Impact of Screening for Salivary Gland by Ultrasonography

Background: Ultrasonography is superior to other imaging modalities for detecting salivary gland diseases. However, there have been no reports of the results of salivary gland screening with ultrasonography. In this study, the salivary glands were also observed during thyroid ultrasonography to determine the degree of salivary gland abnormalities detected by ultrasonography. Methods: This study was conducted retrospectively using medical records. It assessed the association between the following abnormal findings detected during thyroid ultrasonography and their final diagnoses: atrophy/swelling, unclear demarcation from surrounding tissues, decreased salivary gland parenchyma echo level, heterogeneity of parenchyma, hypervascularity of salivary gland parenchyma, dilatation of the ducts, and a mass within the gland. Results: Of the 908 patients who underwent thyroid ultrasonography, salivary gland abnormalities were detected in 36 (4.0%) patients. Of the 36 patients with abnormal ultrasonographic findings, 22 underwent further examination. Of the 22 patients, 16 received definitive diagnoses of salivary gland diseases. Salivary gland disorders were considered to be absent in patients with only heterogeneity of the salivary glands observed on ultrasonography. Salivary gland disorders in all patients with further abnormal ultrasonographic findings such as atrophy/swelling, unclear boundary, or hypervascularity in addition to internal heterogeneity were confirmed by further blood examinations and imaging studies. We were able to detect autoimmune sialadenitis such as Sj ögren’s syndrome and IgG4-related sialadenitis by ultrasonography in patients without obvious symptoms. Conclusion: Salivary gland screening during thyroid ultrasonography revealed abnormal findings including Sjögren’s syndrome and IgG4-related sialadenitis in about 4% of the patients. Thus, ultrasonography may also be useful for early detection of autoimmune diseases of salivary glands

Expression of DNA Methyltransferase (DNMT) 1, 3a and 3b Proteins in Human Hepatocellular Carcinoma

Alteration of aberrant DNA methylation is one of the most consistent epigenetic changes found in human cancers. DNA methylation is catalyzed by DNA methyltransferase (DNMT). In this study, we examined DNMT protein expression by immunohistochemistry in surgically resected hepatocellular carcinomas (HCCs). Sections of paraffin-embedded specimens were obtained from 95 patients with HCC between 1989 and 2002. The specimens were stained with anti-DNMTs (DNMT1, DNMT3a and DNMT3b) antibodies. There were statistically significant associations between DNMT protein expression and tumor differentiation (P < 0.05) and intrahepatic metastasis (P < 0.05). DNMT3a protein expression was significantly correlated with portal vein involvement of tumors (P < 0.05). The overall survival rates of patients with DNMT3a-positive HCCs and DNMT3b-positive HCCs were significantly lower than those of patients negative for these proteins (P < 0.005, respectively). To further evaluate the correlation between DNMT protein expression and patient survival, we classified patients into 3 groups: Group 1, DNMT1(+), 3a(–) and 3b(–); Group 2) DNMT1(+), 3a or 3b(+); and Group 3) DNMT1(+), 3a(+) and 3b(+). The overall survival rate of patients in Group 3 was significantly lower than those of patients in Groups 1 and 2 (P = 0.0009). In conclusion, the results of this study suggest that DNMT1, DNMT3a and DNMT3b are cooperatively involved in determining the extent of HCCs, and that DNMT protein overexpression in HCCs may be a predictive factor for poor survival

Expression of Phospho-Akt and PTEN Proteins in Human Breast Cancer in Relation to Tumor Progression and Patient Survival

Phosphatidylinositol 3-kinase (PI3-kinase) controls mitogenesis, cellular growth and transformation in a variety of cancers. The serine-threonine kinase Akt is a downstream target of PI3-kinase, and phosphorylated Akt (Phospho-Akt) inhibits apoptosis. Phosphatase and tensin homolog detected on chromosome ten (PTEN) is a tumor suppressor that antagonizes PI3-kinase activity, negatively regulates its downstream-target, Akt, inhibits phosphorylation of Akt, and medicates cell-cycle arrest and apoptosis. To clarify whether the PI3-kinase/Akt pathway and PTEN relate to breast cancer, we examined the expression of pathway-related proteins such as Phospho-Akt and PTEN in clinical specimens. Immunohistochemical analysis was performed on tissue specimens surgically obtained from 221 patients with breast cancer. The association of Phospho-Akt and PTEN expression with clinicopathological variables and the prognosis of patients were analyzed. Of 221 breast carcinomas, positive Phospho-Akt expression was observed in 91 (41.1%) and positive PTEN expression in 119 (53.8%). Phospho-Akt expression and loss of PTEN expression significantly correlated with tumor staging, tumor size and lymph node metastasis. Patients with Phospho-Akt-positive tumors had significantly inferior disease-free survival or over-all survival to those with Phospho-Akt-negative tumors, while those with PTEN positive tumors were better than those with PTEN negative tumors. Moreover, patients with Phospho-Akt-positive and PTEN-negative tumors had a significantly inferior disease-free survival and over-all survival compared to those with Phospho-Akt-negative and PTEN-positive tumors. Multivariate analysis revealed that expression of Phospho-Akt and tumor size were the independent factors (P = 0.024). We demonstrated that the expression of Phospho-Akt significantly correlated with tumor progression and patients survival with breast cancer. Phospho-Akt/PTEN expression status is possibly a definitive prognostic factor in clinical breast cancer

Transabdominal Ultrasonography for Assessing the Depth of Tumor Invasion in Gastric Cancer

[Background] Although endoscopy and endoscopic ultrasonography are generally used to diagnose the depth of gastric tumor invasion, endoscopy is invasive and frequently results in patient discomfort. Transabdominal ultrasonography (TUS) is noninvasive and may be useful in determining this depth. We investigated the usefulness of TUS in determining the depth of tumor invasion in patients with gastric cancer. [Methods] This retrospective study included 190 patients with gastric cancer and 200 lesions who underwent curative resection at the Department of Gastrointestinal Surgery of Tottori University Hospital from July 2007 to July 2015. The results of conventional diagnostic imaging and TUS were compared with those of pathological analysis obtained after surgery. Furthermore, the ruptured form of the third layer on TUS imaging was reviewed and investigated to differentiate between the SM2 and MP lesions. [Results] The accuracy of TUS was similar to that of conventional diagnostic imaging for all depths of tumor invasion. Eight lesions could not be assessed by TUS, including four that could not be identified and four in which TUS was unable to diagnose the depth. In cases where the ruptured form of the third layer could be determined in MP lesions, the forms were observed toward the inside of the gastric lumen. [Conclusion] The results of this study suggested that the accuracy of TUS was equivalent to that of conventional diagnostic imaging in determining the depth of tumor invasion. TUS assessment criteria may be useful to classify this depth. Furthermore, the ruptured form of the third layer is believed to be important in distinguishing between early and advanced gastric cancer

Usefulness of a Novel Ultrasonographic Classification Based on Anechoic Area Patterns for Differentiating Warthin Tumors from Pleomorphic Adenomas of the Parotid Gland

[Background]Ultrasonographic homogeneity is an important differential finding between Warthin tumor and pleomorphic adenoma, two types of benign parotid gland tumors, with the former likely to be heterogeneous and the latter homogeneous. However, differences in the performance of ultrasound machines or the homogeneity cut-off level affect the judgment of ultrasonographic homogeneity. Therefore, in this study, we adopted a novel system for classifying the composition of tumors via ultrasonography, using anechoic area as a substitute for differences in homogeneity to differentiate between Warthin tumors and pleomorphic adenomas. [Methods]We evaluated 68 tumors that were histopathologically diagnosed as Warthin tumor or pleomorphic adenoma between July 2009 and November 2015. Ultrasonographic images of the tumors were evaluated on the basis of key differentiating features, including features on B-mode imaging and color Doppler imaging. Additionally, the tumors were classified into four groups based on anechoic area, and findings were compared between Warthin tumors and pleomorphic adenomas. [Results]While 38 of the tumors were pleomorphic adenomas, 30 were Warthin tumors. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for detection of Warthin tumors using our novel classification system were 73.3%, 76.3%, 71.0%, 78.4% and 75.0%, respectively. Compared to pleomorphic adenomas, Warthin tumors showed large or sponge-like anechoic areas, rich vascularization and an oval shape even at large tumor sizes, and the difference was significant. On defining Warthin tumor as a tumor demonstrating two or more of the findings noted above, the sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy for its detection were 73.3%, 84.2%, 78.6%, 80.0% and 79.4%, respectively. [Conclusion]Our novel classification system based on anechoic area patterns demonstrated by the tumors had high sensitivity, specificity and diagnostic accuracy for differentiating Warthin tumors from pleomorphic adenomas

Investigation of the Utility and Safety of Dynamic Computed Tomography with Vasodilators

Background: Dynamic computed tomography (CT) angiography is useful for evaluating of hepatic vascularity. Although vasodilators increase hepatic blood flow, the utility of dynamic CT with vasodilators is unclear. Here we investigated the utility and safety of dynamic CT with vasodilators. Methods: A prospective case-control radiographic evaluation using abdominal dynamic CT with and without vasodilator was performed at a single center between October 2015 and September 2016. We compared the CT values in Hounsfield units of the aorta; celiac artery; and common, right, and left hepatic arteries in the arterial phase and the main trunk; right and left branches of the portal vein; and right, middle, and left hepatic veins in the portal phase with and without vasodilators. The region of interest was set in each element of the liver vasculature. Four radiological technologists independently and visually compared the scores of the portal vein (P-score) and hepatic vein (V-score) on a 5-point scale with and without vasodilators. Results: The CT values of arteries and veins using vasodilators were significantly higher than those without vasodilators. With and without vasodilators, the P-scores were 3.1 ± 1.2 and 4.0 ± 1.1 (P < 0.05) and the V-scores were 3.3 ± 1.4 and 4.3 ± 1.0 (P < 0.05). Only one patient with vasodilator use had transient hypotension and recovered immediately without medication. Conclusion: Dynamic CT with vasodilators can provides better visualization of vascular structures

Expression of phospho-Akt and PTEN Proteins Predicts the Survival of Patients with Pancreatic Cancer

The phosphatidylinositol-3 kinase (PI3K)-Akt signaling pathway is known to protect a variety of cells from apoptosis. Phospho-Akt (p-Akt) can facilitate cell survival and inactivating pro-apoptotic proteins. The phosphatase and tensin homologue deleted on chromosome ten (PTEN) is a natural biological inhibitor of p-Akt in the PI3K-Akt pathway. The relationship between the expressions of p-Akt and PTEN and pancreatic cancer is unknown. Here, we designed a study to clarify the prognostic significance of p-Akt and PTEN expression in patients with pancreatic cancer. Immunohistochemical analysis of p-Akt and PTEN protein was performed on 51 specimens of pancreatic cancer. The expression of p-Akt was detected in 32 patients (62.7%). The expression of p-Akt was frequently detected in patients with advanced stage pancreatic cancer (P = 0.0233). Patients with p-Akt-positive tumors had significantly worse prognoses than those with p-Akt-negative tumors (overall survival; 11.3% versus 25.7%). The expression of PTEN was detected in 26 patients (51.0%). Patients with PTEN-positive tumors had significantly better prognoses than those with PTEN-negative tumors (overall survival; 29.9% versus 0%). Patients with p-Akt-positive and PTEN-negative tumors had significantly worse prognoses than those with p-Akt-negative and PTEN-positive tumors (overall survival; 0% versus 39.1%). Multivariate analysis revealed that expression of p-Akt was an independent prognostic factor as well as arterial invasion and lymph node metastasis. The expression of p-Akt and PTEN proteins determined by immunohistochemistry may be a new method for predicting the prognosis of patients with pancreatic cancer

Recent Advances in Ultrasound Imaging of Breast Lesions

Helminth parasites are known to elicit the immune response towards T helper 2 (Th2)-type, characterized by Th2 related cytokines, that typically include interleukin-4 (IL-4), IL-5 and IL-13. In this review we will describe the mechanisms involved in helminth induced Th2 immune response. Intestinal epithelial cells (IECs) produce thymic stromal lymphopoietin (TSLP), which is both necessary and sufficient for the initiation of Th2 cytokine-driven inflammation. IL-33 mRNA is expressed early during parasite infection and IL-33 binds ST2 receptor, both of which are associated with optimal CD4+ Th2 polarization. Following innate immune cell recognition, basophils and mast cell can secrete Th2 type cytokines that are thought to contribute to CD4+ Th2 differentiation. Additionaly, dendritic cell conditioned with some helminth products can promote CD4+ Th2 differentiation. Alternatively activated macrophages, activated by the Th2 cytokines IL-4 and IL-13 in parasitic infections, contribute to the host protective response: control of Th1-type inflammation, wound healing and worm expulsion. Experimentally, helminths have been associated with protection against a number of autoimmune disorders, including inflammatory bowel diseases and type 1 diabetes. It may be a novel strategy to ameliorate autoimmune inflammation by expanding and activating the Th2 response originated from parasites