Eda Yilmaz Akcay

Role of tumor-associated macrophages in the Hexim1 and TGFβ/SMAD pathway, and their influence on progression of prostatic adenocarcinoma

BACKGROUND Hexamethylene bisacetamide-inducible protein 1 (Hexim1) regulates transforming growth factor-β (TGFβ) activity and turnover of SMAD proteins in a cyclin-dependent kinase 9-dependent way. It does so specifically through inhibiting function of this enzyme and by inhibiting the transcriptional activity of positive transcription elongation factor b (P-TEFb). Tumor-associated macrophages (TAMs) play a role in the progression of prostate adenocarcinomas. We investigated the clinicopathological significance of Hexim1, TGFβ, SMAD2, and SMAD7 expression in prostate adenocarcinoma cells, and assessed associations between TAMs density and these proteins. METHODS The cases of 100 patients diagnosed with prostate acinar adenocarcinoma who had undergone radical prostatectomy were retrospectively examined. Each was reviewed for Gleason score, cancer stage, and specific histopathological features. Original slides were re-examined, and new slides were prepared and immunostained with Hexim1, TGFβ, SMAD2, SMAD7 and CD68. RESULTS Hexim1 expression was positively correlated with Gleason score, cancer stage, lymphovascular invasion, perineural invasion, extracapsular extension, and positive surgical margin. TAMs density was positively correlated with Gleason score, cancer stage, perineural invasion, extracapsular extension, and positive surgical margin. TAMs density was positively correlated with Hexim1 expression and TGFβ expression. More advanced cancer stage, lymphovascular invasion, perineural invasion, and extracapsular extension were correlated with strong Hexim1 expression, strong SMAD2 expression, and mild SMAD7 expression, respectively. Strong Hexim1 expression, strong TGFβ expression, and mild SMAD7 expression were associated with higher Gleason score. Strong Hexim1 expression was correlated with strong TGFβ expression and mild SMAD7 expression. Strong Hexim1 expression, strong SMAD2 expression, and mild expression of SMAD7 were associated with disease progression. Strong SMAD2 expression was associated with shorter disease-free survival. CONCLUSION The results suggest that greater TAMs density, strong Hexim1 expression, strong SMAD2 expression, and mild SMAD7 expression play important roles in the progression of prostate adenocarcinoma. Further investigation of these proteins will help facilitate the definitive prognosis of prostate adenocarcinomas. Ultimately, these proteins may be therapeutic targets for patients with prostate cancer.

Comparison of Recipients with Early and Later Presentation Polyomavirus Nephropathy (PVN) with Regard to Histological Findings and Graft Survival: What is the Influence of CD4/CD8 Ration on the Presenting Time of PVN

Introduction PVN is a common complication occurring around 12 months after transplant (Tx). Although unusual, the number of patients with late-presenting PVN is too much to underestimate. Thus, we aimed to understand if there are any differences between early and late-presenting PVN with regard to histological findings and graft survival. Materials and Methods All indication and follow-up biopsies of 71 patients with PVN re-evaluated and examined for the development of interstitial fibrosis (IF). Interstitial plasma cells, neutrophils, and CD3, CD4, CD8, HLA-DR positive cells, and macrophages graded. Patients separated into four groups in regards to the time of the development of PVN after Tx [Group A: <12 months (n:35), Group B: 12-24 months (n:13), Group C: 24-48 months (n:15), Group D: >48 months (n:8)]. Also, recipients correlated in two groups as Group 1 (n:48) early PVN (⩽12 months) and Group 2 (n: 23) late PVN (>12 months). Results The mean interval between the diagnosis of PVN and Tx was 17±22 months. Group 1 had higher mean hemodialysis (HD) time before Tx than Group 2 (p<.05). At the same time with PVN, CMV viremia was found in 27 patients. The mean viral load in urine and plasma at diagnosis was found higher in Group 1 than those Group 2 (p<0,01). Group 1 showed lower stages and higher degrees of polyoma viral load (Pvl) in biopsy compared to Group 2 (p<.05). Viral load in urine, plasma, and biopsy found to increase from Group A to Group D. Compared to Group 2; Group 1 showed higher degrees of interstitial neutrophil, plasma, macrophage, lymphocyte, DR-positive cell infiltration and lower degrees of the CD4/CD8 ratio (p<.01). All inflammatory cell types in interstitium found to increase from Group A to Group D. Interstitial CD4/CD8 ratio showed a significant negative correlation with Pvl (r=-0.320, p=.01), viremia (r=-0.602, p<.001) and viruria (r=-0.748, p<.001). Total 43 patients (60.6%) developed IF during follow-up, and 31 (43.7%) cases lost their graft at a mean time of 18±14 months after PVN. The risk of the development of IF increases from Group A to Group D (p<.01). Compared to Group 2 (28.7±16 months), the mean time of the graft loss after PVN was significantly early in Group 1 (13.3±9 months). The mean time of graft loss also decreases from group A to D (p<.05). Positive correlation found between the graft loss and CD4/CD8 ratio (r=0.391, p<.05). Conclusion This study pointed out that late-onset PVN is not uncommon. Recipients with late-onset PVN had a better prognosis than early-onset cases. Although the cause of late-onset PVN remains unclear, it is possible that host cells could influence the time of the onset of PVN. We showed that lower CD4 and higher CD8 proportions were risk factors for early-onset of PVN and poor graft survival. Contrarily patients who had high CD4/CD8 ratio developed late-onset PVN and better graft survival.

Can strain elastography combined with ultrasound breast imaging reporting and data system be a more effective method in the differentiation of benign and malignant breast lesions

PurposeTo investigate whether a novel method that combines breast imaging reporting and data system (BI-RADS) with strain elastography contributes to diagnostic performance in differentiation of malignant and benign breast lesions.MethodsIn 81 patients, 81 breast lesions were prospectively investigated. Breast lesions were separately evaluated with ultrasonography and strain elastography. While evaluations with ultrasonography were based on 2003 BI-RADS-US, strain elastography evaluations were based on a 5-point scale and strain ratio. Diagnostic performances of ultrasonography, strain elastography, and the combined method were compared.ResultsAmong 81 lesions, 43 (53.1%) were benign and 38 (46.9%) were malignant. When a cutoff point of category 3 was used, sensitivity, specificity, positive and negative predictive values, and accuracy for BI-RADS were 100, 11.6, 50, 100, and 53%, respectively. When BI-RADS and strain ratio were combined, sensitivity, specificity, positive and negative predictive values, and accuracy were 89.5, 93, 91.9, 90.9, and 91.3%, respectively. When BI-RADS and elastography scores were combined, sensitivity, specificity, positive and negative predictive values, and accuracy were 86.8, 97.7, 97.1, 89.4, and 92.5%, respectively.ConclusionsThe combination of strain elastography and BI-RADS was found to have better diagnostic performances to diagnose breast lesions than BI-RADS alone.

Human papilloma virus (HPV) negatif verrusiform ksantom: Skrotumda nadir görülen benign tümör

Verrusiform ksantom oldukca nadir gorulen ve genellikle oral mukozayi tutan benign bir neoplazidir. Mukoza disinda az sayida vaka ile vulva, skrotum, penis, anal bolge ve ekstremitelerde yerlestigi bildirilmistir. Makroskopik gorunumu nedeniyle klinik olarak kondiloma akuminatum, verrukoz karsinom ve skuamoz hucreli karsinom ile karisabilir. Ayirici tani icin mutlaka lezyonun eksizyonu ve histopatolojik incelemesi gereklidir. Bu lezyonun etyopatogenezi hala tartismalidir. Literaturde HPV enfeksiyonu pozitif vakalar bildirilmistir. Ancak HPV ile iliskisi net aciklanamamistir. Bu yazida, skrotumda yerlesim gosteren bir verrusiform ksantom olgusunu, nadir gorulmesi, HPV negatif olmasi ve klinik olarak malignite ile karismasi sebebiyle sunmayi amacladik.

Breast cancer or an insidious disease? Idiopathic granulomatous mastitis, its ultrasonographic, dynamic contrast-enhanced MR and diffusion MR characteristics with a literature review

Introduction: Idiopathic granulomatous mastitis is a rare, benign inflammatory breast disease which can mimic breast carcinoma radiologically. Ultrasound and magnetic resonance imaging findings may help for diagnosis. The aim of this study is to evaluate ultrasound, MRI, diffusion-weighted and dynamic contrast-enhanced MRI findings of idiopathic granulomatous mastitis. Material and Methods: 12 patients were enrolled in this study. All patients were examined with ultrasound, diffusion-weighted and dynamic contrast-enhanced MRI. Morphological characteristics, apparent diffusion coefficient values and time-intensity curves of lesions were evaluated. Results: Ultrasound and non-contrast magnetic resonance imaging showed heterogenous masses and dilated ducts. Non-mass-like enhancement, mass-like enhancement and ring-like enhancement were identified on dynamic contrast-enhanced MRI. Lesions showed type 1, type 2 or type 3 enhancement patterns. Type 3 curve changed into type 1 curve after steroid therapy in one patient. The mean apparent diffusion coefficient value of lesions was 1.01 ± 0.06 (× 10 -3 mm2/s). Discussion and Conclusion: Dynamic contrast-enhanced MRI findings may generally help to differantiate malignancy from idiopathic granulomatous mastitis, however, idiopathic granulomatous mastitis can show type 3

Effect of the Bioadhesive, BioGlue, on Impaired Colonic Anastomose Healing in Rats

Colonic anastomotic leakage is still a problem in general surgery practice. We sought to investigate the effect of a new tissue adhesive, BioGlue, on the healing of normal and impaired colonic anastomoses. Sixty-four rats were randomized into 4 groups. In all animals, a 1-cm segment of the left colon was resected, and an end-to-end sutured anastomosis was created. Animals were then divided into 2 groups: normal and impaired anastomosis. These 2 groups were further subdivided into 2 additional groups: animals that received BioGlue and those that did not. All rats received intraperitoneal injections of either 0.9% NaCl or 5-fluorouracil (5-FU). Anastomotic evaluation was done 7 days after surgery. Macroscopic healing, mechanical strength, and histopathologic healing parameters were evaluated. Leakage of the anastomosis was significantly higher in rats in the impaired group compared with those in the BioGlue groups (P = 0.043). The adhesion formation score was significantly higher in rats in the impaired ana...