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Intracranial aspergillosis is a rare infectious disease of the central nervous system with high mortality rates. Our aim is to present 3 cases of intracranial aspergillosis who were surgically treated with intracavitary amphotericin B administration. First case was a 21-year-old male patient. Allogeneic stem cell transplantation treatment was performed because of aplastic anemia and vocal cord paralysis developed 10 days after treatment. Multiple aspergillosis abscesses were observed in the cranial magnetic resonance imaging (MRI). Cerebral lesions were excised and 0.3 cc of amphotericin B was applied locally. Second case was a 18-year-old male patient treated for acute lymphocytic leukemia. MRI was performed on the development of consciousness change during treatment and right frontal abscess was detected. The abscess was excised and amphotericin B was applied locally. Third case was a 45-year-old woman with mastectomy. She had chemotherapy after surgery and had blood stem cell transplantation because of pancytopenia. Two months after treatments, MRI was performed on the development of ataxia and a cerebellar abscess was detected. The abscess was surgically excised and local amphotericin B was applied. The first case deceased 2 weeks after surgery and the second case died 2.5 years later due to multi-organ failure. The third case is stil alive and neurologically stable after 14 years of surgical treatment. In intracranial aspergillosis, intracavitary amphotericin B therapy may be used as an adjunct after the surgical excision of abscess. This procedure may contributes to the regression of abscess or prevention of the recurrence. But comparative clinical studies are needed for more accurate conclusions. [ABSTRACT FROM AUTHOR]

We analyzed Her2 amplification in breast cancers with equivocal IHC staining to investigate the significance of percentage of Her2 immunostained tumor cells. We especially included the breast cancers with complete/incomplete membrane staining at moderate intensity in less than 10% of the invasive tumor cells. Of 1804 breast cases, 180 had moderate complete/incomplete membrane Her2 immunostaining. According to 2013 ASCO/CAP guideline, 124 were in IHC score 2+ and 56 in 1+ category. The percentage of Her2 immunostained invasive tumor cells were determined by visual estimation at the time of diagnosis and categorized into three groups; <10%, 10–50%, and >50% for this review. FISH was performed by dual DNA probe and data of Her2/cep17 ratio, Her2/cell and Cep17/cell were recorded applying 2013 ASCO/CAP criteria. There were 22 cases (12.2%) in >50% group, 102 (56.7%) in 10–50% group, and 56 (31.1%) in <10% group. Overall Her2 amplification was 25.5%. Her2 was amplified in 12 (54.5%) cases in >50% group; 26 (25.4%) in 10–50% and 8 (14.3%) in <10%. Her2 amplification was more frequent in cancers with >50% moderately immunostained cells in IHC equivocal group. However, most of Her2 IHC equivocal breast cancers contain moderate amount (10–50%) of immunostained cells. Relatively small but non-neglectable number (14%) of cases in <10% group was Her2 amplified by FISH which approaches to overall incidence of Her2 overexpression (15–20%) in all breast cancer. Breast cancers with moderate complete/incomplete membrane Her2 IHC staining in <10% of invasive tumor cells should be regarded as equivocal and reflex FISH should be performed in these cases. [ABSTRACT FROM AUTHOR]

APOBEC3B belongs to a protein family of cytidine deaminases that can insert mutations in DNA and RNA as a result of their ability to deaminate cytidine to uridine. It has been shown that APOBEC3B-catalysed deamination provides a chronic source of DNA damage in breast cancers. We investigated APOBEC3B expression in four drug resistant breast cancer cell lines (Doxorubicin, Etoposide, Paclitaxel and Docetaxel resistant MCF-7 cell lines) using a novel RNA in situ hybridization technology (RNAscope) and compared expression levels with drug sensitive MCF-7 cell line. After RNAscope staining, slides were scanned and saved as digital images using Aperio scanner and software. Quantitative scoring utilizing the number of punctate dots present within each cell boundary was performed for the parameters including positive cell percentage and signal intensity per positive cell. In Doxorubicin and Etoposide resistant MCF-7 cell lines, APOBEC3B expression was approximately five-fold increased (23% and 24% respectively) with higher signal intensity (1.92 and 1.44 signal/cell, respectively) compared to drug sensitive MCF-7 cell line (5%, 1.00 signal/cell) with statistical significance. The increase of APOBEC3B expression in Docataxel resitant and Paclitaxel resistant MCF-7 cell lines was not very high. In conclusion, APOBEC3B expression was increased in some population of tumor cells of drug resistant cell lines. At least for some drugs, APOBEC3B expression may be related to drug resistance, subjecting to some tumor cells to frequent mutation. [ABSTRACT FROM AUTHOR]

Summary: Neo-vascularisation of the acellular dermal matrix (ADM) is an essential procedure if a full-thickness wound is closed with ADM and skin is grafted over the ADM. In this study, we aimed to improve the neo-vascularisation of ADM by combining the effects of negative pressure wound therapy (NPWT) and mesenchymal stem cells (MSCs) on angiogenesis. In this study, 28 female Sprague-Dawley rats were used and divided into four groups. Full-thickness dorsal skin defects were created in 2 × 2 cm dimensions. The wounds were treated with only the ADM in group 1, the ADM and NPWT in group 2, the ADM and MSCs in group 3 and the ADM, NPWT and MSCs in group 4. By the ninth day of surgery, the excisional biopsy samples were histologically examined to identify the rates of ADM adherence to the recipient bed; the newly formed blood vessels which penetrate the ADM vertically and vascularisation were evaluated by immunohistochemical staining. The graft adherence rates were higher in group 4 than in the other groups statistically, p = 0.003. The numbers of cluster of differentiation 31 (CD31)-stained newly formed microvessels were higher in group 4 than in the other groups statistically, p < 0.05. All subjects in group 4 had the vertical vessels in normal calibration with open lumen vessels which penetrate the ADM. These findings suggest that MSC transplantation induces angiogenesis more efficiently than NPWT. The combination of the NPWT with MSC in this study has shown a synergistic effect on angiogenesis and has affected the neo-vascularisation of the ADM significantly. [Copyright &y& Elsevier]

Abstract: The number of mitotic figures in a predefined area is essential in pathologic evaluation for most tumors. This information sometimes provides clues in differentiating neoplastic lesions from nonneoplastic ones and sometimes in defining and grading of the tumors as well as prognosticating expected lifetime of the patient. As a generally accepted concept, scanning a certain number of consecutive nonoverlapping areas that are rich in viable tumor cells is required. Invasion fronts or the periphery of the tumors is preferred for counting mitosis. The target area to be counted for mitotic activity for various tumors is standardized as the number of mitosis in an established number of high-power fields. However, suggested mitotic counts, which constitute the basis of these studies, were obtained via the old microscopes, which usually had narrower visual fields than the state-of-the-art microscopes. Because the visual fields of the present microscopes provide larger areas compared with the older ones, corrections in mitosis counting are needed to make them compatible with the criteria, which had been put forward in the original reference studies. [Copyright &y& Elsevier]

Abstract: Objective: Overdose of acetaminophen (APAP) can lead to severe liver injury in humans and experimental animals. Pentraxin-3 (PTX-3) is produced and released by several cell types. In this study, we aimed to evaluate whether PTX-3 is a potential biomarker in the identification of APAP-induced liver injury. Materials and methods: Thirty adult male Wistar rats were randomly divided into three groups: control, APAP-1 and APAP-2 groups. APAP-1 (1g/kg) and APAP-2 (2g/kg) group rats were given APAP by gastric tube. Liver tissues and blood samples were obtained for biochemical and histopathological analysis. Biochemical parameters, plasma and liver PTX-3 levels and degree of liver necrosis were measured in all groups. Results: APAP treatments caused necrosis in liver and accompanied by elevated liver PTX-3 levels after 48h. In APAP-1 and APAP-2 groups when compared with control group (7.5±3.3ng/mg protein), mean liver PTX-3 concentrations were 14.1±3.0 (p =0.032) and 28.5±8.2 (p <0.001)ng/mg protein, respectively. All rats (100%) in the APAP-2 group had the degree 3 liver necrosis. However 10%, 40% and 50% of rats had the degree 1, the degree 2 and the degree 3 liver necrosis in the APAP-1 group, respectively. The degrees of liver necrosis of the APAP-1 and APAP-2 groups were higher than the group of control (p <0.001 and p <0.001, respectively). Conclusions: PTX-3 may have a role in the APAP-induced liver injury in the rats. The elevated liver PTX-3 in the APAP-induced hepatic necrosis might be a marker of acute histological liver damage. Further prospective studies are necessary to clarify the prognostic value of liver PTX-3 for prediction of histological hepatic necrosis in the APAP-induced liver injury. [Copyright &y& Elsevier]

Abstract: Objective: Novel treatment strategies are needed in the treatment of endometriosis due to limited success rates with the currently available options. As inflammatory and immunological mechanisms have been shown to be involved in the mechanism of the disease, new modalities are likely to emerge. We investigated the effects of infliximab (INF), etanercept (ETA) and letrozole on the regression of experimental endometriosis. Study design: In this experimental randomized trial, endometriosis was induced surgically in 44 adult female Sprague–Dawley rats. Establishment of implants was confirmed in 41 animals by a second operation on the 21st day. The rats were then randomly divided into four groups. Group I (n =10) served as controls. Group II (n =11) received letrozole (0.18mg/kg, i.p.), group III (n =10, i.p.) ETA (2.016mg/kg, i.p.), and group IV (n =10) INF (15.12mg/kg, i.p.) for a second 21-day period. Endometriotic implant size along with peritoneal fluid VEGF level and immunoreactivity were determined before and after the treatment in each group. Results: Endometriotic implant size reduced in all treatment groups. The effect of letrozole and ETA on implant size was similar but was significantly better than INF. Level of VEGF in peritoneal fluid did not change in any treatment group but post-treatment VEGF immunoreactivity was found significantly lower in the letrozole treated group. Conclusions: Letrozole and ETA caused a regression on the implant size in experimental endometriosis. The only group with decreased VEGF expression was letrozole. [Copyright &y& Elsevier]

Objective: To investigate the expression of cyclooxygenase-2 (Cox-2) and vascular endothelial growth factor (VEGF) in ovarian endometriotic cysts and assess their relation with angiogenesis. Design: Experimental clinical study. Setting: University hospital. Patient(s): Fifty patients with ovarian endometriotic cysts. Intervention(s): Surgical excision of 50 ovarian endometriotic cysts. Main Outcome Measure(s): Microvessel density and the expression of Cox-2 and VEGF were analyzed immunohistochemically. Result(s): Cyclooxygenase-2 immunoreactivity was mainly cytoplasmic in glandular epithelial cells in all of the ovarian endometriotic cysts, with low expression in 12 cases (24%), moderate expression in 21 (42%), and high expression in 17 (34%). Vascular endothelial growth factor immunoreactivity was mainly cytoplasmic in stromal cells in 46 (92%) of the ovarian endometriotic cysts, with low expression in 12 cases (24%), moderate expression in 18 (36%), and high expression in 16 (32%). No immunoreactivity was present in 4 cases (8%). Both Cox-2 (r = 0.728) and VEGF (r = 0.670) were closely, statistically significantly related with microvessel density in ovarian endometriotic cysts. Cyclooxygenase-2 and VEGF also were highly statistically significantly correlated (r = 0.777) with each other. Conclusion(s): We observed Cox-2 expression mostly in glandular epithelial cells of ovarian endometriotic cysts, whereas VEGF expression was observed mainly in stromal cells. Cyclooxygenase-2 and VEGF were closely correlated with each other, and both of them appear to play a role in the angiogenesis of ovarian endometriosis. [Copyright &y& Elsevier]

Abstract: Solitary fibrous tumours (SFT) of the central nervous system are rare. Such lesions are mesenchymal neoplasms that resemble meningioma. To date, 73 cases of SFT have been reported in the literature, but there is no reported case of an SFT that extends into both the supratentorial and infratentorial spaces. A 76-year-old man presented with headache, dysarthria and ataxia of 2 months’ duration. MRI revealed a right cerebellar tumour, extending superiorly to the occipital lobe. During surgery, a huge, solid and well-capsulated tumour was observed. The tentorium cerebelli was also damaged by the tumour. Histological and immunohistochemical studies confirmed the diagnosis of SFT. This is the first reported case of SFT located in both the infratentorial and supratentorial spaces. SFT are spindle cell neoplasms with a characteristic immunohistochemical profile of CD34, vimentin and bcl-2 positivity. [Copyright &y& Elsevier]

Purpose: The purpose of the study was to assess the role of atopy on the development of appendicitis. Acute appendicitis is the most common indication for emergent laparotomy especially in the late teens and early 20s. The pathogenesis generally begins with luminal obstruction caused by fecal mass, seeds, stricture, and bacterial, parasitic, or viral infections. The present study was designed to evaluate whether allergic reaction is indeed an undefined leading factor for luminal obstruction.Material and Methods: Mix inhalant and food prick tests were performed in 111 patients who underwent appendectomy for acute appendicitis and in 100 control patients. The material of appendectomy was examined, acute appendicitis was verified and graded according to the severity of inflammation and eosinophilic infiltration rate in the wall of appendix by a pathologist. Demographic data were recorded, and peripheral eosinophil count was also performed.Results: Mix prick test of 33 patients (29.7%) and food prick test of 14 patients (12.6%) were positive in study group when compared with 7 patients (7%) and 1 patient (1%) in control group (p < 0.001). A total of 38 patients (34.2%) in the study group were reactive with mix or food prick test when compared with 8 patients (8%) in control group. There was no significant difference between eosinophilic infiltration rate, peripheral eosinophil count, severity of inflammation, and Alvarado score of mix prick test positive and negative patients in study group.Conclusion: Atopy incidence in patients with acute appendicitis was significantly higher when compared with control group. However, eosinophilic infiltration rate, inflammation grade, and peripheral eosinophil count were not able to explain the relationship between the two conditions. Atopy is a risk factor for acute appendicitis. [ABSTRACT FROM AUTHOR]

Abstract: Intracranial marginal zone B-cell lymphoma presenting as a dural-based mass is rare. A 45-year-old woman who had generalized tonic-clonic seizures and speech disturbance for 6months was referred to our hospital. Radiology suggested a subdural hematoma (SDH). No improvement in the radiological findings or symptoms occurred with conservative follow-up. Therefore, she underwent a craniotomy for drainage of the suspected SDH. Intraoperatively, dural plaque-like thickening was observed, with no SDH, and a biopsy was performed. After histopathological and immunohistochemical studies, a mucosa-associated lymphoid tissue (MALT) lymphoma was diagnosed. The patient underwent radiotherapy with no postoperative complications or recurrence. Early diagnosis and treatment of primary dural lymphoma is important. Histopathological evaluation is necessary for diagnosis. MRI cannot reliably differentiate between SDH and some dural lesions that present as diffuse infiltration. Therefore, these differential diagnoses should be considered. [Copyright &y& Elsevier]

Abstract: The clinical syndrome produced by a cyst in the cerebellopontine angle (CPA) may closely mimic that of an acoustic neuroma, with sensorineural hearing loss, impaired corneal reflex, and cerebellar signs with increased intracranial pressure. Facial palsy is seldom reported. Gliosis of the eighth nerve is common but its association with CPA arachnoid cyst is very rare and not previously reported. We report a patient with a CPA arachnoid cyst associated with gliosis of the eighth cranial nerve. He presented with right peripheral facial palsy, and gliosis of the eighth nerve was diagnosed intraoperatively. CPA arachnoid cysts should be included in the differential diagnosis of peripheral facial palsy and the eighth cranial nerve should be examined during the resection and fenestration of the arachnoid cyst. [Copyright &y& Elsevier]

The use of nanotechnology in cancer treatment offers exciting opportunities, including the possibility of destroying tumors with minimal damage to healthy tissue by novel targeted drug delivery systems. pH differences between healthy and tumor microenvironment provide pH responsive release of drugs at tumor site via smart nanoparticles. In this study, chitosan coated superparamagnetic iron oxide nanoparticles (CS MNPs) were in situ synthesized by ionic crosslinking method as nanocarrier systems and loaded with the drug Bortezomib (Velcade®). The drug loading capacity, drug release and stability of CS MNPs were analyzed. CS MNPs were visualized inside the cells by fluorescence microscopy. The cytotoxicity of Bortezomib, CS MNPs and Bortezomib loaded CS MNPs were tested by XTT analyses in vitro. Gene expression analyses revealed that pro-apoptotic PUMA and NOXA genes were upregulated while anti-apoptotic BCL-2, SURVIVIN and cIAP-2 genes were downregulated at Bortezomib loaded CS MNP treated cells. Immunocytochemical analyses demonstrated an increase in p53 tumor suppressor protein levels at treated cells, which supports the upregulation of PUMA and NOXA genes, while Survivin protein level did not significantly change. This study points out that the pH responsive magnetic targeting of Bortezomib is more efficacious than free drug treatment. Moreover, targeted delivery of Bortezomib would reduce the frequency of drug administration by lowering the required amount of drug dose. [ABSTRACT FROM AUTHOR]

Abstract: Differentiation of low-grade breast carcinomas from fibroadenomas with atypia on fine-needle aspiration cytology material may sometimes be problematic. In some cytological samples of these lesions, both the nuclei of cells and patterns of cell clusters display substantial overlapping morphological characteristics. Nuclear morphometry on cytological material is suggested as an ancillary method for the differential diagnosis in many lesions, including breast tumors. Twenty-five cytological samples obtained from patients with breast lesions, which were histopathologically confirmed as grade I ductal carcinomas (n=10), tubular carcinomas (n=5), and fibroadenomas with atypia (n=10), were utilized in this study. Eight geometric features of about 2002 nuclei from these tumors were measured. Discriminant analysis was performed on this data set in order to test the correct classification based on the eight measured variables. Statistical analyses were carried out with two fundamentally different approaches: in the first one, the entire data from all measured nuclei were used for classification. In the second one, a subset of data representing the 10% most deviated values of variables was extracted from the entire dataset to simulate the “selective examination” performed during classical morphologic evaluation. When the entire data was used in discriminant analysis, the overall performance in the correct classification rate was found to be approximately 50%, which was considered an unacceptable value in routine diagnostic practice. In the subset of data constructed with our systematic and reproducible “selection bias”, the overall performance of correct classification rate of the same discriminant model improved substantially to 97%. Morphologic examination is actually based on selection. The use of data obtained from all of the cells in morphometry, as previously used in nearly all of the statistical methods, may cause a masking effect in diagnostically important features. Morphometric studies may seem to be useless when this effect is not taken into account. However, with a systematic and reproducible selection of the values with a proper “bias”, morphometry may provide some discriminatory information in overlapping lesions. [Copyright &y& Elsevier]

Abstract: Purpose: To present proton magnetic resonance spectroscopy and diffusion-weighted imaging (DWI) findings of central neurocytoma (CN). Methods and Materials: Imaging findings of seven patients with the histopathological diagnosis of CN (five male and two female; age range, 21–28 years of age) were evaluated retrospectively. In addition to conventional magnetic resonance imaging features, we also assessed the metabolite ratios and tumor normalized apparent diffusion coefficient (NADC), which was calculated by dividing the tumor apparent diffusion coefficient (ADC) values by normal ADC. Approval from our institutional review board was obtained for this review. Results: The tumor choline/creatine ratios were 5.17±2.38, while N-acetyl aspartate/choline and N-acetyl aspartate/creatine ratios were 0.33±0.15 and 1.84±1.38, respectively. On DWI, tumors had heterogeneous hyperintense appearances when compared with the contralateral parietal lobe white matter and tumor NADC values were 0.63±0.05. Conclusion: Significantly increased choline/creatine and decreased N-acetyl aspartate/choline ratios with lower NADC values in CN resemble high-grade gliomas and complicate the diagnosis. Familarity its physiologic features would help to presurgical diagnosis of ventricular and exraventricular CNs. [Copyright &y& Elsevier]