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1.
Balkan Med J ; 40(5): 344-350, 2023 09 11.
Article in English | MEDLINE | ID: mdl-37318131

ABSTRACT

Background: The study of ROS1 rearrangement in non-small cell lung carcinoma (NSCLC) has gained importance as it enables personalized treatment of NSCLC with tyrosine kinase inhibitors. Therefore, it is important that the ROS1 assessment tests become more standardized. In this study, we compared the two immunohistochemistry (IHC) antibodies (D4D6 and SP384 clones) and consistency with the fluorescence in situ hybridization (FISH) results in NSCLC. Aims: To investigate the effectiveness of the commonly used two IHC antibodies (SP384 and D4D6 clones) to detect ROS1 rearrangement in NSCLC. Study Design: A retrospective cohort study. Methods: The study included 103 samples diagnosed with NSCLC, confirmed using IHC and FISH ROS1 results (14 positives, four discordant, and 85 consecutive negatives), with sufficient tissue samples (≥ 50 tumor cells). All samples were initially tested with ROS1-IHC antibodies (D4D6 and SP384 clones); their ROS1 status was then analyzed using the FISH method. Finally, samples with discordant IHC and FISH results were confirmed using the reverse transcription polymerase chain reaction method. Results: The sensitivity of SP384 and D4D6 clones of ROS1 antibody was 100% with a ≥ 1 + cut-off. When the ≥ 2 + cut-off was used, the sensitivity rate for the SP384 clone was 100%, whereas the sensitivity for the D4D6 clone was 42.86%. ROS1 FISH rearranged samples were positive for both clones, but SP384 had generally higher intensity than D4D6. The mean IHC score was + 2 for SP384 and + 1.17 for D4D6. SP384 mostly tended to have a higher IHC score intensity, which made the evaluation easier than D4D6. SP384 has a higher sensitivity than D4D6. However, false positives were found in both clones. There was no significant correlation between ROS1 FISH-positivity percentage with SP384 (p = 0.713, p = 0.108) and D4D6 (p = 0.26, p = -0.323) IHC staining intensity. The staining patterns of both clones were similar (homogeneity/heterogeneity). Conclusion: Our findings show that the SP384 clone is more sensitive than D4D6. However, SP384 can also cause false positive results like D4D6. Knowing the variable diagnostic performance of different ROS1 antibodies before using them in clinical applications is necessary. IHC-positive results should be confirmed using FISH.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Immunohistochemistry , In Situ Hybridization, Fluorescence , Lung Neoplasms/diagnosis , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Protein-Tyrosine Kinases/genetics , Proto-Oncogene Proteins/genetics , Retrospective Studies
2.
Turk Patoloji Derg ; 38(3): 185-204, 2022.
Article in English | MEDLINE | ID: mdl-35969220

ABSTRACT

In our manuscript, we propose a common terminology in the Turkish language for the newly adopted WHO classification of the CNS tumors, also known as the WHO CNS 5th edition. We also comment on the applicability of this new scheme in low and middle income countries, and warn about further deepening disparities between the global north and the global south. This division, augmented by the recent COVID-19 pandemic, threatens our ability to coordinate efforts worldwide and may create significant disparities in the diagnosis and treatment of cancers between the "haves" and the "have nots".


Subject(s)
COVID-19 , Central Nervous System Neoplasms , Central Nervous System Neoplasms/diagnosis , Developing Countries , Humans , Language , Pandemics , World Health Organization
3.
J Clin Res Pediatr Endocrinol ; 14(1): 126-130, 2022 03 03.
Article in English | MEDLINE | ID: mdl-33586921

ABSTRACT

Silent corticotroph tumors are composed of corticotroph cells, but do not manifest any biochemical or clinical evidence of hypercortisolism. A choristoma is a benign, congenital proliferation of histologically mature tissue elements normally not present at the site of occurrence. The existence of adrenocortical cells within the pituitary gland, which can be explained as a choristoma, is a very rare entity, and the co-occurrence of these two entities have only been reported in few cases. We report an 11-year-old boy with central hypothyroidism. On cranial magnetic resonance imaging a pituitary tumor was detected, and histopathological studies led to a diagnosis of an adrenal choristoma and a silent corticotroph tumor in the pituitary gland. The presence of adrenocortical cells were confirmed by positive calretinin, inhibin and Melan A staining, and the corticotroph cells by immunohistochemistry demonstrating adrenocorticotropic hormone positivity. Herein, we report the fourth and the youngest case of silent corticotroph tumor with adrenocortical choristoma in the literature. Even though the underlying mechanism is not fully understood, suggested mechanisms are discussed.


Subject(s)
Adenoma , Choristoma , Pituitary Neoplasms , Adrenocorticotropic Hormone , Child , Corticotrophs/metabolism , Corticotrophs/pathology , Humans , Male , Pituitary Neoplasms/pathology
4.
Tumori ; 108(3): 258-262, 2022 Jun.
Article in English | MEDLINE | ID: mdl-33849345

ABSTRACT

INTRODUCTION: Lung cancer is the most common cause of cancer-related death in the world. Changes in the treatment of metastatic lung cancer in recent years have made targetable mutations gain importance. MET alteration is one of these driver mutations and crizotinib is a tyrosine kinase inhibitor used in therapy. METHODS: In our study, data of patients with c-MET amplification who received crizotinib treatment between July 2017 and November 2020 in the Medical Oncology Clinic of Bakirköy Dr. Sadi Konuk Training and Research Hospital were retrospectively analyzed. c-MET scanning was performed by the fluorescent in situ hybridization method by using Cytotest MET/CCP7 probe kit by evaluating 100 tumor cells and the threshold value for positivity was accepted as above 20%. RESULTS: Eight of 28 patients who received crizotinib treatment had c-MET amplification. Seven of these patients were male and one was female. Progression-free survival and overall survival in these eight patients were 9.4 and 10.9 months, respectively, and objective response rate was 50%. Grade 4 nausea was observed in only one patient; there was no grade 4-5 toxicity and no patient discontinued the drug due to toxicity. CONCLUSION: Crizotinib is an effective treatment option other than cytotoxic chemotherapy in the limited number of patients with MET amplification in the stage 4 lung adenocarcinoma subgroup. It is important to investigate this amplification, which can be detected especially in smoking patients in the appropriate patient group, and to use appropriate tyrosine kinase inhibitors in treatment.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Crizotinib/therapeutic use , Female , Humans , In Situ Hybridization, Fluorescence , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Male , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Proto-Oncogene Proteins c-met/genetics , Proto-Oncogene Proteins c-met/therapeutic use , Retrospective Studies
5.
Exp Clin Endocrinol Diabetes ; 130(2): 125-133, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34255320

ABSTRACT

PURPOSE: To investigate the relationship of Fibroblast Growth Factor Receptor-4 (FGFR-4) expression with radiologic, pathologic, and clinical parameters in pituitary adenomas. METHODS: Among 307 patients who underwent pituitary surgery for a pituitary adenoma between 2000 and 2015, we included 161 patients (53 gonadotroph, 26 corticotroph, 25 null cell, 22 lactotroph, 13 somatotroph, 8 adenomas with unusual combination, 7 Pit-1 positive adenomas, and 7 lactosomatotroph) based on availability of pathology specimens. Patients' radiologic, pathologic, and clinical parameters were determined. FGFR-4 immunostaining was evaluated using a semi-quantitative histologic score (H-score). RESULTS: The mean follow-up period was 61 (IQR=32-84) months. The median H-scores for FGFR-4 were higher in patients without remission, those with residual lesion, and T2-hyperintense adenoma (p<0.05). Ki-67 level was higher in patients without remission compared to those in remission (p<0.05). The mean Ki-67 levels did not differ between patients with and without residual lesion or T2-hyperintense tumor (p>0.05). There was no significant difference (p>0.05) when the H-score and Ki-67 levels were assessed in terms of sex, sellar-dural invasion, Knosp and a grading system for superior, inferior, parasellar, anterior and posterior tumor extension Classification, tumor function or presence of poor subtype. Adenomas with Ki-67 expression ≥3% had higher FGFR4 expression levels than those with <3% expression (p=0.002). There was a weak positive correlation between H-score and Ki-67 (p=0.011; r=0.201). CONCLUSIONS: Higher levels of FGFR-4 in pituitary adenomas could be use a marker for more aggressive tumor behavior.


Subject(s)
Adenoma/metabolism , Adenoma/pathology , Biomarkers, Tumor/metabolism , Pituitary Neoplasms/metabolism , Pituitary Neoplasms/pathology , Receptor, Fibroblast Growth Factor, Type 4/metabolism , Adult , Female , Follow-Up Studies , Humans , Ki-67 Antigen/metabolism , Male , Middle Aged
6.
Onco Targets Ther ; 14: 4671-4692, 2021.
Article in English | MEDLINE | ID: mdl-34511936

ABSTRACT

The treatment of patients with advanced non-small-cell lung cancer (NSCLC) in recent years has been increasingly guided by biomarker testing. Testing has centered on driver genetic alterations involving the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) rearrangements. The presence of these mutations is predictive of response to targeted therapies such as EGFR tyrosine kinase inhibitors (TKIs) and ALK TKIs. However, there are substantial challenges for the implementation of biomarker testing, particularly in emerging countries. Understanding the barriers to testing in NSCLC will be key to improving molecular testing rates worldwide and patient outcomes as a result. In this article, we review EGFR mutations and ALK rearrangements as predictive biomarkers for NSCLC, discuss a selection of appropriate tests and review the literature with respect to the global uptake of EGFR and ALK testing. To help improve testing rates and unify procedures, we review our experiences with biomarker testing in China, South Korea, Russia, Turkey, Brazil, Argentina and Mexico, and propose a set of recommendations that pathologists from emerging countries can apply to assist with the diagnosis of NSCLC.

7.
Exp Clin Endocrinol Diabetes ; 129(9): 634-643, 2021 Sep.
Article in English | MEDLINE | ID: mdl-33091936

ABSTRACT

PURPOSE: To evaluate the expression of G-protein coupled estrogen receptor (GPER1), aromatase, estrogen receptor α (ERα), estrogen receptor ß (ERß), pituitary tumor transforming gene (PTTG), and fibroblast growth factor 2 (FGF2) in GH-secreting and non-functioning adenomas (NFA). METHODS: Thirty patients with acromegaly and 27 patients with NFA were included. Gene expression was determined via quantitative reverse transcription polymerase chain reaction (QRT-PCR). Protein expression was determined via immunohistochemistry. RESULTS: There was no difference, in terms of gene expression of aromatase, ERα, PTTG, and FGF2 between the two groups (p>0.05 for all). ERß gene expression was higher and GPER1 gene expression was lower in GH-secreting adenomas than NFAs (p<0.05 for all). Aromatase and ERß protein expression was higher in GH-secreting adenomas than NFAs (p=0.01). None of the tumors expressed ERα. GPER1 expression was detected in 62.2% of the GH-secreting adenomas and 45% of NFAs. There was no difference in terms of GPER1, PTTG, FGF2 H scores between the two groups (p>0.05 for all). GPER1 gene expression was positively correlated to ERα, ERß, PTTG, and FGF2 gene expression (p<0.05 for all). There was a positive correlation between aromatase and GPER1 protein expression (r=0.31; p=0.04). CONCLUSIONS: GPER1 is expressed at both gene and protein level in a substantial portion of GH-secreting adenomas and NFAs. The finding of a positive correlation between GPER1 and ERα, ERß, PTTG, and FGF2 gene expression and aromatase and GPER1 protein expression suggests GPER1 along with aromatase and classical ERs might mediate the effects of estrogen through upregulation of PTTG and FGF2.


Subject(s)
Acromegaly/metabolism , Adenoma/metabolism , Human Growth Hormone/metabolism , Pituitary Neoplasms/metabolism , Receptors, Estrogen/blood , Receptors, G-Protein-Coupled/blood , Acromegaly/blood , Adenoma/blood , Adult , Aged , Female , Humans , Male , Middle Aged , Pituitary Neoplasms/blood
8.
Clin Neurol Neurosurg ; 198: 106201, 2020 11.
Article in English | MEDLINE | ID: mdl-32927330

ABSTRACT

OBJECTIVE: A thorough follow-up study in which the same clinic presents the change in the surgical outcomes of acromegaly over the years, is still lacking in the endoscopic era. In this study, we intended to evaluate the clinical characteristics, radiological features, surgical and late remission rates of newly diagnosed acromegaly patients treated in our clinic between 2014 and 2019 in order to delineate the surgical remission status according to radiological, microscopic, and hormonal features. As a follow-up to our initial report, we also aimed to display the change of surgical remission rates over time in a tertiary center. METHODS: A total of newly diagnosed 106 patients with acromegaly, who underwent endoscopic endonasal trans-sphenoidal approach (EETSA) in the last five years were retrospectively analyzed and presented in this study. Medical records were reviewed in clinical, biochemical, pathological, and radiological aspects to assess the relationship of preoperative patient characteristics with surgical remissions. RESULTS: The percentages of the giant pituitary adenomas (≥4 cm), adenomas with suprasellar extension and adenomas with surgically proven invasion of the cavernous sinus in the present series were 13%, 34%, and 20%, respectively. Gross total resection was achieved in 80% of the patients. Surgical remission and late remission rates were 66% and 86%, respectively. Nine (9.4%) patients in our current report had postoperative transient diabetes insipidus. The mean follow-up period in this series was 36.1 ±â€¯18.1 (range 12-59) months. CONCLUSION: The presented surgical results are considerably better than our published initial series of acromegaly patients operated in the same clinic between 2007 and 2014. The improvement in surgical remission rate support a positive surgical volume - remission rate relationship for acromegaly in the era of endoscopic endonasal skull base approaches. One possible factor for better results may be the increasing surgical experience in EETSA, which follows a trend toward gradual improvement of long-term late remissions via a multidisciplinary approach.


Subject(s)
Acromegaly/surgery , Adenoma/surgery , Nasal Cavity/surgery , Neuroendoscopy/methods , Pituitary Neoplasms/surgery , Sella Turcica/surgery , Acromegaly/blood , Acromegaly/diagnostic imaging , Adenoma/blood , Adenoma/diagnostic imaging , Adolescent , Adult , Aged , Female , Follow-Up Studies , Human Growth Hormone/blood , Humans , Male , Middle Aged , Nasal Cavity/diagnostic imaging , Neuroendoscopy/trends , Pituitary Neoplasms/blood , Pituitary Neoplasms/diagnostic imaging , Retrospective Studies , Sella Turcica/diagnostic imaging , Sphenoid Bone/diagnostic imaging , Sphenoid Bone/surgery , Treatment Outcome , Young Adult
9.
Bosn J Basic Med Sci ; 20(3): 329-335, 2020 Aug 03.
Article in English | MEDLINE | ID: mdl-31999935

ABSTRACT

Programmed death-ligand 1 (PD-L1) is suggested to be a predictive biomarker in non-small-cell lung carcinoma (NSCLC). However, the differential expression of PD-L1 in primary lung tumor vs. synchronous metastases, especially brain metastasis (BM), remains unclear. This study assessed the concordance of PD-L1 expression on tumor cells and tumor-infiltrating lymphocytes (TILs) and CD8+ TIL intensity between primary lung tumors and synchronous BMs from 24 NSCLC patients. PD-L1, CD3, and CD8 positivity was determined by immunohistochemistry (IHC). PD-L1 scoring was based on the proportion of tumor cells with membranous expression of PD-L1 and the cutoff values <1%, 1-49%, and ≥50%. CD3 and CD8 positivity in TILs was evaluated semi-quantitatively and the proportion of CD3+/CD8+ TILs was determined. PD-L1 expression on tumor cells and TILs was evaluated in relation to CD3+/CD8+ TIL proportions and the intensity of CD8+ TILs between the paired primary lung and BM tissues. In the primary lung tumors, PD-L1 positivity was observed in 25%, 37.5%, and 37.5% cases for the cutoff values <1%, 1-49%, and ≥50%, respectively. PD-L1 expression on tumor cells was strongly correlated between the paired primary lung and BM tissues, in all cutoff groups. However, PD-L1 expression on TILs and the proportion of CD3+/CD8+ TILs were not strongly correlated in all three groups between the paired primary lung tumors and BMs. The intensity of CD8+ TILs was concordant in only 54.16% of the paired primary lung tumors and BMs. This study showed a high concordance of PD-L1 expression in neoplastic cells between primary NSCLC and synchronous BMs.


Subject(s)
B7-H1 Antigen/immunology , Brain Neoplasms/secondary , CD8-Positive T-Lymphocytes/pathology , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/pathology , Aged , Brain Neoplasms/immunology , CD8-Positive T-Lymphocytes/immunology , Carcinoma, Non-Small-Cell Lung/immunology , Female , Humans , Lung Neoplasms/immunology , Male , Middle Aged , Neoplasms, Multiple Primary , Tumor Microenvironment
11.
World Neurosurg ; 130: e765-e774, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31295602

ABSTRACT

OBJECTIVE: Plurihormonal pituitary adenomas (PPAs) have recently been divided into 2 subtypes: pituitary specific transcription factor 1-positive plurihormonal pituitary adenomas (PIT-1+ PPAs) and plurihormonal adenomas with unusual immunohistochemical combinations (PAwUIC). The purpose of this study was to review patients with PPAs, elucidate their clinicopathologic characteristics, and present the surgical results. METHODS: Records were analyzed for 665 patients who underwent endoscopic endonasal transsphenoidal surgery for pituitary adenomas between 2007 and 2018. Data were reviewed for 27 patients who met the definition of PPAs and delineated regarding clinical, radiologic, pathologic features, and surgical outcomes. RESULTS: Of the 27 patients, 18 had PAwUIC, and 9 patients were diagnosed with PIT-1+ PPAs. Twenty-four patients (88.8%) had macroadenomas, including 6 giant adenomas (≥4 cm) (22.2%). Cavernous sinus invasion was found in 12 patients (44.4%). Pathologic examinations showed high aggressivity in nearly half of the patients. Most patients with PAwUIC (77.8%) had features of nonfunctioning pituitary adenomas, and only 4 had features of hormone-secreting pituitary adenomas. Gross total resection rates were 57.1% for PAwUIC and 77.8% for PIT-1+ PPAs. The remission rate for hormone-secreting pituitary adenomas was 100% in this case series. Mean follow-up was 74.4 ± 33 months (range, 6-121 months) for overall groups. CONCLUSIONS: To our knowledge, this is the first study to describe the clinicopathologic features of newly classified PPAs, which are characterized by aggressive behavior with higher values of percentage of cavernous sinus invasion. Relevant pathologic diagnosis of PPAs is crucial for appropriate management and follow-up.


Subject(s)
Adenoma/diagnostic imaging , Adenoma/surgery , Neurosurgical Procedures/methods , Pituitary Neoplasms/diagnostic imaging , Pituitary Neoplasms/surgery , Adenoma/blood , Adult , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Pituitary Neoplasms/blood , Retrospective Studies , Treatment Outcome
12.
World Neurosurg ; 127: 199-205, 2019 Jul.
Article in English | MEDLINE | ID: mdl-30928576

ABSTRACT

INTRODUCTION: Endovascular treatment is growing in popularity globally as an important treatment option for intracranial aneurysms. Cerebral infection as a complication of endovascular treatment of aneurysms is sufficiently rare that only 6 isolated cerebral abscess cases have been reported thus far. CASE REPORT: In this report, we present 2 cerebral abscesses from 3 institutions, which developed after coil embolization of anterior communicating artery and middle cerebral artery aneurysms. CONCLUSION: This report was written to discuss the possible mechanisms underlying cerebral abscess after endovascular treatment of aneurysms and to suggest potential treatment and prevention methods.


Subject(s)
Brain Abscess/diagnostic imaging , Endovascular Procedures/adverse effects , Intracranial Aneurysm/diagnostic imaging , Intracranial Aneurysm/surgery , Postoperative Complications/diagnostic imaging , Adult , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , Brain Abscess/drug therapy , Brain Abscess/etiology , Endovascular Procedures/trends , Female , Humans , Male , Postoperative Complications/drug therapy , Postoperative Complications/etiology , Treatment Outcome
13.
Turk Neurosurg ; 29(5): 664-670, 2019.
Article in English | MEDLINE | ID: mdl-30649817

ABSTRACT

AIM: To determine whether neuroradiological assessment of skull base and non-skull base meningioma consistency and vascularity can be used to improve the surgical approach. MATERIAL AND METHODS: Forty meningioma cases were split into skull base (n=16) and non-skull (n=24) base groups, and intraoperative surgical reports of observed tumor consistency (stiffness) and vascularity were compared with preoperative neuroradiological magnetic resonance (MR) perfusion and postoperative histopathological analysis of collagen and CD34 levels. RESULTS: The skull base group had significantly higher CD34 levels (p=0.004) than the non-skull base group. Further comparison of CD34 levels also revealed significantly higher CD34 levels (p=0.032) in transitional versus fibroblastic subtypes. Observationbased vascularity scoring did not reveal a significant correlation between tumor grade and relative cerebral blood volume (p=0.604). In contrast, there was a statistically modest, but significant correlation between intraoperative observation-based consistency and Verhoeff-van Gieson collagen scores (rs=0.400). CONCLUSION: Preoperative assessment of consistency and vascularity using MR imaging was ambiguous. Overall, one of the most important limiting factors was the subjective observational assessment of tumor consistency and vascularity by surgical teams.


Subject(s)
Meningeal Neoplasms/pathology , Meningioma/pathology , Skull Base Neoplasms/pathology , Adult , Aged , Antigens, CD34/analysis , Biomarkers, Tumor/analysis , Female , Humans , Magnetic Resonance Imaging , Male , Meningeal Neoplasms/diagnostic imaging , Meningeal Neoplasms/surgery , Meningioma/diagnostic imaging , Meningioma/surgery , Middle Aged , Preoperative Care , Skull Base Neoplasms/diagnostic imaging , Skull Base Neoplasms/surgery
14.
Tumori ; 105(6): 501-508, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31910789

ABSTRACT

PURPOSE: Rapid diagnosis of genetic mutations is important for targeted therapies such as EGFR tyrosine kinase inhibitors. KRAS mutation and ALK rearrangement are also important in determining treatment. The purpose of our study was to evaluate the diagnostic value of 18F-FDG PET to predict KRAS mutation and ALK rearrangement in order to determine the frequency of these genetic markers in our lung adenocarcinoma cases and contribute to forthcoming meta-analysis studies. METHODS: A total of 218 patients with lung adenocarcinoma (EGFR analyzed) who were seen at our clinic between 2012 and 2014 were included in the study. The results of the 18 F-FDG-PET scans for each patient were retrospectively recorded with the associated medical documents. ALK rearrangements were analyzed in 166 of the 218 patients, while 50 of the 218 patients were analyzed for KRAS mutational status. SPSS 15.0 for Windows was used for statistical analysis. RESULTS: FDG avidity was higher in cases with KRAS mutations and ALK rearrangements than those without, but the difference was not significant. ALK rearrangements were more common in younger, female, and nonsmoking patients with lung adenocarcinoma. CONCLUSIONS: The small numbers of KRAS mutations and ALK rearrangements are the limitation of this study for evaluation of diagnostic imaging. The frequency of these genetic alterations was as reported in the literature. We believe that our work will contribute to future meta-analysis.


Subject(s)
Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/metabolism , Anaplastic Lymphoma Kinase/genetics , Gene Rearrangement , Metabolomics , Mutation , Proto-Oncogene Proteins p21(ras)/genetics , Adenocarcinoma of Lung/diagnostic imaging , Aged , Anaplastic Lymphoma Kinase/metabolism , Biomarkers , ErbB Receptors/genetics , Exons , Female , Gene Expression Regulation, Neoplastic , Humans , Male , Metabolomics/methods , Middle Aged , Positron Emission Tomography Computed Tomography , Proto-Oncogene Proteins p21(ras)/metabolism
15.
Balkan Med J ; 36(3): 184-189, 2019 05 10.
Article in English | MEDLINE | ID: mdl-30592196

ABSTRACT

Background: Prognostic significance of the programmed death-ligand-1 status in non-small cell lung carcinoma remains controversial. Aims: To show the programmed death-ligand-1 expression status in patients with non-small cell lung carcinoma and its effect on the prognosis and the relationship with clinicopathologic data. Study Design: Retrospective cross-sectional study. Methods: The study included 208 cases who were diagnosed with NSCLC and who underwent surgical resection between 2001 and 2012. Programmed death-ligand-1 (SP142 clone) was applied to the histological sections acquired from the microarray paraffin blocks with immunohistochemistry. Staining intensity was scored as weak (+, 1), moderate (++, 2), and strong (+++, 3). Percentage (0%-100%) was multiplied by staining intensity (1-2-3) to calculate the H score. Four different cut-off values were used; 1: ≥1% (independent of intensity), 2: ≥5% (independent of intensity), 3: ≥5% moderate/strong staining (except for weak staining), 4: H score ≥30 values were considered positive. In this study, staining a single cell at any intensity was considered positive. Results: Thirty-four out 208 cases (16.3%) had PDL-1 positive staining. PDL-1 expression was observed in patients with non-small cell lung carcinoma independent of the histological type or subtype (range; 0-25%). When the cut-off level was set to ≥5% with moderate and strong staining, the median overall survival was 45 months for the PD-L1 positive group and not reached for the PD-L1 negative group (p-value 0.024). PD-L1 positivity was significantly higher in patients over the age of 60 years and in cases with a tumor diameter of more than 5 cm (p=0.023 and 0.025, respectively). Conclusion: PD-L1 expression is positive in 16.3% of patients with non-small cell lung cancer and may have a negative prognostic value.


Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Programmed Cell Death 1 Receptor/analysis , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/analysis , Biomarkers, Tumor/blood , Carcinoma, Non-Small-Cell Lung/blood , Carcinoma, Non-Small-Cell Lung/pathology , Chi-Square Distribution , Cross-Sectional Studies , Female , Humans , Immunohistochemistry/methods , Male , Middle Aged , Prognosis , Programmed Cell Death 1 Receptor/blood , Survival Analysis
16.
Semin Thorac Cardiovasc Surg ; 30(3): 369-378, 2018.
Article in English | MEDLINE | ID: mdl-30031945

ABSTRACT

We described disease characteristics, management and outcome of a group of Behçet's syndrome (BS) patients who underwent pulmonary lobectomy, segmentectomy or various pleura interventions for complications due to pulmonary artery or descending aorta involvement. There were 9 patients with BS (8 M/1 F; mean age: 24.8 ±â€¯7.5 and mean disease duration: 4.3 ±â€¯3.8 years) who underwent lung surgery from 2000 to 2017. Their medical files including operation details and radiological and pathological studies were reviewed retrospectively. Lobectomy was done in 6 patients, decortications and pleura interventions in the remaining 3. The reason for the surgical procedures were giant pulmonary arterial aneurysms refractory to the medical treatment (n = 4), pneumothorax due to large cavities (n = 2), pleural effusions refractory to the medical treatment (n = 1), a bronchopleural fistula after embolization (n = 1) and bronchiectasis (n = 1). All patients received medical treatment with cyclophosphamide and corticosteroids before the surgical interventions. The histological examination in patients with pseudo-aneurysms showed destruction of medial elastic fibers, inflammatory cell infiltration of adventitial tissues and penetration into the adjacent bronchi with adherent thrombi. Two patients died: one due to Budd-Chiari syndrome 1 year after the surgery, another because of a massive hemoptysis 3 months after lobectomy. The remaining 7 patients are still alive with a median follow-up of 8 years (inter-quartile range [IQR]: 4-11). Lobectomies in BS patients with giant pulmonary aneurysms refractory to medical treatment can be done with favorable outcome. Also, complications such as large cavities causing pneumothorax, refractory pleural effusions, bronchiectasis, and embolization complications can be managed effectively with surgical interventions.


Subject(s)
Aneurysm/surgery , Behcet Syndrome/complications , Lung Diseases/surgery , Pneumonectomy , Pulmonary Artery/surgery , Adolescent , Adult , Aneurysm/diagnosis , Aneurysm/etiology , Aneurysm/mortality , Behcet Syndrome/diagnosis , Behcet Syndrome/drug therapy , Behcet Syndrome/mortality , Biopsy , Child , Female , Humans , Immunosuppressive Agents/therapeutic use , Lung Diseases/diagnosis , Lung Diseases/etiology , Lung Diseases/mortality , Male , Pneumonectomy/adverse effects , Pneumonectomy/mortality , Pulmonary Artery/pathology , Retrospective Studies , Risk Factors , Time Factors , Tomography, X-Ray Computed , Treatment Outcome , Young Adult
17.
Br J Neurosurg ; 32(4): 436-441, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29792345

ABSTRACT

OBJECT: To analyse the clinical, imaging and histopathological data of patients who were diagnosed to have Dysembrioplastic Neuroepithelial Tumour (DNET) and underwent surgery between 1995-2015. MATERIALS AND METHODS: Age at seizure onset, age at surgery, gender, disease duration, seizure outcome of 44 patients were analysed together with Magnetic Resonance Imaging (MRI) of 21 patients. MRI types were classified as type 1 (cystic/polycystic-like, well-delineated, strongly hypointense T1), type 2 (nodularlike,heterogeneous), type 3 (dysplastic-like, iso/hyposignal T1, poor delineation, gray-white matter blurring). RESULTS: Histopathological classification revealed simple form in 19, complex in 14 and non-specific in 11 patients. Lobar distribution of the lesions was as follows: 21 Temporal (47.7%), 12 parietal (27.3%), 8 frontal (18.2%) and 3 occipital (6.8%). Type 1 MRI was observed in 10, type 2 was in 7, and type 3 in 4 patients on radiological evaluation. All cases with type 1 MRI corresponded to either simple or complex forms and all cases with type 3 MRI corresponded to nonspecific form. The histopathological distribution of cases with type 2 MRI was 4 as non-specific, 2 as simple, 1 as complex. There was no significant difference in the age of onset, age at operation and duration of epilepsy between the patients with different MRI subtypes. The majority of patients (N:36) had Engel I outcome (81,8%). In groups with Engel II and III outcome, duration of epilepsy was significantly higher (p:0,014) and simple form of DNET has significantly higher seizure freedom after surgery compared to complex and nonspecific forms of DNET (p:0,002). CONCLUSION: Patients with DNET constitute a group with favorable outcomes after epilepsy surgery especially with early referral to surgery. Longer duration of epilepsy was associated with worse seizure outcome for DNET patients. There was significant correlation between radiological and histopathological types of DNET especially in type 1 and 3.


Subject(s)
Central Nervous System Neoplasms/surgery , Neoplasms, Neuroepithelial/surgery , Adolescent , Adult , Age of Onset , Central Nervous System Neoplasms/diagnostic imaging , Central Nervous System Neoplasms/pathology , Child , Electroencephalography , Epilepsy/etiology , Female , Humans , Magnetic Resonance Imaging , Male , Neoplasms, Neuroepithelial/diagnostic imaging , Neoplasms, Neuroepithelial/pathology , Seizures/etiology , Sex Factors , Treatment Outcome , Young Adult
18.
World Neurosurg ; 116: e801-e805, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29803067

ABSTRACT

BACKGROUND: Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy. Focal cortical dysplasia is the most common dual pathology found in association with the hippocampal sclerosis. In this study, the effect of dual pathology on freedom from seizure was sought in patients with TLE. METHODS: This study performed a retrospective analysis of patients with TLE who underwent surgery between 2010 and 2017. Histopathologic analysis was performed on patients with and without dual pathology in the temporal neocortex. Seizure outcomes were compared. RESULTS: A total of 54 patients with TLE were included. The rate of overall favorable seizure outcome was found to be 96.3%. In 53.7%, dual pathology was present in the temporal cortices in addition to the hippocampal sclerosis. Patients without dual pathology showed significantly greater freedom from seizure (P = 0.02). CONCLUSIONS: Patients without dual pathology had a significantly higher seizure-free rate after anterior temporal resection than patients with dual pathology. Resection of the temporal cortex in addition to mesial temporal structures seems to be reasonable for better seizure outcome.


Subject(s)
Epilepsy, Temporal Lobe/diagnostic imaging , Malformations of Cortical Development/diagnostic imaging , Neocortex/pathology , Seizures/diagnostic imaging , Adult , Cohort Studies , Epilepsy, Temporal Lobe/epidemiology , Epilepsy, Temporal Lobe/surgery , Female , Follow-Up Studies , Humans , Male , Malformations of Cortical Development/epidemiology , Malformations of Cortical Development/surgery , Retrospective Studies , Seizures/epidemiology , Seizures/surgery , Young Adult
20.
BMC Cancer ; 18(1): 269, 2018 03 09.
Article in English | MEDLINE | ID: mdl-29523116

ABSTRACT

BACKGROUND: The introduction of targeted treatments for subsets of non-small cell lung cancer (NSCLC) has highlighted the importance of accurate molecular diagnosis to determine if an actionable genetic alteration is present. Few data are available for Central and Eastern Europe (CEE) on mutation rates, testing rates, and compliance with testing guidelines. METHODS: A questionnaire about molecular testing and NSCLC management was distributed to relevant specialists in nine CEE countries, and pathologists were asked to provide the results of EGFR and ALK testing over a 1-year period. RESULTS: A very high proportion of lung cancer cases are confirmed histologically/cytologically (75-100%), and molecular testing of NSCLC samples has been established in all evaluated CEE countries in 2014. Most countries follow national or international guidelines on which patients to test for EGFR mutations and ALK rearrangements. In most centers at that time, testing was undertaken on request of the clinician rather than on the preferred reflex basis. Immunohistochemistry, followed by fluorescent in situ hybridization confirmation of positive cases, has been widely adopted for ALK testing in the region. Limited reimbursement is a significant barrier to molecular testing in the region and a disincentive to reflex testing. Multidisciplinary tumor boards are established in most of the countries and centers, with 75-100% of cases being discussed at a multidisciplinary tumor board at specialized centers. CONCLUSIONS: Molecular testing is established throughout the CEE region, but improved and unbiased reimbursement remains a major challenge for the future. Increasing the number of patients reviewed by multidisciplinary boards outside of major centers and access to targeted therapy based on the result of molecular testing are other major challenges.


Subject(s)
Biomarkers, Tumor/genetics , Carcinoma, Non-Small-Cell Lung/diagnosis , Gene Rearrangement , Genetic Testing/methods , Lung Neoplasms/diagnosis , Mutation , Carcinoma, Non-Small-Cell Lung/epidemiology , Carcinoma, Non-Small-Cell Lung/genetics , Europe/epidemiology , Humans , Lung Neoplasms/epidemiology , Lung Neoplasms/genetics , Prognosis
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