Predictive value of CA 125 and CA 72-4 in ovarian borderline tumors

Background: The aim of this study was to assess the prognostic value of cancer antigen (CA) 125 and CA 72-4 in patients with ovarian borderline tumor (BOT). Methods: All women diagnosed and treated for BOT at our institution between 1981 and 2008 were included into this retrospective study (n=101). Preoperatively collected serum samples were analyzed for CA 125 (Architect, Abbott and Elecsys, Roche) and CA 724 (Elecsys, Roche) with reference to clinical data and compared to healthy women (n=109) and ovarian cancer patients (n=130). Results: With a median of 34.7 U/mL (range 18.1-385.0 U/mL) for CA 125 and 2.3 U/mL (range 0.2-277.0 U/mL) for CA 72-4, serum tumor markers in BOT patients were significantly elevated as compared to healthy women with a median CA 125 of 13.5 U/mL (range 4.0-49.7 U/mL) and median CA 72-4 of 0.8 U/mL (range 0.2-20.6 U/mL). In addition, there was a significant difference compared with ovarian cancer patients who showed a median CA 125 of 401.5 U/mL (range 12.5-35,813 U/mL), but no difference was observed for CA 72-4 (median 3.9 U/mL, range 0.3-10,068 U/mL). Patients with a pT1a tumor stage had significantly lower values of CA 125 but not of CA 72-4 compared with individuals with higher tumor stages (median CA 125 29.9 U/mL for pT1a vs. 50.9 U/mL for) pT1a; p=0.014). There was a trend for increased concentrations of CA 125 but not of CA 72-4 in the presence of ascites, endometriosis or peritoneal implants at primary diagnosis. With respect to the prognostic value of CA 125 or CA 72-4, CA 125 was significantly higher at primary diagnosis in patients who later developed recurrence (251.0 U/mL vs. 34.65 U/mL, p=0.012). Conclusions: Serum CA 125 and CA 72-4 concentrations in BOT patients differ from healthy controls and patients with ovarian cancer. CA 125, but not CA 724, at primary diagnosis correlates with tumor stage and tends to be increased in the presence of ascites, endometriosis or peritoneal implants. Moreover, CA 125 at primary diagnosis appears to have prognostic value for recurrence. Clin Chem Lab Med 2009; 47:537-42

The diagnostic accuracy of two human epididymis protein 4 (HE4) testing systems in combination with CA125 in the differential diagnosis of ovarian masses

Background: Cancer antigen 125 (CA125) is the best known single tumor marker for ovarian cancer (OC). We investigated whether the additional information of the human epididymis protein 4 (HE4) improves diagnostic accuracy. Methods: We retrospectively analyzed preoperative sera of 109 healthy women, 285 patients with benign ovarian masses (cystadenoma: n = 78, leimyoma: n = 66, endometriosis: n = 52, functional ovarian cysts: n = 79, other: n = 10), 16 low malignant potential (LMP) ovarian tumors and 125 OC (stage 1: 22, II: 15, III: 78, IV: 10). CA 125 was analyzed using the ARCHITECT system, HE4 using the ARCHITECT(a) system and EIA(e) technology additionally. Results: The lowest concentrations of CA125 and HE4 were observed in healthy individuals, followed by patients with benign adnexal masses and patients with LMP tumors and OC. The area under the curve (AUC) for the differential diagnosis of adnexal masses of CA 125 alone was not significantly different to HE4 alone in premenopausal (CA 125: 86.7, HE4(a): 82.6, HE4(e): 81.6% p > 0.05) but significantly different in postmenopausal {[}CA125: 93.4 vs. HE4(a): 88.3 p = 0.023 and vs. HE4(e): 87.8% p=0.012] patients. For stage I OC, HE4 as a single marker was superior to CA 125, which was the best single marker in stage H-IV. The combination of CA 125 and HE4 using risk of malignancy algorithm (ROMA) gained the highest sensitivity at 95% specificity for the differential diagnosis of adnexal masses {[}CA 125: 70.9, HE4(a): 67.4, HE4(e): 66.0, ROMA(a): 76.6 and ROMA(e): 74.5%], especially in stage I OC {[}CA 125: 27.3, HE4(a): 40.9, HE4(e): 40.9, ROMA(a): 45.5 and ROMA(e): 45.5%]. Conclusions: CA 125 is still the best single marker in the diagnosis of OC. HE4 alone and even more the combined analysis of CA 125 and HE4 using ROMA improve the diagnostic accuracy of adnexal masses, especially in early OC

Changes in gynecologic and breast cancer diagnoses during the first wave of the COVID-19 pandemic: analysis from a tertiary academic gyneco-oncological center in Germany

PURPOSE With the beginning of 2021, the world has been suffering from the COVID-19 pandemic for more than 1 year. More and more, we are able to evaluate side effects of the pandemic in the healthcare sector. A negative impact on cancer diagnoses is one of them. Careful observation of trends in an academic gyneco-oncological context appears important to identify potential negative developments. METHODS We analyzed the case number of gynecologic and breast cancer diagnoses in the period from January to June 2020 compared to 2019 and during the period of the first general German lockdown (March 22nd until May 5th 2020). Patients were characterized by age, tumor type, FIGO or TNM stage and presence of symptoms at initial hospital presentation. RESULTS The frequency of newly diagnosed gynecologic and breast cancer cases from beginning of January until end of June changed by - 10% and by - 12% during the lockdown in 2020 compared to 2019. In both periods, reduction of breast cancer cases was relatively larger than decrease of gynecologic cancers. Moreover, median patient age decreased. For the first half of 2020, we found a shift towards higher tumor stages (N+/M1 or FIGO III-IV). During the lockdown period, the appearance of tumor-associated symptoms at diagnosis increased by about 12%. CONCLUSION This analysis illustrates the anticipated general decrease in diagnoses of primary cancers during the lockdown periods in 2020 due to COVID-19 pandemic for gynecologic and breast cancer cases

KRAS, BRAF genotyping reveals genetic heterogeneity of ovarian borderline tumors and associated implants

Background: Patients diagnosed for a serous ovarian borderline tumor (s-BOT) typically present with an excellent clinical outcome. However there have been controversies concerning the prognostic impact of so-called implants, an extra ovarian spread occurring alongside the s-BOT in certain cases. It remains obscure whether these implants actually resemble metastasis owning the same genetic pattern as the ovarian primary or whether they develop independently. Methods: The current study, in the aim of further clarifying the genetic origin of implants, assessed BRAF/KRAS hot spot mutations and the p53/p16(INK4a) immunophenotype of s-BOTs and corresponding implants (n = 49) of 15 patients by pyro-sequencing and immunostaining, respectively. Results: A significant proportion of both s-BOTs and implants showed KRAS or BRAF mutation and though p16(INK4a) was found to be abundantly expressed, p53 immunoreactivity was rather low. When genotypes of BRAF/KRAS mutated s-BOTs and corresponding implants were compared no patient presented with a fully matching mutation profile of s-BOTs and all corresponding implants. Conclusions: The current study reveals genetic heterogeneity of s-BOTs and implants, as none of the markers examined showed constant reciprocity. Hence, our findings may assist to explain the different clinical presentation of s-BOTs and implants and might encourage to applying more individualized follow up protocols

Therapeutic Outcome of MR-Guided High-Intensity Focused Ultrasound (MR-HIFU) in Solitary versus Multiple Uterine Fibroids

MR-guided high-intensity focused ultrasound (MR-HIFU) is an effective method for treating symptomatic uterine fibroids, especially solitary lesions. The aim of our study was to compare the clinical and morphological outcomes of patients who underwent MR-HIFU due to solitary fibroid (SF) or multiple fibroids (MFs) in a prospective clinical trial. We prospectively included 21 consecutive patients with SF (10) and MF (11) eligible for MR-guided HIFU. The morphological data were assessed using mint Lesion (TM) for MRI. The clinical data were determined using the Uterine Fibroid Symptom and Quality of Life (UFS-QOL) questionnaire before and 6 months after treatment. Unpaired and paired Wilcoxon-test and t-tests were applied, and Pearson's coefficient was used for correlation analysis. A p-value of 0.05 was considered statistically significant. The volume of treated fibroids significantly decreased in both the SF (mean baseline: 118.6 cm(3);mean 6-month follow-up: 64.6 cm(3)) and MF (107.2 cm(3);55.1 cm(3)) groups. The UFS-QOL showed clinical symptoms significantly improved for patients in both the SF and MF groups regarding concern, activities, energy/mood, and control. The short-term outcome for the treatment of symptomatic fibroids in myomatous uterus by MR-guided HIFU is clinically similar to that of solitary fibroids

Gal-2 increases H3K4me3 and H3K9ac in trophoblasts and preeclampsia

Preeclampsia (PE) is a severe pregnancy disorder with a pathophysiology not yet completely understood and without curative therapy. The histone modifications H3K4me(3) and H3K9ac, as well as galectin-2 (Gal-2), are known to be decreased in PE. To gain a better understanding of the development of PE, the influence of Gal-2 on histone modification in trophoblasts and in syncytialisation was investigated. Immunohistochemical stains of 13 PE and 13 control placentas were correlated, followed by cell culture experiments. An analysis of H3K4me(3) and H3K9ac was conducted, as well as cell fusion staining with E-cadherin and β-catenin—both after incubation with Gal-2. The expression of H3K4me(3) and H3K9ac correlated significantly with the expression of Gal-2. Furthermore, we detected an increase in H3K4me(3) and H3K9ac after the addition of Gal-2 to BeWo/HVT cells. Moreover, there was increased fusion of HVT cells after incubation with Gal-2. Gal-2 is associated with the histone modifications H3K4me(3) and H3K9ac in trophoblasts. Furthermore, syncytialisation increased after incubation with Gal-2. Therefore, we postulate that Gal-2 stimulates syncytialisation, possibly mediated by H3K4me(3) and H3K9ac. Since Gal-2, as well as H3K4me(3) and H3K9ac, are decreased in PE, the induction of Gal-2 might be a promising therapeutic target

The intravascular volume effect of Ringer's lactate is below 20%: a prospective study in humans

Introduction: Isotonic crystalloids play a central role in perioperative fluid management. Isooncotic preparations of colloids (for example, human albumin or hydroxyethyl starch) remain nearly completely intravascular when infused to compensate for acute blood losses. Recent data were interpreted to indicate a comparable intravascular volume effect for crystalloids, challenging the occasionally suggested advantage of using colloids to treat hypovolemia. General physiological knowledge and clinical experience, however, suggest otherwise. Methods: In a prospective study, double-tracer blood volume measurements were performed before and after intended normovolemic hemodilution in ten female adults, simultaneously substituting the three-fold amount of withdrawn blood with Ringer's lactate. Any originated deficits were substituted with half the volume of 20% human albumin, followed by a further assessment of blood volume. To assess significance between the measurements, repeated measures analysis of variance (ANOVA) according to Fisher were performed. If significant results were shown, paired t tests (according to Student) for the singular measurements were taken. P < 0.05 was considered to be significant. Results: A total of 1,097 +/- 285 ml of whole blood were withdrawn (641 +/- 155 ml/m2 body surface area) and simultaneously replaced by 3,430 +/- 806 ml of Ringer's lactate. All patients showed a significant decrease in blood volume after hemodilution (-459 +/- 185 ml; P < 0.05) that did not involve relevant hemodynamical changes, and a significant increase in interstitial water content (+ 2,157 +/- 606 ml; P < 0.05). The volume effect of Ringer's lactate was 17 +/- 10%. The infusion of 245 +/- 64 ml of 20% human albumin in this situation restored blood volume back to baseline values, the volume effect being 184 +/- 63%. Conclusions: Substitution of isolated intravascular deficits in cardiopulmonary healthy adults with the three-fold amount of Ringer's lactate impedes maintenance of intravascular normovolemia. The main side effect was an impressive interstitial fluid accumulation, which was partly restored by the intravenous infusion of 20% human albumin. We recommend to substitute the five-fold amount of crystalloids or to use an isooncotic preparation in the face of acute bleeding in patients where edema prevention might be advantageous

Global Study of Electron-Quark Contact Interactions

We perform a global fit of data relevant to $eeqq$ contact interactions, including deep inelastic scattering at high $Q^2$ from ZEUS and H1, atomic physics parity violation in Cesium from JILA, polarized $e^-$ on nuclei scattering experiments at SLAC, Mainz and Bates, Drell-Yan production at the Tevatron, the total hadronic cross section $\sigma_{had}$ at LEP, and neutrino-nucleon scattering from CCFR. With only the new HERA data, the presence of contact interactions improves the fit compared to the Standard Model. When other data sets are included, the size of the contact contributions is reduced and the overall fit represents no real improvement over the Standard Model.Comment: 26 pages (now single-spaced), Revtex, 2 eps figures, uses epsf.sty. Some clarifications, minor corrections, 2 new references, also 3 new tables which present 95% CL bounds on the contact interaction scales Lambd