Issues with the targeted therapy of non­small cell lung cancer with thyroid metastases: A case report.

Lung cancer is a common malignancy that has usually already metastasized at the time of diagnosis; however, thyroid metastases are extremely rare. Echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (ALK) fusion has been observed in 3-7% of cases of lung adenocarcinoma. ALK inhibitor therapy has been shown to exert a positive effect on disease progression. The present study describes the case of a patient with ALK-positive non-small cell lung carcinoma and thyroid metastases who exhibited a minimal response to ALK inhibitor therapy in the primary lesion, but had a complete pathological response in the thyroid, as confirmed by a thyroid biopsy. The present case report undermines the need for further evidence from genomic testing following this different tumor course in thyroid tissue.

Prognostic significance of omental disease and the role of omentectomy in non-endometrioid endometrial cancer.

OBJECTIVES: Non-endometrioid endometrial cancers (non-EEC) have different management from endometrioid endometrial cancers. The purpose of this study was to investigate the prognostic significance of omental disease and the role of omentectomy in non-endometrioid endometrial cancer and discuss the current literature with the findings. MATERIAL AND METHODS: The study included two hundred-three patients with non-EEC who underwent surgical treatment and follow-up between January 1996 and December 2018 in a University Hospital Gynecologic Oncology Center. The patients were divided into three groups according to whether omentectomy was performed and the presence of omental metastasis. The patient's demographics, clinical characteristics such as stage, grade, histopathologic type, lymphovascular space invasion (LVSI), myometrial invasion, lymph node involvement, and survival outcomes were compared between the groups. RESULTS: The study included 203 patients. Twenty-five patients (12%) had omental metastases. LVSI was reported in 57.3%, 88.0%, and 43.2% of the non-omentectomy, no-omental metastasis, and omental metastatic groups, respectively (p = 0.001). The 5-year disease-free survival (DFS) and overall survival (OS) rates according to the tumor grade, peritoneal cytology, and lymphadenectomy were also compared and were found to be statistically similar. The five-year OS rates were 70.6% for the group without omental metastases and 16.2% for the group with omental metastases, respectively (p = 0.001). In the group of omentectomy, the five-year DFS rates were 62.2% in cases without omental metastasis and 13.0% in cases with omental metastasis (p = 0.001). The five-year OS rates of 86.3% and DFS rates of 80.0% in the group without omentectomy. CONCLUSIONS: In non-endometrioid tumors, the survival rate was better in the group that did not undergo omentectomy. Based on these results, we can say that omentectomy may not be necessary for non-endometrioid tumors whose omentum is found to be normal in intraoperative visual examination.

Predictability of lymph node involvement in uterus-confined endometrioid endometrial cancer by tumour size, pattern and location measured with transvaginal ultrasonography: can we save time?

We aimed to investigate whether transvaginal ultrasonography (TVUSG)-measured tumour size, pattern and location were significant predictors for lymph node metastasis in the uterus-confined endometrioid endometrial cancer (EEC) patients. A total of 213 patients with EEC were recruited and 73 of them were considered eligible and were analysed according to lymph node involvement. Tumour size, pattern and location measured by transvaginal ultrasound were recorded. Thereafter, patients were distributed according to their lymph node involvement and were compared with respect to these parameters. The patients' median age was 56 (27-80). Mean of the resected lymph nodes was 29.68 and 33.5 in lymph-node-negative and positive patients, respectively (p=.525). Tumour diameter was measured >2 cm on transvaginal ultrasound in 28 (48.3%) and 13 (86.7%) cases of the lymph node-negative and positive arms, respectively (p=.008). Transvaginal ultrasound revealed that 18 (31.0%) tumours in lymph node-negative and two (13.3%) in the node positive patients had polypoid pattern (p=.171). Seventeen (54.8%) tumours of the lymph node-negative group and three (42.9%) of the node positive group were determined in the lower uterine segment (p=.250). While tumour diameter measured with TVUSG was predictable for lymph node involvement in the uterus-confined EEC, its pattern and location were not.Impact StatementWhat is already known on this subject? In clinically early-stage endometrioid endometrial cancer (EEC), it has been recognised for decades that selective lymphadenectomy is a more acceptable strategy than the systematic lymphadenectomy, owing to the low rate of lymph node metastases in the patients. Preoperative imaging, frozen section and recently accepted lymph node concept are the prominent methods in designating appropriate candidates for lymphadenectomy. The measurement of tumour diameter or size obtained intraoperatively by frozen section assessment is one of the parameters used in MAYO criteria for selective lymphadenectomy in endometrial cancer patients.What do the results of this study add? In our study, tumour diameter measured with transvaginal ultrasonography was predictable for lymph node involvement in the uterus-confined EEC.What are the implications of these findings for clinical practice and/or further research? Transvaginal ultrasonography-measured tumour diameter can be considered in deciding to proceed with pelvic lymphadenectomy while waiting for the frozen section result. It should be remembered that this approach could be considered only in clinics using MAYO criteria for selective lymphadenectomy, and it needs to be confirmed with more prospective studies.

Could the Long-Term Oncological Safety of Laparoscopic Surgery in Low-Risk Endometrial Cancer also Be Valid for the High-Intermediate- and High-Risk Patients? A Multi-Center Turkish Gynecologic Oncology Group Study Conducted with 2745 Endometrial Cancer Cases. (TRSGO-End-001).

This study was conducted to compare the long-term oncological outcomes of laparotomy and laparoscopic surgeries in endometrial cancer under the light of the 2016 ESMO-ESGO-ESTRO risk classification system, with particular focus on the high-intermediate- and high-risk categories. Using multicentric databases between January 2005 and January 2016, disease-free and overall survivals of 2745 endometrial cancer cases were compared according to the surgery route (laparotomy vs. laparoscopy). The high-intermediate- and high-risk patients were defined with respect to the 2016 ESMO-ESGO-ESTRO risk classification system, and they were analyzed with respect to differences in survival rates. Of the 2745 patients, 1743 (63.5%) were operated by laparotomy, and the remaining were operated with laparoscopy. The total numbers of high-intermediate- and high-risk endometrial cancer cases were 734 (45%) patients in the laparotomy group and 307 (30.7%) patients in the laparoscopy group. Disease-free and overall survivals were not statistically different when compared between laparoscopy and laparotomy groups in terms of low-, intermediate-, high-intermediate- and high-risk endometrial cancer. In conclusion, regardless of the endometrial cancer risk category, long-term oncological outcomes of the laparoscopic approach were found to be comparable to those treated with laparotomy. Our results are encouraging to consider laparoscopic surgery for high-intermediate- and high-risk endometrial cancer cases.

Morphological features of the secretory phase endometrium in women with unexplained infertility.

In this study, we evaluated the structural features of the endometrial tissues, the immunohistochemical expression of MUC-1, which plays an important role in implantation, and the biochemical markers during the implantation window. Randomly chosen 18 fertile and 18 unexplained infertile women that have 27-32 days long menstrual cycle, normal hormonal values, normal USG findings of ovary and endometrium were included. Five, six, and seven days after ovulation, endometrial biopsies were taken and prepared in accordance with light and electron microscopy tissue preparation methods. Immunohistochemical methods were used to determine MUC-1 expression in the tissues. Serum hormone levels were determined. The MUC-1 immunoreactivity, as well as the serum levels of FSH, LH, TSH, estrogen, progesterone, and total testosterone did not differ significantly between the two groups; however, prolactin levels were higher in the infertile group. In the unexplained infertile samples, intraepithelial lymphocytes were frequently observed, the microvilli of the surface columnar epithelium were widespread, cells with pinopodes as well as vesiculated cells were minimal, pinopode development was insufficient, and the development of the endometrial glands was deficient. It was concluded that these structural differences observed in the surface and glandular epithelium of the endometrium in unexplained infertile patients may be due to the insufficiency of these cells in responding to steroid hormones; therefore, these changes may affect the implantation of the blastocyst in the endometrium.

Expression of monocyte chemotactic protein 2 and tumor necrosis factor alpha in human normal endometrium and endometriotic tissues.

Endometriosis is a gynocological disease characterized by the presence of the endometrial glands and stroma outside the uterine cavity. This disease affects % 6-10 of women with reproductive age and it causes serious problems such as pelvic pain, dysmenorrhea and infertility. Although endometriosis is one of the most investigated disease of gynecology, its pathogenesis is not clear completely. In recent years, many studies revealed the inflammatory nature of endometriosis. Many of the immune cells and their secretory products cytokines and chemokines has been detected in body fluids of women with endometriosis. Cytokines are protein or glycoprotein in structures and hormon-like molecules that act generally in a paracrine fashion to regulate immun responses. They involved in chemotaxis, cell proliferation, cell activation, motility, adhesion and morphogenesis. Tumor necrosis factor alpha (TNF-α) is a proinflammatory cytokine secreted by the macrophages, monocytes, neutrophiles, T cells and natural killer cells. It stimulates increase in the level of the chemokines in body fluids. Monocyte chemotactic protein 2 (MCP-2) is a chemokine act to recruit and activate monocytes into sites of inflammation area. The aim of this study to investigate the ultrastructural properties and whether the expression and localization of TNF-α and MCP-2 in the eutopic endometrium (normal endometrium of women with endometriosis) and endometritic tissues of women with endometriosis. Eutopic endometrial and endometriotic tissue samples were obtained from women with endometriosis between 20-41 y and normal endometrial tissues were collected from 5 women without endometriosis as a control group. Tissues were processed for light and electron microscopy and examined. The epithelial cells of endometriotic tissues were revealed strongly cytoplasmic TNF-α and MCP-2 immunreactivities. Eutopic endometrial tissues were also stained prominently for both TNF-α and MCP-2. Furthermore, a significant increase in stromal macrophages were observed in endometriotic tissues. Moreover, the ultrastructural observations on the normal and endometriotic tissues were exhibited microvilli-rich cells and ciliated cells. These findings suggest that TNF-α and MCP-2 may be involved in normal endometrial biology and in the pathogenesis of endometriosis.

The impact of morbid obesity on survival of endometrial cancer.

OBJECTIVE: Morbid obesity is identified as patients with a body mass index more than 40 kg/m2. Obesity is known as a risk factor for endometrial cancer due to the increase of the deposited estrogen. This study was conducted to evaluate the effect of morbid obesity on the survival of endometrial cancer. MATERIALS AND METHODS: The archival records and pathologic reports of patients with endometrial cancer who underwent surgery and were followed up in Çukurova University Gynecologic Oncology Center between January 1996 and December 2018 were reviewed, retrospectively. Data regarding body mass index and survival was reported in 520 patients. These patients were stratified into two groups according to their body mass index, <40 and ≥40 kg/m2. The groups' clinic, pathologic features, and survival rates were compared. RESULTS: There were 146 patients in the morbidly obese group and 374 patients in the obese group. The mean age of the groups was 58.5 and 56.2 years, respectively. The mean follow-up time was 51.6 months. Comorbidities were significantly higher in the morbidly obese group. The five-year disease-free and overall survival rates were 78.3% and 85.3% in the morbidly obese group, and 81.6% and 90.1% in the obese group, respectively. Although the groups' clinical and pathologic features were homogeneously distributed, disease-free and overall survival rates were significantly different (p=0.053 and p=0.054, respectively). CONCLUSION: Morbidly obese patients with endometrial cancer were associated with 2.7-fold increased risk of death and 1.7-fold increased risk of recurrence compared with those who had body mass index <40 kg/m2. It is important to deal with the frequent comorbidities in this special group, which could be simply altered by lifestyle changes. Morbidly obese patients with endometrial cancer should be encouraged in lifestyle changes and consulted by dieticians and endocrinologists.

Prognostic significance of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) expression in uterine carcinosarcoma.

OBJECTIVE: The aim of this study was to evaluate the clinical and prognostic importance of programmed death-1 (PD-1) and/ or programmed death-ligand 1 (PD-L1) in uterine carcinosarcoma (UCS). STUDY DESIGN: Formalin-fixed, paraffin-embedded tissue samples from 59 cases with UCS were analyzed. PD-1 and PD-L1 expressions in tumor tissue and microenvironment were detected by immunohistochemistry. Clinical and pathological characteristics including age, stage, initial symptom, surgical approach, myometrial invasion, lymphovascular space invasion (LVSI), lymph node invasion, adjuvant therapy, and survival were evaluated. The Kaplan-Meier and Cox proportional hazards models were used to compare the outcomes and prognostic factors. RESULTS: PD-1 expression in tumor tissue and microenvironment was detected in 15 (25 %) and 18 (30 %) cases, respectively. PD-L1 expression in tumor tissue and microenvironment was detected in 15 (25 %) and 12 cases (20 %), respectively. PD-L1 expression in tumor was associated with longer survival and median survival was 38 and 15 months in cases with and without PD-L1 expressions, respectively (p = 0.019). Lymphovascular space invasion (LVSI) (p = 0.014), myometrial invasion (p = 0.008) and PD-L1 expression were found to be prognostic for UCS's. PD-L1 expression was found to be an independent good prognostic factor with Cox regression analysis (OR 3.9; 95 % CI: 1.4-11.0) for overall survival. CONCLUSION: PD-1 and/or PD-L1 expression are important due to their expressions in one fourth of the cases with UCS and PD-1/PD-L1 blockade may be a new avenue in UCS.

The prognostic analysis of the some clinicopathological parameters and gene protein expressions in malignant mesothelioma.

INTRODUCTION: Mesothelioma is an aggressive tumour that originates in serous surfaces. The primary end point of this study was to invastigate the relationship of progression free survival (PFS) and overall survival (OS) with the c-Met, EGFR, PTEN, PDGFR-alpha, PI3K/AKT and mTOR expression levels in the tumour tissue of pleural and peritoneal mesothelioma cases. MATERIALS AND METHODS: The study included 53 patients diagnosed with mesothelioma between 2005 and 2016. The cases were separated into 2 groups as pleural and peritoneal. The effects on OS and PFS were examined of the c-Met, EGFR, PTEN, PDGFR-alpha, PI3K/AKT and mTOR expression levels and also clinicopathological parameters and the treatments given. In the statistical analysis of the data obtained, IBM SPSS vn 20.0 software was used. RESULT: Of the 53 patients included in the study, 39 (73.6%) were diagnosed with pleural mesothelioma and 14 (26.4%) with peritoneal mesothelioma. According to the c-Met and mTOR expression, OS and PFS of the peritoneal cases with high expression (2+, 3+) was seen to be significantly better than that of the peritoneal cases with low expression (0, 1+) (p<0.05). According to the PDGFR expression, OS and PFS of the pleural cases with low expression (0, 1+) was seen to be significantly better than that of the pleural cases with high expression (2+, 3+) (p<0.05). CONCLUSIONS: The examination of c-MET, PDGFR-alpha and m-TOR expression in the in the tumor tissue of mesothelioma cases may be important in determining prognosis.

Use of the ELISA (Em2-Em18) and Western Blotting Methods on Diagnosis of Alveolar Echinococcosis

Objective: Alveolar echinococcosis (AE) is one of the most lethal parasitic zoonoses in the Northern Hemisphere, and early serological detection is important to start treatment and to improve survival. A total of 50 sera samples of patients diagnosed as having various diseases were examined for by two different serological diagnostic methods. Methods: Em2-Em18 ELISA (Bordier Affinity Products, Crissier, Switzerland) and Echinococcus Western Blot immünoglobulin G (IgG) (LDBIO Diagnostics, Lyon, France) were used for analyisis. Results: A high titer of antibodies was found in 9 of 10 patients diagnosed as having AE with Em2-Em18 ELISA, in 2 of 21 patients with cystic echinococcosis, in 1 of 2 patients with fascioliasis and in 1 patient with chronic hepatitis. The Echinococcus Western Blot IgG test, used as a confirmatory test, showed IgG antibody in 85.7% (18/21) of patients with CE, while all serum samples of 10 patients with AE were evaluated as positive. This method yielded an incorrect diagnosis in the patient with chronic hepatitis and in the patient with granulomatous inflammation with caseification. Samples taken from patients with liver-related diseases and other parasitic-related diseases were found to be negative. Conclusion: The serological methods used in the study were found to be important in the early diagnosis of alveolar echinococcosis in the endemic areas, since it could be used in sero-epidemiological studies.

Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) expressions in type 2 endometrial cancer.

PURPOSE: The aim of this study was to evaluate prognostic importance of programmed death-1 (PD-1) and/ or programmed death-ligand 1 (PD-L1) expressions in type 2 endometrial cancer. Study design Formalin-fixed, paraffin-embedded tissue samples from 53 cases with type 2 endometrial cancer were analyzed. One-third of our cases had serous adenocarcinoma (32%), 11 had clear cell (21%) and 25 had mixed-type adenocarcinoma (47%). PD-1 and PD-L1 expressions in tumor tissue and microenvironment were detected by immunohistochemistry. Clinical and pathological characteristics including age, stage, initial symptom, surgical procedure, myometrial invasion, lymphovascular space invasion (LVSI), lymph node invasion, adjuvant therapy, and survival were reviewed. The Kaplan-Meier and Cox proportional hazards models were used to evaluate the prognostic factors. RESULTS: PD-1 expression in tumor tissue and microenvironment was detected in 22 (42%) and 28 (53%) cases, respectively. PD-L1 expression was detected in tumor and microenvironment in 8 (15%) and in 15 cases (28%), respectively. Expression of PD-1 and PD-L1 expressions in tumor area was associated with shorter survival (p = 0.006 and 0.001, respectively) but PD-1 and PD-L1 expressions in microenvironment were not found to be related with survival. PD-1 (p = 0.006) and PD-L1 expressions (p = 0.001) in addition to LVSI (p = 0.005), myometrial invasion (p = 0.015), lymph node involvement (p = 0.019), and suboptimal cytoreduction (p = 0.042), were found to be associated with poor prognostic indicators. PD-1 and PD-L1 expressions in tumor and lymph node involvement were determined as independent prognostic factors. CONCLUSION: PD-1 and PD-L1 expressions in type 2 endometrial cancers were found to be poor prognostic indicators.

Laparoscopic surgery for low, intermediate and high-risk endometrial cancer.

OBJECTIVE: The aim of the present study was to compare the long-term outcomes of the laparotomy (LT) and laparoscopic surgery and to evaluate the results according to low, intermediate, and high-risk groups of endometrial cancer (EC). METHODS: We identified 801 patients with EC and these patients were classified as group 1, who underwent LT (n=515); and group 2, who underwent laparoscopy (LS) (n=286). Patient's demographics, clinical characteristics such as stage, grade, histopathologic type, lymphovascular space invasion, myometrial invasion, lymph node involvement, and risk groups, peri- and post-operative outcomes, and survival outcomes were compared between the groups according to risk classification. Survival outcomes were assessed using Kaplan-Meier method. RESULTS: The demographic characteristics of both groups were similar except age. Shorter hospital stay and fewer complications were observed in group 2. The overall survival (OS) were similar in the low, low-intermediate, high-intermediate and high-risk groups (p=0.269, 0.476, 0.078, and 0.085; respectively) for LS compared to LT. The covariate analysis revealed that the death and recurrence risks were approximately twice higher in the LT group than in the LS group (odds ratio [OR]=1.9; 95% confidence interval [CI]=1.2-3.1 for OS; OR=2.0; 95% CI=1.2-3.3 for disease-free survival). CONCLUSION: The results of our study support the well-known positive aspects of LS as well as safe and effective use in cases of intermediate and high-risk EC.

Early propranolol treatment ameliorates endothelial dysfunction in experimental septic lung.

BACKGROUND: Recent reports have indicated an improved prognosis in sepsis with ß-blocker agents; however, the underlying action mechanism is still under debate. OBJECTIVES: The aim of this study was to investigate the potential effect of propranolol on endothelial dysfunction in septic rats. MATERIAL AND METHODS: The cecal ligation and puncture model (CLP) was used to generate sepsis. Adult male Wistar-Albino rats were divided into 4 groups: group 1 was a sham group, group 2 received sterile saline, group 3 received 10 mg/kg of propranolol 3 days before the intervention, and group 4 received 10 mg/kg of propranolol 30 min after CLP. Six rats from each group were sacrificed 24 h postoperatively. The remaining rats were followed for survival. We have also evaluated the effects on systemic inflammation, coagulation and the lung tissue with immunohistochemical and electron microscopic evaluation. RESULTS: Serum tumor necrosis factor alpha (TNF-α) and plasminogen activator inhibitor-1 (PAI-1) levels, as well as tissue TNF-α scores were elevated in septic rats. Electron microscopic examination of the lung tissue showed endothelial dysfunction in the sepsis group. Pretreatment significantly improved survival. Moreover, pre-treatment altered serum vascular endothelial growth factor receptor-1 (VEGFR-1) levels and post-treatment reduced serum PAI-1 and VEGFR-1 levels. In both the preand post-treatment groups, electron microscopic examination revealed improvement of the destroyed lung endothelium and showed only mild alterations in the cytoplasmic organelles, especially in the mitochondria of the endothelial cells. CONCLUSIONS: These results suggest that the improved outcome with ß-blockers in sepsis may be due to the ameliorated endothelial dysfunction. Further studies focusing on the potential effect of ß-blockers on the endothelium may lead to a better understanding of sepsis.

PD-1 and PD-L1 expression in thymic epithelial tumours and non-neoplastic thymus.

AIMS: We explored the relationships between programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) expression and the pathological and clinical features of thymic epithelial tumours and thymic hyperplasia. METHODS: We evaluated PD-1 and PDL-1 expressions within epithelial and microenvironmental components in thymic epithelial tumours (n=44) and thymic hyperplasias (n=8), immunohistochemically. We compared the results with demographic, clinical and histopathological features of the cases. RESULTS: We found 48% epithelial expression and 82.7% microenvironment expression for PD-1 and 11.5% epithelial expression and 34.6% microenvironment expression for PD-L1. There was no PD-1 expression, in either the epithelial or microenvironment, in the thymic hyperplasia group. PD-1 and PD-L1 positivity was more significant in thymic epithelial tumours than thymic hyperplasia. Patients with PD-1-positive microenvironments exhibited significantly shorter mean estimated survival time than their negative counterparts. CONCLUSION: These findings suggest that anti-PD-1 and anti-PD-L1 therapies may benefit patients due to high release of PD-1 and PD-L1 in thymic epithelial tumours.

Thymoma: a clinicopathological correlation of 1470 cases.

We present 1470 surgical resections for thymoma identified in the pathology files of 14 institutions from 11 countries with the purpose of determining and correlating a simplified histological classification of thymoma and pathological staging with clinical outcome. The study population was composed of 720 men and 750 women between the ages of 12 and 86 years (average, 54.8 years). Clinically, 137 patients (17%) had a history of myasthenia gravis, 31 patients (3.8%) of other autoimmune disease, and 55 (6.8%) patients of another neoplastic process. Surgical resection was performed in all patients. Histologically, 1284 (87.13%) cases were thymomas (World Health Organization types A, B1, and B2, and mixed histologies), and 186 (12.7%) were atypical thymomas (World Health Organization type B3). Of the entire group, 630 (42.9%) were encapsulated thymomas, and 840 (57.9%) were invasive thymomas in different stages. Follow-up information was obtained in 1339 (91%) patients, who subsequently were analyzed by univariate and multivariate statistical analysis. Follow-up ranging from 1 to 384 months was obtained (mean, 69.2 months) showing tumor recurrence in 136 patients (10.1%), whereas 227 died: 64 (28.2%) due to tumor and 163 (71.8%) due to other causes. Statistical analysis shows that separation of these tumors into thymoma and atypical thymoma is statistically significant (P = .001), whereas tumor staging into categories of encapsulated, minimally invasive, and invasion into adjacent organs offers a meaningful clinical assessment with a P = .038. Our findings suggest that our simplified histological schema and pathological staging system are excellent predictors of clinical outcome.

Diagnostic and Treatment Reproducibility of Cervical Intraepithelial Neoplasia / Squamous Intraepithelial Lesion and Factors Affecting the Diagnosis.

OBJECTIVE: Inter-observer differences in the diagnosis of HPV related cervical lesions are problematic and response of gynecologists to these diagnostic entities is non-standardized. This study evaluated the diagnostic reproducibility of "cervical intraepithelial neoplasia" (CIN) and "squamous intraepithelial lesion" (SIL) diagnoses. MATERIAL AND METHOD: 19 pathologists evaluated 66 cases once using H&E slides and once with immunohistochemical studies (p16, Ki-67 and Pro-ExC). Management response to diagnoses was evaluated amongst 12 gynecologists. Pathologists and gynecologists were also given a questionnaire about how additional information like smear results and age modify diagnosis and management. RESULTS: We show moderate interobserver diagnostic reproducibility amongst pathologists. The overall kappa value was 0.50 and 0.59 using the CIN and SIL classifications respectively. Impact of immunohistochemical evaluation on interpretation of cases differed and there was lack of statistically significant improvement of interobserver diagnostic reproducibility with the addition of immunohistochemistry. We saw that choice of treatment methods amongst gynecologists varied and overall concordance was only fair to moderate. The CIN2 diagnostic category was seen to have the lowest percentage agreement amongst both pathologists and gynecologists. We showed that pathologists had diagnostic "styles" and gynecologists had management "styles". CONCLUSION: In summary each pathologist had different diagnostic tendencies which were affected not only by histopathology and marker studies, but also by the patient management tendencies of the gynecologist that the pathologist worked with. The two-tiered modified Bethesda system improved diagnostic agreement. We concluded that immunohistochemistry should be used only to resolve problems in select cases and not for every case.

Does preoperative neutrophil to lymphocyte or platelet to lymphocyte ratios have a role in predicting borderline ovarian tumors?

BACKGROUND: to investigate the value of using preoperative neutrophil to lymphocyte and platelet to lymphocyte levels in the patients of borderline ovarian tumors. METHODS: During the period between January 2002 and December 2015, the pathology reports and archival files of the Gynecologic Oncology Department of Çukurova University Medical Hospital and the Gynecologic Oncology Department of Dumlupinar University, Evliya Çelebi Education and Research Hospital were retrospectively reviewed, and 144 patients of borderline ovarian tumor (as the study group) and 123 patients of serous cystadenoma (as the control group) were determined for eligibility in this study. Data regarding age, menopausal status, preoperative ultrasound findings, ca125 and complete blood counts were reviewed. Neutrophil to lymphocyte and platelet to lymphocyte ratios were calculated and these parameters were statistically compared between the groups. RESULTS: There was a statistically significant difference between the groups according to neutrophil count, platelet count, neutrophil to lymphocyte ratio and platelet to lymphocyte ratio; in addition to age, ca125 and preoperative ultrasound findings. CONCLUSIONS: It seems that neutrophil to lymphocyte and platelet to lymphocyte ratios are useful in predicting borderline ovarian tumors, preoperatively. However, further prospective studies are needed.

A Single-Institution Radical Surgery Results in Stage IB2/IIA2 (Bulky) Cervical Cancer.

OBJECTIVE: The aim of this study is to evaluate the results of radical surgery in patients with stage IB2 to IIA2 cervical cancer who were operated on at our center between 2002 and 2015. MATERIALS AND METHODS: Forty-seven cases of patients with stage IB2/IIA2 cervical cancer who underwent primary radical surgery between 2002 and 2015 were enrolled in this study. Patients' files and pathological reports were retrospectively reviewed. Surgical, pathological, and clinical variables were analyzed and their impact on survival period was researched. Disease-free survival and overall survival periods were determined using the Kaplan-Meier test. The P value was considered significant if less than 0.05. RESULTS: Type C2 radical hysterectomy with lymphadenectomy (5 pelvic, 42 pelvic and para-aortic) was performed for all of the 47 patients in accordance with the Querleu-Morrow classification. Thirty-three of the cases were stage Ib2 and 14 cases were IIa2. Five years of overall survival was 80%. Recurrence was noted in 10 (7 pelvic, 3 extrapelvic) patients. Adjuvant therapies were needed for 83% of the patients. A univariate analysis was made for all included variables in this research and, other than recurrence, none of them was found to be statistically significant on OS and DFS. CONCLUSIONS: Although adjuvant therapies are often resorted to, primary radical surgery is also a reasonable treatment option for stage IB2/IIA2 cervical cancer, especially in young premenopausal patients when preserving ovarian functions is desired.

Expression of fibroblast growth factor receptor 1, fibroblast growth factor 2, phosphatidyl inositol 3 phosphate kinase and their clinical and prognostic significance in early and advanced stage of squamous cell carcinoma of the lung.

AIM: Non-small cell lung carcinoma is the leading cause of cancer related to death in the world. Squamous cell lung carcinoma (SqCLC) is the second most frequent histological subtype of lung carcinomas. Recently, growth factors, growth factor receptors, and signal transduction system-related gene amplifications and mutations are extensively under investigation to estimate the prognosis and to develop individualized therapies in SqCLC. In this study, besides the signal transduction molecule phosphatidyl inositol-3-phosphate kinase (IP3K) p110α, we explored the expressions of fibroblast growth factor 2 (FGF2) and receptor-1 (FGFR1) in tumor tissue and also their clinical and prognostic significance in patients with early/advanced SqCLC. MATERIALS AND METHODS: From 2005 to 2013, 129 patients (23 early, 106 advanced disease) with a histopathological SqCLC diagnosis were selected from the hospital files of Cukurova University Medical Faculty for this study. Two independent pathologists evaluated FGFR1, FGF2, and PI3K (p110α) expressions in both tumor and stromal tissues from 99 of the patients with sufficient tissue samples, using immunohistochemistry. Considering survival analysis separately for patients with both early and advanced stage diseases, the relationship between the clinical features of the patients and expressions were evaluated by univariate and multivariate analyses. RESULTS: FGFR1 expression was found to be low in 59 (60%) patients and high in 40 (40%) patients. For FGF2; 12 (12%) patients had high, 87 (88%) patients had low expression and for IP3K; 31 (32%) patients had high and 66 (68%) patients had low expressions. In univariate analysis, overall survival (OS) was significantly associated with stage of the disease and the performance status of the patient (P<0.0001 and P<0.001). There was no significant difference in OS of the patients with either low or high expressions of FGFR1, FGF2, and IP3K. When the patients with early or advanced stage disease were separately taken into consideration, the relationship did not differ, either. Any of FGFR1, FGF2 or IP3K expressions was not found predictive for the treatment of early or advanced staged patients. On the other hand, the expressions of both FGFR1 and FGF2 were significantly different with respect to smoking, scar of tuberculosis and scar of radiotherapy (P=0.002; P=0.06 and P=0.05, respectively). DISCUSSION: There has not been identified an effective individualized treatment for SqCLC yet. Therefore, in order to be able to develop such a treatment in the future, it is essential to identify the genetic abnormalities that are responsible for the biological behaviors and carcinogenesis of SqCLC. Although we could not show the prognostic and predictive significance of FGFR1, FGF2 and IP3K expressions in SqCLC, we determined the expression rates of FGFR1, FGF2 and IP3K as a reference for Turkish patients. In conclusion, we want to put some emphasis on the fact that, pulmonary fibrosis which is a late complication of radiotherapy at stage III disease, and the scar of tuberculosis could be associated with FGFR1 and FGF2 expressions.