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Background & objective Colorectal cancer (CRC) is the third most common cancer worldwide with a high mortality rate. The main causes of death in patients are recurrence and metastasis which are mainly attributed to the small subpopulation of cells within tumors called cancer stem cells (CSCs). This study aimed to evaluate the correlation between the expression of ALDH1 and CD133 as CSC associated markers and clinicopathological characteristics in CRC. Methods In this cross-sectional study, a total of 483 CRC tumor samples were immunohistochemically stained for detection of CD133 and ALDH1 markers. Correlations of marker expression with clinicopathological factors were also evaluated. Results There was a significant correlation between the luminal intensity of CD133 and neural invasion (P=0.05) and between the cytoplasmic intensity of CD133 and metastasis (P=0.05). In terms of H-score, a positive significant relation was observed between cytoplasmic expression of CD133 and lymph node (P=0.02), neural (P=0.04) and vascular invasion (P=0.02). The ALDH1 cytoplasmic expression showed a significant correlation with tumor size (P=0.001). Conclusion Our findings showed that increased expression of CD133 and ALDH1 is associated with tumor progression and worse outcomes in CRC patients. These markers can be good candidates for localized targeting of CSCs using antibodies. Future researches need to be improved approaches for early detection of CRC, and treatment monitoring for CRC and other cancers.

Background The crucial oncogenic role of cancer stem cells (CSCs) in tumor maintenance, progression, drug resistance, and relapse has been clarified in different cancers, particularly in colorectal cancer (CRC). The current study was conducted to evaluate the co-expression pattern and clinical significance of epithelial cell adhesion molecules (EpCAM) and activated leukocyte cell adhesion (CD166 or ALCAM) in CRC patients. Methods This study was carried out on 458 paraffin-embedded CRC specimens by immunohistochemistry on tissue microarray (TMA) slides. Results Elevated expression of EpCAM and CD166 was observed in 61.5% (246/427) and 40.5% (164/405) of CRC cases. Our analysis showed a significant positive association of EpCAM expression with tumor size (P = 0.02), tumor stage (P = 0.007), tumor differentiate (P = 0.005), vascular (P = 0.01), neural (P = 0.01), and lymph node (P = 0.001) invasion. There were no significant differences between CD166 expression and clinicopathological parameters. Moreover, the combined analysis demonstrated a reciprocal significant correlation between EpCAM and CD166 expression (P = 0.02). Interestingly, there was a significant positive correlation between EpCAM/CD166 phenotypes expression and tumor stage (P = 0.03), tumor differentiation (P = 0.05), neural, and lymph node invasion (P =0.01). Conclusions The significant correlation of EpCAM and CD166 expression and their association with tumor progression and aggressive behavior is the reason for the suggestion of these two CSC markers as promising targets to promote novel effective targeted-therapy strategies for cancer treatment in the present study.

DNA damage-inducible transcript 4 (DDIT4) is induced in various cellular stress conditions. This study was conducted to investigate expression and prognostic significance of DDIT4 protein as a biomarker in the patients with colorectal cancer (CRC). PPI network and KEGG pathway analysis were applied to identify hub genes among obtained differentially expressed genes in CRC tissues from three GEO Series. In clinical, expression of DDIT4 as one of hub genes in three subcellular locations was evaluated in 198 CRC tissues using immunohistochemistry method on tissue microarrays. The association between DDIT4 expression and clinicopathological features as well as survival outcomes were analyzed. Results of bioinformatics analysis indicated 14 hub genes enriched in significant pathways according to KEGG pathways analysis among which DDIT4 was selected to evaluate CRC tissues. Overexpression of nuclear DDIT4 protein was found in CRC tissues compared to adjacent normal tissues (P = 0.003). Furthermore, higher nuclear expression of DDIT4 was found to be significantly associated with the reduced tumor differentiation and advanced TNM stages (all, P = 0.009). No significant association was observed between survival outcomes and nuclear expression of DDIT4 in CRC cases. Our findings indicated higher nuclear expression of DDIT4 was significantly associated with more aggressive tumor behavior and more advanced stage of disease in the patients with CRC.

Background and Aims Several studies have reported the results of renal biopsies from different registries and single centres. In most series focal and segmental glomerulosclerosis (FSGS), IgA nephropathy (IgAN), membranous glomerulopathy (MG) and lupus nephritis (LN) have been reported as the most common primary and secondary glomerulonephritis (GN). This study was conducted to update the reports of our hospital, as the main referral kidney centre of the country. Method Data from 4713 patients, who had undergone renal biopsy between Sept-1999 to Sept.-2019 were extracted from the GN data registry of our centre. Demographic data, renal syndrome at presentation and laboratory findings were studied. Almost all kidney specimens had been studied with light and immunofluoroscent microscopes and in selected cases with electron microscope. Nephrotic syndrome (NS) was defined as proteinuria >3.5 g/day or >3 g/day, if associated with hyperlipidemia, hypoalbuminemia and edema. Nephritic syndrome was defined as proteinuria >500 mg/day and hematuria, with or without hypertension and/or serum Cr (SCr) ≥1.4 mg/dl. Subnephrotic (SN) proteinuria was defined as proteinuria of 200 -3000 mg/day. Acute kidney injury (AKI) was defined as increase in SCr >1.4 during the past few days to weeks before admission. Results The most frequent type of renal pathology was MG (25.2%) followed by FSGS (13.6%), IgAN (12%), LN (8.9%), minimal change disease (MCD) (7%), crescentic GN (6.2%) and paraprotein associated GN (4.3%). The prevalence of different renal pathologies changed significantly over time (p-value:0.000) (figure).The most common clinical presentation was NS (60.2%), followed by SN proteinuria (15.2%), nephritic syndrome (12%) and AKI (7.5%). Age, sex, clinical syndrome at presentation and hypertension were significantly different between major pathological diagnostic groups (p=0.000). Table shows the detailed clinical features of the most important glomerulonephritides in our centre. Figure shows the changes in prevalence of each pathologic diagnosis over 21 years. Conclusion In our series the most common types of GN were MG, FSGS and IgAN, which are the most frequent glomerulonephritides in other biopsy series with various orders. Most of our patients presented with NS, followed by SN proteinuria. The relative frequency of MPGN and LN have reduced and FSGS has increased over time.

Context: Neuroblastoma is often infiltrated by inflammatory cells, particularly macrophages and T lymphocytes, but the significance of these cells remains unclear. One possible role of these inflammatory cells is that they represent a cell-mediated immune response against cancer. CD8+ lymphocytes are a known crucial component of cell-mediated immunity. The purpose of this study was to explore the prognostic value of tumor-infiltrating CD8+ cytotoxic lymphocytes in Neuroblastoma. Subjects and Methods:Tumor-infiltrating CD8+ lymphocytes were assessed by immunohistochemical staining of tumor tissue from 36 neuroblastoma from April 2008 to May 2015. The number of CD8+ T-cells was counted in tumor nest (intratumoral) and in the fibrovascular stroma of tumor (peritumoral), and their relationship with clinicopathologic outcome was determined. Results: The total number of CD8+ cells was inversely correlated with tumor histology grade (P < 0.001), vascular invasion (P < 0.001), capsular invasion (P < 0.002), calcification (P < 0.005), necrosis of tumor (P < 0.001), regional lymph nodes invasion (P < 0.003), distant metastasis (P < 0.003), stage (P < 0.003), and was positive correlated with N-myc oncogene presentation (P < 0.002) in neuroblastoma. However, there were no correlation between patient's age, sex, and size of tumor with infiltration of CD8+ cells (P < 0.097, P < 0.142, and P < 0.722, respectively). Conclusions: In this analysis, total CD8 T-cell count was a dependent prognostic factor in children. Total number and stromal CD8 lymphocytes were associated with better patient survival (P < 0.003 and P < 0.05, respectively) in children. These results suggest that tumor-infiltrating CD8 T lymphocytes have antitumor activity and influence the behavior of neuroblastoma and might be potentially be exploited in the treatment of neuroblastoma in children.

Prostate cancer is the second cause of cancer-related deaths in men and this is attributed to its aggressiveness and metastatic identity. Our objective was to evaluate the expression patterns of endothelial cell marker CD34 and mast cell marker CD117 in prostate adenocarcinoma (PCa) compared to benign prostate tissue and their relation to the clinicopathological features. A total of 90 prostate samples, including 45 PCa and 45 benign prostate tissues were immunohistochemically examined for the detection of CD34 and CD117 markers. The expression of these markers was also correlated with clinicopathological parameters. Significant overexpression of CD34 was found in PCa group compared to benign prostate tissues ( P ≤ 0.001). The expression of CD34 and CD117 in PCa with advanced Gleason score was more than PCa with early Gleason score ( P = 0.02 and P = 0.005, respectively). A significant positive correlation was observed between CD34 expression and the level of total serum prostate specific antigen (sPSA) ( P = 0.006). In addition, CD34High/CD117High phenotype was frequently observed in PCa cases compared to benign prostate tissues ( P ≤ 0.001). There was a positive significant association between CD34High/CD117High phenotype with advanced Gleason score ( P ≤ 0.001) and total sPSA level ( P = 0.02). Our findings showed that increased expression of CD34 and CD117 markers confer tumor progression and aggressiveness on PCa. These molecules may be good candidates for targeted therapy of PCa patients.

Acute lymphoblastic leukemia is the most common malignancy in children with a 5-year survival rate, accounting for 80% of cases. Melanoma is rare in children and has been reported as a sporadically occurring secondary malignant neoplasm in children with acute lymphoblastic leukemia. This study presented a 10-year-old Iranian child with pre-B-cell acute lymphoblastic leukemia that was diagnosed at age 6. She was fully recovered after 2 years of treatment. One year and six months after cessation of treatment, she was referred with a 1×2 cm mass in her right parietal region of scalp. Biopsy of the lesion confirmed the diagnosis of malignant melanoma. Computed tomography scan of the chest and abdomen also confirmed extensive liver metastasis which was corroborated by liver biopsy. Bone scan also revealed bone metastases. Early diagnosis and treatment of these tumors is extremely important and these patients should be closely monitored and undergo regular physical examination.

Cancer stem cells (CSCs) represent a population with tumour-initiating, self-renewal, and differentiation potential. This study aimed to evaluate the expression patterns and clinical significance of chemokine receptor type 4 (CXCR4) as a novel CSC marker in renal cell carcinoma (RCC). The expression of CXCR4 was examined in 173 well-defined renal tumour tissues, including 106 (61.5 %) clear cell renal cell carcinomas (ccRCCs), 35 (20 %) papillary renal cell carcinomas (pRCCs), and 32 (18.5 %) chromophobe renal cell carcinomas (ChRCCs), by immunohistochemistry on a tissue microarray. The association between expression of this marker and clinicopathologic parameters was then analysed. There was a significant difference in the expression levels of CXCR4 in the ccRCC samples compared to the ChRCC and pRCC samples (P

Distinction between minimal change disease and unsampled Focal Segmental Glomerulosclerosis is a challenging concept in kidney biopsy of patients with nephrotic syndrome with minimal histopathological findings. This study was performed to compare electron microscopic findings in patients with steroid-resistant nephrotic syndrome with minimal histopathological abnormalities and cases with Focal Segmental Glomerulosclerosis. This Cohort study was conducted in Cancer Institute, Imam Khomeini Hospital Complex, Tehran, Iran. Twenty patients with steroid-resistant nephrotic syndrome and minimal changes on the light microscopic study were selected as case group. Similarly, 20 patients with Focal Segmental Glomerulosclerosis were selected as the control group. Ultrastructural findings were re-evaluated and scored qualitatively (0-3+). In patients with minimal changes on light microscopic evaluation, clinical course of the disease was followed after 5 years. Mean ages of the patients (8 women and 12 men) in case and control groups were 12.9 and 15.9 years, respectively (p > 0.05). There was no significant difference in number of examined glomeruli and sampling from cortico-medullary junction area between the groups. The mean percentage of sclerotic glomeruli in control group was 15.4%. Tubular atrophy and interstitial fibrosis were more frequent in control patients. Podocyte proliferation, GBM duplication (involving more than 10% of capillary walls), and moderate to severe multifocal expansion of mesangial matrix were significantly more obvious in FSGS patient samples (p < 0.05). No statistically significant difference was found in severity of cytoplasmic vacuolization, GBM wrinkling and splitting between the groups. Most of (80%) the patients with minimal changes improved during the 5-year follow-up. Generally, we concluded that Podocyte proliferation, GBM remodeling, and moderate to severe mesangial matrix expansion are the most reliable findings on electron microscopic examination in favor of FSGS.

Summary Human telomerase reverse transcriptase (hTERT) is an active component of telomerase and responsible for its catalytic activity, associated with cell proliferation and differentiation. For the first time, the present study was conducted to evaluate the expression and prognostic significance of hTERT in different histological subtypes of renal cell carcinoma (RCC). Expression of hTERT was examined in 176 well-defined renal tumour samples including clear cell RCCs (ccRCCs), papillary and chromophobe RCCs using immunohistochemistry on tissue microarrays. The association between hTERT expression and clinicopathological parameters as well as survival outcomes were then analysed. There was a statistically significant difference in terms of hTERT expression among various RCC subtypes. In ccRCC, increased expression of hTERT was significantly associated with advanced stage, higher grade, presence of microvascular invasion, lymph node invasion, and metastasis. Moreover, in the multivariate analysis, tumour stage and tumour size were independent predictors of the disease-specific survival (DSS). Additionally, expression of hTERT was found to be a significant predictor of worse DSS (p = 0.012) in the univariate analysis. In papillary carcinoma samples (type I and II), significant association was detected between hTERT expression and the tumour stage (p = 0.010, p = 0.050), respectively. In chromophobe RCC, no significant association was detected between expression of hTERT and clinicopathological parameters and survival data. We showed that hTERT protein expression was associated with more aggressive tumour behaviour and more advanced disease in ccRCC patients. Also, hTERT may be a novel poor prognostic indicator of DSS, if the patients are followed for more prolonged time periods.

Many renal cancer patients experience disease recurrence after combined treatments or immunotherapy due to permanence of cancer stem cells (CSCs). This study was conducted to evaluate the expression patterns and clinical significance of octamer-binding transcription factor 4 (OCT4) and NANOG as the key stem cell factors in renal cell carcinoma (RCC). A total of 186 RCC tissues were immunostained on a tissue microarray (TMA) for the putative CSC markers OCT4 and NANOG. Subsequently, the correlation among the expression of these markers, the clinicopathological variables and survival outcomes were determined. OCT4 and NANOG were expressed in both the nucleus and the cytoplasm of RCC cells. Coexpression of OCT4 and NANOG in renal cancer was significantly associated with RCC subtypes. A significant association was found among nuclear coexpression of OCT4 and NANOG, worse PFS in RCC, and the clear cell renal cell carcinomas (ccRCC) subtype. The OCT4-nuclear high/NANOG-nuclear high phenotype in RCC and ccRCC subtype indicated aggressive tumor behavior and predicted a worse clinical outcome, which may be a useful biomarker to identify patients at high risk of postoperative recurrence and metastasis. Cytoplasmic expression of NANOG could be considered as a novel independent prognostic predictor in patients with renal cancer.

Twist1 is a key transcription factor, which confers tumor cells with cancer stem cell (CSC)-like characteristics and enhances epithelial-mesenchymal transition in pathological conditions including tumor malignancy and metastasis. This study aimed to evaluate the expression patterns and clinical significance of Twist1 in renal cell carcinoma (RCC). The cytoplasmic and nuclear expression of Twist1 were examined in 252 well-defined renal tumor tissues, including 173 (68.7%) clear cell renal cell carcinomas (ccRCC), 45 (17.9%) papillary renal cell carcinomas (pRCC) and 34 (13.5%) chromophobe renal cell carcinoma, by immunohistochemistry on a tissue microarray. The association between expression of this marker and clinicopathologic parameters and survival outcomes were then analyzed. Twist1 was mainly localized to the cytoplasm of tumor cells (98.8%). Increased cytoplasmic expression of Twist1 was associated with higher grade tumors (P = 0.045), renal vein invasion (P = 0.031) and microvascular invasion (P = 0.044) in RCC. It was positively correlated with higher grade tumors (P = 0.026), shorter progression-free survival time (P = 0.027) in patients with ccRCC, and also with higher stage in pRCC patients (P = 0.036). Significantly higher cytoplasmic expression levels of Twist1 were found in ccRCC and pRCC subtypes, due to their more aggressive tumor behavior. Increased cytoplasmic expression of Twist1 had a critical role in worse prognosis in ccRCC. These findings suggest that cytoplasmic, rather than nuclear expression of Twist1 can be considered as a prognostic and therapeutic marker for targeted therapy of RCC, especially for ccRCC patients.

Background: Amplification and overexpression of human epidermal growth factor receptor 2 (HER2 / neu) oncogene has considerable prognostic value in breast and gastric cancers. This study aimed to evaluate the frequency, overexpression pattern, clinical significance, and concordance between the results for protein expression and gene amplification of HER-2/neu in gastric and gastro-esophageal junction carcinomas. Materials and Methods: In this study, 101 gastric tissue samples which were included in tissue microarray were immunohistochemically examined for overexpression of HER2/neu. Chromogenic in situ hybridization (CISH) was used for HER-2/neu amplification. The correlation of HER2/neu amplification with clinicopathological parameters was also assessed. In addition, concordance between CISH and IHC was detected. Results: This study demonstrated a significant difference in the overexpression of HER2/neu in gastric tumors. The overexpression of HER2/neu was significantly higher in intestinal type, poorly differentiated grade, large size (5 cm≤) and positive nodal involvement tumors (p-value=0.041, 0.015, 0.038 and 0.071, respectively). Also, amplification of HER2/neu according to CISH test, had a significant positive correlation with tumor size and tumor type (p-value=0.018 and 0.058, respectively).Concordance between CISH and IHC was 76.9% in 101 evaluable samples. Conclusions: IHC/CISH differences were attributed to basolateral membranous immunoreactivity of glandular cells resulting in incomplete membranous reactivity and/or a higher rate of tumor heterogeneity in gastric cancers compared to breast cancers. Therefore, this can be a potential marker for targeted therapy of malignant gastric tumors.

Introduction: The oncogenic form of anaplastic lymphoma kinase (ALK) gene is an attractive candidate marker for diagnostic and therapeutic purposes in several malignancies, including nonsmall cell lung cancer (NSCLC). This study aimed to examine the expression levels and clinical significance of ALK in a series of NSCLC tumors. Material and Methods: We retrospectively reviewed 140 samples of NSCLC, including 64 (46%) squamous cell carcinoma (SCC), 62 (44%) adenocarcinoma (ADC), and 14 (10%) large cell carcinoma (LCC) for expression of ALK using immunohistochemistry; and immunostaining patterns were correlated with clinicopathological parameters. Results: Expression of ALK was significantly different between SCC with ADC (P < 0.001) and LCC samples (P < 0.001). The highest level of ALK expression was found in ADC cases with poor differentiation and high nuclear grade (P = 0.005 and P = 0.005, respectively). Furthermore, high level of ALK expression was more often observed in ADC cases with poor prognosis features (P = 0.013). Conclusions: These findings suggested that ALK can be considered as a promising target in the targeted therapy in patients with lung ADC.

Based on the cancer stem cell (CSC) concept model, a small population of cells with unique self-renewal properties and malignant potential exists in tumors. Immunohistochemistry was performed to detect the expression of CSC markers, CD133 and CD44, in a series of pediatric tumors. The association between expression of these markers and tumor characteristics was then analyzed. In Wilms tumors (WT), a significant positive correlation was found between expression of CD133 and the National Wilms Tumor Stage (NWTS) (p = 0.047). In neuroblastomas (NB), expression of CD133 was positively correlated with the International Neuroblastoma Staging System (INSS) (p-value = 0.012), indicating that the rate of CD133 positivity increased with the stage of these tumors. CD133, as a putative stem cell marker, is associated with more advanced stages of Wilms and NB tumors; therefore, this molecule can be a potential clinical prognostic marker in children suffering from NB or Wilms tumor.

The objective of this study was to investigate the immunohistochemical (IHC) detection of c-erbB2 receptor (crbP) and TP53, the co-expression of these two markers and their relationship with histological type and histological grade in canine mammary carcinoma. After histological diagnosis according to the WHO classification of 30 mammary carcinomas, their histologic grade was identified by the Elston and Ellis method for human breast tumours. Proliferation activity was detected by Ki67 protein. IHC staining was carried out for crbP and TP53 expression. Results of semiquantitative IHC assessment of crbP and 3+ TP53 expression were 23.3% and 53.3% of canine mammary carcinoma, respectively. There were significant relationships between Tp53 and histopathological grade and TP53 and Pki67. No significant results were obtained between crbP and TP53 even with overexpression of TP53 in positive crbP cases. These results suggest that using crbP and TP53 may be useful for malignancy detection accompanied by Pki67, and additional research in this subject is essential.

Canine mammary gland carcinoma is ranked second after skin tumours in dogs in terms of frequency. Due to certain microscopic and biological features, canine tumours are very similar to human carcinomas, which may make the dog a good animal model. The objective of this study was to describe Ki67 protein expression properties using immuno-histochemical (IHC) staining using human antibody. In this study, 30 mammary gland tumour samples were studied. The histological diagnosis was made on the basis of the current World Health Organization classification for canine mammary tumours. Tumours were then graded histologically in accordance with the Elston and Ellis method for human breast tumours. IHC staining using MIB-1 antibody for detecting expression of Ki67 proteins (pKi67), was performed on canine mammary gland carcinoma tissue. Results from the semi-quantitative IHC assessment of pKi67 showed that 20% were negative, 20% were one plus, 36.5% were two plus, 23.3% were three plus. There was a significant difference between histological grade and pKi67 expression. This method would help the pathologist and clinician in determining a more accurate prognosis and treatment in canine mammary carcinoma and facilitate comparative studies of canine and human research.

Introduction Renal cell carcinoma (RCC) is the most common neoplasm in adult kidneys. One of the most important unmet medical needs in RCC is a prognostic biomarker to enable identification of patients at high risk of relapse after nephrectomy. New biomarkers can help improve diagnosis and hence the management of patients with renal cancer. Thus, this systematic review aims to clarify the prognostic and diagnostic accuracy of miR-21 in patients with RCC. Methods and analysis We will include observational studies evaluating the diagnostic and prognostic roles of miR-21 in patients with renal cancer. The index test and reference standards should ideally be performed on all patients. We will search PubMed, SCOPUS and ISI Web of Science with no restriction of language. The outcome will be survival measures in adult patients with RCC. Study selection and data extraction will be performed by two independent reviewers. QUADAS-1 will be used to assess study quality. Publication bias and data synthesis will be assessed by funnel plots and Begg9s and Egger9s tests using Stata software V.11.1. Ethics and dissemination No ethical issues are predicted. These findings will be published in a peer-reviewed journal and presented at national and international conferences. Trail registration number This systematic review protocol is registered in the PROSPERO International Prospective Register of Systematic Reviews, registration number CRD42015025001.

BACKGROUND HER2/neu overexpression on cell membranes of breast cancer cells is due to HER2/neu gene amplification and it is important to identify potential candidates for anti HER2 therapy with trastuzumab. IHC, FISH and CISH are standard FDA approved assays currently used to determine HER2 status in routine practice. The aim of this study was to determine HER2 gene amplification, using the CISH method in breast carcinoma samples which had IHC +2 reactions. MATERIALS AND METHODS This study was conducted from 2008- 2010 using 334 consecutive breast carcinoma samples referred from local laboratories to Mehr Hospital. CISH assays were performed for all cases, and IHC tests were also done for determining efficacy and accuracy of local labs. HER2 status in local IHC tests was compared with central IHC and CISH results. RESULTS Of 334 breast cancer patients, 16 were negative for HER2 IHC (0, +1), 201 cases were equivocal (+2), and 31 positive (+3). Of 334 referral cases, 88 were CISH positive (26.3%) and 246 were CISH negative (73.7%). Of 201 IHC +2 cases, HER2 gene amplification was observed in 42 cases (kappa: 0.42). A 29.9% concordance was found between local IHC and central IHC. Sensitivity and specificity of local IHC were 90% and 53.8%, respectively. CONCLUSIONS Low accuracy of IHC results in local labs was associated with the following factors: using former FDA-approved criteria for HER2 interpretation, utilizing non-validated kits, and lack of any quality assurance program. Therefore, following the new 2014 ASCO/CAP guideline and comprehensive quality assurance should be implemented to ensure accuracy of HER2 testing.

Hypertension is a late outcome of refl ux nephropathy and renal parenchymal scar secondary to urinary tract infection (UTI). We presumed that it might be detected much earlier after episodes of UTI and the associated cardiovascular risk factors assessed. Between 2009 and 2011, 85 (67 female and 18 male) children aged 5-15 years with a history of febrile UTI, followed-up for at least one year from the fi rst episode of febrile UTI, were enrolled in the study. The variables included 24-hour ambulatory blood pressure monitoring (ABPM), echocardiography, carotid sonography, renal 99mcTc-DMSA, glomerular fi ltration rate, and microalbuminuria. Masked hypertension was detected in 18.8%, hypertension in 7.1% and white coat hypertension in 9.4% of cases. Prehypertension was seen in 20% of children. Out of 85 cases, 43.5% were non-dippers. Out of 56 children with hypertensive and prehypertensive parameters on ABPM, 9.1% showed left ventricular mass index >51g/m2.7 (p>0.05). Signifi cant correlation was only recorded between abnormal blood pressure and the severity of renal parenchymal scar (p, Hipertenzija je kasni ishod refl uksne nefropatije i ožiljaka na bubrežnom parenhimu koji nastaju nakon mokraćne infekcije. Pretpostavili smo da bi se to moglo otkriti znatno ranije nakon epizoda mokraćne infekcije te procijeniti pridružene kardiovaskularne čimbenike rizika. Od 2009. do 2011. godine, u ispitivanje je uključeno 85 (67 Ž, 18 M) djece u dobi od pet do 15 godina s anamnezom febrilne mokraćne infekcije koja su bila praćena najmanje jednu godinu od prve epizode febrilne mokraćne infekcije. Praćene su sljedeće varijable: 24-satno ambulatorno praćenje krvnog tlaka (ambulatory blood pressure monitoring, ABPM), ehokardiografi ja, karotidni ultrazvuk, 99mcTc-DMSA bubrega, glomerularna stopa fi ltracije i mikroalbuminurija. Maskirana hipertenzija otkrivena je u 18,8%, hipertenzija u 7,1% i hipertenzija “bijele kute” u 9,4% slučajeva. Prehipertenzija je zabilježena u 20% djece. Od 85 slučajeva 43,5% ih nije pokazalo odgovarajući pad krvnog tlaka tijekom noći (non-dipper). Od 56 djece s hipertenzivnim i prehipertenzivnim parametrima na ABPM 9,1% ih je imalo indeks lijeve ventrikularne mase veći od 51g/m2.7 (p>0,05). Značajna korelacija zabilježena je između nenormalnog krvnog tlaka i težine ožiljka na bubrežnom parenhimu (p

Background: Plasma neutrophil gelatinase associated lipocalin (NGAL) level is increased in sepsis irrespective of renal dysfunction. We investigated the effect of sepsis on the plasma level of NGAL in neonates. Objectives: The aim of this study was to find whether serum NGAL is a reliable marker for early diagnosis of sepsis in neonates. Patients and Methods: We conducted a prospective observational study in a university hospital neonatal intensive care unit. Serum NGAL was measured in 120 neonates admitted to the neonatal intensive care unit. Neonates were classified according to the presence of sepsis. Fifty-two Patients had sepsis. Results: The NGAL levels were significantly higher in septic neonates compared with non-septic neonates (102.9 ± 69.9 ng/mL versus 29.2 ± 13.3 ng/mL, P value = 0.0001). An optimal cut off-point of 48 ng/mL for serum NGAL could potentially detect neonates with sepsis with a sensitivity and specificity of 92% and 91%, respectively. Conclusions: Sepsis enhances the production of plasma NGAL in critically ill neonates. Thus Plasma NGAL can help clinicians diagnose sepsis in critically ill neonates during early phases.

BACKGROUND: According to the cancer stem cell theory, tumors originate from a subset of cells known as cancer stem cells (CSCs) that are responsible for tumor initiation, resistance and relapse. CD44 is a cell adhesion molecule that can aid in the identification of CSCs in various malignancies. OBJECTIVE: The purpose of the current study is to evaluate the expression level and clinical significance of CD44 in lung cancer samples. METHODS: One hundred and ninety-five lung tumor samples including 74 (38%) squamous cell carcinomas (SCC), 61 (31%) adenocarcinomas (ADC), 23 (12%) large cell carcinoma (LCC) in non-small cell lung cancer (NSCLC) group and 37 (19%) small cell lung cancer (SCLC) samples were examined for the expression of CD44 using immunohistochemistry method. The correlation of CD44 expression with clinicopathological parameters as well as Ki-67 status was also assessed. RESULTS: Univariate analysis demonstrated that CD44 expression was significantly higher in NSCLC compared to SCLC (P < 0.001). Among NSCLC, higher level of CD44 expression was found in SCC compared to ADC (P< 0.001) and LCC (P=0.046). Increased expression of CD44 was significantly correlated with higher grade tumors which correspond to poor prognosis in SCC (P=0.012) and the lower level of CD44 expression was more often found in well differentiated ADC tumors (P=0.03). In addition, high expression of CD44 was significantly associated with decreased level of proliferative marker Ki-67 (P=0.04). CONCLUSIONS: CD44 could be a valuable tool for the study of lung CSCs and provide a novel therapeutic target for treatment of the patients with lung cancer in combination with conventional therapy.

Calciphylaxis is a complication of chronic kidney disease characterized by necrotic lesion in the skin. Histological examination reveals microcalcification of medium-sized blood vessels. We report on a 21-month-old girl with end-stage renal disease with severe calcium-phosphate imbalance. Calciphylaxis process started when she received calcium gluconate intravenously the day before the surgery to correct hypocalcemia and continued progressively despite peritoneal dialysis and forced stopping calcium-containing medication. Pamidronate, 0.5 mg/kg/d, was administered for 6 days and then once a week for 5 weeks. After 1 week, the skin lesion started to heal and circulation improved, and after 6 weeks, all skin lesions completely recovered. Pamidronate was effective to stop calciphylaxis in this case with advanced renal insufficiency and severe calcium-phosphate imbalance. Medical or surgical debridement are not suggested and lesions might recover without scar by pamidronate.

Background: Revealing data on the role of vitamin D and calcium supplementation in bone health has led some to suggest that vitamin D and calcium treatment could also play a role in protecting bone against microgravity-induced mineral loss. Objectives: The aim of the present study was to investigate the effects of vitamin D and calcium administration on microscopic and densitometric changes of rat femur in a Microgravity Simulator Model. Materials and Methods: After designing a Microgravity Simulator Model, 14 rats were placed in the cages as follows: seven rats as osteoporosis group and seven rats received oral supplement of calcium/vitamin D as the treatment group. Animals were sacrificed after eight weeks and then both femurs were removed. Bone mineral density was measured for one femur from each animal, and morphologic studies were evaluated for the contralateral femur. Results: Bone mineral density of the whole femur in the treatment group was significantly higher than the osteoporosis group (0.168 ± 0.005 vs. 0.153 ± 0.006, P = 0.003). Also, bone mineral content of the whole femur was significantly higher in treatment group (0.415 ± 0.016 vs. 0.372 ± 0.019, P = 0.003). However, resorption eroded surface percentage was higher in the osteoporosis group (18.86 ± 3.71% vs. 9.71 ± 1.61%, P = 0.002). Conclusions: According to the results of this study, vitamin D and calcium administration might have protective effects against microgravity-induced mineral loss in a Rat Microgravity Simulator Model.

Background: Neuroblastoma (NB), is a neuroectodermal tumor derived from neural crest cells, and it is the second most common pediatric malignant tumor. The biological and clinical behavior of NB is very heterogeneous. This study was conducted to evaluate the expression of Ki-67, p53 and VEGF markers in tissues obtained from NB patients with different histologic types and stage. Materials and Methods: Tissue microarray (TMA) blocks were constructed from paraffin blocks of the NB tissues. Immunohistochemical staining was performed on TMA sections to detect the expression of Ki-67, p53 and VEGF markers. The association between the expression of these markers and clinicopathological parameters were then analyzed. Results: We had 18 patients with NB, one patient with ganglioneuroblastoma (GNB) and one with ganglioneuroma. Ki-67 was expressed in 13 (65%) tumors, and negatively correlated with age, prognosis, histologic type and stage of NB (all p

Pancreatic neuroendocrine tumor is rarely seen, particularly in children. One of the symptoms of this tumor is jaundice that may be misdiagnosed as the sign of hepatitis A, especially in countries with a high prevalence of this infectious disease.We present a 3.5-year-old girl with four weeks of icterus, who was misdiagnosed with hepatitis A.The patient was finally diagnosed as having a low grade pancreatic neuroendocrine carcinoma.Pediatricians should be aware of or consider a tumor in differential diagnosis of jaundice, especially prolonged one in children.

Results: A total of 71 patients with a mean age of 29.1 ± 38.5 months were enrolled in this study. The prevalence of VRE rectal colonization was 66.2%. None of the potential risk factors including age, gender, comorbidities, previous admission into ICU, length of stay in ICU, presence of invasive devices were significantly associated with VRE colonization. Linezolid-susceptible isolated strains accounted 97.9%. Conclusions: The prevalence of VRE was higher compared to previous reports from local and international studies. In order to control the spread of VRE, appropriate use of antibiotics, adherence to infection control measures, and shortening the duration of ICU stay is highly recommended.

Fibroblast growth factor 2 (FGF2) is a potent mitogenic factor of cortical fibroblasts and induces kidney fibrosis. We hypothesized that serum levels of FGF2 has an association with the severity of vesicoureteral reflux (VUR) and renal parenchymal scar.Between 2007 and 2009, a total of 28 children with VUR were enrolled in this study and were compared with 52 healthy children. All children with VUR underwent technetium Tc 99m dimercaptosuccinic acid renal scintigraphy. Fibroblast growth factor 2 was measured in both groups.The mean level of FGF2 was 65.0 ± 19.0 pg/mL in the VUR group and 62.5 ± 15.3 pg/mL in the control group (P.05). There was no correlation between serum levels of FGF2 and sex, age, or the grade of VUR. Of the 28 children with VUR, 19 had renal parenchymal scar on dimercaptosuccinic acid renal scintigraphy. The mean serum level of FGF2 was not significantly different in the children with and without renal parenchymal scar.This study showed no correlation between serum FGF2 and renal parenchymal scar or grade of VUR.

Cyclosporine induced pain syndrome (CIPS) is a newly diagnosed complication of calcineurine inhibitors, mainly observed in solid organ and hematopoetic transplantations. The present case is a male child with steroid resistant nephrotic syndrome on low therapeutic level cyclosporine treatment. He presented with intractable and debilitating leg pain, with no reported history of previous injury or trauma. The pain was reluctant to antimicrobial and sedative treatment. MRI revealed bone marrow and soft tissue edema in the mid shaft of patient's right leg. Inspite of unusual manifestations, CIPS was suggested and cyclosporine discontinued. However, the pain did not improve and was resistant to calcium blocker. Subsequently, core decompression was performed as an unusual treatment of CIPS, revealing normal bone morphology. The pain improved rapidly and the patient was discharged a few days later.

Renal involvement is the major cause of mortality and morbidity in children with Henoch-Schonlein purpura. The purpose of this study was to determine the predictive factors of Henoch-Schonlein nephritis (HSN) and correlations between clinical and pathologic findings.Demographic characteristics and clinical manifestations of 105 children with Henoch-Schonlein purpura were retrospectively evaluated. Kidney biopsy with pathologic scoring was performed in 17 patients.Sixty-one boys and 44 girls were included in this study. The mean age at presentation was 73.0 ± 33.4 months (range, 12 to 156 months). Thirty-nine percent of patients had renal involvement. Their mean age at presentation of HSN was 87.4 ± 30.9 months, which was significantly higher than the age of those without nephritis. Age at presentation was the only predictor of renal involvement. Hematuria and proteinuria were the most common laboratory findings of HSN, followed by nephrotic syndrome and acute nephritis. The most common histologic findings were grades 3 (especially 3B) and 2 of the International Study of Kidney Disease in Children classification, respectively. Higher pathologic grades were more frequent in patients with nephrotic syndrome and acute nephritis. Similarly, there was a positive relationship between the severity of proteinuria and both pathologic grading and scoring, especially crescent formation, endocapillary proliferation, and tubular atrophy.There was a significant correlation between the severity of renal involvement and pathologic grading and scoring in HSN. The severity of proteinuria was a significant determinant of renal pathologic findings.

Kefirs are natural probiotic compounds with antibacterial and anti-inflammatory properties which were tested in experimental burn injury. Kefir gels were prepared from an extract of continuously cultured kefir grains in MRS Broth medium for 24, 48 and 96h. Similar burn injuries were made on dorsal skin surface of 56 rats. After 24h the wounds were infected with Pseudomonas aeruginosa. The infected rats were divided in to 7 groups of 8 rats each. The base gel, silver sulfadiazine ointment, kefir 24h gel, kefir 48h gel, kefir 96h gel and kefir grains 96h gel were applied twice a day. Burn wound area was measured at baseline, one and two weeks. After two weeks the animals in all groups were sacrificed and whole skin wound areas were removed and percentage of epithelization, scar formation, inflammation and angiogenesis were evaluated. Results indicated that at the end of the 2nd week the percentage of wound size were lowest in order of kefir 96h gel

Congenital nephrotic syndrome (CNS), an uncommon form of kidney disease, presents during the first year of life and is a diagnostic and therapeutic challenge for the pediatricians as well as pediatric nephrologists. Our study is the first study of Iranian children with CNS in two pediatric nephrology centers in Tehran, Iran.We reviewed medical charts of 30 infants diagnosed with CNS from 1990 to 2005.There were 15 boys and 15 girls with CNS (mean age, 1.7 months). The presentation of the disease was nephrotic syndrome in 96.6% of the patients. Eighty percent of the patients presented within 3 months of life and 16 in the neonatal period. The Finnish type of CNS was seen in 43.3% and diffuse mesangial sclerosis in 50%. Preterm labor and low birth weight was seen in 20%. A family history of nephrotic syndrome in infancy was noted for 8 children (26.7%). Numerous complications of nephrotic syndrome occurred in 73.3%. Seventy percent of the patients had 27 episodes of infections. Sepsis was seen in 43.3% of the children, of which 61.5% were caused by gram-negative bacteria and 38.6% were caused by Staphylococcus aureus. Thrombotic complications and hypertension developed in 6.6% and 23.3% of the patients, respectively. The mortality rate of patients was 86.6%.Diffuse mesangial sclerosis is an important cause of CNS. The outcome of our patients was poor and most of our patients died before reaching the age of 5 years old.

Atypical hemolytic uremic syndrome (HUS) is accompanied by a poor prognosis and high mortality rate. We investigated the predictive value of severity of renal involvement, as evaluated by pathologic examination, for long-term outcome of atypical HUS.Kidney biopsies of 29 children diagnosed with atypical HUS between 1992 and 2005 were reviewed. The severity of glomerular, vascular (arteriolar and arterial), interstitial, and tubular involvement were determined. Scores of renal involvement were determined by re-evaluating kidney specimens. The outcome measures were death, chronic kidney disease (CKD), hypertension, and proteinuria.After a mean of 3.7 years of follow-up, 24.1% of the patients had normal kidney function and blood pressure, 24.1% showed proteinuria, and 41.4% had CKD, and 10.3% had unknown prognosis. Overall, 24.1% of the patients died due to emergent hypertension with or without CKD. The existence of arteriolar and arterial thrombosis attributed to severe CKD (risk ratio, 3.67; 95% confidence interval, 1.63 to 8.2). Presence of thrombosis in the vessels, and thickening of the arterial medial and intimal layers had brought about a significantly higher mortality rate. Chronic kidney disease was more frequent in the children with vascular scores higher than 0.14 and a final score of more than 0.2.The severity of renal pathological involvement, especially the degree of vascular damage, is a good predictor of long-term outcome of patient with atypical HUS.