Denosumab in Patients with Giant Cell Tumor and Its Recurrence: A Systematic Review.

Recent studies suggest that Denosumab reduces tumor size, therefore, makes the surgery easier with lower morbidity. However, some studies have reported several complications for this drug. So, this systematic review was performed to determine the effectiveness and safety of Denosumab in reducing bone destructions activity of giant cell tumor and skeletal-related events (SRE) in affected patients with giant cell tumor of bone (GCTB) and its recurrence. We explored studies in PubMed, and Cochrane Library. For this purpose, articles of various levels were retrieved until October 22, 2016. Two reviewers assessed the articles independently based on predefined criteria to extract the relevant data. Primary outcomes associated with skeletal-related event, overall survival, and secondary outcomes such as pain, quality of life and adverse events were evaluated and analyzed. The total population of this meta-analysis consisted of 686 patients. Of this population, 55% had primary GCTB and 45% had giant cell tumor recurrence, with 2% experiencing secondary recurrence. The results showed the effectiveness of Denosumab in reducing the tumor size due to inhibiting the Osteoclastogenesis. Denosumab didnot show any effect on reducing tumor recurrence, but, in cases where complete tumor surgery is not possible and tumor residuals may remain, Denosumab can be helpful. Also, the clinicians should consider the risk benefit of Denosumab.

Knowledge and attitude of women regarding breast cancer screening tests in Eastern Iran.

INTRODUCTION: According to recent statistics, there has been a rapid growth of breast cancer in developing countries. Thus, early detection is essential. This study is based on the perception of people in the Northeast of Iran regarding breast cancer screening. METHODS: In a cross-sectional study, 1469 women were selected randomly in the period from April to November 2016. The study population consisted of women or their companions referring to outpatient clinics or people in public urban areas who filled out a breast cancer screening questionnaire in an interview. RESULTS: The patients' age was in the range of 14 to 84 years (mean = 38.8). More than 84% of interviewees were not informed of breast cancer and screening tests. The main reasons mentioned by patients for their failure to do screening tests was 'absence of any symptom or problem' and 'they did not think it was necessary'.There was not a significant difference between income level, marital status and knowledge of people about breast cancer screening tests (P > 0.05). However, employment, education level and family history had a positive effect on people's awareness of breast cancer and its screening tests (P < 0.05). CONCLUSION: The lack of knowledge in people from low socio-economic classes was the main barrier to breast cancer screening. In this regard, organizing training programs by physicians and the media can help raise screening rates.

ROC-king onwards: intraepithelial lymphocyte counts, distribution & role in coeliac disease mucosal interpretation.

OBJECTIVES: Counting intraepithelial lymphocytes (IEL) is central to the histological diagnosis of coeliac disease (CD), but no definitive 'normal' IEL range has ever been published. In this multicentre study, receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off between normal and CD (Marsh III lesion) duodenal mucosa, based on IEL counts on >400 mucosal biopsy specimens. DESIGN: The study was designed at the International Meeting on Digestive Pathology, Bucharest 2015. Investigators from 19 centres, eight countries of three continents, recruited 198 patients with Marsh III histology and 203 controls and used one agreed protocol to count IEL/100 enterocytes in well-oriented duodenal biopsies. Demographic and serological data were also collected. RESULTS: The mean ages of CD and control groups were 45.5 (neonate to 82) and 38.3 (2-88) years. Mean IEL count was 54±18/100 enterocytes in CD and 13±8 in normal controls (p=0.0001). ROC analysis indicated an optimal cut-off point of 25 IEL/100 enterocytes, with 99% sensitivity, 92% specificity and 99.5% area under the curve. Other cut-offs between 20 and 40 IEL were less discriminatory. Additionally, there was a sufficiently high number of biopsies to explore IEL counts across the subclassification of the Marsh III lesion. CONCLUSION: Our ROC curve analyses demonstrate that for Marsh III lesions, a cut-off of 25 IEL/100 enterocytes optimises discrimination between normal control and CD biopsies. No differences in IEL counts were found between Marsh III a, b and c lesions. There was an indication of a continuously graded dose-response by IEL to environmental (gluten) antigenic influence.

Evaluation of serum HBV viral load, transaminases and histological features in chronic HBeAg-negative hepatitis B patients.

AIM: To evaluate the association between biochemical, virologic and histologic features in patients with HBeAg-negative chronic hepatitis B (CHB). BACKGROUND: Hepatitis-B e-antigen (HBeAg)-negative is common in Iran, is progressive with poor prognosis. Therefore, it seems necessary to perform a comprehensive evaluation of different spectrum of laboratory measurements accompanying histological findings. METHODS: HBeAg- negative CHB patients referring to two university hospitals during two years were enrolled. Alcohol consumption, liver mass, fatty liver and positive results of Anti HDV, Anti HCV or Anti HIV were excluded. The relationship between viral loads, liver enzymes (old and new cutoffs) and histopathological features was analyzed using descriptive and analytic statistical methods. RESULTS: A total of 150 HBeAg-negative CHB (males=110, mean age=38.44±11.34 years) were assessed. ALT had a significant relation with the logarithm of serum HBV-DNA (P<0.0001), grade and stage on liver biopsy (P<0.001, P=0.034, respectively). Serum viral load, AST and ALT were independent predictors of histological grade, age was the only independent predictor of the stage of liver fibrosis. There was a significant relationship between serum ALT and stage of liver fibrosis (P<0.0001) when new cutoff values for ALT were considered. We found that age had a significant relation with histological grade but it showed a reverse relation with ALT levels (P=0.009). CONCLUSION: In HBeAg-negative CHB, AST had a better prediction for liver necrosis and inflammation. Age could be an independent predictor for liver fibrosis. New cutoff values for ALT had superiority over conventional values to identify higher risk of liver fibrosis.

Resolution of Bile Duct Adenoma over Follow-up Period; A Case Report.

Bile duct adenoma (BDA) is a rare neoplasm of bile ducts with various clinical manifestations and imaging appearances. A few cases of BDA and their predisposing factors have been described. We report a 35-year-old woman with right upper quadrant pain who consumed oral contraceptive pills. Ultrasound study revealed three hypoechoic subcapsular liver masses; two of them were hypodense in computed tomography. Fine needle biopsy of the largest mass showed bile duct adenoma. Liver masses disappeared after discontinuing the pills over a 2-year follow-up. BDAs can manifest in imaging. Although previous studies have not reported tumor resolution over a follow-up period, we suggest paying more attention to predisposing factors in order to give an opportunity for tumor resolution by risk factor elimination.

Efficacy of Conversational Hypnosis and Propofol in Reducing Adverse Effects of Endoscopy.

BACKGROUND: As pain and nausea is usually associated with endoscopy procedure, its management is important to alleviate patients' anxious in this regard. OBJECTIVES: The present study aimed to examine the effectiveness of conversational hypnosis in reducing anxiety and endoscopy-related complications as well as its role in increasing the satisfaction of patients exposed to endoscopic procedures. PATIENTS AND METHODS: The participants of upper GI endoscopy procedure were randomly assigned to an experiment group (with conversational hypnosis intervention, n = 93) and a control group (n = 47). The participants' hemodynamic indexes (HR, blood pressure, pulse oximetry), anxiety, satisfaction level, and complications resulted from the procedure were monitored and included in the self-administered questionnaire. RESULTS: The results indicated that the participants in experiment group had a significant reduction of anxiety in the posttest. The adverse side effects such as vomiting, nausea, and hiccups in the experimental group was less than the control group, though this difference was not significant (P = 0.54). CONCLUSIONS: The results suggested that conversational hypnosis technique could reduce anxiety as well as the sedation process in invasive procedures such as endoscopy.

Estrogen receptor alpha gene expression in breast cancer tissues from the Iranian population--a pilot study.

Estrogen receptor alpha (ERα) is one of the major sub-types of estrogen receptors. ERα plays an important role in cellular proliferation and differentiation, chiefly in mammary tissues. In the present study we aimed to quantify of ERα mRNA and protein expression in breast tissues from the Iranian population using a real-time PCR assay. Twenty nine breast tissues including 19 adenocarcinomas and 10 normal controls were recruited from the Iranian population. mRNA extraction and cDNA synthesis were performed from these tissues using commercial kits. ERα mRNA and protein expression was quantified using real-time PCR and immunohistochemistry respectively. The results showed high expression of ERα mRNA (68%) and protein (53%) in the majority of breast cancer tissues compared to normal breast tissues (p=0.035). Also, high ERα mRNA was associated with tumour size of breast carcinomas. In this study, we first reported the expression of ERα in Iranian patients with breast cancers and demonstrated prevalence of the expression to be similar to breast cancers noted in other populations.

Serum chemokine ligand 5 (CCL5/RANTES) level might be utilized as a predictive marker of tumor behavior and disease prognosis in patients with gastric adenocarcinoma.

PURPOSE: Gastric cancer is the second leading cause of cancer-related deaths worldwide and the most common gastrointestinal cancer in Iran. Chemokine ligand 5 (CCL5/RANTES) is one of the most potent angiogenic factors that plays an important role in tumor growth, invasion, and metastasis. We aimed to assess the serum level of CCL5 in patients with gastric adenocarcinoma and its relation with histological grade and tumor stage, as well as the disease prognosis. METHODS: Seventy-four patients with gastric adenocarcinoma that had undergone gastrectomy and 96 non-tumoral cases in which gastric cancer was ruled out by gastroscopy and biopsy were enrolled. Demographic and epidemiological characteristics and patient survival data were reviewed. Histological type, grade, and tumor stage (TNM) were determined by a single expert pathologist. Helicobacter pylori infection status and CCL5 serum level were measured by ELISA. Data were analyzed using SPSS software version 16. RESULTS: Patients with gastric adenocarcinoma had significantly higher serum CCL5 level compared with control group (P < .001). Higher serum CCL5 levels were associated with lower histological differentiation (P < .001), higher depth of tumor invasion (P = .022), more frequent lymph nodes involvement (P = .028), and advanced tumor stage (P = .002). The overall survival of patients with CCL5 levels higher than 70,671 pg/ml was significantly lower than those with lower than this cutoff (P = .043). CONCLUSIONS: Serum CCL5 levels might be utilized as a predictive marker of tumor behavior and disease prognosis in patients with gastric adenocarcinoma. Further studies to assess tissue expression of CCL5 and its gene polymorphisms are suggested.

Knowledge and perception toward colorectal cancer screening in east of Iran.

BACKGROUND: Colorectal Cancer (CRC) is the third most common cancer in Iran and its early detection is necessary. This study is based on perception of people in the east of Iran toward CRC screening. METHODS: In a cross-sectional study, 1060 randomly selected individuals who referred to Razavi Hospital of Mashhad, Iran, between September the 1(st), 2012 and February the 28(th), 2013 as patients or their visitors involved in an interview to fill a questionnaire on CRC screening. RESULTS: The participants' age ranged from 40 to 88 years (mean= 55). More than 90% had no knowledge of CRC and screening tests. The most cited reasons for not having screening tests were "did not have any problem" and "did not think it was needed". Although, older people had more knowledge of CRC (P= 0.033), there was no relationship between gender, health insurance status, family history of individuals and their knowledge about CRC (P> 0.050). Employment, education and higher income had positive effect on the perception of people toward CRC screening (P< 0.050). CONCLUSION: Lack of knowledge in people in lower socio-economical class with limited literacy is the most important barrier to CRC screening. As such, designing educational programs involving physicians and media is important to improve CRC screening rates.

Clinicopathological significance of macrophage migration inhibitory factor and its relation with p53 in gastric cancer.

AIM: Based on previous investigations, the progress of gastritis may lead to gastric carcinomas. In some epithelial tumors, macrophage migration inhibitory factor (MIF), which is an inflammatory cytokine may inactivate p53 and play a role in tumorigenesis process. We decided to evaluate clinicopathological significance of MIF expression and the relation between p53 and MIF expressions in gastric adenocarcinomas. METHODS: Seventy-three consecutive cases of gastric adenocarcinomas, the tissue samples of which were available, were included in this study. Tissue sections were stained for MIF and p53 expression by immunohistochemistry and the expression was defined as positive (for more than 10%) and negative (for less than 10%) groups. Location of the tumor, histological subtypes, and grade of the tumor were determined by using routine H&E staining. Distant metastasis, lymph node involvement, and consequently the stage of tumor were specified. The patients' age and gender were obtained from their medical records. The relationship between expression of MIF and these variables was determined. RESULTS: Overexpression of MIF was observed in the cytoplasm of cancer cells in 46.6% (34/73) of cases and nuclear immunostaining of p53 was observed in 37% (27/73) of cases. Expression of MIF was significantly correlated with the location of tumor, but this expression has no statistically significant correlation with variables including: age, gender histological subtypes, distant metastasis, and lymph node involvement, stage and grade of the tumor, and p53 tumor suppressor gene expression. CONCLUSIONS: Our study suggests that MIF in gastric adenocarcinomas versus many other epithelial tumors cannot have a prominent role in tumor progress and inactivation of p53 tumor suppressor gene.

Soluble Fas might serve as a diagnostic tool for gastric adenocarcinoma.

BACKGROUND: Fas (Apo-1/CD95) and its specific ligand (FasL) are key elements in apoptosis. They have been studied in different malignancies but there are few published studies about the soluble forms of these markers (i.e. sFas/sFasL) in gastric cancer. We have compared the serum levels of sFas/sFasL in gastric adenocarcinoma patients and cases with pre-neoplastic lesions as potential markers for early diagnosis, and investigated their relation with clinicopathological characteristics. METHODS: Fifty-nine newly-diagnosed cases of gastric adenocarcinoma who had undergone gastrectomy, along with 62 endoscopically- and histologically-confirmed non-cancer individuals were enrolled in this study. sFas/sFasL serum levels were detected by Enzyme Linked Immunosurbent Assay. RESULTS: Mean serum sFas level was significantly higher in gastric cancer patients than in control group (305.97 +/- 63.71 (pg/ml) vs. 92.98 +/- 4.95 (pg/ml), P < 0.001); while the mean serum level of sFasL was lower in patients with gastric adenocarcinoma (0.138 +/- 0.04 (pg/ml) vs. 0.150 +/- 0.02 (pg/ml), P < 0.001). Mean serum levels of sFas/sFasL were significantly different in both intestinal/diffuse and cardiac/non-cardiac subtypes when compared to the control group (P < 0.001). There was an increase in the serum level of sFas from the first steps of pre-neoplastic lesions to gastric adenocarcinoma (P < 0.001). Patients who had no lymph node involvement (N0) showed significantly higher serum levels of sFas compared to others (P = 0.044). CONCLUSIONS: Production of sFas may play a critical role in the carcinogenesis of intestinal-type gastric cancer. sFas serum level may serve as a non-invasive tool for early diagnosis of gastric cancer.

Expression of cell adhesion molecule CD44 in gastric adenocarcinoma and its prognostic importance.

AIM: To evaluate the relation of cluster of differentiation 44 (CD44) expression with clinicopathological features of gastric adenocarcinoma, and also its effect on prognosis with an emphasis on the differences between intestinal and diffuse types. METHODS: From 2000 to 2006, 100 patients with gastric adenocarcinoma, who had undergone total or subtotal gastrectomy without any prior treatment, were studied. Haematoxylin and eosin (HE) staining was used for histological evaluation, including the type (Lauren's classification) and grading of the tumor. The expression of CD44 in the gastric adenocarcinoma mucosa and the adjacent mucosa were determined by immunohistochemistry. The survival analysis was obtained using the Kaplan-Meier test. RESULTS: Of 100 patients, 74 (74%) patients were male. The tumors were categorized as intestinal type (78%) or diffuse type (22%). Sixty-five percent of patients were CD44-positive. CD44 expression was not detected in normal gastric mucosa. Rather, CD44 was more commonly expressed in the intestinal subtype (P=0.002). A significant relation was seen between the grade of tumor and the expression of CD44 (P=0.014). The survival analysis showed a poor prognosis of patients with CD44-positive tumors (P=0.008); and this was more prominent in the intestinal (P=0.001) rather than diffuse type. CONCLUSION: Cell adhesion molecule CD44 is highly expressed in gastric adenocarcinoma. CD44 expression is correlated with a poor prognosis in patients with the intestinal type of gastric adenocarcinoma. CD44 can, therefore, be utilized as a prognostic marker for this group of patients.