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Selman Emiroglu,1 Enver Özkurt,2 Neslihan Cabıoglu,1 Abdullah Igci,3 Pinar Saip,4 Hulya Yazici,4 Tolga Ozmen,5 Vahit Ozmen,1 Mahmut Muslumanoglu,1 Mustafa Tukenmez1 1Breast Surgery Unit, Department of General Surgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey; 2Department of Surgery, Ozel Basari Hospital, Istanbul, Turkey; 3Department of Surgery, American Hospital, Istanbul, Turkey; 4Department of Medical Oncology, Institute of Oncology, Istanbul University, Istanbul, Turkey; 5Division of Gastrointestinal and Oncologic Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USACorrespondence: Selman Emiroglu, Breast Surgery Service, Department of General Surgery, Istanbul Faculty of Medicine, Istanbul University, Fatih, Istanbul, 34390, Turkey, Email selman.emirikci.82@istanbul.edu.trBackground: The optimal surgical therapy for newly diagnosed breast cancer with germline mutations in susceptibility genes is still uncertain for many physicians. In this study, we aimed to determine the efficacy of breast conserving surgery (BCS) in breast cancer patients with BRCA1 or BRCA2 mutation by assessing its outcomes and locoregional recurrence (LR) rates.Materials and Methods: Seventy-five patients operated with BCS or mastectomy for breast cancer between 2006 and 2017 and had BRCA1 or BRCA2 mutation were included in the study. Effects of the performed breast surgery and clinicopathological characteristics on surgical outcomes, LR rates and survival were analyzed with showing the distribution of BRCA1 and BRCA2 germline mutations.Results: The median age of the patients was 42 years (20– 77). BRCA1 mutations were found in 46 (61.3%) patients and BRCA2 mutations in 29 (38.7%) patients. Compared to BRCA2 carriers, BRCA1 carriers were more likely to have higher tumor grade (84.8% vs 44.8%; p = 0.001) and non-luminal subtype tumors (67.4% vs 13.8%; p = 0.001). A total of 44 (58.7%) patients underwent unilateral mastectomy and 31 (41.3%) patients underwent BCS. At a median follow-up time of 60 (12– 240) months, LR was observed in 6 patients equally divided in both BCS and mastectomy groups. LR rates were slightly higher after BCS versus mastectomy (9.7% and 6.8%, respectively). Additionally, there were no statistically significant differences in disease-free survival (DFS) and disease-specific survival (DSS) rates after 10 years in the BCS group versus the mastectomy group (p = 0.117 and 0.109, respectively), but in fact, the rates were better in the BCS group.Conclusion: Our findings indicate that BCS may serve as an efficacious alternative to mastectomy for breast cancer patients with BRCA1 or BRCA2 mutation. Additionally, tumor size, lymph node positivity, and TNM stage should be taken into consideration for a better surgical decision-making.Keywords: BRCA1 or BRCA2 germline mutation, breast conserving surgery, surgical decision, locoregional recurrence

To find BRCA1/2 test selection criteria unique to the Turkish population, as well as to provide the BRCA1/2 gene mutation distributions of patient population to the literature.

Objective:Published studies on male breast cancer (MBC) and BRCA mutations are scarce and usually include, a small number of patients. The clinicopathological characteristics of BRCA mutant and wild-type MBC patients were compared in more than forty patients in this study.Materials and Methods:A retrospective review of MBC patients’ clinical and histopathological data was conducted. To compare the patients’ characteristics, chi-square test and Fisher's Exact test were utilized. Kaplan–Meier analysis was used to examine the survival analysis.Results:In total 43 cases were reviewed. The average duration of follow-up was 35.8 months. BRCA mutations were found in 11 (25.6%) of the patients. BRCA1 mutations were found in four patients (9.3%), BRCA2 mutations in six patients (14%), and BRCA1 and BRCA2 mutations in one patient (2.3%). The median age at diagnosis was 58 years old, and there was no statistically significant difference between groups (p = 0.7). Tumor location (p = 0.3), human epidermal growth factor receptor 2 overexpression (p = 0.5), estrogen receptor status (p = 0.05), progesterone receptor status (p = 0.6), tumor stage (p = 0.9), lymph node positivity (p = 0.5), tumor histology (p = 0.06), and recurrence status (p = 0.6) were similar between BRCA-wild type and -mutated patients. Overall survival averaged 115.6 months (range: 76.0–155.3), with no statistically significant differences between groups (p = 0.6).Conclusion:This study investigated clinical and pathological characteristics and prognoses of BRCA wild and mutant-type MBC and these were similar in all groups studied.

Background:The synthesis of CDK4/6 inhibitors with endocrine treatment in two series of treatment has been widely accepted as the standard for patients with estrogen receptor-positive metastatic breast cancer. In spite of this, the activity of CDK4/6 inhibitors in patients with metastatic breast cancer who have progressed despite receiving multiple lines of treatment is not well understood.Aims:To report the activity and safety of a CDK4/6 inhibitor (palbociclib) in patients in whom at least three lines of treatment for ER+ metastatic breast cancer had failed.Study Design:Multicenter retrospective observational cohort study.Methods:In this retrospective observational cohort study, we included 43 patients who received palbociclib after at least three lines of systemic treatment for ER+/HER2− metastatic breast cancer.Results:The median progression-free survival in our population was 7 months (25th-75th percentile, 4-10), and the median overall survival was 11 months (25th-75th percentile, 6-19). Although there were some adverse events, palbociclib was generally well tolerated, so dose reduction was needed for only six patients (14%).Conclusion:The efficacy of palbociclib among heavily treated hormone receptor-positive/HER2− patients with advanced breast cancer was acceptable in terms of clinical benefit, and it was generally well tolerated among this population.

Since the treatability of Oriental spruce wood (Picea orientalis) with preservative solutions is difficult and considered as a refractory wood species, this study was intended to bring its treatability class by a bioincising process to the level of sapwood of Scots pine (Pinus sylvestris), a desirable wood species for the forest products industry. Bioincising process by Physisporinus vitreus fungus was applied to wood samples from sapwood and heartwood portions of spruce wood. The samples with two different weight loss groups (5–10 % and 10–15 %) in the bioincising process were used to detect changes in treatability with wood preservative solutions caused by the fungus. The bioincised and unincised control samples were treated with either micronized copper quat (MCQ) or alkaline copper quat type D (ACQ-D) wood preservative solutions by either dipping or vacuum methods. Following impregnation with the preservative solutions, the effects of the bioincising process on CuO (copper oxide) retention, and the leaching of Cu (copper) element were determined. The results showed that CuO retention levels increased after the bioincising process. Moreover, there was greater CuO retention in the spruce heartwood samples compared to the spruce and Scots pine sapwood samples. Amount of Cu element released from the Scots pine sapwood samples was found to be lower than that from the spruce sapwood and heartwood samples after the bioincising. process. The results suggest that the bioincising process by P. vitreus in refractory wood species might improve the treatability of wood by Cu-based wood preservatives.

Behçet’s disease is an idiopathic chronic relapsing multisystem vascular-inflammatory disease of unknown origin, which usually presents with orogenital ulceration and uveitis and is identified as the triple-symptom complex. Primary neurological involvement in Behçet’s disease is known as neuro-Behçet’s syndrome (NBS). Clinical findings and neuroimaging demonstrate that there are two major forms of NBS: a central nervous system inflammatory parenchymal disease, and a less common nonparenchymal form that involves the large extraparenchymal vascular structures, mainly the venous dural sinuses. Cranial magnetic resonance imaging (MRI) typically reveals brainstem lesions with parenchymal involvement and an occluded dural sinus may be seen in the extraparenchymal type. Cerebrospinal fluid studies typically indicate inflammatory changes in the parenchyma and increased pressure with extraparenchymal involvement. Drugs used for the preventive treatment of NBS include azathioprine, cyclophosphamide, and anti-TNF agents.

Background: The protease-activated receptor 1 (PAR1) is associated with increased invasiveness of breast cancer (BC) cell lines and its overexpression is significantly correlated with advanced stage and poor prognosis. The aim of this study was to determine the clinical significance of the serum PAR1 levels in BC patients. Methods: We enrolled 96 female patients with pathologically diagnosed BC who did not receive chemotherapy (CT) or radiotherapy. Serum PAR1 levels were measured by ELISA method and compared with 30 healthy controls. Results: The mean serum PAR1 level of BC patients was significantly higher than controls (3.07 vs 2.82 ng/ml, p = 0.011). The levels of PAR1 tended to be higher among CT responders (p = 0.052) and grade I disease than others (p = 0.055). However, there was no significant difference in PAR1 levels according to other clinic-pathological or laboratory parameters. Serum PAR1 level did not have a significant impact on overall survival in both univariate (p = 0.73) and multivariate analysis (p = 0.67). Conclusion: Serum PAR1 level is elevated in BC patients and may have predictive role for CT response. However, it has no prognostic role on survival.

Background: In general, people speak and swallow frequently in their daily lives rather than making exaggerated tongue movements. Aim: The aim was to compare the effect of tongue movements on lingual sulcus depth, during the border molding process of impression making of mandibular complete dentures. Settings and Design: In total, 32 double master impressions were made. One of these pairs was obtained by allowing the patient to swallow and the other by enabling the tongue to make excessive movements. Materials and Methods: Measurements were taken from different regions of the lingual sulcus by determining the length of the parallel lines drawn from fixed points marked on the residual ridge crest to the deepest point of the alveolingual sulcus. These measurements were performed using a RMI three-dimensional measurement system. Statistical Analysis Used: Data were compared using the paired t-test (alpha = 0.05). Results and Conclusion: The high value found in casts with border molding, while swallowing was statistically significant in vertical and horizontal directions of the anterior lingual sulcus region (

Ocrelizumab is a recombinant humanized anti-CD20 monoclonal IgG1, approved by FDA and EMA for adult patients with multiple sclerosis (MS). The data on the efficacy and safety of Ocrelizumab for pediatric MS cases are limited. Here, we describe pediatric relapsing-remitting MS (P-RRMS) cases who were treated with Ocrelizumab as a disease-modifying drug. P-RRMS cases who were started Ocrelizumab below 18 years-of-age and followed-up >12 months with Ocrelizumab treatment were included. The primary end-points were annualized relapse rate (ARR) and magnetic resonance imaging (MRI) activity (new/enlarging T2 lesions and new gadolinium (Gd) enhancing lesions). The secondary end-points were the percentage of patients who remain relapse-free and/or free from Gd enhancing lesions, Expanded Disability Status Scale (EDSS) score, and the safety profile of Ocrelizumab. Of 18 P-RRMS cases receiving Ocrelizumab, 10 patients fulfilled the inclusion criteria for our study. The median duration of follow-up under Ocrelizumab was 28,3 months (min: 15 months, max: 46 months). Mean ARR decreased from 2.01 (±0.71) to 0 during the follow-up of Ocrelizumab treatment (P < 0.0001). None of the patients had MRI activity during the treatment. Mean EDSS decreased from 1.75 (±1.09) to 1.20 (±0.63) from the initiation of Ocrelizumab to the last follow-up of the patients (P = 0.024). None of the patients had serious side effects, except one patient who experienced anaphylaxis. Ocrelizumab can be considered a safe and effective treatment option in highly active P-RRMS. [ABSTRACT FROM AUTHOR]

Objective: The prevalence and incidence of multiple sclerosis may vary according to the influence of the altitude of a geographical area as well as the genetic and environmental factors. This study ained to determine the incidence and prevalence of multiple sclerosis in Edirne population.Material and Methods: Patients with a definite diagnosis of MS according to McDonald’s criteria, admitted to one of the three MS clinics in Edirne, were included in this two-stage study. Also the records of hospitals in İstanbul serving patients from Edirne, have been evaluated. Results: The prevalence rate of confirmed MS patients was 33.9/100000 (95% CI: 32-36) in 2003. The mean annual incidence was 3.48/100000 (95% CI: 2.90-4.00). Mean age of the patients was 36.5±9.6 years. Mean age at onset was 29.2±8.5 years. Mean duration of disease was 6.9±5.2 years. Overall, 69.2% had a relapsing-remitting course, 20.5% had a primary progressive course and 10.3% had a secondary progressive course. Mean Expanded Disability Status Scale score was 3.04±2.18. The prevalence and annual incidence after one year was 36.5 per 100000 (95% CI: 33.2-38.6) and 2.60 per 100000 (95% CI: 2.1-3.8), respectively.Conclusion: This is the first city-based MS prevalence study performed in Turkey. The MS prevalence in Edirne is similar to that of Greece and Bulgaria but lower than that of European countries.

Multiple sclerosis (MS) is an immune-mediated, neuro-inflammatory, demyelinating and neurodegenerative disease of the central nervous system (CNS) with a heterogeneous clinical presentation and course. There is a remarkable phenotypic heterogeneity in MS, and the molecular mechanisms underlying it remain unknown. We aimed to investigate further the etiopathogenesis related molecular pathways in subclinical types of MS using proteomic and bioinformatics approaches in cerebrospinal fluids of patients with clinically isolated syndrome, relapsing remitting MS and progressive MS (n=179). Comparison of disease groups with controls revealed a total of 151 proteins that are differentially expressed in clinically different MS subtypes. KEGG analysis using PANOGA tool revealed the disease related pathways including aldosterone-regulated sodium reabsorption (p=8.02x10-5) which is important in the immune cell migration, renin-angiotensin (p=6.88x10-5) system that induces Th17 dependent immunity, notch signaling (p=1.83x10-10) pathway indicating the activated remyelination and vitamin digestion and absorption pathways (p=1.73x10-5). An emerging theme from our studies is that whilst all MS clinical forms share common biological pathways, there are also clinical subtypes specific and pathophysiology related pathways which may have further therapeutic implications.