Transient Elastography for Noninvasive Evaluation of Posttransplant Liver Graft Fibrosis in Turkish Children, Ege University Children Hospital Experience.

OBJECTIVES: The influence of advancing fibrosis on graft survival in the context of pediatric liver transplantation accentuates the critical role of protocol-driven liver biopsies, a practice adopted by numerous medical centers. Consequently, the exigency for noninvasive methodologies to assess graft fibrosis assumes heightened importance when conventional clinical and laboratory parameters fail to reveal signs of liver damage. METHODS: This study aimed to assess the reliability of transient elastography (TE) in pediatric liver transplant recipients to detect graft fibrosis and compare the results of TE in patients who underwent biopsy. RESULTS: This prospective cohort study included liver transplanted children who underwent biopsy at Ege University Children's Hospital between October 1, 2021, and October 31, 2022, and a healthy control group. According to TE, fibrosis was detected in 40 patients, and no fibrosis was detected in 50. The median time to develop fibrosis was 100 months (95% CI [83.1-116.8]). A statistically significant positive correlation existed between LSM and METAVIR fibrosis score (r = 0.562, p = 0.001). There was a statistically significant difference in LSM between patients with F2 fibrosis (7.8-8.8 kPa ± 3.2) compared to patients with F0 fibrosis (5.2 kPa ± 0.7) (p = 0.005) and F1 fibrosis (6.1 kPa ± 1.5) (p = 0.041), on ANOVA. CONCLUSION: Liver allograft fibrosis is common in long-term follow-up in children who have undergone liver transplantation. Abnormal TE may guide physicians to consider liver biopsy to detect late allograft fibrosis in these children.

Evaluation of surgical strategies and long-term outcomes in pediatric hepatocellular carcinoma.

PURPOSE: Hepatocellular carcinoma (HCC), the second most common pediatric malignant liver tumor after hepatoblastoma, represents 1% of all pediatric tumors. METHODS: A retrospective study was conducted on children with HCC treated at our center from March 2002 to October 2022, excluding those with inadequate follow-up or records. Demographic data, initial complaints, alpha-fetoprotein (AFP) values, underlying disease, size and histopathological features of the masses, chemotherapy, and long-term outcomes were analyzed. RESULTS: Fifteen patients (8 boys, 7 girls) with a mean age of 11.4 ± 4.1 years (0.8-16.4 years) were analyzed. The majority presented with abdominal pain, with a median AFP of 3.9 ng/mL. Hepatitis B cirrhosis in one patient (6.6%) and metabolic disease (tyrosinemia type 1) in two patients (13.3%) were the underlying diseases. Histopathological diagnoses were fibrolamellar HCC (n:8; 53.3%), HCC (n:6; 40%). Four of the 15 patients underwent liver transplantation, and 9 underwent surgical resection. Due to late diagnosis, two patients were considered inoperable (13.3%). The survival rate for the four patients who underwent liver transplantation was found to be 75%. CONCLUSION: Surgical treatment of various variants of HCC can be safely performed in experienced centers with a multidisciplinary approach, and outcomes are better than in adults.

Hepatocellular adenomas in the Turkish population: reclassification according to updated World Health Organization criteria.

AIMS: Hepatocellular adenoma (HCA) is an uncommon liver neoplasm, and studies of HCA subtypes have been primarily limited to France, the USA, and Japan. The aim of this study was to describe the clinicopathological features of HCA subtypes in Turkey. METHODS AND RESULTS: The resection specimens of 59 cases diagnosed as 'hepatocellular adenoma' collected from 15 institutions were reviewed to confirm the diagnosis and to classify them according to the current World Health Organization 2019 classification. Immunostaining for glutamine synthetase, liver fatty acid-binding protein, C-reactive protein, ß-catenin and reticulin was performed. Of the 59 cases, 48 (81%) were diagnosed as HCA. We identified 24 (50%) hepatocyte nuclear factor 1α (HNF1α)-inactivated HCAs, five (10%) inflammatory HCAs, 15 (32%) ß-catenin-activated HCAs, three (6%) ß-catenin-activated inflammatory HCAs, and one (2%) unclassified HCA. HCA patients were predominantly female (female/male ratio of 5:1); they had a median age of 34 years and a median tumour diameter of 60 mm. In the ß-catenin-activated HCA group, nine cases (19%) showed cytoarchitectural atypia, and were also referred to as atypical hepatocellular neoplasms. In the ß-catenin-activated HCA group, three cases (6%) showed focal areas supportive of transition to HCA. The original diagnosis of HCA was changed to well-differentiated hepatocellular carcinoma in nine cases and to focal nodular hyperplasia in two cases. CONCLUSION: In our series, the major HCA subtype was HNF1α-inactivated HCA. We found a low incidence of inflammatory-type HCA. Our data also showed that ß-catenin-activated hepatocellular neoplasms, including cases with atypical histology, constituted a relatively high proportion of the cases. These findings are in contrast to those of most other studies of HCA subtypes.

Intracellular localization of beta-catenin expression plays a possible prognostic role on the outcome of hepatoblastoma patients.

PURPOSE: Wnt/Beta-catenin pathway plays an essential role in liver development and regeneration. Abnormal activation in this pathway leads to development of hepatoblastoma (HB). Although its importance has invoked attention, its prognostic role is debatable. We aimed to evaluate the significance of intracellular localization of beta-catenin (BC) expression in the outcome of hepatoblastoma patients. METHODS: Medical records of HB patients between 2004 and 2018 were reviewed. Patients were grouped according to intracellular localization of BC expression by immunohistochemistry as being cytoplasmic or nuclear. Demographics, radiological images, PRETEXT classifications, vascular involvement, risk groups, chemotherapy responses, and survival rates were analyzed and compared between groups. RESULTS: There were 41 patients. Thirteen patients were excluded for unavailability of records in four, negative/unclear BC expressions in seven. Cytoplasmic expression of BC was observed in 17 patients whereas 13 patients displayed nuclear expression. Demographics were similar in both groups. Cytoplasmic BC expression was associated with poor chemotherapy response (p = 0.001) and increased vascular involvement (p = 0.0162) requiring more extensive surgeries (p = 0.039). CONCLUSION: Although the numbers are limited in our series, the intracellular localization of BC expression has been found to be a promising determining factor for hepatoblastoma prognosis. With larger patient series, more reliable results can be achieved.

Molecular testing for the clinical diagnosis of fibrolamellar carcinoma.

Fibrolamellar carcinoma has a distinctive morphology and immunophenotype, including cytokeratin 7 and CD68 co-expression. Despite the distinct findings, accurate diagnosis of fibrolamellar carcinoma continues to be a challenge. Recently, fibrolamellar carcinomas were found to harbor a characteristic somatic gene fusion, DNAJB1-PRKACA. A break-apart fluorescence in situ hybridization (FISH) assay was designed to detect this fusion event and to examine its diagnostic performance in a large, multicenter, multinational study. Cases initially classified as fibrolamellar carcinoma based on histological features were reviewed from 124 patients. Upon central review, 104 of the 124 cases were classified histologically as typical of fibrolamellar carcinoma, 12 cases as 'possible fibrolamellar carcinoma' and 8 cases as 'unlikely to be fibrolamellar carcinoma'. PRKACA FISH was positive for rearrangement in 102 of 103 (99%) typical fibrolamellar carcinomas, 9 of 12 'possible fibrolamellar carcinomas' and 0 of 8 cases 'unlikely to be fibrolamellar carcinomas'. Within the morphologically typical group of fibrolamellar carcinomas, two tumors with unusual FISH patterns were also identified. Both cases had the fusion gene DNAJB1-PRKACA, but one also had amplification of the fusion gene and one had heterozygous deletion of the normal PRKACA locus. In addition, 88 conventional hepatocellular carcinomas were evaluated with PRKACA FISH and all were negative. These findings demonstrate that FISH for the PRKACA rearrangement is a clinically useful tool to confirm the diagnosis of fibrolamellar carcinoma, with high sensitivity and specificity. A diagnosis of fibrolamellar carcinoma is more accurate when based on morphology plus confirmatory testing than when based on morphology alone.

Primary mesenchymal liver tumors: radiological spectrum, differential diagnosis, and pathologic correlation.

With the exception of hemangioma, benign or malignant primary mesenchymal tumors of the liver are seldom encountered. The aim of this review was to discuss the clinical, histopathological, and imaging features of liver hemangiomas (cavernous, capillary, and sclerosed types), liver lipoma, angiomyolipoma, mesenchymal hamartoma, neurofibroma, infantile hemangioendothelioma, epithelioid hemangioendothelioma, myofibroblastoma, angiosarcoma, malignant fibrous histiocytoma, undifferentiated embryonal sarcoma, and nested stromal tumor. In most of these rare liver tumors, radiological findings obtained by cross-sectional imaging may reflect the characteristic pathologic features required for differential diagnosis; however, definitive diagnosis should be confirmed using histopathological examination.

Rare cause of weight loss in a kidney transplant recipient: iron overload.

Various reasons such as malignancies and chronic infections may cause weight loss in kidney transplant patients. In this report, iron overload as a rare cause of weight loss in a kidney transplant patient is presented. Forty-seven-year-old male patient who transplanted from a deceased donor 5 years ago was hospitalized because of 20 kg of weight loss. In medical history, he had history of hemodialysis for 89 months and received 100-300 mg of intravenous iron therapy per week before transplantation and transfused eight units of blood. In physical examination, weight and height were 45 kg and 185 cm, respectively. Respiratory and cardiac auscultation was normal. Laboratory results revealed as follow: glucose 76 mg/dL, urea 60 mg/dL, creatinine 1.35 mg/dL, aspartate aminotransferase 74 U/L, alanine aminotransferase 77 U/L, C-reactive protein 2.59 mg/dL, albumin 3.3 g/dL, globulin 3.4 g/dL, white blood cells 3200/mm(3), hemoglobin 13.1 g/dL and platelets 190,000/mm(3). Chest and abdominal tomography didn't reveal any pathology. Portal Doppler ultrasound showed signs of early cirrhosis. Viral and autoimmune hepatitis markers were negative. Ferritin was 5300 ng/mL and transferrin saturation was 82%. In liver biopsy, hemosiderosis was diagnosed and heterozygous H63D gene mutation was detected. Totally, 19 units of phlebotomy were performed. Liver function tests and serum ferritin decreased gradually. At outpatient follow-up in 6 months, he returned to former weight. In conclusion, there can be several causes of weight loss in kidney transplant patients. Iron overload can come across as a rare cause of weight loss. In these patients, ferritin levels should be checked and diagnosis should be clarified by liver biopsy and gene mutation analysis.

Cardiac Amyloidosis: Clinical Features, Pathogenesis, Diagnosis, and Treatment.

Cardiac amyloidosis is a type of amyloidosis that deserves special attention as organ involvement significantly worsens the prognosis. Cardiac amyloidosis can be grouped under three main headings: immunoglobulin light chain (AL) amyloidosis that is dependent on amyloidogenic monoclonal light chain production; hereditary Transthyretin (TTR) amyloidosis that results from accumulation of mutated TTR; and wild-type (non-hereditary) TTR amyloidosis formerly known as senile amyloidosis. Although all three types cause morbidity and mortality due to severe heart failure when untreated, they contain differences in their pathogenesis, clinical findings, and treatment. In this article, the clinical features, pathogenesis, diagnosis, and treatment methods of cardiac amyloidosis will be explained with an overview, and an awareness will be raised in the diagnosis of this disease.

Diagnostic Efficacy of Cell Block and Liquid-Based Cytology for Endoscopic Ultrasound-Guided Fine Needle Aspiration in Pancreatic Tumors.

This study aimed to evaluate the diagnostic efficacy of cell block (CB) and liquid-based cytology (LBC) for endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in pancreatic tumors. The study included patients who underwent EUS-FNA for pancreatic tumors between January 2015 and February 2021 and whose cytology samples were both processed for LBC and CB. Data of 390 patients (220 men, mean age: 64.2 ± 11.4 years) were retrospectively analyzed. Of the detected lesions (size: 17-120 mm; mean: 39.9 ± 13.9 mm), 220 (56.4%) were located in the head and uncinate process of the pancreas. Lesions in 339 (86.9%) patients were diagnosed as malignant using CB and/or LBC and suspicious for malignancy in 44 (11.3%) patients. In 7 patients with non-diagnostic (6 cases) or negative for malignancy (1 case) EUS-FNA results using both methods, the diagnosis of malignancy was established via ultrasound-guided percutaneous biopsy. Malignancy was detected in 324 (92.4%), 313 (87.9%), and 298 (87.9%) patients using CB, LBC, and both CB and LBC, respectively. Final diagnosis was obtained in 339 (98%) patients by using CB and/or LBC. The combined use of the both methods exhibited significantly superior diagnostic accuracy compared with CB and LBC alone (P < .001). Liquid-based cytology and CB exhibit high diagnostic accuracy for the detection of pancreatic tumors in patients undergoing EUS-FNA. The combined use of both methods showed a significantly higher diagnostic accuracy than LBC and CB alone.

Next generation sequence-based targeted somatic mutation analysis in thyroid nodules with pathologically diagnosed as indeterminate cytology.

PURPOSE: The management of indeterminate thyroid nodules remains a topic of ongoing debate, particularly regarding the differentiation of malignancy. Somatic mutation analysis offers crucial insights into tumor characteristics. This study aimed to assist the clinical management of indeterminate nodules with somatic mutation analysis. METHODS: Aspiration samples from 20 indeterminate thyroid nodules were included in the study. A next-generation sequencing panel containing 67 genes was used for molecular profiling. The results were compared with pathology data from surgical material, which is considered the gold standard. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. RESULTS: Variants in six genes (NRAS, BRAF, TP53, TERT, PTEN, PIK3CA) were detected in 10 out of 20 samples. We identified nine Tier 1 or 2 variants in 10 (67 %) out of 15 malignant nodules (NRAS, BRAF, TP53, TERT, PTEN, PIK3CA) and one Tier 2 (PIK3CA) variant in one out of five benign nodules. The study demonstrated an NPV of 40 %, a PPV of 90 %, a specificity of 80 %, and a sensitivity of 60 %. CONCLUSION: Based on the detected molecular markers, at least nine patients (45 %) could be managed correctly without needing a repeat FNAB attempt. This study underscores the clinical practicality of molecular tests in managing nodules with indeterminate cytology. Additionally, this study emphasizes the importance of considering the patient's age when determining the DNA- or RNA-based genetic testing method. Finally, we discussed the significance of the somatic mutation profile and its impact on the current pathological classification.

The effectiveness of the liquid-based preparation method in cerebrospinal fluid cytology.

OBJECTIVES: Since malignant cells were first detected in the cerebrospinal fluid (CSF), numerous methods have been used for CSF examination. The cytocentrifugation and liquid-based cytology (LBC) methods are two of these. We aimed to investigate whether the results from the LBC method were different from the results of the cytological diagnosis of the CSF materials that were prepared using the cytocentrifugation method. MATERIALS AND METHODS: A retrospective analysis was conducted using the pathological records of 3,491 (cytocentrifugation on 1,306 and LBC on 2,185) cytological specimens of CSF which were diagnosed over a 4-year period between January 2007 and December 2011. The Fisher exact test was used to compare the results of the LBC and cytocentrifugation methods. RESULTS: While there was a noticeable decrease in nondiagnostic diagnosis and a slight decrease in suspicious diagnosis, there was an increase in malignant and benign diagnosis with the LBC method in comparison to the centrifugation method. Statistically, the decrease in nondiagnostic diagnosis was considered significant (p < 0.0001). DISCUSSION: The LBC method seems like a better option than the cytocentrifugation method, because of many preparatory, screening and diagnostic advantages, especially in pathology departments where materials come from far away and large volumes are examined.

[The role of endotracheal aspiration in the diagnosis of ventilator associated pneumonia]. / Ventilatörle iliskili pnömoni tanisinda endotrakeal aspiratin degeri.

INTRODUCTION: Ventilator associated pneumonia (VAP) is one of the most important causes of mortality in patients treated with invasive mechanical ventilation (IMV) in intensive care unit (ICU). Microbiological examinations are required as clinical and radiological findings are usually insufficient in the diagnosis. MATERIALS AND METHODS: Twenty four patients who were receiving IMV because of respiratory failure, had a Clinical Pulmonary Infection Score (CPIS) of ≥ 6 in the follow-up and died with the suspicion of VAP were enrolled in our study. Six patients were excluded as post-mortem biopsy could not be performed. The patients who had pre-mortem CPIS ≥ 6, in whom a causative organism was identified from the culture of post-mortem lung biopsy and/or histopathological examination of lung biopsy was compatible with pneumonia were diagnosed as VAP. In the 18 patients in whom a post-mortem lung biopsy was performed, quantitative culture results of endotracheal aspirate performed 48 hours prior to death were compared with microbiological and histopathological results of post-mortem lung biopsy specimens, and the role of endotracheal aspirate in the diagnosis of VAP was evaluated retrospectively. RESULTS: Out of 18 patients (12 men, mean age 67.0 ± 13.0 years) included in the study, 11 (61.1%) were diagnosed as VAP. The quantitative culture of endotracheal aspirate was positive in 9 (81.8%) out of 11 patients diagnosed as VAP. The sensitivity, specificity, positive and negative predictive values of endotracheal aspirate culture for identifying VAP were found to be 81.8%, 14.3%, 60.0% and 33.3%, respectively. CONCLUSION: Our study shown that quantitative culture of endotracheal aspirate is a practical and reliable method that can be used for the diagnosis of VAP in patients receiving IMV in ICU and having CPIS ≥ 6.

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.

Diagnostic efficacy of intraoperative histopathological examination of lesions with unknown diagnosis suspicious for malignancy.

Objective: In this study, the efficiency of intraoperative histopathological examination (frozen section examination; FS) in patients operated per suspected lung malignancy was evaluated. Methods: The data of 136 patients who underwent surgery in our clinic due to suspected lung malignancy between January 2020 and June 2021 was evaluated prospectively. Results: The FS was inconclusive in 7.3 % of the 136 patients. In contrast, the accuracy of differentiating between benign and malignant lesions was 99.2 %, while the rate of false negative was 0.8 % in 126 patients with a prediagnosis. FS examination led to an accurate diagnosis in 91.9 % of the 98 patients without a history of extrapulmonary malignancy (EPM), with a false negativity rate of 1 %, whereas a paraffin-embedded examination was recommended in 7.1 %. The accuracy of the FS was 98.9 % in 91 patients prediagnosed based on an FS, with a false negativity rate of 1.1 %. In the same group of patients, the FS examination was successful in establishing the subtype in 32.9 % of the patients with primary lung cancer (PLC), whereas the efficacy of the FS examination in determining the subtype was better in benign diseases (63.6 % vs 32.9 %, p = 0.009). The FS examination was unable to differentiate between benign and malignant lesions in 92.1 % of patients with EPM but differentiated between primary and metastatic lesions in 48.3 % of patients who had malignancy. Furthermore, FS examination successfully guided surgery in 89 patients with no history of EPM (90.8 %) and 20 patients (52.6 %) with a history of EPM. Conclusion: Although FS is insufficient in subtyping lung cancers and distinguishing PLC and metastasis, it is an important and effective diagnostic approach with its overall ability to distinguish benign and malignant lesions and guiding surgical procedures.

Real-life comparison of afatinib and erlotinib in non-small cell lung cancer with rare EGFR exon 18 and exon 20 mutations: a Turkish Oncology Group (TOG) study.

OBJECTIVES: To compare the survival of first- and second-generation tyrosine kinase inhibitors (TKIs) in patients with rare EGFR exon 18 and exon 20 mutation-positive non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: We retrospectively evaluated survival characteristics of 125 patients with EGFR exon 18 and exon 20 mutated NSCLC who received erlotinib or afatinib as first line treatment between 2012 and 2021 from 34 oncology centres. Since exon 20 insertion is associated with TKI resistance, these 18 patients were excluded from the study. RESULTS: EGFR exon 18 mutations were seen in 60%, exon 20 mutations in 16%, and complex mutations in 24% of the patients with NSCLC who were evaluated for the study. There were 75 patients in erlotinib treated arm and 50 patients in afatinib arm. Patients treated with erlotinib had progression-free survival time (PFS) of 8.0 months and PFS was 7.0 months in the afatinib arm (p = 0.869), while overall survival time (OS) was 20.0 vs 24.8 months, respectively (p = 0.190). PFS of exon 18 mutated arm was 7.0 months, exon 20 mutated arm was 4.3 months, and complex mutation positive group was 17.3 months, and this was statistically significant (p = 0.036). The longest OS was 32.5 months, seen in the complex mutations group, which was not statistically different than exon 18 and in exon 20 mutated groups (21.0 and 21.2 months, respectively) (p = 0.323). CONCLUSION: In this patient group, especially patients with complex mutations are as sensitive to EGFR TKI treatment similar to classical mutations, and in patients with rare exon 18 and exon 20 EGFR mutation both first- and second-generation EGFR-TKIs should be considered, especially as first- and second-line options.

Predictive role of neutropenia under crizotinib treatment in ALK-rearranged nonsmall cell lung cancer patients: A single-institution retrospective analysis.

Background: Anaplastic lymphoma kinase (ALK)-rearranged nonsmall cell lung cancer (NSCLC) represents a molecular subgroup with high sensitivity to ALK inhibitors. Tyrosine kinase inhibitor crizotinib, an anticancer drug acting as an ALK inhibitor, has shown remarkable response in ALK-positive NSCLC. The aim of our study is to explore the adverse events (AEs) of patients on crizotinib therapy and analyze the predictability of AEs for better survival or response on NSCLC patients. Methods: The medical records of our ALK-positive metastatic NSCLC patients who applied between years 2013 and 2018 had been reviewed retrospectively. ALK positivity of all patients had been detected by fluorescence in situ hybridization and no other driver mutations were present. Patient demographics, performance status, smoking history, previous treatments, metastatic sites, and AEs were recorded for further analyses. Results: Thirty-six ALK-positive metastatic NSCLC patients were included in the study. Median follow-up was 30.1 months. Median progression-free survival (PFS) for patients who developed hepatic, cardiac, or endocrine toxicities was similar when compared to patients who did not develop. Although there was a numeric median PFS difference between patients who did develop visual disorders (18.4 months) and did not develop visual disorders (15.5 month), this was not regarded as statistically significant. However, median PFS of the patients who developed neutropenia upon crizotinib treatment (31.9 months) was found to be more favorable than the patients with normal neutrophil counts (12.8 months) (P = 0.026). Conclusion: Neutropenia under crizotinib treatment was found to be associated with improved PFS suggesting that neutropenia might be an important determinant in treatment and survival strategies.

Evaluation of Treatment Efficacy of Tyrosine Kinase Inhibitors in Rare Single EGFR Exon 21 L861Q Mutation: Single Center Experience.

OBJECTIVE: Epidermal growth factor receptor mutations are the second most common oncogenic driver event in non-small cell lung cancer. We aimed to compare the first generation erlotinib treatment with the second generation afatinib treatment in patients with non- small cell lung cancer with epidermal growth factor receptor exon 21 L861Q mutation. MATERIAL AND METHODS: Progression-free survival and overall survival of 30 non-small cell lung cancer patients treated with erlo- tinib or afatinib due to single epidermal growth factor receptor L861Q positivity were compared retrospectively. The number of patients included in the first, second, and third treatment line was 15 (50.0%), 11 (36.7%), and 4 (13.3%), respectively. RESULTS: There were 23 patients in the erlotinib arm and 7 patients in the afatinib arm. Median progression-free survival was 12.8 months in the erlotinib group and 9.3 months in the afatinib group. Median overall survival in erlotinib and afatinib groups was 77.9 months and 30.3 months, respectively. No statistically significant difference was found in the comparison of these survival times. CONCLUSION: Survival times of erlotinib and afatinib treatment are similar in patients with a single epidermal growth factor receptor L861Q mutation. In patients receiving tyrosine kinase inhibitors treatment, the female gender has a positive effect on progression-free survival, and being a non-smoker has a positive effect on overall survival. In patients with rare mutation exon 21 L861Q positivity, both first-generation and second-generation tyrosine kinase inhibitors should be considered.

PDL-1 Expression and Survival in Metastatic Non-small Cell Lung Cancer Patients Who Received Chemotherapy as First-Line Treatment.

OBJECTIVE: To show the effect of programmed cell death protein-1ligand (PDL-1) level on survival times in patients with metastatic non-small cell lung cancer (mNSCLC) receiving chemotherapy, to determine the relationship between PDL-1 level, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). MATERIAL AND METHODS: The data of 158 patients who received chemotherapy for mNSCLC were evaluated retrospectively. Clinical and demographic data, PDL-1 expression levels and follow-up periods of the patients were recorded. The patients were divided into 2 groups according to PDL-1 levels. RESULTS: In all patients, progression free survival (PFS) was 5.6 months and overall survival (OS) was 18.8 months. Patients with low PDL-1 had a longer PFS than patients with high PDL-1 (p:0.038). In the gemcitabine and taxane groups, patients with low PDL-1 had a longer PFS than patients with high PDL-1 (p:0.047). There was a significant correlation between NLR and PDL-1 levels. In the groups with high PDL-1, patients with low NLR levels had higher OS than patients with high NLR level (p:0.043). Also, there was a significant difference between the OS patients with low and high PLR levels (p:0.520). CONCLUSION: In patients with mNSCLC whose PDL-1 levels and NLR levels are low, immunogenic chemotherapies such as gemcitabine and taxane can be tried as an alternative treatment.

Co-analysis of pancreatic cyst fluid carcinoembryonic antigen and glucose with novel cut-off levels better distinguishes between mucinous and non-mucinous neoplastic pancreatic cystic lesions.

BACKGROUND: Pancreatic cyst fluid analysis plays an important role in distinguishing between mucinous and non-mucinous cyst lesions. We aimed to compare the diagnostic performances of cyst fluid carcinoembryonic antigen (CEA), CA 19-9, and glucose in differentiating mucinous from non-mucinous neoplastic pancreatic cystic lesions (PCLs) and determine the best cut-off levels. METHODS: Patients' data were evaluated retrospectively. 102 patients' PCLs were grouped as non-neoplastic (n = 25), non-mucinous neoplastic (n = 20), mucinous neoplastic (n = 47) and pancreatic adenocarcinomas with cystic degeneration (n = 10); and CEA, CA 19-9, and glucose levels were compared. Receiver-operating characteristic analysis was performed, and the ideal cut-off values were determined. RESULTS: Cyst fluid CEA and CA 19-9, levels were significantly higher (P < 0.001, P < 0.001, respectively) and glucose levels were significantly lower (P = 0.001) in mucinous than in non-mucinous neoplastic PCLs. Area under curve with 95% confidence interval of CEA, glucose and CEA and glucose test combination was 0.939 (95% CI = 0.885-0.993, P = 0.001), 0.809 (95% CI = 0.695-0.924, P < 0.001) and 0.937 (95% CI = 0.879-0.995), respectively. CEA cut-offs to rule-in and rule-out mucinous neoplastic were 135.1 ng/mL (sensitivity = 62%, specificity = 94.7%) and 6.12 ng/mL (sensitivity = 94.1%, specificity = 80.4%), respectively. Glucose cut-off of 2.8 mmol/L was chosen both to rule-in and rule-out mucinous neoplastic PCLs (sensitivity = 78%, specificity = 80%). Co-analysis of CEA and glucose to distinguish mucinous from non-mucinous neoplastic PCLs had sensitivity = 87.8%, specificity = 93.3%, and diagnostic accuracy = 89.3%. CONCLUSIONS: We concluded that co-analysis of cyst fluid CEA (cut-off = 135.1 ng/mL) and glucose (cut-off = 2.8 mmol/L) at novel cut-offs had the best testing performance to rule-in mucinous neoplastic PCLs. To rule-out mucinous PCLs co-analysis of CEA (cut-off = 6.12 ng/mL) and glucose (cut-off = 2.8 mmol/L) added value to prediction.

A single-center experience: Liver biopsy results during a year.

Background and Aim: Liver biopsy is the gold standard method for the diagnosis and treatment of liver diseases. In this study, we aimed to evaluate the results of liver biopsies performed in a year in our clinic. In addition, we also aimed if these liver biopsies could reveal the etiology of liver disease in patients with elevations of transaminases or/and alkaline phosphatase levels or liver masses. Materials and Methods: Patients who had liver biopsies for persistently elevated transaminases or/and alkaline phosphatase levels, protocol biopsies after liver transplantation, or liver masses in our hepatology clinic between 2011 and 2012 were included in the study. Liver biopsy decisions were made by experts during the hepatology council. Liver biopsies were previously performed using classical percutaneous liver biopsy or ultrasonography-guided Sonocan® liver biopsy sets. The pathology results of liver biopsies and clinical data of the matching patients were obtained from the liver biopsy record archives and patient files, respectively. Results: Totally, 479 liver biopsy results (male=252, 52.6%, mean age 49±14.5 years) were evaluated in the study. Of these patients, 432 (male=228) underwent percutaneous liver biopsy and 47 (male=24) underwent Sonocan® needle biopsy. The most common histopathologic diagnoses in the percutaneous liver biopsy group were chronic hepatitis B (n=127, 29.4%), normal histopathological findings (n=50, 11.6% and 32 of them were protocol biopsies after liver transplantation), and nonalcoholic steatohepatitis (NASH, n=41, 9.5%). The most common histopathologic diagnoses in the Sonocan® group were 25 liver metastasis out of 29 liver tumors (n=25, 53.2% of all) chronic hepatitis B (n=5, 10.6%), and NASH (n=3, 6.4%). Conclusion: In this study, diversity in liver biopsy results indicates the importance of histopathological evaluation. The most prevalent pathology in the liver biopsies was chronic hepatitis B, which is the most common chronic liver disease in Turkey. The metastatic liver tumor was the most common among the liver masses.