Petraki C.,Metropolitan Hospital
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine | Year: 2012
The prognosis of patients with colorectal cancer (CRC) is assessed through conventional clinicopathological parameters, which are not always accurate. Members of the human kallikrein-related peptidases gene family represent potential cancer biomarkers. The aim of this study was to investigate the expression of human tissue kallikrein-related peptidase 10 (KLK10) by immunohistochemistry in CRC, to correlate this expression with various histopathological and clinical variables, and to evaluate its significance as a predictor of disease outcome. KLK10 expression was evaluated by immunohistochemistry and a combined expression score was calculated for each case based on intensity and percentage of positivity. A statistically significant positive association was observed between KLK10 and tumor stage and liver metastases (p = 0.015 and p = 0.035, respectively). Paradoxically, a negative association was observed between KLK10 and tumor grade (p = 0.009). Kaplan-Meier survival curves and univariate analysis showed that both KLK10 expression and stage had statistically significant correlations with disease-free survival (DFS) (p = 0.030 and p < 0.001, respectively) and overall survival (p = 0.010 and p = 0.001, respectively). Cox multivariate analysis showed that both KLK10 expression and stage were independent predictors of unfavorable DFS (p = 0.057 and p = 0.001, respectively) and overall survival (p = 0.009 and p = 0.001, respectively). In conclusion, KLK10 immunostaining is an independent prognostic marker in patients with CRC.
Murray S.,GeneKOR |
Briasoulis E.,University of Ioannina |
Linardou H.,Metropolitan Hospital |
Bafaloukos D.,University of Ioannina |
Papadimitriou C.,National and Kapodistrian University of Athens
Cancer Treatment Reviews | Year: 2012
Background: Taxanes are established in the treatment of metastatic breast cancer (MBC) and early breast cancer (EBC) as potent chemotherapy agents. However, their therapeutic usefulness is limited by de-novo refractoriness or acquired resistance, which are common drawbacks to most anti-cancer cytotoxics. Considering that the taxanes will remain principle chemotherapeutic agents for the treatment of breast cancer, we reviewed known mechanisms of resistance in with an outlook of optimizing their clinical use. Methods: We searched the PubMed and MEDLINE databases for articles (from inception through to 9th January 2012; last search 10/01/2012) and journals known to publish information relevant to taxane chemotherapy. We imposed no language restrictions. Search terms included: cancer, breast cancer, response, resistance, taxane, paclitaxel, docetaxel, taxol. Due to the possibility of alternative mechanisms of resistance all combination chemotherapy treated data sets were removed from our overview. Results: Over-expression of the MDR-1 gene product Pgp was extensively studied in vitro in association with taxane resistance, but data are conflicting. Similarly, the target components microtubules, which are thought to mediate refractoriness through alterations of the expression pattern of tubulins or microtubule associated proteins and the expression of alternative tubulin isoforms, failed to confirm such associations. Little consensus has been generated for reported associations between taxane-sensitivity and mutated p53, or taxane-resistance and overexpression of Bcl-2, Bcl-xL or NFkB. In contrary sufficient in vitro data support an association of spindle assembly checkpoint (SAC) defects with resistance. Clinical data have been limited and inconsistent, which relate to the variety of methods used, lack of standardization of cut-offs for quantitation, differences in clinical endpoints measured and in methods of tissue collection preparation and storage, and study/patient heterogeneity. The most prominent finding is that pharmaceutical down-regulation of HER-2 appears to reverse the taxane resistance. Conclusions: Currently no valid practical biomarkers exist that can predict resistance to the taxanes in breast cancer supporting the principle of individualized cancer therapy. The incorporation of several biomarker analyses into prospectively designed studies in this setting are needed. © 2012 Elsevier Ltd.
Dimopoulos J.C.A.,Metropolitan Hospital |
Schmid M.P.,Medical University of Vienna |
Fidarova E.,Medical University of Vienna |
Berger D.,Medical University of Vienna |
And 2 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2012
Purpose: To investigate the clinical feasibility of magnetic resonance image-guided adaptive brachytherapy (IGABT) for patients with locally advanced vaginal cancer and to report treatment outcomes. Methods and Materials: Thirteen patients with vaginal cancer were treated with external beam radiotherapy (45-50.4 Gy) plus IGABT with or without chemotherapy. Distribution of International Federation of Gynecology and Obstetrics stages among patients were as follows: 4 patients had Stage II cancer, 5 patients had Stage III cancer, and 4 patients had Stage IV cancer. The concept of IGABT as developed for cervix cancer was transferred and adapted for vaginal cancer, with corresponding treatment planning and reporting. Doses were converted to the equivalent dose in 2 Gy, applying the linear quadratic model (α/β = 10 Gy for tumor; α/β = 3 for organs at risk). Endpoints studied were gross tumor volume (GTV), dose-volume parameters for high-risk clinical target volume (HRCTV), and organs at risk, local control (LC), adverse side effects, and survival. Results: The mean GTV (± 1 standard deviation) at diagnosis was 45.3 (±30) cm 3, and the mean GTV at brachytherapy was 10 (±14) cm 3. The mean D90 for the HRCTV was 86 (±13) Gy. The mean D2cc for bladder, urethra, rectum, and sigmoid colon were 80 (±20) Gy, 76 (±16) Gy, 70 (±9) Gy, and 60 (±9) Gy, respectively. After a median follow-up of 43 months (range, 19-87 months), one local recurrence and two distant metastases cases were observed. Actuarial LC and overall survival rates at 3 years were 92% and 85%. One patient with Stage IVA and 1 patient with Stage III disease experienced fistulas (one vesicovaginal, one rectovaginal), and 1 patient developed periurethral necrosis. Conclusions: The concept of IGABT, originally developed for treating cervix cancer, appears to be applicable to vaginal cancer treatment with only minor adaptations. Dose-volume parameters for HRCTV and organs at risk are in a comparable range. First clinical results indicate excellent LC. Further prospective multicenter studies are needed to establish this method and to confirm these results. © 2012 Elsevier Inc.
Panagopoulos A.,University of Patras |
Van Niekerk L.,Center for Sports Injury Surgery |
Triantafillopoulos I.,Metropolitan Hospital
Orthopedics | Year: 2012
Few studies have assessed the results of autologous chondrocyte implantation in patients with high-impact activities. The purpose of this study was to evaluate the early functional outcome and activity level after 2-stage autologous chondrocyte implantation in professional soldiers and athletes. Nineteen patients with an average age of 32.2 years were treated with autologous chondrocyte implantation and followed up for a minimum of 2 years. All patients except 2 had received previous arthroscopic treatment with debridement and/or microfracture. The mean size of the postdebridement defect was 6.54 cm 2. Using Novocart technology (B. Braun-Tetec, Reutlingen, Germany), periosteal patch and matrix-assisted autologous chondrocyte implantation was sequentially performed with no randomization. The average subjective knee evaluation score and Lysholm score improved from 39.16 and 42.42, respectively, preoperatively to 62.4 and 69.4, respectively, at latest follow-up. Median Tegner activity score was 8.8 before injury, 3.8 preoperatively, and 6.15 at latest follow-up. Second-look arthroscopy was performed in 11 patients due to persistent pain, decreased range of movement, and mechanical symptoms. Six of 19 (31.5%) patients with professional or recreational athletic activities returned to preinjury levels of athletic performance. This study shows that mid-term results with autologous chondrocyte implantation in high-performance patients are not as good as have been reported with other similar technologies. Motivational issues during prolonged rehabilitation, multiple surgical interventions before autologous chondrocyte implantation, patient age, and large defects can potentially influence the outcome and overall performance in this selected group of patients.
Gonzalez-Andrade F.,Metropolitan Hospital |
Lopez-Pulles R.,Central University of Ecuador
Public Health Genomics | Year: 2010
Ecuador has a heterogeneous population of almost 14 million people and a complex health care system provided through provincial and national health programs by government and private hospitals. There are public health facilities at regional and territorial level. Ecuador has a small cadre of genetic professionals that provide clinical genetic services in a few private medical centers in the main cities. Prenatal screening is offered exclusively in a few individual hospitals, with variable uptake as part of prenatal care. Surveillance of the effect of prenatal screening and diagnosis on the birth prevalence of congenital anomalies is limited by gaps and variations in surveillance systems. Newborn screening programs are almost inexistent. There is broad variation in optional participation in laboratory quality assurance schemes, and there are no regulatory frameworks that are directly pertinent to genetic testing services or population genetics. Health technology assessment in Ecuador is conducted by a diverse collection of organizations, several of which have produced reports related to genetics. Copyright © 2009 S. Karger AG.