Inoperable and metastatic hepatocellular carcinoma (HCC) is associated with a poor prognosis and low chemotherapeutic efficiency. Sorafenib is an oral multi-kinase inhibitor exerting its effects via ...the RAF/ MEK/ERK pathway, vascular endothelial growth factor receptor (VEGFR) and platelet derived growth factor receptor beta (PDGFR-β) tyrosine kinases. Randomized studies have shown a significant contribution of sorafenib to life expectancy and quality of life of cancer patients. The aim of the present study is to evaluate the efficacy and side effects of sorafenib therapy in Turkey.
Data for 103 patients (82 males, 21 females) receiving sorafenib therapy in 13 centers from February 2008 to December 2012 were evaluated. Median age was 61 years and median ECOG performance status was 1 (range: 0-2). 60 patients (58%) had hepatitis B, 15 patients (15%) had hepatitis C infection and 12 patients (12%) had a history of alcohol consumption. All of the patients had Child scores meeting the utilization permit of the drug in our country (Child A).
A total of 571 cycles of sorafenib therapy were administered with a median of four per patient. Among the evaluable cases, there was partial response in 15 (15%), stable disease in 52 (50%), and progressive disease in 36 (35%). Median progression-free survival was 18 weeks and median overall survival was 48 weeks. The dose was reduced only in 6 patients and discontinued in 2 patients due to grade 3-4 toxicity, 18 patients (17%) suffering hand-foot syndrome, 7 (7%) diarrhea, and 2 (2%) vomiting.
This retrospective study demonstrated better efficacy of sorafenib therapy in patients with advanced HCC compared to the literature while progression-free survival and overall survival findings were comparable. The side effect rates indicate that the drug was tolerated well. In conclusion, among the available treatment options, sorafenib is an efficient and tolerable agent in patients with inoperable or metastatic HCC.
Pancreatic neuroendocrine tumors (pNETs) are rare and heterogenous tumors and surgery to remove the primary tumor is the mainstay of treatment for resectable disease. However, curative surgery is ...often not feasible, because half of patients with pNET have metastases at the time of diagnosis. Palliative dubulking surgery and liver-directed therapies are appropriate options for these patients. Streptozocin-based regimens are standard, although temozolamide-based treatments are rapidly gaining wide clinical application. Somatostatin analogs are mainly indicated in hormonally active tumors to ameliorate symptoms. In addition, anti-tumoral activity has been proven in well-differentiated NETs. Recently, there has been tremendous progress in the molecular biology of pNETs; thereby, the efficacy of sunitinib and everolimus in the treatment of patients with metastatic pNETs has been proven by large placebo-controlled phase III trials. Currently, there are no definitively proven predictive biomarkers to evaluate response to medical therapies in patients with pNET. Therefore, further studies are needed to individualize and optimize their management. This article reviews systemic chemotherapy, targeted therapies, and anti-secretory treatments for the management of patients with unresectable or metastatic pNETs, summarized in the light of recent advances.
After the Fukushima Dai-Ichi Nuclear Power Plant (FDNPP) accident, .sup.134Cs and .sup.137Cs were spread widely into the environment. Spatial distribution maps giving radiocesium activities in ...contaminated soils for post-accident risk modeling were obtained using the Kriging method. We used Generalized extreme-value distribution, Lognormal probability distribution (PDF) and Weibull PDFs for risk assessment of the data. Root mean square error values and coefficient of determination (R.sup.2) were calculated for each distribution function. Weibull PDF was found to be more successful in modeling .sup.134Cs and .sup.137Cs activities. Graphic abstract
Purpose
We aim to compare FDG-PET/CT and cross-sectional imaging (contrastenhanced CT/MRI) diagnostic abilities in detecting recurrence/progression of pancreaticobiliary system tumors and to reveal ...the clinical impact of integrated FDGPET/CT to CT/MRI on patient management.
Materials and Methods
FDG-PET/CT and CT/MRI scans of 70 patients from initiation of treatment until proven recurrence/progression were retrospectively evaluated. FDGPET/CT and contrast-enhanced CT/MRI accuracy, sensitivity, specificity, PPV and NPV are compared in terms of overall recurrence/progression diagnosis and sitespecific concern; local disease, local lymph node, and distant organ metastasis. The impact of integrated FDG-PET/CT on patient management is scrutinized.
Results
CT/MRI has higher sensitivity than FDG-PET/CT in detecting loco-regional involvement (90% vs 76.7%
P
: 0.152), local lymph node metastasis (88.9% vs 77.8%,
P
: 0.380) and distant organ metastasis (96.5% vs 80.7%;
P
: 0.006) in tumor recurrence/progression. In overall diagnosis, CT/MRI is more sensitive and accurate but less specific than FDG-PET/CT (92.3% vs 87.7%; 87.1% vs 84.2%; 40% vs 20%, respectively). In 8% (6/70) of patients FDG-PET/CT had a major impact on patient management.
Conclusion
FDG-PET/CT and cross-sectional imaging have different advantages and shortcomings. In recurrence/progression, recognition of early changes is more feasible by CT/MRI. However, inconsistency of morphologic and metabolic findings is important reason of cross-sectional imaging failure. FDG-PET/CT is superior in showing extraabdominal metastases, but missing small-volume lesions and misinterpreting inflammatory changes are still a problem lowering its sensitivity. Nevertheless FDGPET/CT is good option for guiding undetermined imaging findings or clinic-radiologic mismatch.
The positions distribution of the regional variables in space have irregular or sometimes random scatter. In such a case, their study can be rather difficult and sometimes impossible by means of ...differential equations. Although variogram or semi-variogram (SV) methodology in the literature is employed to model the regional variable, in this paper, the use of the point cumulative SV (PCSV) procedure application is suggested for the
137
Cs data, which is one of the most important radioactive nuclei not only for radioactive contamination of the environment after the Fukushima Dai-Ichi Nuclear Power Plant, but any nuclear accident whatsoever. As a result of the PCSV models, the categorical description of the
137
Cs concentrations spatial distribution and transport characteristics are determined and interpreted. Prior to the application of the model, log-transformation is performed to fit the
137
Cs data to the classical normal probability distribution and the normality of data is tested by Kolmogorov–Smirnov test. According to the PCSV models, five different categories describe whole spatial distribution and transport properties of
137
Cs concentrations and also iso-radioactivity map is obtained for
137
Cs.
The aim of this study was to demonstrate an assessment of left internal mammary artery (LIMA) patency and anatomy by standard left ventriculography, and to define a proposal for predicting LIMA ...function according to left ventriculography outcome. A total of 335 patients with an indication of coronary angiography were included. Standard coronary angiography and left ventriculography were performed initially. Visualization of LIMA occurred in the late phase of ventriculography and the LIMA visualization frame rate was counted for each patient. Then selective LIMA angiography was performed and LIMA diameter, LIMA course and anatomy, and subclavian artery anatomy were noted. Finally, the results of left ventriculography and LIMA angiography were compared by statistical analysis. During left ventriculography, LIMA was visualized in 96.4% of the patients. The mean LIMA visualization frame rate was 53.8 ± 17.7 and the mean LIMA diameter was 2.60 ± 0.36 mm. There was a strong correlation between LIMA visualization frame rate and LIMA diameter, LIMA course, and also asymptomatic subclavian artery disease (P < 0.001). Regression analysis showed that LIMA visualization frame rate is the major independent determinant for LIMA diameter prediction (P < 0.001); LIMA diameter, LIMA course, proximal LIMA side branch, and subclavian artery disease are the major predictors of LIMA visualization on left ventriculography (P < 0.001). LIMA patency and anatomy can be evaluated accurately with a simple method using left ventriculography. Besides direct visualization of LIMA, the visualization frame rate may constitute a reliable parameter for assessing LIMA function. A LIMA visualization frame rate of less than 50 is associated with a healthy and well-sized LIMA.PUBLICATION ABSTRACT
Aim: The purpose of this study was to determine the effects of initial symptoms on the prognosis in patients with stomach cancer. Methods: The study was carried out first retrospectively reviewing ...the records of patients with stomach cancer treated and followed up in Hamidiye Şişli Etfal Training and Research Hospital Medical Oncology Clinic. Patients with stomach cancer admitted to our clinic from 2005 to 2014, followed up routinely, and with known final statuses were included in the present study. Initial symptoms of the patients were recorded, and the main symptom was identified in patients with multiple symptoms. Furthermore, demographic, clinical and pathological features of the patients were recorded, and survival analyses were performed based on the symptoms. Results: One hundred twenty nine stomach cancer cases were evaluated in the study. The median age was found to be 64 years. 69% of patients (n=89) were male and 31% (n=40) were female. The median survival was found to be 24.43 months (19.66-29.20). The initial complaint in 47% of patients (n=57) was dyspeptic problems, and in 39% (n=37) it was detected to be weight lose. While median survival was 7.57 months in patients complaining of weight loss, it was 26.19 months and 14 months in patients suffering from vomiting and bleeding, and in those with dyspepsia, respectively. Conclusion: Initial symptoms are directly correlated with survival in patients with stomach cancer. In our study, weight loss was the most significant prognostic symptom. If a patient complains of weight loss, the symptom should be taken into due consideration and prompt diagnostic interventions should be performed. (The Medical Bulletin of Haseki 2015; 53: 241-5)
Markov Chain models serve two purposes firstly, subdivide the main data based on the mean value and one and two standard deviation plus and minus values around the mean value. The second stage of ...modeling, after calculating the transition probabilities between these categories from the available data, is completed by repeatedly multiplying the categorization date groups until the steady-state transition probability values are obtained. This procedure provides a convenient modeling approach for radon gas transient measurement records. After a brief presentation of Markov Chain procedure in this paper, the application is carried out by considering five categories that lead to a better transition probability matrix. Such a matrix provides information about the probabilities of future transition at the radon data measuring station. In addition, it is possible to associate these transition probabilities with the possibility of an earthquake.
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•Markov Chain Simulation model is obtained for radon gas emission from soil.•ArTificial intelligence applications for soil Rn release in relation to earthquakes.•Results are obtained with approximately 5 years (1785 days) of Radon gas release.
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Background: Secreted protein acidic and cysteine-rich (SPARC) was highly expressed in non-small cell lung cancer (NSCLC) tissue. Studies have indicated the association between SPARC expression ...and immune-cell infiltration and the prognosis of lung cancer. Despite the optimal first-line treatment approach in advanced NSCLC that lacks a driver mutation includes immunotherapy with or without chemotherapy, a well-defined tool or test for predicting response has yet to be created. We aimed to elucidate the influence of SPARC expression terms of clinicopathology, pembrolizumab response and prognosis in metastatic NSCLC patients. Methods: Thirty-six patients diagnosed with advanced-stage NSCLC without actionable driver mutation and recieved pembrolizumab in the first line setting were included in this study. Programmed death ligand-1(PD-L1) and SPARC expression were assessed by means of PD-L1 IHC 22C3 pharmDx and BenchMark ULTRA assay(Ventana Medical Systems, Tucson, AZ) in paraffin-embedded blocks. The expressions were categorised according to the tumor proportion score. Staining intensity of SPARC was graded according to the following criteria: 1+ (weak), 2+ (moderate), and 3+(strong). Results:The median age was 62 (range 45-81). One patient was female, and four patients did not have a smoking history.Twenty-seven of tumor were adenocarcinoma, and six were squamous cell carcinoma. PDL-1 status was < 1% in 4 (11.4%), 1-49% in 12 (34.3%), and > 50% in 20 (54.3%) patients.There was no significant correlation between SPARC expression and smoking status, histologic type of tumour, T and N status, and liver and bone metastasis. Central nervous system (CNS) metastasis and progression was seen in 8 (57.1%), 2 (12.5%), and 1 (16.7%) and in 6 (16.7%), 0, and 6 (37.5%) patients with SPARC 1+,2+, and 3 +, respectively. Controversially, higher SPARC expression was significantly correlated with lower rates of brain metastasis but higher rates of CNS progression (p = 0.022 and p = 0.011, respectively). While PD-L1 and SPARC expression were not significantly correlated, a trend toward low SPARC expression was seen in patients with PD-L1 > 50%. The objective response rate (ORR) trended to be higher in the SPARC 1+ group (85.7%, 43.8%, and 50.0% in SPARC 1+, 2+ and 3+ group, respectively, p = 0.052). Univariate analysis revealed that SPARC expression was not a significant prognostic factor for both PFS (p = 0.7) and OS (p = 0.07). But, low SPARC expression was a significant predictive factor for the first-line pembrolizumab treatment response (p = 0.04, OR:0.11, 95%CI 0.01-0.92) in NSLC patients. Conclusions: Our study lightened a new area in the literature that SPARC expression might predict the pembrolizumab response and might be a marker for CNS progression in NSLC patients. These results should be explored in further studies to address the potential therapeutic implications of SPARC expression.
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Background: Many prognostic biomarkers for survival have been studied in the neoadjuvant setting for locally advanced breast cancer (LABC). Our study assessed the correlation between the change ...in tumour-infiltrating lymphocytes (TIL) before and after neoadjuvant chemotherapy (NAC) in breast tissue and its impact on survival in patients with LABC. Methods: Eighty-four LACB patients were retrospectively analysed in this study. TIL was assessed by means of immunohystochemistry (Eclipse Ni, Nikon, Japan) in paraffin-embedded blocks obtained by core-needle biopsy or surgical specimen with respect to the 'TIL working group' criteria. Results: TIL scores were grouped as 0%, <10%, 10-50%, and >50%, the median TIL percentage was 17.5% before NAC and 5% after NAC, and the difference was statistically significant (p<0.001). Postop-Ki-67 (p=0.005), molecular subtype (p=0.027), pre-NAC TIL score (p=0.006), post-NAC TIL score (p<0.001), postop-Ki-67 (p=0.005) and preoperative residual cancer burden tumour-infiltrating lymphocyte (RCB-TIL) (p<0.001) were significantly correlated with pCR. Higher TIL scores were significantly associated with higher PCR rates. Univariate analysis for disease-free survival (DFS) and overall survival (OS) revealed that postop-Ki-67 level and presence of pCR and postoperative ki-67 score (p=0.031) were significant prognostic factors, respectively. The independent prognostic factor for DFS were postop-Ki-67 score (p=0.012, RR: 6.16, 95% CI: 1.48-9.12), post-NAC TIL score (p=0.041, RR: 0.42, 95% CI: 0.16-1.06) and the presence of pCR (p=0.038, RR: 0.10, 95% CI: 0.01-0.87). Logistic regression analysis showed that a preoperative ki-67 score greater than 14% (p=0.001, OR: 4.55; 95% CI: 0.11-1.49), a postoperative ki-67 score equal to or lower than 14% (p=0.011, OR: 1.10; 95% CI: 0.42-2.29), preop-grade 3 (p=0.01, OR: 2.65; 95% CI: 0.85-3.14), low postop-TIL score (p<0.001, OR: 3.14; 95% CI: 0.79-4.11) were significant predictive factors for pCR. Conclusions: Our study confirms the hypothesis that TIL expressions may be therapeutic targets, especially in specific molecular breast cancer subtypes.
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