Radiation exposure during TACE procedures using additional cone-beam CT (CBCT) for guidance: safety and precautions.

Background During transarterial chemoembolization (TACE), cone-beam computed tomography (CBCT) can be used for tumor and feeding vessel detection as well as postembolization CT imaging. However, there will be additional radiation exposure from CBCT. Purpose To evaluate the additional dose raised through CBCT-assisted guidance in comparison to TACE procedures guided with pulsed digital subtraction angiography (DSA) alone. Material and Methods In 70 of 140 consecutive patients undergoing TACE for liver cancer, CBCT was used to facilitate the TACE. Cumulative dose area product (DAP), cumulative kerma(air), DAP values of DSA, total and cine specific fluoroscopy times (FT) of 1375 DSA runs, and DAP of 91 CBCTs were recorded and analyzed using Spearman's correlation, Mann-Whitney U-test, and Kruskal-Wallis test. P values < 0.05 were considered significant. Results Additional CBCT increased DAP by 2% ( P = 0.737), kerma(air) by 24.6% ( P = 0.206), and FT by 0.02% ( P = 0.453). Subgroup analysis revealed that postembolization CBCT for detection of ethiodized oil deposits added more DAP to the procedure. Performing CBCT-assisted TACE, DSA until first CBCT contributed about 38% to the total DAP. Guidance CBCT acquisitions conduced to 6% of the procedure's DAP. Additional DSA for guidance after CBCT acquisition required approximately 46% of the mean DAP. The last DSA run for documentation purposes contributed about 10% of the DAP. Conclusion CBCT adds radiation exposure in TACE. However, the capability of CBCT to detect vessels and overlay in real-time during fluoroscopy facilitates TACE with resultant reduction of DAPs up to 46%.

Pazopanib (GW786034) and cyclophosphamide in patients with platinum-resistant, recurrent, pre-treated ovarian cancer - Results of the PACOVAR-trial.

PURPOSE: The prognosis is poor for patients with recurrent, platinum-resistant epithelial ovarian cancer (EOC). Evidence suggests that antiangiogenic treatment modalities could play a major role in EOC. A combined therapy consisting of the investigational oral antiangiogenic agent pazopanib and metronomic oral cyclophosphamide may offer a well-tolerable treatment option to patients with recurrent, previously treated EOC. PATIENTS AND METHODS: This study was designed as a multicenter phase I trial evaluating the optimal dose as well as activity and tolerability of pazopanib with metronomic cyclophosphamide in the treatment of patients with recurrent, platinum-resistant, previously treated ovarian, peritoneal, or fallopian tube cancer. Here, 50mg cyclophosphamide were combined with 400 to 800mg pazopanib daily. RESULTS: Sixteen patients were treated; mean age was 66years. At dose levels (DL) I and II, one instance of dose-limiting toxicity (DLT) was seen in one of 6 patients. At DL III, two of four patients showed a DLT, leading to a maximum tolerated dose (MTD) of 600mg pazopanib daily. Median number of administered cycles was 6 (2-13), with three patients being treated for at least 13months. Median progression-free survival (PFS) and overall survival (OS) were 8.35months and 24.95months, respectively. 155 adverse events (AE) occurred, most frequently elevation of liver enzymes, leukopenia, diarrhea and fatigue. Altogether, five serious adverse events (SAE) developed in four patients. CONCLUSION: Pazopanib 600mg daily p.o. and metronomic cyclophosphamide 50mg daily p.o. is a feasible regimen for patients with recurrent platinum-resistant EOC and showed promising activity in this previously treated patient population. TRIAL REGISTRATION: Clin.trial.gov registry no.: NCT01238770.

Influence of zoledronic acid on disseminated tumor cells in primary breast cancer patients.

BACKGROUND: The presence of disseminated tumor cells (DTCs) in bone marrow of patients with early breast cancer (EBC) has been correlated with increased risk of metastatic disease or locoregional relapse. Zoledronic acid (ZOL) treatment has reduced DTCs in the bone marrow of patients with EBC in several studies. This controlled study sought to confirm these observations. PATIENTS AND METHODS: Patients with EBC and DTC-positive bone marrow were randomized (N = 96) to treatment with ZOL plus adjuvant systemic therapy or adjuvant systemic therapy alone. The change in DTC numbers at 12 months versus baseline was measured. RESULTS: DTC-positive patients treated with ZOL were more likely to become DTC-negative after 12 months of treatment compared with the controls (67% versus 35%; P = 0.009). At 12 months, DTC counts decreased to a mean of 0.5 ± 0.8 DTCs in the ZOL group and to 0.9 ± 0.8 DTCs in the control group. In addition, ZOL was generally well tolerated. CONCLUSIONS: Treatment with ZOL improves elimination of DTCs. Further studies are needed to determine whether the reduction in DTCs by ZOL provides clinical benefit.

Stable isotope signatures confirm carbon and nitrogen gain through ectomycorrhizas in the ghost orchid Epipogium aphyllum Swartz.

Epipogium aphyllum is a rare Eurasian achlorophyllous forest orchid known to associate with fungi that form ectomycorrhizas, while closely related orchids of warm humid climates depend on wood- or litter-decomposer fungi. We conducted (13) C and (15) N stable isotope natural abundance analyses to identify the organic nutrient source of E. aphyllum from Central Norway. These data for orchid shoot tissues, in comparison to accompanying autotrophic plants, document C and N flow from ectomycorrhizal fungi to the orchid. DNA data from fungal pelotons in the orchid root cortex confirm the presence of Inocybe and Hebeloma, which are both fungi that form ectomycorrhizas. The enrichment factors for (13) C and (15) N of E. aphyllum are used to calculate a new overall average enrichment factor for mycoheterotrophic plants living in association with ectomycorrhizal fungi (ε(13) C ± 1 SD of 7.2 ± 1.6 ‰ and ε(15) N ± 1 SD of 12.8 ± 3.9 ‰). These can be used to estimate the fungal contribution to organic nutrient uptake by partially mycoheterotrophic plants where fully mycoheterotrophic plants are lacking. N concentrations in orchid tissue were unusually high and significantly higher than in accompanying autotrophic leaf samples. This may be caused by N gain of E. aphyllum from obligate ectomycorrhizal fungi. We show that E. aphyllum is an epiparasitic mycoheterotrophic orchid that depends on ectomycorrhizal Inocybe and Hebeloma to obtain C and N through a tripartite system linking mycoheterotrophic plants through fungi with forest trees.

Gains of chromosome region 3q26 in intraepithelial neoplasia and invasive squamous cell carcinoma of the vulva are frequent and independent of HPV status.

AIMS: Two different forms of vulvar intraepithelial neoplasia (VIN) are recognised: (1) usual-type (bowenoid) VIN, which is related to high-risk papillomavirus infection, and (2) differentiated (simplex) VIN, which is associated with chronic inflammation. The aim of this study was to investigate the presence of chromosome 3q26 gains in the spectrum of precancerous lesions and invasive squamous cell carcinomas (SCCs) of the vulva. METHODS: 3q26 gains were analysed using fluorescence in situ hybridisation in a series of usual-type VINs, VINs of the differentiated type and invasive squamous cell carcinomas. In addition, all cases were examined for human papillomavirus (HPV) DNA, p53 mutations, and p16 and p53 protein expression. RESULTS: Gains of chromosome 3q26 were present in all VINs of the differentiated type and in 50% of the usual-type VIN lesions. 81% of SCCs were positive for 3q26 gains irrespective of the HPV status and of the associated precursor lesion. HPV-associated lesions exhibited the typical, strong cytoplasmic p16 accumulation while mutated p53 was only detected in HPV-negative VINs or SCCs, and was associated with an overexpression of p53 protein. CONCLUSIONS: Immunohistochemical evaluation of p16 and p53 expression aids in the differential diagnosis of squamous cell alterations of the vulva. However, detection of 3q26 imbalance is of additional diagnostic value in difficult cases of HPV-unrelated usual-type VINs and VINs of the differentiated type.

Detection of disseminated tumor cells in patients with gynecological cancers.

OBJECTIVES: The presence of disseminated tumor cells (DTC) in breast cancer patients is associated with poor prognosis. However, there are limited data about the prevalence and prognostic impact of DTC in patients with gynecological tumors. The aim of this study was to evaluate the presence of DTC in the bone marrow (BM) of patients with gynecological cancers and to correlate their presence with established prognostic factors. METHODS: BM aspirates of 201 patients with primary ovarian (n=69), cervical (n=54) and endometrial cancer (n=78), undergoing surgery at the Department of Gynecology and Obstetrics, University Hospital, Tuebingen, Germany between 1/2002 and 01/2006, were included into the study. Cytokeratin (CK)-positive cells were identified by immunocytochemistry using the pancytokeratin antibody A45B/B3. RESULTS: The bone marrow positivity rate was 36% in ovarian, 26% in cervical and 17% in endometrial cancer, respectively. Presence of DTC was significantly correlated with FIGO (International Federation of Gynecology and Obstetrics) tumor stage (p<0.05). The recurrence rate was 14% in patients with CK-positive cells compared to 8% in CK-negative patients (p=0.2). There was no correlation between DTC and other established prognostic factors including nodal status or grading except for cervical cancer. Patients with positive lymph node status were more likely to be bone marrow positive compared to those with negative lymph node status (p<0.05). CONCLUSIONS: Disseminated tumor cells seem to be a general phenomenon in epithelial tumors even though their clinical impact remains to be evaluated. The hypothesis that bone marrow is the homing site of disseminated tumor cells is further supported by these data since gynecological tumors only rarely metastasize to the skeletal system.

[Analysis of the Nuchal Transparency (NT) screening concept at the gynecologocial clinic of MHH: a prospective follow-up study]. / Analyse des Nackentransparenz (NT-)Screeningkonzepts an der Frauenklinik der MHH: Eine prospektive Follow-up-Studie.

BACKGROUND: To date, various and partly competitive screening strategies for the risk calculation of trisomy 21 are applied in Germany. The aim of this study was to control the published test performance data of different methods in an unselected group of patients, thus allowing us to clearly assess the practical value of the respective methods. PATIENTS AND METHODS: At the MH Hannover, 744 women with a singleton pregnancy underwent an NT measurement according to the FMF guidelines. Additionally, 590 of these women had a PAPP-A and free ssHCG testing in a laboratory accredited by the FMF London. The fetal outcome of all 744 patients examined was assessed. Based on these data, test performance values were calculated for each test strategy under the hypothetical assumption that every women would have followed the same screening strategy. RESULTS: Age-related screening revealed to have the highest false-positive rate (25 %). Age screening combined with serum markers showed to have the highest sensitivity (100 %). Screening combining age, NT measurement and serum markers yielded the highest specificity (97 %). Combined screening by NT and age achieved the same sensitivity as age-related screening with a markedly lower false-positive rate than screening combining age and serum markers. Invasive tests were performed in 11 % of the patients. In 8 % of these, a pathologic karyotype was detected. CONCLUSIONS: In comparison to age-related screening, first trimester screening allows us to define groups at risk for trisomy 21 more clearly. This seems to justify the clinical importance of this search strategy, and accordingly, invasive procedures are done less frequently in a higher proportion of younger women.

Methods for isolating circulating epithelial cells and criteria for their classification as carcinoma cells.

Novel assay methods developed for the isolation and characterization of circulating tumor cells (CTC) of epithelial origin offer the potential of markers for the non-invasive gathering of clinical information relevant to the diagnosis, evolution and treatment of carcinoma. Of the numerous techniques currently used to analyze CTC, slide-based assays are perhaps the most common. While traditional combined immunocytochemical/brightfield microscopy systems continue to be the most frequently employed, fluorescence-based analysis is gaining in importance. This is partly because fluorescence microscopy analysis of slide-mounted CTC can provide simultaneously cytogenetic as well as morphologic and multiple phenotypic information. In particular, fluorescence microscopy analysis of slide-mounted CTC can accurately determine genetic changes at the chromosomal level in patients with recurrent disease. More importantly, by identifying genetic aberrations in CTC, it becomes possible to choose those patients most likely to benefit from a given treatment. The potential of this technique has already been demonstrated by employing fluorescence in situ hybridization (FISH) methods to measure expression of the HER2/neu gene in tissue from patients with breast carcinoma for the specific purpose of identifying those patients most likely to respond to Trastuzumab targeted therapy. Here, we review the major methodologies used in the preparation and analysis of the slide-based assays.

Ultrasound simulators: experience with the SonoTrainer and comparative review of other training systems.

Ultrasound has become indispensable in prenatal diagnosis. Ultrasound training, however, still lacks proper quality assessment and control. Moreover, most fetal anomalies which must be diagnosed during pregnancy are extremely rare. Ultrasound simulators could provide an opportunity to overcome this dilemma. This review summarizes the potential benefits of simulator-based ultrasound training, briefly describes the properties of a variety of ultrasound simulators that have been developed for various applications including prenatal diagnosis, and presents the SonoTrainer sonography simulation system which makes it possible to run a real-time simulation of a complete prenatal ultrasound examination. We evaluated the system for the training of first- and second-trimester screening for both normal and pathological findings and found that physicians who received theoretical training and were additionally trained with the simulator (T + S) significantly improved their skills in measurements of nuchal translucency thickness (NT) and crown-rump length (CRL) as compared with colleagues who only underwent theoretical instruction (T) [mean +/- SD NT deviation: 0.31 +/- 0.1 mm (T + S) vs. 0.62 +/- 0.2 mm (T), P < 0.05; mean +/- SD CRL deviation: 1.48 +/- 2.0 mm (T + S) vs. 3.27 +/- 2.5 (T), P < 0.05]. Simulator-based training enabled physicians to diagnose rare fetal anomalies in the second trimester with a sensitivity of 86% and a specificity of 100%. In a study in which second-trimester scans including fetal anomalies were presented to physicians, 96% of the participants subjectively estimated their training effect as being good. We therefore conclude that simulator-based training would provide an ideal educational tool to test, improve and monitor a physician's or technician's ultrasound skills in detecting fetal anomalies.

Uptake of nitrogen and carbon from double-labelled (15 N and 13 C) glycine by mycorrhizal pine seedlings.

• While it is accepted that many ectomycorrhizal fungi can assimilate organic substrates and facilitate transfer of their elemental components to plants, the fate of the carbon contained in these materials remains uncertain. Here we investigate the compartmentation of carbon and nitrogen in ectomycorrhizal seedlings of Pinus sylvestris fed with double-labelled (15 N and 13 C) glycine as their sole N source. • Using isotope ratio mass spectrometry, the quantities of N and C derived from this glycine were determined in sequentially harvested samples of mycorrhizas, roots and shoots. • Whereas considerable quantities of 15 N were observed in the mycorrhizal tips, roots and shoots, comparable amounts of 13 C were observed only in mycorrhizal tips and roots. • It is clearly important to resolve the role of compound specificity as a factor determining the extent of amino-acid C transfer from roots to shoots. However, from the standpoint of the C budget of the whole plant, wherever heterotrophically acquired C is available as an energy source it will reduce demands on photosynthetically fixed sources of the element.

Changes of serum HER2 status during clinical course of metastatic breast cancer patients.

BACKGROUND: Serum HER2 testing allows the determination of the real-time HER2 status of breast cancer patients. The aim of this investigation was to study (i) whether changes of serum HER2 status occur during the clinical course of breast cancer and (ii) to evaluate the prognostic significance of serum HER2 status, at the time of first diagnosis of primary breast cancer and at the onset of metastatic disease, for survival after relapse (SAR). MATERIALS AND METHODS: HER2 serum levels were retrospectively measured in 152 breast cancer patients at the time of first diagnosis of breast cancer and at the onset of metastatic disease by enzyme immunoassay. RESULTS: Twenty-seven out of 152 (18%) patients had elevated HER2 serum levels at the time of first diagnosis of breast cancer. In contrast, 56 out of 152 (37%) patients showed elevated serum HER2 levels when metastases were diagnosed. A change of serum HER2 status during clinical course was observed in 43 out of 152 (28%) patients. Serum HER2 status at the time of first diagnosis of breast cancer had no impact on survival after relapse (SAR) (p = 0.4). However, the median SAR for serum HER2-positive patients at the onset of metastatic disease was significantly shorter (8 months, 95% CI: 3-12) compared to patients serum HER2-negative at this time (18 months, 95% CI: 14-22) (p < 0.01). CONCLUSION: Serum HER2 status can change during the course of disease. Therefore, the serum HER2 status should be re-evaluated at the time of diagnosis of metastatic disease to optimize treatment decisions.

Tree species of the Central Amazon and soil moisture alter stable isotope composition of nitrogen and oxygen in nitrous oxide evolved from soil.

The use of stable isotopes of N and O in N2O has been proposed as a way to better constrain the global budget of atmospheric N2O and to better understand the relative contributions of the main microbial processes (nitrification and denitrification) responsible for N2O formation in soil. This study compared the isotopic composition of N2O emitted from soils under different tree species in the Brazilian Amazon. We also compared the effect of tree species with that of soil moisture, as we expected the latter to be the main factor regulating the proportion of nitrifier- and denitrifier-derived N2O and, consequently, isotopic signatures of N2O. Tree species significantly affected delta15N in nitrous oxide. However, there was no evidence that the observed variation in delta15N in N2O was determined by varying proportions of nitrifier- vs. denitrifier-derived N2O. We submit that the large variation in delta15N-N2O is the result of competition between denitrifying and immobilizing microorganisms for NO3(-). In addition to altering delta15N-N2O, tree species affected net rates of N2O emission from soil in laboratory incubations. These results suggest that tree species contribute to the large isotopic variation in N2O observed in a range tropical forest soils. We found that soil water affects both 15N and 18O in N2O, with wetter soils leading to more depleted N2O in both 15N and 18O. This is likely caused by a shift in biological processes for 15N and possible direct exchange of 18O between H2O and N2O.

15 N and 13 C natural abundance of autotrophic and myco-heterotrophic orchids provides insight into nitrogen and carbon gain from fungal association.

• Whereas mycorrhizal fungi are acknowledged to be the sources of nitrogen (N) and carbon (C) in achlorophyllous (myco-heterotrophic) orchids, the sources of these elements in autotrophic orchids are unknown. We have determined the stable isotope abundance of N and C to quantify their gain from different sources in these two functional groups and in non-orchids of distinctive mycorrhizal types. • Leaves of each plant were collected from four forest and four grassland sites in Europe. The N and C isotope abundance, and total N concentrations of their tissues and of associated soils were determined. • Myco-heterotrophic orchids were significantly more enriched in 15 N (ɛMHO-R = 11.5‰) and 13 C (ɛMHO-R = 8.4‰) than co-occurring non-orchids. δ15 N and δ13 C signatures of autotrophic orchids ranged from values typical of non-orchids to those more representative of myco-heterotrophic orchids. • Utilization of fungi-derived N and C probably explains the relative 15 N and 13 C enrichment in the myco-heterotrophs. A linear two-source isotopic mixing model was used to estimate N and C gain of autotrophic orchids from their fungal associates. Of the putatively autotrophic species, Cephalanthera damasonium obtained the most N and C by the fungal route, but several other species also fell into the partially myco-heterotrophic category.

Carcinoembryonic antigen and CA19-9: implications of quantitative marker measurement in tissues for prognosis of colorectal cancer.

Measurement of tumor markers in serum of colorectal cancer patients after surgery is a sensitive method in early diagnosis of systemic spread of tumor cells. Moreover, prognostic association of carcinoembryonic antigen (CEA) content in serum at the time of surgery is well known. However, fairly unclear is whether quantitative content of CEA and CA19-9 in cancer tissue and adjacent normal mucosa of colorectal cancer patients is correlated to prognosis. Concentrations of CEA and CA]9-9 were analyzed simultaneously in serum, cancer tissue, and normal colonic mucosa of 41 colorectal cancer patients operated for cure. Follow-up data were available for up to 82 months (median, 47 months) after surgery. During the follow-up period, 20 patients had a tumor recurrence, and all these patients died of metastatic disease. Using the median concentration of CEA and CA19-9 in tissues as a cut-off, no difference in overall and disease-free survival was observed between patients with elevated or normal CEA or CA19-9 concentrations in tumor tissue. However, in adjacent histologically normal mucosa, elevated CEA content was associated with significantly shorter overall survival (P = .0385) and disease-free survival (P = .0141) but not CA19-9 content. Despite the unknown biological function of tumor markers in malignant disease, measurement of tumor-associated antigens in colorectal tissues can become an interesting prognostic marker.

Epithelial cells in bone marrow of breast cancer patients at time of primary surgery: clinical outcome during long-term follow-up.

PURPOSE: To evaluate the detection of epithelial cells in bone marrow of breast cancer patients as an indicator of metastatic disease. PATIENTS AND METHODS: Between 1989 and 1994, bone marrow biopsies were performed on 393 breast cancer patients during primary surgery. Specimens were stained immunocytochemically for epithelial cells expressing cytokeratins or the epithelial membrane antigen. The long-term outcomes of these patients were analyzed in this study. RESULTS: In 166 of 393 patients, epithelial cells were found in bone marrow (BM) aspirates. These patients were designated BM+. The rate of tumor recurrence or cancer-related death was significantly higher in BM+ patients than in BM- patients. Multivariate analysis using the Cox regression model revealed BM status as a prognostic parameter independent of tumor size and axillary lymph node status. However, tumor size and axillary lymph node status were clearly superior prognostic parameters. CONCLUSION: Disseminated epithelial cells in BM are associated with poor clinical outcome in breast cancer patients. However, the presence of these cells is not a sufficient parameter to predict growing metastases in the majority of patients, suggesting that epithelial cells in the BM of breast cancer patients at the time of surgery have limited metastatic potential. The role of these cells needs to be further evaluated.

Missed and associated injuries after subtalar dislocation: the role of CT.

Subtalar joint dislocation (STJD) is an uncommon injury, but carries with it a potential for significant functional disability. We hypothesized that a significant number of injuries associated with subtalar joint dislocation may be unrecognized by plain radiographic examination. Therefore, we reviewed the records of all STJDs over a three-year period, identifying nine cases. The majority of injuries occurred in men (78%) with a mean age of 29 years. Overall, the mean age at injury was 32 years. The right lower extremity was most frequently injured (87.5%). Plain films initially diagnosed a STJ dislocation in all patients. A CT scan was performed in all cases. In 100% of patients, CT identified additional injuries missed on initial plain radiographs. In 44% of patient, new information gathered by CT dictated a change in treatment. Based on our findings, we conclude that CT is an invaluable tool to assess for associated injuries in STJ dislocation, and should be performed in all cases of STJ dislocation.

On-line analysis of nitrogen stable isotopes in NO from ambient air samples.

A method was developed for the on-line analysis of nitrogen stable isotopes at the natural abundance level in NO in order to study the NO contribution to the nitrogen cycle in ecosystems and in the atmosphere. The method enables a quick and accurate determination of 15N/14N ratios for NO and consists of the following steps: (a) accumulation of NO from air samples on a molecular sieve of 5 A, (b) desorption of NO from the molecular sieve during 15 min of heating at 350 degrees C (an offset of Deltadelta 4.6% must be corrected for), (c) trapping and cryofocusation of the desorbed NO on a PoraPlot Q matrix at -196 degrees C during heating, (d) release of the trapped NO from the PoraPlot Q matrix followed by chromatographic separation, reduction to N2, and isotopic composition analysis. A minimum sample size of 125 nmol of NO is recommended. A correction function for the calculation of the delta15N-NO values was introduced for sample sizes from 125 to 220 nmol of NO. Measurements of NO in automobile exhaust have proven the applicability of the developed method.

Role of hysteroscopy in detection and extraction of endometrial polyps: results of a prospective study.

OBJECTIVE: The aim of this study was to determine whether hysteroscopy improves the detection and extraction of endometrial polyps in postmenopausal women. This method was compared with curettage complemented by Randall polyp forceps. STUDY DESIGN: In a prospective study hysteroscopy was performed before and after curettage in postmenopausal women. In addition to curettage, the Randall polyp forceps was used to extract endometrial polyps. Curettage and polyp extraction by Randall forceps were performed by a second surgical team that did not know the results of hysteroscopy. RESULTS: A total of 83 patients were included in the study because of either postmenopausal bleeding (n = 40) or ultrasonographic abnormal endometrium (n = 37), or both (n = 6). Thirty-two patients received either hormone replacement therapy or tamoxifen. Hysteroscopy revealed endometrial polyps in 51 patients. Polyps were diagnosed by curettage alone in 22 (43%) cases. In 18 of these 22 cases remnants of polyps were extracted by Randall forceps, and in another 23 cases polyps were only found by use of the Randall forceps. Thus in 45 (88%) of 51 patients the detection of endometrial polyps by curettage and Randall forceps was possible. A second hysteroscopy procedure revealed remnants of polyps or polyps in 31 cases. These patients with incomplete curettage predominantly had a preoperative endometrial thickness of > or =10mm. CONCLUSIONS: Curettage alone in postmenopausal patients is not sufficient for detection and extraction of endometrial polyps. Additional use of Randall forceps improves detection of polyps considerably. However, with both procedures complete extraction of polyps was not achieved in a considerable number of patients. Hysteroscopy-controlled extraction was superior, especially in those patients with an endometrial thickness of >10 mm.

Cisplatin-resistance involves the defective processing of MEKK1 in human ovarian adenocarcinoma 2008/C13 cells.

Cisplatin has been widely used as a chemotherapeutic agent to treat different types of tumors. However, its use is limited by the ability of the tumor cells to develop cisplatin-resistance. The molecular lesion that produces cisplatin-resistance is poorly understood. In this report, we show that cisplatin activates a robust apoptotic pathway involving the activation of JNK and p38MAPK whereas it fails to elicit such a response in cisplatin-resistant 2008/C13 cells. Analysis of the defective apoptotic pathway in 2008/C13 cells indicates that these cells are deficient in the proteolytic activation of MEKK1 by caspase-3. The blunted activity of caspase-3 appears to be closely related to the increased levels of the anti-apoptotic protein Bcl-xL seen in the resistant cells. These studies, for the first time, demonstrate that inadequate caspase-3 processing and MEKK1 activation can lead to a drug-resistant phenotype.