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.

Investigation of the effects of ellagic, vanillic and rosmarinic acid on reperfusion-induced renal injury.

INTRODUCTION: The aim of this study was to investigate the effects of ellagic, vanillic and rosmarinic acid on reperfusion-related kidney damage, developed in an experimental lower-extremity ischaemia/reperfusion (I/R) model. METHODS: Forty-eight female Sprague-Dawley rats were divided into six groups. A median laparotomy and dissection were performed. In the I/R group, 60 minutes of ischaemia followed by 120 minutes of reperfusion was achieved. In addition one group was given 100 mg/kg ellagic acid, one group was given 12 mg/kg vanillic acid, one group was given 50 mg/kg rosmarinic acid and one group was given all three drugs 15 minutes before clamp removal. Bilateral kidney and blood samples were taken in all groups. RESULTS: Tubular epithelial degeneration, necrosis of the tubule epithelium and vessel wall thickening were significantly higher in the I/R group. Some parameters in the groups that were given drugs were found to be lower than in the I/R group and close to that of the control group. Total oxidant status (TOS) and oxidative stress index (OSI) were significantly higher and total antioxidant status (TAS) was significantly lower in the I/R group. Although not statistically significant in the groups given drugs, TAS was higher, and TOS and OSI were lower than in the I/R group. CONCLUSION: The antioxidant effect of ellagic, vanillic and rosmarinic acid administration may have beneficial effects on renal damage after reperfusion in acute lower-extremity ischaemia. This study is expected to provide information for future clinical trials.

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.

Adequacy of surgical margins, re-excision, and evaluation of factors associated with recurrence: a retrospective study of 769 basal cell carcinomas

Abstract Background: Achieving adequate surgical margins and preventing recurrence are important in the treatment of basal cell carcinoma (BCC). Objectives: The objectives of this study were to evaluate the adequacy of surgical margins and the re-excision rates in patients with primary BCC who underwent standard surgical treatment using our proposed algorithm and to define the risk factors in patients with recurrent BCC. Methods: The medical records of patients who were histopathologically diagnosed with BCC were reviewed. An algorithm created based on previous literature was used to determine the distribution of optimal surgical margins adequacy and re-excision rates. Results: Statistically significant differences were observed between the cases with and without recurrence in age at diagnosis (p = 0.004), tumor size (p = 0.023), tumor location in the H zone of the face (p = 0.005), and aggressive histopathological subtype (p = 0.000). When the tumors were evaluated for adequacy of deep and lateral surgical margins and re-excision rates, higher rates of adequate excision (457 cases, 68.0%) and re-excision (43 cases, 33.9%) were noted for tumors in the H or M zone. Study limitations: Inadequate follow-up of newly diagnosed patients in terms of recurrence and metastasis and the retrospective application of our proposed algorithm are the limitations of the present study. Conclusions: Our results showed that if BCC was detected at an early age and at an early stage, recurrence was lower. The H and M zones were the regions with the highest rates of optimal surgical outcomes.

Adequacy of surgical margins, re-excision, and evaluation of factors associated with recurrence: a retrospective study of 769 basal cell carcinomas.

BACKGROUND: Achieving adequate surgical margins and preventing recurrence are important in the treatment of basal cell carcinoma (BCC). OBJECTIVES: The objectives of this study were to evaluate the adequacy of surgical margins and the re-excision rates in patients with primary BCC who underwent standard surgical treatment using our proposed algorithm and to define the risk factors in patients with recurrent BCC. METHODS: The medical records of patients who were histopathologically diagnosed with BCC were reviewed. An algorithm created based on previous literature was used to determine the distribution of optimal surgical margins adequacy and re-excision rates. RESULTS: Statistically significant differences were observed between the cases with and without recurrence in age at diagnosis (p=0.004), tumor size (p=0.023), tumor location in the H zone of the face (p=0.005), and aggressive histopathological subtype (p=0.000). When the tumors were evaluated for adequacy of deep and lateral surgical margins and re-excision rates, higher rates of adequate excision (457 cases, 68.0%) and re-excision (43 cases, 33.9%) were noted for tumors in the H or M zone. STUDY LIMITATIONS: Inadequate follow-up of newly diagnosed patients in terms of recurrence and metastasis and the retrospective application of our proposed algorithm are the limitations of the present study. CONCLUSIONS: Our results showed that if BCC was detected at an early age and at an early stage, recurrence was lower. The H and M zones were the regions with the highest rates of optimal surgical outcomes.

Clinical, Dermoscopic and Histopathological Evaluation of Basal Cell Carcinoma.

INTRODUCTION: Dermoscopy aids in identifying histopathological subtypes and the presence of clinically undetectable pigmentation in basal cell carcinoma (BCC). OBJECTIVES: To investigate the dermoscopic features of BCC subtypes and better understand non-classical dermoscopic patterns. METHODS: Clinical and histopathological findings were recorded by a dermatologist who was blinded to the dermoscopic images. Dermoscopic images were interpreted by two independent dermatologists blinded to the patients' clinical and histopathologic diagnosis. Agreement between the two evaluators and with histopathological findings was evaluated using Cohen's kappa coefficient analysis. RESULTS: The study included a total of 96 BBC patients with 6 histopathologic variants: nodular (n=48, 50%), infiltrative (n=14, 14.6%), mixed (n=11, 11.5%), superficial (n=10, 10.4%), basosquamous (n=10, 10.4%), and micronodular (n=3, 3.1%). Clinical and dermoscopic diagnosis of pigmented BCC showed high agreement with histopathological diagnosis. The most common dermoscopic findings according to subtype were as follows: nodular BCC: shiny white-red structureless background (85.4%), white structureless areas (75%), and arborizing vessels (70.7%); infiltrative BCC: shiny white-red structureless background (92.9%), white structureless areas (78.6%), arborizing vessels (71.4%); mixed BCC: shiny white-red structureless background (72.7%), white structureless areas (54.4%), and short fine telangiectasias (54.4%); superficial BCC: shiny white-red structureless background (100%), short fine telangiectasias (70%); basosquamous BCC: shiny white-red structureless background (100%), white structureless areas (80%), keratin masses (80%); micronodular BCC: short fine telangiectasias (100%). CONCLUSIONS: In this study, arborizing vessels were the most common classical dermoscopic feature of BCC, while shiny white-red structureless background and white structureless areas were the most frequent non-classical dermoscopic features.

The relation between tissue galectin-3 level and platinum resistance in neoadjuvant bladder cancer treatment.

PURPOSE: This study aimed to reveal the relationship between the level of galectin-3 expression and the depth of response to neoadjuvant therapy in bladder tumor tissue with muscle invasion revealed by transurethral biopsy. METHODS: The percentage of galectin-3 staining in transurethral biopsy tissue with muscle invasion was determined by immunohistochemistry. The patients were divided into two groups: the down-staging (+) group consisting of patients with pathological complete response or non-invasive bladder cancer, and the down-staging (-) group consisting of patients with stage 2 and above. RESULTS: There were 11 patients in the down-staging (+) group and 12 patients in the down-staging (-) group. There was no significant difference between the two groups in terms of median age, gender, smoking, clinical stage at the time of diagnosis, distribution of carboplatin or cisplatin used as a platinum agent. Galectin-3 was positive in 2 patients (18.2%) in the group where down-staging was achieved with neoadjuvant therapy, while it was positive in 9 patients (75%) in the other group (p = 0.01). The median follow-up period of the patients was 31.6 months (95% CI 25.1-39.3). Overall survival was 43.4 months in the down-staging (+) group (95% CI 25.1-61.6) and 31.6 months in the down-staging (-) group (95% CI 12.7-50.6). Although there was a numerical difference, it did not reach statistical significance (p=0.37). CONCLUSION: The rate of down-staging after platinum-based neoadjuvant chemotherapy is significantly higher in patients with low galectin-3 staining in transurethral bladder biopsy tissue.

Mucins, trefoil factors and pancreatic duodenal homeobox 1 expression in spasmolytic polypeptide expressing metaplasia and intestinal metaplasia adjacent to gastric carcinomas.

INTRODUCTION: Gastric cancers are the second cause of cancer related deaths all around the world but gastric carcinogenesis remains a mystery. Intestinal metaplasia (IM) and spasmolytic polypeptide expressing metaplasia (SPEM) are the two types of preneoplastic metaplasias. In this study, we aimed to investigate expression of Pancreatic duodenal homeobox 1 (PDX1), mucins (MUCs), trefoil factors (TFFs) in SPEM and IM surrounding gastric carcinomas. MATERIAL AND METHODS: Tissue samples of tumor adjacent gastric mucosa including IM (n = 61) and SPEM (n = 36) from 70 gastrectomy specimens were used for immunohistochemical analysis of PDX1, mucins (MUC5AC, MUC6) and trefoil factors (TFF2, TFF3). RESULTS: Nuclear expression of PDX1 was present in both SPEM (32/36) and IM (60/61) and there was no significant difference in expression of PDX1 between the two types of metaplasias. While TFF3 and MUC5AC were abundant in IM, SPEM showed 100% expression of TFF2 and MUC6 and also lower positivity with TFF3 and MUC5AC. PDX1 positivity was related to expression of MUC5AC (60/61, p < 0.001) and TFF3 (60/61, p < 0.001) in IM and also associated with expression of MUC5AC (14/32, p < 0.05), MUC6 (32/32, p < 0.001), TFF2 (32/32, p < 0.001) and TFF3 (9/32, p < 0.05) in SPEM. Coexpression of TFF3 and TFF2 was present in 10 of 36 (27.7%) samples of SPEM and also 29 of 61 (47.5%) samples of IM exhibited dual expression of trefoil peptides. CONCLUSIONS: PDX1 may affect the development of SPEM and IM. Expression patterns of TFFs and MUCs may indicate that IM evolves from SPEM.

The relation between BRAFV600E mutation and clinicopathological characteristics of papillary thyroid cancer.

Aim BRAF mutation inhibits many tumour suppressor genes, increases pro-angiogenic molecules and reduces radioactive iodine uptake of tumour in papillary thyroid cancer (PTC), giving it more aggressive clinical characteristics. In this study, we aimed to evaluate the effect of BRAF V600E mutation on the clinicopathological features in patients with PTC. Methods The laboratory and clinical findings of 256 PTC patients who were referred to our clinic between 2007 and 2017 were assessed. Subjects involved in the study were divided into two groups depending on the presence of BRAF V600E mutation. Results BRAF V600E mutation testing gave positive results for 65 (25.4%) out of 256 patients. No significant correlation between BRAF V600E mutation, age and gender was detected. There was no difference between the groups in terms of tumour variant, tumour localization, tumour focality, and perineural invasion. In terms of histopathologic characteristics, presence of tumour capsular invasion (p=0.027), extrathyroidal extension (ETE) (p=0.002), absence of pathologically detected lymphocytic thyroiditis (p=0.006) and radio iodine I-131 treatment (p=0.001) were significantly higher in BRAF V600E (+) patients. During a followup period, four patients with BRAF V600E (+) and two patients with BRAF V600E (-) status underwent lateral neck dissection due to lymph node metastasis (p=0.01). Conclusion The presence of BRAF V600E mutation was proved to be a poor prognostic factor. However, in order to further assess the prognostic effect of BRAF V600E mutation in this group of patients and particularly its effect on mortality, long term followup results must be evaluated.

Comparison of clinicopathological features in patients with noninvasive follicular thyroid neoplasm with papillary-like nuclear features and follicular variant papillary thyroid cancer.

INTRODUCTION: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a newly defined entity accepted as a tumor precursor. OBJECTIVES: We aimed to examine the features of patients diagnosed with follicular variant papillary thyroid carcinoma (FVPTC), which are classified as NIFTP in the recent classification. This study compares clinical, radiological, histopathological, and molecular featur es of NIFTP and FVPTC. PATIENTS AND METHODS: A total of 247 patients with FVPTC were retrospectively examined and pathology specimens were reviewed. RESULTS: Patients were divided into 2 groups (NIFTP group: 107 patients; FVPTC group: 140 patients). There was a difference in terms of the percentage of pathologic nodules with irregular borders detected on preoperative neck ultrasonography (NIFTP group: 6.5%, FVPTC group: 15.7%; P = 0.02). Central lymph node dissection specimens of 50 patients in the NIFTP group were normal, while 4 of 70 patients (5.7%) in the FVPTC group had lymph node metastasis (P = 0.14). In addition, multivariable analysis (binary logistic regression) showed that FVPTC was positively associated only with irregular borders and extrathyroidal extensions (P = 0.02 and P <0.001, respectively). CONCLUSIONS: We suggest that patients diagnosed with NIFTP according to the new classification are considered lowrisk, and margin characteristics of the nodule detected on preoperative ultrasonography may be helpful in the differential diagnosis.

Sesamin ameliorates mucosal tissue injury of mesenteric ischemia and reperfusion in an experimental rat model.

INTRODUCTION: Mesenteric ischemia/reperfusion (I/R) injury is a serious clinical condition. There were a lot of experimental studies performed in the treatment of I/R injury. To our knowledge, this is the first experimental study with effects of sesamin on I/R injury model. We aimed to investigate the protective effect of sesamin on mesenteric I/R injury model. MATERIAL AND METHODS: A total of 32 male Sprague-Dawley rats were divided into four groups. Control group: superior mesenteric artery (SMA) exposed without clamping. I/R group: SMA was clamped for 60 min and then reperfused for 2 h. Sesamin group (S): 30 mg/kg sesamin were given for 5 days, and SMA exposed without clamping. I/R + S group: 30 mg/kg sesamin were given for 5 days, SMA was clamped for 60 min, and then reperfused for 2 h. Plasma and tissue oxidant parameters were investigated as well as histopathological evaluation. RESULTS: Plasma and tissue total antioxidant status (TAS) levels were significantly higher in I/R + S group compared to the rest (p < 0.005). The plasma TAS levels in I/R group was significantly low. The highest tissue TAS levels were detected in I/R + S group. The high levels of plasma and tissue TOS were found in I/R + S group. Plasma and tissue OSI levels were significantly higher in I/R group. Histopathologic evaluation showed that the mean level of intestinal tissue injury score in I/R group was 2.75 and 1.38 in I/R + S group. CONCLUSIONS: Sesamin helps to protect the intestinal tissue at the cellular level by reducing the oxidative stress and inflammation at both the plasma and tissue levels in the experimental I/R model.

Musculoskeletal Simulation Tools for Understanding Mechanisms of Lower-Limb Sports Injuries.

Musculoskeletal simulation and dynamic modeling programs have been used to gain insight into lower-limb musculoskeletal injury mechanisms. In addition to the temporospatial, kinematic, and kinetic data obtained from motion analysis systems, musculoskeletal simulation programs also can provide information on joint contact and muscle forces, musculotendinous lengths and velocities, and muscle activation levels. Musculoskeletal simulation platforms may help in the assessment of risk factors for sports-related injuries. Using musculoskeletal simulations for injury prevention programs may help lower the incidence of sports injuries, and may allow for fast recovery from injury. In this review, injury mechanisms and risk factors of some of the most common lower-limb musculoskeletal injuries, including anterior cruciate ligament, patellofemoral, and hamstring injuries were summarized from a biomechanical perspective. Also, the efficacy of musculoskeletal modeling and dynamic simulation tools in helping our understanding of these injury mechanisms was discussed.

Unprecedented recurrence of carpal tunnel syndrome by metaplastic synovial cyst in the carpal tunnel.

Metaplastic synovial cyst (MSC) is a benign cystic lesion observed after surgical intervention and recurrent skin trauma. Because of its rarity, the etiology is not fully understood. The most emphasized etiologic factors are recurrent surgical procedures and cutaneous pathologies, which cause cutaneous fragility and abnormal wound formation. In the literature, MSC is exemplified as a mass that can be observed by the naked eye and palpated. All patients had a history of previous surgical procedures in the area. In the present case, we report a 48 -year-old woman with recurrent carpal tunnel syndrome due to a MSC. This report showed that MSC can be detected at deeper locations than the regions described in the literature. To our knowledge, this is the first report of MSC causing carpal tunnel syndrome recurrence. It is thought that previous operations are the most important etiologic factor in MSC occurrence.

CD56, CD57, HBME1, CK19, Galectin-3 and p63 immunohistochemical stains in differentiating diagnosis of thyroid benign/malign lesions and NIFTP.

Detection of thyroid carcinoma has been steadily increased in the past few decades. After the recognition of NIFTP, also gain importance to differentiate benign tumors (follicular adenoma) from follicular patterned variants of papillary thyroid carcinoma (invasive and infiltrative follicular variant papillary thyroid carcinoma), and low-risk lesions of thyroid (NIFTP). Follicular patterned proliferations of thyroid still persists as a battle for pathologists. In this study, we aimed to analyze the most commonly used immunohistochemical stains "HBME1, CK19, Galectin-3", adding the new ones "CD56, CD57, and p63". Study groups were; nodular hyperplasia, follicular adenoma, NIFTP, infiltrative follicular variant PTC, classical variant PTC (CVPTC) and follicular carcinoma. Each group consisted of twenty cases. The sections were stained with CD56, CD57, p63, CK19, HBME1 (Mesotel cell), Galectin-3 antibody. Although the expression of CD56 was high in benign follicular lesions, FC could not be excluded in this group. CD57 was high in malignant follicular group and NIFTP. Interestingly, p63 was found highly expressed in FVPTC, which might be promising to predict invasiveness in follicular group of lesions. CK19, Galectin-3 and HBME1 were found quietly prominent in CVPTC in concordance with the previous reports.

A case of chronic ulcer due to subcutaneous arteriolosclerosis in an obese patient mimicking pyoderma gangrenosum.

The differential diagnosis of chronic ulcers covers a wide range of diseases and poses a diagnostic challenge. Subcutaneous ischemic arteriolosclerosis can lead to local ischaemia and ulceration as a result of arteriolar narrowing and reduction of tissue perfusion. This pathophysiological feature can be seen in eutrophication (nonuremic calciphylaxis) in morbid obesity, hypertensive ischemic leg ulcer (Martorell ulcer) and calciphylaxis in chronic renal insufficiency. All of the ulcers happened in this way can be wrongly diagnosed as pyoderma gangrenosum because of clinical similarity and inadequate biopsies. We report a case of chronic ulcer due to subcutaneous arteriolosclerosis in morbid obesity, wrongly diagnosed as pyoderma gangrenosum. It can be detrimental to misdiagnose the ulcers due to subcutaneous arteriolosclerosis as pyoderma gangrenosum since they need a diametrically different approach.

Protective therapeutic effects of peptide nanofiber and hyaluronic acid hybrid membrane in in vivo osteoarthritis model.

Osteoarthritis (OA) is a condition where tissue function is lost through a combination of secondary inflammation and deterioration in articular cartilage. One of the most common causes of OA is age-related tissue impairment because of wear and tear due to mechanical erosion. Hyaluronic acid-based viscoelastic supplements have been widely used for the treatment of knee injuries. However, the current formulations of hyaluronic acid are unable to provide efficient healing and recovery. Here, a nanofiber-hyaluronic acid membrane system that was prepared by using a quarter of the concentration of commercially available hyaluronic acid supplement, Hyalgan®, was used for the treatment of an osteoarthritis model, and Synvisc®, which is another commercially available hyaluronic acid containing viscoelastic supplement, was used as a control. The results show that this system provides efficient protection of arthritic cartilage tissue through the preservation of cartilage morphology with reduced osteophyte formation, protection of the subchondral region from deterioration, and maintenance of cartilage specific matrix proteins in vivo. In addition, the hybrid nanofiber membrane enabled chondrocyte encapsulation and provided a suitable culturing environment for stem cell growth in vitro. Overall, our results suggest that this hybrid nanofibrous scaffold provides a potential platform the treatment of OA. STATEMENT OF SIGNIFICANCE: Osteoarthritis is a debilitating joint disease affecting millions of people worldwide. It occurs especially in knees due to aging, sport injuries or obesity. Although hyaluronic acid-based viscoelastic supplements are widely used, there is still no effective treatment method for osteoarthritis, which necessitates surgical operation as an only choice for severe cases. Therefore, there is an urgent need for efficient therapeutics. In this study, a nanofiber-HA membrane system was developed for the efficient protection of arthritic cartilage tissue from degeneration. This hybrid nanofiber system provided superior therapeutic activity at a relatively lower concentration of hyaluronic acid than Hyalgan® and Synvisc® gels, which are currently used in clinics. This work demonstrates for the first time that this hybrid nanofiber membrane scaffold can be utilized as a potential candidate for osteoarthritis treatment.

BRAF V600 Mutation Profile of Metastatic Melanoma in the Thrace Region of Turkey.

OBJECTIVE: BRAF is the most common mutation in melanoma. The most common subtype is BRAF V600E, followed by V600K. Initially, the authors aimed to investigate whether clinicopathological features of melanoma are associated with BRAF mutations. We then aimed to present the relationships between the clinicopathological features and the mutated subtype (V600E vs V600K). MATERIAL AND METHOD: 61 patients with metastatic malignant melanoma (affecting the lymph node or other distant sites) were selected. Patient data regarding age at the time of diagnosis, sex, metastatic site (lymph node, distant metastasis or both) and primary tumour site were obtained from the hospital's database. Tissue samples containing at least 30% tumour cells were isolated from the specimens of 61 patients (24 samples from primary tumours and 37 from metastatic foci) for BRAF analysis. Comparisons between the BRAF V600 mutation and clinicopathological and histopathological features were performed. RESULTS: BRAF V600 mutation was detected in 34 (55.7%) patients. The subtype was BRAF V600E in 22 (64.7%) patients, BRAF V600K in 11(32.4%) patients and BRAF V600R in 1(2.9%) patient. The crucial results of the present study may be summarized as follows: i) BRAF V600 mutation was more common in older patients and tumors with BRAF V600 mutation revealed necrosis and LVI more commonly than wild-type tumors, ii) BRAF V600K mutation was more common in older patients and BRAF V600K mutated tumors exhibited ulceration more commonly than tumors with BRAF V600E mutation (close to significant). CONCLUSION: The BRAF V600 mutation may have interactions with prognostic clinicoptahological features of melanoma including necrosis and lymphovascular invasion. V600K mutation may be more common than expected and may have different associations with properties of the tumor such as tumor ulceration and patient age. Investigation of the mutated subtype of the BRAF gene may therefore reveal more detailed data about the management of melanoma and may also prevent missing of candidates for BRAF inhibitor therapies.