Medicina, Volume 50, Issue 4 (August 2014) – 9 articles , Pages 197-254

Background and objective: The internal mammary lymph nodes (IMN) have been recognized as a potential site of regional breast cancer spread. The aim of this study was to evaluate the impact of internal mammary node radiotherapy (RT) to on clinical outcomes in breast cancer patients treated with mastectomy and postoperative radiation therapy.
Materials and methods: This cohort study included 588 patients with breast cancers located in the central and medial quadrants. IMN RT was applied to 320 patients and 268 patients did not receive it IMN RT. Inside the IMN RT group, 165 patients received external beam IMN irradiation (IMN-EB). Mastectomy combined with using Californium-252 neutron source implantation was applied to 155 patients (IMN-BT). Cox proportional hazards modeling was used to determine the influence of IMN RT on clinical outcome. Age, tumor size, lymph nodal status, adjuvant radiotherapy, chemotherapy and hormonal therapy were assessed.
Results: IMN-EB resulted in a significant improvement of distant metastasis-free survival, breast cancer-specific survival and overall survival (P = 0.033, P = 0.037 and P = 0.011, respectively). The IMN-EB radiotherapy has a significant impact on event-free survival (HR, 0.67; 95% CI, 0.46–0.91; P = 0.043) and breast cancer-specific survival (HR, 0.64; 95% CI, 45–0.91; P = 0.013) in patients with moderate-risk (stage T_1–2 N₁). There was no association between IMN RT and clinical outcomes of patients with high-risk disease (stage T_3–4 N_2–3) in any of the study end points.
Conclusions: The effects of IMN-EB radiotherapy on event-free survival and breast cancer- specific survival were benefit for women with moderate-risk breast cancer. Full article

Background and objective: Superparamagnetic iron oxide nanoparticles (SPIONs) emerge as a promising tool for early cancer diagnostics and targeted therapy. However, both toxicity and biological activity of SPIONs should be evaluated in detail. The aim of this study was to synthesize superparamagnetic cobalt ferrite nanoparticles (Co-SPIONs), and to investigate their uptake, toxicity and effects on cancer stem-like properties in human pancreatic cancer cell line MiaPaCa2 and human ovarian cancer cell line A2780.
Materials and methods: Co-SPIONs were produced by Massart's co-precipitation method. The cells were treated with Co-SPIONs at three different concentrations (0.095, 0.48, and 0.95 μg/mL) for 24 and 48 h. Cell viability and proliferation were analyzed after treatment. The stemlike properties of cells were assessed by investigating the cell clonogenicity and expression of cancer stem cell-associated markers, including CD24/ESA in A2780 cell line and CD44/ALDH1 in MiaPaCa2 cell line. Magnetically activated cell sorting was used for the separation of magnetically labeled and unlabeled cells.
Results: Both cancer cell lines accumulated Co-SPIONs, however differences in response to nanoparticles were observed between MiaPaCa2 and A2780 cell. In particular, A2780 cells were more sensitive to exposition to Co-SPIONs than MiaPaCa2 cells, indicating that a safe concentration of nanoparticles must be estimated individually for a particular cell type. Higher doses of Co-SPIONs decreased both the clonogenicity and ESA marker expression in A2780 cells.
Conclusions: Co-SPIONs are not cytotoxic to cancer cells, at least when used at a concentration of up to 0.95 μg/mL. Co-SPIONs have a dose-dependent effect on the clonogenic potential and ESA marker expression in A2780 cells. Magnetic detection of low concentrations of Co-SPIONS in cancer cells is a promising tool for further applications of these nanoparticles in cancer diagnosis and treatment; however, extensive research in this field is needed. Full article

Sacral insufficiency fractures can occur as a complication after pelvic radiotherapy. Despite several recent studies showing high incidence of sacral insufficiency fractures in elderly women after pelvic radiotherapy this condition still remains underdiagnosed. We present a case of sudden onset of low back pain in a female patient with a history of cervical cancer radiotherapy. Initial diagnostic imaging misinterpreted SIF for metastasis. Bone scan and single-photon emission-computed tomography with low-dose computed tomography revealed the correct diagnosis. Due to the reasons that sacral insufficiency fractures still remain underdiagnosed this report is important to practical routine work of oncologists and radiologists. Full article

Background and objective: To determine changes in reduced glutathione (GSH) and glutathione S-transferase (GST) during neoadjuvant chemotherapy followed by concurrent chemoradiation for patients with stage IIB–IIIB cervical cancer, and to evaluate their significance to the efficacy of the treatment.
Materials and methods: According to the prospective phase II study protocol, 36 patients with stage IIB–IIIB cervical cancer were enrolled. A short course of intensive weekly neoadjuvant cisplatin and gemcitabine chemotherapy followed by concurrent weekly cisplatin and gemcitabine-based chemoradiation was administered. Blood samples for GSH, GST analysis were collected and analyzed before the start of the treatment, after neoadjuvant chemotherapy, and after the end of the chemoradiation.
Results: A statistically significant increase in the concentration of GSH after neoadjuvant chemotherapy was identified. After chemoradiation, values of this rate significantly decreased in contrast with GSH concentration after neoadjuvant chemotherapy in cases of stage IIB, regional metastases negative patients group, patients with a positive response to treatment, and patients who had no progression of the disease during the first 2 years after treatment. Statistically significant changes in GST during the treatment were not identified; the GST concentration after chemoradiation showed a statistically significant difference in GST con- centrations in terms of the progression of the disease and disease without progression.
Conclusions: The results suggest that changes in the concentration of GSH during the treatment of locally advanced cervical cancer might be important for the prediction of the efficacy of the treatment. Statistically significant changes in GST concentration levels during the treatment were not observed. Full article

Background and objective: In vivo reflectance confocal microscopy (RCM) is a promising novel technology for non-invasive early diagnostics of cutaneous melanoma. However, the possibility to detect melanocytic atypia in nevi by means of in vivo RCM remains unknown. The aim of the study was to evaluate the significance of in vivo RCM features of melanocytic atypia for the diagnosis of melanocytic nevi, dysplastic nevi and cutaneous melanoma.
Materials and methods: A total of 138 melanocytic skin lesions comprising 25 melanocytic nevi, 69 dysplastic nevi and 44 melanomas were analyzed by means of dermoscopy, in vivo RCM and routine histopathology. In vivo RCM images were analyzed for the arrangement of keratinocytes in epidermis, pagetoid cells and junctional melanocytic nests and correlated refractivity aspects of nests with histopathology.
Results: Separately and all together taken the in vivo RCM features of melanocytic atypia were significant in differential diagnosis of benign and malignant melanocytic skin lesions, though none of the features was significant in discriminating nevi without cytologic atypia of dysplastic nevi. In vivo RCM feature of dense cell clusters corresponded with melanin containing nevomelanocytes on histopathology though exact correspon- dence of non-homogeneous and atypical sparse cell clusters remained questionable.
Conclusions: Nevus with histopathologically confirmed nevomelanocytic atypia (dysplastic nevus) could not be distinguished from nevus without atypia using analyzed in vivo RCM features of melanocytic atypia. More accurate diagnostics by means of in vivo RCM needs further investigation on reflectance of single and nested cutaneous melanocytes in benign and malignant skin lesions.
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The aim of this article is to inform about cancer treatment-induced bone loss, to identify patients at risk and those that can benefit from bone targeted treatment as well as highlight the importance of the multidisciplinary approach in the bone health in cancer care. Patients with breast cancer treated or intended to be treated with aromatase inhibitors belong to a high-risk group becausetheir fracture risk increases up to 30% due to a significant decrease in bone mineral density within 6–12 months after the start of hormonal treatment. To evaluate bone status and predict risk for fractures, lateral thoracic and lumbar spine X-ray imaging, bone mineral density measurement by dual energy X-ray absorptiometry at the lumbar spine L1–L4 vertebrae and/or hip and fracture risk factors assessment are mandatory tests prior to hormonal treatment. Morbidity and mortality associated with bone loss can be prevented with appropriate screening, lifestyle interventions, and therapy. Algorithm for the management of bone health in breast cancer patients was established in Lithuania to screen patients with increased risk for bone loss and to provide adequate specific osteoporosis treatment. Full article

Background and objective: Endometrial cancer (EC) is the most commonly diagnosed gynecologic malignancy among women worldwide and may be classified on the basis of different molecular, pathologic and genetic alterations, including microsatellite instability (MSI). Although MSI is associated with a more favorable outcome in colorectal cancer, its relationship with prognosis in EC cancer is not yet clear. The aim of our study is to identify whether MSI correlates with survival of patients in EC.
Materials and methods: We examined MSI status and survival of 109 women. MSI was detected by employing the Promega MSI Analysis System, which used 5 mononucleotides markers (BAT-25, BAT-26, NR-21, NR-24, and MONO-27) to identify MSI in a tumor and normal tissue DNA and 2 pentanucleotide markers (Penta C and Penta D) for specimen identification. Median follow-up of patients was 40.4 months (range 5.2–47.9). Survival was estimated by the Kaplan–Meier method and Cox regression analysis was used to assess the effects of different variables on patient survival.
Results: MSI-high was detected in 15.6% EC cases, all of which were associated with endometrioid type histology. Kaplan–Meier survival analysis showed no statistically significant differences between patients with MSI-high and MSI stable tumors (P = 0.4) and multivariate analysis concluded that MSI status remained insignificant after stage, histology and tumor grade adjustment (P = 0.5).
Conclusions: Our study showed no statistically significant relationship between MSI-high and survival of endometrial cancer patients.
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Background and objective: Several markers were found to be potential prognostic factors in ovarian cancer. Among markers resembling systemic changes in the host's organism are markers of the oxidative stress. In this study we attempted to analyze the oxidant and antioxidant parameters of ovarian cancer patients.
Materials and methods: A total of 42 patients with newly diagnosed stages I–IV primary ovary cancer were examined. Level of malondialdehyde (MDA) and catalytic activity catalase (CAT) were determined spectrophotometrically.
Results: Significantly lower CAT (28.2 ± 15.5 vs. 36.1 ± 14.6 nmol/L/min, P = 0.019) activity and higher MDA levels (8.7 ± 3.0 vs. 6.7 ± 2.7 nmol/L, P = 0.002) were observed in cancer patients compared with healthy volunteers. Both variables were not confirmed as prognostic factors according to Kaplan–Meier survival estimates.
Conclusions: MDA and CAT demonstrate oxidative stress in cancer patients: CAT activity was significantly lower and MDA levels higher in cancer patients compared to healthy controls. These variables were not confirmed to be prognostic factors in ovarian cancer, possibly due to small size of the study group. Full article

Cetuximab (CTX) is used for the concurrent treatment with radiotherapy (RT) in squamous cell carcinoma of head and neck (HNSCC). There are no reliable clinical predictive markers of effectiveness of CTX at yet. We describe the clinical case of patient who received a CTX/RT to cure locoregionally advanced hypopharyngeal SCC. 2-Deoxy-2-[¹⁸F]fluoro-D-glucose positron emission tomography and computed tomography (¹⁸FDG-PET/CT) was performed before the treatment and repeated 10 days after CTX induction dose. A repeated ¹⁸FDGPET/ CT scan showed dramatic decrease of metabolic parameters. Patient had a complete response after treatment and is still alive and cured after 5 years. Full article