Investigation of natural and artificial radioactivity levels in travertines of the Cappadocia region in Turkey.

This study determined natural and artificial radionuclide concentrations to evaluate natural radioactivity and health risk levels of nine travertines in the Yaprakhisar and Balkayasi regions in Turkey. The samples coded B1-M, B2, B5, B7, B8, and B10 represent waste derived from the Yaprakhisar travertines, as well as samples T5-M, T12, and Z1 travertines derived from Balkayasi. The levels of natural and artificial radionuclide concentrations (232Th, 40K, and 137Cs) were measured using a high-purity germanium (HpGe) detector system. The travertine activity ranged from 2.09 to 12.07 Bq kg-1 for 232Th, 4.21 to 13.41 Bq kg-1 for 40K, and 0.42-3.26 Bq kg-1 for 137Cs. The results showed that the activity concentration values for 232Th, 40K, and 137Cs were coherent with the travertine analysis results in the UNSCEAR, 2000; 2008 publications. The values obtained were lower than the average values in the UNSEAR reports. The radiological hazard parameters calculated in this study were absorbed gamma dose rate (D), radium equivalent activity (Raeq), annual gonadal dose equivalent (AGDE), exposure dose (ER), total annual effective dose (AEDEtotal), excess lifetime cancer risk (ELCRtotal), gamma representative level (GRL), internal hazard index (Hin) and external hazard index (Hex).

A quantitative sonoelastography evaluation of ocular and periocular elasticity after intravitreal ranibizumab injection.

PURPOSE: We evaluated changes in ocular and periocular elasticity by ultrasound (US) elastography in intravitreal ranibizumab-treated eyes and the healthy fellow eyes of patients with neovascular AMD. METHODS: The study was performed on 52 eyes of 26 volunteers who ranged in age from 59 to 89 (mean 72±7.78) years old. The study group consisted of the patients with neovascular AMD treated with intravitreal ranibizumab. The fellow eyes (without choroidal neovascularization) of the study group were selected as the control group. All patients were examined with sonoelastography before intravitreal injection and at 1day, 1week, and 1month after intravitreal injection. All images were acquired with a Toshiba Aplio 500 ultrasound system (Tokyo, Japan) including software with a combined autocorrelation method and a multifrequency linear probe. The elastography values of the anterior vitreous (AV), posterior vitreous (PV), retina-choroid-sclera complex (RCS), retrobulbar fat tissue (RF), optic nerve head (ONH) and retrobulbar optic nerve (RON) were measured in each eye. RESULTS: There were 13 male (50%) and 13 female (50%) participants in our study. Anterior vitreous, posterior vitreous, RCS, retrobulbar fat tissue, ONH, and RON US elastography values were similar in both groups (P˃0.05 for all). On the other hand, there was a positive correlation between the difference between baseline and 1-month PV sonoelastography values and age (r=0.47, P=0.035). CONCLUSION: A single dose intravitreal Ranibizumab (Lucentis®, Genentech, USA) injection does not alter the elasticity of ocular and periocular structures.

Tono-pen and Schiotz tonometer measurements in gas-filled eyes.

PURPOSE: This study aims to assess the difference between Tono-Pen and Schiotz tonometer measurements in gas-filled eyes and to create a nomogram and equation which can be used to estimate actual intraocular pressure in order to provide a safe IOP level at the end of the surgery. METHODS: Twenty-two eyes that underwent pars plana vitrectomy were included in the study. Perioperative Tono-Pen and Schiotz tonometer measurements were performed when the eyes were filled with air in the setting of certain vitrectomy infusion pressure levels. Measurements were performed when the eyes were filled with fluid to test the accuracy of the systems. The mean value of the Tono-Pen and Schiotz readings in air-filled eyes corresponding to certain actual intraocular pressure levels were analyzed to create nomograms. RESULTS: Both Tono-Pen and Schiotz tonometers underestimated the actual intraocular pressure set on the screen of the vitrectomy system in the air-filled eyes. The Tono-Pen deviation was 4.5mmHg at a level of 15mmHg actual intraocular pressure, and 16.9mmHg at a level of 55mmHg actual intraocular pressure. The Schiotz tonometer deviation was 10mmHg at a level of 15mmHg actual intraocular pressure, and 8.9mmHg at a level of 55mmHg actual intraocular pressure. All the mean differences between tonometer readings and actual intraocular pressure were statistically significant. (P<0.001) CONCLUSION: To achieve an adequate and safe tamponade at an actual IOP range of 20 - 25mmHg, one should adjust the IOP with Schiotz readings to a level of 9-12mmHg, or Tono-Pen readings to 12-18mmHg.

Oligometastatic Prostate Cancer.

BACKGROUND: With advancements in diagnostic techniques, oligometastatic prostate cancer is diagnosed in patients who were, in the past, considered to have localized disease. Moreover, evidence of the effectiveness of treatment intensification for this disease is increasing, focusing on primary tumors as well as metastatic lesions. Thus, we can delay the start of systemic palliative treatment and improve overall survival. Many questions remain unclear, such as the definition of oligometastasis disease, or which patients should be offered aggressive treatment. Data are limited and come from small retrospective studies but show conclusively the benefits of survival in targeted primary prostate and metastatic prostate cancer therapy with surgery or radiotherapy. Often, stereotactic radiotherapy is used in this indication, with minimal side effects. In retrospective studies, 3-5 metastatic lesions were generally accepted for definition of oligometastatic disease, but patient subgroups were heterogeneous. A recent study attempts to better define oligometastatic disease and find out the right degree of intensification of treatment. When and in which patient to use metastasis-targeted therapy and when the standard systemic treatment is already meaningful. It is already clear that selected patients benefit from targeted personalized treatment. PURPOSE: The purpose of this review is to offer an update of the problem of oligometastatic prostate cancer. The article presents an overview of data from contemporary literature, modern possibilities of diagnostic imaging methods and treatment options of oligometastatic prostate cancer including surgery and radiotherapy.  authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 8. 2. 2019 Accepted: 5. 3. 2019.

Effect of aflibercept on persistent macular edema secondary to central retinal vein occlusion.

PURPOSE: To evaluate the efficacy of switching treatment from intravitreal ranibizumab to intravitreal aflibercept on the treatment of refractory macular edema secondary to central retinal vein occlusion (CRVO). METHODS: In this retrospective study; 12 eyes with refractory macular edema secondary to CRVO after multiple monthly repeated intravitreal 0.5mg/0.05mL ranibizumab injections prior to switching therapy to intravitreal 2mg/0.05mL aflibercept, between March 2012 and April 2016 were reviewed. The follow-up time was 12 months. Changes in best-corrected visual acuity (BCVA), central macular thickness (CMT), central retinal volume (CRV) and injection interval between baseline and month 1, 3, 6 and 12 after switching therapy to aflibercept were reviewed and evaluated. RESULTS: Mean baseline CRT decreased from 516±101 mic. to 252±114 mic. at month 12 (P=0.008). Mean baseline CRV decreased from 8.74±2.13 mm3 to 6.82±1.64 mm3 at month 12 (P=0.005). Baseline BCVA improved from 0.73±0.21 to 0.53±0.17 logMAR at month 12 (P=0.004). Mean BCVA gain was two logMar lines (10 letters) at month 12. After switching therapy to aflibercept; the mean injection interval increased significantly from 1.34 months at baseline to 1.86 months at month 12, by an increase of 0.52 months (P=0.02). CONCLUSION: Intravitreal aflibercept is evaluated to be presenting significant visual and anatomical improvements in patients with persistent macular edema due to CRVO despite previous intravitreal ranibizumab.

Histomorphometric changes in the placenta and umbilical cord during complications of pregnancy.

Pregnancy complications may cause morphological changes and circulation defects in the placenta, which may lead to morbidity and mortality in fetuses and newborns. We investigated structural changes in the placenta and umbilical cord under various abnormal maternal conditions. Placenta and umbilical cord specimens were obtained from pregnant women during labor at 37 - 42 weeks gestation. Volumetric measurements were made for each placenta and umbilical cord using the Cavalieri method. Significant differences were observed for volumetric densities of total villi, syncytial knots, intervillous vessels and perivillous fibrin deposition. We observed particular increases in the volumetric parameters of the pre-eclampsia group compared to the other groups. The tunica media of the umbilical arteries was increased significantly with intrahepatic cholestasis.

Evaluation of the possible protective role of naringenin on gentamicin-induced ototoxicity: A preliminary study.

OBJECTIVES: The purpose of this study is to evaluate the possible protective role of naringenin in gentamicin-induced ototoxicity through an audiological, biochemical and histopathological evaluation. METHODS: This study was conducted on 32 adult male rats that were randomized into 4 groups(control, gentamicin, naringenin + gentamicin, and naringenin). Naringenin was given to the rats via oral gavage in a dose of 50 mg/kg/day during the 14 day study period. Gentamicin was given by the intraperitoneal route in a dose of 120 mg/kg/day. Audiological assessment was performed by the distortion product otoacoustic emission (DPOAE) and auditory brainstem response (ABR) measurements, applied to all rats at the beginning of the study, and also on day 14. Biochemical parameters were calculated on day 14 to evaluate the oxidative and antioxidative status. Their cochleae were removed and examined histopathologically, also on day 14. The cochlea of animals were evaluated with the terminal deoxynucleotidyl transferase-mediated dUTPbiotin nick end labeling (TUNEL) method for apoptosis. RESULTS: On days 14, DPOAE values and ABR thresholds were preserved in group 3(naringenin + gentamicin) when compared with group 2(gentamicin)(p < 0.008). The total oxidant status values and oxidative stress index values were significantly higher in group 2(gentamicin) than in other groups (p < 0.008). The total antioxidant status value was significantly higher in group 3(naringenin + gentamicin) and group 4(naringenin) than in group 2(gentamicin)(p < 0.008). The number of TUNEL positive cells in both the organ of Corti and the stria vascularis were found to be statistically lower in group 3(naringenin + gentamicin) than in group 2(gentamicin)(p < 0.05). CONCLUSION: Our study has demonstrated that the ototoxic effect generated by gentamicin could be ameliorated with the concurrent use of naringenin.

A comparison of piezosurgery with conventional techniques for internal osteotomy.

To compare conventional osteotomy with the piezosurgery medical device, in terms of postoperative edema, ecchymosis, pain, operation time, and mucosal integrity, in rhinoplasty patients. In this prospective study, 49 rhinoplasty patients were randomly divided into two groups according to osteotomy technique used, either conventional osteotomy or piezosurgery. For all patients, the total duration of the operation was recorded, and photographs were taken and scored for ecchymosis and edema on postoperative days 2, 4, and 7. In addition, pain level was evaluated on postoperative day 2, and mucosal integrity was assessed on day 4. All scoring and evaluation was conducted by a physician who was blinded to the osteotomy procedure. In the piezosurgery group, edema scores on postoperative day 2 and ecchymosis scores on postoperative days 2, 4, and 7 were significantly lower than in the conventional osteotomy group (p < 0.05). On postoperative day 2, the pain level was lower in the piezosurgery group than in the conventional osteotomy group (p < 0.05). In an endoscopic examination on postoperative day 4, while 24% of the patients in the conventional osteotomy group had mucosal damage, no such damage was observed in the piezosurgery group. When total operation duration was compared, there was no significant difference between the groups (p > 0.05). Piezosurgery is a safe osteotomy method, with less edema (in the early postoperative period) and ecchymosis compared with conventional osteotomy, as well as less pain, a similar operation duration, and no mucosal damage.

Genetic risk factors of cisplatin induced ototoxicity in adult patients.

Ototoxicity is an important adverse effect of using Cisplatin (cis-diamminedichloroplatinum) (CDDP) as a form of chemotherapy. The clinical picture of CDDP induced ototoxicity includes perceptive hearing impairment (reversible or permanent) and tinnitus. Ototoxicity manifests with considerable variability between patients. The objective of this prospective study was to investigate a possible genetic background to this variability. We assessed ototoxicity induced by therapeutic doses of CDDP in adult patients with germinative testicular tumors, or other tumors treated with an identical CDDP dosage scheme. Audiological examination before, during and after the treatment has shown deterioration in hearing; first in the high-frequencies and with increased CDDP cumulative doses, impairment in other frequencies as well. Occurrence of tinnitus was not dependent on the administered dose of CDDP, or the other risk factors examined in this study. The association of CDDP induced ototoxicity with genetic polymorphisms in candidate genes was examined. Our study has demonstrated an association of early onset of CDDP induced ototoxicity with the presence of two copies of GSTT1 gene (p=0,009) and with T allele of rs9332377 polymorphism in COMT gene (p=0,001).

Is parturition-timing machinery related to the number of inhibitor CD94/NKG2A positive uterine natural killer cells?

PURPOSE: Prematurity is the most common cause of infant mortality and morbidity. To prevent this, the timing of parturition and its mechanisms should be understood. It is likely that inhibitor CD94/NKG2A positive decidual natural killer cells (uNK) provide for the continuation of pregnancy. Here, we aimed to evaluate whether CD94/NKG2A positive uNK cells are highest in elective cesarian section (C/S) (suggesting ongoing gestation), moderate in normal full-term birth, and lowest in pre-eclamptic parturition. METHODS: Of 48 pregnant women, 21 C/S, 16 normal, and 11 pre-eclamptic deliveries were included in this study. Five placentas in each group were assigned randomly. After staining, the volumetric analysis of the placental villi and villous blood vessels was performed via the Cavalieri principle. The CD94/NKG2A positive uNK cells were counted using the physical disector method. RESULTS: The gestation periods and birth weights of the pre-eclamptic deliveries were lower than those of the other two groups. Additionally, the villi and villous vascular volumes were lowest in the pre-eclamptic placentas. As proposed in our hypothesis, the inhibitor CD94/NKG2A positive uNK cells were the highest in the C/S, moderate in the normal, and lowest in the pre-eclamptic placentas. CONCLUSIONS: These data suggest that CD94/NKG2A positive uNK cells are related with the continuation of pregnancy, and that our human model could be used to search for parturition-timing machinery. We believe that CD94/NKG2A positive uNK cells are also related to the timing of birth.

Comparison of different formulas for intraocular lens power calculation using a new optical biometer.

PURPOSE: To evaluate and compare the predictability of different formulas for intraocular lens (IOL) power calculation using a new optical biometer (Aladdin). METHODS: This prospective cross-sectional study included 70 eyes of 70 patients who underwent uneventful phacoemulsification with IOL implantation. Preoperative IOL power calculations were performed using the Aladdin optical biometer. Postoperative actual refractive errors and errors predicted by the SRK/T, SRK II, Holladay 1, Hoffer Q and Haigis formulas were analyzed. The mean estimation error (EE), mean absolute estimation error (AEE) and the percentage of eyes within ± 0.50 and ± 1.00 D of the target refraction for each of five formulas were calculated and compared. This analysis was also repeated in three groups formed based on axial length (AL) (group 1: <22.5mm, group 2: 22.5-24 mm, group 3: >24 mm). RESULTS: In the overall study group, the smallest mean AEE was provided by the Holladay 1 formula, however there was no statistically significant difference in the mean AEE's predicted by the five formulas (P=0.34). The highest percentage of eyes within ± 0.50 and ± 1.00 D of the target refraction was also found by using Holladay 1 (71% and 97%). SRK/T provided smallest mean AEE for groups 1 (n=13) and 3 (n=16). In group 2 (n=41), the smallest mean AEE was obtained using Holladay 1. CONCLUSIONS: Based on the Aladdin biometric data used in our study, better results can be obtained using SRK/T formula in eyes with short or long AL. The Holladay 1 formula may be preferred in eyes with moderate AL.

The influence of the learning effect on automated perimetry in a Turkish population.

PURPOSE: To evaluate the influence of learning effect on the outcome of automated perimetry and to assess the factors associated with the learning effect in a Turkish population. METHODS: The Swedish Interactive Threshold Algorithm (SITA) standard 30-2 test was performed on a Humphrey Visual Field Analyzer in 102 normal Turkish subjects who had not previously undertaken any form of perimetry. Each subject completed three testing sessions, each separated by at least one day. The SITA standard 30-2 testing sessions included both eyes. The right eye was always tested before left eye. The reliability parameters, test duration and visual field (VF) global indices (mean deviation [MD] and pattern standard deviation [PSD]) obtained from right eyes in the first and third sessions were compared to assess the learning effect. Change in these parameters between the first and third sessions was calculated, and the effect of gender, age and educational level on this change was evaluated. RESULTS: The reliability parameters, test duration and VF global indices each improved between the first and third sessions (P ≤ 0.001). The change in the parameters was greater in subjects over 50 years of age and with an educational level less than high school (P ≤ 0.01). No correlation was found between learning effect and gender. CONCLUSION: In normal Turkish subjects, a significant learning effect was observed during VF testing with the SITA standard 30-2. The learning effect was correlated with age and educational level.

Long term experience of patients with unresectable or metastatic KIT positive gastrointestinal stromal tumours.

A retrospective analysis of consecutive patients (183 in total, of which 105 were males and 78 females) with gastrointestinal stromal tumour (GIST) was performed. The mean age was 61 years, median age 64 years. The most frequent localization of the tumour was stomach in 74 patients (40.4 %) and the small intestine in 46 patients (25.1 %). Two or more different synchronous or metachronous cancers occurred in 34 (18.6 %) patients with histologically confirmed GIST. Ninety-six patients were treated with imatinib mesylate in palliative setting during the course of their disease. The therapy was finished in 60 patients and 36 patients have been treated so far. The median progression-free survival reached 32.9 months in the group of 96 patients treated with imatinib. The median overall survival in the group of 96 patients treated for metastatic disease reached 77 months. Two-year and 5-year survival was 85.2 % and 63.1 %, respectively. The second-line therapy with sunitinib malate was administered in 37 patients, of which 31 finished and 6 continued in the therapy. The median progression free survival and median survival since the sunitinib therapy initiation reached 8.4 and 22.1 months, respectively (Tab. 2, Fig. 2, Ref. 16).

Comparison of transepithelial corneal collagen crosslinking with epithelium-off crosslinking in progressive keratoconus.

PURPOSE: To evaluate the safety and efficacy of transepithelial corneal collagen crosslinking (TE-CXL) as compared to epithelium-off crosslinking (epi-off CXL) in progressive keratoconus. METHODS: Records of keratoconus patients treated with TE-CXL or epi-off CXL were reviewed retrospectively. Patients were included if they had at least 12months follow-up. Pre- and postoperative measurements of visual acuity, refractive errors, keratometry, corneal topography and pachymetry were assessed and compared. RESULTS: There was no statistically significant difference between two groups at baseline in terms of demographic, refractive and corneal parameters. Mean maximum cone apex curvature (apical K) increased from 51.62±5. Eighty-four diopters (D) to 53.70±5.49 D in the TE-CXL group (n=17), and decreased from 52.02±4.07 D to 51.22±3.51 in the epi-off CXL group (n=19) at the end of the follow-up period. The difference between two groups was statistically significant (P=0.0002). An increase of≥1D in apical K was observed in two of 19 eyes (11%) in the epi-off CXL group, and 11 of 17 eyes (65%) in TE-CXL group at the last follow-up visit, compared to baseline (P<0.0001). Fourteen patients in the epi-off CXL group exhibited corneal edema that resolved without haze with topical corticosteroid treatment by 4months. No postoperative corneal edema was observed in TE-CXL group. CONCLUSIONS: Although it is safe and well tolerated, TE-CXL does not effectively halt the progression of keratoconus. Epi-off CXL appears to be effective in stopping progression and even improves corneal parameters.

Significant antitumor effectiveness of imatinib in c- kit negative gastrointestinal stromal tumor -  case report.

Inoperable c- kit negative gastrointestinal stromal tumor (GIST) is commonly considered to be highly resistant to systemic therapy. We present a case of a woman with an abdominal sarcomalike tumor diagnosed at the age of 26. The patient underwent several surgical procedures and courses of cytostatic therapy without any substantial effect. Later, the tumor was reclassified as c- kit negative GIST harbouring the mutation in exon 12 of PDGFRA gene. Hence, the therapy with imatinib mesylate was initiated, resulting in partial remission of metastatic lesions and further stabilization of the disease for five years to date. We therefore consider imatinib mesylate an appropriate therapy for c- kit negative GIST bearing PDGFRA mutations.

Impact of cabazitaxel on 2-year survival and palliation of tumour-related pain in men with metastatic castration-resistant prostate cancer treated in the TROPIC trial.

BACKGROUND: Cabazitaxel significantly improves overall survival (OS) versus mitoxantrone in patients with metastatic castration-resistant prostate cancer after docetaxel failure. We examined patient survival at 2 years and tumour-related pain with cabazitaxel versus mitoxantrone. METHODS: Updated TROPIC data (cut-off 10 March 2010) were used to compare 2-year survival between treatment groups and assess patient demographics and disease characteristics. Factors prognostic for survival ≥2 years were assessed. Pain and Eastern Cooperative Oncology Group performance status were evaluated in the overall patient population. RESULTS: Median follow-up was 25.5 months. After 2 years, more patients remained alive following cabazitaxel than mitoxantrone [odds ratio 2.11; 95% confidence interval (CI) 1.33-3.33]. Treatment with cabazitaxel was prognostic for survival ≥2 years. Demographics/baseline characteristics were balanced between treatment arms irrespective of survival. Pain at baseline and pain response were comparable between treatment groups. Average daily pain performance index was lower for cabazitaxel versus mitoxantrone (all cycles; 95% CI -0.27 to -0.01; P = 0.035) and analgesic scores were similar. Grade ≥3 peripheral neuropathies were uncommon and comparable between treatment groups. CONCLUSIONS: Cabazitaxel prolongs OS at 2 years versus mitoxantrone and has low rates of peripheral neuropathy. Palliation benefits of cabazitaxel were comparable to those of mitoxantrone. The study was registered with www.ClinicalTrials.gov (NCT00417079).

[Epidemiological and clinico-pathological characteristics of patients with renal carcinoma: a single institution analysis of 544 cases]. / Epidemiologická a klinicko-patologická charakteristika pacientu s renálním karcinomem: analýza 544 prípadu z jednoho centra.

BACKGROUND: The incidence of renal cell carcinoma in the Czech Republic is one of the highest in the world. Curative treatment is still possible only surgically, while in the palliative treatment, partial success was reached using targeted therapies. While prognostic factors and models are commonly used in clinical practice, unfortunately, predictive biomarkers have not been found. The aim of our study was to verify the validity of selected prognostic factors on a consecutive patient cohort from the Czech population. PATIENTS AND METHODS: The patient cohort consisted of 544 patients with RCC diagnosed and/or treated at our institute from 2003 to 2010. Individual clinical and histological prognostic factors and Heng prognostic model were validated. RESULTS: Median time of follow-up for our cohort was 42 months (range 0.3-326 months), median age at diagnosis was 62 years, and almost 64% of patients were men. Distribution of clinical stages was as follows: 46.5% of I, II. 10.7%, III. 13.1%, IV. 20%. 26.4% of patients in stage I-III relapsed. We diagnosed mainly clear cell (84.6%) and papillary carcinoma (9.2%). Initially, 95.8% of patients underwent surgical treatment, systemic adjuvant and palliative treatment was applied in 3.7 and 37.7% of patients, respectively. Palliative targeted therapy was received by a total of 163 patients (30%). In first-line targeted therapy, the following median TTP was reached (in months): 10.8 for sunitinib, 6.3 for sorafenib and 5.2 months for immunotherapy. The most significant prognostic factors (p < 0.00001) were: stage of disease (HR = 9.61), size of the primary tumor (HR = 5.83), lymph nodes (HR = 8.26), presence of sarcomatoid tumor sections in the tumor (HR = 7.29), and tumor grade (HR = 4.0). Besides these, we also confirmed the prognostic importance of presence of eosinophilic granulations in the tumor (HR = 1.91, p = 0.02). When applying the Heng prognostic model, we achieved similar results for patients treated with targeted therapies. CONCLUSION: The obtained epidemiological and clinico-pathological data are consistent with previously published data. These prognostic factors can be used for a differentiated approach to patients with RCC, both for establishing follow-up plan for patients after surgery as well as indication for targeted therapies.