Elevated Cancer Antigen 125 Levels Research Articles

Pseudo-Meigs syndrome caused by a rapidly enlarging hydropic leiomyoma with elevated CA125 levels mimicking ovarian malignancy: a case report and literature review

Pseudo-Meigs syndrome is a rare syndrome characterized by hydrothorax and ascites associated with pelvic masses, and patients occasionally present with elevated serum cancer antigen-125 (CA125) levels. Hydropic leiomyoma (HLM) is an uncommon subtype of uterine leiomyoma characterized by hydropic degeneration and secondary cystic changes. Rapidly enlarging HLMs accompanied by hydrothorax, ascites, and elevated CA125 levels may be misdiagnosed as malignant tumors. Here, we report a case of HLM in a 45-year-old Chinese woman who presented with ascites and hydrothorax. Preoperative abdominopelvic CT revealed a giant solid mass in the fundus uteri measuring 20 × 15 × 12 cm. Her serum CA125 level was elevated to 247.7 U/ml, while her hydrothorax CA125 level was 304.60 U/ml. The patient was initially diagnosed with uterine malignancy and underwent total abdominal hysterectomy and adhesiolysis. Pathological examination confirmed the presence of a uterine hydropic leiomyoma with cystic changes. After tumor removal, the ascites and hydrothorax subsided quickly, with no evidence of recurrence. The patient’s serum CA125 level decreased to 116.90 U/mL on Day 7 and 5.6 U/mL on Day 40 postsurgery. Follow-up data were obtained at 6 months, 1 year, and 2 years after surgery, and no recurrence of ascites or hydrothorax was observed. This case highlights the importance of accurate diagnosis and appropriate management of HLM to achieve successful outcomes.

19 Phase II Trial of Ubamatamab in MUC16-Expressing SMARCB1-Deficient Renal Medullary Carcinoma and Epithelioid Sarcoma

Abstract Background Mucin 16 (MUC16) is a large integral membrane glycoprotein that is highly expressed in malignancies such as ovarian cancer but only at low abundance in epithelial cells of normal tissues. Proteolytic cleavage of cell surface MUC16 results in the shedding of its extracellular portion, known as cancer antigen 125 (CA-125), into the bloodstream and a short, membrane-associated C-terminal MUC16 domain that remains on the cell surface. Renal medullary carcinoma (RMC) and epithelioid sarcoma (ES) are aggressive SMARCB1-deficient malignancies found to have elevated serum CA-125 levels in 70-80% of cases. Our preclinical studies suggest that upregulation of MUC16 upon SMARCB1 loss is a viable and attractive tumor target for SMARCB1-deficient malignancies such as ES and RMC. Ubamatamab is a human IgG4-based anti-MUC16 x anti-CD3 bispecific antibody that specifically targets the cell surface bound C-terminal MUC16 domain and can thus induce T cell–redirected killing of tumor cells even in the presence of high concentrations of CA-125. It would thus be a rationale therapy to use in SMARCB1-deficient malignancies expressing MUC16, including those such as RMC known to downregulate MHC Class I as a resistance mechanism to conventional immunotherapy. This is because CD3-targeting bispecific antibodies such as ubamatamab replace conventional signal 1 by engaging T cells regardless of MHC class I expression. As proof of concept, a 20-year-old patient with metastatic SMARCB1-negative ES expressing high levels of serum CA-125 achieved a durable (12+ months) partial response to ubamatamab after progressing on multiple prior therapies, including EZH2 inhibition with tazemetostat as well as anti-PD1/CTLA4 immune checkpoint inhibition with nivolumab plus ipilimumab. The patient reported Grade 2 CRS, pleural effusion, and pericardial effusion, all of which resolved without intervention1. This serves as proof-of-concept for the ability of CD3-targeted bispecifics to overcome resistance to immune checkpoint inhibition. Given this strong preclinical and clinical evidence, we have developed a phase II clinical trial of ubamatamab alone or in combination with the anti-PD1 immune-checkpoint inhibitor cemiplimab in patients with MUC16-expressing RMC and ES who have progressed on at least one line of prior therapy. Up to 20 patients will be enrolled from each disease cohort (ES and RMC) for a total of up to 40 patients. Patients enrolled in Stage I of the trial will receive ubamatamab monotherapy. Patients with disease progression on ubamatamab monotherapy during Stage I can proceed to stage II, which will evaluate the combination of ubamatamab with cemiplimab combination. The co-primary endpoints will be objective response rate (ORR) at any time during the trial and disease control rate (DCR) through 18 weeks. Secondary endpoints will include overall survival, progression-free survival, duration of response, and safety. All endpoints will be analyzed and reported separately for each disease cohort (RMC and ES), and for each Stage (ubamatamab monotherapy and combination ubamatamab with cemiplimab). The trial will utilize the time-to-event Bayesian Optimal Phase II (TOP) design, which maximizes statistical power with well-controlled type I errors. For patients with ES, the joint null hypotheses are that the objective response rate (ORR) is 15% and the disease control rate (DCR) is 26%. The regimen will be promising if either ORR is greater than 15% or DCR is greater than 26% with 69.6% power to declare this an interesting regimen if ORR is 30% and the DCR is 43%. For patients with RMC, the joint null hypotheses are that the objective response rate (ORR) is 15% and the disease control rate (DCR) is 15%. The regimen will be promising if either ORR is greater than 15% or DCR is greater than 15% with 71.4% power to declare this an interesting regimen if ORR is 30% and the DCR is 30%. Pre- and post-treatment correlative analyses will be performed in blood and tumor biopsy tissues to identify changes in specific immune cell subsets and elucidate the dynamic evolution of tumor and immune cell compartments as well as their spatial relationships following ubamatamab alone or in combination with cemiplimab. References 1 Revon-Riviere G, Chami R, Mills D, et al. Mucin 16 (cancer antigen 125) Expression in Epithelioid Sarcoma leads to Single-Patient Study with Bispecific T-Cell Engager Ubamatamab (Mucin16xCD3): A Bench-To-Bedside Experience. Connective Tissue Oncology Society, Nov 16–19, 2022, Vancouver, Canada.

Clinical analysis of 12 cases of ovarian yolk sac tumor

Objective: To investigate the diagnosis, treatment and prognosis of ovarian yolk sac tumor (OYST). Methods: The clinicopathological data and follow-up data of 12 patients with OYST admitted to the Affiliated Hospital of Qingdao University from January 2013 to December 2020 were retrospectively analyzed, and the diagnosis, treatment and prognosis of OYST patients were summarized. Results: (1) The age of 12 patients with OYST ranged from 11 to 37 years, with a median age of 20 years. At the first visit, all 12 patients had pelvic masses. Reasons for seeing a doctor: 6 cases of abdominal distension and abdominal pain, 4 cases of mass in the lower abdomen, 1 case of vaginal bleeding, and 1 case of appendicitis. International Federation of Obstetrics and Gynecology (FIGO) 2014 staging: 4 cases in stage Ⅰa, 2 cases in stage Ⅰc, 1 case in stage Ⅱc, 4 cases in stage Ⅲc, and 1 case in stage Ⅳb. (2) All 12 patients were examined by color Doppler ultrasound before operation, among which 10 cases showed unilateral adnexal masses and 2 cases bilateral adnexal masses. The median maximum diameter of tumor was 16.5 cm (range: 6.0-28.0 cm). The preoperative levels of alpha fetoprotein (AFP) in 12 patients (all >1 210 μg/L) were significantly higher than normal (<25 μg/L). Among the 11 patients with cancer antigen 125 (CA125) detection results, 9 patients showed elevated serum CA125 levels. (3) Among the 12 patients, 8 young infertile patients who needed to preserve their reproductive function underwent appendectomy, 3 infertile patients underwent staged surgery for ovarian malignant germ cell tumor, and only one bilateral lesion and infertile patient underwent unsatisfactory staged surgery for ovarian malignant germ cell tumor. Of the 12 patients, 11 patients were given combined chemotherapy regimen of bleomycin, cisplatin, and etoposide (BEP) after operation. One patient without chemotherapy developed metastasis 3 months after operation, and was given BEP chemotherapy, and her condition was controlled. (4) The deadline for follow-up was December 31st, 2022, and the median follow-up time was 60 months (range: 25-115 months). All the 12 patients survived without tumor during the follow-up period, and the median disease-free survival time was 84.5 months (range: 25-115 months). Conclusions: OYST mostly occurs in children and young women. Color Doppler ultrasound examination and serum AFP and CA125 detection have diagnostic value for OYST. Surgical treatment after diagnosis of OYST includes surgery to preserve reproductive function and timely and standardized chemotherapy after operation. The prognosis of patients is good regardless of stage.

Prevalence, Surgical, and Medical Management of Patients with Endometriosis amongst Indian Women

Objective: This study aims to determine the prevalence of endometriosis in women in South India, the epidemiological factors involved, and evaluate the symptomatic burden associated with it. Design: A large-scale Hospital-based study was conducted among women of reproductive age (16 to 44 years) in the state of Telangana between March 2018 and March 2023. A randomized multi-stage stratified sampling method was adopted and included 2,400 women who were screened using a validated structured questionnaire. Patients presenting with symptoms indicative of endometriosis underwent additional assessment using abdominal ultrasonography (AUS) and serum cancer antigen 125 (CA125) tests. For confirmation, laparoscopy was offered to the patients who consented. Patients who declined laparoscopy were given the option of undergoing magnetic resonance imaging (MRI) instead. Results: Among 2,400 women who participated, 60 women have been diagnosed with endometriosis during the 5-year study period. The prevalence of endometriosis was found to be 2.5%. The mean age of participants was 15.2 ± 3.5 years and the mean age at menarche was found to be 12.9 ± 1.1 years. Out of 60 participants diagnosed with endometriosis 30% (n = 18) experienced irregular menstrual cycles. Approximately 33.3% (n = 20) of the women reported experiencing Dysmenorrhea, with 28.4% (n = 17) complaining of dyspareunia. Among the cases with menstrual pain, exhibited ultrasound findings suggestive of endometriosis, with elevated CA125 levels observed in 45% (n = 27) of these cases. All 60 patients who consented to laparoscopic confirmation, exhibited positive histo-pathological evidence of endometriosis. The prevalence of endometriosis is found to be significant in women of reproductive age group and found to be associated with high rates of infertility in 15 (25%) patients. The results of this study showed that the prevalence of endometriosis is found to be 2.5% which is similar to the other studies reported. The severity of endometriosis during laparoscopy was assessed using the rAFS staging system, revealing rates of 55% and 45% for disease in Stages I &amp; II, Stages III, &amp; IV, respectively. Conclusion: Our study concludes that endometriosis predominantly affects women in the reproductive age group and is often associated with primary infertility. The laparoscopic findings are identified as a standard tool for both diagnosis and treatment of endometriosis.

The accuracy of whole-body 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in the detection of ovarian cancer relapse in patients with rising cancer antigen 125 (CA-125) levels

Background18F-fluorodeoxyglucose (FDG) PET/CT is a noninvasive imaging tool that has been used successfully for the diagnosis, staging, restaging, therapy monitoring, and prognostic prediction of ovarian cancer. For ovarian cancer surveillance, rising CA-125 levels raise the suspicion of recurrence despite its reported low specificity; being elevated in other benign and inflammatory conditions, and thus, confirmation is required. This work aimed to evaluate the role of 18F-FDG PET/CT in suspected ovarian cancer recurrence in patients presenting with elevated CA-125 levels.ResultsFifty female patients with suspected ovarian cancer recurrence owing to elevated CA-125 levels were included in this study. Recurrence was confirmed in 46/50 cases whether by histopathological confirmation or by serial follow-up imaging and clinical follow-up. Positive PET/CT findings were reported in 45/50 cases with 2 false-negative cases and 1 false-positive case. PET/CT examination was found to be superior to contrast-enhanced CT in the detection of peritoneal metastatic nodules and metastatic lymph nodes. According to this study, the estimated sensitivity, specificity, and overall diagnostic accuracy of PET/CT in the detection of recurrent ovarian cancer were 95.6%, 75%, and 94%, respectively.ConclusionsIn ovarian cancer surveillance, 18F-FDG PET/CT was found to be a sensitive and accurate noninvasive imaging tool that can be used in the detection of recurrent ovarian cancer in patients with elevated CA-125 levels, thus interfering with the management plan. The advantage of whole-body imaging in PET/CT allows for the detection and precise localization of recurrent or metastatic foci in abdominal and extra-abdominal sites as well.

Exploring the landscape of CA-125 testing: A comprehensive analysis of Ministry of Health data.

The aim of this study was to investigate the utilization patterns and clinical implications of cancer antigen 125 (CA-125) testing in the diagnosis of ovarian and endometrial cancers using a large-scale dataset obtained from the Ministry of Health. A retrospective analysis was conducted on anonymized data collected between 2017 and 2021, comprising 3.917.240 individuals who underwent CA-125 testing. The data included demographic information, test results, diagnoses, and clinical characteristics. Descriptive statistics and comparative analyses were performed to assess the utilization trends and clinical outcomes associated with CA-125 testing. Among the study population, CA-125 testing was primarily requested for female individuals, with the highest number of tests performed in the age group of 18-64 years. The overall positive rate for CA-125 was 13.31%, with slightly lower rates observed in females (13.18%) than males (14.07%). The study identified a significant association between elevated CA-125 levels and cancer diagnoses, with 19.88% of positive CA-125 results indicating cancer, whereas 10.51% had no cancer diagnosis. Furthermore, the study revealed a higher likelihood of cancer detection among individuals aged 65 years and above, with a positive rate of 17.79%. Our findings provide valuable insights into the utilization patterns and clinical implications of CA-125 testing in ovarian and endometrial cancer diagnosis. While CA-125 remains a prominent tumor marker, its interpretation should consider age, gender, and clinical context. The study emphasizes the potential benefits of integrating additional markers and imaging modalities to enhance diagnostic accuracy. These findings contribute to optimizing the use of CA-125 testing for early detection and management of gynecological malignancies, thereby improving patient outcomes.

The Potential Role of MUC16 (CA125) Biomarker in Lung Cancer: A Magic Biomarker but with Adversity.

Lung cancer is the second most commonly diagnosed cancer in the world. In terms of the diagnosis of lung cancer, combination carcinoembryonic antigen (CEA) and cancer antigen 125 (CA125) detection had higher sensitivity, specificity, and diagnostic odds ratios than CEA detection alone. Most individuals with elevated serum CA125 levels had lung cancer that was either in stage 3 or stage 4. Serum CA125 levels were similarly elevated in lung cancer patients who also had pleural effusions or ascites. Furthermore, there is strong evidence that human lung cancer produces CA125 in vitro, which suggests that other clinical illnesses outside of ovarian cancer could also be responsible for the rise of CA125. MUC16 (CA125) is a natural killer cell inhibitor. As a screening test for lung and ovarian cancer diagnosis and prognosis in the early stages, CA125 has been widely used as a marker in three different clinical settings. MUC16 mRNA levels in lung cancer are increased regardless of gender. As well, increased expression of mutated MUC16 enhances lung cancer cells proliferation and growth. Additionally, the CA125 serum level is thought to be a key indicator for lung cancer metastasis to the liver. Further, CA125 could be a useful biomarker in other cancer types diagnoses like ovarian, breast, and pancreatic cancers. One of the important limitations of CA125 as a first step in such a screening technique is that up to 20% of ovarian tumors lack antigen expression. Each of the 10 possible serum markers was expressed in 29-100% of ovarian tumors with minimal or no CA125 expression. Therefore, there is a controversy regarding CA125 in the diagnosis and prognosis of lung cancer and other cancer types. In this state, preclinical and clinical studies are warranted to elucidate the clinical benefit of CA125 in the diagnosis and prognosis of lung cancer.

CA125 as a predictor of endometrial cancer lymphovascular space invasion and lymph node metastasis for risk stratification in the preoperative setting

Endometrial cancer (EC) is the most common malignancy of the female reproductive system. Cancer antigen 125 (CA125) is a serum tumor marker widely reported in EC patients, particularly those with poor prognostic factors such as grade 3 tumors, deep myometrial invasion, lymph node metastasis (LNM), and extra-uterine disease. This retrospective study stratifies pre-operative CA125 levels to evaluate odds ratios (OR) and relative risk (RR) between CA125 levels and the likelihood of +LNM, lymphovascular space invasion (LVSI), grade, and stage. Patient charts for women 18 years or older with a diagnosis of EC and pre-operative or within one week CA125 measurement from January 2000 to January 2015 at a regional hospital were reviewed. OR and RR were determined by unconditional maximum likelihood estimation for CA125 levels as the predictor with staging, grade, +LVSI and +LNM as outcomes. The largest increase in risk for patients having stage I/II/III disease was 52% greater (1.52-fold risk) while largest increase in risk for patients having stage III/IV disease was 67% greater (1.67-fold risk), both at CA125 ≥ 222U/ml. Patients with CA125 ≥ 122U/ml had significantly increased risk of +LNM, with maximum increase in risk of 98% (1.98-fold risk) at 222U/ml. Patients with CA125 ≥ 175U/ml had significantly increased risk of +LVSI, with maximum increase in risk of 39% (1.39-fold risk) at 222U/ml. This study shows that elevated CA125 levels correspond to increased stage, +LVSI, and +LNM in patients with EC.

Clinical usefulness of cancer antigen 125 biomarker for tuberculosis diagnosis: experience in Cali, Colombia

Introduction: Diagnosing extra-pulmonary tuberculosis (EPTB) is a challenge for physicians. It has been suggested that cancer antigen 125 (CA-125), which is produced by mesothelial cells, may be an EPTB diagnostic biomarker. Objective: To describe serum CA-125 levels behavior in patients with TB treated in a referral university hospital located in Cali, Colombia. Materials and methods: A cross-sectional study was conducted in 99 TB patients with CA-125 measurements (U/mL) made before TB treatment was started, and treated at Fundación Valle del Lili between 2007 and 2016. Cases were classified as pulmonary TB (PTB) (n=33) or EPTB (n=66). A bivariate analysis was performed to compare the variables of interest (sociodemographic, clinical, and laboratory findings data) between EPTB and PTB groups, and to determine differences between patients with CA-125 positive results and those with negative results in relation to mortality. Results: Elevated CA-125 levels were reported in 55 patients (55.56%). Positive CA-125 results (&gt;35 U/mL) were more frequent in the EPTB group (59.09% vs. 48.48%). In the EPTB group, positive results were found in tuberculous serositis cases (100% pericardial TB, 68.42% peritoneal TB and 66.66% pleural TB), and in 66.66% of miliary TB and TB of the spine cases, respectively. Also, 15 TB infection-related deaths were reported in the follow-up period (n=66), of which 13 had a CA-125 positive result, finding a significant difference with those with negative results (p=0.021), however 47.05% of the surviving patients also had a positive result. Conclusions: Most of tuberculous serositis, miliary and TB of the spine cases showed elevated CA-125 levels before starting TB treatment. CA-125 may prove to be useful for prognostic purposes in these patients.

Incidence of and risk factors associated with lung metastases in newly diagnosed epithelial ovarian cancer with a look on prognosis after diagnosis: a population-based cohort study of the SEER database.

Patients with lung metastases (LM) from epithelial ovarian cancer (EOC) (EOCLM) usually have a poor prognosis. However, there is no consensus on the optimal management of these patients. In this study, we aimed to take a look at the incidence of LM and factors associated with its occurrence as well as the prognosis in newly diagnosed EOC with LM on a population level. EOC patients diagnosed between the years 2010 and 2016 were identified from the Surveillance, Epidemiology, and End Results (SEER) program database. Multivariable logistic regression and multivariable Cox regression were used to investigate the factors that could predict the occurrence of and prognosis after diagnosis of EOC with LM. Of the 33,418 qualified EOC patients, 2240 (6.7%) were noted to have LMs at the time of EOC diagnosis. Higher T stage, N1 stage, advanced tumor grade, and elevated cancer antigen-125 levels were found to be associated with a higher risk of having LM at the time of EOC diagnosis. The median survival time after diagnosis with EOCLM was found to be 13.0months (interquartile range: 3.0-34.0months). Being unmarried and having mucinous histology were both associated with increased all-cause death risk from EOCLM. However, the primary tumor originated from the midline of ovaries, surgical management, and whether patient received chemotherapy or not predicted improved overall survival. The median survival time of patients was significantly longer for EOCLM cases managed surgically (31.0months) versus those who did not have surgery (4.0months), as well as EOCLM cases received chemotherapy (23.0months) versus those who did not have chemotherapy (2.0months). This retrospective cohort study showed that de novo LM was infrequent in EOC patients overall and when present predicted poor prognosis. The findings can be potentially useful in formulating for follow-up strategies, screening tools, and personalized interventions.

Systemic thromboembolism including multiple cerebral infarctions with middle cerebral artery occlusion caused by the progression of adenomyosis with benign gynecological tumor: a case report

BackgroundAdenomyosis, a benign gynecological disease, causes cerebral infarction. Similar to Trousseau’s syndrome, it elevates cancer antigen 125 (CA125) and D-dimer levels; causes hypercoagulability; and results in cerebral infarction. However, no case of adenomyosis causing major cerebral artery occlusion and requiring endovascular thrombectomy has yet been reported. We report on a woman with middle cerebral artery occlusion caused by adenomyosis progression with a benign gynecological tumor and recurrent cerebral infarction. She was successfully treated by endovascular thrombectomy and hysterectomy.Case presentationA 48-year-old woman with heavy uterine bleeding was transported by ambulance to our hospital. Upon arrival, she presented with impaired consciousness. Laboratory test results revealed decreased hemoglobin (8.2 g/dL) and elevated D-dimer (79.3 µg/mL) levels. Radiological imaging revealed adenomyosis, a left ovarian tumor, multiple uterine myomas, and old and new bilateral renal infarctions. She experienced repeated episodes of excessive menstruation caused by adenomyosis and was scheduled for hysterectomy in 2 months at another hospital. After hospital admission, uterine bleeding stopped. However, 5 days after initial bleeding, she had another episode of heavy uterine bleeding and developed left hemiparesis and dysarthria 20 min later. Brain magnetic resonance imaging revealed bilateral multiple cerebral infarctions indicating right middle cerebral artery occlusion. Thus, endovascular thrombectomy was performed, and anticoagulant therapy was administered. Laboratory test results after thrombectomy revealed elevated CA125 (3536 U/mL) and CA19-9 (892 U/mL) levels. She was at a risk of recurrent heavy uterine bleeding leading to repeated cerebral infarction because of anticoagulant treatment. Therefore, we performed hysterectomy and ovariectomy 11 days after initial bleeding. Histopathological assessment revealed no malignancy. Although she developed asymptomatic pulmonary thromboembolism 14 days after initial bleeding, D-dimer and tumor marker levels returned to normal soon after gynecological surgery. At 15 months post-surgery, she had not experienced further ischemic events.ConclusionsAdenomyosis with benign gynecological tumors may be associated with elevated D-dimer and tumor marker levels; excessive menstruation; and anemia. It may cause systemic thromboembolism, including cerebral infarction. To our knowledge, no other study has reported that adenomyosis causes major cerebral artery occlusion requiring endovascular thrombectomy. Hysterectomy may be an effective radical treatment of this condition.

Inflammatory signals induce MUC16 expression in ovarian cancer cells via NF-κB activation.

Cancer antigen 125 (CA125), encoded by the mucin 16 cell surface associated (MUC16) gene, has been widely used as a biomarker for ovarian cancer (OC) screening. However, it has yet to be elucidated as to why its levels increase with tumor progression as well as with certain other non-malignant conditions. Based on our knowledge of the inflammatory microenvironment (IME) in OC, HEY cells were treated with several inflammation-associated factors as well as their antagonists, and it was observed that inflammation-associated factors upregulated MUC16 gene expression. Considering the role of nuclear factor (NF)-κB in the inflammatory signaling network and our previous research on OC, chromatin immunoprecipitation was performed, and it was observed that activated NF-κB bound to the MUC16 gene promoter and enhanced its expression, thereby elevating secreted CA125 levels. These findings demonstrated that IME and MUC16 gene expression were associated in OC, partly elucidating the role of IME in tumor progression, explaining the elevated serum CA125 levels in some non-malignant conditions, and confirming IME as a potential target for OC therapy.

Elevated CA-125 Level and ER-Negative as Prognostic Factors for Ovarian Metastasis in Patients with Endometrial Cancer: A Retrospective Cohort Study.

BackgroundThe utility of cancer antigen 125 (CA-125), estrogen receptor (ER), and progesterone receptor (PR) in evaluation for ovarian metastasis of endometrial cancer has yet to be determined. The purpose of this study was to investigate the incidence and the possible risk factors of ovarian metastasis.Material/MethodsA retrospective study was performed in endometrial cancer patients who accepted surgical intervention of hysterectomy and oophorectomy during 2002–2013 in Sun Yat-sen Memorial Hospital, Sun Yat-sen University, China. Clinico-pathologic characteristics and the possible risk factors were investigated.ResultsA total of 565 patients were identified, of which 5.7% had ovarian metastasis. Univariate analysis and multivariate analysis revealed that deeper myometrial invasion, tubal involvement, and parametrial involvement were independent risk factors. In subgroup analysis, univariate analysis showed that elevated CA-125 level and negative ER were associated with ovarian metastasis (P<0.05), however multivariate analysis revealed that only high CA-125 level was an independent risk factor (P<0.05). The incidence of ovarian metastasis in patients with high CA-125 level and who were ER-negative was 24%. For patients with normal CA-125 level and who were ER-positive, the incidence was 1.19%. The optimal cutoff value that provided the best sensitivity and specificity was 110.5 U/ml.ConclusionsThe incidence of ovarian metastasis in endometrial cancer is low. Ovarian preservation should be considered for women without abnormal CA-125 level and who have deeper myometrial invasion, tubal involvement, parametrial involvement, and who are ER-negative. These findings may facilitate clinical decision-making.

The role of adjuvant radiotherapy in stage I endometrial cancer: A single-institution outcome

ObjectivePostoperative radiotherapy for early endometrial cancer has been investigated in several randomized trials. These trials demonstrate that it reduces loco-regional recurrence, but has no impact on overall survival. The aims of this study were to better understand the role of adjuvant radiotherapy and determine predictors for loco-regional recurrence or development of distant metastasis. Materials and methodsA retrospective medical records review was performed on patients with surgical stage I endometrial cancer treated at Taipei Veterans General Hospital between 2006 and 2013. Multivariable analysis was conducted using Cox regression for prognostic predictors. ResultsA total of 337 patients were identified. The estimated five-year overall survival and loco-regional recurrence-free survival were 96.3% and 97.9% in the non-radiotherapy group, and 91.6% and 97.1% in the radiotherapy group (p = 0.06 overall survival, p = 0.956 loco-regional recurrence-free survival). Multivariable analysis revealed that elevated preoperative serum Cancer Antigen 125 (CA-125) level (hazard ratio (HR) = 2.54), age older than 60 years old (HR = 3.34), and depth of myometrial invasion > 50% (HR = 3.37) were significant factors in overall survival. Elevated preoperative CA-125 level (HR = 5.37), age older than 60 years (HR = 6.57), positive lymphovascular space invasion (HR = 50.20), and adjuvant radiotherapy (HR = 0.05) were independent predictors of loco-regional recurrence-free survival. For distant metastasis, deep myometrial invasion was a significant risk factor. ConclusionsPostoperative radiotherapy delivery is an independent predictor for loco-regional recurrence-free survival but has no impact on overall survival in this population. Preoperative CA-125 level is a risk factor for loco-regional recurrence, and deep myometrial invasion was correlated with distant metastasis.

Comparison between Serum HE4 and CA125 as Tumor Markers in Premenopausal Women with Benign Pelvic Mass

The aim of the study was to evaluate the role of human epididymal secretory protein (HE4), cancer antigen 125 (CA125), and the Risk of Ovarian Malignancy Algorithm (ROMA) in diagnosing benign pelvic masses in premenopausal women. Serum was collected from 391 premenopausal women with benign pelvic mass prior to surgery and from 45 healthy individuals. Serum HE4 and CA125 levels and ROMA scores were evaluated separately. Among the 391 women with benign pelvic mass, 2.3% (9/391) had elevated HE4 levels (> 70 pmol/L), while 37.1% (145/391) had elevated CA125 levels (> 35 U/mL) (p < 0001). Endometriosis provided false-positive results for CA125 levels in more than half of the cases but resulted in no significant change for HE4 level. In 13 gravid women with a mass, 30.8% (4/13) and 38.5% (5/13) had elevated HE4 and CA125 levels, respectively; however, the difference was not significant (p > 0.05). Moreover, serum levels and patient percentages for CA125 elevation significantly increased with increase in mass diameter, whereas those for HE4 did not. CA125 elevation showed random results for benign pelvic masses, while HE4 elevation showed a higher specificity. Thus, serum HE4 testing is a better approach than CA125 testing for diagnosing benign pelvic masses in premenopausal women.

CA-125 Significance in Cirrhosis and Correlation with Disease Severity and Portal Hypertension: A Retrospective Study

Background and Aims: To evaluate the prevalence and significance of elevated cancer antigen-125 (CA-125) levels in patients with cirrhosis being treated in a tertiary care liver center and its correlation with objective markers of disease severity.Methods: We retrospectively reviewed medical records of 172 adult patients with cirrhosis (due to any etiology) after obtaining CA-125 serum analysis. Demographics, etiology of cirrhosis, model of end-stage liver disease (MELD) score, Child’s Turcotte-Pugh classification, albumin bilirubin (ALBI) score, degree of ascites, presence of esophageal varices, serum CA-125 level and various other parameters were collected. Statistical analysis was performed using SPSS software and descriptive statistics.Results: Elevated CA-125 levels were noted in 147 patients (85%) of the study population. Higher MELD score was associated with higher CA-125 levels (p = 0.001). Statistically significant correlation was observed between elevated CA-125 levels and degree of ascites (p < 0.001), ALBI score (p < 0.001) and Child’s Turcotte-Pugh class (p < 0.001). No correlation was observed with presence or absence of esophageal varices. Near-normal CA-125 levels were noted in patients with cirrhosis but undetectable ascites on ultrasound imaging. No differences were observed in mean values between male and female patients (p = 0.207). Regression analysis confirmed that CA-125 levels had a better correlation with degree of ascites than MELD score or ALBI score.Conclusions: Elevated CA-125 levels were noted in 85% of patients with cirrhosis at our center. Our study establishes that the more advanced the degree of decompensation based on MELD score, Child’s Turcotte-Pugh classification and ALBI score, the higher the elevation in CA-125. Absence of ascites was associated with normal CA-125 level, with a direct correlation between high levels and worsening ascites, but there was no statistically significant correlation with esophageal varices, indicating that elevated CA-125 levels could be related to mechanical stretch of the peritoneum rather than portal hypertension itself. Further multi-centered studies are required to confirm and validate these findings.

Biomarkers of gastric cancer-related ischemic stroke and its underlying pathogenesis.

This study aimed to investigate the biomarkers and underlying pathogenesis of ischemic stroke in patients with gastric cancer (GC).Patients with active gastric cancer who had experienced acute ischemic stroke without conventional vascular risk factors (gastric cancer-related stroke [GCS] group) and visited The First Affiliated Hospital of Guangxi Medical University and First Affiliated Hospital of Sun Yat-sen University from January 2003 to December 2016 were retrospectively enrolled. The patients’ clinical features and laboratory findings were compared with those of age-, sex-, and disease progression-matched patients with GC without ischemic stroke (GC group) who had been admitted to the same hospital during the same period (GCS:GC ratio = 1:2).Among the 9166 patients diagnosed with GC, 70 had experienced a cerebral infarction and were enrolled in this study. Among them, 53 (75.71%) harbored multiple lesions in multiple vascular territories. Notably, patients in the GCS group exhibited significant increases in the D-dimer and cancer antigen 125 (CA125) levels and platelet-to-neutrophil ratio (PNR), compared to their counterparts in the GC group. A multiple logistic regression analysis identified all 3 factors as independent risk factors for cerebral infarction in patients with GC (D-dimer, odds ratio [OR] = 1.006 per 1 ng/mL increase, 95% confidence interval [CI], 1.004–1.009, P = .000; CA125, OR = 1.016 per 1 U/mL increase, 95% CI, 1.005–1.027, P = .005; PNR, OR = 1.025 per 1 point increase, 95% CI: 1.003–1.048, P = .023).Elevated plasma D-dimer and CA125 levels and an increased PNR might affect the occurrence of GC-related ischemic stroke and could therefore serve as potential biomarkers.

CA-125 in Disease Progression and Treatment of Lymphangioleiomyomatosis

Lymphangioleiomyomatosis (LAM) is a destructive lung disease of women caused by proliferation of neoplastic-like LAM cells, with mutations in the TSC1/2 tumor suppressor genes. Based on case reports, levels of cancer antigen 125 (CA-125), an ovarian cancer biomarker, can be elevated in patients with LAM. We hypothesized that elevated serum CA-125 levels seen in some patients with LAM were due to LAM, not other malignancies, and might respond to sirolimus treatment. Serum CA-125 levels were measured for 241 patients at each visit. Medical records were reviewed for co-morbidities, disease progression, and response to sirolimus treatment. CA-125 expression in LAM cells was determined by using immunohistochemical analysis. Almost 25%of patients with LAM had at least one elevated serum CA-125 measurement. Higher serum CA-125 levels correlated with lower FEV1, premenopausal status, and pleural effusion in a multivariate model (each P< .001). Serum CA-125 levels decreased following sirolimus treatment (P= .002). CA-125 and α-smooth muscle actin were co-expressed in LAM lung nodules. Higher serum CA-125 levels were associated with pleural effusions and reduced pulmonary function and were decreased with sirolimus therapy. LAM cells express CA-125. Some elevated serum CA-125 levels may reflect serosal membrane involvement.

Tubo-ovarian abscesses with elevated CA-125: A case report

Introduction: The detection of pelvic masses with an elevated blood cancer antigen 125 (CA-125) level is highly suggestive of ovarian cancer. However, various benign and inflammatory gynecological conditions and non-gynecological processes, such as liver and pulmonary diseases, may be associated with an elevated serum CA-125 level, especially in premenopausal women. Case Report: An 18-year-old female patient with lower abdominal pain for three days presented to our hospital. No fever was noted. Blood cancer antigen 125 (CA-125) level was elevated (660 U/mL; normal value, <35 U/mL), while the levels of other tumor markers (α-fetoprotein, carcinoembryonic antigen, β-human chorionic gonadotropin, and CA-199) were within normal limits. Transabdominal ultrasonography showed multicystic lesions with interior septation in the adnexal regions on both sides, suggesting the presence of cystic masses in both ovaries. Contrast-enhanced magnetic resonance imaging (MRI) revealed dilated and tubular structures with fluid-fluid level, wall thickening, and enhancement in the right pelvic cavity, and oval and septated masses with wall thickening and enhancement in both adnexal regions. A MRI diagnosis of right tubo-ovarian abscess and left ovarian abscess was made. Laparoscopy confirmed bilateral tubo-ovarian abscesses with pelvic adhesion. Right salpingectomy, left partial salpingectomy with end-to-end anastomosis, and adhesiolysis were performed. The patient was discharged with an uneventful course five days later. The blood CA-125 level dropped to 127 U/mL in 1 week, and to a normal value (6.5 U/mL) five months after surgery. Conclusion: Using CA-125 in isolation has limited value in differentiating benign from malignant pelvic masses. CA-125 levels are elevated in ovarian malignancy, as well as in pelvic inflammation, especially in a young woman with a sexual history. Clinical history and radiological information from US, CT, MRI and PET/CT provide important additional information for the disease entity. (This page in not part of the published article.) International Journal of Case Reports and Images, Vol. 7 No. 9, September 2016. ISSN – [0976-3198] Int J Case Rep Images 2016;7(9):583–586. www.ijcasereportsandimages.com Yeung et al. 583 CASE REPORT OPEN ACCESS Tubo-ovarian abscesses with elevated CA-125: A case report Kwok Wan Yeung, Hsin Chih Chao

Editorial

A 64-year-old woman referred to Gynaecological Oncology secondary to the finding of pelvic mass and ascites. Imaging showed multiple pelvic masses, with the largest mass measuring 20 cm in diameter, as well as bilateral pleural effusions and abdominal ascites, suspicious for ovarian carcinoma. Laboratory findings included elevated cancer antigen 125 (CA-125) of 2124 units/mL. The patient underwent an exploratory laparotomy, total abdominal hysterectomy and bilateral salpingo-oophorectomy for pathological evaluation. Postoperatively, the patient had resolution of ascites and pleural effusion. Surgical pathology revealed a 26 cm right ovarian fibroma, confirming the diagnosis of Meigs syndrome. Despite the high suspicion for ovarian carcinoma in patients presenting with elevated CA-125 level, pelvic mass, ascites and pleural effusion, the diagnosis of Meigs syndrome cannot be excluded without pathological evaluation of mass.