[German Registry for Acute Aortic Dissection Type A (GERAADA): initial results]. / Deutsches Register für akute Aortendissektion Typ A (GERAADA): Erste Ergebnisse.

BACKGROUND: The working group "Aortic Surgery and Interventional Vascular Surgery" of the German Society for Thoracic and Cardiovascular Surgery (GSTCVS) set up the German registry for acute aortic dissection type A (GERAADA) in July 2006. This web-based database was developed to record data of patients who had undergone surgery for aortic dissection type A (AADA). The aim of GERAADA is to learn from analyzing the data of AADA patients how to improve the perioperative management and surgical treatment of patients with AADA and to identify possible parameters affecting patient risk and outcome. PATIENTS AND METHODS: Between July 2006 and June 2009 (2010), 1558 (2137) patients with AADA were enrolled in the multi-center, prospective GERAADA database by 50 cardiac surgery centers in German-speaking countries in Europe. Data on patients' preoperative and intraoperative status, postoperative complications, midterm results and circumstances of death were recorded. Data were analyzed to identify risk factors influencing the outcome of these patients. The Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI) in Mainz performed the statistical analyses. RESULTS: Analyses from GERAADA reveal a thirty-day mortality of 17% in 2137 AADA patients. Only short interventions in aortic arch surgery are safe during hypothermic circulatory arrest even without selective cerebral perfusion. If circulatory arrest times of over 30 min. are anticipated, antegrade cerebral perfusion is strongly recommended during the entire arch intervention using cardiopulmonary bypass. Surgical strategy in terms of isolated ascending aortic replacement versus ascending aortic replacement combined with aortic arch repair had no statistical relevant influence on 30-day mortality. AADA surgical results in elderly patients are more encouraging than those treated without surgery. Surgery is even feasible in octogenarians with a 35% mortality rate. CONCLUSION: The aim of this registry is to optimize AADA patients' medical care, thereby reducing their morbidity and mortality. AADA treatment should always involve open surgery. Initial analyses from GERAADA provide clinically relevant insights concerning patients with AADA, and may enable therapeutic recommendations for improving perioperative and surgical management. Our latest study detected significant influencing risk factors for the outcome of AADA patients and may contribute to a consensus in setting guidelines for standard medical treatment. PERSPECTIVE: A European Registry of Aortic Diseases ("EuRADa") is being established this year under the leadership of the "Vascular Domain" of the European Association for Cardio-Thoracic Surgery (EACTS). This database will collect parameters on all aortic diseases, dissection types A and B, aneurysms, perforating ulcer (PAU), intramural wall hematoma (IMH), traumatic aortic ruptures, and all potential treatment strategies (medical treatment, open surgical and endovascular).

German Registry for Acute Aortic Dissection Type A (GERAADA)--new software design, parameters and their definitions.

BACKGROUND: The working group for aortic surgery and interventional vascular surgery of the German Society for Thoracic and Cardiovascular Surgery (GSTCVS) initiated the web-based German Registry for Acute Aortic Dissection type A (GERAADA). It is the project's aim to collect standardized data from a large pool of patients with acute aortic dissections type A (AADA) to gain a deeper insight and knowledge to improve surgical therapies and perioperative management for these patients in the future. METHODS: In addition to new medical insights, the working group has gained more experience over the last 4 years in how to collect valid and high-quality data. This experience led us to revise the database completely. In this article we describe the new version of GERAADA, providing an overview as well as defining the parameters, and explaining the new features. This overview fulfills a request by the users of GERAADA in the participating centers. RESULTS: Since its inception, 50 cardiac centers in Germany, Austria and Switzerland have provided over 2000 records and the first statistical results have been published. CONCLUSION: GERAADA's new design allows it to stay abreast of changes in medicine and to focus on the essentials necessary for statistically relevant results, while keeping the work load low for the data providers at each cardiac center.

German registry for acute aortic dissection type A (GERAADA)--lessons learned from the registry.

A German registry for acute aortic dissection type A (GERAADA) was initiated by the Working Group for Aortic Surgery and Interventional Vascular Surgery of the German Society for Thoracic and Cardiovascular Surgery (GSTCVS) in July 2006. This web-based database was developed to record the data of patients who had undergone surgery for aortic dissection type A. From analyzing the data, we aim to learn how to improve surgical treatment and to identify parameters affecting patient outcome. In the beginning, 33 cardiac centers participated via online access to the registry on the GSTCVS' homepage. Since then, 43 centers in Germany, Switzerland and Austria have begun entering data on the pre- and intraoperative status of their patients, postoperative complications, mid-term results and circumstances of death. We have succeeded in interpreting the initial results and trends from the registry now available to all of the participating centers, which benefit from this shared pool of analyzed data by optimizing their therapy regimes and comparing their success with that in the other centers.

Beating heart valve surgery using stentless xenografts as a surgical alternative for patients with end-stage renal failure.

Patients suffering from end-stage renal disease are an inhomogeneous high-risk group with a substantial perioperative mortality and morbidity when undergoing cardiac surgical procedures[1-3]. Myocardial ischemia, reperfusion injury and myocardial edema are a few of the deleterious consequences of the traditional use of cardioplegic arrest when performing valve surgery,irrespective of the type of cardioplegia used [4-7]. Novel operative techniques are required to reduce these induced perioperative risks. Clinical studies in the past have demonstrated the efficacy of beating heart valve surgery in the high-risk patient using retrograde, antegrade or combined coronary perfusion with warm oxygenated blood [8, 9]. We chose to combine the superior hemodynamic profile of stentless xenografts with the concept of performing valve replacement on the empty beating heart with continuous antegrade application of oxygenated blood in 2 chronic hemodialysis patients.

Minimally invasive direct coronary artery bypass grafting: a systematic review.

AIM: Recently minimally invasive direct coronary artery bypass grafting (MIDCAB) has become an interesting alternative to conventional coronary artery bypass grafting, especially in patients with a high-grade left anterior descending coronary artery (LAD) stenosis unsuitable for balloon angioplasty. Although MIDCAB offers several advantages such as the avoidance of sternotomy and cardiopulmonary bypass, concerns have been raised about the technical accuracy of the anastomoses that can be performed on a beating heart. Therefore, clinical and angiographic outcomes after MIDCAB are the subject of current controversy. METHODS: A literature search for all published outcome studies of MIDCAB grafting was performed for the period from January 1995 through April 2003. Sixteen articles were enrolled in this review. The data presented in the studies was analysed with regard to clinical outcome and angiographic results. RESULTS: Early mortality ranged from 0% to 4.9% and late mortality (>30 days after MIDCAB) ranged from 0.3% to 12.6%. Infarct rates (non-fatal myocardial infarction) ranged between 0% and 3.1%. Intra- and postoperative complications (wound infections, reoperation for management of bleeding, arrhythmias, stroke, etc.) occurred in 1.6-40%. The conversion rate to sternotomy/cardiopulmonary bypass ranged between 0% and 6.2%. Reinterventions due to graft failure were necessary in up to 8.9% of patients (surgical revision or percutaneous transluminal coronary angioplasty, PTCA). Short-term and mid-term angiographic outcomes are given in Table I. CONCLUSION: Clinical outcomes and immediate graft patency after MIDCAB are acceptable. However, long-term follow-up results and further randomized prospective clinical trials comparing this new technique with standard revascularization procedures are needed.

Coronary endothelial injury after local occlusion on the human beating heart.

BACKGROUND: Occlusion of coronary arteries during beating heart surgery bears the potential for mechanical trauma to the arterial wall with consequent endothelial injury. The aim of this study was to elucidate the effects of local occlusion on the beating heart in human coronary arteries. METHODS: Coronary arteries of patients with dilated cardiomyopathy (n = 7) or ischemic heart disease (n = 10) undergoing heart transplantation were locally occluded after starting cardiopulmonary bypass. Immediately after excision of the diseased heart, the vessels were fixed. Unoccluded segments served as controls. Integrity of endothelial lining was observed with scanning electron microscopy. RESULTS: Scanning electron microscopy revealed significantly more severe endothelial injury in the area of occlusion than in the adjacent, not manipulated control segments. In the region of local occlusion, plaque rupture was noted in three of 34 atherosclerotic vessel specimens, injury to side branches was evident in two of 44, and local microthrombus formation was evident in six of 44 samples. CONCLUSIONS: Local occlusion of human coronary arteries during beating heart coronary surgery may cause focal endothelial denudation, local microthrombosis, atherosclerotic plaque rupture, and injury to target vessel side branches.

Multiple blue nevi of the vagina. A case report.

BACKGROUND: Melanotic lesions of the vagina are very rare; clinically, most are suspected to be malignant melanomas. Occasional benign cases, however, require differential diagnostic consideration. We report a case of multiple (benign) blue nevi of the vagina. CASE: A 51-year-old woman presented with bluish black macules irregularly distributed throughout the vagina. Biopsies revealed pigmented cells in the dermis that proved to be melanocytes. The patient received no therapy. The lesions remained unchanged in the follow-up period. CONCLUSION: Multiple blue nevi could be a differential diagnosis for malignant melanoma of the vagina. Our patient showed no malignant transformation over a 29-year period. Therapy for blue nevi in the vagina does not require complete excision.

Simultaneous carotid and coronary artery surgery: indications and perioperative outcome.

BACKGROUND: A significant number of patients with coronary artery disease is diagnosed with additional carotid artery disease. This subset of patients has been identified as a high-risk group for cardiac and cerebral complications following surgical intervention. METHODS: In a retrospective analysis we investigated the perioperative outcome of combined single-stage carotid endarterectomy (CEA) and coronary artery bypass grafting (CABG) in 63 patients operated between January 1989 and August 1998. In all of these patients, CEA was performed prior to CABG and before initiation of cardiopulmonary bypass. RESULTS: Perioperative mortality rate was 7.9% (5/63) for simultaneous CEA and CABG and was due to cardiac complications in all patients. Postoperative unilateral neurological symptoms were diagnosed in 1 patient (1.7%) and were completely reversible. No neurologic events suggestive for permanent cerebral damage were observed during the 30 d postoperative period. CONCLUSIONS: In our study combined single-stage CEA and CABG was associated with low cerebral morbidity and patient outcome was mainly determined by cardiac complications. In this subset of patients, simultaneous CEA and CABG appears to be a safe method.

Intracoronary shunt insertion prevents myocardial stunning in a juvenile porcine MIDCAB model absent of coronary artery disease.

OBJECTIVE: The relevance of regional LV myocardial ischemia/reperfusion induced by temporary left anterior descending (LAD) coronary artery occlusion during minimally invasive direct coronary artery bypass (MIDCAB) grafting is controversial. The purpose of our study was (1) to determine the impact of conventional LAD occlusion during left internal thoracic artery (LITA)-LAD anastomosis on regional LV myocardial ischemia and function, and (2) to evaluate if intra-LAD shunt insertion during LITA-LAD anastomosis prevents potential regional LV ischemia and dysfunction in a pig model. METHODS: In 20 anesthetized, mechanically ventilated pigs we performed LITA-LAD anastomosis on the beating heart without cardiopulmonary bypass during either 15 min LAD occlusion (occlusion-group; n = 10) or 15 min intra-LAD shunt insertion to maintain blood supply to the myocardium beyond the anastomosis (shunt-group; n = 10). Besides standard hemodynamics we determined the global and regional LV wall motion score index (WMSI) using epimyocardial echocardiography. To quantitate structural myocardial alteration we determined the inducible heat-shock protein-70 (HSP-70) in LV anterior wall myocardial biopsies. Data were recorded at baseline, at 15 min of LAD occlusion or shunt insertion, respectively, and at 30 min of reperfusion. At the end of the experiments we determined myocardial adenine nucleotide (ATP, ADP, AMP) and glycogen content. RESULTS: In both groups WMSI was not significantly different at 15 min LAD occlusion or shunt insertion, respectively, as compared to baseline. However, at 30 min reperfusion both global and regional WMSI demonstrated significant LV dysfunction in the occlusion-group, whereas LV function in the shunt-group remained normal. This was associated with higher myocardial HSP-70 expression in the occlusion-group (P < 0.05). Myocardial adenine nucleotide and glycogen contents were significantly better preserved in the shunt-group. CONCLUSIONS: Our data show that in a porcine MIDCAB model 15 min LAD occlusion and 30 min reperfusion result in significant myocardial stunning. In contrast, maintenance of LAD perfusion using intracoronary shunt insertion minimizes ischemia/reperfusion injury and prevents regional LV dysfunction. Although our experiments were conducted in healthy pig hearts absent from coronary artery disease, similar results may--at least partially--be expected in humans, and thus, intracoronary shunts could be a useful tool for myocardial protection during 'off-pump revascularization'.

Ovarian preservation in the surgical treatment of cervical carcinoma.

OBJECTIVES: In the surgical treatment of cervical carcinoma the conservation of ovaries in premenopausal women is a common procedure. To date, however, there have been no controlled studies to prove that the risk of recurrence or death from disease is not elevated among women who do not undergo oophorectomy. STUDY DESIGN: We performed a matched pairs analysis according to the tumor volume, comparing the outcomes of patients with in situ conservation of >/=1 ovary with those of control subjects who underwent bilateral oophorectomy. From among 658 patients, 150 pairs with International Federation of Gynecology and Obstetrics stage I disease were matched. Kaplan-Meier survival curves were compared with the log rank test. RESULTS: Among patients who retained their ovaries 5- and 10-year overall survival rates were 98% and 96%, respectively, versus 97% and 97% for the oophorectomy control group. The corresponding figures for progression-free survival were 95% and 94%, respectively, versus 97% and 93%. Outcomes were equal with sufficient power to detect a 10% difference. Three of 214 patients with conservation of ovaries (1.3%) subsequently required oophorectomy, all because of benign ovarian diseases. CONCLUSIONS: Our results confirm that ovarian conservation is safe in International Federation of Gynecology and Obstetrics stage I disease and that the occurrence of subsequent complications in ovaries retained in situ is rare.

Beta-blockade versus Buckberg blood-cardioplegia in coronary bypass operation.

OBJECTIVE: Continuous perfusion of the coronary arteries with beta-blocker (esmolol)-enriched normothermic blood during cardiac surgery has been suggested as an alternative technique for myocardial protection. The aim of the present study was to compare the beta-blocker technique to Buckberg's blood cardioplegia during coronary artery bypass grafting (CABG). METHODS: Sixty patients with coronary artery disease were randomly assigned to either the esmolol group (ES, n = 30) or the blood cardioplegia group (BC, n = 30). During aortic crossclamp ES patients received continuous normothermic coronary perfusion with esmolol-enriched blood. Hearts of the BC group were protected by antegrade cold blood cardioplegia according to Buckberg. We measured left ventricular (LV) contractility using TEE (fractional area of contraction, FAC) and hemodynamic parameters prior to cannulation for cardiopulmonary bypass (CPB), after decannulation, and 4 h postoperatively. Myocardial lactate release was measured prior to aortic cross-clamp, during cross-clamp, and after decannulation. LV biopsies for determination of heat-shock protein (HSP-70), actin pattern and intercellular adhesion-molecule (ICAM-I) as indicators for structural changes were collected prior CPB, at the end of the aortic cross-clamp period, and prior to weaning off CPB. RESULTS: There was no significant difference between both groups with respect to grafts and cross-clamp time. ES hearts did not release lactate during cross-clamp. In contrast, BC hearts released significant amounts of lactate. Post CPB FAC and hemodynamics under similar inotropic stimulation showed no difference between groups, whereas at 4 h post CPB measurements showed slightly better values in the ES group: cardiac index: ES: 2.9+/-0.1 (SEM) versus BC: 2.6+/-0.1 L/min per m2 (P < 0.05); FAC: ES: 55+/-3 versus BC: 48+/-3% (P < 0.05). HSP-70 and actin pattern showed no difference between groups; however, ICAM-I showed a significantly higher degree of structural changes in BC hearts: 18+/-2 versus ES: 11+/-1% (P < 0.05). CONCLUSION: Our data demonstrate that application of the beta-blocker technique during routine CABG was associated with slightly better functional recovery and less structural myocardial alteration as compared with intermittent cold blood cardioplegia, however, both techniques provided equivalent myocardial protection in terms of patient outcome. Future studies are required to investigate if myocardial ischemia minimization by use of the beta-blocker technique may be beneficial in compromized hearts.

Single coronary artery bypass grafting--a comparison between minimally invasive 'off pump' techniques and conventional procedures.

OBJECTIVE: At present, few studies directly comparing minimally invasive and conventional coronary artery bypass grafting are available. The aim of the present study was to evaluate the clinical outcome of the two techniques. METHODS: We retrospectively compared our first consecutive 20 patients undergoing minimally invasive coronary artery single bypass grafting on the beating heart (group I) with 23 consecutive patients receiving single coronary artery bypass via sternotomy using cardiopulmonary bypass and cardioplegia (group II). The procedures were performed during the period from Jan 1, 1994 to Feb 20, 1997. There were no significant differences in demographic data. RESULTS: Statistically significant differences were found concerning total operative time (172.6 min in group I and 149.6 min in group II P = 0.0009) and myocardial ischemic time (23.7 min local coronary occlusion time in group I and 17.6 min aortic cross-clamp time in group II P = 0.03. Patients treated minimally invasive received significantly fewer blood transfusions (25.0% vs. 69.6% P = 0.0035) and were discharged significantly earlier from the hospital (admission rate on the fifth postoperative day 68.4% in group I vs. 100.0% in group II P = 0.0004). CONCLUSION: We conclude that minimally invasive coronary artery bypass grafting on the beating heart in comparison to conventional single coronary artery bypass grafting during the learning curve requires longer operative times but can reduce blood transfusion requirements and hospital stay.

Different intracellular compartmentations of cardiac troponins and myosin heavy chains: a causal connection to their different early release after myocardial damage.

We investigated the net myocardial release of creatine kinase isoenzyme MB (CKMB), myoglobin, cardiac troponin T (cTnT), cardiac troponin I (cTnI), and cardiac beta-type myosin heavy chain (beta-MHC) into the coronary circulation after cardioplegic cardiac arrest in humans. Cardiac markers were measured in paired arterial, central venous, and coronary sinus blood in 19 patients undergoing elective coronary artery bypass grafting (CABG) before aortic cross-clamping and 1, 5, 10, and 20 min after aortic declamping. cTnT and cTnI were released into the coronary sinus in parallel to each other and almost simultaneously to myoglobin and CKMB within 20 min of reperfusion. In contrast, no beta-MHC was released in the same patients during the study period. The average soluble cTnT and cTnI pools in right atrial appendages of 11 patients with right atrial and right ventricular pressures within reference values were comparable and were approximately 8% of total myocardial troponin content. The soluble beta-MHC pool was <0.1% in all patients. Our results demonstrate the impact of the different intracellular compartmention of regulatory and contractile proteins on their early release from damaged myocardium.

Atrial natriuretic peptide-induced release of cyclic guanosine monophosphate by coronary bypass grafts.

BACKGROUND: Superior long-term patency rates of the internal mammary artery (IMA) versus saphenous vein (SV) after coronary artery bypass grafting are well documented. Higher production rates of vasodilating and platelet-inhibiting mediators (prostacyclin and nitric oxide) by the IMA seem to have a major impact on its long-term durability and resistance to coronary artery graft disease. For the right gastroepiploic artery (RGEA) marked release of protective mediators is reported as well. The vasodilating effect of cyclic guanosine monophosphate (cGMP) released after stimulation by atrial natriuretic peptide might serve as another graft protective system. The aim of the present study was to determine cGMP release by IMA, RGEA, and SV after atrial natriuretic peptide challenge. METHODS: Samples of human IMA (n = 19), RGEA (n = 7), and SV (n = 18) discarded during coronary artery bypass grafting were stimulated with 10(-6) mol/L atrial natriuretic peptide after a resting phase in nutrient medium. Release of cGMP was determined by 125-iodide radioimmunoassay. RESULTS: Basal cGMP production rates of the IMA (759.9 +/- 277.0 fmol/cm2) and RGEA (739.9 +/- 186.0 fmol/cm2) were higher than production rates of SV (281.2 +/- 64.0 fmol/cm2). Application of atrial natriuretic peptide led to a statistically significant increase of cGMP release in IMA grafts (1,939.3 +/- 778.0 fmol/cm2), whereas RGEA (618.4 +/- 141.3 fmol/cm2) and SV (221.7 +/- 64.5 fmol/cm2) remained at basal levels (p < 0.05). CONCLUSIONS: From these data we conclude that the IMA in comparison with the RGEA and SV produces more extracellular cGMP when stimulated by atrial natriuretic peptide. This effect might support the cGMP-mediated protective properties of nitric oxide and could underline the extraordinary suitability of the IMA as a bypass conduit.

Stimulated prostacyclin release by conduits used for coronary artery bypass grafting.

A direct comparison of the three coronary artery bypass conduits internal mammary artery (IMA), right gastroepiploic artery (RGEA), and saphenous vein (SV) concerning arachidonic acid (AA) stimulated release of the vasodilating and platelet inhibiting mediator prostacyclin was the aim of the present study. Pieces of saphenous vein (n = 16), right gastroepiploic artery (n = 8), and internal mammary artery (n = 19) were obtained from patients undergoing coronary artery bypass grafting. After a resting phase of 30 min in HEPES medium arachidonic acid (AA) was added in order to stimulate prostacyclin release. Time-dependent production of the stable prostacyclin metabolite 6-keto-prostaglandin F1 alpha was determined following stimulation. Under basal conditions the IMA (12.4 ng/cm2) and RGEA (12.0 ng/cm2) released more prostacyclin than saphenous vein (4.0 ng/cm2). After AA stimulation 6-keto-prostaglandin F1 alpha release at 30 min was as follows: IMA 806.0 ng/cm2, RGEA 35.9 ng/cm2, SV 82.3 ng/cm2 (p < 0.0001 within grafts, p < 0.0001 between grafts, ANOVA for repeated measures). The internal mammary artery in comparison with the right gastroepiploic artery and saphenous vein seems to be better protected against local thrombotic events and development of coronary artery graft disease with the aid of the vasodilating and platelet inhibiting mediator prostacyclin.

Ascitic interleukin-12 is an independent prognostic factor in ovarian cancer.

PURPOSE: The clinical impact of endogenous cytokines supplied with deterministic properties in the generation of either T helper (Th)1 -type or Th2-type immune response was investigated in patients with ovarian cancer. Whereas interleukin (IL)- 12 initiates the differentiation of naive Th0 cells toward Th1 phenotype, IL-4 and IL-10 mediate the development of Th2-type immunity. PATIENTS AND METHODS: Cytokines were determined before treatment by means of enzyme-linked immunosorbent assay (ELISA) in ascites fluid and serum of 76 patients with ovarian cancer. Cytokine levels were compared with each other and with standard clinicopathologic parameters. A stepwise logistic regression was calculated to rule out interdependence in the associations of the various variables. Survival analyses were performed with the Kaplan-Meier method and differences in survival were examined according to Mantel and Breslow. Cox proportional hazards analysis was used to identify independent prognostic factors. RESULTS: Whereas IL-10 and IL-12 were detectable in all ascites-fluid samples, IL-4 was measurable in only 43% of the specimens. With the exception of neopterin, macrophage colony-stimulating factor (M-CSF), and IL-4, determined cytokine levels were significantly elevated in ascites fluid compared with serum (P < .01). In univariate analyses, high ascitic-fluid concentrations of either neopterin, tumor necrosis factor-alpha (TNF-alpha), or IL-12 were associated with poor disease-free (P < .005) and overall (P < .01) survival. Multivariate Cox regression analysis showed ascitic-fluid IL-12 levels to be the only immunologic variable that retained independent prognostic significance (P < .03 for disease-free and P < .01 for overall survival), together with residual disease, Fédération Internationale de Gynécologie et d'Obstétrique (FIGO)-stage, and patient age. CONCLUSION: In ovarian cancer, high ascitic-fluid IL-12 levels, which may indicate a local Th1-generated immune response, are associated with disease progression.

[Developments in surgical gynecology]. / [Entwicklungen in der operativen Gynäkologie]

This farewell lecture presents an overview of the development of operative gynecology on the basis of oncological surgery, removal of the uterus with or without pelvic floor reconstruction as well as corrective surgery of the uterovaginal canal. Without doubt the significance of endoscopic surgery, especially involving the adnexa and the cavum uteri, has increased. Uterus extirpation should remain in the domain of the vaginal approach. An experienced 'vaginalist' has has hardly any need for parasocpic assistance which should influence the renaissa lance of the vaginal method. Emphasis should be put on vaginal reconstruction of the affected pelvic floor in the course of incontinence surgery. Thanks to new diagnostic means malformations of the uterus can be detected more frequently, and it appears essential to develop and improve these methods further if one is to prevent laparoscopic polypragmatism. The author's opinion about the insufficient surgical experience and training in medical specialist education will be discussed.

Paclitaxel- and docetaxel-dependent activation of CA-125 expression in human ovarian carcinoma cells.

Taxanes represent a new class of antineoplastic agents that are being evaluated in several malignant tumors; they have been shown to induce a high remission rate and to prolong survival in ovarian cancer patients. However, CA-125 has been suggested to be an unreliable marker for monitoring response to paclitaxel therapy. Therefore, we were interested in whether taxanes may directly modulate CA-125 expression. Human ovarian carcinoma cell lines OVCAR-3, HOC-7, SKOV-6, 2780, 2774, and HTB-77 were treated with paclitaxel or docetaxel. Secreted, surface-associated, and cytosolic CA-125 were estimated by means of a sandwich solid-phase RIA or by immuno-flow cytometry. In addition to in vitro antiproliferative activity, paclitaxel and docetaxel augmented the expression of the tumor marker CA-125 in the three ovarian carcinoma cell lines, OVCAR-3, HOC-7, and SKOV-6, constitutively expressing this tumor marker. The three CA-125-negative cell lines, 2780, 2774, and HTB-77, did not respond to taxane treatment by expressing this tumor marker, although their proliferation was markedly inhibited. The taxane-mediated induction of CA-125 was found to be dependent on intact protein and RNA biosynthesis. However, CA-125 concentration was increased in the supernatant medium only and not on cell surface or cytosol. Our results demonstrate an in vitro activation of ovarian carcinoma cells in terms of CA-125 secretion by taxanes. This may explain the CA-125 fluctuations observed in vivo under paclitaxel treatment and may indicate that CA-125 is not a reliable tumor marker during taxane chemotherapy.

Modulation of CA-125 release by inflammatory cytokines in human peritoneal mesothelial and ovarian cancer cells.

In the present study the modulatory effects of inflammatory cytokines, interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), on CA-125 release in established ovarian cancer cell lines and in human peritoneal mesothelial cells (HPMC) both grown as monolayers, were investigated. The purity of mesothelial cell cultures were confirmed by the positivity of the cells for vimentin and cytokeratins 8 and 18, and their negativity for markers CD34 and CD68, thus excluding contamination by endothelial cells and macrophages. The preliminary results of CA-125 measurements in the culture medium clearly indicated differences in the pattern of CA-125 expression and release between normal and malignant cells under the influence of inflammatory cytokines. Furthermore, it seems that normal mesothelial cells play a crucial role as a source of CA-125 found in ascitic fluid or in pleural effusions and possibly even in the serum since secretion of this tumor marker into the culture medium was found to be significantly higher in HPMC than in ovarian cancer cells.