chemotherapy or endocrine therapy alone is inadequate . Although exact cutoffs for ki67 and PR were not de- fined in St. Gallen International Expert Consensus, how- ever, some proposals were given, stating that a cutoff value of < 14% ki67 can be used to define luminal cancers in the absence of HER2neu expression based on single ref- erence laboratory . On the other hand, Prat et al. expressed that a cutoff value of > 20% can be adapted to ascertain luminal A cancers. These proposals were derived from the results of five cohorts, which were combined and interpreted by experts . It is also well established that enormous heterogeneity exists in genetic and morpho- logical characteristics of breast tumors. On account of this heterogeneity, therapeutic regimens must be tailored to the loco-regional breast cancer profiles. Studies have dem- onstrated a different behavior of breast cancer in Pakistan with higher prevalence in a younger age group with ag- gressive nature and poor survival rates [8–10]. There- fore, we aimed to determine prognostic parameters of luminal breast cancers in our population which can help in devising targeted and personalized therapeutic regimens tailored to the needs of the loco-regional population.
R etinoblastoma, a highly malignant tumor of the primitive neural retina, is the most common intraocular tumor of childhood. It occurs in 1 of 18,000 –30,000 live births world- wide. The average age at diagnosis is 18 months, and 80% of cases occur during the first 3– 4 years of life. The most com- mon clinical sign of retinoblastoma is leukokoria (60%), fol- lowed by strabismus (20%). 1-5 Identified pathologic and clin- ical prognostic parameters of retinoblastoma include degree of histologic differentiation, tumor size, laterality, invasion of the choroid, and extension into the optic nerve. 6-9 If the optic
index, S-phase fraction determined by flow cytometry and immunohistochemistry (IHC). Overall, proliferative index determined by IHC correlates well with S phase fraction measured by flow cytometry . Although, there is still no consensus over an optimal cutoff value used to decide chemotherapy, but several studies found that high ki67 index is associated with higher rate of relapse and worse breast cancer survival [3, 4]. It is widely accepted that cancer management should be according to loco- regional profile and therapeutic protocols should be devised accordingly, however no large-scale cancer reg- istry is available in this part of the world. Moreover ki67 may serve as a useful marker in tailoring treatment regi- men as response to chemotherapy may be altered by the proliferative activity of cancer cells . Therefore we aimed to determine the ki67 in newly defined intrinsic breast cancer subtypes and its association with other prognostic parameters in our set up.
Abstract: Previous studies on the prognostic value of osteopontin (OPN) and β-catenin in colorectal carcinoma (CRC) revealed conflicting results. To date, only two immunohistochemical studies investigated their association in CRC with discrepant results. Moreover, the relevance of their co-expression to clinicopathological parameters was not previously reported. This study was designed to investigate the relationship between these markers and prognostic parameters in CRC and study further the relationship between them. Immunohistochemical expression of OPN and β-catenin was evaluated in 72 CRCs. Cytoplasmic OPN was detected in 45.83% of CRCs while normal mucosa was immunonegative. Strong continuous membranous β-catenin was present in normal mucosa. However, abnormal membranous, nuclear and cytoplasmic expressions were observed in 36.11%, 31.94% and 52.78% of CRCs, re- spectively. A highly significant relationship was detected between each of OPN and nuclear β-catenin expression and lymph node metastasis (P = 0.0001 and 0.004 respectively), depth of invasion (P = 0.001 and 0.004 respectively), TNM stages (P = 0.0001 and 0.001 respectively) and Dukes’ stages (P = 0.0001 and 0.004 respectively). A signifi- cant association was found between OPN and distant metastases. A strong agreement was observed between OPN and nuclear β-catenin (kappa = 0.656). A highly significant relationship was found between their co-expression and poor prognostic parameters. OPN overexpression and nuclear β-catenin expression appeared to be associated with unfavorable prognostic factors in CRC. A direct relationship was observed between them. Further understanding their role in colorectal carcinogenesis as well as targeting the interaction between them might be effective in the future development of therapeutic agents for CRC patients.
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Abstract: Background: Carcinogenesis is associated with several critical regulatory molecules which are involved in different signaling pathways such as the WNT signaling pathways. Among which the β-catenin dependent pathway has been associated with human endometrial cancer. Genetic and biochemical studies have demonstrated that glypicans can regulate several signaling pathways including those triggered by Wnts. Glypican 3 is one of six mam- malian members of the glypican family of proteoglycans. Overexpression of glypican 3 has been reported in some types of cancers but only few data are available about its expression in endometrial carcinoma and its role in endo- metrial carcinogenesis. The aim of this study was to examine the immunohistochemical expression of glypican 3 in endometrioid endometrial carcinoma (EEC) and serous endometrial carcinoma (SEC), and to correlate its expres- sion with prognostic factors of endometrial carcinoma. Materials and methods: Immunohistochemical expression of glypican 3 was studied in fifty two EEC and nineteen SEC cases. Results: Glypican 3 expression showed a significant difference between EEC and SEC (P = 0.027) and it was significantly correlated with tumor grade, stage and myo- metrial invasion (P = 0.001). Conclusion: Glypican 3 expression can be used as an adjunct in the differentiation between EEC and SEC. Glypican 3 is associated with poor prognostic parameters in both EEC and SEC, and it can be a promising molecule for targeted immunotherapy in positive cases.
immunolabelling of cyclin D1 depend on prognostic parameters such as age, sex and tumor size which the cyclin D1 expression were included in the univariate analysis to determinethe thyroid cancer univariate analysis using test, chi square, crosses tab and frequencies to determine the influence of the cyclin D1 in different prognostic parameters.
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Included studies were divided into three groups for ana- lysis: OS, DFS, and clinicopathological parameters. S100A4 was considered as having a ‘high’ or ‘low’ expression ac- cording to the cut-off values provided by the authors in each publication, because of variation on the definition for the ‘high’ or ‘low’ expression of S100A4 between studies. Hazard ratios (HRs) and their 95% CIs were combined to measure the effective value. If HRs and corresponding 95% CIs were not available, they were calculated from available numerical data using methods reported by Parmar et al. . Data from the Kaplan-Meier survival curves were read using Engauge Digitizer version 4.1. Three independ- ent persons read the curves to reduce reading variability. For the pooled analysis of the relation between S100A4 overexpression and clinicopathological parameters, ORs and their 95% CIs were combined to give the effective value. The impact of S100A4 on prognosis was considered statistically significant if the 95% CI for the overall HR did not overlap 1.
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Cluster of differentiation 147 (CD147), also known as extracellular matrix metalloproteinase inducer (EMMPRIN) or basigin, encoded by the BSG gene, is a transmembrane glycoprotein, which is involved in various physiological as well as pathophysiological processes. In many solid tumors CD147 is overexpressed and associated with tumor progression, invasion and metastasis . The oncogenic potential is attributed in parts to its well-known function to induce matrix metalloproteinases (MMPs) by tumor cells and mainly by neighboring stromal fibroblasts [2, 3]. In addition, CD147 has been shown to increase the production of vascular endothelial growth factor (VEGF), thereby promoting tumor angiogenesis [4, 5]. Furthermore, CD147 represents the obligatory binding partner for several proteins involved in carcinogenesis, e.g., the monocarboxylate transporters (MCT) 1 and MCT4 (encoded by SLC16A1 and SLC16A3, respectively) , which mediate the export of lactate from highly glycolytic tumor cells. Inhibition of MCT1 and MCT4, thereby interfering with the glycolytic metabolism of tumor cells, is an attractive approach in cancer therapy. In clear cell renal cell carcinoma (ccRCC), which is characterized by a glycolytic Warburg phenotype, MCT4 has not only been shown to be a metabolic target to reverse the Warburg effect , as shown by Gerlinger et al in a genome-wide siRNA screening study in RCC cell lines, but is also proposed to be a prognostic marker for patient outcome. In a recent study, we could show that MCT4 expression is regulated by DNA methylation in the SLC16A3 promoter and that DNA methylation status at single cytosine phosphate guanine (CpG) sites is predictive for patient survival . Due to its tumorigenic properties, CD147 also represents a promising target for therapeutic intervention [9, 10] and it is suggested that CD147 expression alone or together with other factors such as VEGF expression, could also serve as a marker for prognosis and outcome in ccRCC [11-13].
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RDW is a quantitative measure of anisocytosis, the variability in size of the circulating erythrocytes. In the past RDW usually had been used for the differential diagnosis of iron-deficiency anemia and acute appendicitis (Karagoz et al., 2013; Miyamoto et al., 2015). In recent years, RDW has been demonstrated to predict mortality and other outcome in septic and septic shock in aged adults. In our study, the mean red cell distribution width on the day of presenting the illness was significantly higher in non survivors than survivors. Those patients who had a high red cell distribution width during admission were associated with poor survival. These patients also developed associated complications like acute kidney injury, coagulopathy, and encephalopathy. Red cell distribution width was highest among patients with septic shock followed by severe sepsis and with sepsis (Mean 18.06; 16.73; 15.92).These parameters showed strong statistically significant
initial increase and subsequent overall decrease of K trans of enhancing tumors were observed in nonresponders during CCRT in glioblastoma. 28 The study by these researchers also did not find prognostic value by multivariate Cox regression analysis, except for interval change of K trans between the pre- and midtreatment scanning during CCRT. A possible explana- tion of our finding is that the subsequent change in DCE pa- rameters after CCRT could reduce differences between better and worse PFS groups. In addition, some areas of nonenhancing T2 high-signal-intensity lesions were removed by an operation, and the nature of nonenhancing T2 high-signal-intensity lesions might not be the same between baseline and posttreatment examinations.
In conclusion, this study indicates the prognostic role of Ki-67 LI in different age groups of patients with TNBC. In the young, high Ki-67 LI is a good independent prognostic factor for BCSS, and these patients may benefit from chemotherapy with agents that engage DNA damage signaling response pathways. While in older populations, low Ki-67 LI may predict a positive result. In the future, more studies are needed to determine whether prognostic factors, useful biomarkers and/or more complex molecular signatures will contribute to the development of innovative classifications that reflect the clinical behavior of each TNBC subtype and consequently guide treatment choices.
To evaluate the changes of tumor parameters with time during treatment and follow-up, we constructed 2 separate mixed-effects models for all time points before the end of RT (baseline and during RT) and after RT. The combined average fit of these 2 models is illustrated in Fig 2 by the dashed red lines. Details of the models are presented in On-line Table 2. Our model suggested a quadratic behavior (P ⬍ .0001) for tumor ASL-CBF during RT: it first decreased and then increased during RT, followed by a grad- ual linear decline after RT (P ⫽ .0002). Tumor volume, on the contrary, showed an opposite trend: it had a nonlinear decline during RT (P ⫽ .0001) and then a gradual nonlinear increase after RT (P ⫽ .0002). Both CBF and CBV linearly increased during RT (P ⫽ .0003 and P ⫽ .0001, respectively), followed by a gradual linear decrease (P ⫽ .0015 and P ⫽ .0035, respectively) after RT. A cross-sectional Spearman rank correlation analysis between tu- mor perfusion and tumor volume showed no convincing overall association of tumor perfusion with tumor volume, except for a suggestive positive correlation between CBF and tumor volume at the end of RT (On-line Table 3).
Abstract: Background: Studies have shown that myocardial injury and hemodynamic instability are common signs of sepsis and can influence patients’ prognosis. We aim to evaluate the prognostic role of the myocardial injury marker hs-TnI and the hemodynamic parameters in patients with sepsis during their hospitalization. Methods: In this study, patients with sepsis were allocated into a survival group and a death group based on their hospitalization outcomes. Laboratory parameters including infection, inflammation and myocardial injury markers were collected on admission. The hemodynamic parameters were measured by pulse indicator continuous cardiac output (PICCO). The SOFA and qSOFA scores were calculated based on the standard forms. Results: The Hs-TnI, NT-proBNP, and PCT levels were significantly higher in the death group than they were in the survival group (all P < 0.05). As to the hemo- dynamic parameters, there was a significant difference in multiple parameters between the two groups (P < 0.05). In addition, hs-CRP was positively correlated with the SOFA (r = 0.523) and qSOFA (0.547) scores (both P < 0.01). A further multivariate logistic regression analysis demonstrated that hs-TnI (OR = 3.455, 95% CI: 3.207-3.918, P < 0.01), PCT (OR = 1.736, 95% CI: 1.096-2.073, P = 0.044), the cardiac index (OR = 2.840, 95% CI: 2.336-4.096, P = 0.018), and the qSOFA scores (OR = 2.331, 95% CI: 2.175-2.627, P = 0.021) but not the SOFA scores were independent predictors of sepsis mortality. Conclusion: Increased hs-TnI and hemodynamic instability could be very useful predictors of the mortality of sepsis patients. More large, prospective studies with a long-term follow-up are warranted to confirm the long-term prognostic roles of hs-TnI and the hemodynamic parameters in sepsis.
This study has some limitations. First, this is a retrospective study with a limited number of patients, particularly those with DW-MRI measurement. Second, the follow-up duration was relatively short. Third, our study population was heterogeneous, with patients having different clinical FIGO stages and undergoing different treatment modalities. However, we evaluated the potential of pretreatment prognostic biomarkers, which are by definition independent of any treatment received. Finally, the fact that the MRI protocols and particularly the DW-MRI were not standardized in our study may have limited the evaluation of DW-MRI; however reflecting a routine setting not inter- fering with the diagnostic work-up in cervical cancer.
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Higher histological grade was associated with higher SWV (P = 0.001) and SWV ratio values (P = 0.007) (Tables 2, 3; Figures 2-4). In univari- ate analysis, large invasive size (P < 0.001), lymph node involvement (P < 0.001) and C-erbB-2 expression (P = 0.029) were statisti- cally associated with high SWV. Large invasive size (P < 0.001) and lymph node involvement (P = 0.001) all showed significantly association with high SWV ratio (Table 3). There were no correlation between SWV or SWV ratio and cer- tain clinicopathologic prognostic factors in invasive ductal cancers, including age, ER expression, and PR expression (P > 0.05), and the same result was found between SWV ratio and C-erbB-2 expression (Tables 2, 3). Multiple linear regression indicated that invasive size was the strongest pathologic determinant of SWV and its ratio (P < 0.001), while histological grade (P = 0.018) for SWV and lymph nodal metastasis (P = 0.031) for SWV ratio also had specific influence, respectively (Tables 4, 5). Table 2. Relationships between mean SWV and clinicopathologic features of 143 invasive ductal cancers
is large, but the number of patients in many centers is small. This many-strata (sparse data) situation occurs for example when enrollment of large number of patients is not possible at each individual center. Furthermore, the sparse situation will become more serious in the data analysis when adjustment for other prognostic factors is necessary. Under the many-strata (sparse data) situation, since the total sample size increases with the number of nuisance parameters (here due to center eects and prognostic factors), the standard generalized estimating equations (GEE) approach and the standard likelihood method for correlated categorical data will fail; see Liang and Zeger (1995) for further explanation. Similarly the general weighted least squares (WLS) method (Koch, et al., 1977) for analysis of correlated categorical data will be invalid in the many-strata (sparse data) situation.
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Materials and methods: Among 738 cervical cancer patients with International Federation of Gynecology and Obstetrics (FIGO) stages IA–IV treated at our institution, 96 (13%) presented with CA histology. The blood samples, collected within 10 days before treatment, were ana- lyzed using a Sysmex XN-2000 system. The statistical tests included Mann–Whitney U-tests, log-rank tests, and Cox regression models. The cutoff points for the calculated hematological coefficients (NLR, PLR, and MLR) were determined using the MedCalc statistical program. Results: The prognostic factor for overall survival (OS) and recurrence-free survival (RFS) in CA was clinical stage according to FIGO classification (FIGO IIB–IV vs I–IIA) (P=0.0001; P= 0.002). Among patients with FIGO stage IIB–IV treated with radiotherapy/chemoradio- therapy, an elevated PLR was a negative prognostic factor for OS (P=0.017; HR: 2.96; 95% CI: 2.069–3.853). Among all patients, an elevated pretreatment NLR was a poor prognostic factor for OS (P=0.014; HR: 2.85; 95% CI: 2.011–3.685) and RFS (P=0.049; HR: 4.0; 95% CI: 2.612–5.392). The white blood cell count (WBC) before treatment was significantly higher in patients who died during follow-up (P=0.009).
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This is to certify that this dissertation titled “PROGNOSTIC VALUE OF ULTRASONOGRAPHY IN DENGUE FEVER, COMPARED WITH CLINICAL AND LABORATORY PARAMETERS” of the candidate Dr.KIRAN TRESA KURUVILLA with registration number 201611109 for the award of M.D degree in the branch of GENERAL MEDICINE. I personally verified the urkund.com website for the purpose of plagiarism check. I found that the uploaded thesis file contains from introduction to conclusion pages and result shows 24 percentage of plagiarism in the dissertation.
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Th e aim of the study was to investigate the relationship between the expression of the HER- membrane protein and other clinical-pathological parameters such as: histological size of the tumor, degree of the tumor’s diﬀ erentiation, presence of vascular invasion and pres- ence of metastases in regional lymph nodes, in cases of ductal inﬁ ltrative breast cancer. We have investigated cases of ductal inﬁ ltrative breast cancer. In all patients a mastectomy with a dissection of axillary lymph nodes has been performed. All tissue samples, taken by biopsy, were embedded in the paraffin, stained by hematoxylin-eosin technique and screened, and evaluation was performed by using a semiquantitative method of the im- munohistochemical expression of the HER- protein. A decrease of the protein HER- expression was noticed in cases of an increase of the tumor’s diameter above mm. In- creased expression of the HER- protein was noticed in cases of moderate (grade II) and poor (grade III) diﬀ erentiation of carcinoma, as well as in cases where there was no me- tastases in the regional lymph nodes. No relationship has been observed between the expression of HER- and occurrence of vascular invasion. In cases of ductal inﬁ ltrative breast cancer the expression of HER- protein is in correlation with the size and degree of tumor’s diﬀ erentiation, as well as with the presence of metastases in regional lymph nodes.
IgM deposition associated with IgA was report- ed to be higher in patients with IgAN and cres- cents compared to those with general IgAN . Additionally, the presence of IgG has been associated with histological and clinical mark- ers of unfavorable prognosis [27, 28]. In our cohort, however, the same intensity of IgM and IgG was observed across the three groups. The presence of glomerular capillary wall IgA depos- its was reported to associate with greater pro- teinuria and histological severity [27, 29, 30], including more frequent crescent formation [27, 31]. IgA deposits along the capillary wall have been observed in 42% of crescentic, ANCA-negative IgAN patients, in contrast to their absence in all ANCA-positive patients . This finding is consistent with our results, where IgA deposits in peripheral capillary loops were found in 53.8% of patients with ≥ 50% crescent involvement. Therefore, to better characterize the different prognostic factors, it is recom- mended that the location and intensity of immunoglobulins and complement immunos- taining be routinely included in the renal biopsy report.