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Objective: Methotrexate (MTX) is a commonly used chemotherapeutic agent in clinical oncology practice and in treatment of autoimmune diseases. The major side effect during treatment is mucositis. Recently published studies reported that this effect may be due to direct intestinal epithelial injury and disturbance of intestinal microbiota. In this study, we aimed to characterize the intestinal histological changes caused by MTX and to investigate the effects and safety of Sildenafil and probiotic Bacillus clausii on intestinal mucositis in a rat model. Materials and Methods: The rats were divided in 4 groups; Group1(n=8) received MTX + B. clausii, Group 2 (n=8) received only MTX, Group3 (n=8) received MTX + Sildenafil and Group 4 (n=7) was served as control (received no treatment). Results: The rate of villus atrophy, villous fusion and erosion in the MTX + B. clausii group were found to be statistically significantly lower than in the MTX group and the MTX + Sildenafil group. Conclusion: The study demonstrated the effect of B. clausii on repairing of intestinal mucosa after MTX-treatment. The better understanding of the effects of probiotics on intestinal mucosal protection may lead to new therapeutic approaches in chemotherapy-induced mucositis.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a newly identified, very rare, highly aggressive hematopoietic neoplasm, primarily found in elderly males. They typically present in the form of skin involvement with a high frequency of lymph node and bone marrow involvement. BPDCN has a very poor prognosis, with no consensus on a widely accepted treatment modality. Here we present a very young patient with BPDCN, who presented with generalized lymphadenopathy, skin involvement, and leukemic blasts in the bone marrow. She was treated with high-risk acute lymphocytic leukemia protocol, followed by allogeneic hematopoietic stem-cell transplantation, and has been in clinical remission for 12 months.

Glycogen storage disease (GSD) type III is an autosomal recessive metabolic disorder and inborn error of metabolism characterized by a deficiency of glycogen debranching enzymes which is affecting 1/100000 every live birth. Clinical presentation is classified into four groups according to the muscular and liver involvement. GSD IIIa, the most common form of GSD III, primarily affects the liver, cardiac muscle, and skeletal muscle. Treatment mainly involves a high-protein diet, to facilitate gluconeogenesis. A 28-year-old male presented to our outpatient clinic with a 2-month history of white asymptomatic lesions on his tongue. He was diagnosed with GSD type 3 when he was six months old, and he has no other systemic disease, drug use or smoking history. A punch biopsy was performed, in superficial dermis band type lymphohistiocytic lichenoid infiltration was detected, also vacuolization of muscle cells and positive PAS staining were seen histologically. Topical high potent corticosteroids and dietary recommendations were offered to him. We want to present this case because of the rarity of lingual muscle involvement in glycogen storage disorders., Glikojen depo hastalığı (GDH) Tip 3, yaklaşık her 100000 canlı doğumda 1 sıklıkta görülen, glikojenin yıkımınısağlayan enzimlerde defektle karakterize otozomal resesif kalıtılan bir metabolizma hastalığıdır. Klinik bulgularınagöre dört ayrı gruba ayrılan bu hastalıkta kas ve karaciğer tutulumu izlenebilmektedir. GDH tip 3a bu gruptaen sık görülen alt tiptir ve öncelikle karaciğer, kalp kası ve iskelet kasını etkilemektedir. Tedavide proteindenzengin diyet ile glukoneogenez baskılanması amaçlanmaktadır. Yirmi sekiz yaşında erkek hasta kliniğimize dilüzerinde 2 aydır var olan, herhangi bir yakınmaya neden olmayan beyaz lekeler şikayetiyle başvurdu. Özgeçmişinde 6 aylıkken glikojen depo hastalığı tanısı aldığı ve diyetle takipte olduğu, ek hastalığının, ilaç kullanımının veya sigara kullanımının olmadığı öğrenildi. Dil üzerinden alınan biyopsinin histopatolojik incelemesinde yüzeyel dermiste bant tarzı lenfositik infiltrasyon, kaslarda vaküolizasyon ve PAS boya ile pozitiflik izlendi. Likenoid infiltrasyona yönelik yüksek güçte yerel kortikosteroid krem ve diyet önerildi. Bu olguyuglikojen depo hastalarında dil kası tutulumunun nadir olması ve karbonhidrat metabolizmasındaki değişikliklerin likenoid reaksiyonlar üzerine olası tetikleyici rolünü vurgulamak amacıyla sunmak istiyoruz.

Inherited pathogenic variants account for 5% to 10% of all breast cancer (BC) and colorectal cancer (CRC) cases. Here, we sought to profile the pathogenic variants in 25 cancer susceptibility genes in Turkish population. Germline pathogenic variants were screened in 732 BC patients, 189 CRC patients and 490 cancer-free elderly controls, using next-generation sequencing-based multigene panel testing and multiplex ligation-dependent probe amplification testing. Pathogenic variants were detected in 17.2% of high-risk BC patients and 26.4% of high-risk CRC patients. More than 95% of these variants were clinically actionable. BRCA1/2 and mismatch repair genes (MLH1, MSH2 and MSH6) accounted for two-thirds of all pathogenic variants detected in high-risk BC and CRC patients, respectively. Pathogenic variants in PALB2, CHEK2, ATM and TP53 were also prevalent in high-risk BC patients (4.5%). BRCA1 exons 17-18 deletion and CHEK2 c.592+3A>T were the most common variants predisposing to BC, and they are likely to be founder variants. Three frequent MUTYH pathogenic variants (c.884C>T, c.1437_1439delGGA and c.1187G>A) were responsible for all MUTYH biallelic cases (4.4% of high-risk CRC patients). The total pathogenic variant frequency was very low in controls (2.4%) and in low-risk BC (3.9%) and CRC (6.1%) patients. Our study depicts the pathogenic variant spectrum and prevalence in Turkish BC and CRC patients, guiding clinicians and health authorities for genetic testing applications and variant classification in Turkish population.

OBJECTIVE: Differential diagnosis of mycosis fungoides (MF) in the early stages can be challenging. Dermoscopy has been reported to be useful in the evaluation of early MF. However, to our knowledge, there is no study that specifies these early stages as stage IA, IB or IIA. The present study aims to evaluate the dermoscopic findings of stage IIA MF in comparison with plaque psoriasis (PP). METHODS: Thirty-four patients aged between 16-70 years with stage IIA MF (n=17) and PP (n=17) were evaluated in this prospective study. Dermoscopic examinations were performed by manual dermatoscopy (Dermlite DL4). χ2 test was used. RESULTS: In patients with stage IIA MF, orange-yellow patches (88.2%), short, fine and linear vessels (82.3%), geometric white scales (70.5%), perifollicular white scales (47%) and white patches (35.2%) were common, while dotted vessels (94.1%), diffuse lamellar white scales (88.2%) and dotted and globular vessels (70.5%) were common in patients with PP. Although spermatozoa-like structures, purpuric dots, collarette white scales and Y-shaped arborizing vessels were common in patients with MF, this was not statistically significant. Geometric white scales (clinically; cigarette paper-like wrinkly scales) correlated with alternating parakeratosis and orthokeratosis in the stratum corneum histopathologically. CONCLUSION: A unique aspect of our study is that this study provides insights about the importance of scales in differentiating MF from PP. Orange-yellow and white patches, short, fine and linear vessels, geometric and perifollicular white scales may be useful in distinguishing stage IIA MF from PP by hand-held dermoscopy.

Superficial CD34-positive fibroblastic tumor (SCPFT), a newly described neoplasm is a rare mesenchymal neoplasm of intermediate malignancy. A 63-year-old man presented with a painless, slow-growing, skin-colored nodule of 8 × 4 mm in diameter on the right side of the neck. It was completely resected. Histologically, a tumor located in the subcutis with the minimally infiltrative pattern was detected. The tumor was composed of variably enlarged bizarre and pleomorphic spindle to polygonal cells. Tumor cells were stained strongly diffuse positive with CD34 and weak positive with keratin, negative with STAT6, FLI-1, ERG, S100, desmin, and smooth muscle actin. The fluorescence in-situ hybridization (FISH) analysis was negative for

Background: Lymphadenopathy is an abnormality in the size or the character of the lymph node. It may be a manifestation of infectious and malignant diseases. Reactive lymphoid hyperplasia is a benign form of lymphadenopathy. Cells develop numerous adaptive responses regulated by hypoxia inducible factor-1 alpha (Hif-1 alpha) against hypoxic stress. Purpose: Hif-1alpha may play a role in the process of carcinogenesis in the early stage of cancer. We aimed to investigate the most common polymorphism of Hif-1α C1772T and G1790A gene polymorphisms in reactive lymphoid hyperplasia and lymphoma cases. Methods: Eighty-six paraffin-embedded blocs [51 (59,3%) reactive lymphoid hyperplasia; (40,7%) lymphoma] were examined. DNA was extracted from these samples and the polymerase chain reaction (PCR) was carried out. After DNA isolation, Hif-1α C1772T and G1790A polymorphisms were investigated with pyrosequencing. Results: Cases were (29,1%) girls and 61 (70,9%) boys. The mean age was 91,47±57,96 and 142,46±41,66 for reactive lymphoid hyperplasia and lymphoma group, respectively. There was no Hif-1α C1772T gene polymorphism in both group, but Hif-1α G1790A gene polymorphism was recorded in 14 cases (reactive lymphoid hyperplasia 10, lymphoma 4). Although Hif-1α G1790A gene polymorphism was seen a little higher in reactive lymphoid hyperplasia cases than that of lymphoma, no meaningful relationship was found statistically between two groups (p>0,05). Conclusion: Hif-1α C1772T and G1790A gene polymorphisms had been interrogated in cancer etiology and emphasized in some cancers. In our study, considering of a few of Hif-1α G1790A gene polymorphism in reactive lymphoid hyperplasia group, it should be investigated with large studies in terms of understanding of the behavior of Hif- 1α gene polymorphisms in children with lymphadenopathy.

Epithelial-myoepithelial carcinoma is a biphasic low-grade malignant tumor, which represents approximately 1% of all salivary gland tumors. This tumor occurs mostly in the parotid gland, followed by submandibular gland and minor salivary glands. Women, mostly fifth to the eighth decade of life, are commonly affected. Histopathologically, epithelial-myoepithelial carcinoma is composed of an inner single layer of eosinophilic cuboidal ductal cells and outer single or multiple layers of clear myoepithelial cells. We present a case of a 69 years old man who had a scar on lower the lip for 10 years and voice annoyance for three months. The biopsy for lower lip was reported 'infiltrative clear cell epithelioid neoplasm' and vocal cord biopsy result was 'verrucous carcinoma'. After cordectomy and wedge resection of the lower lip, histopathology revealed Epithelial-Myoepithelial Carcinoma for the lower lip and microinvasive verrucous carcinoma for the left vocal cord. Our case has a very uncommon location and presentation for EMC. The tumor location was minor salivary glands of the lower lip and the clinical presentation was quite different. Coexistence with microinvasive verrucous carcinoma of the vocal cord is the other unique part of our case.

Renal cell carcinoma (RCC) is the predominant type of kidney cancer. Mammalian target of rapamycin (mTOR) inhibitor everolimus is currently used as a second-line therapy for sorafenib or sunitinib-refractory metastatic RCC patients. The clinical limitation confronted during everolimus therapy is the onset of drug resistance that decreases the efficacy of the drug. Elevated level of anti-apoptotic Bcl-2 protein is proposed to be an emerging feedback loop for the acquired drug-resistance in various cancer types. In this study, the Bcl-2 inhibitor ABT-737 was used in combination with everolimus to enhance its anti-tumor effectiveness in everolimus-resistant RCC cell lines. Everolimus and ABT-737 combination synergistically led to a decrease in the proliferation of primary site A-498 and metastatic site Caki-1 RCC cell lines, which was accompanied by a reduction in protein levels of cell cycle and mTOR pathway proteins. In both RCC cell lines, everolimus-ABT-737 combination not only induced apoptosis, caspase and PARP-1 cleavage but also a decrease in Bcl-2 protein levels in parallel with a concomitant increase in Bim and Noxa levels. In order to confirm our in vitro findings, we have generated everolimus-resistant RenCa cell line (RenCares) to establish a RCC mouse xenograft model. Animals co-treated with everolimus and ABT-737 exhibited a complete suppression of tumor growth without any notable toxicity. This study thus proposes the everolimus-ABT-737 combination as a novel therapeutic strategy for the treatment of RCC to overcome the current clinical problem of everolimus resistance.

Breast cancer, a heterogeneous disease, has the highest incidence rate and is a major cause of death in females worldwide. Drug delivery by using nanotechnology has shown great promise for improving cancer treatment. Nanoliposomes are known to have enhanced accumulation ability in tumors due to prolonged systemic circulation. Peptide 18 (P18), a tumor homing peptide targeting keratin-1 (KRT-1), was previously shown to have high binding affinity towards breast cancer cells. In this study, we investigate the ability of P18 conjugated PEtOxDOPE nanoliposomes (P18-PEtOx-DOPE) for the targeted delivery of doxorubicin to AU565 breast cancer model. Toxicology studies of PEtOx-DOPE nanoliposomes performed on normal breast epithelial cells (MCF10A), showed minimal toxicity. Doxorubicin delivery by P18-PEtOx-DOPE to AU565 cells induces cytotoxicity in a dose and time dependent manner causing mitotic arrest in G2/M phase at 24 h. Anti-cancer activity of P18-PEtOxDOPE-DOX nanoliposomes on AU565 cells was detected by Annexin V/PI apoptosis assay. In terms of in vivo antitumor efficacy, P18-PEtOx-DOPE-DOX nanoliposomes administration to AU565 CD-1 nu/nu mice model showed significant decrease in tumor volume suggesting that DOX delivered by these nanoliposomes elicited a strong antitumor response comparable to the free delivery of doxorubicin. Overall, our results offered preclinical proof for the use of P18-PEtOx-DOPE-DOX nanoliposomes in KRT-1+ breast cancer therapy. Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [213M726] Financial support from the Scientific and Technological Research Council of Turkey (TUBITAK, grant number 213M726) is gratefully acknowledged. All in-vitro cell culture and in-vivo experiments were conducted at Yeditepe University. The authors thank Ayla Burcin Asutay and Cansu Umran Tunc for technical support on flow cytometer. Also, we thank Engin Sumer, Ayse Hande Nayman and Halime Ilhan-Siginc for technical support in in vivo experiments.

Objectives: The aim of this study was to evaluate the effect of amyloid deposition in colon mucosa on the results of anorectal manometry test and the use of ROME III questionnaire in patients with Familial Mediterranean Fever (FMF). Methods: The files of patients diagnosed with FMF were scanned to evaluate the patients at risk for amyloid deposition. Predisposing factors were identified. The patients were sampled using anorectal manometry test, Rome III questionnaire and the rectal mucosa suction biopsy and the test results were compared. Results: 17 (63%) of the patients were female and 10 (37%) were male. The mean age was 12.15 ± 2.40 years. The number of patients with amyloid deposition in the rectal mucosa sample was 2 (7.4%). Both of these patients had regularly used colchicine. Amyloid deposition was found to be high in patients with M694V homozygous mutation (P = 0.05). According to the Rome III questionnaire, findings suggestive of irritable bowel syndrome were found in 5 patients and abdominal migraine was found in 3 patients. However, no statistical difference was found when the results of the Rome III questionnaire were compared with the results obtained from the anorectal manometry test (P > 0.05). Conclusions: Amyloidosis can be seen due to various environmental factors, regardless of age, even when colchicine is regularly used. Anorectal manometry is an easy to perform test, helping diagnosis in this patient group. Although it has been shown that in patients with predisposing factors for amyloid deposition RAIR can be detected at lower pressures in anorectal manometry, the clinical significance of this finding is unclear. Since the Rome III questionnaire showed findings consistent with functional abdominal pain disease in one third of the patients, independent of the presence of FMF, it was found that the application of this questionnaire in patients with FMF could be misleading.

Immunoglobulin G4-related disease (IgG4-RD) is an inflammatory disease characterized by a tumor-like infiltration of IgG4 positive plasma cells and fibrosis in various organs. The exact pathogenesis remains unknown. In this article, we discuss the diagnostic management of IgG4-RD with reference to clinical, serologic, pathological and radiological data on a 17-year-old male patient with lumbar vertebral involvement.

The diagnosis of psoriasis is mainly made by clinical examination but on some occasions according to the localization or duration of the lesions when spongiosis is more prominent, it can be challenging and may be considered as overlapping eczema. To evaluate the patients for "eczema in psoriatico" and to present the differences between psoriasis. Biopsy outcomes of thirty-one patients who were histologically diagnosed with psoriasis and psoriasiform dermatitis because of the erythematous and scaly plaque lesions located on hands and feet, between 2013 and 2015, were evaluated retrospectively. Histopathologic findings compatible with psoriasis and accompanied by spongiosis and spongiotic vesicles were evaluated as eczema in psoriatico and compared with psoriasis. In this study thirty-one patients, including 18 patients with eczema in psoriatico and 13 patients with psoriasis of hands and/or feet were included. Of the 31 patients, 15 (48.4%) were women and 16 (51.6%) were men, in 61.3% of cases, biopsies were taken from hands (61.1% of "eczema in psoriatico", 61.5% of psoriasis) and 38.7% from feet (38.9% of "eczema in psoriatico", 38.5% of psoriasis). There was a statistically significant difference between two groups in terms of parakeratosis severity and distribution, the presence of neutrophil and plasma in stratum corneum, the presence of granular layer loss and suprapapillar plate thinning, the shape of retes, the presence of lymphocytic exocytosis, spongiosis and spongiotic vesicles, the intensity of infiltrates in the papillar dermis and the presence of dermal edema (P < .05). Histology supports a continuum between psoriasis and eczema that share histological similarities and at the same time should be considered a separate entity, eczema in psoriatico.

Aim Molecular subtyping has become increasingly important in bladder cancer, and it is mainly divided into “luminal” and “basal” types. Despite the large amount of studies about the molecular pathway of bladder cancer, there are few studies about BAP-1. The aim of this study is to evaluate the BAP-1 expression molecularly and immunohistochemically and compare it with GATA-3 and CK5/6 immunohistochemical stains. Materials and method A BAP-1 antibody was applied by western blotting to the tumor and normal tissues of 11 patients with known primary bladder tumors. The paraffin blocks of 150 non-invasive and 150 invasive tumor tissues were selected from transurethral resection materials. BAP-1, GATA-3, and CK5/6 immunohistochemical stains were applied to them, and the results were evaluated. Results The protein expression levels of BAP-1 increased more in the tumor tissues compared to the normal tissues. The immunohistochemical BAP-1 expression was strong in the muscle-invasive group. The immunohistochemical GATA-3 expression was higher in the non-invasive group, and the CK5/6 expression was higher in the muscle-invasive group. The GATA-3 and CK5/6 immunohistochemical stains had a negative correlation in the muscle-invasive group. The immunohistochemical expression of BAP-1 had no correlation with GATA-3 and CK5/6 in all groups. Conclusions Molecular subtyping has become increasingly important in bladder cancer and it is mainly divided into “luminal” and “basal” type. Despite the large amount of studies about molecular pathway of the bladder cancer, there are a few studies about BAP-1. The aim of this study is to evaluate the BAP-1 expression molecularly and immunohistochemically and compare it with GATA-3 and CK5/6 immunohistochemical stains.

Background The aim of this study was to evaluate the effect of amyloid deposition in colon mucosa on the results of anorectal manometry test and the use of ROME III questionnaire in patients with Familial Mediterranean Fever (FMF). Methods The files of patients diagnosed with FMF were scanned to evaluate the patients at risk for amyloid deposition. Predisposing factors were identified. The patients were sampled using anorectal manometry test, Rome III questionnaire and the rectal mucosa suction biopsy and the test results were compared. Results 17 of the patients were female (63%) and 10 were male (37%). The mean age was 12.15 ± 2.40 years. The number of patients with amyloid deposition in the rectal mucosa sample was 2 (7.4%). Both patients regularly used colchicine. Amyloid deposition was found to be high in patients with M694V homozygous mutation (p 0.05). Conclusions Amyloidosis can be seen due to various environmental factors, regardless of age, even when colchicine is regularly used. Anorectal manometry is an easy to perform test, helping diagnosis in this patient group. Although it has been shown that in patients with predisposing factors for amyloid deposition RAIR can be detected at lower pressures in anorectal manometry, the clinical significance of this finding is unclear. Since the Rome III questionnaire showed findings consistent with functional abdominal pain disease in one third of the patients, independent of the presence of FMF, it was found that the application of this questionnaire in patients with FMF could be misleading.

WOS: 000429276400012 PubMed: 28838263 Introduction: Oxidative stress is the imbalance between oxidant-antioxidant systems and may play a major role in the psoriasis pathogenesis. Cytochrome (CYP) is a family of enzymes that are responsible for the metabolism of various endogenous and exogenous substances such as drug metabolism. Most importantly, the antioxidant system is the glutathione S-transferases (GST), which decrease oxidative stress by reducing oxidative products.Aim: We aimed to evaluate the expressions of isoenzymes of GST and CYP families and the beneficial role of metotrexate (MTX) in this process.Material and methods: This study included 21 patients with psoriasis and 22 healthy subjects. We treated all the patients with 10-15mg/week of MTX for minimum 12weeks. Expressions of GST and CYP enzymes were assessed by immunohistochemical staining.Results: GSTK1, GSTM1 and GSTT1 expressions were significantly higher in the psoriasis tissues than in the control tissues (p

Background Bag-1 (Bcl-2-associated athanogene) is a multifunctional anti-apoptotic protein frequently overexpressed in cancer. Bag-1 interacts with a variety of cellular targets including Hsp70/Hsc70 chaperones, Bcl-2, nuclear hormone receptors, Akt and Raf kinases. In this study, we investigated in detail the effects of Bag-1 on major cell survival pathways associated with breast cancer. Methods Using immunoblot analysis, we examined Bag-1 expression profiles in tumor and normal tissues of breast cancer patients with different receptor status. We investigated the effects of Bag-1 on cell proliferation, apoptosis, Akt and Raf kinase pathways, and Bad phosphorylation by implementing ectopic expression or knockdown of Bag-1 in MCF-7, BT-474, MDA-MB-231 and MCF-10A breast cell lines. We also tested these in tumor and normal tissues from breast cancer patients. We investigated the interactions between Bag-1, Akt and Raf kinases in cell lines and tumor tissues by co-immunoprecipitation, and their subcellular localization by immunocytochemistry and immunohistochemistry. Results We observed that Bag-1 is overexpressed in breast tumors in all molecular subtypes, i.e., regardless of their ER, PR and Her2 expression profile. Ectopic expression of Bag-1 in breast cancer cell lines results in the activation of B-Raf, C-Raf and Akt kinases, which are also upregulated in breast tumors. Bag-1 forms complexes with B-Raf, C-Raf and Akt in breast cancer cells, enhancing their phosphorylation and activation, and ultimately leading to phosphorylation of the pro-apoptotic Bad protein at Ser112 and Ser136. This causes Bad’s re-localization to the nucleus, and inhibits apoptosis in favor of cell survival. Conclusions Overall, Bad inhibition by Bag-1 through activation of Raf and Akt kinases is an effective survival and growth strategy exploited by breast cancer cells. Therefore, targeting the molecular interactions between Bag-1 and these kinases might prove an effective anticancer therapy.

Interferon beta (IFNβ) is a drug used successfully in the treatment of multiple sclerosis (MS). Although IFNβ is a safe and well-tolerated drug, dermatological side effects are common. The most common dermatological adverse effect is a local reaction at the injection site. It may also cause inflammatory and immune-mediated dermatological side effects. However, morphea induced by IFNβ1b injection is very rare.

Uzuncakmak, Tugba Kevser Ustunbas/0000-0001-8057-3463; Bozer, Busra/0000-0002-7280-4417 WOS: 000393798500034 PubMed: 27613512 Oxidative stress may play an important role in the pathogenesis of psoriasis. Glutathione S-transferases (GSTs) make up a group of antioxidant enzymes. Cytochrome p450 (CYP) enzymes can influence oxidation and reduction reactions. We investigated the potential effects of GST and CYP enzymes in the pathogenesis of psoriasis. The study included 32 psoriasis patients and 22 healthy subjects. Psoriasis patients were administered 20 sessions of narrowband ultraviolet B phototherapy. Expressions of GST and CYP enzymes were assessed by immunohistochemical staining. Expression levels of GSTK1, GSTM1, and GSTT1 were significantly higher in psoriasis than in control tissues (P = 0.022, P = 0.001, and P = 0.006, respectively). Pre- and post-treatment expression was similar. Expression of CYP1A1 and CYP2E1 was significantly higher in pre- (P = 0.003 and P = 0.001, respectively) and post-treatment (P = 0.003 and P = 0.001, respectively) psoriatic tissues than in control tissues. No significant differences in CYP1B1 levels between the study and control groups were detected before treatment (P > 0.05). However, CYP1B1 levels were higher in post-treatment psoriatic tissue than in control tissue (P = 0.045). The significant increases in expression of GSTK1, GSTM1, and GSTT1 in psoriasis may reflect the increased activation of GST in response to excessive free radical formation from activated neutrophils or ultraviolet exposure to maintain antioxidant capacity in psoriasis. Furthermore, expressions of CYP1A1 and CYP2E1 represent important enzymatic systems in psoriasis. These findings suggest that psoriasis is an oxidative stress condition, although phototherapy does not affect these enzymatic systems. Further investigation is required. Istanbul Medeniyet University Scientific Research Project [TTU-2013-431] This study was supported by Istanbul Medeniyet University Scientific Research Project 2013 (TTU-2013-431).

Many inflammatory mediators and cytokines play important roles in the pathogenesis of acne vulgaris (AV). Information about the roles of these factors in the pathogenesis of the disease is limited. The purpose of this study was to evaluate levels of matrix metalloproteinase-1 (MMP-1), MMP-2, and tumor necrosis factor-α (TNF-α) in AV lesions. We selected 80 patients who presented at our dermatology department with AV. Their lesions included papules, pustules, nodules, and comedones. Each specimen was evaluated by histopathology with hematoxylin and eosin staining, and subsequently by immunohistochemical analysis for MMP-1, MMP-2, and TNF-α antibodies. A statistically significant difference between lesion groups emerged for MMP-1 (P = 0.012) and TNF-α (P = 0.029) scores. The MMP-1 score was highest in nodules and lowest in comedones. The TNF-α score was also highest in nodules but lowest in papules. We conclude that different levels of MMP expression can contribute to the development of different types of acne lesion and that the amount of TNF-α released may contribute to lesion development. Further studies of novel treatment modalities might evaluate the different clinical types of AV.

Epidermoid vulvar cystic lesions are proliferations of epidermal cells that can occur as a complication of female genital mutilation (FGM), which is still a common practice in many cultures, especially in Africa. A 36-year-old Sudanese woman presented with an enlarged clitoral mass that had first appeared 2 years earlier. Her medical history showed that she had undergone FGM when she was 3 years old. A perineal examination revealed a mobile, nontender, rounded cystic swelling with vitiligo lesions. After the cyst was excised, it revealed a 13 ×11 × 11 cm unilocular round mass. An epidermoid cyst was reported following microscopy. Follow-up 6 months later revealed a good result with no recurrence. To date, this is the largest epidermoid cyst following FGM and the first one with vitiligo lesions reported in the literature.

Introduction Methotrexate and acitretin are known to be effective in the treatment of psoriasis, but the mechanisms of the effects of these drugs are not fully known. Aim To investigate the effect of methotrexate and acitretin on microvessel density (MVD) in psoriasis. Material and methods Eighteen patients with psoriasis treated with methotrexate and 9 patients with psoriasis treated with acitretin (AT) were included in this study. MVD was evaluated immunohistochemically by using CD31 and CD105 (endoglin) antibodies. Results In the methotrexate group, the decrease in CD31 levels after treatment was found to be statistically significant, while in the AT group it was found to be highly significant. In both methotrexate and AT group, there was a statistically highly significant decrease in CD105 levels after treatment. There was no statistically significant difference between CD31 measurements of methotrexate and AT groups. When CD105 levels were measured before and after treatment, no statistically significant difference was found between methotrexate and AT. According to the results of CD31 changes before and after treatment, the CD31 difference was not statistically significant in both groups while the difference was higher in the AT group. CD105 differences were not statistically significant in both treatment groups before and after treatment. Conclusions CD31 and CD105 dyes indicate the effects of therapies on vascular proliferation and may be indicators that can be used in daily routine and follow-up studies for psoriasis.

Goblet cell carcinoid tumor of the appendix is an uncommon neoplasia that shares the histological attributes of both adenocarcinoma and carcinoid tumors. Its prognosis has a more aggressive course than the other known carcinoid tumors. Clinical diagnosis of goblet cell carcinoid is seldom made preoperatively. The most common clinical presentation of goblet cell carcinoid tumor is acute appendicitis. In this study, we report a patient on whom right hemicolectomy was performed because of a cacal sessile polyp with high grade dysplasia; goblet cell carcinoid tumor of the appendix was revealed incidentally during microscopic evaluation of the appendectomy specimen. The patient healed uneventfully and no recurrence was observed after the 12-month follow-up period. Careful microscopic examination of the appendectomy specimen is key for the diagnosis of appendiceal tumors such as goblet cell carcinoid, especially in elderly patients.

Uzuncakmak, Tugba Kevser Ustunbas/0000-0001-8057-3463 WOS: 000451077200021 …

WOS: 000313803300010, PubMed ID: 23297805, Objectives: The aim of the current study was to investigate the prevalence and predictive significance of the KRAS and BRAF mutations in Turkish patients with colorectal cancer (CRC). Methods: Totally, 53 fresh tumoral tissue specimens were investigated in patients with CRC. All specimens were obtained during routine surgery of patients who were histopathologically diagnosed and genotyped for common KRAS and BRAF point mutations. After DNA extraction, the target mutations were analyzed using the AutoGenomics INFINITI (R) assay, and some samples were confirmed by quantitative real-time polymerase chain reaction fluorescence melting curve analyses. Results: KRAS mutations were found in 26 (49.05%) CRC samples. Twenty-seven samples (50.95%) had wild-type profiles for KRAS codon 12, 13, and 61 in the current cohort. In 17 (65.38%) samples, codon 12; in 7 (26.93%) samples, codon 13; and in 2 (7.69%) samples, codon 61 were found to be mutated, particularly in grade 2 of tumoral tissues. No point mutation was detected in BRAF codon Val600Glu for the studied CRC patients. Conclusions: Our study, based on a representative collection of human CRC tumors, indicates that KRAS gene mutations were detected in 49.05% of the samples, and the most frequent mutation was in the G12D codon. Results also showed that codons 12 and 13 of KRAS are relatively frequently without BRAF mutation in a CRC cohort from the Turkish population.

Myxoid melanoma is a rare variant of melanoma, which is characterized by atypical spindle cells and dense mucin deposition in dermis. This tumor is usually seen in elderly people with a similar progress in other variants of melanoma. A 28-year-old male presented to our outpatient clinic with a 6-month history of a slowly growing asymptomatic pink lesion on his arm. Dermoscopic examination revealed pink-white cristalline structures and blue-grayish ovoid globules. The lesion was totally excised with initial diagnosis of basosquamous carcinoma, amelanotic melanoma and basal cell carcinoma. Histopathological examination was consistent with myxoid melanoma. We present this case due to the rarity of myxoid melanoma and occurence in such a young age.

Psoriasis is a chronic and inflammatory skin disease. Few studies in the literature evaluate the responses to the treatment histopathologically.In this study, we evaluated and compared skin biopsies taken from patients with psoriasis before and after phototherapy and therapy with acitretin and methotrexate.We included 64 patients with a diagnosis of psoriasis vulgaris in our study. We performed phototherapy on 33 patients (51.6%), while 19 patients (29.7%) were treated with methotrexate and 12 patients (18.8%) were treated with acitretin.All of the patients had chronic plaque psoriasis, and they had skin lesions on more than 10% of their total body surface area and a score of PASI of 7.2-21.8 (average: 12.2). The histopathological parameter scores were similar in the initial evaluations of the pre-treatment treatment groups. When the biopsy specimens of all cases were evaluated together, a significant decrease was observed in terms of parakeratosis, Munro's microabscesses, regular acanthosis, pustules of Kogoj, lymphocyte infiltration in the papillary dermis, loss of the granular layer, spongiosis, suprapapillary thinning, vascularity in the papillary dermis and neutrophile infiltration in the papillary dermis.We found in our study that conventional treatment modalities provided histopathologically significant recovery in psoriasis, but they did not have an effect on some histopathological findings. To our knowledge, it is one of the few studies to assess these parameters in psoriasis under the continuous effect of acitretin, methotrexate and phototherapy for three months. There is a need for studies with larger series to examine the histopathological effects of these treatment modalities in terms of immunopathology.

Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease. NAFLD is a complex disease and inflammation is a crucial component in the disease pathogenesis. Recent genome wide association studies in hepatology area highlighted significant relations with human leukocyte antigen (HLA) DQ region and certain liver diseases. The previous animal models also emphasized the involvement of adaptive immune system in the liver damage pathways. To investigate possible polymorphisms in the HLA region that can contribute to the immune response affecting the NAFLD, we enrolled 93 consecutive biopsy proven NAFLD patients and a control group consisted of 101 healthy people and genotyped HLA DQB1 alleles at high resolution by sequence specific primers-polymerase chain reaction. The mean NAFLD activity score (NAS) was 5.2 ± 1.2, fibrosis score was 0.9 ± 0.9, ALT was 77 ± 47.4 U/L, AST was 49.4 ± 26.3 U/L. Among 13 HLA DQB1 alleles analyzed in this study, DQB1*06:04 was observed significantly at a more frequent rate among the NAFLD patients compared to that of healthy controls (12.9 vs. 2 % χ2 = 8.6, P = 0.003, P c = 0.039, OR: 7.3 95 % CI 1.6–33.7). In addition, the frequency of DQB1*03:02 was significantly higher in the healthy control group than the NAFLD patients (24.8 vs. 7.5 %, χ2 = 10.4, P = 0.001, P c = 0.013, OR: 0.2, 95 % CI 0.1–0.6). NAFLD patients were grouped according to their fibrosis score and NAS. The distribution of DQB1 alleles over stratified NAFLD patients did not reveal any statistically significant relation. Taken together, immune repertoire of individuals may have an effect on NAFLD pathogenesis and therefore, in NAFLD, adaptive immunity pathways should be investigated.

OBJECTIVE: In this study, we investigated the efficacy of nuclear matrix protein 22 (NMP22) in the diagnosis and surveillance of bladder cancer. MATERIAL AND METHODS: Patients with hematuria or who applied for cystoscopic control of proven bladder cancer were prospectively enrolled in this study. Routine cytologic examination and NMP22 test were performed on the voided urine sample obtained before the cystoscopy. The patients who had been diagnosed with bladder cancer were categorized according to stage, grade, number, size of the tumor and risk of the disease. Then the diagnostic performance of the NMP22 and the cytology test, alone or in combination, were evaluated separately using ROC curves in the diagnosis and surveillance groups. RESULTS: A total of 87 patients (87/136) were investigated because of hematuria. The sensitivity, specificity, positive and, negative predictive values, and positive likelihood ratio (LR+) of the NMP22 test were 70, 80, 68, 81, and 3.42%, respectively. While, the sensitivity, specificity, positive and, negative predictive values, and positive likelihood ratio (LR+) of the cytology examination were 27, 96, 82, 68, and 7.36%, respectively. There were 49 patients in the bladder cancer group. The sensitivity, specificity, positive, and negative predictive values and positive likelihood ratio (LR+) of the NMP22 test in these patients were 33, 76, 31, 78 and 1.37%, respectively. The sensitivity, specificity, positive and, negative predictive values, and positive likelihood ratio (LR+) of the cytology examination were 25%, 97%, 75%, 80% and 9.25, respectively. CONCLUSION: NMP22 test can be used as an adjunctive tool for the detection of bladder cancer, but its diagnostic performance is limited in surveillance when used alone or in combination with a cytology examination.

Drug-related skin disorders may occur in many different ways. Despite pigmentary changes being less important for morbidity, these changes precipitate depressed mood and reduce self-confidence. Testosterone is a steroid hormone from the androgen group and primarily used for the treatment of hypogonadism in males. Testosterone replacement can cause skin problems like acne, hair loss, redness, pain, or infection at the injection site. The study was conducted on a 49-year-old man with adult onset idiopathic hypogonadotropic hypogonadism, which is an acquired form of isolated gonadotropin-releasing hormone deficiency. He was presented with lack of energy and decreased sexual function 10 years ago and was given an oil-based injectable blend of four esterized testosterone compounds as hormone replacement treatment in a urology polyclinic. He was referred to our polyclinic by endocrinologist because of progressive hyperpigmentation marked on his face and oral mucosa. In the present study, we report the first testosterone therapy-related facial and oral mucosal hyperpigmentation and acanthosis nigricans in the same patient.

INTRODUCTION Amyloid goiter (AG) is characterized by enlargement of the thyroid gland as a result of extensive amyloid deposition in a bilateral and diffuse manner.

Prostate specidic antigen (PSA) and digital rectal examination (DRE) are the known predictive factors for positive prostate biopsies differing according to the age, region and race. There have been only very limited studies about the impact of PSA on histological findings at prostate biopsy in Turkey. The aim of this study was to evaluate the impact of PSA and clinical stage on histologic findings of prostate biopsy in men older than 75 years of age as a first study in the Turkish population. A total of 1,645 consecutive prostate biopsies were included, with 194 men aged 75 or older. Cancer was identified in 104 patients (53.6%). Of the 104 positive biopsies, Gleason scores were less than 7 in 53 (49%) patients, 7 or greater in 51 (51%) patients. Positive prostate biopsies were significantly correlated with advanced age (p=0.0001), abnormal DRE (p=0.0001) and raised PSA (p=0.0001). The prostate volume was significantly correlated with advanced age especially in prostate cancer patients over 75 years, compared with those under 75 (p=0.0001). These results are useful for counseling men older than 75 years for prostate cancer detection. However, PCa screening decisions are currently based on urologist judgment and detection of latent asymptomatic disease is an important concern regarding costs, overdiagnosis, overtreatment and quality of life (QOL) for men aged 75 years and older. Healthy old patients with a long life expectancy need to be carefully evaluated for eligibility for PCa screening.

Synovial Sarcoma (SS) is a soft tissue neoplasm that occurs generally in the proximity of large joints. Here, we report a case of a 45-year-old man who was diagnosed with Primary SS of the kidney which is an extremely rare tumor that accounts for less than 2% of malignant renal tumors. We also review the literature on primary synovial sarcomas of the kidney and focus especially on the renal tumors' differential diagnosis.

Lipoma is the most common benign tumor of adipose tissue. Lipomas can occur almost anywhere in the body, but are rarely found in parietal peritoneum of abdominal wall. Occasionally lipomas are detected incidentally during abdominal surgery for other organ pathologies. Presently described is rare case of torsion of pedunculated lipoma originating in parietal peritoneum of anterior abdominal wall causing abdominal pain that mimicked acute appendicitis in 35-year-old woman.

Molluscum contagiosum is a benign cutaneous viral infection which is caused by double- stranded DNA poxvirus. It affects mainly children and young adults and usually presents with single or multiple umblicated papules or nodules on face, arms, legs and anogenital regions. It may present in atypical size and clinical appearance in patients with altered or impaired immunity and rarely in immuncompetent patients. Herein we present an immuncompetent young adult patient with isolated giant molluscum contagiosum, which was mimicking epidermoid cyst clinically..

Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) is a type IV hypersensitivity reaction characterized by a symmetrical erythematous rash in the gluteal and intertriginous areas. SDRIFE was previously considered to be the same presentation as Baboon Syndrome, however, has been suggested to be a different entity in the recent publications. The lesions are generally maculopapular and there is no mucosal involvement. To date, no case with petechial findings and mucosal involvement has been reported in the literature. The present study reports a SDRIFE case with a symmetrical erythematous petechial rash and oral mucosal involvement after taking oral amoxicillin.

In this study, we aimed to investigate the relationship between the histological features of nonalcoholic fatty liver disease (NAFLD) and serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-5 (IGFBP-5) to determine the usefulness of this relationship in clinical practice.Serum samples were collected from 92 patients with biopsy-proven NAFLD and 51 healthy controls and serum levels of IGF-1 and IGFBP-5 were assayed by enzyme-linked immunosorbent assay.Serum IGFBP-5 levels were correlated with liver steatosis, fibrosis, and nonalcoholic steatohepatitis scores. IGF-1 levels were significantly decreased in patients with moderate-to-severe fibrosis compared with patients with no or mild fibrosis.Serum IGFBP-5 levels may be useful to differentiate both advanced fibrosis and definite nonalcoholic steatohepatitis from other NAFLD groups. Also, serum IGF-1 levels may be useful to differentiate advanced fibrosis in patients with NAFLD.

Background.There are not many studies investigating histomorphological changes in 48 sessions in patients with early-stage MF after narrowband UVB (NBUVB) treatment. Our purpose is to evaluate histological features of phototherapy after 48 sessions and determine which parameters are more reliable for controlling skin biopsies.Methods.Biopsies of 32 patients with early stage of MF, who were treated with NBUVB phototherapy, were histologically evaluated before and after the treatments, including epidermotropism, stratum corneum, epidermal thickness, dermal infiltration, papillary dermal fibrosis, vascular alterations, and other dermal changes. We discuss the histomorphological effects of NBUVB phototherapy on skin biopsies by comparing the responders with nonresponders, with before and after the treatment.Results.9 patients (28%) did not give any response to treatment. Alleviation in epidermotropism, increases in parakeratosis and normal keratosis, perivascular infiltration, and melanophages, decrease in the lichenoid/patchy lichenoid infiltration pattern after the treatment was statistically significant. Comparing by response, normalization of stratum corneum and epidermis, orthohyperkeratosis, decrease in linearly arranged cells, the lichenoid/patchy lichenoid infiltration, the loss of inflammation were statistically significant in responders group.Conclusion.We detected a significant decrease in linearly arranged cells after phototherapy, indicating that it is an “important diagnostic parameter" in evaluation of therapeutic response.

A 53-year-old female patient was admitted to our clinic for generalized hypo/hyper-pigmented, partially firm and sclerotic plaques with undefined borders. As the skin biopsy taken from the lesion was compatible with lichen sclerosus et atrophicus (LSA), the patient was treated with ultraviolet A1 (UVA1) treatment. Upon follow-up, she developed abdominal pain and diarrhea. Further investigation (including endoscopic and laboratory tests) showed signs consistent with celiac disease. After 30 sessions of UVA1 treatment, the skin lesions partially regressed. We present this case because the co-occurrence of LSA and celiac disease is very rare.

Background: The present study gathers a single institutional experience of symptomatic omphalomesenteric duct (OMD) remnants in children with an emphasis on the age and modes of presentation, the surgical intervention and the histopathological findings. Methods: The data on children who underwent surgical treatment for symptomatic OMD remnants during a 17-year period were reviewed retrospectively, excluding incidental diverticulectomies. Results: A total of 59 children with a median age of 36 months underwent operations for symptomatic OMD remnants. There were 48 boys and 11 girls. The presenting signs were gastrointestinal tract (GIT) obstruction in 21 (36%) patients, acute abdomen in 18 (31%), umbilical abnormalities in 17 (29%), and rectal bleeding in three (5%). Patients presenting with umbilical anomalies were significantly younger than others. At surgery, a wedge resection of the remnant was carried out in 32 cases and an ileal resection was carried out in 27. Children presenting with GIT obstruction underwent segmentary ileal resection more often than other groups. Histopathology revealed inflammation in 26 (44%) specimens, ectopic tissue in 18 (31%) and necrosis in four (7%). Ectopic gastric mucosa was detected in 15 specimens, pancreatic tissue in two and both gastric and pancreatic tissue in one. Conclusions: Symptomatic OMD remnants in children most commonly presented with GIT obstruction, acute abdomen and umbilical anomalies. Rectal bleeding was not a predominant finding in the present series. Surgery is curative and can safely be done either by way of wedge resection or ileal segmentary resection. Ectopic tissue is detected in approximately one third of symptomatic remnants.

Survivin, β-catenin, and p53 are well-known cell-cycle and apoptosis regulators of tumorigenesis. Urothelial carcinomas (UCs) are the most common of the human cancers. Compared to superficial tumors (Ta, CIS, or T1), invasive UCs are important with regard to recurrence, progression, and mortality. Therefore, we examined whether survivin, β-catenin, and p53 could be used as the biomarkers for the early prediction of the invasiveness of UCs and the overall survival of the patients. We investigated the prognostic expressions of those biomarkers in UC (n=147) and in non-muscle invasive UC (NMI-UC) (n=113), using tissue microarray and immunohistochemistry. Spearman's correlation analysis and multivariate Cox regression analyses were used for statistical interpretation. High expressions of β-catenin, survivin, and p53 were associated with a high T stage, recurrence, progression, mortality, low recurrence-free survival, low progression-free survival and low overall survival (p < 0.01). Similar findings were achieved for recurrence and progression in the NMI-UC group, except for mortality. Moreover, a positive correlation was shown between p53 and β-catenin and between p53 and survivin (r=0.221, p < 0.01; r=0.236, p < 0.01, respectively). Survivin, p53, and β-catenin overexpression, as prognostic markers, might suggest that the UCs are biologically aggressive with the poor prognosis. Thus, dysregulation of those these cell-cycle and apoptosis regulators in bladder carcinoma could be used as a molecular marker to determine the best treatment strategy and could contribute to the development of targeted therapies.