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).

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.

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).

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).

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.

[Genetic background of cisplatin induced ototoxicity]. / Genetické pozadí ototoxicity cisplatiny.

BACKGROUND: Cisplatin induced ototoxicity is a serious adverse effect of cisplatin therapy. Cisplatin induced ototoxicity shows significant interindividual variability. This variability is probably based on genetic background. Recent papers describe association of cisplatin ototoxicity with allelic variants of glutathion-S-transferase coding genes. PATIENTS AND METHODS: We have analyzed 55 patients treated with cisplatin therapy without any previous hearing impairment. Audiometric examination was performed before the start of cisplatin therapy and then before and after each cycle of cisplatin. DNA isolated from peripheral blood samples was used to analyze genetic polymorphisms of selected genes coding for glutathion-S-transferases. RESULTS: We have demonstrated association of early onset of cisplatin induced hearing impairment with absence of null allele of GSTT1 (p = 0.009). Both GSTM1 gene deletion and single nucleotide polymorphism in GSTP1 gene (rs1695) did not show any association with cisplatin induced ototoxicity. CONCLUSION: Early onset of cisplatin induced hearing impairment is more probable in persons with two functional alleles of GSTT1 gene.

[Hand-foot syndrome after administration of tyrosinkinase inhibitors]. / Hand-foot syndrom po podání inhibitoru tyrozinkinázové aktivity.

At present, the dermal toxicity of anti-cancer drugs is ever more apparent in cancer patients. This phenomenon appears, in particular, in relation to the increased administration of targeted anti-cancer treatment, especially of monoclonal antibodies and tyrosinkinase inhibitors (TKI), towards various receptors of growth factors which are applied in the ethiopathogenesis of a tumour cell. Our article focuses on the palmoplantar erythrodysesthesia syndrome, designated also as the hand-foot skin reaction (HFSR), which most frequently occurs in patients treated with TKI sorafenib and sunitinib. Developed HFSR may be a strongly perceived adverse effect for patients and may lead to dose intensity reduction in the targeted treatment, or to its interruption if necessary. However, a correct approach from the oncologist and dermatologist, including instructions to be provided to the patient on how to prevent a serious grade of HFSR from being developed, may ensure a smooth anti-cancer treatment and a satisfactory quality of life for cancer patients.

A phase I/II study of siltuximab (CNTO 328), an anti-interleukin-6 monoclonal antibody, in metastatic renal cell cancer.

BACKGROUND: Serum interleukin (IL)-6 levels correlate with disease outcomes in renal cell carcinoma (RCC) patients. Siltuximab, a chimeric, murine-human mAb against IL-6, was evaluated in a three-part phase I/II study in patients with progressive metastatic RCC. METHODS: In part 1, 11 patients received 1, 3, 6, or 12mgkg-¹ at weeks 1, 4 and q2w × 2 thereafter; in part 2, 37 patients randomly received 3 or 6 mgkg-¹ q3w × 4; in part 3, 20 low-risk patients received 6mgkg-¹ q2w × 6. Modified WHO response criteria were assessed at weeks 7, 11, the 6-week follow-up, and when clinically indicated. RESULTS: Siltuximab was well tolerated overall, with no maximum tolerated dose or immune response observed. In all, 5 out of 11, 17 out of 37, and 9 out of 20 patients in parts 1, 2, and 3, respectively, received extended treatment beyond 4-6 initial infusions. In part 2, stable disease (SD) (≥11weeks) or better was achieved by 11 out of 17 (65%) 3 mgkg-¹ treated patients (one partial response (PR) ~8 months, 10 SD) and 10 out of 20 (50%) 6mgkg-¹ treated patients (10 SD). In part 3, documented complete or PR was not observed, but 13 out of 20 (65%) patients achieved SD. CONCLUSION: Siltuximab stabilised disease in >50% of progressive metastatic RCC patients. One PR was observed. Given the favourable safety profile of siltuximab and poor correlation of tumour shrinkage with clinical benefit demonstrated for other non-cytotoxic therapies, further evaluation of dose-escalation strategies and/or combination therapy may be considered for patients with RCC.

[Pneumosurgery in the management of colorectal carcinomas]. / Pneumochirurgie v resení karcinomu kolorekta.

OBJECTIVE: Surgically solved lung involvement in patients after surgery of colorectal cancer. MATERIALS AND METHODS: Altogether 15 patients, 9 men (median age in the time of lung diagnosis 67 years) and 6 women (median age 59 years) underwent classical open pulmonary surgery during 2003-2008 years from the follow-up cohort of 836 persons after operation due to colorectal cancer in the time period of 1996-2008 years. The indication for lung surgery: solitary pulmonary lesion. Procedures distribution: pulmonary lobectomy 7, bilobectomy 2, segmentectomy 4, wedge resection 2. The requirement of the European Society of Thoracic Surgeons (ESTS) guidelines of complete pulmonary resection has been met by 10 operations (66.7%) with lobe specific lymphadenectomy. Histopathology investigation: Formalin fixed, paraffin embedded samples were investigated after hematoxylin-and-eosin staining, supplemented in case of need by immunohistochemistry of CK7, CK20 and TTF1. RESULTS: Eleven pulmonary metastases were found, in two cases with interlobar lymfatics involvement. Two metachronous primary adenocarcinomas of the lung (ADL) were diagnosed, one of them with metastases into hilar lymphatics. In remaining two patients pulmonary chondrohamartoma was discovered. CONCLUSION: Solitary pulmonary opacity in patient after colorectal surgery might not represent simple metastasis explicitly. Complete resection is needed.

[Bevacizumab in combination with capecitabine and irinotecan (XELIRI) in treatment of metastatic colorectal cancer]. / Bevacizumab v kombinaci s kapecitabinem a irinotekanem (XELIRI) v lécbe metastatického kolorektálního karcinomu.

BACKGROUND: Incidence and mortality rates of colorectal malignancies in the Czech Republic are one of the highest in the world since over 7,500 patients are diagnosed yearly. About 25% of patients are diagnosed in clinical stage IV and in average more than 50% of patients who are diagnosed initially with resectable disease will relapse sooner or later. Management of palliative treatment of colorectal cancer therefore is becoming of a great importance. OBSERVATION: We designed a study protocol in 2005 and 16 patients with metastatic colorectal cancer were treated accordingly in the first line setting with XELIRI regimen (capecitabin, irinotecan) + bevacizumab. The regimen has proven high antitumor effectiveness (78% responses to treatment, median TTP: 12 months, 1-year survival reached 100% of patients) and excellent tolerance. No serious grade G3 or G4 toxicity was observed. Increase of blood pressure was observed sporadically within the group. We present below the case of 55 year old patient who underwent treatment of 4 cycles of XELIRI + bevacizumab and reached complete remission of the disease which lasted over the next 9 months (TTP 13 months). CONCLUSION: Successful choice of a regimen of the first line treatment determines the next course of a disease including duration of patient's overall survival. We have confirmed within our pivotal population that combination treatment XELIRI + bevacizumab is a very effective and well tolerated regimen moreover suitable for administration at outpatient setting.

[Adjuvant treatment for stage I of testicular germ cell tumours]. / Adjuvantní lecba u i. stádia germinálních nádoru varlat.

BACKGROUND: Testicular germ cell tumors (TGCT) are the most frequent malignancy seen in young men. More than 95% of patients diagnosed with early stage TGCT are cured. In management of stage I seminoma there are several treatment options, including adjuvant radiotherapy, adjuvant chemotherapy with one cycle of carboplatin or surveillance. Patients with stage I nonseminoma are treated with adjuvant chemotherapy, with nerve sparing retroperitoneal lymph node dissection or surveillance being considered another treatment alternatives for stage I disease. METHODS AND RESULTS: Fifty five patients with stage I TGCT were diagnosed and treated in Masaryk Memorial Cancer Institute between January 2000 to December 2004. In a retrospective analysis, we reviewed treatment outcome and treatment strategy used in these patients. Patients characteristics also included histological subtype, risk status, age at the time of diagnosis, relapse rate, delayed toxicity, etc. Despite the small number of patients included in the analysis (55), there was observed a clear preference toward adjuvant radiotherapy in seminoma patients (95%) and adjuvant chemotherapy in nonseminoma patients (97%). During median follow up (5,6 years in seminoma group, 5,7 years in nonseminoma group) only two patients experienced relapse of disease in the seminoma group and none in the nonseminoma group. One patient died of metastatic colorectal cancer. Acute toxicity was acceptable, with no treatment related death. The long- term side effects were not significant (no grade 3 or 4 toxicity). CONCLUSION: The achieved cure rates were high, with acceptable toxicity. The role of adjuvant chemotherapy with carboplatin in stage I seminoma remains controversial. Further management of TGCT should be guided by complete and correct assessment of known risk factors to ensure the potential for cure.