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Steatosis is an important cofactor in hepatitis C virus (HCV) because it is associated with fibrosis and reduces early and sustained virologic response. Recent studies suggest that HCV genotype 1 is not steatogenic if additional risk factors are not present. Because hypoadiponectinemia was found to be a feature of nonalcoholic steatohepatitis (NASH) independent of insulin resistance, its level in patients with hepatitis C genotype can reveal the optimal therapeutic strategy. This study was conducted to determine the role of the relationship between steatosis and serum adiponectin levels in the progression of liver damage in HCV genotype 1 without known risk factors for NASH. Patients (n=50) with biopsy-proven chronic hepatitis C (CHC), positive HCV RNA, and raised alanine aminotransferase were enrolled. They were carefully selected to rule out possible confounding factors for the presence of steatosis and additional systemic or liver disease. Associations between serum adiponectin levels and grade of steatosis, histologic activity index (HAI), fibrosis grade of liver biopsies, patient age, HCV viral load, and serum transaminase activities were studied. Also, adiponectin levels were compared with those of a control group of 30 healthy volunteers with normal ultrasound findings of the upper abdomen who had no known NASH risk factors. The investigators found that adiponectin levels in patients with CHC genotype 1 were similar to those in healthy subjects. No significant association was found between adiponectin levels and severity of steatosis, HCV RNA levels, HAI, transaminases, and fibrosis. Steatosis was present in 41 patients (82%) with CHC. Multivariate analysis of data on 50 patients revealed that severity of steatosis was independently related to age alone (P=.03). A correlation between HCV RNA load and HAI was observed (P=.02; r=0.712). HAI also was associated with stage of fibrosis (P=.00; r= 0.612). In cases of chronic HCV genotype 1 hepatitis, steatosis is a common histologic feature, although no risk factors are known. Results presented here cannot establish an association between adiponectin and severity of steatosis when risk factors for steatosis are unknown. Additional studies are needed to discover a metabolic treatment that would seek to improve the progression of hepatic steatosis in CHC infection. [ABSTRACT FROM AUTHOR]

Reportedly, soluble CD27 (sCD27) is a sensitive and specific marker for leptomeningeal involvement (LI) of CD27-expressing lymphoproliferations, such as B-cell non-Hodgkin's lymphoma and chronic B-lymphocytic leukemia. On morphologic analysis of cerebrospinal fluid (CSF), one third of patients suspected of LI have false negatives, so a diagnostic marker for LI in B-cell non-Hodgkin's lymphoma or B-lymphocytic leukemia would be extremely valuable. sCD27 was detected in the serum and CSF samples from 35 selected patients in whom 18 cases of acute lymphoblastic leukemia (ALL) (3 with LI), 7 of non-Hodgkin's lymphoma, and 5 of acute myelogenous leukemia (3 with LI) were submitted for (immuno)morphologic detection of malignant cells and intrathecal therapy, along with samples from 5 control patients (2 submitted for epidural hemorrhage, 3 for lumbar disc protrusion). Concentrations of CSF-sCD27 were determined by enzyme-linked immunosorbent assay (PeliKine Compact Human Soluble CD27 ELISA Kit, Cat. No. M1960; Research Diagnostics Inc., Concord, Mass). The cutoff value was 350 U/mL. Serum and CSF-sCD27 concentrations above the cutoff value were not detected. Although it is unlikely that LI would be present in patients with chronic lymphoproliferation who have normal sCD27 concentrations in CSF samples, the determination of CSF-sCD27 is not sufficiently specific to allow it to serve as a reliable tumor marker. [ABSTRACT FROM AUTHOR]

Investigators in this study explored levels of soluble CD27 (sCD27), interleukin (IL)-8, and IL-10 in B-cell chronic lymphocytic leukemia (B-CLL), and the correlation of these levels with disease stage and prognosis. Plasma IL-8, IL-10, and sCD27 levels were assessed with enzyme-linked immunosorbent assay tests in 22 healthy donors and 70 patients with B-CLL (49 men and 21 women). Mean patient age was 61.57 y (range, 44-75 y). Mean healthy donor age was 62.09 y (range, 40-72 y). In the study group, mean values were as follows: plasma IL-8, 284.758 pg/mL (0-1000 pg/mL) plasma IL-10, 26.152 pg/mL (0-100 pg/mL) sCD27, 731.357 U/mL (139.9-1000 U/mL) white blood cell count, 59.9 x 10(9)/L (0.8-250.0 x 10(9)/L) hemoglobin count, 11.2 g/dL (5.0-16.2 g/dL) platelet count, 162.5 x 10(9)/L (29.8-317 x 10(9)/L) B(2) microglobulin (B(2)M) 3350.2 mg/L (274.7-7499.9 mg/L) CD38, 19.5% and lactate dehydrogenase (count, 497.5 U/L (263.0-1507 U/L). Patients represented all Rai stages, with 22.9% at stage 0, 11.4% at stage I, 11.4% at stage II, 41.4% at stage III, and 12.9% at stage IV. Plasma levels of IL-8, IL-10, and sCD27 were correlated between study and control groups; significantly higher IL-8 (P=.001) and sCD27 (P=.000) levels were found, but the IL-10 level was not significant (P=.139). Plasma IL-10 (P=.01) and sCD27 (P=.008) were positively correlated with Rai stage, but IL-8 was not (P=.146). Levels of sCD27 were significantly correlated with values for B2M (P=.000), hemoglobin (P=.028), lactate dehydrogenase (P=.001), CD19 (P=.03), and IL-10 (P=.000). IL-8 was significantly correlated with white blood cell (P=.000) count, and CD38 (P=.001) and CD5 (P=.006) levels. IL-10 was significantly correlated with B(2)M (P=.017), CD19 (P=.000), platelet (P=.002), and CD27 (P=.000). In survival distributions for CD27, IL-8 and IL-10 were found to have more significant relationships for all parameters (P=.0000). In conclusion, the authors suggest that sCD27, IL-8, and IL-10 are more significant prognostic factors for B-CLL when compared with others, and these values should correlate with new prognostic factors (eg, zeta-associated protein-70, mutated/unmutated immunoglobulin variable heavy chain). [ABSTRACT FROM AUTHOR]

Angiogenesis is a process that plays an important role in the growth and progression of cancer; growing evidence suggests that neovascularization is important in hematologic malignancies. Increased angiogenic potential has been identified in multiple myeloma (MM). In this study, investigators simultaneously measured the levels of hepatocyte growth factor (HGF), platelet-derived growth factor-AB (PDGFAB), and transforming growth factor-alpha (TGF-alpha) through enzyme-linked immunosorbent assay in the bone marrow (BM) and peripheral blood (PB) of 30 patients with MM and 10 healthy controls. Differences in HGF values in BM sera were significant (P=.001) between patients and controls. In detailed analyses of HGF, PDGF-AB, and TGF-alpha, according to disease stage, a significant correlation was found between disease stage and BM HGF (P=.047), BM TGF-alpha (P=.021), and PB PDGF-AB (P=.006), respectively. When correlations between all other parameters were analyzed, significance was noted between PB TGF-alpha and lactate dehydrogenase (P=.02), PB TGF-alpha and PB HGF (P=.002), BM TGF-alpha and CD38 (P=.046), BM TGF-alpha and BM HGF (P=.000), BM TGF-alpha and BM PDGF-AB (P=.048), BM HGF and PB HGF (P=.044), and BM PDGF-AB and PB PDGF-AB (P=.000). BM HGF levels had a significant effect on overall survival, with disease severity assessed in terms of disease stage (P=.0018, log-rank test). These data show that in patients with MM, high levels of BM HGF, BM TGF-alpha, and PB PDGF-AB were associated with advanced disease stage; in addition, HGF played a significant role in disease processing and was related to disease severity. These findings have also led to the concept of a symbiotic relationship between the growth of myeloma cells and HGF, TGF-alpha, and PDGFAB in BM. [ABSTRACT FROM AUTHOR]

Background : The purposes of neoadjuvant chemotherapy are to tumor size to improve the tumor removal rate, extend survival, and prevent metastasis. In this study, the importance of CRP/albumin ratio and CEA/albumin ratio in the prediction of neoadjuvant treatment response in gastric cancer patients was evaluated. Methods : This study retrospectively included 135 gastric cancer patients who received neoadjuvant chemotherapy at Çukurova University Balcalı Hospital between January 2018 and December 2023. Preoperative CRP/albumin and CEA/albumin ratios were compared according to treatment response and multivariate logistic regression analysis was performed to determine the potential importance of these ratios in predicting pathological response. Results : The mean age of the 135 patients was 58.79 ± 10.83 (min = 26-max = 78). The CRP/albumin and CEA/albumin ratios were found to be significantly lower in patients who did not respond to neoadjuvant therapy. Each 1-unit increase in the CRP/albumin ratio was associated with a 1.16-fold decrease in the odds of pathological complete response to neoadjuvant therapy. Both CRP/albumin and CEA/albumin ratios were found to be significant in distinguishing neoadjuvant therapy response. The optimal cut-off value was 2.74 for the CRP/albumin ratio (sensitivity = 60%, specificity = 78.4%) and 1.40 for the CEA/albumin ratio (sensitivity = 74.2%, specificity = 67.6%). Values below these cut-off points favored neoadjuvant therapy response. Pathological complete response to neoadjuvant therapy was 4.75 times higher in patients with a CRP/albumin ratio below 2.74 and 5.14 times higher in patients with a CEA/albumin ratio below 1.40. Conclusions : Findings demonstrate that in patients with locally advanced gastric cancer receiving neoadjuvant treatment, CRP/Albumin and CEA/Albumin ratios are significant markers of pathological response.

(1) Background: The introduction of novel therapies has led to a considerable evolution in the management of Multiple Myeloma, and chromosomal abnormalities predict the success of treatment. We aimed to characterize cytogenetic abnormalities for risk stratification in the patient population and to evaluate the predictive and prognostic value of the specified abnormalities in distinct treatment modalities. (2) Methods: This study included patients with Multiple Myeloma who applied to the Internal Medicine Clinic of the Cukurova University Faculty of Medicine. Between 2010 and 2023, 98 cases with cytogenetic abnormality data were identified. We analysed the effects of cytogenetic abnormalities on survival and response rates to first chemotherapies. (3) Results: P53 del was the most prevalent abnormality, and t(11;14) was the most common translocation. There was no significant difference in the mean survival and treatment response rates for specific cytogenetic abnormalities. When chemotherapies based on lenalidomide were initiated, patients' life-death statuses differed significantly from those of treatments without lenalidomide. Regardless of the type of chromosomal aberration, lenalidomide-based treatments independently enhanced average survival 14-fold, while there was no significant difference in overall survival among treatments. (4) Conclusions: In individuals with cytogenetic abnormalities, lenalidomide-based treatments should be started regardless of the chemotherapy to be used for the condition.

Aim: To evaluate the inhibitory effects of ornidazole on the proliferation and migration of metastatic melanoma cell line (B16F10) in vitro and its anti-cancer effects in vivo using a melanoma mouse model., Methods: We investigated the effects of ornidazole on cell viability (Crystal Violet and MTT assay) and migration ability (wound-healing assay) of B16F10 melanoma cells, and its ability to trigger DNA damage (Comet assay) in vitro. We also sorted CD133+ and CD133- cells from B16F10 melanoma cell line and injected them subcutaneously into Swiss albino mice to induce tumor formation. Tumor-bearing mice were divided into control and treatment groups. Treatment group received intraperitoneal ornidazole injections. Tumors were resected. Real-time polymerase chain reaction was used to determine the expression of genes involved into Sonic hedgehog (Shh) signaling pathway, stemness, apoptosis, endoplasmic reticulum (ER) stress, ER stress-mediated apoptosis, and autophagy. Shh signaling pathway-related proteins and CD133 protein were analyzed by ELISA., Results: Ornidazole effectively induced DNA damage in CD133+ melanoma cells and reduced their viability and migration ability in vitro. Moreover, it significantly suppressed tumor growth in melanoma mouse model seemingly by inhibiting the Shh signaling pathway and ER-stress mediated autophagy, as well as by activating multiple apoptosis pathways., Conclusions: Our preclinical findings suggest the therapeutic potential of ornidazole in the treatment of metastatic melanoma. However, larger and more comprehensive studies are required to validate our results and to further explore the safety and clinical effectiveness of ornidazole.

Objectives: Regorafenib improved overall survival in patients with metastatic colorectal cancer (mCRC) refractory to standard therapies in two randomised, phase III trials, but has not been evaluated in Turkey. REGARD evaluated the safety and efficacy of regorafenib in Turkish patients with treatment-refractory mCRC., Design: Open-label, single-arm, phase IIIb study conducted between July 2013 and April 2015., Setting: 11 tertiary centres in Turkey., Participants: Eligible patients were adults with mCRC who had disease progression within 3 months after receiving their last dose of approved standard therapies and who had an Eastern Cooperative Oncology Group performance status ≤1. Patients were excluded if they had previously received regorafenib. Of 139 patients screened, 100 were treated and completed the study, and all 100 were analysed. Fifty-eight per cent were male., Interventions: Patients received oral regorafenib, 160 mg once daily, for the first 3 weeks of each 4-week cycle until disease progression, death or unacceptable toxicity., Primary and Secondary Outcome Measures: The primary endpoint was safety, assessed by incidence of treatment-emergent adverse events (TEAEs). Progression-free survival (PFS) per investigator was the primary efficacy endpoint. There were no secondary endpoints., Results: The median treatment duration was 2.5 months (range 0.1 to 20.6). Ninety-six per cent of patients had at least one TEAE and 77% had a grade ≥3 TEAE. The most common grade ≥3 regorafenib-related TEAEs were hypophosphataemia (11%), fatigue (8%), hyperbilirubinaemia (6%), hand-foot skin reaction (5%), hypertension (5%), anorexia (5%) and increased alanine aminotransferase (5%). TEAEs led to dose reduction in 30% of patients. Regorafenib-related TEAEs led to treatment discontinuation in 17% of patients. Median PFS was 3.1 months (95% CI 2.9 to 3.8)., Conclusion: The regorafenib safety profile and PFS in REGARD were consistent with the results of previous trials of regorafenib in mCRC. Regorafenib is an option for patients in Turkey with treatment-refractory mCRC., Trial Registration Number: NCT01853319, ClinicalTrials.gov., Competing Interests: Competing interests: KO is an employee of Bayer HealthCare Pharmaceuticals; ŞY has received personal fees from Bayer, Roche, Sanofi, Amgen, Eli Lilly, Merck Serono, and has received grants from Celgene; FD, MB, NFA, İY, MÖ, TE, AS, HŞC, UAS, IOK and PFY have no conflicts of interest to declare., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Mesothelioma is an aggressive tumour that originates in serous surfaces. The primary end point of this study was to invastigate the relationship of progression free survival (PFS) and overall survival (OS) with the c-Met, EGFR, PTEN, PDGFR-alpha, PI3K/AKT and mTOR expression levels in the tumour tissue of pleural and peritoneal mesothelioma cases., Materials and Methods: The study included 53 patients diagnosed with mesothelioma between 2005 and 2016. The cases were separated into 2 groups as pleural and peritoneal. The effects on OS and PFS were examined of the c-Met, EGFR, PTEN, PDGFR-alpha, PI3K/AKT and mTOR expression levels and also clinicopathological parameters and the treatments given. In the statistical analysis of the data obtained, IBM SPSS vn 20.0 software was used., Result: Of the 53 patients included in the study, 39 (73.6%) were diagnosed with pleural mesothelioma and 14 (26.4%) with peritoneal mesothelioma. According to the c-Met and mTOR expression, OS and PFS of the peritoneal cases with high expression (2+, 3+) was seen to be significantly better than that of the peritoneal cases with low expression (0, 1+) (p<0.05). According to the PDGFR expression, OS and PFS of the pleural cases with low expression (0, 1+) was seen to be significantly better than that of the pleural cases with high expression (2+, 3+) (p<0.05)., Conclusions: The examination of c-MET, PDGFR-alpha and m-TOR expression in the in the tumor tissue of mesothelioma cases may be important in determining prognosis.

Background: Trastuzumab is a recombinant humanized monoclonal antibody used to treat human epidermal growth factor receptor 2 positive breast cancer, with recognized associated cardiotoxicity. In this retrospective observational study, we investigated associated cardiotoxicity on clinical outcomes using trastuzumab in women referred to our clinic., Materials and Methods: The study was made up of 111 women with human epidermal growth factor receptor 2-overexpressing breast cancer who received trastuzumab in the Medical Oncology Department, between 2010 and 2013., Results: A > 10% reduction of the baseline fraction of the left ventricular ejection fraction was observed in 18 (16.21%) women. Two individuals (1.8%) suffered from symptomatic heart failure, seven women showed cardiac symptoms and nine women showed asymptomatic decline of left ventricular ejection fraction. Risk factors for cardiotoxicity in the group included: postmenopausal status (p = 0.01), hypertension (p = 0.002), obesity (p = 0.0001), previously diagnosed coronary artery disease (p = 0.0001) and smoking (p = 0.03)., Conclusion: The aforementioned factors pose a risk for cardiotoxicity. We found postmenopausal status, hypertension, obesity, previous coronary artery disease and smoking to be associated with an increased risk of cardiac dysfunction in women using trastuzumab. While administering trastuzumab to women who have these conditions, one must be aware of the risk of cardiotoxicity of trastuzumab., (© The Author(s) 2015.)

Aim: Non-small cell lung carcinoma is the leading cause of cancer related to death in the world. Squamous cell lung carcinoma (SqCLC) is the second most frequent histological subtype of lung carcinomas. Recently, growth factors, growth factor receptors, and signal transduction system-related gene amplifications and mutations are extensively under investigation to estimate the prognosis and to develop individualized therapies in SqCLC. In this study, besides the signal transduction molecule phosphatidyl inositol-3-phosphate kinase (IP3K) p110α, we explored the expressions of fibroblast growth factor 2 (FGF2) and receptor-1 (FGFR1) in tumor tissue and also their clinical and prognostic significance in patients with early/advanced SqCLC., Materials and Methods: From 2005 to 2013, 129 patients (23 early, 106 advanced disease) with a histopathological SqCLC diagnosis were selected from the hospital files of Cukurova University Medical Faculty for this study. Two independent pathologists evaluated FGFR1, FGF2, and PI3K (p110α) expressions in both tumor and stromal tissues from 99 of the patients with sufficient tissue samples, using immunohistochemistry. Considering survival analysis separately for patients with both early and advanced stage diseases, the relationship between the clinical features of the patients and expressions were evaluated by univariate and multivariate analyses., Results: FGFR1 expression was found to be low in 59 (60%) patients and high in 40 (40%) patients. For FGF2; 12 (12%) patients had high, 87 (88%) patients had low expression and for IP3K; 31 (32%) patients had high and 66 (68%) patients had low expressions. In univariate analysis, overall survival (OS) was significantly associated with stage of the disease and the performance status of the patient (P<0.0001 and P<0.001). There was no significant difference in OS of the patients with either low or high expressions of FGFR1, FGF2, and IP3K. When the patients with early or advanced stage disease were separately taken into consideration, the relationship did not differ, either. Any of FGFR1, FGF2 or IP3K expressions was not found predictive for the treatment of early or advanced staged patients. On the other hand, the expressions of both FGFR1 and FGF2 were significantly different with respect to smoking, scar of tuberculosis and scar of radiotherapy (P=0.002; P=0.06 and P=0.05, respectively)., Discussion: There has not been identified an effective individualized treatment for SqCLC yet. Therefore, in order to be able to develop such a treatment in the future, it is essential to identify the genetic abnormalities that are responsible for the biological behaviors and carcinogenesis of SqCLC. Although we could not show the prognostic and predictive significance of FGFR1, FGF2 and IP3K expressions in SqCLC, we determined the expression rates of FGFR1, FGF2 and IP3K as a reference for Turkish patients. In conclusion, we want to put some emphasis on the fact that, pulmonary fibrosis which is a late complication of radiotherapy at stage III disease, and the scar of tuberculosis could be associated with FGFR1 and FGF2 expressions.

Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is a severe bone disease for which the pathogenetic mechanisms and risk factors are not fully understood. The present study evaluated the data of 652 patients with bone metastasis that had undergone treatment with biphosphonates. Subsequently, 24 patients with BRONJ and 20 control patients without BRONJ that were treated with zoledronic acid were enrolled. It was found that BRONJ occurred in 3.6% of patients. The mean age and the administration of dental treatment were found to be significantly associated with BRONJ development (P=0.049 and P=0.013, respectively). The cumulative dose median in the BRONJ group was found to be significantly higher compared with the cumulative dose average in the control group (P=0.037). In addition, at the time of BRONJ development, improvement in the disease was determined to be better in the BRONJ group than in the control group (P=0.031). The present study determined that age, the existence of dental extraction and the cumulative dose of zoledronate were all important risk factors in BRONJ development.

Paragangliomas are relatively rare chromaffin cell tumors which may be cured through resection. Patients with paragangliomas may develop metastatic diseases. There is no consensus regarding refractory chemotherapy for treatment of metastatic disease. In this report, we presented a case of a 43-year-old woman who was admitted to the hospital with a history of episodic headaches, diaphoresis, and weakness. Elevated plasma catecholamine levels and a right paraaortic mass were observed on computed tomography. The mass was excised, and a diagnosis of paraganglioma was confirmed. After 20 months of follow-up, local recurrence and metastases were detected in the thorax, abdomen, and skeletal system. Plasma and urinary catecholamine levels were high. Chemotherapy was administered, and no improvement was observed. Therefore, following this palliative conventional chemotherapy, sorafenib was administered for three months, and, finally, positron emission tomography showed that the patient's lesions had completely regressed.

Background: Several previous studies have examined the effect of CYP2D6 gene polymorphism on the efficacy and metabolism of tamoxifen (Tamoxifen Teva, Nolvadex) in the treatment of breast cancer. In the present study, the metabolic profiles associated with various CYP2D6 genotypes were evaluated., Method: In the present study 92 Turkish breast cancer patients with early-stage hormone receptor-positive tumors treated with adjuvant tamoxifen (20 mg) were evaluated for CYP2D6 genotype and metabolic profiles. Known side effects of tamoxifen treatment, including endometrial thickening, changes in serum lipid levels and bone density, and hepatosteatosis, were evaluated according to the CYP2D6 polymorphism., Result: The distribution of metabolic characteristics in the Turkish population was as follows: 77.1% normal metabolism, 11.5% intermediate metabolism, 5.2% ultrarapid metabolism, and 2.1% poor metabolism. The CYP2D6 genotypes associated with rapid metabolism were CYP2D6 3X*1/*1 duplication (DUP) and CYP2D6 2X*1/*2, while poor metabolism was associated with the genotypes CYP2D6 *3/*4 and CYP2D6 *6/*6. There was no statistically significant relationship between metabolic characteristics and bone density or hepatosteatosis. A statistically significant difference in total cholesterol and triglycerides was detected in lipid profile analysis (p = 0.003, p = 0.02). Assessment of endometrial thickness revealed a significant association of hyperplasia and poor metabolism, and an association between atrophy and ultrarapid metabolism (p = 0.01)., Conclusion: Significant development of endometrial hyperplasia was identified among individuals with poor tamoxifen metabolism. As a result, tamoxifen may be a significant predictor of endometrial thickening among individuals with poor metabolic characteristics., (© 2014 S. Karger AG, Basel.)

Background: The aim of this study was to investigate the general characteristics of patients with deep vein thrombosis (DVT) and pancreatic cancer as well as evaluate the relationship between mean platelet volume (MPV), DVT and survival., Materials and Methods: Seventy-seven patients with pancreatic cancer, who were admitted to Cukurova University Medical Faculty, Department of Medical Oncology, were enrolled in the study, Results: The mean age was 59±20. Forty-nine (63.6%) were men and 28 women (36.4%) . Sixty-eight (88.3%) patients had adenocarcinoma and 9 (11.7%) had a malignant epithelial tumor. Thirty-six (46.7%) had liver metastasis at diagnosis. Twenty-six (33.8%) patients were alive, 20 (26%) were dead and in 31 (40.2%) the status was unknown. Only 14 (18.1%) patients had DVT. In 42 (54.5%) patients MPV values were normal, in 28 (36.4%) patients they were above normal, and in 7 (9.1%) patients they were below normal. There was no statistically significant difference between gender, tumour localization, chemotherapy and survival rates (p:0.56, p:0.11, p:0.21). There was no significant difference between DVT, gender, localisation, histological subtype, the presence of metastasis, stage and if the patient had been treated with chemotherapy (p:0.5, p:0.6, p:0.2, p:0.32, p:0.1, p:0.84). There was also no significant difference between MPV and DVT (p:0.57) but there was a significant difference between liver metastasis and DVT (p:0.02). Age, stage, the presence of metastasis and DVT were prognostic in pancreatic cancer patients., Conclusions: Cases of pancreatic cancer with liver metastasis should be studied more carefully as thrombosis is more common in these patients.

Background: Neurofibromatosis type 1 (NF1) is a genetic syndrome that predisposes patients to benign and malignant tumor development. Patients with NF1 develop multiple neurofibromas that can transform into aggressive sarcomas known as malignant peripheral nerve sheath tumors. In contrast, malignant tumors unrelated to the nervous system rarely coexist with neurofibromatosis. The aim of this article was to present four cases of adult NF1 patients with malignant tumors unrelated to the nervous system as well as a bibliographic search for papers describing these tumors in NF1, focusing on osteosarcomas, gastrointestinal stromal tumors (GISTs), leiomyosarcomas and somatostatinomas and their genetic alterations in NF1., Methods: Search engines such as PubMed and MEDLINE were browsed for English-language articles since 1989 using a list of keywords, as well as references from review articles. Search terms were NF1, osteosarcoma, leiomyosarcoma, somatostatinoma and GIST. Data were summarized in a table at the end of the Results section., Results: In our four NF1 cases, there were one osteosarcoma, one leiomyosarcoma, one somatostatinoma and GIST and one GIST. NF1 was diagnosed at an adult age when these patients were admitted to our oncology department. The results generated by the literature search yielded 75 articles about NF and GIST. We summarized the clinical characteristics of 43 patients with NF1 and somatostatinoma. Forty-five articles involving NF and osteosarcoma were found, and of these, 26 involved NF1; from these articles, we identified the clinical features of 8 patients. Twenty-five articles were found concerning NF1 and leiomyosarcoma, and of those, we summarized the clinical features of 15 patients., Conclusions: Here we reviewed somatostatinomas, GISTs, osteosarcomas and leiomyosarcomas occurring in NF1 patients. Patients with NF1 who present with gastrointestinal symptoms, should be carefully evaluated carefully with a high index of suspicion of potential GISTs, periampullary and duodenal tumors. Patients with pathological fractures or bone pain along with NF1 should be carefully screened for malignant bone tumors. Patients with NF1 can develop leiomyosarcoma less frequently than other malignancies, but the association of uterine leiomyoma and NF1 may not be fortuitous. Somatic mutations were defined for frequent tumors, including neurogenic tumors and GISTs but not for sarcomas due to the complexity of underlying mechanisms of the disease and tumorigenesis. Based on the findings; all NF patients can develop malignant tumors, including the less frequently observed ones. Therefore, we recommend that new genetic studies should be performed for rare malignancies in cases of NF1., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Multiple myeloma (MM) patients relapse after a period of time despite longer disease-free survival due to novel treatment options. In this study we aimed to assess the value of real-time polymerase chain reaction (RT-PCR) for detecting the immunoglobulin heavy chain (IgH) gene rearrangement using allele-specific molecular beacons as fluorescence probes to quantify minimal residual disease (MRD) and also to correlate post-treatment flow cytometric detection of plasma cells' (PCs) expression of CD19, CD38, CD45, CD56 and CD138 in MM., Methods: After diagnosis of 17 MM patients, the CDR1, CDR2 and CDR3 regions of the IgH gene were analysed and sequenced to identify IgH's clonal nature. Unique sequences of the clonal IgH rearrangement were used to design specific molecular beacon probes for each MM patient. Examined were also the co-expression of CD19, CD38, CD45, CD56, and CD138 molecules in bone marrow aspirates of patients with MM by flow cytometry., Results: Detection of MRD was positive in 13 (76%) of 17 patients by RT-PCR. The infiltration ratio was significantly correlated with CD138 expression (p=0.009). Significant correlation was also found between RT-PCR detection of MRD and CD138 expression (p=0.006). Nevertheless, no correlation was observed among other surface antigens (CD38, CD45, CD56)., Conclusion: Our results indicated that RT-PCR with specific molecular beacons provide a feasible, accurate and reproducible method for the determination of MRD in MM. Flow cytometry detection of CD138 expression may be used as a disease marker in addition to RT-PCR.

Background: Neoadjuvant systemic chemotherapy is the accepted approach for women with locally advanced breast cancer. Anthracycline- and taxane-based regimens have been extensively studied in clinical trials and consequently are widely used. In this study aimed to research the complete response (pCR) rates in different regimens for neoadjuvant setting and determine associated clinical and biological factors., Methods: This study included 63 patients diagnosed with breast carcinoma among 95 patients that had been treated with neoadjuvant chemotherapy between 2007 and 2010. TNM staging system was used for staging. The histologic response to neoadjuvant chemotherapy was characterized as a pCR when there was no evidence of residual invasive tumor in the breast or axillary lymph nodes. Biologic subclassification using estrogen receptor (ER), progesterone receptor (PR), HER2 were performed. Luminal A was defined as ER+, PR+, HER2-; Luminal B tumor was defined as ER+, PR-, HER2-; ER+, PR-, HER2+; ER-, PR+, HER2-; ER+, PR+, HER2+, HER2 like tumor ER-, PR+, HER2+; and triple negative tumor ER, PR, HER2 negative., Results: Patients median age was 54.14 (min-max: 30-75). Thirty-two patients (50.8%) were premenopausal and 31 (49.2%) were postmenopausal. Staging was performed postoperatively based on the pathology report and appropriated imaging modalities The TNM (tumor, lymph node, metastasis) system was used for clinical and pathological staging. Fifty-seven (90.5%) were invasive ductal carcinomas, 6 (9.5%) were other subtypes. Thirty nine (61.9%) were grade II and 24 (38.1%) were grade III. Seven (11.1%) patients were stage II and 56 (88.9) patients were stage III. The patients were classified for ER, PR receptor and HER2 positivity. Seventeen patients had complete response to chemotherapy. Forty patients (63.5%) were treated with dose dense regimen (cyclophosphamide 600 mg/m2 and doxorubicine 60 mg/m every two weeks than paclitaxel 175 mg/m2 every two weeks with filgrastim support) 40 patients (48%) were treated anthracycline and taxane containing regimens. Thirteen patients (76%) from 17 patients with pCR were treated with the dose dense regimen but without statistical significance (p=0.06). pCR was higher in HER2(-), ER(-), grade III, premenopausal patients., Conclusion: pCR rate was higher in the group that treated with dose dense regimen, which should thus be the selected regimen in neoadjuvant setting. Some other factors can predict pCR in Turkish patients, like grade, menopausal status, triple negativity, percentage of ER positivity, and HER2 expression.

Background and Objectives: This study aimed to present the clinicopathological characteristics and treatment of patients with bladder carcinoma with sarcomatoid differentiation at our institution., Methods: Between 1995- 2009, 950 patients were followed-up for bladder carcinoma. Among them, 14 patients with sarcomatoid carcinoma were retrospectively reviewed, and their clinical, pathological features and treatment were recorded., Results: Median age of the patients was 65 years (range: 41-86 years), 12 (86%) being male and 2 (14%) female. All the patients presented with hematuria and 11 (88%) had a history of smoking. The tumor growth pattern was solid in 10 patients, papillary in 2, and mixed in 2. In all, 5 of the patients had urothelial carcinoma with sarcomatoid differentiation and 9 were diagnosed with sarcomatoid carcinoma. Five patients underwent radical cystectomy with ileal conduit surgery, 2 patients refused cystectomy, and 8 patients underwent re-TUR. Following diagnosis ,12 of the patients died in mean 10.7 months (range: 1-48 months)., Conclusion: Urothelial carcinomas with sarcomatoid features are aggressive and are usually at advanced stage at the time of diagnosis. The outcomes of multimodal treatment are not satisfactory. Significant findings of the present study are that early diagnosis positively affect survival and that gemcitabine and cisplatin in combination can positively affect survival.

Background: Myeloid sarcoma rarely presents in the absence of systemic myeloid disease., Case Report: In this study, we present a case of intracerebral myeloid sarcoma with no diagnosis of any hematological disease in a 22-year-old male patient in whom brain magnetic resonance image revealed a meningioma. However, biopsy showed myeloid sarcoma. No myeloid disease was determined. The mass disappeared following 8 cycles of chemotherapy. In the literature, we determined only 8 similar cases cited between 1970 and 2011., Conclusion: Intracerebral myeloid sarcoma has currently no standard treatment and may be confused with a primary brain disease. Chemotherapy and/or radiotherapy are the most viable and widely used treatment modalities. Potential occurrence of hematological disease should also be closely followed due to conversion risks.

Most commonly arising in the gastrointestinal and genitourinary tracts, extrapulmonary small-cell carcinoma is quite rare. Although its prognosis is very poor, complete remission or even cure can be achieved by combination of different treatment modalities. We report here a 32-year-old woman with a cutaneous gluteal mass diagnosed as small-cell carcinoma of the skin. Combination chemotherapy containing cisplatin and etoposide was started. Radiotherapy was administered after two courses of chemotherapy. Following radiotherapy, additional 4 courses of chemotherapy were given. She has been in remission for three years with no evidence of tumor recurrence.

Introduction: Malignant mixed Müllerian tumor (MMMT) of the ovary is a rare and highly aggressive tumor. It accounts <1% of all ovarian carcinomas. It is characterized by the presence of both carcinomatous and sarcomatous components and tends to occur in low parity postmenopausal woman. These are mixed, mostly monoclonal tumors, and the predominance of the stromal component aggravates the prognosis. The staging system for ovarian and primary peritoneal cancer is also used for MMMT. After complete surgical staging, patient with stage II-IV at the time of surgery should have postoperative chemotherapy. Chemotherapy can be considered for stage I MMMT. Its optimal treatment is debatable. Taxane and platinum combination is standard for the epithelial ovarian carcinoma. There is very limited literature reporting this combination therapy in ovarian MMMTs. CASE 1 AND CASE 2: We presented two cases of stage III primary ovarian MMMT. The patients were treated with the taxane/platin combination, without adverse events following surgery, and remained in clinical remission in Case 1 at follow-up. Case 2 has progressed after first line taxane/platin regimen and treated like epithelial ovarian carcinoma. Case 1 was in complete remission in the follow-up visit 2 years later. Case 2 died 14 months later after the tumor was initially diagnosed., Conclusion: Predominating carcinomatous or sarcomatous component should be taken into consideration in predicting the response and planning the chemotherapy protocol.

Background and Purpose: It has been suggested that liver regeneration can occur either by differentiated adult hepatocytes which retain the capability for several rounds of replication or by hepatic progenitor cells, depending on the number of hepatocytes lost. We sought to study the differentiation potential of hepatocytes following partial hepatectomy (PH) in rats., Methods: Using immunohistochemistry and confocal microscopy we studied the distribution of cytokeratin 7 (CK7), CK19, vimentin, desmin, CD34, and c-kit among adult rat liver hepatocytes after PH at various times just after hepatectomy and after 8, 16, 24, 36, 48, and 60 hour and 6 and 16 days., Results: Vimentin, c-kit, and desmin positivity were observed in regenerating hepatocytes in the early stages. Desmin and vimentin staining were also demonstrated in stellate cells. Staining enhancement in stellate cells progressed from day 3 to day 6. No liver sections were stained positive for CD34, CK19, or CK7., Conclusion: After PH, mature hepatocytes revealed their potential to regain the markers that they do not express when they are quiescent. This result supported the plasticity and differentiation potential of adult hepatocytes during regeneration.

Among patients with haematologic disorders, mucormycosis most commonly occurs in those with acute leukaemia or lymphoma who have developed neutropenia due to malignancy or to chemotherapy, and in transplanted patients receiving immunosuppressive treatment. Here, we aim to present a retrospective study conducted over a 5-year period (2001-2005). The study included 20 patients with haematologic malignancies with a proven mucormycosis admitted in Medical Oncology Divisions in Cukurova University Hospital. The most frequent sites of infection were paranasal sinuses (95%) and lung (5%). Antifungal treatment was empirically administered in 18 (90%) patients; 18 patients underwent radical surgical debridement (90%). The therapy was successful for only eight patients (40%). Eleven patients died within 1 months of the diagnosis of fungal infection: the cause of death was only by mucormycosis in four patients (36.6%), mucormucosis and systematic inflamatuar response syndrome (SIRS) in two patients (18.2%) and progression of haematologic disease in five patients (45.5%). At univariate analysis, the factors that correlated with a positive outcome from infection were the following: amphotericin B treatment, neutrophil recovery from postchemotherapy aplasia. At multivariate analysis, the factors that significantly correlated with recovery from infection were the liposomal amphotericin B treatment (p = 0.026), doses of L-AmB (p = 0.008) and the length of the treatment (p = 0.01), respectively. It seems to have increased in recent years. Although a reduction of mortality has been observed recently, the mortality rate still remains high. Extensive and aggressive diagnostic and therapeutic procedures are essential to improve the prognosis in these patients.

Aim: There are more than 350 million people worldwide chronically infected with hepatitis B virus (HBV), who are at high risk for the development of hepatitis, cirrhosis and hepatocellular carcinoma (HCC). Because of the conflicting results about c-kit expression in HCC and the key role played by c-kit in gastrointestinal stromal tumours (GIST) and other solid tumours, the aim of this study was to determine c-kit expression in the course of hepatitis B infection., Materials and Methods: Paraffin-embedded tissues in Cukurova University Faculty of Medicine Department of Pathology between January 2002 and February 2006 were searched restrospectively to investigate this issue. We performed immunohistochemistry on biopsies of 125 patients with HBV infection, grouped as: mild, moderate and severe hepatitis, cirrhosis and HCC, 25 patients in each of them, using anti c-kit monoclonal antibody. The severity of parenchymal inflammation and of interface hepatitis was semiquantitatively graded on a haematoxylin and eosin stained paraffin sections. Additionally, 50 more HCC, formed on HBV basis, were studied to determine the prevalence of c-kit overexpression., Results: In cirrhotic liver, lower intensity of staining and rarely c-kit positivity were present. The greatest number of the c-kit positivity and higher intensity of staining was found in the livers of patients with severe hepatitis and HCC. In chronic hepatitis B infection, the staining intensity was parallel with the grade and stage of the disease. In the areas where fibrosis was seen, c-kit positivity was rare or absent. In the HCC specimens, c-kit positivity appeared both inside and around the cancerous nodes. C-kit expression was observed in 62 of 75 HCC tissue specimens (82%) (p < 0.001)., Conclusions: C-kit positivity was observed in the mitotic, proliferating and also dysplastic hepatic cells. These results suggest that c-kit expression may be used as an early diagnostic indicator for HBV induced HCC.

Palmar-plantar erythrodysesthesia (PPE) is a distinctive and relatively frequent toxic reaction related to some chemotherapeutic agents. Doxorubicin, cytarabine, docetaxel, fluorouracil, and capecitabine are the most frequently implicated agents. Recently, taxanes, especially docetaxel, have been widely used in combination with capecitabine in patients with metastatic breast cancer (MBC). A high percentage of PPE has been seen in patients undergoing this combination therapy. PPE seems to be dose dependent and both peak drug concentration and total cumulative dose determine its occurrence. Withdrawal or dose reduction of the implicated drug usually gives rise to amelioration of the symptoms. Supportive treatments such as topical wound care, elevation, and cold compresses may help to relieve the pain. Use of systemic corticosteroids, pyridoxine (vitamin B6), blood flow reduction, and, recently, topical 99% dimethyl-sulfoxide have been used with variable outcomes. Vitamin E treatment has not been published before, especially without dose reduction of docetaxel-capecitabine therapy. Here we present five MBC patients treated with docetaxel-capecitabine combination therapy in whom PPE was observed during the clinical follow-up period. In all patients grade 2-3 PPE was observed. Vitamin E therapy was started at 300 mg/day p.o. without dose reduction of therapy and after 1 week of treatment PPE began to disappear. We suggest that it could be of interest to consider vitamin E as a preventive drug when drugs with a strong association with PPE are going to be administered.

Objective: Within soft-tissue sarcoma, primitive neuroectodermal tumors have been shown to cover a wide spectrum of small round cell sarcomas, including Ewing's sarcomas (ES) and primitive neuroectodermal tumors (PNET). The role of the stem cell factor/kit pathway has been investigated in different human tumors especially in chronic myelocytic leukemia and gastrointestinal stromal tumor and an autocrine loop has been assumed in small cell lung carcinoma, and recently in ES and PNET. Our aim is to investigate the c-kit expression in ES and PNET and also to assessed if c-kit has any role in disease process., Methods: We thoroughly searched the archives of the Department of Pathology, Faculty of Medicine, Cukurova University Turkey, between 2000 and 2004; and found 14 ES and 14 PNET paraffin embedded tissues. We carried out the detection of the c-kit expression by immunohistochemical staining., Results: The patient's median age was 23.7 +/-14.6 (12 male and 16 female). Five were diagnosed as metastatic disease whereas 23 were diagnosed as non-metastatic disease at admission. The mean follow up period was 38.9 +/- 22.3 months. The main localization of the disease was lower extremity (32.1%), and others were as follows: head and neck 25%, thorax and abdomen 14.3%, pelvic and upper extremity 7.1% (11 were localized skeletal and 17 were extraskeletal). According to treatment modalities, 10 were treated with surgery alone, 11 with surgery and chemotherapy, and 7 with surgery, radiation therapy and also with chemotherapy. The primary tumor was lower than 5 cm in its dimension in 21 patients. While in 5 patients, tumor was more than 5 cm but did not exceed 10 cm, it was >10 cm in 2 patients. The c-kit expression was positive in 7 patients both cytoplasmic and membranously, whereas 8 patients were positive cytoplasmically. In 5 PNET patients, c-kit expression were stained immunohistochemically in over 50% and in 3 of ES patients. There was no significant correlation between c-kit expression and gender, localization, metastatic status, treatment modalities and tumor. Although in survival analysis, patients treated with surgery alone lived longer, while >50% of patients treated with c-kit expression lived for a shorter period., Conclusion: We suggest that therapy with tyrosine kinase inhibitor for PNET and ES patients may be an alternative in addition to standard therapy modalities, especially in patients non-responsive to standard therapy.

We present a case of granulocytic sarcoma (GS) of the heart. A 28-year-old man with relapsed acute myelogenous leukemia (AML-M2) had undergone a non-myeloablative allogeneic peripheral stem cell transplantation. Three years following transplantation, masses were evidenced in his heart by echocardiography but had completely disappeared following a common chemotherapy etoposide, mitoxantrone, ara-C (EMA) regimen for relapsed AML. The involvement of the heart with GS is very rare and this is the first case of extramedullary disease in the heart after allogeneic transplantation. Here we present the case history and related literature has been reviewed.

Objective: To examine the co-expression of CD19, CD45, CD38, CD56, and CD138 molecules in plasma cells of bone marrow (BM) aspirates and their relation with BM infiltration, and treatment in patients with multiple myeloma by flow cytometry., Methods: Forty BM aspirate samples were assessed from 40 patients at diagnosis and on follow-up at the Medical Oncology Department, Cukurova University, Balcali Hospital, Turkey, between 2002 and 2004. The mean age was 56.83 +/- 9.1 and male:female ratio was 2.6. All patients received at least 4 courses of VAD(vincristine, adriamycin, dexamethasone) regimens and 20 of them were also treated with high dose melphalan and peripheral autologous stem cell transplantation. The median follow-up period was 19.1 +/- 22.7 months., Results: Using light microscopy the BM smears stained with hematoxylin and eosin from patients on follow up were classified into one of 3 categories, complete remission (CR) (<5%), partial remission (PR) (>5% and <30%), and extensive infiltration (EI) (>30%). According to infiltration ratio 23 were evaluated CR, 2 were PR and 15 were EI. The mean value of CD19 was 6.01 +/- 9.5%, CD56 = 9.9 +/- 6.8%, CD138 = 8.6 +/- 5.6%, CD45 = 84.2 +/- 22.3% and CD38 = 59.5 +/- 25.4%. The flow cytometric analyses revealed that only the mean value of CD38 and CD45 expression were significantly high. We correlated infiltration ratio with each parametric and found statistically significant relations. We also correlated independent variables with each other and found a relation between CD38 and CD19 (p=0.005). We also defined the groups whether treated with peripheral autologous transplantation or not and compared the independent variables between them, in which CD138 was statistically significant (p=0.02)., Conclusion: We suggest BM plasma cells expressed mainly by CD38 and CD45 may have a role in generation of BM plasma cells and that CD138 expression may be considered in follow-up for minimal residual disease after autologous transplantation in myeloma patients.

Breast cancer is the malignant neoplasm most commonly associated with hypercalcemia. In breast cancer the majority of the hypercalcemia cases result from osteolytic metastatic bone disease of the primary tumor. In a few patients hypercalcemia results from other conditions like primary hyperparathyroidism. Here, we present two female patients who were treated for breast cancer. Hypercalcemia in these two patients was diagnosed as being due to primary hyperparathyroidism. One of them was submitted to surgery and the calcium level dropped to the normal level thereafter. The other one refused surgery and was treated with biphosphonate and calcitonin. We suggest that when hypercalcemia occurs in breast cancer, primary hyperparathyroidism should be considered as possible cause.

Here we describe a case of Rosai-Dorfman Disease (RDD) in a 25-year-old female patient from Turkey who was previously misdiagnosed with Toxoplasma Lymphadenitis, and review the manifestations and treatment of this rare entity. To the best of our knowledge this is the third description of RDD [Sinus Histiocytosis with Massive Lymphadenopathy (SHML)], involving bilateral cervical lymphadenopathy and nephromegaly previously misdiagnosed as Toxoplasma Lymphadenitis. Representative clinical, radiographic and histological findings are presented. Its etiology, diagnosis and management are also reviewed. Sinus Histiocytosis with Massive Lymphadenopathy is a rare disorder of unknown etiology, usually associated with lymph node enlargement in various superficial or deep sites. The key histologic feature of SHML is the presence of various numbers of large, pale histiocytic cells that contain within their cellular borders apparently engulfed lymphocytes (emperipolesis); these distinctive large, pale cells are S-100 protein positive CD-68 positive and CD1a negative by immunostaining. According to the literature the most effective treatment found was surgical debulking.