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Slovenia

Cancer Statistics
Population in 2012: 2.0m
People newly diagnosed with cancer (excluding NMSC) / yr: 11,500
Age-standardised rate, incidence per 100,000 people/yr: 296.3
Risk of getting cancer before age 75:29.4%
People dying from cancer /yr: 5,900
Data from IARC GlobalCan (2012)
Slovenia: Cancer Organisations and Resources
Latest Research Publications from Slovenia

Slovenia: Cancer Organisations and Resources (7 links)


Latest Research Publications from Slovenia

Jensterle M, Kravos NA, Goričar K, Janez A
Short-term effectiveness of low dose liraglutide in combination with metformin versus high dose liraglutide alone in treatment of obese PCOS: randomized trial.
BMC Endocr Disord. 2017; 17(1):5 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Liraglutide 3 mg was recently approved as an anti-obesity drug. Metformin is weight neutral, yet it could enhance the therapeutic index of GLP-1 agonist. We compared weight-lowering potential of liraglutide 1.2 mg in combination with metformin to liraglutide 3 mg monotherapy in obese PCOS.
METHODS: Thirty obese women with PCOS (aged 33.1 ± 6.1 years, BMI 38.3 ± 5.4 kg/m(2)) were randomized to combination (COMBO) of metformin (MET) 1000 mg BID and liraglutide 1.2 mg QD (N = 15) or liraglutide 3 mg (LIRA3) QD alone (N = 15) for 12 weeks. The primary outcome was change in anthropometric measures of obesity.
RESULTS: Both treatments led to significant weight loss (-3.6 ± 2.5 kg, p = 0.002 in COMBO vs -6.3 ± 3.7 kg, p = 0.001 in LIRA3). BMI and waist circumference reduction in LIRA3 was greater than in COMBO (-2.2 ± 1.3 vs -1.3 ± 0.9 kg/m(2), p = 0.05 and -4.2 ± 3.4 vs -2.2 ± 6.2 cm, p = 0.014, respectively). Both interventions resulted in a significant decrease of post-OGTT glucose levels. COMBO significantly reduced total testosterone and was associated with less nausea.
CONCLUSIONS: Short-term interventions with COMBO and LIRA3 both led to significant improvement of measures of obesity in obese PCOS, LIRA3 being superior to COMBO. However, COMBO further improved androgen profile beyond weight reduction and was associated with better tolerability.
TRIAL REGISTRATION: The study was retrospectively registered with ClinicalTrials.gov ( NCT02909933 ) on 16(th) of September 2016.

Kavčič J, Božič M
Schwannoma of the tongue.
BMJ Case Rep. 2016; 2016 [PubMed] Related Publications
Schwannoma, neurilemmoma or neurinoma is a rare, benign nerve sheath neoplasm composed of Schwann cells. It is usually solitary, slow growing and asymptomatic. Approximately 1-12% of the tumours occur intraorally with the tongue being the most common location. We report a rare case of lingual schwannoma in a 20-year-old female patient involving the tip of the tongue, which was slow growing and asymptomatic. For diagnosis histopathological examination and also immunohistochemistry testing were carried out to confirm the nature of tissue fragments. The treatment was complete surgical excision.

Strojan Fležar M, Srebotnik-Kirbiš I, Gutnik H
Use of vimentin immunocytochemical staining for evaluation of atypical cells in voided urine samples.
Diagn Cytopathol. 2017; 45(2):85-90 [PubMed] Related Publications
BACKGROUND: Cytomorphology of exfoliated atypical reactive/repair renal tubular cells (RRTC) can resemble atypical urothelial cells thus suggesting a differential diagnostic question of urothelial neoplasia in urinary cytology. Vimentin expression has been shown in RRTC and used for differentiation from atypical urothelial cells.
METHODS: The institutional computer database was searched for urinary cytology cases with vimentin immunocytochemical staining (2008-2012). Original cytopathological diagnoses based on cytomorphology and the results of vimentin immunostaining were compared to follow-up data, including histopathological diagnosis, subsequent urinary cytopathology reports, and clinical findings.
RESULTS: Of the 42 cases with vimentin immunocytochemical staining, 33 were positive and 9 negative. Consequently, significant renal disease was found in 9/33 (27%) of vimentin positive cases and nehrolithiasis in 4/33 (12%) of vimentin positive and 1/9 (11%) of vimentin negative cases. Erythrocyturia of undetermined origin was diagnosed in nine cases (seven vimentin positive and two negative). Urinary cytology follow-up was negative in three vimentin positive cases. Urothelial carcinoma was found in 3/9 (30%) of vimentin negative cases. Thirteen patients were lost to follow-up.
CONCLUSIONS: Vimentin immunocytochemical staining could be used as an ancillary method for evaluation of atypical cells in urinary specimens in selected cases with RRTC exhibiting cytological atypia. Unnecessary diagnostic procedures for evaluation of urothelial carcinoma could be avoided in vimentin positive cases and further diagnostic work-up for evaluation of a significant renal disease could be suggested in vimentin positive cases. Diagn. Cytopathol. 2017;45:85-90. © 2016 Wiley Periodicals, Inc.

Kumar JK, Aronsson AC, Pilko G, et al.
A clinical evaluation of the TK 210 ELISA in sera from breast cancer patients demonstrates high sensitivity and specificity in all stages of disease.
Tumour Biol. 2016; 37(9):11937-11945 [PubMed] Free Access to Full Article Related Publications
Thymidine kinase (TK1) is an enzyme involved in DNA synthesis that leaks into the blood as a result of high cell turnover, particularly in the case of cancer. Serum TK1 activity has been used for prognosis and monitoring of leukemia and lymphoma patients for many years. Here, we describe the first clinical results with the newly developed TK 210 ELISA from AroCell AB. Sera from 124 breast cancer patients with known TNM classification along with sera from 53 healthy females were analyzed by TK 210 ELISA for TK1 protein and TK1 activity levels by the (3)[H]-deoxythymidine (dThd) phosphorylation assay. The limit of detection for the TK 210 ELISA was 0.17 ng/ml, and 60 % of the sera from female blood donors were below this value. The median TK1 levels found in sera from breast cancer patients with T1 to T4 stage disease were 0.31, 0.46, 0.47, and 0.55 ng/ml, and these levels significantly differed from healthy controls. The median values of the biomarker CA 15-3 were also increased in patient sera from T1 to T4 patients (16, 34, 36, 40 U/ml, respectively). TK 210 ELISA showed significantly higher sensitivity for the T1 and T2 breast cancer patients compared to the TK activity assay. The combination of the TK1 ELISA and CA 15-3 biomarkers demonstrated a significant increase in sensitivity up to 15 % compared to each marker alone. This evaluation of the TK 210 ELISA strongly suggests that it can provide independent and complementary information for patients with breast cancer.

Ravnik J, Smigoc T, Bunc G, et al.
Hypophyseal metastases: A report of three cases and literature review.
Neurol Neurochir Pol. 2016 Nov - Dec; 50(6):511-516 [PubMed] Related Publications
Metastatic tumours to the pituitary gland are rare. The most frequent are metastases from breast and lung. We describe three patients with metastatic tumours: (I) a 54-year-old patient with metastatic renal clear-cell carcinoma and consequent disturbances in visual acuity, cranial nerve paresis and panhypopituitarism, (II) a 60-year-old patient with a diffuse large B-cell lymphoma with panhypopituitarism and diabetes insipidus and (III) a 57-year-old patient with metastasis of breast cancer and panhypopituitarism, visual impairment and cranial nerve paresis. A transnasal endoscopic biopsy and resection of the tumour was performed in all patients, followed by the oncological treatment. Despite the rarity of the disease, it is important to suspect a metastatic pituitary tumour especially in the case of diabetes insipidus, ophthalmoplegia, rapid course of the disease and headaches. In 20-30% of patients, a metastasis to the pituitary is the first manifestation of a tumour of unknown origin. Surgical and adjuvant therapy may improve the quality of life. The survival is not affected, however, and the prognosis of the disease is usually poor.

Schwarzlin R, Pušenjak N, Makuc D, et al.
Synergistic complex from plants Solanaceae exhibits cytotoxicity for the human hepatocellular carcinoma cell line HepG2.
BMC Complement Altern Med. 2016; 16(1):395 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: It had been demonstrated that sugars from various plants can act as potent agents, which induce apoptosis of cancer cells.
METHODS: Using HPLC, we fractionated a mixture of two plant extracts from the plant family Solanaceae, namely Capsicum chinense and the plant family Amaryllidaceae namely Allium sativum. We evaluated the effect of different fractions on apoptosis of HepG2 cell line. The most effective fraction was further studied to determine its molecular composition using mass spectrometry (MS) and NMR. We further evaluated the effect of determined molecular composition found in the selected fraction by using a mixture of commercially available substances, which were found in the fraction and tested its pro-apoptotic effect on HepG2 cells. To get some insight into potential apoptotic mechanisms we studied caspase-3 activity and mitochondrial integrity in treated cells.
RESULTS: Out of 93 fractions obtained by HPLC from the plant extract we found HPLC fraction 10 (10 min elution) was the most effective. MS and NMR studies revealed high presence of cellobiose together with vitamin C, sulphur (S) and trace amounts of selenium (Se). HPLC fraction 10 triggered apoptosis of HepG2 within 3 h in the 0.01-1.0 mg/mL concentration range. Furthermore, a mixture of pure cellobiose, vitamin C, S and Se (complex cellobiose/C/S/Se) had a very similar capacity in inducing apoptosis of HepG2 cells compared to HPLC fraction 10. Complex cellobiose/C/S/Se was capable of inducing caspase-3 activity and led to loss of mitochondrial integrity. The capacity of cellobiose alone to induce apoptosis of HepG2 was approximately 1000-fold lower compared to complex cellobiose/C/S/Se.
CONCLUSION: In this study we present the highly synergistic effect of a unique complex consisting of cellobiose, vitamin C, sulphur and selenium on triggering the apoptosis of human hepatocellular carcinoma (HepG2) cell line.

Falconieri G, Cataldi P, Kavalar R, et al.
Cutaneous Osteoblastic Osteosarcoma: Report of 2 New Cases Integrated With SATB2 Immunohistochemistry and Review of the Literature.
Am J Dermatopathol. 2016; 38(11):824-831 [PubMed] Related Publications
We report 2 cases of primary dermal osteosarcoma. The patients were an 88-year-old man and a 72-year-old man complaining of masses occurring in the ear pavilion and the palm, deemed suspicious for basal cell carcinoma and metastatic colonic carcinoma, and were treated by resection. Microscopically, both featured a dermal lesion mostly composed of atypical spindle cells within a fibrous to hyaline matrix often showing mineralization. Osteoid material was rimmed by atypical tumor cells and was also associated with osteoclast-like giant cells. Tumor cells were positive for SATB2 and negative for markers of epithelial (low-molecular and high-molecular weight cytokeratins, epithelial membrane antigen, p63), melanocytic (S100 protein, HMB45, Melan A), and skeletal/smooth muscle differentiation (desmin, myogenin). No further therapy has been administered. Follow-up at 6 (case 1) and 8 months (case 2) was uneventful. A brief differential diagnosis discussing cutaneous tumors capable of showing osseous differentiation is summarized, along with a review of the pertinent literature. The specificity and sensitivity of SATB2 is also shortly addressed.

Rades D, Seidl D, Janssen S, et al.
Comparing two lower-dose cisplatin programs for radio-chemotherapy of locally advanced head-and-neck cancers.
Eur Arch Otorhinolaryngol. 2017; 274(2):1021-1027 [PubMed] Related Publications
Radio-chemotherapy is a common treatment for locally advanced squamous cell head-and-neck cancers (LA-SCCHN). Cisplatin (100 mg/m(2)) every 3 weeks is very common but associated with considerable toxicity. Therefore, cisplatin programs with lower daily doses were introduced. There is a lack of studies comparing lower-dose programs. In this study, 85 patients receiving radio-chemotherapy with 20 mg/m(2) cisplatin on 5 days every 4 weeks (group A) were retrospectively compared to 85 patients receiving radio-chemotherapy with 30-40 mg/m(2) cisplatin weekly (group B). Groups were matched for nine factors including age, gender, performance score, tumor site, T-/N-category, surgery, hemoglobin before radio-chemotherapy, and radiation technique. One- and 3-year loco-regional control rates were 83 and 69 % in group A versus 74 and 63 % in group B (p = 0.12). One- and 3-year survival rates were 93 % and 73 % in group A versus 91 and 49 % in group B (p = 0.011). On multivariate analysis, survival was significantly better for group A (HR 1.17; p = 0.002). In groups A and B, 12 and 28 % of patients, respectively, did not receive a cumulative cisplatin dose ≥180 mg/m(2) (p = 0.016). Toxicity rates were not significantly different. On subgroup analyses, group A patients had better loco-regional control (p = 0.040) and survival (p = 0.005) than group B patients after definitive radio-chemotherapy. In patients receiving adjuvant radio-chemotherapy, outcomes were not significantly different. Thus, 20 mg/m(2) cisplatin on 5 days every 4 weeks resulted in better loco-regional control and survival in patients receiving definitive radio-chemotherapy and may be preferable for these patients. Confirmation of these results in a randomized trial is warranted.

Slemc L, Kunej T
Transcription factor HIF1A: downstream targets, associated pathways, polymorphic hypoxia response element (HRE) sites, and initiative for standardization of reporting in scientific literature.
Tumour Biol. 2016; 37(11):14851-14861 [PubMed] Related Publications
Hypoxia-inducible factor-1α (HIF-1α) has crucial role in adapting cells to hypoxia through expression regulation of many genes. Identification of HIF-1α target genes (HIF-1α-TGs) is important for understanding the adapting mechanism. The aim of the present study was to collect known HIF-1α-TGs and identify their associated pathways. Targets and associated genomics data were retrieved using PubMed, WoS ( http://apps.webofknowledge.com/ ), HGNC ( http://www.genenames.org/ ), NCBI ( http://www.ncbi.nlm.nih.gov/ ), Ensemblv.84 ( http://www.ensembl.org/index.html ), DAVID Bioinformatics Resources ( https://david.ncifcrf.gov /), and Disease Ontology database ( http://disease-ontology.org/ ). From 51 papers, we collected 98 HIF-1α TGs found to be associated with 20 pathways, including metabolism of carbohydrates and pathways in cancer. Reanalysis of genomic coordinates of published HREs (hypoxia response elements) revealed six polymorphisms within HRE sites (HRE-SNPs): ABCG2, ACE, CA9, and CP. Due to large heterogeneity of results presentation in scientific literature, we also propose a first step towards reporting standardization of HIF-1α-target interactions consisting of ten relevant data types. Suggested minimal checklist for reporting will enable faster development of a complete catalog of HIF-1α-TGs, data sharing, bioinformatics analyses, and setting novel more targeted hypotheses. The proposed format for data standardization is not yet complete but presents a baseline for further optimization of the protocol with additional details, for example, regarding the experimental validation.

Bober P, Alexovic M, Talian I, et al.
Proteomic analysis of the vitamin C effect on the doxorubicin cytotoxicity in the MCF-7 breast cancer cell line.
J Cancer Res Clin Oncol. 2017; 143(1):35-42 [PubMed] Related Publications
PURPOSE: Doxorubicin is an anthracycline drug which inhibits the growth of breast cancer cell lines. However, a major factor limiting its use is a cumulative, dose-dependent cardiotoxicity, resulting in a permanent loss of cardiomyocytes. Vitamin C was found to potentiate the cytotoxic effects of a variety of chemotherapeutic drugs including doxorubicin. The aim of the study was to describe the changes in protein expression and proliferation of the MCF-7 cells induced by the vitamin C applied with doxorubicin.
METHODS: Label-free quantitative proteomics and real-time cell analysis methods were used to search for proteome and cell proliferation changes. These changes were induced by the pure DOX and by DOX combined with vitamin C applied on the MCF-7 cell line.
RESULTS: From the real-time cell analysis experiments, it is clear that the highest anti-proliferative effect occurs with the addition of 200 µM of vitamin C to 1 µM of doxorubicin. By applying both the label-free protein quantification method and total ion current assay, we found statistically significant changes (p ≤ 0.05) of 26 proteins induced by the addition of vitamin C to doxorubicin on the MCF-7 cell line. These differentially expressed proteins are involved in processes such as structural molecule activity, transcription and translation, immune system process and antioxidant, cellular signalling and transport.
CONCLUSION: The detected proteins may be capable of predicting response to DOX therapy. This is a key tool in the treatment of breast cancer, and the combination with vit C seems to be of particular interest due to the fact that it can potentiate anti-proliferative effect of DOX.

Garbajs M, Popovic P
Contrast-enhanced ultrasound for assessment of therapeutic response after percutaneous radiofrequency ablation of small renal tumors.
J BUON. 2016 May-Jun; 21(3):685-90 [PubMed] Related Publications
PURPOSE: The purpose of this study was to evaluate the efficacy of contrast-enhanced ultrasound (CEUS) in the assessment of therapeutic response, after percutaneous radiofrequency ablation (RFA) of small renal tumors.
METHODS: Twenty patients (12 men, 8 women; median age, 77.4 years; median tumor size, 2.7 cm) were treated with RFA. All patients were examined by contrast-enhanced computed tomography (CECT), followed by CEUS one week later. Tumor enhancement characteristics and thickness of the enhancing area in viable lesions were evaluated.
RESULTS: Median time from RFA to diagnostic imaging was 16.8 months. All 20 patients underwent CT. CEUS was finally performed in only 14 out of 20 patients (70%), since 2 out of 6 had contraindications for the application of a US contrast agent. Also, one patient refused the application and a further 3 had tumors that were impossible to differentiate adequately on the conventional B-mode US, in order to satisfactorily monitor the contrast enhancement. CEUS showed a complete response in 9 out of 14 (64.3%) patients, residual tumor in 4 (28.6%) and tumor progression in 1 patient (7.1%). Median thickness of the enhancing area on CECT and CEUS was 20 mm vs 17 mm, respectively, with no statistically significant difference in the thickness (t =-0.816, p=0.461) between both modalities. The concordance between CECT and CEUS in the assessment of tumor response and detection of residual vascular enhancement was 100%.
CONCLUSIONS: CEUS is an effective and safe imaging modality in assessing the therapeutic response, after percutaneous radiofrequency ablation of small renal tumors. Disadvantages can be overcome with improved CEUS technology.

Cardoso F, van't Veer LJ, Bogaerts J, et al.
70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer.
N Engl J Med. 2016; 375(8):717-29 [PubMed] Related Publications
BACKGROUND: The 70-gene signature test (MammaPrint) has been shown to improve prediction of clinical outcome in women with early-stage breast cancer. We sought to provide prospective evidence of the clinical utility of the addition of the 70-gene signature to standard clinical-pathological criteria in selecting patients for adjuvant chemotherapy.
METHODS: In this randomized, phase 3 study, we enrolled 6693 women with early-stage breast cancer and determined their genomic risk (using the 70-gene signature) and their clinical risk (using a modified version of Adjuvant! Online). Women at low clinical and genomic risk did not receive chemotherapy, whereas those at high clinical and genomic risk did receive such therapy. In patients with discordant risk results, either the genomic risk or the clinical risk was used to determine the use of chemotherapy. The primary goal was to assess whether, among patients with high-risk clinical features and a low-risk gene-expression profile who did not receive chemotherapy, the lower boundary of the 95% confidence interval for the rate of 5-year survival without distant metastasis would be 92% (i.e., the noninferiority boundary) or higher.
RESULTS: A total of 1550 patients (23.2%) were deemed to be at high clinical risk and low genomic risk. At 5 years, the rate of survival without distant metastasis in this group was 94.7% (95% confidence interval, 92.5 to 96.2) among those not receiving chemotherapy. The absolute difference in this survival rate between these patients and those who received chemotherapy was 1.5 percentage points, with the rate being lower without chemotherapy. Similar rates of survival without distant metastasis were reported in the subgroup of patients who had estrogen-receptor-positive, human epidermal growth factor receptor 2-negative, and either node-negative or node-positive disease.
CONCLUSIONS: Among women with early-stage breast cancer who were at high clinical risk and low genomic risk for recurrence, the receipt of no chemotherapy on the basis of the 70-gene signature led to a 5-year rate of survival without distant metastasis that was 1.5 percentage points lower than the rate with chemotherapy. Given these findings, approximately 46% of women with breast cancer who are at high clinical risk might not require chemotherapy. (Funded by the European Commission Sixth Framework Program and others; ClinicalTrials.gov number, NCT00433589; EudraCT number, 2005-002625-31.).

Burnik Papler T, Frković Grazio S, Kobal B
Sertoli - Leydig cell tumor with retiform areas and overgrowth of rhabdomyosarcomatous elements: case report and literature review.
J Ovarian Res. 2016; 9(1):46 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Sertoli - Leydig cell tumors (SLCTs) are sex-cord stromal tumors that account less than 0.5 % of primary ovarian neoplasms. They are mostly benign and occur in reproductive age women. Variants with heterologous mesenchymal elements are exceptionaly rare. The usual presentation of SLCTs is with signs of androgen excess as majority of them produce androgens.
CASE PRESENTATION: We present a case of a SLCT occurring in a 70 year old woman. Her presenting complaint was abdominal distension and pain. She had no signs of androgen or estrogen excess. Transvaginal ultrasound (TVUS) and CT scan showed a multilocular adnexal tumor and level of CA 125 was raised. A complete cytoreduction was achieved with surgical procedure. Histopathological examination revealed moderately differentiated SLCT with retiform areas and owergrowth of heterologous component in form of embrional rhabdomyosarcoma (RMS). She returned 7 months after the surgery with a large abdominal mass, ascites, right- sided hydronephrosis and massive pulmonary embolism. Due to the widespread disease and her poor general condition, she received only palliative care. She died 15 days after the admission. No autopsy was performed.
CONCLUSIONS: Due to the rarity of SLCTs, especially those with retiform areas and heterologous elements, their management remains challenging. There is no firm evidence that adjuvant chemotherapy is effective in improving survival in SLCTs with malignant heterologous elements. Further studies with a higher number of cases and a longer follow-up are needed to better predicting the prognosis and determine the role of chemotherapy in such cases.

Krstanoski Z, Vokac NK, Zagorac A, et al.
TMPRSS2:ERG gene aberrations may provide insight into pT stage in prostate cancer.
BMC Urol. 2016; 16(1):35 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: TMPRSS2:ERG gene aberration may be a novel marker that improves risk stratification of prostate cancer before definitive cancer therapy, but studies have been inconclusive.
METHODS: The study cohort consisted of 202 operable prostate cancer Slovenian patients who underwent laparoscopic radical prostatectomy. We retrospectively constructed tissue microarrays of their prostatic specimens for fluorescence in situ hybridization, with appropriate signals obtained in 148 patients for subsequent statistical analyses.
RESULTS: The following genetic aberrations were found: TMPRSS2:ERG fusion, TMPRSS2 split (a non-ERG translocation) and ERG split (an ERG translocation without involvement of TMPRSS2). TMPRSS2:ERG gene fusion happened in 63 patients (42 %), TMPRSS2 split in 12 patients and ERG split in 8 patients. Association was tested between TMPRSS2:ERG gene fusion and several clinicopathological variables, i.e., pT stage, extended lymph node dissection status, and Gleason score, correcting for multiple comparisons. Only the association with pT stage was significant at p = 0.05: Of 62 patients with pT3 stage, 34 (55 %) had TMPRSS2:ERG gene fusion. In pT3 stage patients, stronger (but not significant) association between eLND status and TMPRSS2:ERG gene fusion was detected. We detected TMPRSS2:ERG gene fusion in 64 % of the pT3 stage patients where we did not perform an extended lymph node dissection.
CONCLUSIONS: Our results indicate that it is possible to predict pT3 stage at final histology from TMPRSS2:ERG gene fusion at initial core needle biopsy. FISH determination of TMPRSS2:ERG gene fusion may be particularly useful for patients scheduled to undergo a radical prostatectomy in order to improve oncological and functional results.

Ban HY, Schweiger M, Kavuri VC, et al.
Heterodyne frequency-domain multispectral diffuse optical tomography of breast cancer in the parallel-plane transmission geometry.
Med Phys. 2016; 43(7):4383 [PubMed] Article available free on PMC after 01/07/2017 Related Publications
PURPOSE: The authors introduce a state-of-the-art all-optical clinical diffuse optical tomography (DOT) imaging instrument which collects spatially dense, multispectral, frequency-domain breast data in the parallel-plate geometry.
METHODS: The instrument utilizes a CCD-based heterodyne detection scheme that permits massively parallel detection of diffuse photon density wave amplitude and phase for a large number of source-detector pairs (10(6)). The stand-alone clinical DOT instrument thus offers high spatial resolution with reduced crosstalk between absorption and scattering. Other novel features include a fringe profilometry system for breast boundary segmentation, real-time data normalization, and a patient bed design which permits both axial and sagittal breast measurements.
RESULTS: The authors validated the instrument using tissue simulating phantoms with two different chromophore-containing targets and one scattering target. The authors also demonstrated the instrument in a case study breast cancer patient; the reconstructed 3D image of endogenous chromophores and scattering gave tumor localization in agreement with MRI.
CONCLUSIONS: Imaging with a novel parallel-plate DOT breast imager that employs highly parallel, high-resolution CCD detection in the frequency-domain was demonstrated.

Costa CL, López-Ureña D, de Oliveira Assis T, et al.
A MLST Clade 2 Clostridium difficile strain with a variant TcdB induces severe inflammatory and oxidative response associated with mucosal disruption.
Anaerobe. 2016; 40:76-84 [PubMed] Related Publications
The epidemiology of Clostridium difficile infections is highly dynamic as new strains continue to emerge worldwide. Here we present a detailed analysis of a new C. difficile strain (ICC-45) recovered from a cancer patient in Brazil that died from severe diarrhea. A polyphasic approach assigned a new PCR-ribotype and PFGE macrorestriction pattern to strain ICC-45, which is toxigenic (tcdA(+), tcdB(+) and ctdB(+)) and classified as ST41 from MLST Clade 2 and toxinotype IXb. Strain ICC-45 encodes for a variant TcdB that induces a distinct CPE in agreement with its toxinotype. Unlike epidemic NAP1/027 strains, which are also classified to MLST Clade 2, strain ICC-45 is susceptible to fluoroquinolones and does not overproduce toxins TcdA and TcdB. However, supernatants from strain ICC-45 and a NAP1/027 strain produced similar expression of pro-inflammatory cytokines, epithelial damage, and oxidative stress response in the mouse ileal loop model. These results highlight inflammation and oxidative stress as common features in the pathogenesis of C. difficile Clade 2 strains. Finally, this work contributes to the description of differences in virulence among various C. difficile strains.

Rades D, Conde-Moreno AJ, Cacicedo J, et al.
Radiation Therapy Alone Provides Excellent Outcomes for Spinal Cord Compression from Vertebral Lymphoma.
Anticancer Res. 2016; 36(6):3081-3 [PubMed] Related Publications
AIM: Malignant spinal cord compression (SCC) is treated with radiotherapy (RT). Additional neurosurgery has become more widely used since a trial showed a benefit for selected patients. Although lymphomas were excluded from that trial, neurosurgery is also increasingly being performed in these patients. This study investigated whether neurosurgery is actually required for this group.
PATIENTS AND METHODS: Twenty-nine patients receiving RT alone for SCC from vertebral lymphoma were analyzed for motor function, walking ability, in-field recurrence and survival.
RESULTS: Overall response was 100% (72% improvement, 28% stable). At 1, 6 and 12 months after RT, 83%, 100% and 100% of patients were able to walk; 64%, 100%, and 100% of non-ambulatory patients regained their walking ability. Freedom from in-field recurrence was 100% at 6 and 12 months. Survival rates at 6 and 12 months were 79% and 75%.
CONCLUSION: RT alone resulted in excellent outcomes for SCC from lymphoma. These patients may not require surgery.

Rades D, Janssen S, Bajrovic A, et al.
A Total Radiation Dose of 70 Gy Is Required After Macroscopically Incomplete Resection of Squamous Cell Carcinoma of the Head and Neck.
Anticancer Res. 2016; 36(6):2989-92 [PubMed] Related Publications
AIM: To contribute to the definition of the optimal total radiation dose and to determine the role of concurrent chemotherapy after macroscopically incomplete resection of squamous cell carcinoma of the head and neck (SCCHN).
PATIENTS AND METHODS: Twenty-six patients treated with postoperative radio(chemo)therapy following macroscopically incomplete resection were evaluated. Total radiation dose (70 Gy vs. 59.4-66 Gy), concurrent chemotherapy (yes vs. no) plus six factors were investigated for locoregional control (LRC) and overall survival (OS).
RESULTS: On analyses of LRC, 70 Gy was significantly superior to 59.4-66.0 Gy. Two-year LCR rates were 94% and 25%, respectively (p<0.001). Concurrent chemotherapy significantly improved 2-year LRC (90% vs. 0%, p<0.001). Both 70 Gy (92% vs. 11%, p<0.001) and concurrent chemotherapy (80% vs.0%, p<0.001) also resulted in better OS.
CONCLUSION: A total radiation dose of 70 Gy was significantly superior to lower doses regarding both LCR and OS. Concurrent chemotherapy is also very important to achieve optimal outcomes.

Ribnikar D, Cardoso F
Tailoring Chemotherapy in Early-Stage Breast Cancer: Based on Tumor Biology or Tumor Burden?
Am Soc Clin Oncol Educ Book. 2016; 35:e31-8 [PubMed] Related Publications
The question of whether to offer adjuvant chemotherapy to patients with early-stage breast cancer has always been challenging to answer. It is well known that a substantial proportion of patients with early-stage breast cancer are over treated, especially when staging and hormonal and HER2 receptors are solely taken into consideration. The advances in our knowledge of breast cancer biology and its clinical implications were the basis for the discovery of additional reliable prognostic markers to aid decision making for adjuvant treatment. Gene expression profiling is a molecular tool that more precisely defines the intrinsic characteristics of each individual tumor. The application of this technology has led to the development of gene signatures/profiles with relevant prognostic-and some predictive-value that have become important tools in defining which patients with early-stage breast cancer can be safely spared from chemotherapy. However, the exact clinical utility of these tools will only be determined after the results of two large prospective randomized trials, MINDACT and TailorX, evaluating their role become available. Notwithstanding the existence of these genomic tools, tumor burden (defined as tumor size and nodal status) still has independent prognostic value and must be incorporated in decision making. In addition, these gene signatures have limited predictive value, and new biomarkers and new targets are needed. Therefore close collaboration between clinicians and scientists is crucial. Lastly, issues of cost-effectiveness, reimbursement, and availability are crucial and widely variable around the globe.

Mlakar J, Volavšek M
Influence of gross specimen sampling on the incidence of incidental prostatic carcinoma in cystoprostatectomy specimens of patients with bladder carcinoma.
Pol J Pathol. 2016; 67(1):8-12 [PubMed] Related Publications
Reported prostate cancer incidence rates vary greatly among cystoprostatectomy samples. We investigated how the thoroughness of prostate sampling influences prostatic carcinoma incidence in bladder cancer patients. In a retrospective study, 313 cystoprostatectomy cases of urinary bladder carcinoma were analysed for the presence of concurrent prostatic carcinoma. Patients were divided into two groups: patients who had undergone the operation before and after 2007, when a policy of preferably complete prostate sampling in cystoprostatectomy specimens was introduced at our institution. Cases processed after the 2007 recommended sampling changes had a significantly higher rate of incidental prostatic carcinoma and clinically significant prostatic carcinoma than the pre-2007 group (p < 0.0001 and p = 0.003, respectively). Complete prostate processing in cystoprostatectomy specimens results in a higher incidence of incidental prostatic carcinoma than with partial processing. More patients with clinically significant prostate cancer are consequently discovered. In conclusion, we believe that complete prostate sampling should be mandatory.

Seidl D, Janssen S, Strojan P, et al.
Prognostic Factors After Definitive Radio(Chemo)Therapy of Locally Advanced Head and Neck Cancer.
Anticancer Res. 2016; 36(5):2523-6 [PubMed] Related Publications
AIM: To identify predictors of locoregional control (LRC) and overall survival (OS) after definitive radio(chemo)therapy for squamous cell carcinoma of the head and neck (SCCHN).
PATIENTS AND METHODS: Two hundred and seventy-five patients were evaluated; 261 patients received radiochemotherapy with 30-40 mg/m(2) of cisplatin weekly, three courses of cisplatin 100 mg/m(2), two courses of cisplatin 5x20 mg/m(2) or two courses of cisplatin 5×20 mg/m(2)plus 5-fluorouracil. Ten characteristics were analyzed: Pre-radiotherapy hemoglobin, T-/N-category, Karnofsky performance-score (KPS), gender, age, chemotherapy type, tumor site, grading and radiation dose.
RESULTS: On multivariate analyses, hemoglobin 12-14 g/dl (p=0.040), lower T-category (p=0.010), lower N-category (p=0.042) and female gender (p=0.006) were predictive of LRC. Hemoglobin >12 g/dl (p=0.020), lower N-category (p<0.001), KPS ≥80 (p<0.001), female gender (p=0.024) and cisplatin 100 mg/m(2) or 5×20 mg/m(2) (p<0.001) were predictors of improved OS.
CONCLUSION: Predictors of LRC and OS were identified that can improve personalization of treatment. Since chemotherapy type was associated with OS, studies comparing different regimens are warranted.

Seidl D, Janssen S, Strojan P, et al.
Importance of Chemotherapy and Radiation Dose After Microscopically Incomplete Resection of Stage III/IV Head and Neck Cancer.
Anticancer Res. 2016; 36(5):2487-91 [PubMed] Related Publications
AIM: To investigate the importance of chemotherapy and radiation dose after R1 resection of squamous cell carcinoma of the head-and-neck (SCCHN).
PATIENTS AND METHODS: One hundred and twenty-two patients receiving radiotherapy alone or with concurrent chemotherapy [cisplatin or cisplatin/5-fluorouracil (5-FU)] were retrospectively analyzed.
RESULTS: On multivariate analysis, chemotherapy was significantly associated with improved locoregional control (p=0.048). Three-year locoregional control rates were 61% for those treated without chemotherapy, 83% for those treated with cisplatin and 77% for those treated with cisplatin/5-FU. Radiation doses of 66 and 70 Gy were non-significantly superior to 60-64 Gy (p=0.18). On multivariate analysis, chemotherapy showed a trend for improving survival (p=0.055). Three-year OS rates were 51% for those without chemotherapy, 65% for those treated with cisplatin and 57% for those treated with cisplatin/5-FU. Radiation doses of 66 Gy (3-year survival=61%) and 70 Gy (70%) were superior to 60-64 Gy (25%) (p=0.021).
CONCLUSION: Concurrent chemotherapy and a radiation dose of 66 Gy resulted in better outcomes. Cisplatin and cisplatin/5-FU were similarly effective. Radiation doses >66 Gy appear not to be necessary.

Rades D, Bartscht T, Janssen S, et al.
Forecasting Survival Probabilities After Radiotherapy of Metastatic Epidural Spinal Cord Compression from Colorectal Cancer in the Elderly.
Anticancer Res. 2016; 36(4):1829-33 [PubMed] Related Publications
AIM: To develop a tool forecasting survival of elderly patients with metastatic epidural spinal cord compression (MESCC) from colorectal cancer (CRC).
PATIENTS AND METHODS: Fifty-seven patients were retrospectively evaluated. Eleven characteristics were investigated for survival. Independent characteristics were used for the tool. Scores were obtained from dividing 6-month survival rates by 10. From summing these points, patient scores were obtained.
RESULTS: On survival analysis (Cox regression model), organ metastases (p=0.006), performance status (p<0.001), pre-radiotherapy walking ability (p<0.001) and the dynamic of developing motor weakness (p=0.033) were significant factors affecting survival and were incorporated into the tool. Possible patient scores were 5, 9, 10, 13, 14, 16, 20 or 24 points. Three groups were created with scores of 5-10, 13-16 and 20-24 points, with 6-month survival rates of 4%, 23% and 79%, respectively (p<0.001).
CONCLUSION: By applying this tool, it is possible to forecast the survival of elderly patients experiencing MESCC from CRC, which is important for optimal treatment personalization.

Bajuk P, Furlan T, Černelč P, et al.
Monoclonal B-cell lymphocytosis in the population of Slovenian region of Lower Carniola.
Int J Lab Hematol. 2016; 38(4):341-6 [PubMed] Related Publications
INTRODUCTION: Monoclonal B-cell lymphocytosis (MBL) is a premalignant asymptomatic condition characterized by the presence of a small population of monoclonal B lymphocytes (less than 5 × 10(9) /L) in the venous blood of otherwise healthy individuals. Incidence of MBL is higher among first-degree relatives of patients with chronic lymphocytic leukemia (CLL) and also increases with age and among men. We compared the incidence of MBL found in the same environment in both an open general population and relatives of CLL patients.
METHODS: Samples were analyzed with 5-parameter flow cytometry using following monoclonal antibodies: kappa and lambda clonality, CD5, CD19, CD20. We analyzed 216 samples of patients in the Slovenian area of Lower Carniola aged 23-88 years. Fifty-four patients who came from families where CLL is present were compared by age and gender to 162 healthy individuals from the general population of the same region.
RESULTS: We found 10 cases of MBL (4.6%). In 9.4% of younger (≤ 50 years) first-degree relatives of CLL patients with immunophenotypic characteristics of atypical MBL, we observed a prevailingly normal κ to λ ratio. The difference in incidence of MBL cases between relatives and the general population decreases with age.
CONCLUSION: MBL in Slovenia can be coincidentally found with a similar frequency to previously studied populations of other parts of Europe. We found, however, a higher incidence of atypical MBL among first-degree relatives.

Rietjens JA, Korfage IJ, Dunleavy L, et al.
Advance care planning--a multi-centre cluster randomised clinical trial: the research protocol of the ACTION study.
BMC Cancer. 2016; 16:264 [PubMed] Article available free on PMC after 01/07/2017 Related Publications
BACKGROUND: Awareness of preferences regarding medical care should be a central component of the care of patients with advanced cancer. Open communication can facilitate this but can occur in an ad hoc or variable manner. Advance care planning (ACP) is a formalized process of communication between patients, relatives and professional caregivers about patients' values and care preferences. It raises awareness of the need to anticipate possible future deterioration of health. ACP has the potential to improve current and future healthcare decision-making, provide patients with a sense of control, and improve their quality of life.
METHODS/DESIGN: We will study the effects of the ACP program Respecting Choices on the quality of life of patients with advanced lung or colorectal cancer. In a phase III multicenter cluster randomised controlled trial, 22 hospitals in 6 countries will be randomised. In the intervention sites, patients will be offered interviews with a trained facilitator. In the control sites, patients will receive care as usual. In total, 1360 patients will be included. All participating patients will be asked to complete questionnaires at inclusion, and again after 2.5 and 4.5 months. If a patient dies within a year after inclusion, a relative will be asked to complete a questionnaire on end-of-life care. Use of medical care will be assessed by checking medical files. The primary endpoint is patients' quality of life at 2.5 months post-inclusion. Secondary endpoints are the extent to which care as received is aligned with patients' preferences, patients' evaluation of decision-making processes, quality of end-of-life care and cost-effectiveness of the intervention. A complementary qualitative study will be carried out to explore the lived experience of engagement with the Respecting Choices program from the perspectives of patients, their Personal Representatives, healthcare providers and facilitators.
DISCUSSION: Transferring the concept of ACP from care of the elderly to patients with advanced cancer, who on average are younger and retain their mental capacity for a larger part of their disease trajectory, is an important next step in an era of increased focus on patient centered healthcare and shared decision-making.
TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number: ISRCTN63110516. Date of registration: 10/3/2014.

Hrovat A, Kravos NA, Goričar K, et al.
SORCS1 polymorphism and insulin secretion in obese women with polycystic ovary syndrome.
Gynecol Endocrinol. 2016; 32(5):395-8 [PubMed] Related Publications
We investigated the influence of SORCS1 polymorphisms on insulin secretion in obese women with PCOS. Metabolic status was recorded in 50 clinically well characterized PCOS patients. Oral glucose tolerance test was performed and laboratory parameters of insulin resistance measured. All patients were genotyped for SORCS1 rs1358030, rs1416406 and rs11192966 polymorphisms. Statistical analysis was performed using the Mann-Whitney test. SORCS1 rs1416406 significantly influenced stimulated glucose plasma levels (p = 0.006) and increased glucose stimulated insulin secretion (p = 0.034). None of the polymorphisms influenced insulin resistance as measured by homeostatic model assessment. We report for the first time the relevance of SORCS1 polymorphisms for glycemic control and glucose stimulated insulin secretion in obese women with PCOS.

Novotnik B, Ščančar J, Milačič R, et al.
Cytotoxic and genotoxic potential of Cr(VI), Cr(III)-nitrate and Cr(III)-EDTA complex in human hepatoma (HepG2) cells.
Chemosphere. 2016; 154:124-31 [PubMed] Related Publications
Chromium (Cr) and ethylenediaminetetraacetate (EDTA) are common environmental pollutants and can be present in high concentrations in surface waters at the same time. Therefore, chelation of Cr with EDTA can occur and thereby stable Cr(III)-EDTA complex is formed. Since there are no literature data on Cr(III)-EDTA toxicity, the aim of our work was to evaluate and compare Cr(III)-EDTA cytotoxic and genotoxic activity with those of Cr(VI) and Cr(III)-nitrate in human hepatoma (HepG2) cell line. First the effect of Cr(VI), Cr(III)-nitrate and Cr(III)-EDTA on cell viability was studied in the concentration range from 0.04 μg mL(-1) to 25 μg mL(-1) after 24 h exposure. Further the influence of non-cytotoxic concentrations of Cr(VI), Cr(III)-nitrate and Cr(III)-EDTA on DNA damage and genomic stability was determined with the comet assay and cytokinesis block micronucleus cytome assay, respectively. Cell viability was decreased only by Cr(VI) at concentrations above 1.0 μg mL(-1). Cr(VI) at ≥0.2 μg mL(-1) and Cr(III) at ≥1.0 μg mL(-1) induced DNA damage, while after Cr(III)-EDTA exposure no formation DNA strand breaks was determined. Statistically significant formation of micronuclei was induced only by Cr(VI) at ≥0.2 μg mL(-1), while no influence on the frequency of nuclear buds nor nucleoplasmic bridges was observed at any exposure. This study provides the first evidence that Cr(III)-EDTA did not induce DNA damage and had no influence on the genomic stability of HepG2 cells.

Kašalynas I, Venckevičius R, Minkevičius L, et al.
Spectroscopic Terahertz Imaging at Room Temperature Employing Microbolometer Terahertz Sensors and Its Application to the Study of Carcinoma Tissues.
Sensors (Basel). 2016; 16(4):432 [PubMed] Article available free on PMC after 01/07/2017 Related Publications
A terahertz (THz) imaging system based on narrow band microbolometer sensors (NBMS) and a novel diffractive lens was developed for spectroscopic microscopy applications. The frequency response characteristics of the THz antenna-coupled NBMS were determined employing Fourier transform spectroscopy. The NBMS was found to be a very sensitive frequency selective sensor which was used to develop a compact all-electronic system for multispectral THz measurements. This system was successfully applied for principal components analysis of optically opaque packed samples. A thin diffractive lens with a numerical aperture of 0.62 was proposed for the reduction of system dimensions. The THz imaging system enhanced with novel optics was used to image for the first time non-neoplastic and neoplastic human colon tissues with close to wavelength-limited spatial resolution at 584 GHz frequency. The results demonstrated the new potential of compact RT THz imaging systems in the fields of spectroscopic analysis of materials and medical diagnostics.

Prosen L, Hudoklin S, Cemazar M, et al.
Magnetic field contributes to the cellular uptake for effective therapy with magnetofection using plasmid DNA encoding against Mcam in B16F10 melanoma in vivo.
Nanomedicine (Lond). 2016; 11(6):627-41 [PubMed] Related Publications
AIM: We explored the distribution and cellular uptake of intratumorally injected SPIONs-PAA-PEI-pDNA (magnetofection complexes), and antitumor effectiveness of magnetofection with plasmid DNA encoding short hairpin RNA (shRNA) against Mcam (pDNA(anti-MCAM)).
MATERIALS & METHODS: Analyses were made based on the histology, ultrastructure and quantitative measurements of magnetofection complexes, and quantification of the antitumor effectiveness in B16F10 melanoma in vivo.
RESULTS: Injected magnetofection complexes were distributed around the injection site. Exposure of tumors to external magnetic field contributed to the uptake of magnetofection complexes from extracellular matrix into melanoma cells. Three consecutive magnetofections of tumors with pDNA(anti-MCAM) resulted in significant reduction of tumor volume.
CONCLUSION: Magnetofection is effective for gene delivery to melanoma tumors, but requires a magnetic field for cellular uptake and antitumor effect.

Suárez C, Barnes L, Silver CE, et al.
Cervical lymph node metastasis in adenoid cystic carcinoma of oral cavity and oropharynx: A collective international review.
Auris Nasus Larynx. 2016; 43(5):477-84 [PubMed] Article available free on PMC after 01/10/2017 Related Publications
The purpose of this study was to suggest general guidelines in the management of the N0 neck of oral cavity and oropharyngeal adenoid cystic carcinoma (AdCC) in order to improve the survival of these patients and/or reduce the risk of neck recurrences. The incidence of cervical node metastasis at diagnosis of head and neck AdCC is variable, and ranges between 3% and 16%. Metastasis to the cervical lymph nodes of intraoral and oropharyngeal AdCC varies from 2% to 43%, with the lower rates pertaining to palatal AdCC and the higher rates to base of the tongue. Neck node recurrence may happen after treatment in 0-14% of AdCC, is highly dependent on the extent of the treatment and is very rare in patients who have been treated with therapeutic or elective neck dissections, or elective neck irradiation. Lymph node involvement with or without extracapsular extension in AdCC has been shown in most reports to be independently associated with decreased overall and cause-specific survival, probably because lymph node involvement is a risk factor for subsequent distant metastasis. The overall rate of occult neck metastasis in patients with head and neck AdCC ranges from 15% to 44%, but occult neck metastasis from oral cavity and/or oropharynx seems to occur more frequently than from other locations, such as the sinonasal tract and major salivary glands. Nevertheless, the benefit of elective neck dissection (END) in AdCC is not comparable to that of squamous cell carcinoma, because the main cause of failure is not related to neck or local recurrence, but rather, to distant failure. Therefore, END should be considered in patients with a cN0 neck with AdCC in some high risk oral and oropharyngeal locations when postoperative RT is not planned, or the rare AdCC-high grade transformation.

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