Olaparib plus bevacizumab first-line maintenance in ovarian cancer: final overall survival results from the PAOLA-1/ENGOT-ov25 trial.

BACKGROUND: In the PAOLA-1/ENGOT-ov25 primary analysis, maintenance olaparib plus bevacizumab demonstrated a significant progression-free survival (PFS) benefit in newly diagnosed advanced ovarian cancer patients in clinical response after first-line platinum-based chemotherapy plus bevacizumab, irrespective of surgical status. Prespecified, exploratory analyses by molecular biomarker status showed substantial benefit in patients with a BRCA1/BRCA2 mutation (BRCAm) or homologous recombination deficiency (HRD; BRCAm and/or genomic instability). We report the prespecified final overall survival (OS) analysis, including analyses by HRD status. PATIENTS AND METHODS: Patients were randomized 2 : 1 to olaparib (300 mg twice daily; up to 24 months) plus bevacizumab (15 mg/kg every 3 weeks; 15 months total) or placebo plus bevacizumab. Analysis of OS, a key secondary endpoint in hierarchical testing, was planned for ∼60% maturity or 3 years after the primary analysis. RESULTS: After median follow-up of 61.7 and 61.9 months in the olaparib and placebo arms, respectively, median OS was 56.5 versus 51.6 months in the intention-to-treat population [hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.76-1.12; P = 0.4118]. Subsequent poly(ADP-ribose) polymerase inhibitor therapy was received by 105 (19.6%) olaparib patients versus 123 (45.7%) placebo patients. In the HRD-positive population, OS was longer with olaparib plus bevacizumab (HR 0.62, 95% CI 0.45-0.85; 5-year OS rate, 65.5% versus 48.4%); at 5 years, updated PFS also showed a higher proportion of olaparib plus bevacizumab patients without relapse (HR 0.41, 95% CI 0.32-0.54; 5-year PFS rate, 46.1% versus 19.2%). Myelodysplastic syndrome, acute myeloid leukemia, aplastic anemia, and new primary malignancy incidence remained low and balanced between arms. CONCLUSIONS: Olaparib plus bevacizumab provided clinically meaningful OS improvement for first-line patients with HRD-positive ovarian cancer. These prespecified exploratory analyses demonstrated improvement despite a high proportion of patients in the placebo arm receiving poly(ADP-ribose) polymerase inhibitors after progression, confirming the combination as one of the standards of care in this setting with the potential to enhance cure.

Long-term significance of urinary neopterin in ovarian cancer: a study by the Austrian Association for Gynecologic Oncology (AGO).

BACKGROUND: Neopterin is produced by activated macrophages upon stimulation with interferon-γ (IFN-γ) and thus, elevated neopterin concentrations in patients indicate cellular inate immune response. Most studies in patients with malignant diseases found an association between higher neopterin concentrations and reduced survival and impaired prognosis. Nevertheless, neopterin is not a classical tumor marker since it is not produced by the cancer cells themselves. PATIENTS AND METHODS: In a study conducted by the Austrian Gynecologic Oncology Group (AGO) in 114 patients with ovarian cystadenomas and 223 patients with invasive ovarian cancer, patients' urinary neopterin was determined before and after primary therapy. The relevance of neopterin in long-term median follow-up was assessed. RESULTS: Elevated levels (cut-off 250 µmol/mol creatinine) were found less frequently in women with benign ovarian cystadenomas (24%) than in patients with malignant disease (58%). After 10 years, only 57% of ovarian cancer patients with elevated urinary neopterin levels survived without disease progression following primary therapy when compared with 86% of women with normal levels (P < 0.001). Along with residual tumor, FIGO stage, age and histological type, neopterin was significantly associated with overall survival (OS) and progression-free survival (PFS). The median PFS was 52 and 12 months and the median OS was 81 and 24 months for patients with normal and elevated neopterin, respectively, P < 0.001. In a multivariate Cox regression analysis, only residual tumor, neopterin and age were independently associated with OS, while only residual tumor was predictive for PFS. Thirty patients with early-stage invasive ovarian cancer (FIGO I and II) were analyzed separately. Of 3 patients with elevated neopterin, 2 died of disease in contrast to 2 out of 27 patients with normal neopterin (P = 0.004). CONCLUSION: In ovarian cancer, the negative impact of elevated urinary neopterin levels indicates a detrimental effect of cancer-associated inflammatory reaction.

Hypertensive Disorders of Pregnancy - A Life-Long Risk?!

Background: Arterial hypertension is one of the most important causes of cardiovascular diseases, and the latter are responsible for almost half of the deaths in the industrialised nations. Hypertensive disorders of pregnancy constitute one of the most frequent causes of feto-maternal morbidity and mortality; on the other hand the occurrence of a hypertensive disorder of pregnancy represents a risk for the later development of hypertension and the cardiovascular risks resulting therefrom. The aim of this article is to demonstrate the association of hypertensive disorders of pregnancy with consecutive cardiovascular diseases. Materials and Methods: Specific selective literature research. Results: After the occurrence of a hypertensive disorder of pregnancy the relative risks for hypertension are 3.7 (2.70-5.05), for ischaemic heart disease 2.2 (1.86-2.52), for cerebral insult 1.8 (1.45-2.27) and for mortality resulting from cardiovascular causes 1.5 (1.05-2.14) and are thus significant. According to a recent study 56 % of internal specialists and 23 % of gynecologists do not know about the association of preeclampsia with ischemic heart disease, 48 % and 38 % respectively are not aware of the link with stroke and 79 % and 77 % respectively are not aware of the association with a reduced life expectancy after preeclampsia. The presence of hypertension is not known by many of the patients, merely 28-38 % receive an appropriate therapy. Conclusion: Adequate follow-up after hypertensive disorders of pregnancy and the early recognition of and therapy for hypertension represent the cornerstones in the prevention of late cardiovascular sequelae. General practitioners, specialist for internal medicine and gynaecologists have a special responsibility with regard to the reduction of later complications.

Influence of so far neglected psychosomatic factors, BMI and smoking on pregnancy-induced hypertension (PIH).

OBJECTIVE: Correlation of descriptive psychosomatic factors and birth parameters for pregnancy-induced hypertension (PIH). STUDY DESIGN: For this prospective study 508 pregnant (singleton) women from 16th-22nd gestational week (GW) were investigated by means of a semi-standardized questionnaire. Complete data concerning delivery were obtained from medical records. In addition to medical and sociodemographic risk factors, so far neglected parameters such as biographical information, personality factors, social environment, stress coping strategies and pregnancy-related anxieties were examined. A factor analysis was performed using a principal component method with subsequent varimax rotation. MAIN OUTCOME MEASURES: Main outcome measures were imminent preterm delivery, PIH, factual preterm delivery before 37GW and birth weight <10th percentile. RESULTS: Four hundred and eighty-eight qualified for evaluation and got included in the univariate logistic regression - 12.6% of them had PIH. The development of PIH showed a significant correlation with age (OR, 95% CI). Very young and older women were more likely to develop PIH. Development of PIH is significantly more frequent in women, whose parents adhered to an authoritarian educational style, had no emotional support of female friends, and a higher BMI. Women who always had been non-smokers and women who did not give up smoking during pregnancy, but only reduced the amount of cigarettes had the least probability of developing PIH, whereas total abandoning of smoking before and especially during pregnancy was associated with a significantly increased risk for the development of PIH. CONCLUSIONS: This study suggests psychosomatic factors, BMI and smoking behavior to be relevant for the development of PIH.

Combined transvaginal B-mode and color Doppler sonography for differential diagnosis of ovarian tumors: results of a multivariate logistic regression analysis.

OBJECTIVE: Transvaginal sonography is limited in its ability to assess early stage cancers of the ovary as well as in distinguishing benign processes. As a method for characterization of tumor vascularization, color-coded Doppler sonography may be able to improve the diagnostic accuracy of B-mode sonography. METHODS: Preoperative transvaginal B-mode and Doppler sonography was performed in 63 patients with unclear adnexal lesions prior to operation. Using multiple logistic regression, the independent variables of each procedure were selected and combined to yield a diagnostic flow chart. The diagnostic accuracy of this decision matrix was tested on 257 patients with unclear adnexal tumors. RESULTS: In the 63 adnexal tumors investigated, the diagnostic impact of isolated sonomorphological assessment with evidence of a "solid area" was 78%. Using Doppler sonography, the best discrimination was achieved by displaying the vascular distribution ("central vascularization"). Combining these independent significant variables of the two procedures raised the diagnostic accuracy to 90% (sensitivity 86%, specificity 93%). The validity achieved by this combination was confirmed by the independent application of this method to the 257 adnexal tumors with unclear malignancy status (diagnostic accuracy 93%, sensitivity 92%, specificity 94%). CONCLUSIONS: The combination of sonography and Doppler sonography achieves high and reproducible diagnostic accuracy in preoperative malignancy status assessment of adnexal tumors. The additional use of Doppler sonography can thus provide significant aid both for differential diagnostics of adnexal lesions and for the choice of surgical route in the case of an existing indication for operative therapy.

Postpartal endomyometritis in a case of unknown tertian malaria.

A 28-year-old woman developed puerperal endomyometritis and tertian malaria simultaneously. She delivered her child by vacuum extraction during week 41 of pregnancy in September 1994. The peripartal period was uneventful. Nine days post partum the patient was readmitted to hospital with fever and pain in the area of the episiotomy. On day 13 post partum a hysterectomy was performed because of suspected abscess-forming endomyometritis. Two days after the hysterectomy the patient developed septic temperatures, which persisted for 10 days. Tertian malaria due to Plasmodium vivax was found to be the cause of fever. The patient had been in Indonesia without anti-malarial prophylaxis in 1991. Two years later she travelled to Ghana, having taken mefloquine as prophylaxis. Malaria was obviously caused by reactivated hypnozoites in the liver, although the patient had never had an episode of fever associated with malaria before. This case proves that tertian malaria may "recur" even without previous manifestation, years after a stay in a region endemic for malaria.

First trimester three-dimensional ultrasound volumetry of the gestational sac.

First trimester amniotic fluid is an ultrafiltrate of maternal plasma and constitutes the major component of gestational sac volume (GSV). We hypothesized that GSV, assessed by 3-dimensional (3-D) ultrasound volumetry, would reflect function of the early uteroplacental unit and therefore provide a basis for predicting pregnancy outcome. We tested this hypothesis in 38 pregnancies which had first trimester GSV measurements by two investigators thus allowing determination of interobserver variation. Gestational age (GA) was based on a careful history and conventional 2-dimensional ultrasound measurements. Serum for beta-hCG, estradiol (E2) and progesterone (P) was obtained at the time of ultrasound examinations. "Normal" outcome was defined as confirmation of a viable fetus. "Abnormal outcome" was defined as either a "blighted ovum" or embryonic demise. Statistical analysis was performed by Independent t-test and regression analysis. There were 31 "normal" and 7 "abnormal" pregnancies studied between 5 and 11 weeks gestation (mean +/- SD 8.3 +/- 1.3 weeks). GSV was significantly correlated to GA (r = 0.74, P < 0.001), higher than to beta-hCG (r = 0.40, P = 0.034), E2 (r = 0.70, P < 0.001) and P (r = 0.21, P = 0.334), respectively. In the abnormal group 2/2 pregnancies with a twin sac had a GSV within 1 SD of the mean. 3/5 cases of missed abortions or blighted ovum had a GSV < 2 SD of the mean. The interobserver correlation was high (r = 0.99, P < 0.00f2p4This is the first clinical study investigating the diagnostic use of 3-D ultrasound volumetry in first trimester pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

[Coccygodynia--a diagnostic and therapeutic problem in orthopedics]. / Die Coccygodynie--ein diagnostisches und therapeutisches Problem der Orthopädie.

Coccygodynia means a lot of complaints with the most important of them, namely the spontaneous pain in the coccyx, in the top of the coccyx respectively. One can differ posttraumatic coccygodynias from others, which are the symptom of other diseases like lumbar pain, sciatica, tumors in the spinal canal, visceral diseases, that means disturbances in the gynaecologic system. By the mean of 19 predominantly female patients remarkable facts of the history, of the x-ray and clinical findings are listed up and compared in three different groups. To this examination the results of longtime-results of eleven patients who have been operated are united. The resection of the "os coccygis" doesn't seem to be a satisfying possibility to influence coccygodynias caused by traumas for a long time.

[Visceral diseases as cause of lumbar syndromes]. / Viszerale Erkrankungen als Ursache von Lumbalsyndromen.

30 patients with hepatitis, 50 patients with gynecological diseases, and 100 with urological diseases were investigated with regards to lumbago to find out whether there is a correlation between the internal disease and the signs of low back pain. The patients were compared with a control group of 33 healthy people. The vertebral localisation of the pain and its radiation were investigated and discussed in certain diseases as well as any correlation between lumbago and average age. The various possibilities of pain radiation are described and the importance of the vertebral column as secondary seat of low back pain is pointed out.

[Faulty mechanics and spinal dysfunction. Investigations of the mechanism in patients with "lumbar syndrome" (author's transl)]. / Zum Problem Fehlstatik und Wirbelsäulenstörungen. Untersuchungen der Statik bei Patienten mit Lumbalysndromen

50 patients admitted for lumbago or sciatica are examined for their "static". Radiographs of the lumbar-pelvis-hip-joint region are taken in 2 planes with the patient standing. An oblique pelvis is a certain, a reduced angle of Leger a probable influence of lumbosciatic pain. The high-assimilation-pelvis of Gutmann produces an unfavorable prognosis.

[Symptomatology in osteoarthrosis of the hip (author's transl)]. / Zur Symptomatik der Coxarthrose

The pain symptom is examined in 91 hospitalized patients with osteoarthrosis of the hip. The impaired hipfunction, as determined by hip-rotation is compared to the severity of the arthrosis as determined by X-ray. Elected severe cases are contrasted as to their symptoms with patients suffering from still mild osteoarthrosis of the hip. Both groups consisted only of patients in whom the clinical severity grade conformed with the results of the X-ray. The differences between both groups are worked out.