Investigation of the Relationship of Nesfatin-1, Adropin Levels and Claudin-2, Renalase Immunoreactivity with Kidney Function in an Experimental Hypertension Model.

OBJECTIVE: Hypertension is one of the cardiovascular diseases that causes the most mortality, and 95% of the causes are unknown. The aim of the study was to examine the possible correlation of nesfatin-1 levels, adropin levels, claudin-2 immunoreactivity (claudin-2 expression in the renal proximal tubule), and renalase immunoreactivity (renalase expression in the renal proximal tubule) with arterial blood pressure, kidney function, and kidney damage. METHODS: Adult male Sprague Dawley rats were divided into control and hypertension groups (8 per group). Angiotensin II vehicle was given to the control group and angiotensin II (0.7 mg/kg/day) to the hypertension group, both via an osmotic mini pump for 7 days. The animals blood pressures were measured by tail cuff plethysmography on days 1, 3, 5, and 7. On day 7, 24-hour urine, blood, and tissues were collected from the rats. RESULTS: In the hypertension group compared with the control group, there was an increase in systolic blood pressure levels after day 1. While claudin-2 immunoreactivity was reduced in the kidneys, renalase immunoreactivity was increased. There was a decrease in creatinine clearance and an increase in fractional potassium excretion (P < .05). CONCLUSION: Our results showed that claudin-2 and renalase are associated with renal glomerular and tubular dysfunction and may play discrete roles in the pathogenesis of hypertension. We believe that these potential roles warrant further investigation.

The Impact of Total Tumor Diameter on Lymph Node Metastasis and Tumor Recurrence in Papillary Thyroid Carcinomas.

(1) Introduction: The impact of multifocality/bilaterality on the prognosis of papillary thyroid carcinoma (PTC) is a matter of debate. In order to clarify this debate, several studies have attempted to identify additional parameters associated with poor prognosis, including total tumor diameter (TTD), in the context of multifocal PTCs. In this context, this study was carried out to investigate the impact of TTD on tumor recurrence and lymph node metastasis (LNM) in PTCs. (2) Materials and Methods: The sample of this single-center retrospective study consisted of 706 patients diagnosed with PTC. TTD was calculated as the sum of the largest diameters of tumor foci in multifocal tumors. The resulting TTDs were grouped into TTDs ≤ 10 mm, TTDs > 10 mm, TTDs ≤ 20 mm, and TTDs > 20 mm, using 10 mm and 20 mm as cutoff values. (3) Results: There was no significant difference between multifocal papillary microcarcinomas (PTMCs) with a TTD of >10 mm and unifocal PTCs with a primary tumor diameter (PTD) of >10 mm except for advanced age and lymphovascular invasion (LVI). In addition, perineural invasion (PNI) and TTD > 10 mm were found to be significant risk factors for LNM, and PNI, TTD > 10 mm, TTD > 20 mm, and bilaterality were found to be significant risk factors for recurrence. LVI, and TTD > 10 mm were found to be independent significant predictors for recurrence, and LVI and extrathyroidal extension (ETE) were found to be independent significant predictors for LNM. (4) Conclusions: Considering TTD > 10 mm in recurrence risk categorization models and adopting a clinical approach that takes into account multifocal PTMCs with TTD > 10 mm along with unifocal PTCs with PTD > 10 mm may be more useful in terms of clinical management of the disease.

A Comprehensive Approach to the Thyroid Bethesda Category III (AUS) in the Transition Zone Between 2nd Edition and 3rd Edition of The Bethesda System for Reporting Thyroid Cytopathology: Subcategorization, Nuclear Scoring, and More.

Significant interobserver variabilities exist for Bethesda category III: atypia of undetermined significance (AUS) of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). Thus, subcategorization of AUS including AUS "nuclear" and AUS "other" is proposed in the recent 3rd edition of TBSRTC. This study investigated the impact of the nuclear features/architectural features/nuclear score (NS) (3-tiered)/subcategories and subgroups on risk of malignancy (ROM) in thyroid fine-needle aspirations (FNA). 6940 FNAs were evaluated. 1224 (17.6%) cases diagnosed as AUS were reviewed, and 240 patients (initial FNAs of 260 nodules and 240 thyroidectomies) were included. Subcategories and subgroups were defined according to TBSRTC 2nd and 3rd editions. Histological diagnostic groups included nonneoplastic disease, benign neoplasm, low-risk neoplasm, and malignant neoplasm. Overall, ROM was 30.7%. ROM was significantly higher in FNAs with nuclear overlapping (35.5%), nuclear molding (56.9%), irregular contours (42.1%), nuclear grooves (74.1%), chromatin clearing (49.4%), and chromatin margination (57.7%), and these features were independent significant predictors for malignancy. FNAs with NS3 had significantly higher ROM (64.2%). Three-dimensional groups were significantly more frequent in malignant neoplasms (35.7%). ROM was significantly higher in AUS-nuclear subcategory (48.2%) and in AUS-nuclear and architectural subcategory (38.3%). The highest ROM was detected in AUS-nuclear1 subgroup (65.2%). ROM was significantly higher in the group including AUS-nuclear and AUS-nuclear and architectural subcategories, namely "high-risk group" than the group including other subcategories, namely "low-risk group" (42.0%vs 13.9%). In conclusion, subcategorization may not be the end point, and nuclear scoring and evaluation of architectural patterns according to strict criteria may provide data for remodeling of TBSRTC categories.

The Role of 5-Hydroxymethylcytosine as a Potential Epigenetic Biomarker in a Large Series of Thyroid Neoplasms.

Cytosine modifications at the 5-carbon position play a critical role in gene expression regulation and have been implicated in cancer development. 5-Hydroxymethylcytosine (5hmC), arising from 5-methylcytosine (5-mC) oxidation, has shown promise as a potential malignancy marker due to its depletion in various human cancers. However, its significance in thyroid tumors remains underexplored, primarily due to limited data. In our study, we evaluated 5hmC expression levels by immunohistochemistry in a cohort of 318 thyroid tumors. Our analysis revealed significant correlations between 5hmC staining extension scores and nodule size, vascular invasion, and oncocytic morphology. Nuclear 5hmC staining intensity demonstrated associations with focality, capsule status, extrathyroidal extension, vascular invasion, and oncocytic morphology. Follicular/oncocytic adenomas exhibited higher 5hmC expression than uncertain malignant potential (UMP) or noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP), as well as malignant neoplasms, including papillary thyroid carcinomas (PTCs), oncocytic carcinomas (OCAs), follicular thyroid carcinomas (FTCs), and invasive encapsulated follicular variants of PTC (IEFV-PTC). TERT promoter mutation cases showed notably lower values for the 5hmC expression, while RAS (H, N, or K) mutations, particularly HRAS mutations, were associated with higher 5hmC expression. Additionally, we identified, for the first time, a significant link between 5hmC expression and oncocytic morphology. However, despite the merits of these discoveries, we acknowledge that 5hmC currently cannot segregate minimally invasive from widely invasive tumors, although 5hmC levels were lower in wi-FPTCs. Further research is needed to explore the potential clinical implications of 5hmC in thyroid tumors.

The Effect of Pirfenidone on Peyronie Plaques and Erectile Function in a Peyronie's Rat Model.

OBJECTIVE: To investigate the anti-fibrotic effects of pirfenidone on Peyronie's disease in an experimental rat model with intracavernosal injection of TGF-ß and whether pirfenidone improves erectile function. STUDY DESIGN: Experimental study. Place and Duration of the Study: Faculty of Medical Experimental Animals and Research Laboratory, Trakya University, from January to March 2021. METHODOLOGY: In this study, 27 male Sprague Dawley rats were used, and three groups were randomly identified. The rats in Group 1 served as the control group. Group 2 was not treated, and Group 3 was treated with pirfenidone therapy. The rats in Group 3 were administered pirfenidone 30 mg/kg/day by oral gavage, every day for four weeks, three weeks after the start of the experiment. At the end of seven weeks, a haemodynamic study was performed with cavernosal nerve stimulation to evaluate the erectile function, the rats were sacrificed, and the penile tissues were evaluated immunohistochemically. RESULTS: MeICP/MIBP values were found to be higher in treated rats compared to rats in the untreated group but no statistically significant difference was found in MeICP/MIBP values between the control, Peyronie model, and treatment groups (p=0.25). According to the histopathological examination, the rate of fibrosis with H&E staining was mild (100%) in the control group, severe (100%) in the Peyronie group, and severe (87.5% severe and 12.5% moderate) in the Peyronie + treatment group. CONCLUSION: In the study, pirfenidone used in the treatment of Peyronie's disease had a positive effect on erectile function, though not considered statistically significant. It has been shown that it has no histopathological effect on Peyronie's plaques. KEY WORDS: Anti-fibrotic agent, Erectile function, Experimental study, Peyronie's disease, Pirfenidone.

Conventional Tools for Predicting Satisfactory Response to Neoadjuvant Chemotherapy in HR+/HER2- Breast Cancer Patients.

Aim: The aim of the study was to assess the role of Magee Equation 3 (MagEq3), IHC4 score, and HER2-low status in predicting "satisfactory response (SR)" to neoadjuvant chemotherapy (NAC) in HR+/HER2- breast cancer (BC) patients. Methods: In a retrospective study, female patients of any age with T1-4, N0-2, M0 HR+/HER2- BC who received NAC and underwent adequate locoregional surgical treatment were included. Patients were grouped according to 2 outcomes: (a) overall response to NAC in breast and axilla by using residual cancer burden (RCB) criteria and (b) axillary downstaging after NAC by using N staging. 2 cohorts for overall response were overall SR (RCB 0-1) and no SR (RCB 2-3). On the other hand, for axillary downstaging, 2 cohorts constituted from axillary SR (ypN0 and ypN0i+) and no SR (ypNmic-N3). MagEq3 and IHC4 scores were calculated from their pathological tumor slides in each patient. HER2 status was categorized as either "no" or "low." In addition, patient age, family history, tumor histology, stage at admission, and Ki-67 status were compared between cohorts according to predefined outcomes. Results: In a total of 230 BC patients, 228 patients were included to compare according to their RCB levels. The mean age of patients with overall SR was significantly lower than those without. Patients with high Ki-67 expression, high (>30) MagEq3 score, high ICH4 quartile, and HER2-low status had significantly more overall SR. On the other hand, only patients with high Ki-67 expression had significantly more axillary SR. MagEq3 score levels, ICH4 quartiles, and HER2 status were similar between patients with axillary SR and not. Conclusion: MagEq3 and IHC4 tools seemed to be useful to predict those HR+/HER2- BC patients who are most likely to get benefit from NAC. But, only high Ki-67 expression level significantly predicted satisfactory axillary downstaging in HR+/HER2- BC patients.

Molecular Pattern and Clinical Implications of KRAS/NRAS and BRAF Mutations in Colorectal Cancer.

The aim of our study was to evaluate the incidence of KRAS/NRAS and BRAF mutations, analyze molecular patterns, and investigate associations with clinical parameters of these mutations in CRC KRAS/NRAS and BRAF mutations analyzed by next-generation sequencing. The detection rates of these mutations and patients' demographics were recorded and the relationship between them was evaluated using the chi-square test. KRAS mutation was detected in 332 of 694 patients, while the mutation rates in KRAS exons 2/3 and 4 were 39.6%/3.2% and 5%, respectively. The most common mutation pattern was KRAS G12D. Five atypical variants were detected: V14I in KRAS exon 2, A18D, Q22K and T50I in exon 3, and T148P in exon 4. NRAS mutation was detected in 29 (4.5%) patients. One atypical variant L80W was detected in NRAS exon 3. BRAF mutation was seen in 37 (5.3%) patients, with BRAFV600E (83.8%) being the most common mutation pattern. NRAS mutation was significantly more frequent in patients > 64 years of age, BRAF mutation in women, and NRAS/BRAF mutations in right colon tumors. Grouping BRAF mutations into BRAFV600E and BRAFnon-V600E and their analysis according to specific tumor localizations showed that all four BRAFnon-V600E mutations originated in the rectum. In our study, KRAS exon 2 and other RAS mutation rates were higher than in the literature, while the BRAF v.600E mutation rate was similar. NRAS and BRAF mutations were significantly more frequent in the right colon. BRAF mutation was more common in women and in the right colon.

Tumor Microenvironment Features as Predictive Biomarkers in Metastatic Differentiated Thyroid Cancer and Their Relationship With 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT) Metabolic Parameters.

OBJECTIVE: The role of the tumor microenvironment in tumor progression and treatment response is being investigated for different types of cancer. This study aimed to determine the relationships between tumor microenvironment, histopathology, 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT)-based metabolic parameters, treatment response, and overall survival (OS) in metastatic differentiated thyroid cancer (DTC).  Methods: Metastatic DTC patients who underwent 18F-FDG PET/CT between 2015-2019 were evaluated. Clinicopathological, histopathological features and PET/CT parameters of patients were recorded. Microenvironmental characteristics of the primary tumor, such as mitosis, intratumoral and peritumoral lymphocytosis, intratumoral and peritumoral fibrosis, were evaluated from the tissue samples. The relationships between these factors were statistically analyzed. RESULTS:  Sixty-five patients (38 females, 27 males, age: 49±15 years) were included. Mitosis, intra/peritumoral lymphocytosis, and intra/peritumoral fibrosis were frequent; however, none of them had a statistically significant association with PET-positive metastases, treatment response, or OS. Univariate analysis showed that gender, size, thyroglobulin values, residual thyroid tissue, PET-positive metastases, and maximum standardized uptake value (SUVmax) were significant predictors of OS. At multivariate analysis, PET-positive metastases (HR=-2.65, 95%CI 0.007-0.707, p=0.024) and SUVmax (HR=-2.74, 95%CI 0.006-0.687, p=0.023) were the only independent predictors for OS.  Conclusion: Our study revealed that microenvironmental characteristics of the primary tumor did not show prognostic significance in metastatic DTC. PET-positive metastases and SUVmax levels were the only significant factors that predicted overall survival in DTC. Supporting the results of our study with further studies with a larger sample size may be necessary to determine the relationship between the tumor microenvironment and prognosis in DTC.

Impact of the 3rd Edition of the Bethesda System for Reporting Thyroid Cytopathology on Grey Zone Categories.

INTRODUCTION: Thyroid Bethesda Reporting System is a six-tiered system that aims to bring uniformity in reporting thyroid cytology and improve the communication with clinicians. The system has achieved its goal as a presurgical diagnostic method; however, it remains a screening method in the grey zone categories, namely atypia of undetermined significance (AUS) and follicular neoplasm (FN). The book recently released the 3rd edition, following the recent changes in thyroid pathology. One of the most important novelties is subgrouping AUS category and FN to be able to make a better risk stratification in these categories. Our group aims to retrospectively analyze a large dataset based on the new TBSRTC, with a focus on the grey zone categories. METHODS: Only patients who underwent lobectomy or total thyroidectomy were included, allowing for direct comparison between cytological and histopathological results. Cytological evaluations, based on the TBSRTC 3rd edition, were methodically compared with their respective histopathological results, enabling a comprehensive analysis. RESULTS: Of the 244 patients (female:male ratio = 8.8:1, mean age = 56), a total of 252 nodules were evaluated. A distinction was noted with 79 nodules (31%) diagnosed as AUS and 173 nodules (69%) as FN. Intriguingly, the risk of malignancy (ROM) for AUS-overall stood at 44.3%, with AUS-nuclear atypia at 50% and AUS-other at 43.2%. Although the AUS subdivisions did not demonstrate statistical significance, a significant disparity was observed in their distribution, with 15% as AUS-nuclear atypia compared to 85% as AUS-other. This disparity raises the question: Could AUS-other be considered the new waste-basket category in the TBSRTC 3rd edition? Using the TBSRTC 3rd edition as a base, we added a subclassification for FN nodules based on the presence or absence of papillary thyroid carcinoma (PTC) nuclear features. Our findings showed that differentiating FN with oncocytic characteristics correlated well with histological outcomes and ROMs. Though retrospective in design with inherent bias potential, our data suggest a possible improvement in PTC case segregation in the FN category when differentiating between FN nodules with and without PTC nuclear features. CONCLUSION: Our retrospective study sheds light on the potential advantages of the TBSRTC 3rd edition, particularly in refining the AUS and FN categories for thyroid nodules. The clear disparity in AUS subcategories raises important questions about their classification and potential future refinements. Moreover, the differentiation of FN nodules based on PTC nuclear features holds a promising approach for better risk stratification.

Clinicopathological and molecular analyses of uterine carcinosarcomas using next-generation sequencing: A single-center experience.

Background: Uterine carcinosarcomas (UCS) constitute 3-4% of all uterine malignancies and 16% of deaths caused due to uterine neoplasms. Aim: In this study, we aimed to perform DNA-based mutation analysis in 12 genes (KRAS, NRAS, EGFR, C-KIT, BRAF, PDGFRA, ALK, ERBB2, ERBB3, ESR1, RAF1, PIK3CA) to determine the molecular subtypes of UCS using next-generation sequencing (NGS) in patients with aggressive UCS and poor prognosis. We aimed to compare the results of our analysis with clinicopathological data to contribute to the development of targeted therapy approaches related to the molecular changes of UCS. Materials and Methods: In this study, we included 12 cases diagnosed with uterine carcinosarcomas and examined the changes in oncogenes that play a role in UCS pathogenesis. For the analysis of mutation, the clinicopathological data were compared with the variations in the DNA-based gene panel consisting of 12 genes and 1237 variants in the UCS using the NGS method. Results: EGFR mutation was found in 91.7% of the cases, mutation in 41.7%, PDGFRA mutation in 25%, KRAS and PIK3CA mutation in 16.7%, and C-KIT mutation in 8.3% of the cases. Although no statistical significance was found between the detected mutation and clinicopathological data, it was concluded that PDGFRA mutation might be associated with advanced-stage disease development. Conclusion: This study's findings regarding different molecular types of UCS and information on oncogenesis of UCS can provide inferences for targeted therapies in the future by identifying targetable mutations representing early oncogenic events and thereby contribute toward further studies on this subject.

Gastric Teratoma in an Adult Female Patient: A Case Report.

BACKGROUND: Gastric teratoma (GT) occurs as a rule in infancy and is an extremely unusual gastric tumor in adult patients. CASE PRESENTATION: In this paper, we present the clinical and imaging findings of a 56-year-old female patient with a GT. The patient's main symptoms were increasing abdominal discomfort and pain. After the physical examination, she underwent ultrasound (US) and computed tomography (CT), which showed a large mass at the posterior wall of the stomach, and a teratoma was initially considered. After surgery, pathology confirmed the diagnosis of GT. The patient recovered after surgery and was discharged in good health. To the best of our knowledge, this study is the first reported case of gastric teratoma in an adult woman in the literature. CONCLUSION: Gastric teratoma of the adult period is a rare benign neoplasm that may have several complications; therefore, imaging is crucial for diagnosis and accurate treatment management. The aim of this study is to emphasize the value of US and CT in the diagnosis and treatment monitoring of mature gastric teratomas.

Classifying invasive lobular carcinoma as special type breast cancer may be reducing its treatment success: A comparison of survival among invasive lobular carcinoma, invasive ductal carcinoma, and no-lobular special type breast cancer.

PURPOSE: The literature contains different information about the prognosis of invasive lobular carcinoma of breast cancer (BC). We aimed to address the inconsistency by comparatively examining the clinical features and prognosis of invasive lobular carcinoma patients in our university and to report our experience by dividing our patients into various subgroups. PATIENTS AND METHODS: Records of patients with BC admitted to Trakya University School of Medicine Department of Oncology between July 1999 and December 2021 were reviewed. The patients were divided into three groups (No-Special Type BC, Invasive Lobular Special Type BC, No-Lobular Special Type BC). Patient characteristics, treatment methods and oncological results are presented. Survival curves were generated using the Kaplan-Meier method. Statistical significance of survival among the selected variables was compared by using the log-rank test. RESULTS: The patients in our study consisted of 2142 female and 15 male BC patients. There were 1814 patients with No-Special Type BC, 193 patients with Invasive Lobular Special Type BC, and 150 patients with No-Lobular Special Type BC. The duration of disease-free survival (DFS) was 226.5 months for the No-Special Type BC group, 216.7 months for the No-Lobular Special Type BC group, and 197.2 months for the Invasive Lobular Special Type BC group, whereas the duration of overall survival (OS) was 233.2 months for the No-Special Type BC group, 227.9 for the No-Lobular Special Type BC group, and 209.8 for the Invasive Lobular Special Type BC group. The duration of both DFS and OS was the lowest in the Invasive Lobular Special Type BC group. Multivariate factors that were significant risk factors for OS were Invasive Lobular Special Type BC histopathology (p = .045), T stage, N stage, stage, skin infiltration, positive surgical margins, high histological grade, and mitotic index. Modified radical mastectomy, chemotherapy, radiotherapy and use of tamoxifen and aromatase inhibitors for more than 5 years were significant protective factors for overall survival. CONCLUSION: The histopathological subgroup with the worst prognosis in our study was Invasive Lobular Special Type BC. Duration of DFS and OS were significantly shorter in Invasive Lobular Special Type BC than No-Lobular Special Type BC group. The classification of Invasive Lobular BC under the title of Special Type BC should be reconsidered and a more accurate treatment and follow-up process may be required.

An experimental study: the effect of S. boulardii on abemaciclibinduced diarrhea.

BACKGROUND: In our study, we aimed to investigate the protective effects of Saccharomyces boulardii on abemaciclib-induced diarrhea model, which is a commonly used drug in breast cancer. METHODS: Thirty rats were divided into 3 groups as control (Group 1), abemaciclib (Group 2), and abemaciclib + Saccharomyces boulardii (Group 3) groups. The clinical status, body weight, and defecation status were monitored daily. At the end of the 15-day experiment period, the rats were killed with high-dose anesthesia and the resected small intestine segments were evaluated histopathologically. Lesions were classified according to thickening of the villus, inflammation and edema of mucosa and intraepithelial leukocyte accumulation. Then, mean values of both crypt depths and villi thicknesses were calculated for each rat. Normal distribution assumption was controlled with the Shapiro-Wilk test. One-way analysis of variance for normally distributed variables in the comparisons of more than two independent groups and Kruskal-Wallis test for nonnormally distributed variables were used. The significance value was accepted as 0.05. RESULTS: : There was one death in Group 3, but none in the others. There were no findings of mucositis in Group I. There was mild diarrhea and weight loss in only one rat in Group 1. For the comparison of the severity of diarrhea (72.5%/39%) and weight loss (72.5%/45%), a decrease was found in Group 3 according to Group 2 (p < 0.01). Histopathological findings such as edema, inflammation, and intraepithelial leukocyte accumulation also showed a decrease in Group 3 compared to Group 2 (p < 0.01). DISCUSSION: Saccharomyces boulardii should be considered as a treatment option in abaemaciclib (chemotherapy)-induced diarrhea. Further comparative studies and in vivo human randomized controlled studies can be conducted in the future.

Breast Cancer Subtypes and Prognosis: Answers to Subgroup Classification Questions, Identifying the Worst Subgroup in Our Single-Center Series.

Purpose: Many studies report the triple negative breast cancer (TNBC) as the worst subgroup, as such patients do not benefit from anti-hormonal therapy and human epidermal growth factor receptor 2 (HER2) antagonists. While HER2 overexpression was a poor prognostic factor in breast cancer before trastuzumab (Herceptin) was available, TNBC is often reported as the worst BC subgroup since targeted therapy is currently not possible. Since the patience-specific experiences and the current literature did not always align, we aimed to determine the BC subgroup with the shortest survival in our center. Methods: The records of patients with BC who were admitted to Trakya University Faculty of Medicine Department of Medical and Radiation Oncology between July 1999 and December 2019 were reviewed. Patients were divided into four main groups (Luminal A, Luminal B, TNBC, and HER2-enriched) according to the St Gallen International Consensus Panel and four subgroups in accordance with estrogen receptor, progestin receptor and HER2 positivity. Patient characteristics, treatment characteristics and clinical outcomes of the four main subgroups were evaluated. Survival curves were generated using the Kaplan-Meier method, and the significance of survival differences among the selected variables was compared by using the Log rank test. Factors affecting disease-free survival (DFS) and overall survival (OS) were analyzed by Cox regression analysis. Results: Statistical analysis was performed on 2017 patients, after excluding patients with phyllodes tumor, carcinoma-in-situ and missing information from a total of 2474 patients with BC. There were 952 (47.1%) patients in the Luminal A group, 236 (34.1%) in the Luminal B group, 236 (11.7%) in the TNBC group and 142 (7.1%) patients in the HER2 enriched group. HER2-enriched patients had the shortest survival (p < 0.001), with 113.70 ± 7.17 months of DFS and 125.45 ± 3.03 months of OS. For patients who received Herceptin, DFS was 101.50 ± 6.4 months and OS was 118.14 ± 6.16. Patients who did not receive Herceptin had 92.79 ± 18 months of DFS and 94.44 ± 15.23 months of OS. Conclusion: The HER2-enriched subgroup had the worst prognosis despite receiving targeted therapy. While the duration of DFS and OS had no significant difference between TNBC and Luminal A-B subgroups, HER2 enriched subgroup had significantly shorter survival when compared to any other subgroup. HER2-enriched subgroup had a 10-fold greater risk of death compared to the Luminal A subgroup.

Diffusion tensor imaging and diffusion-weighted imaging on axillary lymph node status in breast cancer patients.

PURPOSE This article will examine the usefulness of diffusion tensor imaging (DTI) and diffusion-weighted imaging (DWI) on the assessment of axillary lymph nodes (ALN) of breast cancer patients. METHODS Axillary lymph nodes in 66 breast cancer patients were examined by DTI and DWI, and the largest lymph node with increased cortical thickness in axilla was selected. Morphological features, apparent diffusion coefficient (ADC), volume anisotropy, and fractional anisotropy values were measured by using a special software. Imaging findings and histopathological results were recorded. RESULTS Metastatic ALN were detected in 43 (65.1%) patients. Cortical thickness of the metastatic ALN was significantly higher than the non-metastatic ALNs (P < .001), and the long-axis-to-shortaxis ratio was significantly lower in metastatic ALNs (P < .001). There was a statistically significant difference between the ALN status and fatty hilum presence (P < .001). Apparent diffusion coefficient values of metastatic ALNs were statistically lower than those of non-metastatic ALNs (P < .001) using a cutoff value of 1.26 × 10-3 mm2 /s for b=500 ADC and 1.21 × 10-3 mm2 /s for b=800 ADC which had 97.7% sensitivity and 91.3% specificity. Fractional anisotropy and volume anisotropy values were significantly different between both groups. A cutoff value of 0.47 for b-500 fractional anisotropy had 83.7% sensitivity, 69.6% specificity 69.6% positive predictive value, and 83.7% negative predictive value. A cutoff value of 0.33 for b=500 volume anisotropy had 76.7% sensitivity, 78.3% specificity, 86.8% positive predictive value, and 64.3% negative predictive value. CONCLUSION Apparent diffusion coefficient value of metastatic ALNs was found to be significantly lower than those of non-metastatic ALN, and DTI metrics of metastatic ALN were found to be significantly higher than those of non-metastatic ALN. Overall, ADC had a better diagnostic performance than morphological features, fractional anisotropy, and volume anisotropy. Diffusion tensor imagingderived diffusion metrics may be used to complement breast magnetic resonance imaging in the future after further standardization of the imaging parameters.

Prognostic importance of microvessel density, VEGF expression and perineural invasion in laryngeal cancer treated with adjuvant radiotherapy.

Background and Aims: We aimed to investigate the prognostic importance of the microvessel density (MVD) value, the vascular endothelial growth factor (VEGF) expression, and the presence of perineural invasion (PNI) in laryngeal cancer (LSCC) patients. Methods: Pathological specimens of 62 LSCC patients were assessed for the evaluation of the MVD value, the VEGF expression level, and the presence of PNI of the tumors. The tumor characteristics and prognostic effects of these parameters on local control (LC) and overall survival (OS) were analyzed. Statistical Analysis: Descriptive analyses were done using frequencies for the demographic variables. The survival estimates were calculated by the Kaplan-Meier survival curves. The effects of the parameters on LC and OS were investigated by using the log-rank test comparing the survival rates. Cox regression analysis was used for multivariable analysis. Results: The 5-year LC and OS rates of the 62 LSCC patients were 64.5 and 53.9%, respectively. Twenty-two patients (35.5%) had PNI and the frequency of PNI was higher in the patients with a high-grade disease (P = 0.01). The MVD value was higher in the tumors of older patients (P = 0.035) and was correlated with the VEGF expression (P = 0.009). A higher tumor grade was related to a higher VEGF expression (P = 0.01) and the increase in the VEGF expression was associated with a significant decrease in the OS (P = 0.03). Conclusion: The VEGF expression, the MVD value, and the presence of PNI had no prognostic significance on the LC in the LSCC patients while only the VEGF expression was associated with the OS.

Follicular Growth Pattern Disease on Thyroid Fine-needle Aspiration Biopsy

Thyroid nodules are a common worldwide health problem and a diagnostic challenge for clinicians and cytopathologists. Follicular growth pattern constitutes the majority of thyroid lesions. Thyroid nodules can be neoplastic or non-neoplastic, and neoplastic nodules can be classified as benign, malignant, or gray zone. Gray zone lesions include different benign and malignant entities that might be resulted in unnecessary thyroidectomies with risk of morbidity and higher health care costs. Depending on the cellularity, most cases might fall into the follicular neoplasia (FN)/ suspicious for FN (SFN) category or follicular lesion of undetermined significance (FLUS) in The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). Pathologists must be aware of the relationship between this diagnostic category and follow-up patient management and avoid over-diagnosing by mastering the diagnostic criteria.

Assessing the correlation between FDG PET findings of IDC breast carcinoma and histopathology of coexisting ductal carcinoma in-situ.

BACKGROUND: Ductal carcinoma in-situ (DCIS) often coexists with invasive ductal carcinoma (IDC) of the breast. DCIS is considered as a non-obligate precursor of IDC when both coexist. 18F-fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) imaging is commonly used in the staging and follow-up assessment of breast cancer. In this study, we aimed to assess if there is any correlation between primary tumor PET and histopathology findings and histopathological features of the coexisting DCIS. MATERIAL AND METHODS: FDG PET/CT images and histopathology results of the patients with newly diagnosed breast cancer (IDC) with coexisting DCIS were analyzed in this retrospective study. The grade and size of the primary tumor and histopathological features of the coexisting DCIS (nuclear grade and architectural pattern) were obtained from the postoperative histopathology results. Maximum standardized uptake values (SUV: SUVmax and SULmax) of the primary tumor normalized by weight and lean body mass were measured. Statistical analysis was performed to assess the correlation between various parameters of IDC and DCIS. RESULTS: This study included sixty-two (62) patients with IDC-DCIS. Primary tumor grade was significantly correlated and associated with the nuclear grade of the coexisting DCIS (polychoric correlation r = 0.736, and Fisher exact test, PV < 0.001, respectively). Primary tumor SUV was not correlated with the nuclear grade and architectural pattern of the coexisting DCIS (polyserial correlation r = 0.172, PV = 0.155, and Point Bi-Serial correlation r = -0.009, PV = 0.955, respectively). Median primary tumor size was marginally significantly different among DCIS nuclear grades but it was not significantly different in comedo and non-comedo cases (Kruskal-Wallis test PV = 0.053, and Mann-Whitney U test PV = 0.890, respectively). CONCLUSIONS: Primary tumor grade is correlated with the nuclear grade of the coexisting DCIS. SUV of primary tumor does not seem to be correlated with the histopathological features of coexisting DCIS (nuclear grade and architectural pattern) but this may be further studied in a larger number of patients.

Dramatic response to crizotinib in a breast cancer patient with ALK gene rearrangement.

Rearrangements of the anaplastic lymphoma kinase (ALK) gene are present in 3-5% of non-small-cell lung cancer (NSCLC), while it was 0.2% in NSCLC tumors. Due to its low frequency, it is extremely challenging to conduct randomized clinical trials of ALK-targeted therapies in NSCLC tumors. In the present case, we describe the first reported case of triple-negative breast cancer (TNBC) harboring the ALK fusion mutation that responded to ALK-targeted therapy after progression with two lines of chemotherapy. Searching for ALK gene rearrangement or other fusion, especially in patients with chemotherapy-resistant TNBC, opens the door to new treatment strategies.