THE DIAGNOSTIC ACCURACY OF A COMBINATION OF PREOPERATIVE 68-Ga PSMA PET/CT AND MULTIPARAMETRIC MRI IN LOCALIZED PROSTATE CANCER.

INTRODUCTION: Prostate cancer (PCa) is a common and leading course of cancer-related death in men. Although there are studies on multiparametric magnetic resonance imaging (MpMRI) with good diagnostic results in detecting clinically significant prostate cancer, new methods have been investigated due to the low positive predictive values. In this context, Prostate Specific Membrane Antigen Positron Emission Tomography (PSMA PET) emerges as an alternative imaging method to MpMRI. This study aims to compare 68Ga PSMA I&T-PET/CT and MpMRI in determining tumor location. METHODS: Preoperative MpMRI and 68Ga PSMA I&T-PET/CT scans and pathology specimens of who underwent radical prostatectomy for PCa at our clinic between 2018-2021 were retrospectively evaluated. PSMA I&T-PET/CT, MpMRI, combined imaging were compared for tumor localization according to histopathological data. RESULTS: In terms of tumor localization, MpMRI demonstrated overall accuracy rates 75.9% (p kappa (κ) 0.0001* (0.525)). 68Ga PSMA I&T-PET/CT showed 71.5% (p κ 0.0001* (0.438)). For the combined imaging approach overall accuracy rate were calculated as 79.2% (p κ 0.0001* (0.576)). Additionally, high diagnostic accuracy was achieved for the combined imaging approach, particularly in the intermediate ISUP group. Moreover, SUVmax was calculated as 6.37. CONCLUSION: The combined use of 68Ga PSMA I&T-PET/CT and MpMRI has high diagnostic rates. However, the high cost is a significant disadvantage that limits their routine combined use.

Confirmation of PSMA expression measured on [68Ga]Ga-PSMA PET/CT by immunohistochemistry in prostate adenocarcinoma.

BACKGROUND: Our aim is to determine the accuracy of [68Ga]Ga-PSMA PET/CT in showing PSMA expression in primary prostate cancer and to investigate the relationship between SUVmax and immunohistochemical PSMA expression, Gleason score, and PSA value. MATERIAL AND METHODS: We retrospectively analyzed 66 male patients who were diagnosed with primary prostate adenocarcinoma, underwent pre-treatment [68Ga]Ga-PSMA PET/CT examination for staging, and performed radical prostatectomy between March 2018-August 2020. Immunohistochemical staining was applied to the radical prostatectomy specimens of all patients to detect PSMA expression. The results were evaluated as an immunoreactive score (IRS) and a modified IRS was obtained. Gleason score groups and prostate-specific antigen (PSA) serum values of the patients were obtained from the patient files. RESULTS: The high SUVmax of primary prostate tumors was significantly correlated with a high modified IRS score (score 2; 3), high PSA value, high Gleason score, and metastasis. In correlation analysis, a positive correlation was found between SUVmax and PSA value and modified IRS score (r = 0.69, p = 0.001; r = 0.39, p = 0.001). In addition, there was a statistically significant weak correlation between PSA serum concentration and modified IRS scores (r = 0.267; p = 0.03). In regression analysis, the percentage of positive cells had a statistically significant and increasing effect on SUVmax (p = 0.031; std beta = 0.268; 95% CI = 0.231-4.596). CONCLUSIONS: In prostate adenocarcinoma, SUVmax of the primary tumor in [68Ga]Ga-PSMA PET/CT correlates with immunohistochemical PSMA expression. In addition, high SUVmax is associated with markers of poor prognoses, such as high PSMA expression, PSA value, and Gleason score.

Is CONUT score a prognostic index in patients with diffuse large cell lymphoma?

Background/aim: The aim of the study was to evaluate the effect of Controlling Nutritional Status (CONUT) score on the prognosis in patients with diffuse large B-cell lymphoma (DLBCL). Materials and methods: The present study was a retrospective study. The CONUT score was calculated based on serum albumin, total cholesterol and lymphocyte levels. This study included a total of 266 patients, 131 (49.2%) were female and 135 (50.8%) were male. The median follow-up period was 51 months (range: 1­190). Results: The median age was 64 years. The cut off CONUT was 1.5. There was a significant difference between patients with high (≥ 2) or low (< 2) CONUT scores in terms of overall survival (OS) and progression-free survival (PFS). The 5-year OS and PFS in patients with high CONUT score was 52.1% and 49.7%. The 5-year OS and PFS in patients with low CONUT score was 79.8% and 75.6% (p < 0.001). In the multivariate analysis for OS, age ≥ 65 years (HR = 1.80, p = 0.028), Eastern Cooperative Oncology Group (ECOG) > 1 (HR = 2.04, p = 0.006), stage IIIA­IVB disease (HR = 2.75, p = 0.001) and the CONUT score (HR = 1.15, p = 0.003) were found statistically significant. In the multivariate analysis for PFS, age ≥ 65 years (HR = 2.02, p = 0.007), stage IIIA­IVB disease (HR = 2.42, p = 0.002) and the CONUT score (HR = 1.19, p = 0.001) were found to be significant parameters. Conclusion: High CONUT score reduces OS and PFS in DLBCL. CONUT score is an independent, strong prognostic index in patients with DLBCL.

The renoprotective effects of mannitol and udenafil in renal ischemia-reperfusion injury model.

PURPOSE: The aim of this study was to investigate and compare the effects of udenafil and mannitol in an experimental renal ischemia-reperfusion (I/R) injury model. MATERIALS AND METHODS: A total of 64 female Wister Albino rats were used. Right nephrectomy was performed in all groups. In the control group; I/R injury was not performed. In the I/R group; left renal pedicle was clamped for 45 minutes and then underwent 60 minutes and 24 hours of reperfusion. In the mannitol group; 1 mL 20% mannitol was given intravenously 15 minutes before clamping. In the udenafil group; 10-mg/kg udenafil was given orally 1 hour before clamping. Creatinine (Cr), blood urea nitrogen (BUN), Cr clearance, malondialdehyde, neutrophil gelatinase associated lipocalin (NGAL), histological examination and DNA damage (Comet Assay method) levels were compared in tissue, serum and urine samples. RESULTS: Udenafil had a better protective effect than mannitol according to biochemical parameters (Cr, BUN, Cr clearance, and NGAL levels) and histopathological findings when compared with the I/R group. In the Comet sampling analysis no significant difference was detected. CONCLUSIONS: Udenafil has a better renoprotective effect than mannitol against I/R injury and this effect supports more functional improvements. Further clinical trials are needed to demonstrate those effects and clinical utility of udenafil for that purpose in humans.

MYD88 expression and L265P mutation in mature B-cell non-Hodgkin lymphomas.

BACKGROUND: Myeloid differentiation primary response 88 (MYD88) is a common adaptor protein that is responsible for signaling from several receptors; mutations in this gene may play a role in the pathogenesis of lymphoma. AIM: We aimed to determine the MYD88 L265P mutation frequency, the level of MYD88 expression, and their associations with clinicopathological parameters in mature B-cell non-Hodgkin lymphomas (NHLs). METHODS: A total of 68 patients were included in the study. The presence of the MYD88 L265P mutation was analyzed by real-time polymerase chain reaction and direct sequencing. MYD88 protein expression was evaluated by immunohistochemistry (IHC) using two different scoring systems. RESULTS: MYD88 L265P mutation was present in eight (18.6%) diffuse large B-cell lymphoma (DLBCL) patients. We also observed a significant association between the loss of MYD88 expression and advanced stage in both mature B-cell NHL and DLBCL according to the first IHC scoring systems (p=0.015 and p=0.024, respectively). An association was also seen between MYD88 overexpression and low clinical risk in both mature B-cell NHL and DLBCL according to the second IHC scoring system (p=0.027 and p=0.024, respectively). CONCLUSIONS: The L265P mutation may be helpful for understanding the pathogenesis of immune-privileged site-associated DLBCLs. The presence of the mutation, together with its protein overexpression, could also be used as a prognostic marker in advanced stage DLBCLs.

Possible Role of GADD45γ Methylation in Diffuse Large B-Cell Lymphoma: Does It Affect the Progression and Tissue Involvement?

OBJECTIVE: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma among adults and is characterized by heterogeneous clinical, immunophenotypic, and genetic features. Different mechanisms deregulating cell cycle and apoptosis play a role in the pathogenesis of DLBCL. Growth arrest DNA damage-inducible 45 (GADD45γ) is an important gene family involved in these mechanisms. The aims of this study are to determine the frequency of GADD45γ methylation, to evaluate the correlation between GADD45γ methylation and protein expression, and to investigate the relation between methylation status and clinicopathologic parameters in DLBCL tissues and reactive lymphoid node tissues from patients with reactive lymphoid hyperplasia. MATERIALS AND METHODS: Thirty-six tissue samples of DLBCL and 40 nonmalignant reactive lymphoid node tissues were analyzed in this study. Methylation-sensitive high-resolution melting analysis was used for the determination of GADD45γ methylation status. The GADD45γ protein expression was determined by immunohistochemistry. RESULTS: GADD45γ methylation was frequent (50.0%) in DLBCL. It was also significantly higher in advanced-stage tumors compared with early-stage (p=0.041). In contrast, unmethylated GADD45γ was associated with nodal involvement as the primary anatomical site (p=0.040). CONCLUSION: The results of this study show that, in contrast to solid tumors, the frequency of GADD45γ methylation is higher and this epigenetic alteration of GADD45γ may be associated with progression in DLBCL. In addition, nodal involvement is more likely to be present in patients with unmethylated GADD45γ.

Acute Brucella melitensis M16 infection model in mice treated with tumor necrosis factor-alpha inhibitors.

INTRODUCTION: There is limited data in the literature about brucellosis related to an intracellular pathogen and anti-tumor necrosis factor alpha (anti-TNFα) medication. The aim of this study was to evaluate acute Brucella infections in mice receiving anti-TNFα drug treatment. METHODOLOGY: Anti-TNFα drugs were injected in mice on the first and fifth days of the study, after which the mice were infected with B. melitensis M16 strain. Mice were sacrificed on the fourteenth day after infection. Bacterial loads in the liver and spleen were defined, and histopathological changes were evaluated. RESULTS: Neither the liver nor the spleen showed an increased bacterial load in all anti-TNFα drug groups when compared to a non-treated, infected group. The most significant histopathological findings were neutrophil infiltrations in the red pulp of the spleen and apoptotic cells with hepatocellular pleomorphism in the liver. There was no significant difference among the groups in terms of previously reported histopathological findings, such as extramedullary hematopoiesis and granuloma formation. CONCLUSIONS: There were no differences in hepatic and splenic bacterial load and granuloma formation, which indicate worsening of the acute Brucella infection in mice; in other words, anti-TNFα treatment did not exacerbate the acute Brucella spp. infection in mice.

Efficacy of 5-fluorouracil in inhibition of unintended bone formation in spinal surgery: a histological evaluation on a rat model of spontaneous spinal fusion.

OBJECTIVE: The aim of this study was to investigate the influence of the antiproliferative agent 5-Fluorouracil (5FU) over inhibition of spinal bone formation in an experimental rat model. METHODS: The study included 30 6-month-old Sprague-Dawley rats divided into 3 groups. Aggressive periosteal denuding was performed by scalpel to induce punctuate bleeding in the posterior elements of the L4-L5 vertebrae in the spontaneous fusion model. Spinous processes were fixated by wires and no graft substitute was applied. Adcon-L was applied in Group 1, single-touch technique 5FU in Group 2. Group 3 was the control group. Rats were sacrificed at 4 weeks and specimens acquired for histological examination. RESULTS: 5FU substantially inhibited fibroblast and inflammatory cell densities as well as bone formation compared to the control group. 5FU was considerably superior to Adcon-L with regard to inhibition of bone formation and inflammatory cells (p=0.0001). CONCLUSION: 5FU can inhibit fusion, fibrosis and unwanted scar tissue in spinal surgery. We believe that after further studies on its local delivery dose, it can be used in humans for inhibition of unintended fusion.

Expression and amplification of Topoisomerase-2α in type 1 and type 2 papillary renal cell carcinomas and its correlation with HER2/neu amplification.

The current study was undertaken to investigate chromosomal and genetical aberrations leading to overexpression of Topoisomerase-2α (TOP2α) and to reveal the possible association of these aberrations with HER2/neu overexpression and gene amplification, and to search for the relationship between TOP2α and HER2/neu status with prognostical biomarkers in papillary renal cell carcinoma (RCC), a group of tumors with diverse molecular, chromosomal and clinical features. Archival cases of papillary RCC obtained from Departments of Pathology of Pamukkale, Ege and Dokuz Eylul Universities were studied in two groups (type 1 and type 2) each containing 20 cases. The level of TOP2α and HER2/neu expression by tumor cells were determined immunohistochemically. A multicolor FISH probe was used to define both amplification of HER2/neu and TOP2α genes, and polysomy 17. The ratio of cells expressing TOP2α in type 1 and type 2 papillary RCC were 24.29% and 6.89%, respectively. The difference was statistically significant comparing the average or median values of groups separately (p = 0.002). The expression levels of TOP2α and HER2/neu were also correlated. TOP2α and HER2/neu were co-amplified in both groups. Immunohistochemical expression was not observed in 15 of 23 cases with HER2/neu amplification. The most frequent finding detected by FISH method was polysomy of chromosome 17. We had contradictory results compared with the findings reported in the limited numbers of literature. It shows us that papillary RCC constitute a heterogenous group of tumors with various cytogenetic features and morphological classification of these tumors may not be compatible with their molecular characteristics.

Determination of apoptosis, proliferation status and O6-methylguanine DNA methyltransferase methylation profiles in different immunophenotypic profiles of diffuse large B-cell lymphoma.

OBJECTIVE: Our aim was to investigate the expression of apoptosis-associated proteins (bcl-2, bcl-xl, bax, bak, bid), apoptotic index (AI) and proliferation index (PI) in germinal center B-cell-like immunophenotypic profile (GCB) and non-GCB of diffuse large B-cell lymphoma (DLBCL). METHODS: The methylation status of the promoter region of O6-methylguanine-DNA yerine O6-methylguanine-DNA methyltransferase (MGMT) gene and its relation with immunophenotypic differentiation of DLBCLs were also investigated. 101 cases were classified as GCB (29 cases) or non-GCB (72 cases). Apoptosis-associated proteins and PI were determined by IHC, and TUNEL method was used to determine AI. MGMT methylation analysis was performed by real-time PCR. RESULTS: The PI was significantly higher in GCB compared with non-GCB (p=0.011). Percentage of cells stained with bcl-6 was positively correlated with the percentage of cells expressing bcl-2 (p=0.023), AI (p=0.006) and PI (p<0.001), while a significant negative correlation was observed with the percentage of cells expressing bax (p=0.027). The percentage of cells stained with MUM1 showed a significantly positive correlation with the percentage of cells expressing bcl-xl (p=0.003), bid (p=0.002), AI (p<0.001), and PI (p=0.001). MGMT methylation analysis was performed in 95 samples, and methylated profile was found in 31 cases (32.6%). GCB was found in 6 cases (22.2%) and non-GCB was determined in 25 cases (36.8%) out of 31 with MGMT methylated samples. There was no significant association between MGMT methylation status and immunophenotypic profiles (p=0.173). CONCLUSION: These results suggest that bcl-6 protein expression may be responsible for the high PI in GCB. Additionally, we found that apoptosis-associated proteins were not significantly associated with immunophenotypic profiles.