Intramural pregnancy: A case report.

A 24-year-old woman, who had undergone neither fertility treatment nor uterine surgery other than a cesarean section, presented with an intramural ectopic pregnancy. A laparotomy with uterine wedge resection including the embryonic tissue was performed. The postoperative course was uneventful, with falling ßHCG levels. Two months after surgery she presented again with an intrauterine pregnancy.

[Calciphylaxis]. / Kalziphylaxie.

Calciphylaxis (calcific uremic arteriolopathy, CUA) is a rare disease at the interface of nephrology, dermatology and cardiovascular medicine. CUA typically occurs in chronic dialysis patients. However, anecdotal reports also exist about cases in patients without relevant kidney disease. Clinically CUA is characterized by the stepwise development of superficial painful sensations and cutaneous lesions similar to livedo reticularis. Skin necrosis and ulceration represent the full-blown, "late" clinical picture. Panniculitis and circumferential calcification of cutaneous arterioles dominate the histological picture together with endothelial detachment. The prognosis of CUA is poor due to high morbidity and mortality largely resulting from underlying cardiovascular disease or septicemia. The aetiology of CUA is incompletely understood. Previous oral anticoagulation with vitamin K antagonists is considered as a risk factor. Unfortunately, evidence-based therapeutic options are absent, since controlled treatment trials have not been conducted yet. Long-term pain and wound management are mandatory. In the absence of controlled prospective trials registry studies such as the German CUA registry (www.calciphylaxis.net) support data collecting and analysis upon good clinical practice and may stimulate exchange of expertise and networking.

Intensity-modulated whole abdomen irradiation following adjuvant carboplatin/taxane chemotherapy for FIGO stage III ovarian cancer : four-year outcomes.

INTRODUCTION: A prospective study to assess toxicity and survival outcomes after intensity-modulated whole-abdominal irradiation (IM-WAI) following surgery and adjuvant intravenous carboplatin/taxane chemotherapy in advanced FIGO stage III ovarian cancer. PATIENTS AND METHODS: Between 2006 and 2009, 16 patients with optimally resected FIGO stage III ovarian cancer, who had received six cycles of adjuvant carboplatin/taxane chemotherapy were treated with consolidation IM-WAI. Radiotherapy was delivered to a total dose of 30 Gy in 1.5-Gy fractions, using step-and-shoot (n = 3) or helical tomotherapy (n = 13). The first 10 patients were treated within a phase I trial; the following patients received the same treatment modality. The target volume included the entire peritoneal cavity, the diaphragm, the liver capsule, and the pelvic and para-aortic node regions. Organs at risk were kidneys, liver, heart, and bone marrow. RESULTS: Median follow-up was 44 months (range 19.2-67.2 months). No grade 4 toxicities occurred during IM-WAI. Common Toxicity Criteria for Adverse Events (CTCAE) grade 3 toxicities were: diarrhea (25 %), leucopenia (19 %), nausea/vomiting (6 %), and thrombocytopenia (6 %). No toxicity-related treatment break was necessary. Small bowel obstruction occurred in a total of 6 patients: in 3 cases (19 %) due to postsurgical adhesions and in 3 cases due to local tumor recurrence (19 %). Median recurrence-free survival (RFS) was 27.6 months (95 % confidence interval, CI = 24-44 months) and median overall survival (OS) was 42.1 months (95 %CI = 17-68 months). The peritoneal cavity was the most frequent site of initial failure. CONCLUSION: Consolidation IM-WAI following surgery and adjuvant chemotherapy is feasible and can be performed with manageable acute and late toxicity. The favorable RFS outcome is promising and justifies further clinical trials.

Treatment of advanced metastasized breast cancer with bone marrow-derived tumour-reactive memory T cells: a pilot clinical study.

BACKGROUND: Breast cancer patients frequently harbour tumour-reactive memory T cells in their bone marrow (BM) but not in the blood. After reactivation ex-vivo these cells rejected autologous breast tumours in xenotransplanted mice demonstrating therapeutic potential upon reactivation and mobilization into the blood. We conducted a clinical pilot study on metastasized breast cancer patients to investigate if ex-vivo reactivation of tumour-reactive BM memory T cells and their adoptive transfer is feasible and increases the frequencies of tumour-reactive T cells in the blood. METHODS: The study protocol involved one transfusion of T cells which were reactivated in vitro with autologous dendritic cells pulsed with lysate of MCF7 breast cancer cells as source of tumour antigens. Immunomonitoring included characterization of T cell activation in vitro and of tumour-specific T cells in the blood by interferon (IFN)-gamma ELISPOT assay, HLA-tetramers and antigen-induced interleukin (IL)-4 secretion. RESULTS: Twelve patients with pre-existing tumour-reactive BM memory T cells were included into the study. In all cases, the treatment was feasible and well tolerated. Six patients (responders) showed by ELISPOT assay de-novo tumour antigen-specific, IFN-gamma-secreting T cells in the blood after 7 days. In contrast, non responders showed in the blood tumour antigen-induced IL-4 responses. All responders received more than 6.5 x 10(3) tumour-reactive T cells. In contrast, all non responders received lower numbers of tumour antigen-reactive T cells. This was associated with reduced activation of memory T cells in activation cultures, increased amounts of CD4(+) CD25(high) regulatory T cells in the BM and increased tumour antigen-dependent IL-10 secretion. The latter was prevented by preceding depletion of regulatory T cells suggesting that regulatory T cells in the BM can inhibit reactivation of tumour-specific T cells. CONCLUSION: Taken together, adoptive transfer of ex-vivo re-stimulated tumour-reactive memory T cells from BM of metastasized breast cancer patients can induce the presence of tumour antigen-reactive type-1 T cells in the peripheral blood.

Benchmarking the quality of breast cancer care in a nationwide voluntary system: the first five-year results (2003-2007) from Germany as a proof of concept.

BACKGROUND: The main study objectives were: to establish a nationwide voluntary collaborative network of breast centres with independent data analysis; to define suitable quality indicators (QIs) for benchmarking the quality of breast cancer (BC) care; to demonstrate existing differences in BC care quality; and to show that BC care quality improved with benchmarking from 2003 to 2007. METHODS: BC centres participated voluntarily in a scientific benchmarking procedure. A generic XML-based data set was developed and used for data collection. Nine guideline-based quality targets serving as rate-based QIs were initially defined, reviewed annually and modified or expanded accordingly. QI changes over time were analysed descriptively. RESULTS: During 2003-2007, respective increases in participating breast centres and postoperatively confirmed BCs were from 59 to 220 and from 5,994 to 31,656 (> 60% of new BCs/year in Germany). Starting from 9 process QIs, 12 QIs were developed by 2007 as surrogates for long-term outcome. Results for most QIs increased. From 2003 to 2007, the most notable increases seen were for preoperative histological confirmation of diagnosis (58% (in 2003) to 88% (in 2007)), appropriate endocrine therapy in hormone receptor-positive patients (27 to 93%), appropriate radiotherapy after breast-conserving therapy (20 to 79%) and appropriate radiotherapy after mastectomy (8 to 65%). CONCLUSION: Nationwide external benchmarking of BC care is feasible and successful. The benchmarking system described allows both comparisons among participating institutions as well as the tracking of changes in average quality of care over time for the network as a whole. Marked QI increases indicate improved quality of BC care.

The shaping of a polyvalent and highly individual T-cell repertoire in the bone marrow of breast cancer patients.

We analyzed the T-cell repertoires from the bone marrow of 39 primary operated breast cancer patients and 11 healthy female donors for the presence and frequencies of spontaneously induced effector/memory T lymphocytes with peptide-HLA-A2-restricted reactivity against 10 breast tumor-associated antigens (TAA) and 3 normal breast tissue-associated antigens by short-term IFN-gamma enzyme-linked immunospot (ELISpot) analysis. Sixty-seven percent of the patients recognized TAAs with a mean frequency of 144 TAA reactive cells per 10(6) T cells. These patients recognized simultaneously an average of 47% of the tested TAAs. The T-cell repertoire was highly polyvalent and exhibited pronounced interindividual differences in the pattern of TAAs recognized by each patient. Strong differences of reactivity were noticed between TAAs, ranging from 100% recognition of prostate-specific antigen(p141-149) to only 25% recognition of MUC1(p12-20) or Her-2/neu(p369-377). In comparison with TAAs, reactivity to normal breast tissue-associated antigens was lower with respect to the proportions of responding patients (30%) and recognized antigens (27%), with a mean frequency of only 85/10(6) T cells. Healthy individuals also contained TAA-reactive T cells but this repertoire was more restricted and the frequencies were in the same range as T cells reacting to normal breast tissue-associated antigens. Our data show a highly individual T-cell repertoire for recognition of TAAs in breast cancer patients. This has potential relevance for T-cell immune diagnostics, for tumor vaccine design, and for predicting immune responsiveness.

Antisense CD11b integrin inhibits the development of a differentiated monocyte/macrophage phenotype in human leukemia cells.

Macrophage-like development of myeloid leukemia cells which can be induced by agents such as phorbol esters (TPA) is accompanied by integrin expression and cell adhesion. Thus, in differentiating myeloid leukemia cells CD11b is predominantly expressed which can associate with CD18 to form the functional heterodimeric integrin Mac-1. To elucidate the role of cell adhesion during macrophage-like differentiation, we transfected human U937 myeloid leukemia cells with a vector containing the CD11b gene in antisense orientation. Expression of the CD11b antisense gene in stably transfected U937 cells (as-CD11b cells) resulted in an attenuated response to TPA. As-CD11b cells demonstrated poor adhesion to solid substrate upon TPA treatment in contrast to U937 control cells. Constitutive expression of c-myc in as-CD11b transfectants was higher than in control cells and failed to be repressed by TPA treatment. Moreover, unlike control cells, antisense transfectants failed to induce expression of early response genes such as c-jun and the redox factor ref-1 upon TPA stimulation. Consequently, the induction of monocytic differentiation markers such as the activity of alpha-naphthyl acetate esterase, the capacity to reduce nitroblue tetrazolium and the expression of the vimentin gene was much lower in antisense transfectants than in control U937 cells. According to the failure to undergo a monocytic differentiation program, TPA treatment of as-CD11b cells resulted in a progressively increasing amount of apoptotic cells whereas the differentiated population of U937 control cells remained alive. Taken together, these data suggest that the integrin-mediated (particularly CD11b-mediated) adhesion of myeloid leukemia cells in the course of induced monocytic differentiation is crucial for cell attachment, development of a monocytic phenotype and subsequent survival.