Symptomatic osteoradionecrosis of pelvic bones in patients with gynecological malignancies—result of a long-term follow-up

The aim of this study was to assess the incidence and risk factors of pelvic fractures as a result of radiation therapy in women with gynecological cancer. We retrospectively reviewed 3530 female patients treated at our institute between 1980 and 1998 with megavoltage radiation with or without brachytherapy for cancer in the pelvic area. Eligible were patients with vulvar, vaginal, cervical, endometrial, and fallopian tube cancer. Median follow-up was 88 months (range 0-240). Emphasis was put on treatment-related and patient-related risk factors. Of the eligible 3155 patients, 15 developed symptomatic bone fracture caused by osteoradionecrosis, which makes an overall incidence of 0.44% The diagnosis was based on anamnesis, clinical course, and X-ray or computed tomography images. Median time of onset was 44 months (range 6-197). All patients had pain as the first symptom. The only independent predictive factor for developing osteoradionecrosis seemed to be preexistent osteoporosis. Other risk factors that are related to osteoporosis include higher age, postmenopausal status, or steroid treatment. We did not find any significant treatment-related predictive factor for pelvic osteoradionecrosis. Patients with osteoporosis are probably at the highest risk for developing osteoradionecrotic fractures after pelvic radiotherapy. More studies are needed to find out other endogenous predictive factors.     

X chromosomal and autosomal loss of heterozygosity and microsatellite instability in human cervical carcinoma

The study analyzes tumor material and normal tissue from 27 patients with pure squamous cell carcinoma of the uterine cervix for loss of heterozygosity (LOH) and microsatellite instability (MSI) on 14 autosomal and 11 X chromosomal loci. Overall, 4-40% of the informative cases showed LOH at autosomal regions with the highest frequency at 3p (21-40%) and a marked frequency at 2q35-q37.1 (12.5%) and 17p13.3 (10%), representing regions with putative tumor suppressor gene (TSG) function. The frequency of X chromosomal LOH ranged from 4% to 20%, with a maximum at Xq28 (20%) and Xq11.2-q12 (17%), again indicating alterations in TSG. A 12% LOH was seen at Xq21.33-q22.3, a region encoding a protein with a regulatory function in the cell cycle via cyclin-dependent kinases. MSI was detected in autosomal regions in up to 7% in regions linked to the X chromosome in up to 11%, probably indicating alterations of mismatch repair mechanisms. Our results and those obtained from the literature suggest that autosomal LOH and MSI in carcinomas of the cervix uteri are predominantly found at regions with putative TSG function. Beside TSG alterations, X chromosomal LOH is probably more strongly connected to disturbances in cell cycle regulation.     

European Committee on Antimicrobial Susceptibility Testing (EUCAST) Technical Notes on antimicrobial susceptibility testing

The main objectives of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) are to harmonise breakpoints for antimicrobial agents in Europe, and to act as the breakpoint committee for the European Medicines Agency (EMEA) during the registration of new antimicrobial agents. Detailed EUCAST procedures for harmonising and setting breakpoints for antimicrobial agents are available on the EUCAST website. Beginning with the current issue, a series of EUCAST Technical Notes will be published in CMI, based on the rationale documents produced by EUCAST for each of the antimicrobial agents studied, with the aim of highlighting important background information underlying decisions on breakpoints made by EUCAST.     

Hood versus mask nebulization in infants with evolving bronchopulmonary dysplasia in the neonatal intensive care unit.

OBJECTIVE: To compare infants' discomfort, nursing-time and caregiver preference, and assess the clinical efficiency (as a secondary outcome) of hood versus facemask nebulization in infants with evolving bronchopulmonary dysplasia (BPD) in the neonatal intensive care unit. STUDY DESIGN: A prospective, open, randomized, controlled crossover clinical trial. In total, 10 infants with BPD who were on inhaled beta-agonist bronchodilators and corticosteroids were randomly assigned to receive their nebulized treatments either by a facemask, or by a hood for 2-3 days, and then crossover to receive the same treatments with the other technique for another 2-3 days. Infants' discomfort, nursing-time, caregiver preference and clinical efficiency were compared. RESULTS: At baseline there was no significant clinical difference between the groups. Nurse-time required for administering the hood nebulization (mean+/-s.e.m.: 1.9+/-0.1 min) was significantly shorter than the time for mask nebulization (12.0+/-0.6 min, P<0.0001). Infants' discomfort score was significantly lower (0.1+/-0.04) for hood versus mask nebulization (2.5+/-0.2, P<0.0001). Nurses and parents unequivocally preferred the hood treatment. During both mask and hood nebulization therapies (2-3 days) clinical efficiency was comparable. While both methods caused an immediate (20 min post) clinical improvement, the immediate respiratory assessment change score was significantly greater for the hood versus the mask nebulization (0.62+/-0.27 versus 0.13+/-0.14, P<0.05). CONCLUSIONS: Nebulization of aerosolized medications in infants with evolving BPD by hood was less time-consuming for caregivers and was much better tolerated by the infants while being at least as effective as the conventional facemask nebulization.     

Characterization of the CXCR4 Signaling in Pancreatic Cancer Cells

CXCL12 and its receptor, CXCR4, are emerging as promising targets for modulating growth, angiogenesis, and metastasis in several human cancers. Indeed, blocking the receptor is sufficient to prevent metastasis and angiogenesis in experimental breast cancer xenografts. Recently, the biological effect of the CXCR4 in pancreatic cancer, one of the most deadly neoplastic diseases, has been reported. However, the molecular mechanism by which CXCR4 contributes to these properties is not completely understood. In this paper, we characterize the signaling pathways activated by CXCR4 in pancreatic cancer. We show that after CXCR4 activation, EGFR becomes tyrosine phosphorylated, and the kinase activity of this receptor, together with the activation of MMPs, Src, and PI3-Kinase, is required for CXCR4-mediated ERK activation. Analysis of this cascade in pancreatic cancer cells revealed that the ERK-mediated pathway regulates genes involved in angiogenesis, such as VEGF, CD44, HIF1α, and IL-8. Furthermore, ERK blockage inhibits the migration and tube formation of endothelial cells induced by CXCL12. Considering that inhibitors for several components of this pathway, including CXCR4 itself, are at different stages of clinical trials, this study provides theoretical justification for the clinical testing of these drugs in pancreatic cancer, thus extending the list of potential targets for treating this dismal disease.     

Comparison of diagnostic usefulness of predictive models in preliminary differentiation of adnexal masses

The purpose of this study was to compare prognostic models evaluating the probability of an ovarian cancer occurrence based on a number of clinical and ultrasonographic data in women with adnexal masses. A total of 686 women with adnexal masses underwent the examinations between 1994 and 2002. The recorded parameters included: age, menopausal status, body mass index, the grayscale and Doppler ultrasonographic examination, and selected markers concentration levels. In order to find the best combination of features, which significantly influences the probability of malignancy, stepwise logistic regression analysis, as well as artificial neural network, was used. The diagnostic efficiency of received models was estimated and compared using receiver-operating characteristics (ROC) curve. The results indicate that 431 and 255 patients had a benign and malignant ovarian tumor, respectively. Application of stepwise logistic regression analysis revealed statistically significant importance of eight features. The sensitivity and specificity for the received model were 65.71% and 77.59%, respectively. Three-layer perceptron network shows 13 features as significant predictors of malignancy. The network gave a sensitivity of 85.7% and specificity of 93.1%. Comparison of area under ROC curve for received models was 0.9679 vs 0.9716. Prognostic values of the analyzed neural model are not optimal but seem to surpass logistic regression model in terms of the predictive possibilities.     

Pseudotumour cerebri in a young obese woman on oral contraceptives.

OBJECTIVES: Pseudotumour cerebri has been previously recognized as a neurological side effect of combined oral contraceptives but has not been diagnosed with a delay of 3 years after initiation of combined oral contraceptives. CASE REPORT: A 19-year-old obese woman developed visual impairment and headache, 4 months after starting combined oral contraceptives. Three years later symptoms deteriorated and she presented with prominent tendon-jerks and congested optical-discs. Normal CSF drained with high pressure from the spinal tap. Pseudotumour cerebri was diagnosed. Headache and visual impairment resolved within 3 weeks after discontinuation of combined oral contraceptives. CONCLUSIONS: Combined oral contraceptives-induced pseudotumour cerebri may remain undetected for years. Young, obese women with visual impairment and headache under combined oral contraceptives should undergo immediate neurological and ophthalmological investigation.     

Female pelvic floor. Descriptive anatomy and clinical exploration by transvaginal ultrasound

In order to assess the state and pathology of the woman's pelvis minor, a number of methods are commonly used among practitioners, encompassing clinical exploration, radiology, MRN, urodynamics, endoscopy and echography.

Echography has been poorly used in clinical pelvic exploration and its reliability is actually a matter of controversy 1. However, echographic surveys can provide us with valuable gynecological data on the state and pathologies of the soft pelvis, within the genital regions or even going beyond them, i.e. the rectal channel, bladder, urethra, anus, vascular plexuses, and all of their supporting tissues.

At our research unit, we have been employing Transvaginal Ultrasound echography (TVU) for a long time in conjunction with other pelvis-focused methods in order to study different kinds of pelvic alterations. TVU has proven to be friendly to use, fast, harmless and inexpensive, allowing serial explorations and producing high-quality dynamic images (loop-cinema, video-tape). Furthermore, this method is fairly aseptic in that the occurrence of faeces in the rectal ampolla is not a nuisance but a bonus in tracking the contours of the rectum walls and other topographical features which would be otherwise difficult to survey.

A complete pelvic floor TVU may add no longer than 5-8 minutes to a routine gynecological examination, can be implemented by the general gynecologist and generates data that can be further studied by the appropriate specialist for a more insightful evaluation 2.