Impression Cytologic Evaluation of the Conjunctiva in Patients Treated with Topical 1% Voriconazole

Objectives: The aim of the present study was to evaluate any conjunctival metaplastic changes by impression cytology in patients who underwent topical 1% voriconazole treatment for severe fungal keratitis. Materials and Methods: The study was conducted at Ege University Faculty of Medicine, Departments of Ophthalmology and Medical Pathology. Patients who were treated with 1% topical voriconazole for fungal keratitis for at least 3 months were included. The used topical voriconazole treatment was initiated as one drop every hour and was tapered according to clinical improvement in all patients. Treatment was continued 4 times a day for at least 3 months. Impression cytology samples were collected at least 3 months after cessation of topical voriconazole from the affected eyes and from the fellow eyes as a control group. Collected specimens were transferred to the pathology department for evaluation and grading (Nelson's grading system). Results: The mean age of the patients was 57.68±17.32 years (range, 22-87 years). The impression cytology grade of the inferior bulbar conjunctiva was 1.73±0.77 (range, 0-3) in the study group and 1.19±0.98 (range, 0-3) in the control group (p=0.03). The impression cytology grade of the temporal bulbar conjunctiva was 1.69±0.73 (range, 0-3) in the study group and 1.15±0.88 (range, 0-3) in the control group (p=0.02). The impression cytology grades of the nasal and superior bulbar conjunctiva did not differ statistically (p values 0.13 and 0.17, respectively). Conclusion: Topical voriconazole is an effective broad-spectrum antifungal drug, but it induces conjunctival squamous metaplasia. Clinicians should be aware of this possible side effect of topical voriconazole and should carefully evaluate the conjunctiva of treated patients at each visit to detect possible metaplastic changes.

Real-Time PCR Detection of Candida Species in Biopsy Samples from Non-Smokers with Oral Dysplasia and Oral Squamous Cell Cancer: A Retrospective Archive Study.

The impact of Candida sp. in the development of oral cancer remains uncertain and requires sensitive analytical approaches for clarification. Given the invasive capabilities of these microorganisms in penetrating and invading host tissues through hyphal invasion, this study sought to detect the presence of five Candida sp. in oral biopsy tissue samples from non-smoker patients. Samples were obtained from patients at varying stages of oral carcinogenesis, including dysplasia, carcinoma in situ, OSCC, and histologically benign lesions, and analyzed using Real-Time PCR. Oral tissue samples from 80 patients (46 males and 34 females) were included. Significantly higher C. albicans presence was detected in the mild/moderate dysplasia group compared to the healthy (p = 0.001), carcinoma in situ (p = 0.031) and OSCC groups (p = 0.000). Similarly, C. tropicalis carriage was higher in tissues with mild/moderate dysplasia compared to healthy (p = 0.004) and carcinoma in situ (p = 0.019). Our results showed a significant increase in the presence of C. albicans and C. tropicalis within the mild/moderate dysplasia group compared to other cohorts. Coexistence of these two microorganisms was observed, suggesting a potential transition from a commensal state to an opportunistic pathogen, which could be particularly linked to the onset of oral neoplasia.

Prognostic impact of mitosis and necrosis in non-mucinous lung adenocarcinomas and correlation with IASLC grading system.

BACKGROUND: In 2020, the International Lung Cancer Study Group (IASLC) Pathology Committee established a grading system for non-mucinous primary lung adenocarcinomas. This grading system is based on whether areas of high-grade patterns are present in more than 20% of the tumor. Parameters, such as necrosis, mitotic activity, lymphovascular invasion (LVI) and spread through air spaces (STAS), are excluded from evaluating the grading system. METHODS: A total of 217 patients' lung resection materials for primary lung adenocarcinoma were re-reviewed using the IASLC grading system. Necrosis, mitotic activity, LVI status and STAS were also evaluated in the resection materials, aiming to demonstrate the relationship between these histopathological features and clinical outcome data. RESULTS: At all stages, overall survival (OS) and recurrence-free survival (RFS) were related to grade (p=0.011 and 0.024, respectively). Additionally, patients with necrosis were associated with worse OS and RFS (p=0.002 and 0.048, respectively). When grade 2 and 3 tumors were analyzed individually, a significant relationship was found between necrosis and OS in grade 3 tumors (p=0.002). Patients with a high mitotic count (≥10/10 high-power fields) had significantly worse OS (p=0.046). The prevalence of LVI and STAS increased with grade; however, their prognostic significance has not been demonstrated. CONCLUSIONS: The new grading system provides a highly efficient prognostic classification for survival. Necrosis and high mitotic count are important prognostic parameters for survival. Additionally, necrosis is a stage-independent prognostic factor for OS in grade 3 tumors, although no effect on prognosis can be demonstrated in grade 2 tumors.

Salivary Lipids of Patients with Non-Small Cell Lung Cancer Show Perturbation with Respect to Plasma.

A comprehensive lipid profile was analyzed in patients with non-small cell lung cancer (NSCLC) using nanoflow ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. This study investigated 297 and 202 lipids in saliva and plasma samples, respectively, comparing NSCLC patients to healthy controls. Lipids with significant changes (>2-fold, p < 0.05) were further analyzed in each sample type. Both saliva and plasma exhibited similar lipid alteration patterns in NSCLC, but saliva showed more pronounced changes. Total triglycerides (TGs) increased (>2-3-fold) in plasma and saliva samples. Three specific TGs (50:2, 52:5, and 54:6) were significantly increased in NSCLC for both sample types. A common ceramide species (d18:1/24:0) and phosphatidylinositol 38:4 decreased in both plasma and saliva by approximately two-fold. Phosphatidylserine 36:1 was selectively detected in saliva and showed a subsequent decrease, making it a potential biomarker for predicting lung cancer. We identified 27 salivary and 10 plasma lipids as candidate markers for NSCLC through statistical evaluations. Moreover, this study highlights the potential of saliva in understanding changes in lipid metabolism associated with NSCLC.

The effect of P53 expression and smoking/alcohol in P16(+) and P16(-) oropharyngeal carcinoma and risk classification: the Turkish Society of Radiation Oncology Head & Neck Study Group 01-002.

OBJECTIVE: The aim of this study is to categorize the risk groups of patients with oropharyngeal carcinoma (OPC) according to p16 and p53 status, smoking/alcohol consumption history, and other prognostic factors. STUDY DESIGN: The immunostaining of p16 and p53 of 290 patients was retrospectively evaluated. The history of smoking/alcohol consumption of each patient was noted. p16 and p53 staining patterns were reviewed. The results were compared with demographic findings and prognostic factors. Risk groups have been classified for the p16 status of patients. RESULTS: The median follow-up was 47 months (range 6-240). Five-year disease-free survival (DFS) rates for patients with p16 (+) and (-) were 76% and 36%, and overall survival rates were 83% vs 40%, respectively (HR = 0.34 [0.21-0.57], P < .0001), HR = 0.22 [0.12-0.40] P < .0001, respectively). p16(-), p53(+), heavy smoking/alcohol consumption, performance status; advanced T and N stages in patients with p16(-), and continuing smoking/alcohol consumption after treatment were found to be unfavorable risk factors. Five-year overall survival rates were 95%, 78%, and 36% for low, intermediate, and high-risk groups, respectively. CONCLUSIONS: The results of our study have shown that p16 negativity in patients with oropharyngeal cancer was found to be an important prognostic factor, especially for those with lower p53 expression and not smoking/consuming alcohol.

Prognostic and predictive role of liquid biopsy in lung cancer patients.

Introduction: Lung cancer (LC) is a leading cause of cancer-related mortality worldwide. Approximately 80% of LC cases are of the non-small cell lung cancer (NSCLC) type, and approximately two-thirds of these cases are diagnosed in advanced stages. Only systemic treatment methods can be applied to patients in the advanced stages when there is no chance of surgical treatment. Identification of mutations that cause LC is of vital importance in determining appropriate treatment methods. New noninvasive methods are needed to repeat and monitor these molecular analyses. In this regard, liquid biopsy (LB) is the most promising method. This study aimed to determine the effectiveness of LB in detecting EGFR executive gene mutations that cause LC. Methods: One hundred forty-six patients in stages IIIB and IV diagnosed with non-squamous cell non-small cell LC were included. Liquid biopsy was performed as a routine procedure in cases where no mutation was detected in solid tissue or in cases with progression after targeted therapy. Liquid biopsy samples were also obtained for the second time from 10 patients who showed progression under the applied treatment. Mutation analyses were performed using the Cobas® EGFR Test, a real-time PCR test designed to detect mutations in exons 18, 20, and 21 and changes in exon 19 of the EGFR gene. Results: Mutation positivity in paraffin blocks was 21.9%, whereas it was 32.2% in LB. Solids and LB were compatible in 16 patients. Additionally, while no mutation was found in solid tissue in the evaluation of 27 cases, it was detected in LB. It has been observed that new mutations can be detected not only at the time of diagnosis, but also in LB samples taken during the follow-up period, leading to the determination of targeted therapy. Discussion: The results showed that "liquid biopsy" is a successful and alternative non-invasive method for detecting cancer-causing executive mutations, given the limitations of conventional biopsies.

The role of the WNT signaling pathway in the maxillary sinus squamous cell carcinoma.

Paranasal sinus tumors are a rare type of cancer. Most of these tumors are of epithelial origin and 80% of them are maxillary sinus squamous cell carcinoma. The WNT signaling pathway is an essential embryonic regulatory pathway known to play an important role in many cancers, including head and neck cancers. However, the effect of this pathway in maxillary sinus tumors has not been studied before. The aim of the study was to determine the changes in the regulatory genes of the WNT signaling pathway in maxillary sinus tumors. For this purpose, total RNA was isolated from the pathological preparations of 85 patients who had previously been operated on for squamous cell maxillary sinus tumor, and gene expression changes were evaluated by real-time RT-qPCR. The interactions among proteins encoded by genes, whose expression levels were found to be decreased and increased, were determined by protein-protein interaction (PPI) network analysis using string database, and signaling pathways that they are involved in were examined by Reactome database. A significant decrease in the expression of 28 genes compared to the control (fold change < 2.00 and p-value < 0.05) and a significant increase in the expression of 23 genes (fold change < 2.00 and p-value < 0.05) were detected. According to in silico analysis results, Signal Transduction (REACTOME:R-HSA-162582) and Signaling by WNT (REACTOME:R-HSA-195721) pathways were determined as most regulated pathways and FZD4-LRP5 and BCL9-CTNNB1 were determined as the strongest interactions. The current study contributes to illuminating the genetic regulation of maxillary sinus carcinoma in which genetic knowledge is limited. Our findings take attention to the dysregulations of the WNT signaling pathway that may support maxillary sinus carcinogenesis. The results will pave the way for further studies that investigate the therapy target potential of the WNT signaling pathway in this rare cancer.

Multi-parametric evaluation of ocular surface disorders during healing process of viral conjunctivitis.

Purpose To evaluate the ocular surface properties in epidemic keratoconjunctivitis (EKC) patients during healing process, and to detect the damage on conjunctival goblet cells. Methods Bilateral EKC patients confirmed with polymerase chain reaction (PCR) testing were included. Firstly (Group 1) and secondly (Group 2) affected eyes were compared. Ocular surface parameters were performed at the first visit and first month. Results The study included 34 eyes of 17 patients. The mean age was 44.54 ± 16.80 (21-70) years (FM/M 20/14). The ocular findings in Groups 1 and 2 were not significant. For Groups 1 and 2, OSDI was 53.53 ± 23.01 and 35.90 ± 22.19 (p 0.03), tear osmolarity was 309.12 ± 19.38 and 297.47 ± 8.27 mOsm/µL (p 0.029), OSSS was 1.00 ± 0.79 and 0.18 ± 0.39 (p 0.001), T-BUT was 3.59 ± 2.29 and 6.00 ± 1.83 s (p 0.002), and Schirmer's 1 test was 10.94 ± 8.42 and 16.76 ± 9.05 mm (p 0.061), respectively. In Groups 1 and 2, the IC was Grade (G) 0 in 23.5% and 17.6%, G1 in 35.3% and 41.2%, and G2 in 41.2% and 41.2%, respectively. The ocular surface properties were worse in Group 1 than Group 2, and the difference was significant except for Schirmer's 1 test and IC. Conclusions Dry eye disorder is a complication of EKC and may cause a significant decrease in quality of life.

Comparison of PD-L1, EGFR, ALK, and ROS1 Status Between Surgical Samples and Cytological Samples in Non-Small Cell Lung Carcinoma.

BACKGROUND: The expression levels of Programmed death ligand-1 (PD-L1), epidermal growth factor receptor (EGFR), anaplastic lymphoma tyrosine kinase gene (ALK), and proto-oncogene tyrosineprotein kinase 1 ROS (ROS1) are important for targeted treatment selection in advanced lung cancer. Most patients with lung cancer are diagnosed at an advanced stage and have no chance of surgery. For this reason, the accuracy and reliability of cytology samples for detecting those markers is important in patients whose histological sampling cannot be performed. AIMS: To test the compatibility of histological and cytological sample analysis results of EGFR, ALK, ROS1 and PDL-1 in patients with NSCLC and to determine the adequacy of cytological analysis for PD-L1 expression. STUDY DESIGN: Retrospective cross-sectional study. METHODS: The results of 231 patients whose PD-L1 was studied in 2018 were analyzed retrospectively. We excluded 11 inappropriate samples. A total of 220 samples were distributed as follows; 66 (30.0%) cytology specimens, 64 (29.1%) small histology biopsies, and 90 (40.9%) surgical biopsies. EGFR, ALK, ROS1 and PD-L1 analysis were performed in 139, 134, 116, and 220 patients, respectively. Samples containing >400 cells were considered suitable for molecular cytological study. RESULTS: A total of 154 (70.0%) histological (surgical biopsy) and 66 (30.0%) cytology samples were analyzed. There was no statistically significant difference between histological and cytological samples in terms of cellular adequacy for all molecular markers [EGFR: 93.7% and 90.9% (P = .556), ALK: 97.8% and 95.3% (P = .436) , ROS1: 89.9% vs. 91.9% (P = .729), PD-L1: 95.5% vs. 92.4% (P = .364)]. There was no statistically significant difference in the expression positivity rates of all biomarkers between histological and cytological samples [EGFR: 9.0% vs. 2.5% (P = .018), ALK: 7.9% vs. 9.8% (P = .719), ROS1 : 1.4% vs. 2.9% (P = .591), PD-L1: 54.4% vs. 41.0% (P = .078)]. CONCLUSION: The cellular adequacy of cytology specimens for molecular testing in patients with NSCLC is satisfactory. This study shows that EGFR, ALK, ROS-1 and PDL-1 expression rates in cytological samples are not statistically different from histological samples.

Multi-parametric evaluation of autologous cultivated Limbal epithelial cell transplantation outcomes of Limbal stem cell deficiency due to chemical burn.

BACKGROUND: The sparsity of established tools for the grading of limbal stem cell deficiency hinder objective assessments of the clinical outcome of cultivated limbal epithelial cell transplantation. To advance towards the development of standards for the comparison of the outcomes of these bio-surgical protocols we have now applied a battery of recognized objective and patient-declared subjective outcome criteria to the autologous modality of cultivated limbal epithelial cell transplantation. METHODS: The prospective study involved ten patients (M/F = 9/1; mean age = 42.1 years) displaying overt unilateral limbal stem cell deficiency complying with the inclusion criteria described in Methods. Limbal biopsies were obtained from the contralateral eye and their outgrowths after 2-week cultures were transplanted on the affected eye after pannus resection. Outcomes were followed up for 12 months. The objective tests were scores for best-corrected visual acuity (BCVA); using the LogMAR scale, a multiparametric ocular surface score (OSS), and the Schirmer's test. Subjective scores were based on patient answers to a) perception of visual improvement/pain; b) the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ 25); and c) the 12-item Ocular Surface Disease Index Questionnaire (OSDI). All procedures were performed under good manufacture practices using solely xeno-free reagents. In all cases, a single biopsy was divided into two pieces and they were expanded in order to prevent outgrowth failure. In 5 patients, both biopsies generated healthy culture sheet. In those cases the lesser outgrowth were used for immune-histological characterization. RESULTS: The experimental parallel outgrowth samples showed a similar percent of p63α+ cells. PreOp and 12-month PostOp BCVAs and OSSs were, respectively, 1.15 ± 0.70; 0.21 ± 0.13 and 7.40 ± 2.01; 2,30 ± 1.30, (p < 0.05). Patient's responses to all three question sets except ocular pain were consistent with significant improvement (p < 0.05). CONCLUSION: Objective clinical metrics demonstrate that in patients with limbal stem cell deficiency, cultivated limbal epithelial cell transplantation improves vision and ocular surface health and subjective visual perceptions.

Concordance in molecular genetic analysis of tumour tissue, plasma, and exhaled breath condensate samples from lung cancer patients.

AIM: Lung adenocarcinoma is characterized by poor prognosis and short survival rates. Therefore, tools to identify the tumoural molecular structure and guide effective diagnosis and therapy decisions are essential. Surgical biopsies are highly invasive and not conducive for patient follow-up. To better understand disease prognosis, novel non-invasive analytic methods are needed. The aim of the present study is to identify the genetic mutations in formalin-fixed paraffin-embedded (FFPE) tissue, plasma, and exhaled breath condensate (EBC) samples by next-generation sequencing and evaluate their utility in the diagnosis and follow-up of patients with lung adenocarcinoma. METHOD: FFPE, plasma, and EBC samples were collected from 12 lung adenocarcinoma patients before treatment. DNA was extracted from the specimens using an Invitrogen PureLink Genomic DNA Kit according to the manufacturer's instructions. Amplicon-based sequencing was performed using Ion AmpliSeq Colon and Lung Cancer Research Panel v2. RESULTS: Genetic alterations were detected in all FFPE, plasma, and EBC specimens. The mutations in PIK3CA, MET, PTEN, SMAD4, and FGFR2 genes were highly correlated in six patients. Somatic and novel mutations detected in tissue and EBC samples were highly correlated in one additional patient. The EGFR p.L858R and KRAS p.G12C driver mutations were found in both the FFPE tissue specimens and the corresponding EBC samples of the lung adenocarcinoma patients. CONCLUSION: The driver mutations were detected in EBC samples from lung adenocarcinoma patients. The analysis of EBC samples represents a promising non-invasive method to detect mutations in lung cancer and guide diagnosis and follow-up.

The effect of topical voriconazole on conjunctiva in rats as revealed by histopathology and immunohistochemistry.

The aim of this study was to evaluate the effects of topical voriconazole with histopathological and immunohistochemical analysis of the conjunctiva in rats. Twenty-eight Sprague Dawley rats were divided into four groups as two study (S1, S2) and two control (C1, C2). Voriconazole was instilled four times daily to S1, S2 rats. Physiologic saline (0.9%) was instilled four times daily in C1 and C2 rats. S1 and C1 were followed in a dark room; S2 and C2 were held in a room with sunlight. Impression cytology was performed at 0, 15, 30, 45 and 60th d after instillations. After 2 months of treatment conjunctival tissue was removed for histological and immunohistochemical analysis. In impression cytology evaluation, there was no difference between S1 and S2. At 60 d the difference between S1 and C1 was significant. In other comparisons, there was no difference between S1 and C1, C2. The scores of S2 was higher than C1 and C2 for all comparisons except 15th day scores of S2 and C2. In study groups, epithelial and gland degeneration were higher in S2, but inflammation scores were similar. The comparison of immunreactivity of ERK, TGFß and E-cadherin were different in the study groups than the control groups for all comparisons. In conclusion, voriconazole has side effects due to phototoxicity including squamous cell carcinoma. Clinicians should particularly be careful with the long-term use of topical voriconazole and should follow-up patients strictly in terms of ocular surface alterations.

Brush Biopsy Sample Quality: Preliminary Investigation of a Metal Brush Prototype

Objective: To qualitatively investigate whether a prototype brush composed of metal bristles collects oral epithelial cells effectively for cytological evaluation of oral mucosal lesions. Material and Methods: Twenty patients with suspicious oral mucosal lesions were enrolled. Patients were asked to gargle with saline and to deposit the oral rinse into specimen cup. Then, oral mucosal cell samples were collected using a metal oral brush, via sweeping motion. Punch biopsy was performed for histological examination. All samples were evaluated with liquid based cytology (LBC) according to the cellularity, the depth of the epithelial layer, cellular integrity by an oral pathologist. Results: Oral rinse provided samples with 100% cellular integrity and cellularity, mostly from the intermediary layers. With metal brush, both inadequate cellularity and cellular integrity was observed in 25% of the cases. Cellular integrity was adequate in 65%, cellularity was adequate in 45% of the lesions. Samples were dominantly from the intermediary layers, but in one case, metal brush collected cells from the parabasal layer. Conclusion: The narrow spiral pitch and width of metal bristles may have resisted to release the cellular samples collected. With adjustment of the spiral pitch and diameter of metal brush bristles, its' efficacy could be enhanced.

Limbal Stem Cell Deficiency and Treatment with Stem Cell Transplantation.

The cornea is the outermost tissue of the eye and it must be transparent for the maintenance of good visual function. The superficial epithelium of the cornea, which is renewed continuously by corneal stem cells, plays a critical role in the permanence of this transparency. These stem cells are localized at the cornea-conjunctival transition zone, referred to as the limbus. When this zone is affected/destroyed, limbal stem cell deficiency ensues. Loss of limbal stem cell function allows colonization of the corneal surface by conjunctival epithelium. Over 6 million people worldwide are affected by corneal blindness, and limbal stem cell deficiency is one of the main causes. Fortunately, it is becoming possible to recover vision by autologous transplantation of limbal cells obtained from the contralateral eye in unilateral cases. Due to the potential risks to the donor eye, only a small amount of tissue can be obtained, in which only 1-2% of the limbal epithelial cells are actually limbal stem cells. Vigorous attempts are being made to expand limbal stem cells in culture to preserve or even enrich the stem cell population. Ex vivo expanded limbal stem cell treatment in limbal stem cell deficiency was first reported in 1997. In the 20 years since, various protocols have been developed for the cultivation of limbal epithelial cells. It is still not clear which method promotes effective stem cell viability and this remains a subject of ongoing research. The most preferred technique for limbal cell culture is the explant culture model. In this approach, a small donor eye limbal biopsy is placed as an explant onto a biocompatible substrate (preferably human amniotic membrane) for expansion. The outgrowth (cultivated limbal epithelial cells) is then surgically transferred to the recipient eye. Due to changing regulations concerning cell-based therapy, the implementation of cultivated limbal epithelial transplantation in accordance with Good Laboratory Practice using xenobiotic-free systems is becoming widely accepted both in Turkey and worldwide.

The importance of EZH2 and MOC-31 expression in the differential diagnosis of benign and malignant effusions.

BACKGROUND: All malignant tumors may spread throughout the pleural, peritoneal, and pericardial cavities. The presence of tumor cells in serosal fluid is a poor prognostic indicator. It may be difficult to differentiate nuclear atypia of mesothelial cells due to injury of serosal surfaces from mesothelioma or malignant epithelial tumor cells. Epithelial and mesothelial immunohistochemical markers can be used in such conditions. The aim of this study was to evaluate the expression of two immunohistochemical markers (MOC-31 and EZH2) in serosal effusions. METHODS: The study included a total of 142 patients diagnosed with benign or malignant cytology between January 2012 and April 2014. MOC-31 and EZH2 were applied to the cell blocks of 53 patients with benign cytology and 89 patients with malignant cytology determined based on the clinical, radiological data, histopathology diagnosis, and clinical follow-up in the absence of any surgical material of the patient in the hospital archive system. RESULTS: None of the benign cases showed MOC-31 and EZH2 expression, although these markers were positive in 96 and 93% respectively of the malignant cases. CONCLUSION: In conclusion, it could be considered cost-effective to use a double immunohistochemical antibody kit for these two markers, MOC-31 membranous and EZH2 nuclear staining, in the diagnosis of malignant effusions. Diagn. Cytopathol. 2017;45:118-124. © 2016 Wiley Periodicals, Inc.

The Role of Microaspiration in the Pathogenesis of Gastroesophageal Reflux-related Chronic Cough.

BACKGROUND/AIMS: Gastroesophageal reflux disease (GERD) is one of the main causes of chronic cough. We evaluated the role of microaspiration in the pathogenesis of reflux-related cough by determining the amount of lipid-laden macrophages (LLMs) in bronchoalveolar lavage (BAL) specimens. METHODS: A total of 161 cases of chronic cough were evaluated, and 36 patients (average age 48.2 years) were recruited for this single center prospective study. Patients with a history of smoking, angiotensin converting enzyme inhibitor usage, any abnormality on pulmonary function tests, abnormal chest X-rays, occupational or environmental exposures, or upper airway cough syndrome were excluded. GERD was evaluated by 24-hour esophageal impedance-pH monitoring. BAL specimens for LLM determination were obtained from 34 patients by flexible bronchoscopy. RESULTS: Patients with pathological intra-esophageal reflux according to multichannel intraluminal impedance and pH monitoring had higher LLM positivity in BAL specimens than patients without pathological reflux (8/14 in reflux positive group vs 1/22 in reflux negative group; P = 0.004). The BAL cell distribution was not different between the 2 groups (P = 0.574 for macrophages, P = 0.348 for lymphocytes, P = 0.873 for neutrophils and P = 0.450 for eosinophils). CONCLUSIONS: Our results confirm the role of the microaspiration of refluxate in the pathogenetic mechanism of chronic cough. While bronchoscopy is indicated in patients with chronic cough, in addition to the routine airway evaluation, BAL and LLM detection should be performed. LLM can be used to diagnose aspiration in reflux-related chronic cough. Future studies are needed to evaluate the response to anti-reflux medications or surgery in patients with LLM positivity.

The role of apelin in the assessment of response to chemotherapyand prognosis in stage 4 nonsmall cell lung cancer.

BACKGROUND/AIM: Prediction of response to chemotherapy and prognosis bears clinical significance in patients with lung cancer. The aim of the study was to examine the association between apelin expression in tumor tissues and overall survival, progression-free survival, chemoresistance, and treatment response in stage 4 nonsmall cell lung cancer (NSCLC) patients undergoing chemotherapy. MATERIALS AND METHODS: A total of 81 patients who received chemotherapy due to a biopsy-documented diagnosis of NSCLC between 2004 and 2011 were retrospectively studied. Bronchoscopic biopsy samples were examined immunohistochemically. RESULTS: Of the overall study population (n = 81), the mean age was 59.0 ± 9.2 years; 83% (n = 67) were male and 17% (n = 14) were female. All patients received chemotherapy. A total of 30 patients (37%) had no apelin positivity, while 21 (30%) had 1 +, 20 (25%) had 2 +, and 10 (12%) had 3 + apelin positivity. We detected no association between apelin positivity and overall survival, 6-month survival, or 1-year survival rates (P = 0.05, 0.74, and 0.63). Patients with apelin expression as compared to those without it had shorter overall survival (P = 0.05). CONCLUSION: Our results suggest that apelin, an angiogenic factor, does not seem to provide significant prognostic information in this patient group.

Conjunctival Biopsy as a First Choice to Confirm a Diagnosis of Sarcoidosis.

BACKGROUND: Sarcoidosis is a granulomatous systemic disease of unknown aetiology. The diagnosis needs histological confirmation of the presence of non-caseating granulomata. One option is a conjunctival biopsy. The aims of this study were to evaluate conjunctival biopsy for the diagnosis of sarcoidosis with respect to its sensitivity and to assess its cost effectiveness by comparison with other histopathological diagnostic procedures. METHODS: Patients were identified from the database of the Interstitial Lung Disease Clinic (ILDC) of the Chest Department of Ege University Hospital from May 2008 to June 2014.  The patients who had biopsy procedures performed for the definitive diagnosis of sarcoidosis were assessed. Their diagnostic procedures and the cost of procedures were recorded. The cost per positive result for each procedure was calculated.  Results: In total, 280 patients were followed up with a diagnosis of sarcoidosis, of whom 174 had histological confirmation; these constitute the study population. There were 127 females and 47 males with a median age of 46 years (range 14-78 years). Forty three patients had conjunctival biopsy and we could establish a diagnosis in 54% of these by means of conjunctival biopsy. Moreover, we showed that this biopsy can provide positive result for sarcoidosis patients who lack abnormal eye findings. Additionally, it is cost effective approach and without complications. CONCLUSION: This study re-asserts the value of  conjunctival biopsy, which was described in the past but is not commonly used nowadays. In the presence of suggestive clinic and radiologic findings, we recommend conjunctival biopsy as the first choice for the histopathological confirmation of sarcoidosis.

Cystic fluid chromogranin A levels in different pancreatic cystic lesions.

BACKGROUND/AIMS: Pancreatic cystic lesions have a broad spectrum of differential diagnosis. There is an ongoing demand to identify specific and sensitive cystic fluid markers for the differential diagnosis of pancreatic cysts. We aimed to evaluate the diagnostic value of cystic fluid chromogranin A (CgA) in the differential diagnosis of pancreatic cysts. MATERIALS AND METHODS: Patients who underwent endoscopic ultrasound (EUS)-guided aspiration for pancreatic cysts were included in the study. Cytopathological analysis and biochemical analysis, including cystic fluid carcinoembryonic antigen (CEA), amylase, Ca 19-9, and CgA, were performed. RESULTS: Fifty-three patients were included in the study. The final diagnosis of patients was 14 pancreatic pseudocysts, 10 intraductal papillary mucinous neoplasms (IPMNs), 8 mucinous cystic neoplasms (MCN), 8 serous cystadenomas (SCAs), 2 cystic pancreatic neuroendocrine tumors (PNETs), and 11 others. The mean CgA levels were 50.51±130.04 ng/mL in pseudocysts, 12.38±8.59 in MCN, and 13.76±10.90 in cystic PNET. There was only one patient with a very high cystic fluid CgA (515.49 ng/mL) and was diagnosed as pseudocyst developed in chronic pancreatitis patient. Two patients with cystic PNET had normal levels of cystic fluid CgA. CONCLUSION: Cystic fluid CgA is not a useful marker for the differential diagnosis of cystic PNETs. It also has no value in the differential diagnosis of other pancreatic cysts.