Explore the vast range of titles available.

Background Angiogenesis appears to play an important role in ovarian cancer. Vascular endothelial growth factor (VEGF) has recently been implicated as a therapeutic target in ovarian cancer. The tissue inhibitor of metalloproteinase 1 (TIMP-1) is involved in tissue invasion and angiogenesis. The application of serum TIMP-1 and VEGF to monitor primary therapy and predict clinical outcome of patients with ovarian cancer is unclear. Methods Patients with epithelial ovarian cancer who presented for primary surgery were included in this study. A total of 148 serum samples from 37 patients were analyzed. Samples were prospectively collected at 4 predefined time points: 1. before radical debulking surgery, 2. after surgery and before platinum/taxane based chemotherapy, 3. during chemotherapy, 4. after chemotherapy. Serum VEGF-165 and TIMP-1 as well as CA-125 were quantified by ELISA or ECLIA and correlation with response and long-term clinical outcome was analyzed. Results Serum levels of all markers changed substantially during first-line therapy. High CA-125 (p = 0.002), TIMP-1 (p = 0.007) and VEGF-165 (p = 0.02) after chemotherapy were associated with reduced overall survival. In addition, elevated CA-125 (p < 0.001) and VEGF-165 (p = 0.006) at this time point predicted poor progression-free survival. TIMP-1 and VEGF-165 were closely correlated at all time-points during therapy. Conclusions TIMP-1 and VEGF serum levels changed significantly during first-line therapy of ovarian cancer patients and predicted prognosis. These findings support the role of angiogenesis in ovarian cancer progression and the use of antiangiogenic therapy.

Background Carbonic anhydrase IX (CAIX) is a membranous expressed metalloenzyme involved in pH homeostasis and cell adhesion. The protein is overexpressed in a variety of tumors and potentially associated with negative outcome. This study was designed to investigate the prognostic role of CAIX in serum and tumor tissue of patients with primary cervical cancer. Methods Tumor samples of 221 consecutive patients with primary cervical cancer who underwent surgery between 1993 and 2008 were analyzed for CAIX expression by immunohistochemistry. Additionally, preoperative serum CAIX concentrations were determined by ELISA in a subset of patients. Correlation with intratumoral CAIX expression as well as clinicopathological factors and outcome was analyzed. Results CAIX expression was observed in 81.9% of the tumor specimens; 62.0% showed a moderate or strong staining intensity. Moderate/strong expression was associated with squamous histology (p = 0.024), advanced tumor stage (p = 0.001), greater invasion depth (p = 0.025), undifferentiated tumor grade (p < 0.001) and high preoperative SCC-Ag values (p = 0.042). Furthermore patients with moderate/strong intratumoral CAIX expression had a higher number of metastatic lymph nodes compared to those with none/weak intratumoral expression levels (p = 0.047) and there was a non-significant association between high intratumoral CAIX expression and shorter survival (p = 0.118). Preoperative serum concentrations of CAIX ranged between 23 and 499 pg/mL and did not correlate with intratumoral expression or other clinicopathological variables. Conclusion CAIX is associated with advanced tumor stages and lymph node metastases in cervical cancer, potentially representing a new target in this disease. In contrast to other epithelial cancers we could not observe a correlation between serum CAIX and its intratumoral expression.

Introduction Despite radical surgery and chemotherapy, most patients with ovarian cancer develop recurrence and die due to progressive disease. To stratify patients for optimal therapy, prognostic and predictive factors are needed. We examined the role of pre- and postoperative CA-125 in this context. Methods A total of 231 patients with primary ovarian cancer who presented for surgery at our institution between 1996 and 2004 were included in this study (25% FIGO stage I/II and 75% FIGO stage III/IV). The prognostic and predictive values of CA-125 serum concentrations before and after surgery as well as their correlation with clinicopathological variables were analyzed. Results Median preoperative CA-125 was 61.6 kU/l (9–1,867 kU/l) in stage I/II patients and 533.15 kU/l (10–22,617 kU/l) in stage III/IV patients. Before surgery, 67% of stage I/II patients and 96% of stage III/IV patients had elevated CA-125 (>35 kU/l). There was a significant decrease in CA-125 after surgery in both patient cohorts (61.6–43.4 kU/l, P  = 0.001 and 533.15–92.3 kU/l, P  < 0.001, respectively). Furthermore, in stage III/IV patients with complete or so-called optimal (<1 cm residual disease) debulking, preoperative CA-125 levels were significantly lower than in patients with residual disease >1 cm ( P  = 0.01, P  = 0.009, respectively). Neither CA-125 concentration before surgery nor its decrease was prognostically relevant for recurrence and survival at any stage. However, in stage III/IV patients, a high postoperative CA-125 was associated with shorter progression-free survival ( P  = 0.024). Conclusions Although CA-125 serum levels differ significantly before and after surgery in early and advanced-stage ovarian cancer and preoperative CA-125 values correlate with surgical outcome in advanced-stage disease, we could not determine a preoperative cutoff value for prediction of the surgical result. A prognostic relevance was only observed for postoperative CA-125 in stage III/IV patients.

Purpose Conization for suspected high grade cervical intraepithelial neoplasia (CIN) is often performed based on abnormal cytology only. Loop electrosurgical excision procedure (LEEP) is a very common technique in this context. The present study analyses the accuracy of preoperative assessment of CIN with cytology plus colposcopic biopsy and assesses the efficacy of LEEP for the treatment of CIN. Methods Two-hundred and sixty-six consecutive patients treated with LEEP for suspected CIN at our center were retrospectively analyzed. Cytology, HPV-DNA testing, colposcopically directed cervical biopsy and/or endocervical curettage were performed to assess cervical lesions before and 3–6 months after surgery. Results Median age of the patients was 34 years. Median follow-up was 50 months. Preoperative HPV testing was positive for high risk types in 77.9 %. All patients underwent LEEP without further ablative procedures. Complete excision of the lesion could be achieved in 84.3 %; in 13.5 % margins were not securely cleared and in 2.2 % the lesion was not excised entirely. Overall complication rate was 5.4 % (mainly postoperative bleeding and pain). Overall concordance of colposcopic biopsy and cone histology was 85.8 %. The concordance rate was higher for CIN 2/3 (95.1 %) compared with CIN 1 (63.2 %). Nine patients (3.4 %) had persistent disease after 3 months, 4 (1.5 %) developed disease recurrence and underwent re-conization. HPV testing at 3–6 months after surgery was negative in 78.5 %; 2 of the patients developing disease recurrence had a persistent HPV infection after surgery. Conclusions Assessment of cervical lesions with colposcopic biopsy is an accurate method (concordance with cone histology 85.8 %). Surgical treatment of high grade CIN with LEEP is a safe procedure with low recurrence rates, resulting in a clearance of cervical HPV infection in the majority of cases.

Background A tumor-free resection margin of at least 8 mm is considered state of the art in vulvar cancer. This standard is based on small and heterogeneous patient cohorts, and its implementation can result in mutilation. Methods One hundred two consecutive patients with primary squamous cell vulvar cancer were analyzed. All patients received resection of the primary tumor and the inguinofemoral lymph nodes via three separate incisions, resulting in complete tumor resection. Median follow-up was 31 months. Minimal margin distances were pathologically determined in all dimensions after fixation. Results Median age of the patients was 62 years; 38.2% had International Federation of Gynecology and Obstetrics (FIGO) stage I, 17.6% stage II, 24.4% stage III, and 8.8% stage IV disease. The median minimal resection margin was 5 mm (range 0.5–25 mm). Sixteen patients (15.6%) developed disease recurrence, of whom 10 (62.5%) at the vulva. Margin distance had no significant impact on disease-free survival when analyzed continuously ( p  = 0.388). When cases were divided into three subgroups of <3 mm (28.4%), ≥3 to <8 mm (42.2%), and ≥8 mm (29.4%) resection margin, neither univariate nor multivariate analysis revealed a difference in disease-free survival. There was no significant difference between any of the subgroups regarding tumor stages and adjuvant radiotherapy of the vulva. These results were independent of the direction of the minimal margin distance and consistent when only vulvar recurrences were analyzed. Conclusions A tumor-free resection margin is essential for locoregional control in vulvar cancer. However, in this large, single-center study, we could not demonstrate any prognostic impact of pathological margin distance.

Background To reduce morbidity of radical groin dissection, the sentinel-node (SLN) procedure was implemented for the treatment of vulvar cancer. It has been proven to be a safe alternative in early-stage disease. Feasibility and safety of the procedure after previous vulvar surgery remain unclear. Methods A total of 106 patients with primary vulvar cancer undergoing the SLN procedure were analyzed. Seventy-four patients received the SLN procedure concomitant to vulvar surgery [primary-sentinel group (PSG)], whereas 32 patients had vulvar surgery before secondary SLN [secondary-sentinel group (SSG)]. Results SLN detection was possible in all patients. Three (9.4 %) patients in the SSG and 30 (40.5 %) in the PSG had metastatic spread to the SLN and underwent radical groin dissection. Median interval between vulva surgery and secondary sentinel was 34 days (range, 7–98). In the SSG tumor, stages were earlier with smaller tumor size (median 19 mm in the PSG vs. 9 mm in the SSG) and lesser invasion depth (4 vs. 2 mm; p  < 0.001). There were no groin recurrences in the SSG and 5.4 % in the PSG. No significant difference regarding disease-free survival (DFS) could be detected (3-year DFS of 72.5 % in the PSG compared with 92.5 % in the SSG (median DFS not reached, p  = 0.114)). Adjusting for potential confounders (tumor stage, nodal status, tumor size, invasion depth) did not alter the results with regards to DFS. Conclusions Our results suggest that a secondary SLN procedure after previous vulvar surgery is feasible and can accurately reflect the groin status of selected patients. Ideally, prospective trials should be conducted to verify accuracy and oncologic safety of the procedure.

Chemotherapy is currently the treatment of choice for patients with high-risk metastatic breast cancer. Clinical response is determined after several cycles of chemotherapy by changes in tumor size as assessed by conventional imaging procedures including CT, MRI, plain film radiography, or ultrasound. The aim of this study was to evaluate the use of sequential 18F-FDG PET to predict response after the first and second cycles of standardized chemotherapy for metastatic breast cancer. Eleven patients with 26 metastatic lesions underwent 31 (18)F-FDG PET examinations (240-400 MBq of 18F-FDG; 10-min 2-dimensional emission and transmission scans). Clinical response, as assessed by conventional imaging after completion of chemotherapy, served as the reference. 18F-FDG PET images after the first and second cycles of chemotherapy were analyzed semiquantitatively for each metastatic lesion using standardized uptake values (SUVs) normalized to patients' blood glucose levels. In addition, whole-body 18F-FDG PET images were viewed for overall changes in the 18F-FDG uptake pattern of metastatic lesions within individual patients and compared with conventional imaging results after the third and sixth cycles of chemotherapy. After completion of chemotherapy, 17 metastatic lesions responded, as assessed by conventional imaging procedures. In those lesions, SUV decreased to 72% +/- 21% after the first cycle and 54% +/- 16% after the second cycle, when compared with the baseline PET scan. In contrast, 18F-FDG uptake in lesions not responding to chemotherapy (n = 9) declined only to 94% +/- 19% after the first cycle and 79% +/- 9% after the second cycle. The differences between responding and nonresponding lesions were statistically significant after the first (P = 0.02) and second (P = 0.003) cycles. Visual analysis of 18F-FDG PET images correctly predicted the response in all patients as early as after the first cycle of chemotherapy. As assessed by 18F-FDG PET, the overall survival in nonresponders (n = 5) was 8.8 mo, compared with 19.2 mo in responders (n = 6). In patients with metastatic breast cancer, sequential 18F-FDG PET allowed prediction of response to treatment after the first cycle of chemotherapy. The use of 18F-FDG PET as a surrogate endpoint for monitoring therapy response offers improved patient care by individualizing treatment and avoiding ineffective chemotherapy.

Introduction:Therapeutic options in advanced or recurrent vulvar cancer are limited. The identification of new prognostic factors and markers for therapy stratification is therefore highly desirable. Carbonic anhydrase IX (CAIX) is up-regulated in various solid tumors and a promising new target. We therefore determined CAIX serum concentration and its prognostic relevance in correlation to intratumoral CAIX expression in patients with primary vulvar cancer.Methods:Thirty-one serum samples of patients with primary vulvar cancer were prospectively collected before surgery and analyzed for CAIX by enzyme-linked immunosorbent assay. In addition, intratumoral CAIX expression was determined by immunohistochemistry and correlation with serum CAIX and clinicopathological factors, and outcome was analyzed.Results:Preoperative serum concentration of CAIX ranged between 56 and 879 pg/mL (median, 147 pg/mL; mean, 237.29) and was significantly higher in patients with high intratumoral expression (median, 269 pg/mL vs 126 pg/mL, P = 0.03). High serum CAIX was not associated with any of the analyzed clinicopathological parameters. However, disease-free survival was shorter in patients with high preoperative serum CAIX (above median; P = 0.012). By immunohistochemistry, 26% of the tumors showed a moderate or strong expression of CAIX, whereas 74% showed weak or no expression. High intratumoral expression of CAIX was also associated with unfavorable disease-free survival (P = 0.043).Conclusions:Carbonic anhydrase IX serum concentration is higher in patients with high intratumoral expression, and elevated preoperative serum values are associated with unfavorable prognosis. Serum CAIX might therefore be an easily assessable marker to stratify patients for adjuvant therapy and potentially monitor response. Carbonic anhydrase IX is differentially expressed in vulvar cancer and potentially associated with negative outcome.

Carbonic anhydrase IX (CAIX) is a strictly membranous expressed metalloenzyme involved in cell adhesion, pH homeostasis, and cancer progression. The protein is specifically overexpressed in a wide variety of malignant tumors. This study was designed to assess the role of CAIX in primary vulvar cancer. One hundred forty-two well-characterized primary vulvar carcinomas were analyzed on a tissue microarray (TMA). Three tissue cores were sampled from each tumor. CAIX expression was determined by immunohistochemistry, using a four-step scoring system. To determine CAIX expression in benign vulvar tissue, we constructed a TMA with 120 samples of normal mucosa and non-neoplastic diseases. CAIX expression was found in 77/135 (57%) of all assessable vulvar cancer specimens and 48 (35.5%) exhibited a moderate or strong expression. CAIX expression in vulvar carcinomas was significantly stronger compared to non-neoplastic vulvar tissue ( p  < 0.001). High levels of CAIX expression were related to pT stage ( p  < 0.01), tumor size ( p  < 0.01), depth of invasion ( p  < 0.05), as well as inguinal lymph node metastases ( p  < 0.05). There was also a trend towards shorter recurrence-free patient survival in CAIX-positive compared to CAIX-negative vulvar cancers. CAIX staining results in different tissue cores from the same tumor were homogeneous, raising the possibility of a hypoxia-independent expression. In conclusion, CAIX is overexpressed in the majority of vulvar carcinomas with relationships to advanced tumor stages and development of lymph node metastases. Our data support the potential therapeutic benefit of newly developed targeting antibodies in advanced vulvar cancer.

Lern- und Bildungsprozesse sind unlösbar mit Zeitlichkeit verbunden. In der aktuellen erziehungswissenschaftlichen Forschung wird dies erkannt, es bleiben aber Desiderata insbesondere in der Verbindung bildungstheoretischer Überlegungen mit qualitativer empirischer Forschung. Deshalb untersuchen wir in einem aktuellen Forschungsprojekt mittels qualitativ-rekonstruktiver Verfahren den Zusammenhang zwischen institutionalisierten Zeitstrukturen, kollektiven Zeitpraktiken und subjektivem Lernzeiterleben in Bildungsurlaubsveranstaltungen. Im Beitrag besprechen wir zunächst grundlegend das Verhältnis von Zeit und Erwachsenenbildung und betten unseren Untersuchungsgegenstand in den Kontext der Programmatik lebenslangen Lernens ein. Auf dieser Grundlage stellen wir das methodische Design unseres Forschungsprojekts vor, bei dem wir auf eine Verbindung von qualitativer Kursforschung einerseits und erwachsenenbildungswissenschaftlicher Biografieforschung andererseits setzen und in diesem Rahmen teilnehmende Beobachtungen von Kursen und narrative Interviews mit Teilnehmenden auf Grundlage der dokumentarischen Methode analytisch verschränken. Anhand eines ausgewählten Falles zeigen wir auf, wie es durch diesen multimethodischen und multiperspektivischen Zugang möglich wird, die komplexen Verhältnisse zwischen kollektiven Zeitpraktiken und subjektivem Lernzeiterleben herauszuarbeiten. Dabei fokussieren wir die praktische Strukturierung der Kurszeit im Unterschied zur Lernzeit jenseits des Kurses und zeigen für letztere auf, wie unterschiedlich die Teilnehmenden diese wahrnehmen und ausgestalten. In einer abschließenden Reflexion verweisen wir auf methodische Anschlussfragen, die sich aus der bisherigen Forschungspraxis ableiten lassen.