Donertas, Ayla;Nayki, Umit;Nayki, Cenk;Ulug, Pasa;Gultekin, Emre;Yildirim, Yusuf
Asian Pacific Journal of Cancer Prevention
/
v.16
no.3
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pp.881-887
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2015
Purpose: To analyze treatment modalities and prognostic factors in patients with Stage I-II endometrial stromal sarcoma (ESS). Materials and Methods: Twenty four patients (nineteen with low-grade ESS [LGESS] and five with high-grade ESS [HGESS]) were assessed retrospectively in terms of general characteristics, prognostic factors, treatment methods and survival. Results: Twenty patients were at Stage I and three were at Stage II. The stage of one patient could not be determined. With respect to age and comorbidity, no statistically significant difference was found among disease-free survival (DFS) (p=0.990; p=0.995). However, DFS was significantly shorter in Stage II than Stage I patients (p=0.002). It was also significantly shorter in HGESS patients than in LGESS patients (p=0.000). There was no statistically significant differences among the overall survival (OVS) times of patients with respect to age at diagnosis and comorbid disease (p=0.905; p=0.979) but OVS was significantly shorter in patients with HGESS (p=0.00) and Stage II disease (p=0.001). No statistically significant difference was found with respect to OVS between patients who received radiotherapy (RT) and those who did not receive RT (p=0.055). It was not statistically possible to include other treatment modalities in the analysis because of the small sample size. Conclusions: Grade and stage of a tumour were found to be the most important prognostic factors. It was not possible to determine the optimal surgical method and the effect of adjuvant treatment since the number of cases was insufficient.
The image analysis is an important and predominant task for classifying the different parts of the image. The analysis of complex image analysis like histopathological define a crucial factor in oncology due to its ability to help pathologists for interpretation of images and therefore various feature extraction techniques have been evolved from time to time for such analysis. Although deep reinforcement learning is a new and emerging technique but very less effort has been made to compare the deep learning and deep reinforcement learning for image analysis. The paper highlights how both techniques differ in feature extraction from complex images and discusses the potential pros and cons. The use of Convolution Neural Network (CNN) in image segmentation, detection and diagnosis of tumour, feature extraction is important but there are several challenges that need to be overcome before Deep Learning can be applied to digital pathology. The one being is the availability of sufficient training examples for medical image datasets, feature extraction from whole area of the image, ground truth localized annotations, adversarial effects of input representations and extremely large size of the digital pathological slides (in gigabytes).Even though formulating Histopathological Image Analysis (HIA) as Multi Instance Learning (MIL) problem is a remarkable step where histopathological image is divided into high resolution patches to make predictions for the patch and then combining them for overall slide predictions but it suffers from loss of contextual and spatial information. In such cases the deep reinforcement learning techniques can be used to learn feature from the limited data without losing contextual and spatial information.
Background: Aberrant promoter hypermethylation has been recognized in human breast carcinogenesis as a frequent molecular alteration associated with the loss of expression of a number of key regulatory genes and may serve as a biomarker. The E-cadherin gene (CDH1), mapping at chromosome 16q22, is an intercellular adhesion molecule in epithelial cells, which plays an important role in establishing and maintaining intercellular connections. The aim of our study was to assess the methylation pattern of CDH1 and to correlate it with the expression of E-cadherin, clinicopathological parameters and hormone receptor status in breast cancer patients of Kashmir. Materials and Methods: Methylation specific PCR (MSP) was used to determine the methylation status of CDH1 in 128 invasive ductal carcinomas (IDCs) paired with the corresponding normal tissue samples. Immunohistochemistry was used to study the expression of E-cadherin, ER and PR. Results: CDH1 hypermethylation was detected in 57.8% of cases and 14.8% of normal adjacent controls. Reduced levels of E-cadherin protein were observed in 71.9% of our samples. Loss of E-cadherin expression was significantly associated with the CDH1 promoter region methylation (p<0.05, OR=3.48, CI: 1.55-7.79). Hypermethylation of CDH1 was significantly associated with age at diagnosis (p=0.030), tumor size (p=0.008), tumor grade (p=0.024) and rate of node positivity or metastasis (p=0.043). Conclusions: Our preliminary findings suggest that abnormal CDH1 methylation occurs in high frequencies in infiltrating breast cancers associated with a decrease in E-cadherin expression. We found significant differences in tumor-related CDH1 gene methylation patterns relevant to tumor grade, tumor size, nodal involvement and age at diagnosis of breast tumors, which could be extended in future to provide diagnostic and prognostic information.
A conversing beam is firstly designed for radiosurgery by a neurosugern Lars Leksell in 1949 with orthogonal x-rays tube moving through horizontal moving arc to focusing the beam at target center. After 2 decades he composits 201 source of the Co-60 for gamma knife which beams focused at locus. Sveral linac-based stereotactic radiosurgery using the circular collimated beam which size range for 0.4~4.0 cm in a diameter by non-coplanar multiarc have been developed over the decades. The irregular lesions can be treated by superimposing with several spherical shots of radiation over the tumour volume. Linac based techniques include the use of between 4 and 11 non-co-planar arcs and a dynamic rotation technique and use photon beam energies in the range of 6~10 MV. Reviews of the characteristics of several treatment techniques can be found in the literature (Podgorsak 1989, Schell 1991). More in recent, static conformal beams defined by custom shaped collimators or a mini- or micro-multileaf collimator (mMLC) have been used in SRS. Finally, in the last few years, intensity-modulated mMLC SRS has also been introduced. Today, many commercial and in-house SRS programs have also introduced non-invasive immobilization systems include the cyberknife and tomotherapy and proton beam. This document will be compared the characteristics of dose distribution of radiosurgery as introduced gamma knife, BrainLab include photon knife in-house SRS program and cyberknife in currently wide used for a cranial SRS.
Objectives: To explore the expression of astrocyte elevated gene-1 (AEG-1) in cervical cancer and analyze its correlation with microvascular density (MVD), nuclear factor kappaB (NF-kB p65) and vascular endothelial growth factor (VEGF). Materials and Methods: Immunohistochemical MaxVision method was adopted to detect the expression level of AEG-1, NF-kB p65 and VEGF in 45 samples of invading cervical cancer and 12 samples of cervicitis from The First Affiliated Hospital of Wenzhou Medical University. Tumor microvascular endothelial marker CD34 combined with Weidner was used to determine the MVD in cervical cancer tissue. The positive expression and staining conditions of AEG-1, NF-kB p65 and VEGF in cervical cancer tissues were observed under a light microscope. Correlations between expression of AEG-1 protein and those of NF-Kb p65 and VEGF, as well as MVD, were analyzed using Pearson correlation. Results: The expression levels of AEG-1 were $0.186{\pm}0.043$ in cervical cancer and $0.051{\pm}0.002$ in chronic cervicitis (p<0.01). Moreover, expression of AEG-1 was related to vascular invasion and lymphatic metastasis of cervical cancer (p<0.01), but not with age of the patients, differentiation degree, tumour size, pathological type and parametrial infiltration (p>0.05). Pearson correlation analysis showed that the expression of AEG-1 was linked with NF-kB p65 (r=0.501, p=0.000), VEGF (r=0.718, p=0.000) as well as MVD in cervical cancer tissue (r=0.815, p=0.000). Conclusions: AEG-1 is highly expressed in cervical cancer and promotes angiogenesis, which might be related to the fact that AEG-1 activating the signal pathway of NF-kB could up-regulate the level of VEGF expression.
The effects of erlotinib combined with celecoxib in a lung cancer xenograft model were here explored with a focus on possible mechanisms. A xenotransplanted lung cancer model was established in nude mice using the human lung cancer cell A549 cell line and animals demonstrating tumour growth were randomly divided into four groups: control, erlotinib, celecoxib and combined (erotinib and celecoxib). The tumor major axis and short diameter were measured twice a week and after 40 days tissues were collected for immunohistochemical analyses of Bcl-2 and Bax positive cells and Western-blotting analyses for the epidermal growth factor recepto (EGFR), P-EGFR, and cyclooxygenase-2 (COX-2). Tumor size in the combined group was smaller than in the others (p<0.01) and the percentage of Bcl-2 positive cells was fewer in most cases (p<0.01), while that of Bax positive cells was greater than in the erlotinib and celecoxib groups (P>0.05). Western blotting showed decreased expression of P-EGFR and COX-2 with both erlotinib and celecoxib treatments, but most pronouncedly in the combined group (P<0.05). Simultaneous blockage of the EGFR and COX-2 signal pathways exerted stronger growth effects in our human xenotransplanted lung cancer model than inhibition of either pathway alone. The anti-tumor effects were accompanied by synergetic inhibition of tumor cell apoptosis, activation of p-EGFR and expression of COX-2.
Background: Breast cancer prognosis is influenced by several histopathology and clinical factors including expression of Ki67 which may have a predictive role in lymph node negative breast cancer patients. The aim of this study was to assess Ki67 expression in breast cancers without axillary lymph node involvement and to evaluate its prognostic value with regard to disease-free survival. Materials and Methods: Subjects were selected from non-metastatic invasive breast cancer patients who were referred to the oncology department of Ghaem hospital during 1 April 2001 to 1 April 2008. Ki67 levels were measured using immunohistochemistry (IHC) and compared with clinicopathological features. The relation of Ki67 expression with disease-free survival was also analysed. Results: A total of 106 women with a mean age of 49 were examined. Some 94.3% were classified as having invasive ductal carcinomas and the mean tumour diameter at the time of diagnosis was 2.8 cm. Some 50.9% of cases were ER positive and 47.2% were PR positive. P53 expression was positive in 48.1% of the cases. According to the IHC results, only 8.5% of the patients were Her2/neu positive. Ki67 was positive in 66 (62.3%) with a significant relation to lower age (p=0.0229) and P53 positivity (p=0.005). After an average of 40-months follow up, 13 (12.3%) demonstrated recurrence, most commonly systemic. Of 13 cases with relapse, 10 patients (77%) were Ki67 positive. Conclusions: In our population Ki67 appeared to be an independent prognostic factor for three-year survival. However, we stress that a survival study with a bigger sample size would help to support this conclusion.
Background: Adverse effects of treatment prolongation beyond 8 weeks with radiotherapy for cervical cancer have been established. Clinical data also show that cisplatin increases the biologically effective dose of radiotherapy. However, there are no data on the effect of overall treatment time in patients with locally advanced cervical cancer treated with concomitant chemo-radiotherapy (CCRT) in an Indian population. The present study concerned the feasibility of concurrent chemotherapy and interspacing brachytherapy during the course of external radiotherapy to reduce the overall treatment time and compare the normal tissue toxicity and loco-regional control with a conventional schedule. Materials and Methods: Between January 2009 and March 2012 fifty patients registered in the Gynaecologic Oncology Clinic of Institute Rotary Cancer Hospital with locally advanced cervical cancer (FIGO stage IIB-IIIB) were enrolled. The patients were randomly allocated to treatment arms based on a computer generated random number. Arm I (n=25) treatment consisted of irradiation of the whole pelvis to a dose of 50 Gy in 27 fractions, and weekly cisplatin $40mg/m^2$. High dose rate intra-cavitary brachytherapy (HDR-ICBT) was performed after one week of completion of external beam radiotherapy (EBRT). The prescribed dose for each session was 7Gy to point A for three insertions at one week intervals. Arm II (n=25) treatment consisted of irradiation of the whole pelvis to a dose of 50 Gy in 27 fractions. Mention HDR-ICBT ICRT was performed after 40Gy and 7Gy was delivered to point A for three insertions (days 23, 30, 37) at one week intervals. Cisplatin $20mg/m^2/day$ was administered from D1-5 and D24-28. Overall treatment time was taken from first day of EBRT to last day of HDR brachytherapy. The overall loco-regional response rate (ORR) was determined at 3 and 6 months. Results: A total of 46 patients completed the planned treatment. The overall treatment times in arm I and arm II were $65{\pm}12$ and $48{\pm}4$ days, respectively (p=0.001). At three and six months of follow-up the ORR for arm I was 96% while that for arm II was 88%. No statistically significant difference was apparent between the two arms. The overall rate of grade ${\geq}3$ toxicity was numerically higher in arm I (n=7) than in arm II (n=4) though statistical significance was not reached. None of the predefined prognostic factors like age, performance status, baseline haemoglobin level, tumour size, lymph node involvement, stage or histopathological subtype showed any impact on outcome. Conclusions: In the setting of concurrent chemoradiotherapy a shorter treatment schedule of 48 days may be feasible by interspacing brachytherapy during external irradiation. The response rates and toxicities were comparable.
Background: To evaluate the pathological characteristics of invasive margins in early-stage cervical squamous cell carcinomas and their association with other clinicopathological features including clinical outcomes. Materials and Methods: Patients with FIGO stage IB-IIA cervical squamous cell carcinomas who received surgical treatment and had available follow-up information were identified. Their histological slides were reviewed for prognostic variables including tumor size, grade, extent of invasion, lymphovascular invasion, involvement of vaginal margin or parametrium, and lymph node metastasis. The characteristics of invasive margins including invasive pattern (closed, finger-like, or spray-like type), degree of stromal desmoplasia, and degree of peritumoral inflammatory reaction were evaluated along the entire invasive fronts of tumours. Associations between the characteristics of invasive margins and other clinicopathological variables and disease-free survival were assessed. Results: A total of 190 patients were included in the study with a median follow-up duration of 73 months. Tumour recurrence was observed in 18 patients (9%). Spray-like invasive pattern was significantly more associated as compared with closed or finger-like invasive pattern (p=0.005), whereas the degree of stromal desmoplasia or peritumoral inflammatory reaction was not. Low degree of peritumoral inflammatory reaction appeared linked with lymph node metastasis (p=0.021). In multivariate analysis, a spray-like invasive pattern was independently associated with marked stromal desmoplasia (p=0.013), whilst marked desmoplasia was also independently associated with low inflammatory reactions (p=0.009). Furthermore, low inflammatory reactions were independently associated with positive margins (p=0.022) and lymphovascular invasion (p=0.034). The patients with spray-like invasive pattern had a significantly lower disease-free survival compared with those with closed or finger-like pattern (p=0.004). Conclusions: There is a complex interaction between cancer tissue at the invasive margin and changes in surrounding stroma. A spray-like invasive pattern has a prognostic value in patients with early-stage cervical squamous cell carcinoma.
Background: The impairment of the appearance is a major problem for patients with carcinomas of the oral cavity. These patients want to recover their preoperative facial appearance. Some do not realize that this is not always possible and hence develop a desire for further cosmetic and reconstructive surgery (CRS) which often causes psychological problems. Method: The desire of patients for CRS (N = 410; 26%) has been acquired in this $D{\ddot{O}}SAK$ rehab study including multiple reasons such as medical, functional, aesthetic and psychosocial aspects. They relate to the parameters of diagnosis, treatment and postoperative rehabilitation. Patients without the wish for CRS (N = 1155; 74%) served as control group. For the surgeons, knowledge of the patient's views is relevant in the wish for CRS. Nevertheless, it has hardly been investigated for patients postoperatively to complete resection of oral cancer. In this retrospective cross-sectional study, questionnaires with 147 variables were completed during control appointments. Thirty-eight departments of Oral and Maxillofacial Surgery took part, and 1652 German patients at least 6 months after complete cancer resection answered the questions. Additionally, a physician's questionnaire (N = 1489) was available. Statistical analysis was performed with SPSS vers. 22. Results: The patient's assessment of their appearance and scarring are the most important criteria resulting in wishes for CRS. Furthermore, functional limitations such as eating/swallowing, pain of the facial muscles, numb regions in the operating field, dealing with the social environment, return to work, tumour size and location, removal and reconstruction are closely related. Conclusion: The wish for CRS depends on diverse functional psychosocial and psychological parameters. Hence, it has to be issued during conversation to improve rehabilitation. A decision on the medical treatment can be of greater satisfaction if the surgeon knows the patients' needs and is able to compare them with the medical capabilities. The informed consent between doctor and patient in regard to these findings is necessary.
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