Genetic testing in ovarian cancer - clinical impact and current practices.

Background Clinical practices and testing strategies in patients with ovarian cancer differ worldwide. We therefor wanted to give an overview over the current data to advise best clinical practice. Materials and methods A systematic review of the literature was performed with the aim to define which ovarian cancer patients to refer for genetic counseling and how to perform genetic testing. We also discuss the timing of genetic testing and clinical relevance of the BRCA mutation status. Results The germline mutation rate in patients with ovarian cancer is high, independent of family history, age at diagnosis and histology. BRCA mutation carriers with ovarian cancer have improved survival rates. In recurrent ovarian cancer treatment by poly ADP ribose polymerase (PARP) inhibitors improves the disease-free survival in patients with BRCA mutations or homologous recombination deficiency with hazard ratios up to 0.23. But also patients with BRCA wild type show a benefit. The recently published SOLO-1 trial demonstrated a significant benefit for patients with germline BRCA mutations in the first line setting. By tumor testing about 7% additional BRCA mutations can be found but the somatic testing and interpretation of the results remains a challenge. Despite the clinical impact, analysis of our own data and also international publications show insufficient referral rates for genetic counseling. Conclusions Genetic testing in ovarian cancer has a prognostic and predictive value. Referral rates must be improved.

Breast cancer and pregnancy.

Background In the past decades the incidence of pregnancy-associated breast cancer (PABC) increased. Possible explanations are the trend to postpone childbearing and the general increase in the incidence of breast cancer. Materials and methods A sytematic review of the literature was performed with the aim to report on incidence, diagnosis, treatment and prognosis of breast cancer during pregnancy. We also cover the issue of pregnancy following a diagnosis of breast cancer including fertility preservation and prognosis. Results Ultrasound is the imaging method of choice in pregnancy, but mammography can also be performed as the fetal irradiation dose is low. To avoid a delay in diagnosis every sonographic mass in pregnant women which does not clearly correspond to a cyst needs further investigation by biopsy. Treatment should follow as close as possible the guidelines for non-pregnant patients. Administration of chemotherapy is possible after the first trimester. There is a large body of evidence for the use of anthracyclines. In contrast radiotherapy, trastuzumab and antihormonal treatment by tamoxifen are contraindicated during pregnancy. Pregnancy does not seem to influence prognosis. Most adverse obstetric outcomes are related to preterm delivery, which should therefore, whenever possible, be avoided. Young patients with breast cancer and incomplete family planning should be referred for counseling about fertility preservation options before the initiation of adjuvant treatment. A pregnancy following breast cancer does not have a negative impact on prognosis. Conclusion Multidisciplinary management of women with breast cancer in pregnancy is mandatory and data should be collected to allow further improvement in management.

Bulkamid (PAHG) in mixed urinary incontinence: What is the outcome?

INTRODUCTION AND HYPOTHESIS: Mixed urinary incontinence (MUI), defined as mixed symptoms of stress urinary incontinence (SUI) and overactive bladder (OAB), is a difficult entity if conservative treatment has failed. Cure rates are low compared with SUI, particularly the OAB component, may deteriorate after sling insertion. Bulking agents pose an appealing alternative for the treatment of MUI. They have shown beneficial effect in small case studies, but larger series are lacking. The aim of this prospective study was an analysis of treatment efficacy and safety profile of the bulking agent, Bulkamid, in female patients with MUI. METHODS: One hundred fifty-four women with MUI symptoms (components of SUI/OAB within the limits of 60-40% either way) received bulking therapy with polyacrylamide hydrogel (Bulkamid). Patients were followed-up 3 months postoperatively. Primary outcome was the domain Incontinence impact on the King's Health Questionnaire (KHQ). Secondary outcomes were the other KHQ domains, visual analog scale (VAS), and International Continence Society (ICS) standardized pad weight test as objective measurement of incontinence. RESULTS: Statistically significant improvements were found for all KHQ domains, pad weight test, and the visual analog scale (VAS) before and after bulking. Overall complication rate was 13%. CONCLUSIONS: This study has shown improvement in MUI after bulking therapy according to both subjective and objective outcomes. We can advocate bulking therapy for treating MUI, as it is simple and safe and shows both objective and subjective improvement and relief. Long-term results (up to 1 year) are awaited.

PET/CT-guided biopsies of metabolically active bone lesions: applications and clinical impact.

PURPOSE: In a minority of cases a definite diagnosis and stage grouping in cancer patients is not possible based on the imaging information of PET/CT. We report our experience with percutaneous PET/CT-guided bone biopsies to histologically verify the aetiology of hypermetabolic bone lesions. METHODS: We retrospectively reviewed the data of 20 consecutive patients who underwent multimodal image-guided bone biopsies using a dedicated PET/CT system in a step-by-step technique. Technical and clinical success rates of PET/CT-guided biopsies were evaluated. Questionnaires were sent to the referring physicians to assess the impact of biopsies on patient management and to check the clinical need for PET/CT-guided biopsies. RESULTS: Clinical indications for biopsy were to histologically verify the aetiology of metabolically active bone lesions without a morphological correlate confirming the suspicion of metastases in 15 patients, to determine the origin of suspected metastases in 3 patients and to evaluate the appropriateness of targeted therapy options in 2 patients. Biopsies were technically successful in all patients. In 19 of 20 patients a definite histological diagnosis was possible. No complications or adverse effects occurred. The result of PET/CT-guided bone biopsies determined a change of the planned treatment in overall 56% of patients, with intramodality changes, e.g. chemotherapy with palliative instead of curative intent, and intermodality changes, e.g. systemic therapy instead of surgery, in 22 and 50%, respectively. CONCLUSION: PET/CT-guided bone biopsies are a promising alternative to conventional techniques to make metabolically active bone lesions-especially without a distinctive morphological correlate-accessible for histological verification. PET/CT-guided biopsies had a major clinical impact in patients who otherwise cannot be reliably stage grouped at the time of treatment decisions.

PET-CT-guided interventions in the management of FDG-positive lesions in patients suffering from solid malignancies: initial experiences.

Positron emission tomography-computed tomography (PET-CT) has gained widespread acceptance as a staging investigation in the diagnostic workup of malignant tumours and may be used to visualize metabolic changes before the evolution of morphological changes. To make histology of PET findings without distinctive structural changes available for treatment decisions, we developed a protocol for multimodal image-guided interventions using an integrated PET-CT machine. We report our first experience in 12 patients admitted for staging and restaging of breast cancer, non-small cell lung cancer, cervical cancer, soft tissue sarcoma, and osteosarcoma. Patients were repositioned according to the findings in PET-CT and intervention was planned based on a subsequent single-bed PET-CT acquisition of the region concerned. The needle was introduced under CT guidance in a step-by-step technique and correct needle position in the centre of the FDG avid lesion was assured by repetition of a single-bed PET-CT acquisition before sampling. The metabolically active part of lesions was accurately targeted in all patients and representative samples were obtained in 92%. No major adverse effects occurred. We conclude that PET-CT guidance for interventions is feasible and may be promising to optimize the diagnostic yield of CT-guided interventions and to make metabolically active lesions without morphological correlate accessible to percutaneous interventions.

Where should bulking agents for female urodynamic stress incontinence be injected?

For bulking agents used for female stress urinary incontinence, the recommendation for the anatomical placement varies as some injectables are to be placed close to the bladder neck and others midurethrally. Aim of the study was to determine if there are differences concerning the outcome after transurethral collagen injections depending on the anatomical placement midurethrally or at the bladder neck. We randomly assigned 30 elderly female patients with urodynamic stress incontinence to either transurethral collagen injection midurethrally or to the bladder neck. Prior to injection and at ten month follow-up, maximum urethral closure pressure (MUCP), functional urethral length (FUL), maximum flow rate and cough test were performed and the patient was asked to estimate her bladder condition using a visual analogue scale. Postoperative contentness was 8 (median, 95% confidence interval 5-9) in the midurethral group and 8 (median, 95% confidence interval 7-10) in the bladder neck group with a p value of 0.012, 95% confidence interval -2.464 to -0.2859, in favour to midurethral injections. MUCP and FUL increased significantly in both groups and flow rate decreased in both groups. Continence was 66.6% in the midurethral group and 60% for the bladder neck group respectively. Both midurethral and bladder neck collagen injections improve patients' satisfaction almost equally with a small advantage for midurethral injections.

C-reactive protein in vaginal fluid of patients with preterm premature rupture of membranes.

OBJECTIVE: To assess whether C-reactive protein (CRP) concentrations in cervical amniotic fluid reflect the condition of the intrauterine environment in patients with preterm premature rupture of membranes (PROM) before 35 weeks of gestation. METHODS: Amniotic fluid was obtained in 29 consecutive patients admitted with the diagnosis of preterm PROM earlier than 35 weeks of gestation either by amniocentesis or by collecting cervical fluid. CRP was measured in maternal blood, amniotic fluid, vaginal fluid and in cord blood obtained at delivery. Intraamniotic infection was defined as a positive amniotic fluid for aerobic or anaerobic bacteria, or Mycoplasma. The placentas and umbilical cords were examined for the presence of chorioamnionitis and funisitis. RESULTS: A significant correlation was found between vaginal fluid CRP concentrations and both amniotic fluid (r = 0.95, p < 0.001) and umbilical cord levels (r = 0.47, p < 0.05). No correlation was found between maternal blood and vaginal fluid CRP concentrations. The proportion of patients with intraamniotic infection was 37.9% (11/29). The median (range) vaginal fluid CRP concentration was higher in patients with intraamniotic infection than in those with sterile amniotic fluid [901 (0-1354) vs. 507 (0-798) ng/mL, p < 0.001]. The median (range) vaginal fluid CRP concentration was higher in fetuses with (n = 12) than in those without funisitis (n = 17) [901 (598-1354) vs. 487 (0-1115) ng/mL, p < 0.01]. After adjustment for gestational age, vaginal fluid CRP concentration > 800 ng/mL remained a predictor of intraamniotic infection and funisitis. CONCLUSIONS: Increased vaginal fluid CRP concentration is associated with intraamniotic infection and funisitis. As CRP is produced by hepatocytes and does not cross the placenta, its measurement in vaginal fluid might be an additional parameter for the assessment of fetal well-being in patients with premature PROM.

Evidence of fetal C-reactive protein urinary excretion in early gestation.

BACKGROUND: C-reactive protein has been measured in amniotic fluid in the second and third trimesters of gestation, and its elevated concentration has been found to be associated with adverse pregnancy outcome. It remains unexplained whether amniotic fluid C-reactive protein is of fetal origin. CASE: We report the measurement of C-reactive protein in fetal urine obtained by transabdominal vescicocentesis in a fetus at 15 weeks' gestation affected by obstructive uropathy. Using an enzyme-linked immunosorbent assay, C-reactive protein was detected at a concentration of 234 ng/mL. CONCLUSION: The fetal kidneys excrete C-reactive protein as early as 15 weeks' gestation.