Elevated CA-125 Levels Research Articles

Localized Hepatosplenic Sarcoidosis with an Elevated Serum CA-125 Level

Sarcoidosis, a granulomatous disorder of unknown etiology, primarily affects the lungs and lymph nodes. Extrapulmonary disease without any pulmonary involvement is rare. Sarcoidosis with an elevated serum CA-125 level has only been reported five times in the literature. We describe a case of localized hepatosplenic sarcoidosis, confirmed by biopsy, with associated CA-125 elevation. In our review of the current literature, this is the first reported case of localized hepatosplenic sarcoidosis with associated serum CA-125 elevation.

Carbonic Anhydrase IX Shedding Through Exosomes in Renal Carcinoma Cells

Carbonic anhydrase IX (CA IX) is a transmembrane glycoprotein highly expressed in clear cell carcinoma of the kidney and in a wide variety of other human cancers. Its expression is largely under the control of intratumoral hypoxia and in some subtypes of renal cell carcinoma (RCC), by the presence of a defective version of the von Hippel Lindau (VHL) gene by which the HIF-1α factor is stabilized. Several notable studies have shown that CA IX is involved in the control of acidity intracellularly. Thus, this enzyme could be involved in the regulation of pH within the tumor and may modulate the tumor microenvironment. Recent studies have also shown that this enzyme could be involved in the control of cell adhesion processes between the cancer cells, contributing to their invasive potential. Here, we have analyzed the effect of increasing the level of CA IX expression in the CA IX negative SKRC-17 renal cancer cells. Our results showed that CA IX is recruited to the lipid rafts of these cancer cells. Our results also highly suggest that the lipid raft component gangliosides are shed in the form of exosomes in this model system as a result of forced CA IX expression. The level of ganglioside shedding positively correlated with the increased level of CA IX expression in these cells. Finally, from a glycobiological perspective, our results indicate that elevated levels of CA IX expression contributes to increased ganglioside shedding in the form of exosomes which in turn may contribute to increased invasiveness and immunological escape in this malignancy.

Laparoscopic peritoneal biopsy can be crucial for diagnosis of tuberculous peritonitis.

A 28-year-old woman was admitted to a nearby hospital because of low-grade fever and lower abdominal pain, where ascites and slightly elevated serum CA125 level were found. Both acid-fast stain (AFS) and polymerase chain reaction (PCR) failed to detect Mycobacterium tuberculosis in her ascitic fluid, sputum, and gastric juice. She was referred to our division under suspicion of tuberculous peritonitis or ovarian carcinoma. Finally, diagnostic laparoscopy was carried out, showing yellowish-white small nodules disseminated on her whole peritoneum with thin fibrous adhesions. Peritoneal biopsy of these nodules showed epithelioid cell granulomas without caseous necrosis. AFS and PCR again failed to show any evidence of Mycobacterium tuberculosis in these biopsied samples. Based on the laparoscopic findings, however, we thought that she suffered from tuberculous peritonitis. Antituberculous therapy was started and she improved soon. Later, Mycobacterium tuberculosis was demonstrated in the 4-week culture of a peritoneal biopsy specimen. We conclude that laparoscopy may be the only way to detect Mycobacterium tuberculosis in tuberculous peritonitis whenever doubtful but no direct evidence is obtained.

Intraspecific Variation inTsuga canadensisFoliar Chemistry

Three groups of Tsuga canadensis (Eastern Hemlock) trees were analyzed to compare their chemical composition and the potential for naturally occurring resistance to Adelges tsugae (Hemlock Woolly Adelgid [HWA]). Potentially resistant “parent” trees located in southern Connecticut were compared with rooted propagules from those same trees and control trees located in northern Vermont, outside of the current HWA range. For trees in each group, we quantified Ca, P, K, C, and N and developed terpenoid profiles using solid-phase microextraction (SPME) and gas chromatography-mass spectrometry (GC/MS). There was no significant variation in terpenoid profiles between the three groups of hemlock trees. Propagules retained elevated levels of Ca and N from fertilization during propagation, suggesting that their chemical composition does not mirror the parent trees. The potentially resistant “parent” trees had higher levels of K compared to control trees. This may impart some level of tolerance/resistance to HWA and explain their persistence in hemlock forests that have otherwise been decimated by HWA. Comparison to regional foliar chemistry databases suggest that while rare, such elevated K levels do exist in natural hemlock populations. Such individuals may persist as HWA continues to spread across the region.

Value of serum CA125 levels in patients with high-risk, early stage epithelial ovarian cancer

Objectives The aim of this study was to ascertain whether serum CA125 level is predictive of disease progression in patients with high-risk, early stage (stage IA/B grade 3, stage IC any grade, stage I clear cell, or stage II) epithelial ovarian cancer who have achieved a complete response to chemotherapy. Methods Between January 1998 and April 2004, we reviewed the records of 95 patients with high-risk, early stage epithelial ovarian cancer who had elevated CA125 levels at the time of diagnosis and were complete responders after 6 cycles of adjuvant paclitaxel/carboplatin chemotherapy. A receiver operating characteristic curve was used to determine the most useful CA125 level in predicting disease progression and Cox proportional hazards models adjusted for covariates were used for analyses. Results The 5-year progression-free survival (PFS) was 70.5%. The optimal cutoff point of CA125 after completing adjuvant chemotherapy to predict disease progression was 12 U/mL (sensitivity, 71.4%; specificity, 82.1%). On multivariate analysis, CA125 level > 12 U/mL after completing adjuvant chemotherapy was an independent prognostic factor predictive for disease progression. The risk of recurrence was higher for CA125 level > 12 U/mL (hazards ratio = 10.567; P < 0.001). The 5-year PFS rate for patients with CA125 level ≤ 12 U/mL was 83.3%, which was higher than a PFS of 37.5% for CA125 > 12 U/mL ( P < 0.001). Conclusions CA125 level after 6 cycles of adjuvant chemotherapy is a strong independent prognostic factor for high-risk, early stage epithelial ovarian cancer after achieving a complete response.

Rejuvenation treatment of stored red blood cells reverses storage‐induced adhesion to vascular endothelial cells

Blood banking procedures are associated with elevated adherence of red blood cells (RBCs) to blood vessel wall endothelial cells (ECs), which can introduce a circulatory risk to recipients. This study was undertaken to examine the possibility of repairing this damage by a poststorage "rejuvenation" procedure before transfusion. Stored RBCs were treated with rejuvenation solution (Rejuvesol, enCyte Systems, Inc.), and their adhesion to cultured human microvascular ECs was determined as a function of shear stress using a cell flow properties analyzer. The adherence of rejuvenation-treated stored RBCs (stRBCs) was compared to that of untreated stRBCs and of freshly donated RBCs. Strong elevation of stRBC/EC adhesion was induced by cold storage and it correlated with translocation of phosphatidylserine (PS) to the RBC surface, a known mediator of RBC/EC adhesion. The role of RBC surface PS in stRBC/EC interaction was confirmed by the suppression of adhesion after the blocking of the stRBC surface PS with annexin V. Concomitantly, RBC storage elevated intracellular levels of reactive oxygen species (ROS) and Ca(2+), the latter known to facilitate PS externalization. Poststorage rejuvenation treatment of stRBCs reversed all the above changes (ROS, Ca(2+), PS), along with complete suppression of the enhanced RBC/EC adhesion, restoring it to that of normal, freshly collected RBCs. Poststorage RBC rejuvenation treatment is effective in reversing the storage-induced RBC/EC interaction. This provides further documentation for the potential clinical benefit of poststorage rejuvenation.

Massive peritoneal fluid and markedly elevated serum CA125 and CA19‐9 levels associated with an ovarian endometrioma

Endometriosis associated with ascites is an uncommon condition, but nevertheless important because it mimics the presentation of ovarian malignancy. We present the case of a 34-year-old woman who was admitted with the acute onset of abdominal pain and distension. A pelvic sonogram showed a large amount of peritoneal fluid with echogenic material and a 10-cm complex cystic structure, which appeared to be an enlarged left ovary. The concentrations of CA125 and CA19-9 were 548.1 and 7604 IU/mL, respectively. On the second day of admission, an exploratory laparoscopy was performed, which revealed a ruptured left ovarian cyst consistent with an endometrioma. A laparoscopic left adnexectomy was therefore performed. The histological examination of the specimen confirmed the diagnosis of an endometrioma. After a 12-month follow-up period, the patient showed no recurrence of the endometrioma or peritoneal fluid accumulation. In most instances, the presence of massive ascites is associated with malignancies, tuberculosis, or a perforated viscus. The information provided in the present report is important to both gynecologists and oncologists because it shows that an ovarian cyst with ascites and highly elevated CA125 and CA19-9 levels might be benign.

Inhibition of mesothelin–CA-125 interaction in patients with mesothelioma by the anti-mesothelin monoclonal antibody MORAb-009: Implications for cancer therapy

Background Mesothelin, a tumor differentiation antigen highly expressed in mesothelioma and ovarian cancer, is the receptor for CA-125 (MUC 16) and this interaction may play a role in tumor metastasis. MORAb-009 is a chimeric anti-mesothelin monoclonal antibody. Methods Twenty-four patients with mesothelin expressing cancers were treated on a phase I study of MORAb-009 administered as an intravenous infusion (12.5–400 mg/m 2) weekly × 4 doses with 2 weeks off before the next cycle. This report summarizes the effect of MORAb-009 on serum CA-125 kinetics in the eight patients with mesothelioma who had CA-125 levels measured before and at different time-points following therapy. Results MORAb-009 treatment led to a marked increase in serum CA-125 levels in all patients including those without elevated CA-125 levels before therapy. The increase in CA-125 levels was not due to disease progression since CA-125 levels decreased rapidly after stopping MORAb-009 therapy. No patients had signs of peritoneal or pleural inflammation as the possible cause of CA-125 rise. In addition, the elevated CA-125 levels were not due to MORAb-009 interfering with the laboratory assay used to measure CA-125. Conclusion The increase in serum CA-125 produced by treatment with MORAb-009 is most likely due to MORAb-009 inhibiting the binding of tumor shed CA-125 to mesothelin present on mesothelial cells lining the pleural and peritoneal cavities. Inhibiting the mesothelin–CA-125 interaction could be a useful strategy to prevent tumor metastasis in mesotheliomas and ovarian cancer.

Diagnosis and management of 57 cases with rectovaginal endometriosis

To study the diagnosis and therapy of the rectovaginal endometriosis. Clinical data of 57 women with rectovaginal endometriosis admitted to the West China Second University Hospital of Sichuan University in last two years,were retrospectively reviewed. The average age of patients was 40.1 years. The main clinical manifestations were dysmenorrheal, changes of menorrhea and digestive stimulation. The diameter of deep endometriosis nodules was between 1-6 cm, and 77% were found to have more than one nodules. Seven of these patients had positive results in transvaginal ultrasonography; 61%(11/18) patients had elevated CA125 levels. Thirteen patients were given preoperational medical treatment, but had no effect. All patients, except one accepted laparotomic therapy of complete excision of endometriosis nodules; 23 cases underwent drug therapy after operation. No patients had recurrence in recto-vaginal septum after complete excision; only one recurred in right ovary. Patients who failed to remove the total lesion showed improvement in pain. Diagnosis of the rectovaginal endometriosis is based on symptoms, vaginal and rectal examination, and auxiliary examination. Complete excision of endometriosis nodules is the main therapeutic method.

The role of calcium in apoptosis induced by 7β‐hydroxycholesterol and cholesterol‐5β,6β‐epoxide

Oxysterols, such as 7beta-hydroxy-cholesterol (7beta-OH) and cholesterol-5beta,6beta-epoxide (beta-epoxide), may have a central role in promoting atherogenesis. This is thought to be predominantly due to their ability to induce apoptosis in cells of the vascular wall and in monocytes/macrophages. Although there has been extensive research regarding the mechanisms through which oxysterols induce apoptosis, much remains to be clarified. Given that experimental evidence has long associated alterations of calcium (Ca(2+)) homeostasis to apoptotic cell death, the aim of the present study was to determine the influence of intracellular Ca(2+) changes on apoptosis induced by 7beta-OH and beta-epoxide. Ca(2+) responses in differentiated U937 cells were assessed by epifluorescence video microscopy, using the ratiometric dye fura-2. Over 15-min exposure of differentiated U937 cells to 30 muM of 7beta-OH induced a slow but significant rise in fura-2 ratio. The Ca(2+) channel blocker nifedipine and the chelating agent EGTA blocked the increase in cytoplasmic Ca(2+). Moreover, dihydropyridine (DHP) binding sites identified with BODIPY-FLX-DHP were blocked following pretreatment with nifedipine, indicating that the influx of Ca(2+) occurred through L-type channels. However, following long-term incubation with 7beta-OH, elevated levels of cytoplasmic Ca(2+) were not maintained and nifedipine did not provide protection against apoptotic cell death. Our results indicate that the increase in Ca(2+) may be an initial trigger of 7beta-OH-induced apoptosis, but following chronic exposure to the oxysterol, the influence of Ca(2+) on apoptotic cell death appears to be less significant. In contrast, Ca(2+) did not appear to be involved in beta-epoxide-induced apoptosis.

A Diagnostic Dilemma: Functioning Noncommunicating Uterine Horn and Elevated Levels of CA125

Background Müllerian duct abnormalities are important to diagnose, considering the various clinical manifestations, implications for reproductive life, different treatment options, and prognoses. However, they are often difficult to diagnose, especially by noninvasive means. Here we discuss the diagnostic difficulty incurred in a case of unicornuate uterus with functioning noncommunicating horn having a high level of cancer antigen 125 as a presenting feature. Case Unicornuate uterus with raised serum CA125. Conclusions Mullerian duct anomaly can be a differential diagnosis in women with adnexal mass and elevated CA125.

Peritoneal Tuberculosis Mimicking Ovarian Cancer—Diagnostic Difficulties. A Report of Two Cases

Tuberculosis, and specially its extrapulmonary location still causes diagnostic difficulties. In 2007, in Poland 7.3% of newly registered cases of tuberculosis in Poland were located extrapulmonary. Peritoneal tuberculosis is often wrongly diagnosed as an ovarian cancer, it is due to similar symptoms like abdominal pain, abdominopelvic masses, ascites and elevated serum CA-125. Two patients who were admitted to our department with suspicion of ovarian cancer are presented. Subjective symptoms suggested the ovarian cancer, elevated levels of CA-125, chest x-rays without abnormal findings or with minimal fibrotic changes and uncharacteristic results of additional investigations were disclosed. A diagnostic laparoscopy was made to establish the diagnosis. Because of clinical and operative picture suggesting ovarian cancer in both cases resections were performed. The procedure consisted of total abdominal hysterectomy and bilateral salpingo-oophorectomy. Biopsy specimens were taken up and verified histopathologically. The peritoneal tuberculosis was recognized in both cases.

SALIVA AS A DIAGNOSTIC MEDIUM

This is a review of current knowledge on the use of saliva, gingival cervical fluid and mucosal transudate in the detection of some oral and systemic diseases as well as drugs. Oral fluid is a diagnostic medium that can be easily collected and with minimal invasion but it has been neglected in the past. Today, saliva is being used more often to diagnose: HIV virus, oro-facial and systemic tumors, cardiovascular disease and in detecting addictive substances. Neutropil levels in saliva may also indicate successful bone marrow transplant. Oral fluid is now systematically being researched and oral fluid analysis is being compared with the analysis of other diagnostic media such as blood and urine. A number of recent studies have focused on oncogenic marker detection and its monitoring in saliva. The latest clinical and laboratory findings on diagnostic markers of oropharyngeal carcinoma in oral fluid could be the beginning of their wider use as a diagnostic medium. Oral fluid can also be also used to diagnose other malignancies such as breast cancer which was one of the first malignant tumors to be detected using genetic protein biomarkers. Raised levels of CA15-3 and the epidermal growth factor (EGF) receptor have been found in patients with breast cancer and elevated levels of CA 125 and the glycoprotein complex in the saliva of ovarian cancer patients. Doubtless, the diagnostic value of saliva, aided by current technological development will increase rapidly in the near future.

Clear Cell Adenocarcinoma Arising From Adenomyosis

A 73-year-old postmenopausal Japanese woman presented with a complaint of slight fever and weight loss. An elevated level of CA125 in the blood favored a diagnosis of malignant uterine body tumor, but was not confirmed by endometrial cytology and biopsy. Resection of the uterus revealed a solid whitish tumor in the myometrium that was diagnosed as clear cell adenocarcinoma (CCA) arising from adenomyosis. There were transitions between endometrial epithelium of adenomyosis, noninvasive CCA, and invasive CCA. Immunohistochemical expression of hepatocyte nuclear factor-1beta supported the diagnosis of CCA. Only one other English language document pertaining to CCA arising from adenomyosis exists. Malignant tumor arising from adenomyosis should be considered as a differential diagnosis when the serum level of tumor markers such as CA125 is high and when the tumor is intramyometrial.

Preoperative Serum CA-125 Levels in Endometrial Cancer

In Brief Objective: The aim of this study was to evaluate properative serum levels of CA-125 for the prediction of advanced stages of endometrial cancer. Method: Retrospective study evaluated 114 women with pathologically proven endometrial carcinoma treated in our institution that had preoperative serum CA-125 levels between January 1990 and December 2005. The association of preoperative serum CA-125 with a different histopathologic factors was evaluated. Statistical analysis was performed using Mann-Whitney U test and Kruskal-Wallis test and a logistic regression. Results: Elevated serum CA-125 levels were significantly correlated with advanced-stage disease, lymph node metastases, increased depth of myometrial invasion (P < 0,01). Similar correlation was seen between levels of CA-125 and positive peritoneal washing cytology, distant metastases and highest histologic grade. Multivariate analyses using logistic regression showed that lymph node metastases had the most significant effect on the elevation of preoperative serum CA-125 levels. Conclusion: The preoperative serum CA-125 level appears to be a significant independent predictor of advanced-stage disease and lymph node metastasis. Therefore, preoperative serum CA-125 may be a useful tool, in the clinical setting, for optimal individualized patient management. A CA-125 level should be included as a part of the preoperative workup for all patients with endometrial cancer. Preoperative serum CA-125 may be a useful tool, in the preoperative workup for all patients with endometrial cancer.

Ovarian cancer and Mayer–Rokitansky–Kuster–Hauser syndrome

A 48-year-old woman with Mayer–Rokitansky–Kuster–Hauser (MRKH) syndrome, right kidney aplasia, a pelvic-abdominal mass, and an elevated CA-125 level underwent bilateral salpingo-oophorectomy, omentectomy, and debulking for a presumed ovarian carcinoma. Intraoperative findings included a pelvic tumor on the surface of both ovaries. Pathological examination revealed a poorly differentiated ovarian carcinoma, mixed type, mainly of transitional and serous types, with minor components of clear cell and mucinous patterns. A stage III ovarian epithelial carcinoma, mixed type was diagnosed. The patient was treated with Paclitaxel and Carboplatin and was asymptomatic 24 months postoperatively. Rarely, ovarian carcinoma may be associated with MRKH syndrome.

CA19-9 serum levels in obstructive jaundice: clinical value in benign and malignant conditions

Background Obstructive jaundice is frequently associated with false CA19-9 elevation in benign conditions. The diagnostic accuracy of this tumor marker was evaluated in the present longitudinal study. Methods In 128 patients admitted for obstructive jaundice (87 with pancreato-biliary malignancy and 41 benign disease) serum CA19-9 was measured. Statistical analysis of marker levels obtained before and after endoscopic biliary drainage was performed in 60 patients. Results Elevated CA19-9 levels (>37 U/mL) were found in 61% of benign cases and 86% of malignancies. After biliary drainage, decrease of serum CA19-9 was observed in 19 of 38 malignant cases and in almost all benign cases (Wilcoxon matched pairs test: P = .207 and P <.001, respectively). Receiver operating characteristic (ROC) analysis identified a cut-off value of 90 U/mL to be associated with improved diagnostic accuracy after biliary drainage (sensitivity 61%, specificity 95%). Conclusions In the presence of successfully drained obstructive jaundice, CA19-9 serum levels that remain unchanged or measure more than 90 U/mL are strongly indicative of a malignant cause of obstruction. However, the real clinical utility of this marker remains controversial.

Clinicopathological aspects and prognostic value with respect to age: An analysis of 3,362 consecutive gastric cancer patients

Several studies have reported controversial results about clinicopathological features and prognoses in gastric cancer patients with respect to age, partly due to variable definitions of young age and inhomogeneity of the patient population. The aim of study was to analyze clinicopathological features and prognostic value of all stages of gastric cancer in a large consecutive series. Between 2000 and 2005, 3,362 patients with all stages of gastric cancer were enrolled in database. Patients were divided into three groups: group 1 (< or =45), group 2 (46-70), and group 3 (> or =71). Upper location and linitis plastica were more frequent in group 1. Young patients had a higher proportion of poorly differentiated and signet ring cell type with elevated CA19-9 level. Depressed type was more frequent in early gastric cancer (EGC) while Bormann type IV and Lauren diffuse type were more common in AGC in group 1. In curatively resected patients, a 5-year survival rate was significantly higher in group 1 than older groups. Stage, vein invasion, curative resection, and CA19-9 level were significant prognostic factors in all gastric cancer. Clinicopathological features associated with young gastric cancer include upper location, linitis plastica, histopathologically diffuse type, and unresectability.

Ascites in puerperium: a rare case of atypical pseudo-Meigs’ syndrome complicating the puerperium

We report the case of puerperal ascites, associated with elevated CA125 levels and secondary to a uterine myoma. The literature on pseudo-Meigs' syndrome associated with pregnancy was reviewed. A 35-year-old woman complained of abdominal distension 2 days after a spontaneous vaginal delivery. A mass of 5 cm in the right uterine corner had been detected during the first trimester ultrasound and had been diagnosed as subserosal myoma. Physical examination and ultrasound revealed massive ascites. Computed tomography confirmed ascites and laboratory investigations showed CA125 raised levels. Cytology of ascitic fluid resulted negative for malignancy. A laparotomy was performed and a large pedunculated myoma was removed. A final diagnosis of atypical pseudo-Meigs' syndrome was performed, being computed tomography and chest X-ray negative for pleural effusion. To the best of our knowledge, this is the first case of pseudo-Meigs' syndrome caused by a uterine leiomyoma described in puerperium and without hydrothorax. Though ascites is very rare in obstetrics, it should be considered when evaluating puerperal patients complaining of abdominal distension.

CA-125 change after chemotherapy in prediction of treatment outcome among advanced mucinous and clear cell epithelial ovarian cancers: a Gynecologic Oncology Group study.

There are limited data regarding unique clinical or laboratory features associated with advanced clear cell (CC) and mucinous (MU) epithelial ovarian cancers (EOC), particularly the relationship between CA-125 antigen levels and prognosis. A retrospective review of 7 previously reported Gynecologic Oncology Group phase 3 trials in patients with stage III/IV EOC was conducted. A variety of clinical parameters were examined, including the impact of baseline and changes in the CA-125 level after treatment of CC and MU EOC on progression-free (PFS) and overall survival (OS). Clinical outcomes among patients with advanced CC and MU EOC were significantly worse when compared with other cell types (median PFS, 9.7 vs 7.0 vs 16.7 months, respectively, P < .001; median OS, 19.4 vs 11.3 vs 40.5 months, respectively, P < .001). Suboptimal debulking was associated with significantly decreased PFS and OS among both. Although baseline CA-125 values were lower in CC (median, 154 micron/mL) and MU (100 micron/mL), compared with other cell types (275 micron/mL), this level did not appear to influence outcome among these 2 specific subtypes of EOC. However, an elevated level of CA-125 at the end of chemotherapy was significantly associated with decreased PFS and OS (P < .01 for all). Surgical debulking status is the most important variable at prechemotherapy predictive of prognosis among advanced CC and MU EOC patients. Changes in the CA-125 levels at the end treatment as compared with baseline can serve as valid indicators of PFS and OS, and likely the degree of inherent chemosensitivity.