The dual role of transforming growth factor-beta signatures in human B viral multistep hepatocarcinogenesis: early and late responsive genes

Background/Aim Transforming growth factor-beta (TGF-β) has a dichotomous role, functioning as a tumor suppressor and tumor promoter. TGF-β signatures, explored in mouse hepatocytes, have been reported to predict the clinical outcomes of hepatocellular carcinoma (HCC) patients; HCCs exhibiting early TGF-β signatures showed a better prognosis than those with late TGF-β signatures. The expression status of early and late TGF-β signatures remains unclear in defined lesions of human B-viral multistep hepatocarcinogenesis. Methods The expression of TGF-β signatures, early and late responsive signatures of TGF-β were investigated and analyzed for their correlation in cirrhosis, low-grade dysplastic nodules (DNs), high-grade DNs, early HCCs and progressed HCCs (pHCCs) by real-time PCR and immunohistochemistry. Results The expression levels of TGF-β signaling genes (TGFB1, TGFBR1, TGFBR2 and SMAD4) gradually increased with the progression of hepatocarcinogenesis, peaking in pHCCs. The expression of early responsive genes of TGF-β (GADD45B, FBP1, CYP1A2 and CYP3A4) gradually decreased, and that of the late TGF-β signatures (TWIST and SNAI1) significantly increased according to the progression of multistep hepatocarcinogenesis. Furthermore, mRNA levels of TWIST and SNAI1 were well correlated with those of stemness markers, with upregulation of TGF-β signaling, whereas FBP1 expression was inversely correlated with that of stemness markers. Conclusions The enrichment of the late responsive signatures of TGF-β with induction of stemness is considered to be involved in the progression of the late stage of multistep hepatocarcinogenesis, whereas the early responsive signatures of TGF-β are suggested to have tumor-suppressive roles in precancerous lesions of the early stage of multistep hepatocarcinogenesis

Diagnostic Accuracy of Vitreous Cytology in Patients with Vitreoretinal Lymphoma

(1) Background: To determine the diagnostic value of vitreous cytology in patients with vitreoretinal lymphoma (VRL) and evaluate its diagnostic accuracy relative to that of other diagnostic tests. (2) Methods: In total, 38 eyes from 38 patients with VRL who underwent diagnostic vitrectomy and were followed up for at least 6 months were analyzed. The clinical manifestations and VRL diagnostic rates for all diagnostic tests were determined. (3) Results: The presence of vitreous cells/opacity was the most common ophthalmic finding (97.4%), followed by sub-retinal pigment epithelial infiltration (65.8%) and retinal hemorrhage (21.1%). The VRL diagnostic rates were 89.3% for interleukin (IL)-10 levels > 50 pg/mL; 82.1% for IL-10/IL-6 ratios > 1; 60.0% and 63.3% for immunoglobulin heavy chain and kappa light chain clonality assays, respectively; and 44.4% for vitreous cytology. The VRL diagnostic rate for vitreous cytology was significantly lower in the steroid pretreatment group than in the non-steroid pretreatment group (p = 0.007). (4) Conclusions: The VRL detection rate for vitreous cytology was lower than that for the other tests, especially in patients who received steroid pretreatment. These findings suggest that even if vitreous cytology findings are negative, other tests and characteristic fundus findings should be evaluated to confirm VRL diagnosis

Treatment of Pseudoangiomatous Stromal Hyperplasia of the Breast: Implant-Based Reconstruction with a Vascularized Dermal Sling

Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a benign mesenchymal lesion with incidental histologic findings. Surgical excision is recommended as the treatment of choice for PASH, although the recurrence rates after excision range from 15% to 22%. A 46-year-old-female presented with a six-month history of bilateral breast enlargement and painful sensation mimicking inflammatory carcinoma. Imaging studies demonstrated innumerable enhancing nodules in both breasts. Due to the growth of the lesions and progressive clinical symptoms, bilateral subcutaneous mastectomy was performed. Grossly, the specimens were round and well-circumscribed, and the histologic examination revealed PASH. After mastectomy, we created a pocket with the pectoralis major muscle and a lower skin flap, which was deepithelized. Anatomical mammary implants were inserted, and the nipple areolar complex was transferred to a new position as a free graft. The aesthetic result was satisfactory after twelve months of follow-up

Thyroid FNA cytology cases Incidence and Malignancy Rates of Diagnoses in the Bethesda System for Reporting Thyroid Aspiration Cytology: An Institutional Experience

The Bethesda System for Reporting Thyroid Cytopathology (BSRTC) was developed in 2008 to facilitate more accurate communication of thyroid fine-needle aspiration (FNA) interpretations between clinicians and cytopathologists. 1 This system, which we adopted in 2010, classifies FNA results into six general diagnostic categories, namely, I) nondiagnostic or unsatisfactory, II) benign, III) atypia of undetermined significance or follicular lesion of undetermined significance, IV) follicular neoplasm or suspicious for a follicular neoplasm, V) suspicious for malignancy, and VI) malignant. 1 Each of these categories is associated with a risk of malignancy as follows: I) 1-4%, II) 0-3%, III) 5-15%, IV) 15-30%, V) 60-75%, and VI) 97-99%. 1 Although this system is useful, some studies that have investigated these risks have had controversial results, especially for category III. Furthermore, other studies have reported differences in malignancy rates among different institutions and have offered various explanations. In this study, we determined the distribution of FNA results and malignancy rates in each diagnostic category of the BSRTC in our hospital to determine whether our cytopathologists are using this system properly. Specifically, by analyzing data from individual cytopathologists, we hoped to ascertain whether our hospital has consistent FNA results in each diagnostic category. Finally, we suggest ways to improve the accuracy of classifying FNA diagnoses. MATERIALS AND METHODS Thyroid FNA cytology cases We retrospectively analyzed 1,538 patients who had thyroid nodules that were diagnosed by FNA between October 1, 2011, and December 31, 2011, in Gangnam Severance Hospital in Korea. This study met criteria for exemption from review from the institutional review board. Each FNA diagnosis was made independently by one of four cytopathologists. Each thyroid aspiration sample was analyzed by using liquid-based preparation or conventional smear. Some FNAs were originally performed by other hospitals; however, in these cases, the slides were re- Background: The Bethesda System for Reporting Thyroid Cytopathology (BSRTC) uses six diagnostic categories to standardize communication of thyroid fine-needle aspiration (FNA) interpretations between clinicians and cytopathologists. Since several studies have questioned the diagnostic accuracy of this system, we examined its accuracy in our hospital. Methods: We calculated the incidences and malignancy rates of each diagnostic category in the BSRTC for 1,730 FNAs that were interpreted by four cytopathologists in Gangnam Severance Hospital between October 1, 2011, and December 31, 2011. Results: The diagnostic incidences of categories I-VI were as follows: 13.3%, 40.6%, 9.1%, 0.4%, 19.3%, and 17.3%, respectively. Similarly, the malignancy rates of these categories were as follows: 35.3%, 5.6%, 69.0%, 50.0%, 98.7%, and 98.9%, respectively. In categories II, V, and VI, there were no statistically significant differences in the ranges of the malignancy rates among the four cytopathologists. However, there were significant differences in the ranges for categories I and III. Conclusions: Our findings suggest that institutions that use the BSRTC should regularly update their diagnostic criteria. We also propose that institutions issue an annual report of incidences and malignancy rates to help other clinicians improve the case management of patients with thyroid nodules. Incidence and Malignancy Rates of Diagnoses in the Bethesd

Microstructure evolution in nanoporous gold thin films made from sputter-deposited precursors

We fabricate almost crack-free 1.5 ??m thick nanoporous gold thin films using free-corrosion dealloying and transfer processes from sputter-deposited precursors. By controlling the temperature and the concentration of the nitric acid solution during free-corrosion dealloying, we obtain ligament sizes in nanoporous gold between 22 and 155 nm. We investigate the effects of dissolution rate of Ag atoms, surface diffusivity of Au atoms and formation of Ag oxide on nanoporosity evolution.close1

The Clinicopathological and Prognostic Significance of Nrf2 and Keap1 Expression in Hepatocellular Carcinoma

Nuclear factor E2-related factor2 (Nrf2) activation is associated with both cytoprotective effects and malignant behavior of cancer cells. This study aimed to evaluate the clinicopathological implications of the expression of Nrf2, pNrf2, and its regulator Keap1 in human hepatocellular carcinomas (HCCs). Tissue microarrays consisting of 285 surgically resected HCCs were immunohistochemically stained with pNrf2, Nrf2, Keap1, stemness-related markers (keratin 19 (K19), epithelial cell adhesion molecule (EpCAM)), carbonic anhydrase IX (CAIX), epithelial–mesenchymal transition (EMT)-related markers (ezrin, uPAR, E-cadherin), and p53, and the results were correlated with the clinicopathological features. pNrf2 expression was significantly associated with increased proliferative activity, as well as EpCAM, ezrin, p53, and CAIX expression and E-cadherin loss (p < 0.05, all). Strong cytoplasmic Nrf2 expression was associated with CAIX and ezrin expression (p < 0.05, both). Keap1 was associated with increased proliferative activity, portal vein invasion, EMT-related markers, and p53 expression in CAIX-negative HCCs (p < 0.05, all). Both pNrf2 and cytoplasmic Nrf2 expression were associated with decreased overall survival (p < 0.05, both), and cytoplasmic Nrf2 expression was an independent predictor of decreased overall survival on multivariate analysis (hazard ratio 4.15, p < 0.001). Both pNrf2 and cytoplasmic Nrf2 expression were associated with poor survival and aggressive behavior of HCC. In addition, Keap1 expression was also associated with aggressive HCC behavior in CAIX-negative HCCs, suggesting that Keap1 expression should be interpreted in the context of hypoxia status