Evaluation of malignancy with thyroid imaging reporting and data system (TI-RADS) in thyroid nodules with persistent nondiagnostic cytology

Background/aim: We aimed to evaluate the utility of thyroid imaging reporting and data system (TI-RADS) in prediction of malignancy in thyroid nodules with persistent nondiagnostic (ND) cytology. Materials and methods: A total of 246 thyroid nodules which were surgically removed and had at least two fine-needle aspirations (FNAs) with ND cytology were included in this study. Ultrasonography features and TI-RADS scores were recorded. Results: Of 246 nodules, 218 (88.6%) had benign and 28 (11.4%) had malignant final histopathology. Frequencies of taller than wide shape, solidity, hypoechogenicity, microcalcifications, and presence of irregular borders were similar between benign and malignant nodules (P > 0.05). The number of nodules categorized as TI-RADS 3, 4a, 4b, and 4c were 12 (4.9%), 53 (21.5%), 104 (42.3%), and 77 (31.3%), respectively. There was not any nodule in TI-RADS 5 category. Malignancy rates of categories 3, 4a, 4b, and 4c were 0%, 13.2%, 9.6%, 14.3%, respectively. No significant differences were detected in TI-RADS categories between benign and malignant nodules (P > 0.05). Conclusion: In this study, we did not demonstrate any suspicious ultrasound (US) finding predictive for malignancy in thyroid nodules with persistent ND cytology and did not determine any difference between malignant and benign nodules regarding TI-RADS scores. Whereas, we found that thyroid nodules in 4a, 4b, and 4c TI-RADS categories had higher malignancy rates than those previously reported in ND cytology. We think that TI-RADS categories in thyroid nodules with persistent ND cytology can be helpful in treatment decision.

Comparison of clinicopathological features and treatments between pre- and postmenopausal female breast cancer patients - a retrospective study.

INTRODUCTION: To find out if there are clinical and biological differences in breast cancer characteristics of premenopausal and postmenopausal women. For this reason, we investigated the differences in terms of the clinicopathological features and treatment methods of premenopausal and postmenopausal breast cancer patients in our study. MATERIAL AND METHODS: In this study, the files of 428 patients who were operated due to breast cancer between 1 January 2007 and 31 December 2017 in Ankara Atatürk Training and Research Hospital were examined retrospectively. The age, tumour size, tumour grade, oestrogen receptor, progesterone receptor, HER2 score, Ki-67 proliferation index, perineural invasion, and lymphovascular invasion were investigated. RESULTS: In patients with premenopausal breast cancer, the tumour diameter was larger (p = 0.047) and the lymph node metastasis was higher (p < 0.001). Oestrogen receptor (OR) expression (p = 0.002), progesterone receptor (PR) expression (p = 0.014), negative human epidermal growth factor receptor 2 (HER2) expression (p = 0.038), and Ki-67 expression (p = 0.017) were higher in the premenopausal group. In the premenopausal group, breast conserving surgery (p = 0.004), chemotherapy (p = 0.007), radiotherapy (p = 0.008), and endocrine therapy (p = 0.025) were higher than in the postmenopausal group. CONCLUSIONS: Premenopausal and postmenopausal female breast cancer patients have significant differences in tumour size, tumour grade, axillary lymph node metastasis, hormone receptor status, HER2 expression, and treatment modalities.

Association between Her2/neu status in colorectal carcinoma and clinicopathological features: a retrospective study using whole - tissue sections.

The human epidermal growth factor receptor 2 (Her2/neu) signal pathway plays a significant role in the occurance of various solid tumor types. The rate of Her2/neu in colorectal carcinoma (CRC) is not clearly elucidated. In this study, we discuss the association between Her2/neu overexpression and clinicopathological parameters in CRC. Her2/neu immunohistochemical (IHC) staining was performed on whole sections of formalin fixed paraffin embedded tumor tissues of 100 CRC resections. Cases with score 3+ and score 2+ expressions were further evaluated by silver in-situ hybridization (ISH) for the existence of Her2/neu gene amplification. Her2/neu membranous overexpression was observed in 12 of the 100 cases (6 cases with a score 3+ and 6 cases with a score 2+) and 6 of these were heterogenous. There were 10 cases with Her2/neu amplification (6/6 score 3+, 4/6 score 2+). Strong cytoplasmic staining was observed in 5 cases. Membranous scores were either 3+ or 2+ in 3 of these 5 cases. Moreover, there was Her2/neu amplification in 2 of these 3 cases. Her2/neu amplification status and overexpression was not related to clinicopathological parameters and overall survival. More clear results can be obtained from studies with Her2/neu IHC and ISH test on whole sections.

Diagnostic accuracy of Thyroid Imaging Reporting and Data System in the prediction of malignancy in nodules with atypia and follicular lesion of undetermined significance cytologies.

OBJECTIVE: Thyroid Imaging Reporting and Data System (TIRADS) is a simple and reliable reporting system for the prediction of malignancy. We aimed to determine the role of TIRADS in the prediction of malignancy in subcategories of Bethesda Category III, atypia of undetermined significance (AUS) and follicular lesion of undetermined significance (FLUS). DESIGN & PATIENTS: A total of 461 nodules with AUS cytology in 450 patients and 179 nodules with FLUS cytology in 168 patients were included. Ultrasonography (US) features and postoperative histopathology results were documented. Every suspicious US feature was scored as 1 and 0 according to the presence or not, respectively. TIRADS category of each nodule was determined. RESULTS: In AUS subcategory, histopathologically malignant nodules had significantly different TIRADS categories compared to benign nodules (P = 0·001), but this was not the case in FLUS subcategory (P = 0·121). In AUS group, malignant nodules had significantly higher prevalance of microcalcification, hypoechogenicity and anteroposterior/transverse ratio than benign ones (P < 0·001, P < 0·001 and P = 0·003, respectively) and TIRADS categories of 4c and 5 were more frequent in malignant nodules (P < 0·05). Microcalcification, hypoechogenicity and TIRADS were found to be associated with malignancy in multivariate logistic regression analysis in this subcategory. TIRADS category ≥4c was associated with malignancy (AUC ± SE: 0·584 ± 0·028). In FLUS subcategory, there was no significant difference between histopathologically malignant and benign nodules with respect to suspicious US features (P > 0·05, all). CONCLUSION: TIRADS seems to be useful in predicting malignancy and planning further management in the AUS subcategory, but not quite so in the FLUS subcategory.

Unique Case of Pseudomembranous Aspergillus Tracheobronchitis: Tracheal Perforation and Horner's Syndrome.

Pseudomembranous aspergillus tracheobronchitis is an uncommon form of invasive pulmonary aspergillosis, and it is generally seen in immunocompromised patients. We report about a mildly immunocompromised case with pseudomembranous aspergillus tracheobronchitis, which caused tracheal perforation, and Horner's syndrome. A 44-year-old female with uncontrolled diabetes mellitus, complaining of fever and dyspnea, was admitted to the hospital. She was hospitalized with community-acquired pneumonia and diabetic ketoacidosis. Insulin infusion and empirical antibiotics were firstly commenced. Bronchoscopy showed left vocal cord paralysis with extensive whitish exudative membranes covering the trachea and the main bronchi. Liposomal amphotericin B was added due to the probability of fungal etiology. Mucosal biopsy revealed aspergillus species. Second bronchoscopic examination demonstrated a large perforation in the tracheobronchial system. Despite all treatments, respiratory failure developed on the 25th day and the patient died within 2 days. Pseudomembranous aspergillus tracheobronchitis is fatal in about 78 % of all cases despite appropriate therapy. Early diagnosis and efficient antifungal therapy may improve the prognosis.

Clinicopathological parameters associated with cervical lymph node metastases in differentiated thyroid cancer.

BACKGROUND:  Lymph node metastasis (LNM) has an important role for the prognosis of diferentiated thyroid cancer (DTC). The aim of the study was to investigate the efect of clinicopathologic parameters on cervical LNM in DTC. METHODS:  The patients who underwent thyroidectomy along with neck dissection were analyzed retrospectively. RESULTS:  Of the 150 patients diagnosed with DTC who underwent neck dissection, 1 had follicular thyroid carcinoma and 149 had papillary thyroid carcinoma (PTC). The median tumor size was 14.0 mm. The tumor diameter with the highest specificity and sensitivity for the detection of LNM was >11.5 mm. Extrathyroidal extension (ETE) was observed in 35.3% of the patients. The rate of multifocality in tumors with extrathyroidal spread was significantly higher than in tumors without ETE. LNM was observed in 60.0% of the patients. ETE was present in 28.9% of the tumors that had LNM. Lymphovascular invasion (LVI), perineural invasion (PNI), and positive surgical margin were observed in 13.3%, 2.7%, and 14% of the patients respectively. A significant positive correlation was found between LNM and tumor diameter, ETE, positive tumor margin and LVI (Pp=.006, P=.031, P = .002, and P=.014, respectively). CONCLUSION:  In this study, ETE, LVI, positive tumor margin, and tumor diameter greater than 11.5 mm were significantly correlated with the presence of LNM. These findings may be useful in bringing to mind the possibility of lymph node metastases that have not been able to be detected before surgery and in monitoring these patients more closely.

Phenotype 2 familial mediterranean fever: evaluation of 22 case series and review of the literature on phenotype 2 FMF.

Familial Mediterranean fever (FMF) is an autosomal recessive autoimmune disorder characterized by recurrent bouts of fever and serosal inflammation. FMF may be complicated by AA-type amyloidosis, worsening the prognosis, with associated renal failure in some patients. Complication rate varies with race, being as high as 60% in Turks and as low as 2% in Armenians. In a few cases of patients with FMF (phenotype 2), amyloid nephropathy may be the presenting manifestation. This study included 420 patients who were admitted to the Nephrology and Rheumatology Departments of Atatürk Education and Research Hospital with unexplained proteinuria/nephrotic syndrome. The initial screening test for amyloidosis was the presence of significant proteinuria (300 mg/24 h). All MEFV gene exons were screened for causative mutations by direct DNA sequencing to check for any mutations. There were 22 phenotype 2 FMF patients with 27 allelic variants. The most prevalent allelic variants were M694V (10/27, 37%) and E148Q (7/27, 26%). Phenotype 2 FMF is not as rare as it was thought before; this should be kept in mind for all patients with unexplained proteinuria and/or acute phase response in high-risk ethnic groups for FMF.

A novel homozygous mutation in the USP53 gene as the cause of benign recurrent intrahepatic cholestasis in children: a case report.

BACKGROUND: Benign recurrent intrahepatic cholestasis (BRIC) is a rare cause of cholestasis with recurrent episodes of jaundice and pruritus without extrahepatic bile duct obstruction. A mutation in the USP53 gene is known to cause BRIC-like cholestasis with normal serum gamma-glutamyltransferase (GGT) levels. CASE: We report a 16-year-old boy with recurrent episodes of cholestasis since 6 months of age with normal serum GGT levels. The liver biopsy showed ballooning degeneration of hepatocytes which is typical for BRIC, and intrahepatic and canalicular cholestasis with bilirubinostasis. We performed whole exome sequencing (WES) and identified a novel homozygous variant (NM_001371399.1:c.1558C > T) of the USP53 gene at exon 14 as the cause of BRIC. CONCLUSION: This is the first case of USP53 disease from Türkiye with a novel mutation in the USP53 gene. This novel identification of the mutation of c.1558C > T at exon 14 can provide elucidative data for those who work in the field of intrahepatic cholestasis. Our case suggests that USP53 disease must be kept in mind in patients with recurrent intrahepatic cholestasis with normal serum GGT levels.

Can tumour budding change the future of pulmonary adenocarcinoma?

BACKGROUND: Pulmonary adenocarcinoma shows different prognosis even in the same pathological subtype and stage. In this study, it is aimed to investigate the relationship between tumour budding and known prognostic values and clinicopathological features in pulmonary adenocarcinoma. METHODS: In this study, there have been 77 patients diagnosed with primary pulmonary adenocarcinoma. In the evaluation process, the number of budding between 0 and 4 is accepted as low budding (Bd1), the number of budding between 5 and 9 is considered as medium budding (Bd2), and the number of budding above 10 is considered as high budding (Bd3). RESULTS: According to the findings of the study, it can be seen that there is a statistical difference between tumour budding and stromal fibrosis (p < 0.001). The presence of pleural invasion, lymph vascular invasion and perineural invasion in patients with Bd3 is found to be statistically higher than the patients with Bd1 (p = 0.048) (p = 0.041) (p = 0.029). CONCLUSIONS: Tumour budding has been associated with pleural invasion, lymph vascular invasion, perineural invasion, and stromal fibrosis. This study is the first to show the relationship between tumour budding and stromal fibrosis in pulmonary adenocarcinomas. The role of tumour budding in lung cancers remains to be clarified.

Celiac crisis with thrombocytopenia and coagulopathy in a child.

BACKGROUND: Celiac disease rarely presents with edema, hypoalbuminemia, acute metabolic deterioration, and electrolyte imbalances. This life-threatening condition is defined as a celiac crisis and may mimic disorders with metabolic derangement and sepsis. The crisis may present at onset or develop in celiac disease patients with poor compliance to a gluten-free diet. The fluid resuscitation and replacement of electrolyte deficits are life-saving modalities. CASE: A 14-month-old girl was admitted with fever, lethargy, severe dehydration, edema, hypotension, and commenced sepsis therapy. However, the patient had a growth delay and loss of weight with diarrhea and delayed motor skills. On admission, laboratory evaluation showed anemia, coagulopathy, hypoalbuminemia, electrolyte disturbances, and metabolic acidosis and developed thrombocytopenia during follow-up. The celiac serological tests and upper gastrointestinal endoscopic duodenal mucosa appearance, and duodenum histopathology findings suggested celiac disease. CONCLUSIONS: This case highlights that a celiac patient may present with a severe illness like sepsis and may be associated with cytopenia and coagulopathy in the celiac crisis.

Targeting lysyl oxidase (LOX) overcomes chemotherapy resistance in triple negative breast cancer.

Chemoresistance is a major obstacle in triple negative breast cancer (TNBC), the most aggressive breast cancer subtype. Here we identify hypoxia-induced ECM re-modeler, lysyl oxidase (LOX) as a key inducer of chemoresistance by developing chemoresistant TNBC tumors in vivo and characterizing their transcriptomes by RNA-sequencing. Inhibiting LOX reduces collagen cross-linking and fibronectin assembly, increases drug penetration, and downregulates ITGA5/FN1 expression, resulting in inhibition of FAK/Src signaling, induction of apoptosis and re-sensitization to chemotherapy. Similarly, inhibiting FAK/Src results in chemosensitization. These effects are observed in 3D-cultured cell lines, tumor organoids, chemoresistant xenografts, syngeneic tumors and PDX models. Re-expressing the hypoxia-repressed miR-142-3p, which targets HIF1A, LOX and ITGA5, causes further suppression of the HIF-1α/LOX/ITGA5/FN1 axis. Notably, higher LOX, ITGA5, or FN1, or lower miR-142-3p levels are associated with shorter survival in chemotherapy-treated TNBC patients. These results provide strong pre-clinical rationale for developing and testing LOX inhibitors to overcome chemoresistance in TNBC patients.

Recurrent mucinous cystadenoma: a laparoscopic approach.

The second most common epithelial tumor of the ovary is mucinous-type, and it constitutes 8-10% of all ovarian tumors. The recurrence of mucinous cystadenoma is very rare after complete excision. Only four such cases have been reported till date. The case presented in this report is the fifth, who had her initial surgery performed by gynecologic oncology team by laparotomy and was followed up by the same group. After recurrence at the same ovary, the patient underwent laparoscopic evaluation and unilateral salpingoophorectomy was performed. The final histopathological diagnosis was mucinous cystadenoma, just the same as the initial cyst.

Is there a difference in the number of interstitial cells, neurons, presence of fibrosis and inflammation in ureteropelvic junction tissues of patients with ureteropelvic junction obstruction with and without crossing vessels?

OBJECTIVE: We compared the number of interstitial cells (ICs), nerves, presence of fibrosis and inflammation at the level of full-thickness human ureteropelvic junction (UPJ) tissues obtained from normal subjects, and patients with UPJ obstruction with and without crossing vessels. MATERIAL AND METHODS: Normal UPJ tissues (n=12) histopathologically confirmed to be without tumor involvement were obtained from subjects who underwent radical nephrectomy for kidney mass. Additional UPJ tissues were obtained from patients who underwent pyeloplasty due to UPJ obstruction. Crossing vessel was identified in 17 patients. In 57 patients, no crossing-vessel was noted. ICs were stained immunohistochemically with anti-human CD117 (c-kit) antibody. Neural tissue was stained with S-100. The numbers of ICs and neurons were compared between the groups: controls with normal UPJ (Group I), Ureteropelvic junction obtruction (UPJO) with crossing vessel (Group II) and UPJ obstruction without crossing vessel (Group III). Groups were also compared in terms of the presence of fibrosis and inflammation. RESULTS: The mean age of total population included in the study was 30.5±18.5 years. No significant differences were detected between the three groups regarding mean and median numbers of ICs at the level of UPJ (lamina propria and muscle layer) and mean and median numbers of neurons at the level of lamina propria (p>0.05). Likewise, no significant differences were detected between the three groups regarding the presence of fibrosis and inflammation (p>0.05). CONCLUSION: Number of ICs, neurons, presence of fibrosis and inflammation seem to be similar in the intact UPJ and UPJ with obstruction with and without crossing vessel. Cellular function rather than the number ICs might play a role that warrants further research.

The diagnostic value of parathyroid hormone washout in primary hyperparathyroidism patients with negative or equivocal 99 m Tc-MIBI results.

BACKGROUND AND OBJECTIVES: The accurate identification of hyper functioning parathyroid gland is needed for definitive surgical treatment in primary hyperparathyroidism. Ultrasonography and 99mTechnetium sestamibi scintigraphy are the two most used methods with varying sensitivities. This study aimed to assess the value of parathyroid hormone (PTH) assay in preoperative ultrasound guided fine needle aspiration (FNA)-PTH washout fluid to verify the correct localisation of lesions with negative or inconclusive scintigraphy results. METHODS: We evaluated data of 28 lesions in 21 patients who underwent US-guided parathyroid fine-needle aspiration (FNA) with PTH washout, retrospectively. The PTH washout results and the reports of parathyroid surgery and imaging studies were reviewed. RESULTS: Of operated 28 lesions 23 had positive and 5 had negative washout results. The median FNA-PTH washout was 2315.5 pg/ ml (min-max: 12.3-6978 pg/ ml). The calculated sensitivity of FNA-PTH washout was 85.7% and the specifity was 28.6%. The positive and negative predictive values were 78.3% and 40.0%, respectively. CONCLUSIONS: FNA-PTH can be used to establish the nature of the lesion, discriminate parathyroid gland from thyroid lesions or cervical lymph nodes, improving the surgical outcomes. It can be used to localise parathyroid lesions preoperatively when negative or discordant ultrasound and scintigraphy findings are obtained.

Role of calcium-sensing receptor, Galectin-3, Cyclin D1, and Ki-67 immunohistochemistry to favor in the diagnosis of parathyroid carcinoma.

BACKGROUND: As histopathological findings of parathyroid carcinoma are not certain, the diagnosis of tumors with degenerative changes may be difficult. In these cases, immunohistochemical markers are beneficial. We aimed to research the acceptability of calcium-sensing receptor (CaSR), Galactin-3, Cyclin D1, and Ki-67 as helpful markers in parathyroid tumors in cases which are difficult to diagnose. MATERIALS AND METHODS: Those cases who had been diagnosed with atypical parathyroid adenoma and parathyroid carcinoma between 2010 and 2015 were reevaluated. Immunohistochemical markers were applied to this cases. RESULTS: About 21 cases were parathyroid adenoma, 14 were atypical adenoma, and 10 cases were parathyroid carcinoma. According to the immunohistochemical results, global loss of CaSR staining was seen in 50% (5/10) of the patients with carcinoma while there was no loss of staining in those with parathyroid adenoma (P = 0,001). Global loss of CaSR staining was found in only one out of 14 cases with atypical adenoma. The expression of Galactin-3 was found to be positive in 40% (4/10) of carcinoma cases, 71.4% (10/14) of those with atypical adenoma, and 14.3% (3/21) of those with adenoma (P = 0,002). Cyclin D1 expression was determined to be positive in 70% (7/10) of patients with carcinoma, 71.4% (10/14) of atypical adenoma cases, and 23.8% (5/21) of those with adenoma. The Ki-67 proliferation index was seen to be above 5% in 50% (5/10) of carcinoma cases and 35,7% (5/14) of those with atypical adenoma. CONCLUSION: In these studies, it has been emphasized that the global loss of CaSR staining was used as a negative marker in the diagnosis of carcinoma. In this study, we have also confirmed that the global loss of CaSR staining is a useful marker to determine potential increased malignancy.

Is ultrasonographically detected nodule diameter concordant with pathological tumor size?

INTRODUCTION: We aimed to compare preoperative ultrasonographical and postoperative histopathological diameters of differentiated thyroid cancer (DTC) lesions and investigate possible factors that can predict the discordance between two measurements. METHODS: Data of patients with histopathologically confirmed DTC were reviewed retrospectively. Nodules evaluated by preoperative US were matched with histopathologically examined nodules. Incidental tumors and nodules that can not be matched in US and histopathology reports were excluded. Preoperative US diameter and postoperative histopathological size were compared and percentage difference between two measurements was calculated for each lesion. RESULTS: There were 607 DTC foci in 562 patients. Mean US diameter was significantly higher than histopathological diameter (21.0 ± 15.6 mm vs 17.3 ± 13.6, p < 0.001). US diameter was higher than tumor size in 444 (73.1%), equal in 15 (2.5%) and lower in 148 (24.4%) nodules. Marginal irregularity was observed in 253 (57%) lesions with US diameter > tumor size and 108 (73%) lesions with US diameter < tumor size (p = 0.010). Rate of nodules with peripheral halo was higher in lesions with US diameter > tumor size (30.6% vs 20.3%, p = 0.015). In nodules with US diameter > tumor size, percentage difference was lower in nodules with microcalcification (p = 0.020) and higher in cytologically benign nodules (p < 0.001). Among nodules with US diameter < tumor size, <1 cm nodules had significantly higher percentage difference compared to 1-1.9, 2-3.9 and ≥ 4 cm nodules (p = 0.005). CONCLUSION: Ultrasonographically determined diameter is higher than histopathologically determined size in a considerable ratio of DTCs. It might be helpful to consider this discordance while deciding surgical extent in these patients.

Can Cutting-Needle Biopsy Be an Alternative to Excisional Biopsy in Lymph Node Pathologies?

OBJECTIVE: We aimed to compare cutting-needle biopsy (CNB) diagnoses with excisional biopsy diagnoses of enlarging lymph nodes and to determine the diagnostic value of CNB. MATERIAL AND METHOD: Out of the 291 cases that underwent CNB from lymph nodes between 2010 and 2016, 60 were included in the study in which pathological lymph nodes were excised after CNB. Demographic information, pathology and imaging reports, the diameters of the lymph nodes and the length of the CNBs of these cases were obtained from the hospital registry system. Diagnoses of the CNBs and excisional biopsies were then compared. RESULTS: According to the excisional biopsy diagnosis, 7 of the 60 cases (11.7%) were benign and 53 of them (88.3%) were malignant. 28 (53%) of the malignant cases were diagnosed as Hodgkin's lymphoma while the others (47%) got a non-Hodgkin's lymphoma diagnosis. In the 8 non-diagnostic CNBs, 3(37%) of them were found to be benign/reactive, while 5 (63%) were diagnosed as malign lymphoma in excisional biopsy. Similarly, 7(64%) of the 11 cases diagnosed as benign/reactive in CNB, were found to be malignant with excisional biopsy. When CNB and excisional biopsy were compared, sensitivity and specificity were 90% and 100%; positive predictive value (PPV) and negative predictive value (NPV) were 100% and 0%, respectively, and the diagnostic accuracy rate (DV) was 86.5%. The mean diameter of the benign lymph nodes was 26.1 mm and the mean diameter of the malignant ones was 35.6 mm. There was no significant difference between malignant and benign lymph node size (p > 0.05). There was also no statistically significant difference between CNB length and correct diagnosis (p=0.233). CONCLUSION: CNB is a non-invasive procedure. It is an alternative to excisional biopsy because of its low morbidity and low cost. However, the sensitivity of CNB is lower than its specificity, and we recommend the surgical excision of lymph nodes with a clinically strong neoplasm suspicion because of the presence of false negatives in 7 cases.

What does the Data of 354,725 Patients from Turkey Tell Us About Cervical Smear Epithelial Cell Abnormalities? - The Epithelial Cell Abnormality Rate is Increasing - Quality Control Studies and Corrective Activity are Musts.

OBJECTIVE: There is no other screening program close to the success rate of PAP test. Cervical cytology constitutes a large workload so that quality control in cervical cytology is important for the quality assurance of pathology laboratories. MATERIAL AND METHOD: In this study, we collected the cervical cytology results from all over Turkey and discussed the parameters influencing the quality of the PAP test. The study was conducted with Turkish gynaecopathology working group and 38 centers (totally 45 hospitals) agreed to contribute from 24 different cities. The study was designed to cover the cervical cytology results during 2013. The results were evaluated from the data based on an online questionnaire. RESULTS: The total number of Epithelial Cell Abnormality was 18,020 and the global Epithelial Cell Abnormality rate was 5.08% in the total 354,725 smears and ranging between 0.3% to 16.64% among centers. The Atypical squamous cells /Squamous intraepithelial lesion ratios changed within the range of 0.21-13.94 with an average of 2.61. When the centers were asked whether they performed quality assurance studies, only 14 out of 28 centers, which shared the information, had such a control study and some quality parameters were better in these centers. CONCLUSION: There is an increase in the global Epithelial Cell Abnormality rate and there are great differences among centers. Quality control studies including the Atypical squamous cells/Squamous intraepithelial lesion ratio are important. Corrective and preventive action according to quality control parameters is a must. A cervical cytology subspecialist in every center can be utopic but a dedicated pathologist in the center is certainly needed.

The miR-644a/CTBP1/p53 axis suppresses drug resistance by simultaneous inhibition of cell survival and epithelial-mesenchymal transition in breast cancer.

Tumor cells develop drug resistance which leads to recurrence and distant metastasis. MicroRNAs are key regulators of tumor pathogenesis; however, little is known whether they can sensitize cells and block metastasis simultaneously. Here, we report miR-644a as a novel inhibitor of both cell survival and EMT whereby acting as pleiotropic therapy-sensitizer in breast cancer. We showed that both miR-644a expression and its gene signature are associated with tumor progression and distant metastasis-free survival. Mechanistically, miR-644a directly targets the transcriptional co-repressor C-Terminal Binding Protein 1 (CTBP1) whose knock-outs by the CRISPR-Cas9 system inhibit tumor growth, metastasis, and drug resistance, mimicking the phenotypes induced by miR-644a. Furthermore, downregulation of CTBP1 by miR-644a upregulates wild type- or mutant-p53 which acts as a 'molecular switch' between G1-arrest and apoptosis by inducing cyclin-dependent kinase inhibitor 1 (p21, CDKN1A, CIP1) or pro-apoptotic phorbol-12-myristate-13-acetate-induced protein 1 (Noxa, PMAIP1), respectively. Interestingly, an increase in mutant-p53 by either overexpression of miR-644a or downregulation of CTBP1 was enough to shift this balance in favor of apoptosis through upregulation of Noxa. Notably, p53-mutant patients, but not p53-wild type ones, with high CTBP1 have a shorter survival suggesting that CTBP1 could be a potential prognostic factor for breast cancer patients with p53 mutations. Overall, re-activation of the miR-644a/CTBP1/p53 axis may represent a new strategy for overcoming both therapy resistance and metastasis.

Endobronchial ultrasound-guided transbronchial needle aspiration in the diagnosis of lymphoma.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is highly accurate in diagnosing mediastinal lymphadenopathies of lung cancer and benign disorders. However, the utility of EBUS-TBNA in the diagnosis of mediastinal lymphomas is unclear. The aim of this study was to determine the diagnostic value of EBUS-TBNA in patients with suspected lymphoma. MATERIALS AND METHODS: Sixty-eight patients with isolated mediastinal lymphadenopathy and suspected of lymphoma were included in the study. EBUS-TBNA was performed on outpatients under moderate sedation. The sensitivity, specificity, negative predictive value and diagnostic accuracy of EBUS-TBNA were calculated. RESULTS: Sixty-four patients were diagnosed by EBUS-TBNA, but four patients with non-diagnostic EBUS-TBNA required surgical procedures. Thirty-five (51.5%) patients had sarcoidosis, six (8.8%) had reactive lymphadenopathy, nine (13.3%) had tuberculosis, one (1.5%) had squamous cell carcinoma, two (2.9%) had sarcoma and fifteen (22%) had lymphoma (follicular center cell, large B-cell primary, and Hodgkin lymphomas in three, two, and ten, respectively). Of the 15 lymphoma patients, thirteen were diagnosed by EBUS and two by thoracotomy and mediastinoscopy. The sensitivity, specificity, negative predictive value, and diagnostic accuracy of EBUS-TBNA for the diagnosis of lymphoma were calculated as 86.7%, 100%, 96.4%, and 97%, respectively. CONCLUSIONS: EBUS-TBNA can be employed in the diagnosis of mediastinal lymphoma, instead of more invasive surgical procedures.