Inter-observer variability between readers in detection of bone metastases comparing different modalities; PET/CT, SPECT/CT and planar bone scintigraphy.

OBJECTIVE: To assess the inter-observer variability between readers in the detection of bone metastases for different modalities [planar bone scintigraphy (BS), single photon emission computed tomography/computed tomography (SPECT/CT), and fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) (F-18 FDG PET/CT)]. METHODS: Patients with known primary tumors referred for metastatic workup either by F-18 FDG PET/CT or conventional planar BS and SPECT/CT were enrolled in this prospective study. The three modalities (BS, SPECT/CT, and PET/CT) were acquired for each patient. Interpretation was done by two independent nuclear medicine physicians separately and blindly; reader 1 (R1) and reader 2 (R2). A three-point subjective scale was used (1 = negative for bone metastases, 2 = equivocal, and 3 = positive). The findings were compared to the final patient status based on clinical and radiological follow-up for at least 6 months. The Kappa test was used to assess the degree of agreement between readers in their interpretation of each modality. RESULTS: A total of 54 patients (39 females and 15 males, ages 26-76; mean: 54.7 ±â€…12) were eligible for this study. Fair agreement 0.372 between R1 and R2 in interpretation of BS was noticed that improved to 0.847 after addition of SPECT/CT. Perfect agreement was achieved between R1 and R2 while interpreting PET/CT images (kappa = 0.964, P < 0.001). CONCLUSION: F-18 FDG PET/CT significantly improved the inter-observer variability between readers, allowing for better diagnosis of bone metastases in known cancer patients. Also, it was superior to BS and SPECT/CT in the detection of bone metastases.

Epistaxis in a Pediatric Outpatient Clinic: Could It be an Alarming Sign?

Abstract Introduction Epistaxis is a common presentation among children. Objective To investigate the suitability of a simple tool of assessment for patients with epistaxis that could guide in subgrouping those with possible bleeding tendencies who may need further assessment. Methods Children who presented to a tertiary outpatient clinic with epistaxis of an unknown cause were recruited. They underwent thorough clinical assessment and answered the pediatric bleeding questionnaire and the epistaxis severity score. All patients underwent complete blood count as well as coagulation profile, and confirmatory diagnostic tests were performed as needed. Results Among the 30,043 patients who presented to the outpatient clinic over a year, 100 children had epistaxis, with an estimated annual frequency of 1 in 300. A total of 84% of the patients were younger than 12, and nearly half of these were younger than 6 years. Seventy-six patients had recurrent epistaxis, and 12 had systemic comorbidities. A significant higher percentage of patients presented with epistaxis in the hot months of the year. A total of 90% of the patients presented anterior bleeding, and the majority were treated with nasal compression only. Forty-three patients presented with epistaxis only; 37 of them were diagnosed as idiopathic epistaxis, and 6 had local causes. Fifty-seven patients presented with other bleeding manifestations, 47 of whom had a definite bleeding disorder and the other 10 had undiagnosed bleeding tendency. Those with other bleeding manifestations showed a higher frequency of positive family history of epistaxis; of being referred from a primary care physician; of having alarming low platelet count, and of presenting less seasonal variability. A bleeding score ≥ 2 showed significant value in suspecting an underlying systemic pathology as a cause of epistaxis. Conclusion The pediatric bleeding questionnaire is a useful and simple tool in the identification of pediatric patients who need further diagnostic testing to detect any underlying bleeding tendency.

FAK inhibition radiosensitizes pancreatic ductal adenocarcinoma cells in vitro.

INTRODUCTION: Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase protein frequently overexpressed in cancer and has been linked to an increase in the stem cell population of tumors, resistance to therapy, and metastatic spread. Pharmacological FAK inhibition in pancreatic cancer has received increased attention over the last few years, either alone or in combination with other therapeutics including chemotherapy and immunotherapy. However, its prognostic value and its role in radioresistance of pancreatic ducal adenocarcinoma (PDAC) is unknown. METHODS AND MATERIALS: Using the TCGA and GTEx databases, we investigated the genetic alterations and mRNA expression levels of PTK2 (the encoding-gene for FAK) in normal pancreatic tissue and pancreatic cancer and its impact on patient survival. Furthermore, we evaluated the expression of FAK and its tyrosine domain Ty-397 in three pancreatic cancer cell lines. We went further and evaluated the role of a commercial FAK tyrosine kinase inhibitor VS-4718 on the viability and radiosensitization of the pancreatic cell lines as well as its effect on the extracellular matrix (ECM) production from the pancreatic stellate cells. Furthermore, we tested the effect of combining radiation with VS-4718 in a three-dimensional (3D) multicellular pancreatic tumor spheroid model. RESULTS: A database analysis revealed a relevant increase in genetic alterations and mRNA expression of the PTK2 in PDAC, which were associated with lower progression-free survival. In vitro, there was only variation in the basal phosphorylation level of FAK in cell lines. VS-4718 radiosensitized pancreatic cell lines only in the presence of ECM-producing pancreatic stellate cells and markedly reduced the ECM production in the stromal cells. Finally, using a 3D multicellular tumor model, the combination of VS-4718 and radiotherapy significantly reduced the growth of tumor aggregates. CONCLUSION: Pharmacological inhibition of FAK in pancreatic cancer could be a novel therapeutic strategy as our results show a radiosensitization effect of VS-4718 in vitro in a multicellular 2D- and in a 3D-model of pancreatic cancer.

Neonatal Gastrointestinal Stromal Tumor of the Sigmoid Colon: A Case Report and Review of Literature.

ABSTACTBackground: Gastrointestinal stromal tumors (GIST) are the most common mesenchymal neoplasms of the digestive tract. They are believed to originate from the interstitial cells of Cajal or their precursors. Case Report: A 10-day-old boy presented with intestinal obstruction. He was operated upon and a mass was found at the sigmoid colon, which was resected and divided colostomy was performed. The diagnosis of neonatal GIST was confirmed by histologic and immunohistochemical studies. Conclusion: This is the ninth case of neonatal GIST that arose from the intestine and the first reported to arise from the sigmoid colon. Colonic GIST can occur in the neonatal age group.