BackgroundAn accident or a catastrophic disease may occasionally lead to brain death (BD) during pregnancy. Management of brain-dead pregnant patients needs to follow special strategies to support the mother in a way that she can deliver a viable and healthy child and, whenever possible, also be an organ donor. This review discusses the management of brain-dead mothers and gives an overview of recommendations concerning the organ supporting therapy.MethodsTo obtain information on brain-dead pregnant women, we performed a systematic review of Medline, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL). The collected data included the age of the mother, the cause of brain death, maternal medical complications, gestational age at BD, duration of extended life support, gestational age at delivery, indication of delivery, neonatal outcome, organ donation of the mothers and patient and graft outcome.ResultsIn our search of the literature, we found 30 cases reported between1982 and 2010. A nontraumatic brain injury was the cause of BD in 26 of 30 mothers. The maternal mean age at the time of BD was 26.5 years. The mean gestational age at the time of BD and the mean gestational age at delivery were 22 and 29.5 weeks, respectively. Twelve viable infants were born and survived the neonatal period.ConclusionThe management of a brain-dead pregnant woman requires a multidisciplinary team which should follow available standards, guidelines and recommendations both for a nontraumatic therapy of the fetus and for an organ-preserving treatment of the potential donor.

LR of hepatic breast cancer metastases within a multimodal treatment concept is a safe procedure in well-selected patients. Both a short time interval to the development of HM and positive resection margins after LR are strongly associated with worse long-term survival.

Helical tomotherapy is feasible and fast for WAI. Tomotherapy enabled excellent coverage of the PTV and effective sparing of liver, kidneys and bone marrow.

IntroductionVaginal intraepithelial neoplasia (VAIN) is a pre-malignant lesion, potentially leading to vaginal cancer. It is a rare disease, representing less than 1% of all intraepithelial neoplasia of the female genital tract. Similar to cervical intraepithelial neoplasia (CIN), there are three different grades of VAIN. VAIN 1 is also known as a low-grade squamous intraepithelial lesion (LSIL), whereas VAIN 2 and VAIN 3 both represent high-grade squamous intraepithelial lesions (HSIL). Risk factors for the development of VAIN are similar to those for cervical neoplasia, i.e. promiscuity, starting sexual activity at an early age, tobacco consumption and infection with human papillomavirus (HPV). However, compared to other intraepithelial neoplasia such as CIN or VIN (vulvar intraepithelial neoplasia), there still is little understanding about the natural course of VAIN and its capacity for pro- or regression. Furthermore, there is controversial data about the HPV detection rate in VAIN lesions.Patients and Methods67 patients with histologically confirmed VAIN, who were diagnosed between 2003 and 2011 at the University Women´s Hospital of Heidelberg Germany, were included in this study. The biopsies of all participating patients were subjected to HPV genotyping. GP-E6/E7 Nested Multiplex PCR (NMPCR) was used to identify and genotype HPV. Eighteen pairs of type-specific nested PCR primers were assessed to detect the following "high-risk" HPV genotypes: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68, as well as the "low-risk" genotypes 6/11, 42, 43 and 44. The data was analyzed with the software SAS (Statistical Analysis System).ResultsAll 67 cases were eligible for DNA analysis. The median age was 53 years. The largest group with 53% (n = 36) was formed by women, who were first diagnosed with VAIN between the age of 41 to 60 years. 50% (n = 37) of the patients presented a VAIN in the upper 1/3 of the vagina. 58 (87%) were diagnosed with HSIL (VAIN). The median age in patients with LSIL (VAIN) was 53 years and in patients with HSIL (VAIN) 53.5 years. 12 women (18%) had an immunosuppression. HPV positivity was confirmed in 37 patients (55%). Except for a single patient, who had a triple infection with HPV types 6/11, 16 and 68, only infections with one single HPV genotype were detected. An infection with the HPV genotypes 31, 39, 45, 51, 58, 59, 66, 42, 43 and 44 couldn’t be found in any of the patients. In 28 patients with diagnosed VAIN, an infection with HPV 16 could be shown, 24 (86%) of them were diagnosed with a HSIL (VAIN). 16 (24%) women presented condylomata and 13 of them (81%) had a positive HPV status. However, only 47% of the women without condylomata presented a positive HPV status, resulting in a significant correlation (p = 0.0164) between condylomata and HPV infection. In 28 of all 67 patients (42%), recurrence of the neoplasia occurred.ConclusionHPV 16 is the main virus-type to be associated with the development of a VAIN. Also, HPV 16 infection, VIN or condylomata acuminata in the past ...

The purpose of this study was to investigate the safety, pharmacokinetics and preliminary efficacy of bivatuzumab mertansine in patients with CD44v6-positive metastatic breast cancer. Anthracycline and taxane-pretreated patients with metastatic breast cancer that expressed CD44v6 received one single infusion of bivatuzumab mertansine and were observed for 21 days within one treatment course. Starting dose was 25 mg/m, while dose was escalated by increments of 25 mg/m. Patients who experienced a disease stabilization were eligible for further courses with bivatuzumab mertansine. Blood serum samples were taken throughout the treatment period for pharmacokinetic analysis. Twenty-four patients were treated at eight different dose levels (25-200 mg/m), seven of these patients received more than one course of bivatuzumab mertansine. Two dose-limiting toxicities occurred: one patient treated with 125 mg/m developed transient National Cancer Institute Common Toxicity Criteria grade 4 elevation of liver enzymes; another patient treated at 175 mg/m experienced National Cancer Institute Common Toxicity Criteria grade 3 vomiting. She died from renal failure, which might have been caused by deterioration of pre-existing renal insufficiency. The most common toxicities were transient and mild skin disorders in 75% of patients. As a consequence of one fatal toxic epidermal necrolysis that occurred in a study running in parallel, the clinical trials programme of bivatuzumab mertansine was discontinued. None of the patients developed antibodies against bivatuzumab mertansine. No objective responses were observed. Disease stabilization was achieved in 50% of patients independently of dose level. In conclusion, bivatuzumab mertansine targets CD44v6 and appears to stabilize heavily pretreated metastatic breast cancer that expresses CD44v6. The maximum tolerated dose could not be determined in this trial as the sponsor discontinued the clinical development of bivatuzumab mertansine.