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Hounsfield unit value has null effect on thyroid nodules at F-18-FDG PET/CT scans
No full textObjective: Detection rate of thyroid nodules is increasing with the use of new imaging modalities, especially in screening for malignancies. Positron emission tomography/computed tomography (PET/CT)-positive thyroid nodules should be differentiated for malignancy to avoid unnecessary operations and further follow-up. Most trials evaluate the role of SUVmax, but there is no definitive information about the utility of Hounsfield unit (HU) values for prediction of malignancy. This study aimed to evaluate the HU values beside SUVmax for detecting malignancy risk of PET/CT-positive thyroid nodules. Subjects and methods: Results of 98 cancer patients who had fine needle aspiration biopsy (FNAB) for thyroid nodules detected on PET/CT between January 2011 and December 2015 were assessed. The FNABs and surgical pathological results were recorded. Results: FNABs revealed benign results in 32 patients (32.7%), malignant in 18 (18.4%), non-diagnostic in 20 (20.4%), and indeterminate in 28 (28.5%). Twenty-four patients underwent thyroidectomy. The mean HU values were not significantly different in benign and malignant nodules (p = 0.73). However, the mean SUVmax was significantly higher (p < 0.001) in malignant ones. Area under curve (AUC) was 0.824 for SUVmax; the cut-off value was over 5.55 (p < 0.001), with 80% sensitivity, 84.5% specificity. Conclusions: Our current study demonstrated that HU value does not add any additional valuable information for discriminating between malignant and benign thyroid nodules. We also defined a SUVmax cut-off value of 5.55 for malignant potential of thyroid nodules detected on PET/CT
Causative Mutations and Mechanism of Androgenetic Hydatidiform Moles
No full textAndrogenetic complete hydatidiform moles are human pregnancies with no embryos and affect 1 in every 1,400 pregnancies. They have mostly androgenetic monospermic genomes with all the chromosomes originating from a haploid sperm and no maternal chromosomes. Androgenetic complete hydatidiform moles were described in 1977, but how they occur has remained an open question. We identified bi-allelic deleterious mutations in MEI1, TOP6BL/C11orf80, and REC114, with roles in meiotic double-strand breaks formation in women with recurrent androgenetic complete hydatidiform moles. We investigated the occurrence of androgenesis in Mei1-deficient female mice and discovered that 8% of their oocytes lose all their chromosomes by extruding them with the spindles into the first polar body. We demonstrate that Mei1−/− oocytes are capable of fertilization and 5% produce androgenetic zygotes. Thus, we uncover a meiotic abnormality in mammals and a mechanism for the genesis of androgenetic zygotes that is the extrusion of all maternal chromosomes and their spindles into the first polar body. © 2018 American Society of Human Genetic
The effect of bleomycin embolization on symptomatic improvement and hemangioma size among patients with giant liver hemangiomas
No full textHER2+ meme kanseri hücrelerinde pan-her inhibitörü dacomitinib'e hücre ölümü cevabının AVEN tarafından düzenlenmesi
No full textMeme kanseri kadınlarda en sık görülen kanser tipidir ve geliştirilen yenilikçi tanı ve
tedavi stratejilerine rağmen mortalite oranları halen yüksek seyretmektedir. Bu
durumun en önemli nedenlerinden birisi hastanın tedavisinin başlangıcında varolan ya
da tedavi sırasında ortaya çıkan terapi direncidir. HER reseptör ailesinin üyelerinin
mutasyon ya da amplifikasyon ile aşırı aktif hale gelmesi birçok meme kanseri tipinde
malign değişikliklerin nedenidir. HER2 amplifikasyonu meme kanseri hastalarının
yaklaşık yüzde 20’sinde görülmektedir ve kötü prognozla ilişkilidir. Trastuzumab ve
lapatinib gibi hedeflenmiş terapiler her ne kadar bu tümörlerde etkinlik gösterseler de
terapi direnci önemli bir sorun olarak karşımıza çıkmaktadır. Bu nedenle tüm HER
ailesi üyelerini eşzamanlı olarak hedefleyen panHER inhibitörleri (neratinib,
dacomitinib, afatinib) geliştirilmiştir. Mitokondriyal apoptotik yolak gerek
konvansiyonel gerekse hedeflenmiş terapilerin kanser hücreleri üzerindeki öncelikli
etki yollarındandır. Mitokondriyal apoptotik yolak BCL-2 protein ailesi tarafından
düzenlenir. BAX ve BAK proteinlerinin aktivatör BH3 proteinleri tarafından aktive
edilmesi, mitokondriyal dış membran geçirgenliğinin artışı, sitokrom c’nin sitozole
geçişi ve kaspaz aktivasyonu mitokondriyal apoptotik yolağın ana basamaklarıdır.
AVEN, mitokondriyal apoptoz yolağının ve DNA hasar yanıtının düzenlenmesinde
kritik rol oynayan sitozolik bir proteindir. BCL-xL proteinin anti-apoptotik aktivitesini
destekleyerek ve Apaf-1 proteinin oligomerizasyonunu engelleyerek apoptoz yanıtnı
inhibe etmektedir. Dahası sahip olduğu sinyal dizisi sayesinde nükleusa göç ederek
ATM ve ATR proteinleri ile etkileşime girmekte ve hücre döngüsünün
regülasyonunda rol oynamaktadır. AVEN’in ifadelenmesindeki ve/veya
aktivasyonundaki artış kanserleşme ve ilaç direnciyle ilişkilendirilmektedir. Bu çalışmada amacımız AVEN’ın HER2+ meme kanseri hücrelerinde dacomitinib
tarafından indüklenen hücre ölümü cevabını nasıl etkilediğini ortaya koymaktı. Bu
amaç çerçevesinde HER2+ SKBR3 meme kanseri hücrelerinde AVEN ifadelenmesini
arttırarak ya da azaltarak hücre ölümü cevabını değerlendirdik. AVEN’ın aşırı
ifadelenmesi dacomitinib tarafından indüklenen mitokondriyal hücre ölümü cevabını
azaltırken, RNAi yoluyla sustumu ise hücre ölümü cevabını arttırdı.
Gerçekleştirdiğimiz çalışma literatürde HER2+ meme kanseri hücrelerinde AVEN’ın
panHER baskılanmasına cevaben mitokondriyal hücre ölümünü nasıl etkilediğine dair
ilk bulguları sağlamıştır.
Breast cancer is the most common malignancy in women and the mortality rates are
still high despite the development of novel diagnostic and therapeutic strategies.
Resistance to therapy is among the leading causes of therapy failure, presenting either
initially or emerges druing the course of the therapy. Overactivation of HER family of
receptor kinases due to mutations or amplifications promotes malign transformation in
various breast cancer cases. HER2 amplification is seen in 20% breast cancer patients
and related to poor prognosis. Targeted therapies including trastuzumab and lapatinib
exerted prominent antitumor effect in these breast cancer tumors, but therapy
resistance significantly circumvents their activities. To cope with this issue, several
panHER inhibitors (neratinib, dacomitinib, afatinib) have been developed.
Mitochondrial apoptotic pathway is among the main mechanisms that modulates the
effects of conventional and targeted therapies on cancer cells. BCL-2 proteins regulate
mitochondrial apoptotic pathway. Activation of BAX and BAK by BH3-only proteins
leads to mitochondrial outer membrane permeabilization, translocation of cytochrome
c into cytosol and caspase activation are key steps of mitochondrial apoptotic
signaling.
AVEN is a cytosolic protein which regulates mitochondrial apoptotic pathway and
DNA damage response. AVEN interferes with apoptotic signaling by enhancing the
antiapoptotic activity of BCL-XL and by preventing Apaf-1 oligomerization. In
addition, AVEN translocates to nucleus by means of its nuclear localization signal and
interacts with ATM and ATR. These interactions regulate cell cycle response.
Furthermore, increased AVEN activity or expression have been shown to trigger
tumorigenesis and tumor maintenance. In this study, we aimed to identify how AVEN regulates dacomitinib-induced cell
death response in HER2+ breast cancer cells. To explore these responses, we
overexpressed or silenced AVEN in HER2+ SKBR3 breast cancer cells. AVEN
overexpression led to attenuation of dacomitinib-induced mitochondrial apoptotic
response and RNAi-mediated suppression of AVEN increased dacomitinib-induced
apoptosis. Our results provided first findings in the literature regarding the modulation
of panHER inhibition-induced apoptosis by AVEN
Iatrogenic vascular injuries due to spinal surgeries: Endovascular perspective
No full textAIM: Iatrogenic vascular injuries due to spinal surgeries are rare but serious complications. Surgical management of these injuries is challenging with high morbidity rates. In this study we aim to present the results of endovascular management of iatrogenic vascular injuries due to spinal surgeries. MATERIAL and METHODS: We retrospectively reviewed 11 patients (5 male, 6 female) who had vascular injuries due to cervical and lumbar spinal surgeries. Clinical findings were bleeding (n=5), leg edema (n=6) and right heart failure with severe dyspnea (n=1). The age range of the patients were between 42-67 (mean: 57.1). Six patients were reviewed with imaging before the procedures and the rest of the patients (n=5) were directly referred to the angiography unit for diagnosis and possible endovascular treatment. RESULTS: The types of surgeries were; cervical surgery (n=5) and lumbar disc operation (n=6). The type of vascular injuries were; vertebral artery stenosis (n=1), vertebral artery pseudoaneurysm (n=3), vertebral artery occlusion (n=1) and iliac arteriovenous fistula (n=6). The type of endovascular treatments were; parent artery occlusion (PAO) (n=2), covered stent graft implantation (n=6) and intrasaccular coil embolization of pseudoaneurysm (n=1). The remaining 2 patients were managed conservatively. No major complications or mortality occured during endovascular interventions. No bleeding or ischemia occured in the follow-up period. CONCLUSION: Iatrogenic vascular injuries due to spinal surgeries are rare but serious complications. Endovascular interventions are safe and effective in the diagnosis and treatment of such vascular injuries. © 2017, Turkish Neurosurgical Society
Endovascular Management of Iatrogenic Vascular Injury in the Craniocervical Region
No full textAIM: To evaluate iatrogenic vascular injuries in the craniocervical region and their endovascular management.
MATERIAL AND METHODS: Twenty-one patients (9 women, 12 men) with a mean age of 53.6 years (range 16-87 years), who underwent endovascular embolization for iatrogenic vascular injury in the craniocervical region between December 2000 and October 2015, were included in this retrospective study. Types of iatrogenic injuries, etiologies that caused these injuries and details of endovascular managements were reported.
RESULTS: The etiologies of the vascular injuries were as follows: transsphenoidal surgery (n=9), skull-base surgery (n=2), cholesteatoma surgery (n=1), tracheostomy (n=2), central venous catheterization (n=2), oropharyngeal tumor operation (n=1), endovascular treatment of internal carotid artery (ICA) stenosis (n=1), suprasellar epidermoid tumor operation (n=1), sphenoid sinus tumor surgery (n=1), and speech prosthesis device placement (n=1). The types of vascular injuries diagnosed at the time of angiography were; 2 occlusions, 2 stenoses, 2 dissections, 1 carotid cavernous fistula, 8 artery rupture with extravasation, and 9 pseudoaneurysms. Endovascular management of these vascular injuries were; parent artery occlusion (PAO) (n=15), aneurysm occlusion (n=3), covered stent (n=1) and conservative management (n=2). All patients except two were successfully treated. No patient had bleeding within a 30-day period after angiography. Long-term follow-up was available in all patients without occurrence of re-bleeding. One patient died due to complications related to primary vascular injury.
CONCLUSION: Although iatrogenic vascular injuries are rare, early diagnosis and management may be lifesaving. Endovascular techniques are reliable and safe in most of the patients
Adrenal Myelolipoma: A Case Presentation
No full textAdrenal myelolipomas are non-functional benign tumors of hematopoietic and mature adipose tissue. Adrenal myelolipomas, which are generally detected in post-mortem examinations, have become more detectable thanks to evolution and frequent use of imaging techniques. This presentation elaborates on a case of 35-year old male patient presenting with no complaint but diagnosed with adrenal myelolipoma in histopathological examination following surrenalectomy operation for an adrenal mass incidentally detected on ultrasonography and computed tomography work-up
Evaluating clonidine response in children and adolescents with attention-deficit/hyperactivity disorder
No full textAttention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in childhood, which is generally treated with stimulant and non-stimulant medications. However, 10-30% of patients in clinical setting do not present with adequate response to initial stimulant treatment. Thereby, clonidine may be considered for those patients who have failed to respond to psychostimulant/atomoxetine monotherapy or as an augmentation for inadequate response/comorbidity. This observational study evaluated its effectiveness as a single drug in ADHD cases unresponsive to previous treatment trials. Seventeen ADHD cases that were non-responders to stimulant, non-stimulant and combination therapy for the primary symptoms of ADHD were included in the study. Four cases dropped out before follow up, leaving thirteen cases who were administered immediate release clonidine treatment alone with a mean dose of 0.2 +/- 0.05 mg/day at baseline. The trial lasted for 12 weeks, and treatment outcomes were evaluated by the Turgay DSM-IV Based Child and Adolescent Behavior Disorders Screening and Rating Scale (T-DSM-IV-S) and the Clinical Global Impressions-Severity (CGI-S) and Improvement (CGI-I) scales. Mean age of the sample was 12.5 years (SD = 3.0) and eleven of the subjects had another comorbid psychopathology. Only two cases were evaluated as "very much improved", while another patient was judged to be "minimally improved" after 12 weeks of clonidine treatment. Attrition during follow-up was associated with higher median scores on the hyperactivity and impulsivity subscales (Mann-Whitney U test, p = 0.02). According to the T-DSM-IV-S, CGI-S, and CGI-I scales, clonidine treatment by itself had minimal benefits in this sample of treatment of refractory cases with ADHD evaluated at the study center. Clonidine is not available in Turkey pharmaceutical marketing system and patients' access to drug is limited. Our results provide first data regarding the use of clonidine in Turkish ADHD patients
In Vitro Susceptibility of Tigecycline and Colistin Against Stenotrophomonas maltophilia
No full textIntroduction: Gram-negative bacillus Stenotrophomonas maltophilia is resistant to drugs (multi-drug resistance-MDR) and it can be isolated from nature. Treatment of the infections resulting from S. maltophilia could be problematic due to multi-resistance.
Materials and Methods: 72 S. maltophilia strains isolated from clinical samples were included into the study. Sensitivity was determined using Tigecycline and Colistin E-test MIC method performed in the Clinical Microbiology laboratory of Baskent University, Medical Faculty between 2010 and 2014.
Results: In our study, colistin MIC range was found as 0.016-8 mg/L. MIC50 and MIC90 values were determined respectively as 1.5 mg/L and 12 mg/L. Tigecycline MIC range was 0-96 mg/L, and MIC50 was 0.19 mg/L and MIC90 was 1.5 mg/L. Furthermore, one tigecycline resistant strain was detected.
Conclusion: We believe that the determination of novel treatments and protocols and their standardization using multidisciplinary approaches can facilitate to cope with problematic and resistant nosocomial infections developed by S. maltophilia
Long term results of total parathyroidectomy/autotransplantation without cryopreservation in secondary hyperparathyroidism
No full textPurpose: The aim of this study was to compare the efficacy and early-late results of subtotal parathyroidectomy and total parathyroidectomy/auto transplantation without cryopreservation conducted on cases with secondary hyperparathyroidism (HPT).
Materials and Methods: 68 patients with secondary HPT who had parathyroidectomy were analysed retrospectively. In group1 (n=47) subtotal parathyroidectomy, in group2 (n=21) total parathyroidectomy/auto transplantation without cryopreservation were performed in our clinic. Patients' demographic characteristics and clinical features were evaluated.
Results: In group1 8 patients (14.9%), in group2 17 patients (76.2%) had concurrent thymectomies. The rates of persistant HPT in group1 and group2 were 14.9% (n=7), 4.8% (n=1) respectively. In group2 no recurrent HPT was seen, in group2 10.6% (n=5) of the patients had recurrent HPT. The reasons of persistent and recurrent HPT were ectopic or supernumerary glands in 69.2% (n=9) of the patients.
Conclusion:. In patients with end stage renal failure and secondary HPT, bilateral cervical thymectomy concurrent with total parathyroidectomy/auto transplantation without cryopreservation can be applied as a safe and efficient surgical procedure