Fusion of old and new: Employing touch imprint slides for next generation sequencing in solid tumors.

BACKGROUND: Cytomorphological evaluation of tissue touch imprints during rapid on-site evaluation or intraoperative pathology consultation has crucial value. However, literature on their utility for molecular testing is limited. In this study, we emphasize a further benefit of touch imprint slides and scrutinize our institutional experience on their use in molecular testing, specifically next generation sequencing (NGS). MATERIALS AND METHODS: NGS-based reports (2019-2023) of Koç University Hospital were retrospectively analyzed and circumstances in which sequencing was conducted on touch imprint slides were retrieved (n = 18). Type/location of the biopsy, diagnosis, results, and quality metrics were recorded. RESULTS: Touch imprints were addressed when they harbored more neoplastic cells compared with permanent biopsies, when suboptimal fixation mitigated deoxyribonucleic acid/ribonucleic acid (DNA/RNA) yield in resections or when the sample was obtained from bone and required decalcification. Diagnoses were diverse, namely non-small-cell lung cancer, gastric adenocarcinoma, glial tumor, Ewing sarcoma, and carcinoma of unknown primary. The percentage of tumor cells on slides stretched between 15% and 70%. Molecular findings ranged from KRAS mutations to TRIM1::NTRK2 and EWSR::FLI1 fusions. For five cases, sequencing did not yield any alteration, one study was not completed because it did not yield high-quality RNA. CONCLUSION: Touch imprint slides provide a reliable alternative, especially when neoplastic cells are scarce in permanent biopsies or decalcification deters nucleic acid quality. Based on our experience, we suggest making touch imprints on a routine basis, especially for every bone biopsy. Once digitally scanned duplicates are made, original slides can be safely used for DNA-/RNA-based molecular studies.

Established and new treatment roadmaps for pleural mesothelioma: opinions of the Turkish Collaborative Group.

Pleural mesothelioma (PM) is a cancer of the pleural surface, which is aggressive and may be rapidly fatal. PM is a rare cancer worldwide, but is a relatively common disease in Turkey. Asbestos exposure is the main risk factor and the most common underlying cause of the disease. There have been significant improvements in diagnoses and treatments of many malignancies; however, there are still therapeutic challenges in PM. In this review, we aimed to increase the awareness of health care professionals, oncologists, and pulmonologists by underlining the unmet needs of patients with PM and by emphasizing the need for a multidisciplinary treatment and management of PM. After reviewing the general information about PM, we further discuss the treatment options for patients with PM using immunotherapy and offer evidence for improvements in the clinical outcomes of these patients because of these newer treatment modalities.

Different Decellularization Methods in Bovine Lung Tissue Reveals Distinct Biochemical Composition, Stiffness, and Viscoelasticity in Reconstituted Hydrogels.

Extracellular matrix (ECM)-derived hydrogels are in demand for use in lung tissue engineering to mimic the native microenvironment of cells in vitro. Decellularization of native tissues has been pursued for preserving organotypic ECM while eliminating cellular content and reconstitution into scaffolds which allows re-cellularization for modeling homeostasis, regeneration, or diseases. Achieving mechanical stability and understanding the effects of the decellularization process on mechanical parameters of the reconstituted ECM hydrogels present a challenge in the field. Stiffness and viscoelasticity are important characteristics of tissue mechanics that regulate crucial cellular processes and their in vitro representation in engineered models is a current aspiration. The effect of decellularization on viscoelastic properties of resulting ECM hydrogels has not yet been addressed. The aim of this study was to establish bovine lung tissue decellularization for the first time via pursuing four different protocols and characterization of reconstituted decellularized lung ECM hydrogels for biochemical and mechanical properties. Our data reveal that bovine lungs provide a reproducible alternative to human lungs for disease modeling with optimal retention of ECM components upon decellularization. We demonstrate that the decellularization method significantly affects ECM content, stiffness, and viscoelastic properties of resulting hydrogels. Lastly, we examined the impact of these aspects on viability, morphology, and growth of lung cancer cells, healthy bronchial epithelial cells, and patient-derived lung organoids.

Scrape cytology and radiological solid size correlation can be used in the intraoperative management of subsolid lung nodules.

BACKGROUND: The term radiologic subsolid lung nodule (SLN) represents a heterogeneous group of non-neoplastic and neoplastic lesions. Intraoperative evaluation (IO) is often required to differentiate and diagnose. The current study aims to investigate the feasibility and reliability of scrape cytology (SC) and radiologic solid size correlation for the IO diagnosis of SLNs. METHODS: Sixty-eight patients with SLN signs were eligible to take part in the study due to intraoperatively prepared SC slides. We managed to complete the blind radiologic solid size measurement and cytologic evaluation retrospectively. Cases were grouped into three categories based on their cytological features: Group-0 (Benign), Group-1 (mild atypical features), and Group-2 (severe atypical features/unequivocally carcinoma). IO diagnoses were given by combining the radiologic solid size and cytological findings. RESULTS: Cytological features of Group-1 were observed in 100%, 93%, 32.5%, and 17% of the AIS, MIA, IA, and benign lesions, respectively. Cytological features of Group-2 were observed in 67.5%, and 7% of the IA and MIA, respectively. By combining cytology with radiologic solid size, 100%, 85%, 71%, and 83% of the AIS, IA, MIA, and benign lesions respectively were diagnosed correctly. Fifteen (15%) percent of the IA cases were underdiagnosed as MIA since their radiological solid sizes were less than 0.5 cm with cytological features of Group-1. Conversely, 29% of the MIA cases were overdiagnosed as IA since their radiological solid sizes were greater than 0.5 cm. CONCLUSION: SLNs should be handled with caution in terms of IO management. SC and radiologic solid size correlation both provide a practical and tissue-protecting approach for the IO evaluation of SLNs, ensuring a high consistency between IO and definitive diagnosis.

Evaluation of MUC1, MUC2, MUC5AC, and MUC6 Expression Differences in Lung Adenocarcinoma Subtypes by Using a Final Immunoreactivity Score (FIRS).

OBJECTIVE: Lung adenocarcinomas are divided into acinar, lepidic, papillary, micropapillary, and solid predominant subtypes according to the current World Health Organization (WHO) classification. We designed this retrospective study to demonstrate profiles of MUC expression (MUC1, MUC2, MUC5AC, and MUC6) of different histologic patterns within the same tumor among pulmonary adenocarcinomas and investigate correlations of MUC expression with clinicopathologic features. MATERIAL AND METHOD: We analyzed the expression of mucins (MUC1, MUC2, MUC5AC, and MUC6) in a series of 99 resected lung adenocarcinomas, which included a total of 193 patterns (71 acinar, 30 lepidic, 25 papillary, 20 micropapillary, 34 solid and 13 mucinous) and calculated a final immune reactivity score (FIRS) per tumor. RESULTS: MUC1 IRS scores were significantly higher in lepidic and solid patterns compared with mucinous patterns (p=0.013). MUC2 expression was seen only in three cases (1 acinar, 2 mucinous). MUC5AC and MUC2 expression was more common in mucinous patterns (p < 0.001 and p=0.028, respectively). MUC6 expression was only detected in seven patterns and the expression was weak. No significant difference was seen among histologic patterns for the staining scores of MUC6. Mucinous adenocarcinoma differed from other histologic subtypes regarding MUC1 and MUC5AC expression. Mucinous adenocarcinoma showed less MUC1 expression with lower IRS scores and higher MUC5AC expression. Tumor size (p=0.006), lymphatic invasion (p=0.018), vascular invasion (p=0.025), perineural invasion (p=0.019), MUC1 IRS scores (p=0.018), and MUC1 IRS scores > 8.5 (p=0.018) were significant predictors for lymph node metastasis. CONCLUSION: An alternative scoring for MUC1 can be used as a predictor for lymph node metastasis regardless of the histologic subtype.

18F-FDG PET/CT texture analysis of anthracotic lymph nodes detected with EBUS and comparison with cytological findings.

OBJECTIVE: Lymph node metastasis is the most important factor both in the selection of treatment since many alternatives have been created in recent years, and in the evaluation of prognosis in lung cancer. The most unpredictable cause of lymph node false positivity in fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) is anthracosis. The aim of this study is to compare 18F-FDG PET/CT texture information of anthracotic (ALN) and metastatic (MLN) lymph nodes, after re-evaluation of the cytological samples obtained from anthracotic lymph nodes by EBUS-TBNA. SUBJECTS AND METHODS: Ninety nine patients, 78 of whom had primary lung cancer were included in the study. Two hundred and three lymph nodes from 99 patients sampled by EBUS-TBNA and diagnosed cytologically as ALN or MLN were evaluated retrospectively. All ALN were classified as grades 1, 2 and 3 cytologically. Volume of interest (VOI) of 203 lymph nodes was re-drawn and maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) values were recorded. RESULTS: There was a statistically significant difference in MTV and TLG values in MLN and all ALN grades. However, only grade 1-2 ALNs could be differentiated from MLNs with SUVmax, and no statistically significant difference was found in grade 3 ALN and MLN. Metabolic tumor volume and TLG values over 4.10cm3 and 26.57 showed 60% and 59% sensitivity and 83% and 94 specificity respectively for the identification of MLN. CONCLUSION: The contribution of MTV and TLG values of 18F-FDG PET/CT to the differential diagnosis of ALN is much more valuable than SUVmax values, especially for grade 3 anthracosis. It was thought that cytological reporting of only grade 3 ALN could make a better contribution to the 18F-FDG PET/CT evaluation analysis.

Warthin-Like Mucoepidermoid Carcinoma: A Morphological Spectrum - A Report of 3 Cases with Histological and Cytological Findings and Review of the Literature.

BACKGROUND: Mucoepidermoid carcinoma (MEC) showing Warthin's tumor (WT)-like features is a low-grade malignancy which should be differentiated from WT. Morphological features may be distinctly different in each case, causing diagnostic difficulties. CASE PRESENTATION: Three cases were presented and discussed with their morphologies. All cases that presented with a mass in the parotid gland went to parotidectomy, and all had preoperative fine-needle aspirations (FNAs). Case 1 was a 16-year-old female; FNA was suggestive of WT and initially interpreted as WT histologically. Case 2 was a 27-year-old male; FNA was interpreted as noninformative due to the presence of cyst fluid only. Case 3 was a 53-year-old male and cytologically was found to be suspicious for MEC which contained squamous and goblet cells on a mucoid background. On histopathological examination, case 2 and case 3 were morphologically consistent with low-grade MEC with WT-like features. Prominent lymphoid stroma and the cystic pattern were the characters of these tumors. Case 1 had the classical WT appearance with some mucinous and squamous metaplasia which could only be interpreted as MEC after the detection of MAML2 rearrangement by FISH. The other 2 showed either focal or relatively diffuse usual low-grade MEC findings, and case 3 was also confirmed by MAML2 rearrangement. CONCLUSION: Cytological and histopathological features revealed a spectrum. Differentiating WT-like MECs from ordinary WTs may be challenging. On the one end of the spectrum, they may look very much like WT, and on the other end, even though usual MEC features are present, still, WT-like appearance may pose diagnostic difficulty. Showing MAML2 rearrangement in these cases is very helpful. The presence of mucinous and squamous cells in an otherwise WT-like looking tumor should be alarming for MEC, and if possible, each case should be analyzed for MAML2 rearrangement.

KRAS signaling in malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) arises from mesothelial cells lining the pleural cavity of asbestos-exposed individuals and rapidly leads to death. MPM harbors loss-of-function mutations in BAP1, NF2, CDKN2A, and TP53, but isolated deletion of these genes alone in mice does not cause MPM and mouse models of the disease are sparse. Here, we show that a proportion of human MPM harbor point mutations, copy number alterations, and overexpression of KRAS with or without TP53 changes. These are likely pathogenic, since ectopic expression of mutant KRASG12D in the pleural mesothelium of conditional mice causes epithelioid MPM and cooperates with TP53 deletion to drive a more aggressive disease form with biphasic features and pleural effusions. Murine MPM cell lines derived from these tumors carry the initiating KRASG12D lesions, secondary Bap1 alterations, and human MPM-like gene expression profiles. Moreover, they are transplantable and actionable by KRAS inhibition. Our results indicate that KRAS alterations alone or in accomplice with TP53 alterations likely play an important and underestimated role in a proportion of patients with MPM, which warrants further exploration.

The role of adjuvant chemotherapy in resected stage I non - small cell lung cancer: A Turkish Oncology Group Study.

PURPOSE: The benefit of adjuvant chemotherapy for tumors smaller than 4 cm is not clear. We aimed to evaluate the prognostic impact of adjuvant platin-based chemotherapy in high-risk stage I patients with non-small cell lung cancer (NSCLC). METHODS: This cooperative group study included 232 NSCLC patients who underwent curative surgery for stage I disease with tumor size 2-4 cm. Re ults: Median age at presentation was 63 years (range 18-90). The mean tumor size was 29.6 ± 7.3 mm. The frequency of patients with specified risk factors were: visceral pleural effusion (VPI): n: 82 (36.6%); lymphovascular invasion (LVI): n: 86 (39.1%); Grade 3: n: 48 (32.7%); Solid micropapillary pattern (SMP): n: 70 (48.3%). Adjuvant platin-based chemotherapy was administered to 51 patients. During a median follow-up period of 50.5 months 68 patients (29.3%) developed recurrence, 54 (23.3%) died from any cause and 38 (16.4%) of them died of lung cancer. Patients who received chemotherapy compared with the non-chemotherapy group had a longer 5-years relapse-free survival (RFS) (84.5 vs 61.1%). Also on multivariate analysis, adjuvant chemotherapy was a significant independent prognostic factor for RFS. CONCLUSION: Adjuvant platin-based chemotherapy should be considered for patients with small tumors with adverse risk factors. Key words: adjuvant chemotherapy, lung cancer, oncology, lymphovascular invasion, solid-micropapillary pattern, platinum-based therapy.

The prediction of spread through air spaces with preoperative 18F-FDG PET/CT in cases with primary lung adenocarcinoma, its effect on the decision for an adjuvant treatment and its prognostic role.

PURPOSE: In lung adenocarcinoma cases, 'spread through air spaces' (STAS) is a new indicator of invasion and directly related to disease survival. The aim of our study is to establish whether a preoperatively performed 18F-Fluorodeoxyglucose (FDG) PET/computed tomography (CT) imaging data can predict the presence of STAS in cases with lung adenocarcinoma and thus predict the decision for the type of surgery and adjuvant chemotherapy. MATERIALS AND METHODS: Between 2000 and 2019, we retrospectively analyzed 63 patients with lung adenocarcinoma cases that had undergone lobectomy or pneumonectomy. Semiquantitative parameters were calculated and metabolic tumor volume (MTV)/CT volume (CTV) ratio was recorded from FDG PET/CT data. The pathological samples from these patients were evaluated for STAS. All these values were evaluated for their correlation with the alveolar spread. RESULTS: There was no statistically significant correlation to be found between CTV, MTV, total lesion glycolysis (TLG), standardized uptake value (SUV)max, SUVmean and STAS (P > 0.05). However, MTV/CTV ratio above 1 had statistically more alveolar spread. In the group with an MTV ratio above 1, STAS positivity was 27 (75%), and 9 (25%) did not have STAS, whereas these were 6 (22.2%) patients who had STAS, and 21 (77.8%) did not have STAS in the group with below 1 (P < 0.001). CONCLUSIONS: In the preoperative PET study inoperable lung adenocarcinoma cases, MTV/CTV ratio higher than 1 was found to predict STAS positivity. As a result, it was found that it provided significant clinical additional information regarding the need for a surgical approach (lobar resection instead of sublobar) and adjuvant chemotherapy.

The importance of histological patterns on PD-L1 staining heterogeneity: Should we use pattern-based approach for selecting tumor samples for PD-L1 testing in lung adenocarcinomas?

Background/aim: Programmed death ligand-1 (PD-L1) is a predictive marker for immunotherapeutic agents. However, heterogeneous staining of PD-L1 can cause false-negative results. The aim of this study is to evaluate the importance of histological patterns on PD-L1 staining heterogeneity in lung adenocarcinomas (LAC). Materials and methods: PD-L1 immunohistochemistry (IHC) stain was performed to two different tissue cores of 128 LAC cases, and cut-off values are given for grouping the cases according to the percentage of staining (1%-10%, 11%-49%, 50%-100%). Staining rates between cores were compared and analyzed by their histological patterns. Also, the relation of the PD-L1 expression with the clinicopathological characteristics of the cases was analyzed. Results: Overall, PD-L1 expression was observed in 53 of 128 cases (41.4%, 1% cut-off), 23.5% of them were positive at 10% cut-off and 14.1% at 50% cut-off. PD-L1 expression was significantly related to the high grade micropapillary and solid patterns of adenocarcinomas (p:0.01). Staining cut-offs were mostly similar between cores (43/50, 86%) (k:0.843). However, 14% of them were positive only in one core (7 of 50). This false negativity was mostly related to the histological patterns. Conclusion: Our data reveal the heterogeneous staining of PD-L1 expression, also micropapillary and solid patterns show higher rates of PDL expression. Therewithal, these findings also highlight the importance of taking into consideration of histological patterns, when choosing a paraffin block for the PDL1.

Efficiency of Cytology Samples for PD-L1 Evaluation and Comparison with Tissue Samples.

OBJECTIVE: Lung cancer is the leading cause of cancer-related death. PD-L1 blockers have become a first-line option for advanced non-small cell lung cancer (NSCLC) patients. Guidelines require the assessment of PD-L1 expression by immunohistochemistry. Although tissue samples are widely used, cytologic samples could be an alternative. In this study, we compared cytologic samples with tissue samples for PD-L1 evaluation in NSCLC cases. MATERIAL AND METHOD: Koç University Hospital, Department of Pathology Laboratory Information System was scanned for all PD-L1 tests performed on NSCLC cases, either on tissue samples or cell blocks. The type of the biopsy/aspiration procedure, the tumor type, patient demographics, and the percentage of PD-L1 positive tumor cells were recorded. A total of 73 tissue samples and 49 cell blocks were found to be eligible for the study. RESULTS: The PD-L1 positivity score was at least 1% in 44 of 73 samples of the tissue group and 19 of 49 samples of the cell block group. Tissue samples showed significantly higher positivity compared to the cell blocks (p=0.020). Comparing the frequency of cases with ≥50% positivity showed no statistically significant difference. A comparison of PD-L1 positivity rates of only the small biopsies and cell blocks also showed no significant difference. CONCLUSION: Although they harbor a limited number of tumor cells, cell blocks prepared from cytologic samples are good alternatives for PD-L1 testing. However, large resections should be used for PD-L1 evaluation whenever possible since even 1% positivity may affect the treatment decision.

Diagnostic value of BRCA1-associated protein-1, glucose transporter-1 and desmin expression in the discrimination between reactive mesothelial proliferation and malignant mesothelioma in tissues and effusions.

OBJECTIVE: The aim of this study was to investigate the utility of BRCA1-associated protein-1 (BAP1), glucose transporter (GLUT)-1 and desmin expression by immunohistochemistry in the discrimination between reactive and malignant mesothelial proliferations. METHODS: A total of 88 biopsies and 30 effusions from mesothelioma cases were studied. Control groups were composed of 35 tissues and 30 cell blocks. The 88 mesothelioma cases were from 43 males and 45 females (mean age 56 years). Tumours were mostly localised to pleura (66/88, 75%) and of epithelioid histology (75/88, 85%). Cytology samples were from 17 males and 13 females (mean age 58 years), and 16 pleural and 14 peritoneal effusions. Twenty cytology cases had corresponding tissue biopsies. RESULTS: BAP1 loss was detected in 61/88 (69%) tissues and in 20/30 (67%) cytology samples from mesothelioma with a specificity of 100% for both sampling methods. BAP1 loss was observed more frequently in pleural and biphasic tumours. GLUT-1 immunoreactivity was identified in 54/81 (67%) and 23/25 (92%) malignant tissues and effusions, and in 6/33 (18%) and 6/30 (20%) benign tissues and effusions, respectively. Desmin loss was observed in 74/80 (92%) malignant biopsy samples, 16/21 (76%) malignant effusions and 10/34 (29%) of benign tissues, but in none of the reactive effusions. Concordance rate of results between biopsy and cytology was as follows: BAP1 20/20 (100%); GLUT-1 13/18 (72%); and desmin 10/14 (71%). CONCLUSIONS: BAP1, GLUT-1 and desmin are useful markers in the discrimination between reactive and malignant mesothelial proliferations. BAP1 loss seems to be diagnostic for mesotheliomas both in biopsy and cytology samples.

Management of cytological material, pre-analytical procedures and bio-banking in effusion cytopathology.

Serous effusion fluid is one of the most commonly encountered specimens in routine cytopathology practice. It provides invaluable information about the patient and the clinical status; but to get the most of it, specimen handling and processing must be carried out properly. Cytomorphology is the basis of a successful analysis which should complemented by ancillary tests when needed. A wide spectrum of ancillary techniques - ranging from immunocytochemistry and flow cytometry to different assays of molecular pathology - can be applied to serous effusions. This article describes the acquisition and management of serous effusion fluids, methods for preservation and transportation, different techniques of cytopreparation, application of immunocytochemistry, flow cytometry, and fluorescence in-situ hybridization (FISH), as well as DNA extraction for polymerase chain reaction (PCR) and next generation sequencing (NGS). Principles of bio-banking of effusion samples are also discussed which is getting more important in correlation with the developments in personalized medicine.

Prognostic significance of carbonic anhydrase IX overexpression in stage III non-small cell lung cancer patients after neoadjuvant treatment.

BACKGROUND: To assess the prognostic importance of carbonic anhydrase IX (CA IX), a hypoxic biomarker, after neoadjuvant treatment in Stage III non-small cell lung cancer (NSCLC) patients. METHODS: Tissue CA IX expression was examined after surgical resection in 77 patients who had undergone neoadjuvant treatment. The effects of CA IX overexpression and other clinical factors on disease-free survival and overall survival were investigated. RESULTS: In multivariate analysis, number of neoadjuvant chemotherapy (CT) courses and gender emerged as significant independent predictors for disease-free survival, where administration of 2-3 courses of neoadjuvant chemotherapy (CT) (HR, 3.2 [95% CI 1.3-7.6], p = 0.009) and female gender were associated with poor survival (HR, 3.2 [95% CI 1.3-7.7], p = 0.009). The only significant independent predictor for overall survival was recurrence (HR, 5.6 [95% CI 2.4-12.8], p < 0.001). On the other hand, CA IX overexpression was not associated with disease free survival (p = 0.560) or overall survival (p = 0.799). DISCUSSION: Our results do not suggest a prognostic role for CA IX overexpression in stage III NSCLC patients who received neoadjuvant treatment.

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.

Role of biochemistry and cytological analysis of cyst fluid for the differential diagnosis of pancreatic cysts: A retrospective cohort study.

BACKGROUND: Management of pancreatic cysts is based on neoplastic-nonneoplastic discrimination. Endoscopic ultrasound (EUS) enables to differentiate neoplastic-nonneoplastic lesions and also allows fine-needle aspiration (FNA). In this study, we aim to assess feasibility and clinical relevance of cytological and biochemical analysis in differential diagnosis of cystic pancreatic lesions in patients who had undergone endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) due to pancreatic cysts. METHODS: Participants were 96 patients who had undergone EUS-FNA for differential diagnosis of pancreatic cysts. Pancreatic cysts were classified as benign-mucinous, nonmucinous, and malignant according to patient history, physical examination, EUS appearance, and cystic fluid assessment. Tumor markers (CEA, CA(cancer antigens) 72.4, CA 19-9) , amylase, lipase and cytological assesment were compared between 3 different groups. Receiver-operating characteristics (ROC) curves were constructed to identify appropriate cut-off values. RESULTS: Fluid CEA and CA 72.4 levels for benign-mucinous and malignant cysts were significantly higher than for nonmucinous cysts (P ≤ 0.04). A cut-off CEA level of 207 ng/mL differentiated mucinous etiology with a sensitivity of 72.7%, specificity of 97.7%, and accuracy of 89.5%. The sensitivity, specificity, and accuracy of the CA 72.4 cut-off level of 3.32 ng/mL were 80%, 69.5%, and 73.6%, respectively. CONCLUSION: Cyst fluid CEA and CA 72.4 levels have a high accuracy in discriminating mucinous from nonmucinous cysts. When combined with cytology their accuracy rate increases.

BRAF, NRAS, KIT, TERT, GNAQ/GNA11 mutation profile analysis of head and neck mucosal melanomas: a study of 42 cases.

Head and neck mucosal melanoma (HNMuM), which occurs mostly in the sinonasal and oral cavity, constitutes less than 1% of all malignant melanomas. Treatment options fail to improve the prognosis of this aggressive tumour that has low overall survival rates. Thus, development of new targeted therapies is essential. Unfortunately, limited data exist regarding their molecular profile. BRAF, NRAS, KIT, TERT and GNAQ/GNA11 oncogene mutations were investigated in 42 HNMuMs (28 sinonasal, 13 oral, 1 nasopharyngeal). Mutation rates were as follows: BRAF (4.8%), NRAS (4.8%), KIT (9.5%), TERT (7.5%), GNAQ/GNA11 (0%). Among 11 cases that harboured mutations (26%), 10 (91%) were located in sinonasal and one (9%) in the oral cavity. The literature was reviewed with comparison of frequencies based on the gathered data. NRAS and TERT promoter mutation rates were significantly higher in sinonasal than in oral location (p<0.05). Our results indicated that BRAF, NRAS, KIT, TERT and GNAQ/GNA11 gene mutations occur at low frequencies in HNMuMs, and subgroups (oral versus sinonasal) differ in their molecular profile. Low rates of aforementioned mutations and activation of oncogenes by pathways other than sun exposure support the distinctive nature of HNMuMs with regard to their cutaneous counterparts.

Concomitant etoposide and cisplatin provided improved survival compared with docetaxel and cisplatin in patients with locally advanced non-small cell lung cancer treated with chemoradiotherapy.

Presently, there is no consensus regarding which chemotherapy regimen is best to administer with radiotherapy in patients with locally advanced non-small-cell lung cancer (LA-NSCLC). Herein, our aim was to compare the outcome of patients treated with either etoposide-cisplatin (EP) or docetaxel-cisplatin (DP) in this curative setting.Patients treated with either EP or DP and concurrent radiotherapy from 2004 to2012 were identified and their detailed medical records and follow-up information were obtained for analysis in this retrospective study. Survival rates were compared using Cox proportional hazards regression models with adjustments for confounding parameters provided by propensity score methods.A total of 105 patients were treated with concurrent chemoradiotherapy for LA-NSCLC (stage IIB-IIIA-IIIB). The median ages were 54 years (range, 32-70 years) and 55 years (range, 37-73 years) in the EP (n = 50) and DP (n = 55) groups, respectively. The median follow-up time was 27 months (range, 1-132 months) in the EP group and 19 months (range, 1-96 months) in DP group. There was no significant difference in baseline clinicopathologic features including age, sex, performance status, histologic subtype, and clinical TNM stages between groups. In the univariate analysis, the median overall survival of patients treated with EP was higher than that of patients treated with DP (41 vs. 20 months, P = 0.003). Multivariate analysis further revealed a survival advantage with EP compared with DP (hazard ratio [HR], 0.46; 95% confidence interval: 0.25-0.83; P = 0.009). The toxicity profile of the 2treatment groups was similar except that pulmonary toxicity was higher in the DP group (grade 3-4: 0% vs. 6%, P = 0.024).Concurrent chemoradiotherapy with EP may provide more favorable outcomes than DP and with an acceptable safety profile.

An Evaluation of Surgical Prophylaxis Procedures in Turkey: A Multi-Center Point Prevalence Study.

OBJECTIVE: The purpose of this study was to evaluate compliance with guidelines in surgical prophylaxis (SP) procedures in Turkey. MATERIALS AND METHODS: A point prevalence study involving 4 university, 5 education and research and 7 public hospitals was performed assessing compliance with guidelines for antibiotic use in SP. Compliance was based on the "Clinical Practice Guidelines for Antimicrobial Surgery (CPGAS) 2013" guideline. RESULTS: Sixteen centers were included in the study, with 166 operations performed at these being evaluated. Parenteral antibiotic for SP was applied in 161 (96.9%) of these. Type of antibiotic was inappropriate in 66 (40.9%) cases and duration of use in 47 (29.1%). The main antibiotics used inappropriately in SP were ceftriaxone, glycopeptides and aminoglycosides. No significant difference was observed between secondary and tertiary hospitals in terms of inappropriate selection. Duration of prophylaxis was also incompatible with guideline recommendations in approximately half of surgical procedures performed in both secondary and tertiary hospitals, however statistical significance was observed between institutions in favor of tertiary hospitals. CONCLUSION: Antibiotics are to a considerable extent used in a manner incompatible with guidelines even in tertiary hospitals in Turkey. It must not be forgotten that several pre-, intra- and postoperative factors can be involved in the development of surgical site infections (SSI), and antibiotics are not the only option available for preventing these. A significant improvement can be achieved in prophylaxis with close observation, educational activities, collaboration with the surgical team and increasing compliance with guidelines. All health institutions must establish and apply their own SP consensus accompanied by the guidelines in order to achieve success in SP.