoreduction. There was insufficient data to assess overall survival. However, a raised preoperative CA-125 level is poor predictor of chance of achieving optimal cytoreduction and the rate of optimal cytoreduction was a weak predictor of overall survival in women who had primary debulking surgery. [ABSTRACT FROM AUTHOR]

Background/Aim: Sarcopenia accompanied by systemic inflammation is associated with poor prognosis in patients with cancer. This study evaluated the prognostic significance of sarcopenia (myopenia and myosteatosis) and systemic inflammatory markers in older patients (aged =80 years) with resected biliary tract cancer. Patients and Methods: Patients who underwent resection for biliary tract cancer between July 2010 and January 2023 at the NHO Fukuyama Medical Center were retrospectively reviewed. Preoperative computed tomography measured myopenia and myosteatosis, using the psoas muscle index and modified intramuscular adipose tissue content. Associations between clinicopathological characteristics, inflammation-based prognostic scores, and overall survival were analyzed using Cox proportional hazards models. Results: Univariate analysis revealed low C-reactive protein-to-albumin ratio (<0.125), low prognostic nutritional index (<42), low modified intramuscular adipose tissue content, higher T-stage (T3-4), lymph node metastasis, and postoperative complications associated with worse overall survival in older patients (aged = 80 years) with resected biliary tract cancer (n=48). Multivariate analysis identified low prognostic nutritional index (<42) (p=0.007), low modified intramuscular adipose tissue content (p=0.015), higher Tstage (T3-4) (p<0.001), lymph node metastasis (p=0.001), and postoperative complications (p=0.017) as independent predictors of overall survival. Conclusion: Preoperative myosteatosis and low prognostic nutritional index are independent prognostic factors for overall survival in older patients (aged =80 years) with resected biliary tract cancer. These factors may be useful for risk stratification and clinical decision-making. Early interventions, such as nutritional support and physical exercise, may improve outcomes after resection of biliary tract cancer. [ABSTRACT FROM AUTHOR]

To assess the prognostic value of human epididymis protein 4 (HE4) kinetics during and after neoadjuvant chemotherapy (NACT) cycles compared with cancer antigen 125 (CA-125), in predicting the surgical outcomes of interval debulking surgery (IDS) in patients with advanced-stage, high-grade serous ovarian cancer. This retrospective cohort study was conducted at Severance Hospital in Seoul, South Korea and involved 123 women with high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who were diagnosed between April 2015 and July 2020. Three outcomes were considered: the chemotherapy response score (CRS) by omentum, residual disease after IDS, and recurrence. Other clinical, imaging, and biological parameters at baseline, during NACT cycles, and pre- and postoperative time were collected and analyzed. We observed a substantial and gradual decrease in both CA-125 level (median from 1612 to 85.55 U/mL; p < 0.001) and HE4 level (514.7 to 87.7 pmol/L; p < 0.001) during NACT cycles, while pre-to-postoperative reduction was only significant for HE4 (median from 77.3 to 62.0 pmol/L (p < 0.001)). Of the total patients, 4.1% showed no response to NACT (chemoresistance) and 65.9% had a partial response. Residual disease was observed in 55 (44.7%) patients. Recurrence occurred in 90 patients (73.2%), with a median progression-free survival of 15.28 months. The percent reduction in CA-125 level– but not HE4 – during NACT was significantly associated with CRS (by omentum); the reduction in CA-125 during NACT cycles was higher when the CRS was found to be 3 and 2 (median = 96.4 [IQR = 8.3] and 93.7 [12.2] respectively) compared to score 1 (68.3 [34.1]), and the difference was statistically significant (p = 0.004). However, no significant association was observed between the percent reduction in CA-125 or HE4 levels during NACT and residual disease or recurrence. The normalization of HE4 – but not CA-125 – before surgery was predictive for surgery outcome; that is, an abnormal preop HE4 level was associated with a residual disease risk ratio of 2.72 (95% CI = 1.27–5.79). Monitoring HE4 or CA-125 levels has low prognostic value in patients with advanced-stage, high-grade serous ovarian cancer who are treated with NACT followed by IDS. However, the preoperative level of the HE4 biomarker may be useful in identifying patients at higher risk for suboptimal cytoreductive surgery or who may require more extensive surgery. Further prospective studies are warranted to explore the prognostic utility of eventual combinations of clinical, radiological, and biological parameters, notably by using artificial intelligence-based models. • The reduction of CA125 during NACT cycles–but not HE4– was significantly associated with chemotherapy response score (CRS). • Pre-to-postop reduction in tumor markers level was only significant for HE4. • The normalization of HE4 level – but not CA125 – before surgery was predictive for surgery outcome. • Complete/near-complete CRS (CRS 3) was the only significant factor for recurrence. [ABSTRACT FROM AUTHOR]

To determine clinical significance of preoperative and pre-chemotherapy CA-125 in high-risk early-stage epithelial ovarian cancer patients. All patients with stage IA/IB and grade 3, stage IC, clear cell, or completed resected stage II cancer were enrolled in a phase III trial and treated with chemotherapy. Kaplan-Meier method and Cox proportional hazards model were used for statistical analyses. 427 patients with high-risk early-stage ovarian cancer were enrolled. Of 213 patients with preoperative CA-125 data, 79% had elevated CA-125. Median preoperative CA-125 level was 103 U/mL. Patients with ≤10, 11–15, and > 15 cm tumors had median preoperative CA-125 levels of 62, 131 and 158 U/mL, respectively (p = 0.002). For the 350 patients with data for pre-chemotherapy CA-125 level, 69% had elevated pre-chemotherapy CA-125 above 35 U/mL with median value of 65 U/mL. However, age, race, stage, cell type and grade of disease were not correlated with CA-125 levels before and after surgery. On multivariate analysis, elevated pre-chemotherapy CA-125 independently predicted worse recurrence-free survival (HR = 2.13, 95% CI: 1.23–3.69; p = 0.007) and overall survival (HR = 1.99, 95% CI: 1.10–3.59; p = 0.022) after adjusting for age, stage, cell type and grade of disease. Compared to those with normal CA-125, patients with elevated pre-chemotherapy CA-125 had lower recurrence-free survival (RFS, 87% vs. 75%; p = 0.007) and overall survival (OS, 88% vs. 82%; p = 0.02). However, preoperative CA-125 was not prognostic of RFS (p = 0.699) or OS (p = 0.701). Preoperative CA-125 was elevated in nearly 80% of high-risk early-stage ovarian cancer patients. Pre-chemotherapy CA-125 was associated with recurrence-free and overall survival; however, preoperative CA-125 was not prognostic. • Eighty percent of high-risk early-stage ovarian cancer patients had elevated preoperative CA-125. • Pre-chemotherapy CA-125 value with recurrence-free/overall survival in women with high-risk early-stage ovarian cancer. • Preoperative CA-125 value was not a prognostic factor for patients with high-risk early-stage ovarian cancer. [ABSTRACT FROM AUTHOR]

Background: Identifying lymph node metastasis areas during surgery for early invasive lung adenocarcinoma remains challenging. The aim of this study was to develop a nomogram mathematical model before the end of surgery for predicting lymph node metastasis in patients with early invasive lung adenocarcinoma. Methods: In this study, we included patients with invasive lung adenocarcinoma measuring ≤ 2 cm who underwent pulmonary resection with definite pathology at Qilu Hospital of Shandong University from January 2020 to January 2022. Preoperative biomarker results, clinical features, and computed tomography characteristics were collected. The enrolled patients were randomized into a training cohort and a validation cohort in a 7:3 ratio. The training cohort was used to construct the predictive model, while the validation cohort was used to test the model independently. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors. The prediction model and nomogram were established based on the independent risk factors. Recipient operating characteristic (ROC) curves were used to assess the discrimination ability of the model. Calibration capability was assessed using the Hosmer–Lemeshow test and calibration curves. The clinical utility of the nomogram was assessed using decision curve analysis (DCA). Results: The overall incidence of lymph node metastasis was 13.23% (61/461). Six indicators were finally determined to be independently associated with lymph node metastasis. These six indicators were: age (P < 0.001), serum amyloid (SA) (P = 0.008); carcinoma antigen 125 (CA125) (P = 0. 042); mucus composition (P = 0.003); novel aspartic proteinase of the pepsin family A (Napsin A) (P = 0.007); and cytokeratin 5/6 (CK5/6) (P = 0.042). The area under the ROC curve (AUC) was 0.843 (95% CI: 0.779–0.908) in the training cohort and 0.838 (95% CI: 0.748–0.927) in the validation cohort. the P-value of the Hosmer–Lemeshow test was 0.0613 in the training cohort and 0.8628 in the validation cohort. the bias of the training cohort corrected C-index was 0.8444 and the bias-corrected C-index for the validation cohort was 0.8375. demonstrating that the prediction model has good discriminative power and good calibration. Conclusions: The column line graphs created showed excellent discrimination and calibration to predict lymph node status in patients with ≤ 2 cm invasive lung adenocarcinoma. In addition, the predictive model has predictive potential before the end of surgery and can inform clinical decision making. [ABSTRACT FROM AUTHOR]

(1) Background: Our aim was to evaluate the efficacy and adverse effects of maintenance chemotherapy in platinum-sensitive recurrent epithelial ovarian cancer after second-line chemotherapy. (2) Methods: A total of 72 patients from a single institute who had been diagnosed with platinum-sensitive recurrent ovarian cancer and had experienced either complete or partial response after six cycles of second-line chemotherapy were divided into a standard group (n = 31) with six cycles or a maintenance group (n = 41) with more than six cycles. We then compared patient characteristics and survival outcomes between these two groups. (3) Results: In all patients, after primary management for the first recurrence, the maintenance group showed worse survival outcomes. Patients who had not undergone either surgery or radiotherapy were divided into complete response and partial response groups after six cycles of chemotherapy. In patients with partial response, maintenance chemotherapy led to a significant improvement in PFS (median, 3.6 vs. 6.7 months, p = 0.007), but no significant change in in OS. The median cycle number of maintenance chemotherapy was four. (4) Conclusions: Maintenance chemotherapy may still play an important role in patients with platinum-sensitive recurrent ovarian cancer, particularly in selected patient groups. [ABSTRACT FROM AUTHOR]

Background: Almost all patients with ovarian cancer will experience relapse and eventually develop platinum-resistant. The poor prognosis and limited treatment options have prompted the search for novel approaches in managing platinum-resistant ovarian cancer (PROC). Therefore, a meta-analysis was conducted to evaluate the efficacy and safety of combination therapy with vascular endothelial growth factor (VEGF) /VEGF receptor (VEGFR) inhibitors for PROC. Methods: A comprehensive search of online databases was conducted to identify randomized clinical trials published until December 31, 2022. Pooled hazard ratios (HR) was calculated for overall survival (OS) and progression-free survival (PFS), while pooled odds ratio (OR) was calculated for objective response rate (ORR) and treatment-related adverse events (TRAEs). Subgroup analysis was further performed to investigate the source of heterogeneity. Results: In total, 1097 patients from eight randomized clinical trials were included in this meta-analysis. The pooled HRs of OS (HR = 0.72; 95% CI: 0.62–0.84, p < 0.0001) and PFS (HR = 0.52; 95% CI: 0.45–0.59, p < 0.0001) demonstrated a significant prolongation in the combination group compared to chemotherapy alone for PROC. In addition, combination therapy demonstrated a superior ORR compared to monotherapy (OR = 2.34; 95%CI: 1.27–4.32, p < 0.0001). Subgroup analysis indicated that the combination treatment of VEGF/VEGFR inhibitors and chemotherapy was significantly more effective than monochemotherapy in terms of OS (HR = 0.71; 95% CI: 0.61–0.84, p < 0.0001), PFS (HR = 0.49; 95% CI: 0.42–0.57, p < 0.0001), and ORR (OR = 2.97; 95% CI: 1.89–4.67, p < 0.0001). Although the combination therapy was associated with higher incidences of hypertension, mucositis, proteinuria, diarrhea, and hand-foot syndrome compared to monochemotherapy, these toxicities were manageable and well-tolerated. Conclusions: The meta-analysis demonstrated that combination therapy with VEGF/VEGFR inhibitors yielded better clinical outcomes for patients with PROC compared to monochemotherapy, especially when combined with chemotherapy. This analysis provides more treatment options for patients with PROC. Systematic review registration: [https://www.crd.york.ac.uk/PROSPERO], Prospective Register of Systematic Reviews (PROSPERO), identifier: CRD42023402050. [ABSTRACT FROM AUTHOR]

Introduction and aim: Ovarian cancer is a prevalent neoplastic condition among females. Early diagnosis is essential in improving patient outcomes. This study aimed to determine the diagnostic value of magnetic resonance imaging (MRI) compared to histopathological diagnosis to distinguish between benign and malignant ovarian masses. Methods: The present cross-sectional study, which was conducted between 2021 and 2022, included a cohort of women with ovarian mass. Gyneco-oncologists referred all patients to the MRI center. The imaging protocol encompassed T1 and T2 weighted images, T1 fat-suppressed sequence, post-contrast and diffusion-weighted images (DWI). After surgery, the histopathological results were compared to the MRI diagnosis. Statistical analysis was done by using SPSS v.25 software. Results: A total of 67 women aged 15-82 years old were included in this study. Compared to histopathological diagnosis, MRI had a sensitivity of 96%, a specificity of 69%, a positive predictive value of 64.9% and a negative predictive value of 96.7%. Among patients under 40 years old, MRI showed a sensitivity of 100%, a specificity of 76.2%, a positive predictive value of 72.2% and a negative predictive value of 100%. Solid component and contrast enhancement within the solid component was significantly more frequent in patients with malignant diagnoses than those with benign masses (p<0.05). Conclusion: According to the results of the study, MRI is valuable for discriminating between benign and malignant ovarian masses, especially in patients under 40. [ABSTRACT FROM AUTHOR]

As the most lethal gynecologic oncological indication, carcinoma of the ovary has been ranked as the 5th cause of cancer-related mortality in women, with a high percentage of the patients being diagnosed at late stages of the disease and a five-year survival of ~ 30%. Ovarian cancer patients conventionally undergo surgery for tumor removal followed by platinum- or taxane-based chemotherapy; however, a high percentage of patients experience tumor relapse. Cancer immunotherapy has been regarded as a silver lining in the treatment of patients with various immunological or oncological indications; however, mirvetuximab soravtansine (a folate receptor α-specific mAb) and bevacizumab (a VEGF-A-specific mAb) are the only immunotherapeutics approved for the treatment of ovarian cancer patients. Chimeric antigen receptor T-cell (CAR-T) therapy has achieved tremendous clinical success in the treatment of patients with certain B-cell lymphomas and leukemias, as well as multiple myeloma. In the context of solid tumors, CAR-T therapies face serious obstacles that limit their therapeutic benefit. Such hindrances include the immunosuppressive nature of solid tumors, impaired tumor infiltration, lack of qualified tumor-associated antigens, and compromised stimulation and persistence of CAR-Ts following administration. Over the past years, researchers have made arduous attempts to apply CAR-T therapy to ovarian cancer. In this review, we outline the principles of CAR-T therapy and then highlight its limitations in the context of solid tumors. Ultimately, we focus on preclinical and clinical findings achieved in CAR-T-mediated targeting of different ovarian cancer-associated target antigens. [ABSTRACT FROM AUTHOR]

Choosing an optimal concomitant drug for combination with poly‐ADP ribose polymerase (PARP) inhibitor based on patient‐specific biomarker status may help increase to improve treatment efficacy in patients with ovarian cancer. However, the efficacy and safety of different PARP inhibitor‐based combinations in patients with homologous recombination repair (HRR) mutations have not been evaluated in ovarian cancer. In this sub‐study of Korean Gynecologic Oncology Group (KGOG) 3045, we compared the efficacy and safety of two olaparib‐based combinations and biomarkers of patients with platinum‐resistant ovarian cancer with HRR gene mutations. Patients were randomized to receive either olaparib (200 mg twice a day) + cediranib (30 mg daily) (Arm 1, n = 16) or olaparib (300 mg) + durvalumab (1,500 mg once every 4 weeks) (Arm 2, n = 14). The objective response rates for Arm 1 and Arm 2 were 50.0% and 42.9%, respectively. Most patients (83.3%) had BRCA mutations, which were similarly distributed between arms. Grade 3 or 4 treatment‐related adverse events were observed in 37.5% and 35.7% of the patients, respectively, but all were managed properly. A high vascular endothelial growth factor signature was associated with favorable outcomes in Arm 1, whereas immune markers (PD‐L1 expression [CPS ≥10], CD8, neutrophil‐to‐lymphocyte ratio and platelet‐to‐lymphocyte ratio) were associated with favorable outcomes in Arm 2. The activation of homologous recombination pathway upon disease progression was associated with poor response to subsequent therapy. Based on comprehensive biomarker profiling, including immunohistochemistry, whole‐exome and RNA sequencing and whole blood‐based analyses, we identified biomarkers that could help inform which of the two combination strategies is appropriate given a patient's biomarker status. Our findings have the potential to improve treatment outcome for patients with ovarian cancer in the PARP inhibitor era. [ABSTRACT FROM AUTHOR]

To investigate the efficacy of new endometriosis biomarkers in diagnosis and treatment. Thirty women with Stage III-IV endometriosis who were given an indication for surgery and 49 control patients were compared. Preoperative and postoperative serum levels of Annexin A5 (ANXA5), soluble intercellular adhesion molecule-1 (sICAM-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), soluble vascular cell adhesion molecule-1 (sVCAM-1), vascular endothelial growth factors (VEGF) and Ca-125 measurements were compared. AUCs of ANXA5, sICAM-1, IL-6, TNF-α, VCAM-1, VEGF biomarkers were not found to be significant in diagnosing endometriosis when evaluated alone (p > 0.05). Only the AUC of the Ca-125 biomarker values were found to be significant with 73% sensitivity and 98% specificity (p < 0.001). However, when Ca-125 and ANXA5 were evaluated together, it was concluded that the diagnosis of endometriosis could be made with 73% sensitivity and 100% specificity. When Ca-125 and ANXA5 are evaluated together, it seems to be more valuable than Ca-125 alone in diagnosing endometriosis. [ABSTRACT FROM AUTHOR]

Background: The pancreatic index (PI) is a useful preoperative imaging predictor for pancreatic ductal adenocarcinoma (PDAC). In this retrospective study, we determined the predictive effect of PI to distinguish patients of pancreatic body/tail cancer (PBTC) with vascular involvement who can benefit from upfront surgery. Method: All patients who received distal pancreatectomy for PDAC from 2016 to 2020 at the Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine were considered for the study. A total of 429 patients with PBTC were assessed in relation to the value of PI. Fifty‐five patients were eventually included and divided into low PI group and 29 patients in the normal PI group. Results: The median overall survival (mOS) was significantly shorter in the low PI group (13.1 vs. 30.0 months, p = 0.002) in this study, and PI ≥ 0.78 (OR = 0.552, 95% CI: 0.301–0.904, p = 0.020) was an independent influencing factor confirmed by multivariate analysis. Subgroup analysis showed that PI was an independent prognostic factor for LA‐PBTC (OR = 0.272, 95% CI: 0.077–0.969, p = 0.045). As for BR PBTC, PI (OR = 0.519, 95% CI: 0.285–0.947, p = 0.033) combined with carbohydrate antigen 125 (CA125) (OR = 2.806, 95% CI: 1.206–6.526, p = 0.017) and chemotherapy (OR = 0.327, 95% CI: 0.140–0.763, p = 0.010) were independent factors. Conclusion: This study suggests that the PI can be used as a predictive factor to optimize the surgical indication for PBTC with vascular involvement. Preoperative patients with normal PI and CA125 can achieve a long‐term prognosis comparable to that of resectable PBTC patients. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study is to examine the risk factors that contribute to the development of liver metastasis (LM) in patients who have suffered radical resection for colorectal cancer (CRC), and to establish a nomogram model that can be used to predict the occurrence of the LM. Methods: The present study enrolled 1377 patients diagnosed with CRC between January 2010 and July 2021. The datasets were allocated to training (n = 965) and validation (n = 412) sets in a randomly stratified manner. The study utilized univariate and multivariate logistic regression analyses to establish a nomogram for predicting LM in patients with CRC. Results: Multivariate analysis revealed that T stage, N stage, number of harvested lymph nodes (LNH), mismatch repair (MMR) status, neutrophil count, monocyte count, postoperative carcinoembryonic antigen (CEA) levels, postoperative cancer antigen 125 (CA125) levels, and postoperative carbohydrate antigen 19–9 (CA19-9) levels were independent predictive factors for LM after radical resection. These factors were then utilized to construct a comprehensive nomogram for predicting LM. The nomogram demonstrated great discrimination, with an area under the curve (AUC) of 0.782 for the training set and 0.768 for the validation set. Additionally, the nomogram exhibited excellent calibration and significant clinical benefit as confirmed by the calibration curves and the decision curve analysis, respectively. Conclusion: This nomogram has the potential to support clinicians in identifying high-risk patients who may develop LM post-surgery. Clinicians can devise personalized treatment and follow-up plans, ultimately leading to an improved prognosis for patients. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) patients often develop liver metastasis. However, curative resection of liver metastasis is not always possible due to poor visualization of tumor margins. The present study reports the characterization of a humanized anti-carcinoembryonic antigen monoclonal antibody conjugated to a PEGylated near-infrared dye, that targets and brightly labels human CRC tumors in metastatic orthotopic mouse models. The hT84.66-M5A (M5A) monoclonal antibody was conjugated with a polyethylene glycol (PEG) chain that incorporated a near infrared (NIR) IR800 dye to establish M5A-IR800 Sidewinder (M5A-IR800-SW). Nude mice with CRC orthotopic primary tumors and liver metastasis both developed from a human CRC cell line, were injected with M5A-IR800-SW and imaged with the Pearl Trilogy Imaging System. M5A-IR800-SW targeted and brightly labeled CRC tumors, both in primary-tumor and liver-metastasis models. M5A-IR800-SW at 75 μg exhibited highly-specific tumor labeling in a primary-tumor orthotopic model with a median tumor-to-background ratio of 9.77 and in a liver-metastasis orthotopic model with a median tumor-to-background ratio of 7.23 at 96 h. The precise labeling of the liver metastasis was due to lack of hepatic accumulation of M5A-IR800-SW in the liver. M5A-IR800-SW provided bright and targeted NIR images of human CRC in orthotopic primary-tumor and liver-metastasis mouse models. The results of the present study suggest the clinical potential of M5A-IR800-SW for fluorescence-guided surgery including metastasectomies for CRC. The lack of hepatic NIR signal is of critical importance to allow for precise labeling of liver tumors. [ABSTRACT FROM AUTHOR]

STUDY QUESTION What metabolic pathways and metabolites in the serum and follicular fluid are associated with peak estradiol levels and the number of mature oocytes? SUMMARY ANSWER In the serum metabolome, mostly fatty acid and amino acid pathways were associated with estradiol levels and mature oocytes while in the follicular fluid metabolome, mostly lipid, vitamin, and hormone pathways were associated with peak estradiol levels and mature oocytes. WHAT IS KNOWN ALREADY Metabolomics has identified several metabolic pathways and metabolites associated with infertility but limited data are available for ovarian stimulation outcomes. STUDY DESIGN, SIZE, DURATION A prospective cohort study of women undergoing IVF from 2009 to 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 125 women undergoing a fresh IVF cycle at a fertility clinic in the Northeast United States who provided a serum and follicular fluid sample. Untargeted metabolomics profiling was conducted using liquid chromatography with high-resolution mass spectrometry in two chromatography columns (C18 and hydrophilic interaction chromatography (HILIC)). The main ovarian stimulation outcomes were peak serum estradiol levels and number of mature oocytes. We utilized adjusted generalized linear regression models to identify significant metabolic features. Models were adjusted for age,BMI, initial infertility diagnosis, and ovarian stimulation protocol. We then conducted pathway analysis using mummichog and metabolite annotation using level-1 evidence. MAIN RESULTS AND ROLE OF CHANCE In the serum metabolome, 480 and 850 features were associated with peak estradiol levels in the C18 and HILIC columns, respectively. Additionally, 437 and 538 features were associated with mature oocytes in the C18 and HILIC columns, respectively. In the follicular fluid metabolome, 752 and 929 features were associated with peak estradiol levels in the C18 and HILIC columns, respectively, Additionally, 993 and 986 features were associated with mature oocytes in the C18 and HILIC columns, respectively. The most common pathways associated with peak estradiol included fatty acids (serum and follicular fluid), hormone (follicular fluid), and lipid pathways (follicular fluid). The most common pathways associated with the number of mature oocytes retrieved included amino acids (serum), fatty acids (serum and follicular fluid), hormone (follicular fluid), and vitamin pathways(follicular fluid). The vitamin D3 pathway had the strongest association with both ovarian stimulation outcomes in the follicularfluid. Four and nine metabolites were identified using level-1 evidence (validated identification) in the serum and follicular fluid metabolomes, respectively. LIMITATIONS, REASONS FOR CAUTION Our sample was majority White and highly educated and may not be generalizable to thewider population. Additionally, residual confounding is possible and the flushing medium used in the follicular fluid could have diluted our results. WIDER IMPLICATIONS OF THE FINDINGS The pathways and metabolites identified by our study provide novel insights into the biologicalmechanisms in the serum and follicular fluid that may underlie follicular and oocyte development, which could potentially be used to improve ovarian stimulation outcomes. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the following grants from the National Institute of Environmental Health Sciences (P30-ES019776, R01-ES009718, R01-ES022955, P30-ES000002, R00-ES026648, and T32-ES012870), and National Institute of Diabetes and Digestive and Kidney Diseases (P30DK046200). The authors have no competing interests to disclose. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Purpose: To explore the efficacy of CT-guided iodine-125 (125I) radioactive particle implantation for the treatment of pelvic local recurrence of cervical cancer after radiotherapy. Material and methods: To analyze clinical data of 46 patients with pelvic local recurrence of cervical cancer after radiotherapy, who underwent 125I particle implantation, post-operative follow-up using Kaplan-Meier method to calculate the rate of local control, and observation of complications. Univariate and multi-factorial analyses were performed with log-rank test and Cox regression statistical method to observe changes in serum SCC-Ag and CEA levels. Results: A total of 57 lesions in 46 patients had a short-term local control rate of 87.72% (50/57) and effective rate of 68.42% (39/57). As of the end of follow-up, the median local progression-free survival time of 46 patients was 12.2 (range, 3.5-32) months, the median overall survival time was 16.3 (range, 3.5-40) months, with 1-year and 2-year OS of 63.04% and 41.30%. Univariate and multi-factorial analyses suggested that local recurrent mass size and recurrence site were the main factors affecting survival. Loco-regional progression-free survival (LPFS) time was 15.5 and 11.25 months in cases with recurrent mass diameter < 3 cm and = 3 cm, respectively (χ² = 10.83, p = 0.001 < 0.05). In patients with pelvic wall recurrence and central recurrence, the time to LPFS was 15.80 and 10.00 months, respectively (χ² = 8.833, p = 0.0030 < 0.05). Tumor markers serum SCC-Ag and CEA decreased to different degrees after treatment, and the difference was statistically significant. The median LPFS in the SCC-Ag = 3.5 ng/ml group was significantly higher than that in the SCC-Ag > 3.5 ng/ml group (χ² = 4.241, p = 0.036 < 0.05). No serious post-operative complications were observed. Conclusions: CT-guided 125I seed implantation has significant short-term efficacy in the treatment of pelvic local recurrence of cervical cancer after radiotherapy. It can improve the effective rate in patients with initial clinical stage II, especially in those with locally recurrent masses < 3 cm and in those with a recurrence in the pelvic wall. [ABSTRACT FROM AUTHOR]

This prospective cross-sectional study compared the diagnostic accuracy of human epididymal protein 4 (HE4) with cancer antigen 125 (CA 125) and validates the risk of malignancy algorithm (ROMA) in differentiating benign from malignant ovarian tumours. The study population included 112 women with an ultrasound diagnosis of an adnexal mass, out of whom 49 women had a diagnosis of ovarian cancer following optimal debulking surgery, and 63 women had a diagnosis of benign ovarian tumour. All diagnosis was confirmed by histopathological analysis. Serum HE4 and CA 125 were assessed preoperatively according to the manufacturer's instructions. CA 125 and HE4 cut-offs were 35 U/mL and 70 pM/L respectively. Serum CA 125 and HE4 were significantly higher in ovarian cancer patients compared to those with benign ovarian tumours (p < 0.001 and p < 0.000, respectively). HE4 had higher sensitivity (77.5% versus 69.4%), specificity (96.8% versus 82.5%), positive predictive value (PPV) (95% versus 75.6%) and negative predictive value (84.7% versus 77.6%) than CA 125. When the two markers were combined with each other in the ROMA index, Specificity and PPV reached 100% each. In the receiver operative characteristics analysis, the area under the curve for CA 125 was 0.679 (95% CI 0.566-0.791, p = 0.001), HE4 was 0.845 (95% CI 0.760-0.930, p = 0.000) and ROMA was 0.902 (95% CI 0.851-0.998, p = 0.000) and this was statistically significant (p < 0.001). Conclusively, HE4 performed better than CA 125 in differentiating benign from malignant ovarian tumours and the combination of the two biomarkers improved the detection of ovarian cancer. In addition, the cut off values corresponding to the highest accuracy for CA 125 and HE4 were 126 U/mL and 42 pM/L respectively in this study. The value for CA 125 is much higher while that of HE4 is much lower than the reference values obtained predominantly from the white population. [ABSTRACT FROM AUTHOR]

Background: One needs to choose wisely between primary neoadjuvant chemotherapy and primary cytoreductive surgery in ovarian cancer. The aim was to determine the recurrence free survival and overall survival after surgery for epithelial ovarian cancer and also the risk factors for recurrence and death. Methods: Electronic medical records of 322 women operated for ovarian, fallopian or primary peritoneal cancer between 2011 and 2015 were reviewed. Descriptive statistics were used to describe patients and their clinical outcomes. Cox proportional hazard models were used for risk factor analysis. Adjusted hazard ratios were obtained for recurrence and death, adjusted for stage, primary treatment modality, residual disease and histology. Kaplan-Meier curves were drawn for probability of recurrence-free survival and overall survival. The log rank test was used to compare survival probabilities. Results: The majority were stage III or stage IV (78%), serous histology (71%) and high grade (64%). Primary cytoreduction was done in 48% and interval cytoreduction in 52%. The median duration of follow up (survival) was 77 months (95% CI 72-82). There were 179 known recurrences (55.6 %). The estimated median time to recurrence was 22 (95% CI 14.5- 29.5) months. The independent risk factors for recurrence were neoadjuvant chemotherapy [HR 2.14, 95% CI 1.48-3.09], stage III/IV [HR 2.75; 95% CI 1.40-5.41], high grade serous histology [HR 1.69; 95% CI 1.12-2.54] and sub-optimal debulking [HR 3.15, 95% CI 2.19-4.55]. There were 78 known deaths (24.2 %) with a mean time to death of 24.3 (SD 16.1) months. The independent risk factors for death were sub-optimal debulking [HR 3.07; 95% CI 1.78-5.29] and stages III and IV cancer [HR 3.07; 95% CI 1.14-8.27]. Conclusions: Most ovarian cancers recur within 2 years. Risk factors for mortality are advanced stage and sub-optimal debulking. Maximal efforts at down staging and surgical resection will increase survival. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the performance of subjective assessment and the Assessment of Different NEoplasias in the adneXa (ADNEX) model in discriminating between benign and malignant adnexal tumors and between metastatic and primary adnexal tumors in patients with a personal history of breast cancer. Methods: This was a retrospective single‐center study including patients with a history of breast cancer who underwent surgery for an adnexal mass between 2013 and 2020. All patients had been examined with transvaginal or transrectal ultrasound using a standardized examination technique and all ultrasound reports had been stored and were retrieved for the purposes of this study. The specific diagnosis suggested by the original ultrasound examiner in the retrieved report was analyzed. For each mass, the ADNEX model risks were calculated prospectively and the highest relative risk was used to categorize each into one of five categories (benign, borderline, primary Stage I, primary Stages II–IV or metastatic ovarian cancer) for analysis of the ADNEX model in predicting the specific tumor type. The performance of subjective assessment and the ADNEX model in discriminating between benign and malignant adnexal tumors and between primary and metastatic adnexal tumors was evaluated, using final histology as the reference standard. Results: Included in the study were 202 women with a history of breast cancer who underwent surgery for an adnexal mass. At histology, 93/202 (46.0%) masses were benign, 76/202 (37.6%) were primary malignancies (four borderline and 72 invasive tumors) and 33/202 (16.3%) were metastases. The original ultrasound examiner classified correctly 79/93 (84.9%) benign adnexal masses, 72/76 (94.7%) primary adnexal malignancies and 30/33 (90.9%) metastatic tumors. Subjective ultrasound evaluation had a sensitivity of 93.6%, specificity of 84.9% and accuracy of 89.6%, while the ADNEX model had higher sensitivity (98.2%) but lower specificity (78.5%), with similar accuracy (89.1%), in discriminating between benign and malignant ovarian masses. Subjective evaluation had a sensitivity of 51.5%, specificity of 88.8% and accuracy of 82.7% in distinguishing metastatic and primary tumors (including benign, borderline and invasive tumors), and the ADNEX model had a sensitivity of 63.6%, specificity of 84.6% and similar accuracy (81.2%). Conclusions: The performance of subjective assessment and the ADNEX model in discriminating between benign and malignant adnexal masses in this series of patients with history of breast cancer was relatively similar. Both subjective assessment and the ADNEX model demonstrated good accuracy and specificity in discriminating between metastatic and primary tumors, but the sensitivity was low. © 2023 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Transcatheter aortic valve replacement (TAVR) has become a widely used therapy for patients with severe aortic stenosis. Carbohydrate antigen 125 (CA‐125) is a promising biomarker in some cardiovascular diseases. This systematic review aims to assess the prognostic role of CA‐125 in patients undergoing TAVR. We searched electronic databases from inception to March 2023 to include cohort studies evaluating the association between preprocedural CA‐125 levels and mortality or heart failure (HF) readmission at 12 months in patients undergoing TAVR. We pooled crude (cHR) and adjusted hazard ratios (aHR) with their 95% confidence interval (CI) using a random‐effects model. The risk of bias was evaluated using the QUIPS tool. The certainty of the evidence was assessed using the GRADE approach. We included five cohort studies involving 1594 patients. Higher levels of CA‐125 were significantly associated with an increased risk of mortality or HF readmission using crude (cHR 2.79, 95% CI 1.45–5.36, I2 = 72%) and adjusted (aHR 3.27, 95% CI 2.07–5.18, I2 = 0%, high certainty) effect estimates compared with lower levels. Similarly, there was also associated with increased mortality using crude (cHR 2.68, 95% CI 1.99–3.60, I2 = 0%) and adjusted (aHR 2.17, 95% CI 1.54–3.07, I2 = 0%, high certainty) effect estimates. The risk of bias varied between low to moderate across studies. Our meta‐analysis suggests that CA‐125 has incremental prognostic value in patients undergoing TAVR. Further studies are needed to determine the clinical utility of CA‐125 in guiding treatment decisions in this population. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of advanced endometriosis remains challenging with considerable limitations in the diagnosis of retroperitoneal and deep infiltrating lesions. Thus, a well-defined panel of inexpensive, noninvasive inflammatory biomarkers could be a crucial tool for appropriate staging for women with suspected endometriosis. The aim of this work is to explore the potential use of serum YKL-40, interleukin-37 (IL-37), and cancer antigen 125 (CA125) for noninvasive staging of endometriosis patients for proper intervention and most optimal management of the condition. Methods: This study was conducted on 90 women, who had undergone laparoscopic or laparotomy surgery due to suspected pelvic endometriosis. Blood samples for serum YKL-40, IL-37, and CA125 levels assay were taken from all participants at admission for laparoscopy or laparotomy. After histopathological confirmation of the diagnosis, the selected cases were immunostained for YKL-40, IL-37, and CA125. Results: YKL-40, IL-37, and CA125 serum levels were significantly elevated in patients with endometriosis than healthy controls. Moreover, the association between the serum level and immunoexpression and grading of endometriosis. A triple combination panel of serum YKL-40, IL-37, and CA125 was found to have the best sensitivity and specificity (96.67% and 100.0%, respectively) compared to any single serum marker alone or double combination panel in predicting the severity of endometriosis. Conclusions: A triple combination panel of serum YKL-40, IL-37, and CA125 could be used in the future for predicting endometriosis stage, providing a practical reference for making better-informed decisions on the best treatment plan. [ABSTRACT FROM AUTHOR]

In UKCTOCS, there was a decrease in the diagnosis of advanced stage tubo-ovarian cancer but no reduction in deaths in the multimodal screening group compared with the no screening group. Therefore, we did exploratory analyses of patients with high-grade serous ovarian cancer to understand the reason for the discrepancy. UKCTOCS was a 13-centre randomised controlled trial of screening postmenopausal women from the general population, aged 50–74 years, with intact ovaries. The trial management system randomly allocated (2:1:1) eligible participants (recruited from April 17, 2001, to Sept 29, 2005) in blocks of 32 using computer generated random numbers to no screening or annual screening (multimodal screening or ultrasound screening) until Dec 31, 2011. Follow-up was through national registries until June 30, 2020. An outcome review committee, masked to randomisation group, adjudicated on ovarian cancer diagnosis, histotype, stage, and cause of death. In this study, analyses were intention-to-screen comparisons of women with high-grade serous cancer at censorship (Dec 31, 2014) in multimodal screening versus no screening, using descriptive statistics for stage and treatment endpoints, and the Versatile test for survival from randomisation. This trial is registered with the ISRCTN Registry, 22488978, and ClinicalTrials.gov , NCT00058032. 202 562 eligible women were recruited (50 625 multimodal screening; 50 623 ultrasound screening; 101 314 no screening). 259 (0·5%) of 50 625 participants in the multimodal screening group and 520 (0·5%) of 101 314 in the no screening group were diagnosed with high-grade serous cancer. In the multimodal screening group compared with the no screening group, fewer were diagnosed with advanced stage disease (195 [75%] of 259 vs 446 [86%] of 520; p=0·0003), more had primary surgery (158 [61%] vs 219 [42%]; p<0·0001), more had zero residual disease following debulking surgery (119 [46%] vs 157 [30%]; p<0·0001), and more received treatment including both surgery and chemotherapy (192 [74%] vs 331 [64%]; p=0·0032). There was no difference in the first-line combination chemotherapy rate (142 [55%] vs 293 [56%]; p=0·69). Median follow-up from randomisation of 779 women with high-grade serous cancer in the multimodal and no screening groups was 9·51 years (IQR 6·04–13·00). At censorship (June 30, 2020), survival from randomisation was longer in women with high-grade serous cancer in the multimodal screening group than in the no screening group with absolute difference in survival of 6·9% (95% CI 0·4–13·0; p=0·042) at 18 years (21% [95% CI 15·6–26·2] vs 14% [95% CI 10·5–17·4]). To our knowledge, this is the first evidence that screening can detect high-grade serous cancer earlier and lead to improved short-term treatment outcomes compared with no screening. The potential survival benefit for women with high-grade serous cancer was small, most likely due to only modest gains in early detection and treatment improvement, and tumour biology. The cumulative results of the trial suggest that surrogate endpoints for disease-specific mortality should not currently be used in screening trials for ovarian cancer. National Institute for Health Research, Medical Research Council, Cancer Research UK, The Eve Appeal. [ABSTRACT FROM AUTHOR]

Background: Women with adnexal masses still pose a diagnostic dilemma and require efficient triaging. The Risk of Malignancy Index (RMI) is an algorithm used for differentiation of malignant from benign ovarian masses. Aims and Objectives: The present study aimed to evaluate the four indices RMI 1, RMI 2, RMI 3, and RMI 4 to discriminate a malignant ovarian tumor from a benign one. Materials and Methods: This cross-sectional study was carried out at a tertiary care hospital of Eastern Uttar Pradesh, India, in 312 patients with ovarian masses. RMI scores were calculated based on pre-operative cancer antigen-125 levels, ultrasonography, and menopausal status followed by post-operative histopathology, taken as gold standard. Using cutoff points of RMI indices, the sensitivity, specificity, positive predictive value, and negative predictive value of RMI were assessed. Results: Out of total 312 patients, 68 (21.8%) had malignant disease and 244 (78.2%) had benign pathology. All indices presented a significantly better performance in detecting malignancy than the use of a single parameter. Each of the RMIs had a different optimal threshold; however, using a threshold of 250, RMI 1, RMI 2, RMI 3, and RMI 4 had a sensitivity and specificity of 64.7%, 70.5%, 64.7%, and 65.2% and 93.4%, 83.6%, 90.2%, and 91.4%, respectively. Conclusion: The RMI is a simple, composite tool that at lower values can reliably predict benign nature of adnexal tumors. However, at values above the cutoff points, it is helpful for appropriate surgical planning and averts radical surgeries in women of reproductive age group. [ABSTRACT FROM AUTHOR]