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. © 2018 By The Archives of Bone and Joint Surgery

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

CD44/CD24 Expression in recurrent gastric cancer: a retrospective analysis

Background: To correlate CD44/CD24 expression with gastric cancer recurrence and prognosis. Gastric cancer is the second leading cause of cancer mortality due to the high recurrence rate, of which the molecular signature has not yet been identified.Methods: We retrospectively reviewed the hospital records of patients with gastric cancer. Among 500 patients receiving curative resection, 95 patients had recurrence. Twenty patients from the recurrence group (95 patients) and 20 patients from the non-recurrence group (405 patients) were randomly selected and identified as “study” and “control” groups, respectively. We reviewed patients’ histological study of CD44/CD24 expression by performing immunohistochemistry and recurrence rate.Results: Study group had higher TNM stage (III-IV) than control group (80% vs. 25%, P = 0.001). Proportion of lymph node metastasis was significantly higher in study group than that in control group (90% vs. 45%, P = 0.002), and proportion of patients with 5 or more metastatic lymph nodes was also significantly higher in study group than in control group (45% vs. 15%, P = 0.007). Univariate analysis revealed no difference in risk of gastric cancer recurrence between CD44+ and CD44- patients (OR = 1.00, 95% CI: 0.29-3.45, P =1.000). CD24+ patients showed no greater significance of gastric cancer recurrence than CD24- patients (OR = 1.86, 95% CI: 0.52-6.61, P = 0.339). After adjusting for other risk factors, the association of CD44 expression (aOR = 0.66, 95% CI: 0.10-4.26, P = 0.658), CD24 expression (aOR = 0.09, 95% CI: 0.01-1.35, P = 0.081) or combined (CD44/CD24) with gastric cancer recurrence were not significant.Conclusion: Neither individual expression of CD24 or CD44, nor combined expression of CD44/CD24 was associated with recurrence of gastric carcinoma

Sequential expression of putative stem cell markers in gastric carcinogenesis

10.1038/bjc.2011.287British Journal of Cancer1055658-665BJCA