Low-dose High-resolution 18F-FDG-PET/CT Using Time-of-flight and Point-spread Function Reconstructions: A Role in the Detection of Breast Carcinoma Axillary Lymph Node Metastases.

AIM: to evaluate the performance of N-staging assessment in clinically-proven T1 breast carcinoma by high-resolution 18F-fluorodeoxyglucose-positron-emission tomography/computed tomography (18F-FDG-PET/CT) using time-of-flight with point-spread function reconstruction. PATIENTS AND METHODS: In 30 women with clinically proven T1 breast carcinoma, imaging before surgery was performed using 18F-FDG-PET/CT. The results of PET/CT in detection of lymph node metastases were compared with those obtained after pathological investigation of axillary biopsy. A four-ring PET subsystem with image reconstruction using time-of-flight and point-spread function was used with the radiopharmaceutical dose reduction to 2.5 MBq/kg. RESULTS: Axillary lymph node metastasis was confirmed by histology in 13 patients, but metastasis was suspected based on PET/CT in 12 of those patients, the absence of metastasis was surgically confirmed in 17 women, 15 of which were suspected based on PET/CT. The sensitivity for detection of axillary lymph node metastasis was 93.3%, with a specificity of 88.2% in the whole patient cohort. Additionally, distant metastatic spread was found in 13.3% of patients. CONCLUSION: The reconstruction of PET images with time-of-flight and point-spread function enabled the improvement of diagnostic performance in N-staging of breast carcinoma, even when the dose of radiopharmaceutical was reduced to 2.5 MBq/kg.

Perioperative Tumour Marker Levels as Prognostic Factors for Surgical Treatment of Breast Cancer Liver Metastases.

BACKGROUND/AIM: The results of surgical treatment of breast cancer liver metastases (BCLM) remain suboptimal. The search for perioperative prognostic factors could help determine high risk groups of patients. The aim of study was to evaluate the significance of tumour markers (TM) on long-term treatment results. PATIENTS AND METHODS: Liver surgery was carried out in 32 women for BCLM. The perioperative serum levels of CEA, CA19-9, TPA, TPS, CYFRA 21-1 and TK were determined. RESULTS: Preoperative levels of CA19-9 were significant for overall survival (OS)(p<0.05) and recurrence-free survival (RFS) (p<0.01). TPA, TPS and CYFRA 21-1 levels were significant for OS (p<0.05; p<0.04; p<0.05). Postoperative levels of CEA, TPS and CYFRA 21-1 were significant for RFS (p<0.04; p<0.01; p<0.02), while CA19-9 postoperative levels were significant for OS and RFS (p<0.03; p<0.01). CONCLUSION: Perioperative TM serum levels may represent prognostic indicators reflecting the results of surgical treatment of BCLM.

CEA, CA 15-3, and TPS as Prognostic Factors in the Follow-up Monitoring of Patients After Radical Surgery for Breast Cancer.

AIM: The aim of this study was to evaluate the ability of tissue polypeptide-specific antigen (TPS), carcinoembryonic antigen (CEA), and cancer antigen 15-3 (CA 15-3) to predict relapse in breast cancer patients, when the measurement of biomarkers is performed within 6 months after surgery. PATIENTS AND METHODS: Four hundred and seventy-two patients with breast cancer were evaluated. TPS, CEA, and CA 15-3 were measured in months 1, 3, and 6, after surgery. Disease recurrence was recorded between 7-12 months after surgery. Disease recurrence occurred in 60 patients, while 412 patients remained in recurrence-free status. RESULTS: TPS levels of the recurrence group differed statistically significantly in the first and sixth month after surgery compared to recurrence-free group (p=0.0339, AUC=0.6056; p<0.0001, AUC=0.7196). CEA and CA 15-3 measurements did not achieve a statistically significant difference for any month examined. CONCLUSION: TPS level in the sixth month after surgery is the best candidate biomarker to predict disease recurrence.

Pre-surgical Multiparametric Assessment of Breast Lesions Using 3-Tesla Magnetic Resonance.

BACKGROUND/AIM: The aim of this study was to evaluate experience with multiparametric breast imaging on 3-Tesla magnetic resonance (3T-MRI) scanner using a dedicated 18-channel coil compared to histological findings in women after surgery. MATERIALS AND METHODS: The study included 100 women with 105 Breast Imaging Reporting and Data System (BI-RADS) 4 to 6 lesions by mammography who were examined using 3T-MRI and subsequently underwent surgery. MRI included non-contrast T1, T2 and T2 short tau inversion recovery (STIR) sequences, diffusion-weighted imaging with apparent diffusion coeficient maps, postcontrast dynamic study and single-voxel MRI spectroscopy. The results were compared to those of histopathological examination. RESULTS: A sensitivity of 98.68% was found for the whole population, with a specificity of 86.20%. The most valuable findings were diffusion restriction with sensitivity of 90.79% and specificity of 89.66%, and increased choline in the spectrum with sensitivity of 68.42% and specificity of 93.10%. Evaluation of the enhancement curve had sensitivity of 45.05% and specificity of 72.41%. In examination of lymph nodes, 3T-MRI had sensitivity of 92.59% and specificity of 93.87%. CONCLUSION: Multiparametric 3T-MRI breast imaging shows excellent results in evaluation of breast cancer compared to histological findings, both for primary tumor and nodal metastases. The greatest contribution to improving diagnostic performance is the evaluation of diffusion.

Circulating Growth and Angiogenic Factors and Lymph Node Status in Early-stage Breast Cancer - A Pilot Study.

AIM: To evaluate the possibility of selected biomarkers for breast cancer diagnostics and/or treatment monitoring, lymph node (LN) status determination and clinical decision regarding axillary node dissection. PATIENTS AND METHODS: Two hundred and eleven patients with malignant breast cancer and 42 age-matched healthy controls were enrolled. Serum insulin-like growth factor 1 (IGF1) and insulin-like growth factor binding protein 3 (IGFBP3) and plasma epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), osteoprotegerin (OPG) and osteopontin (OPN) were measured. We compared patients versus controls, patients with negative versus positive lymph node and patients with and without axillary lymph node dissection (ALND). RESULTS: We found elevated IGF1 and VEGF levels in patients with lymph node metastases compared to controls (p=0.0179 and p=0.0091, respectively) and in patients with ALND (p=0.0337 and p=0.0438, respectively). CONCLUSION: Circulating IGF1 and VEGF levels may predict the presence of lymph node metastases and help in the decision to avoid ALND in patients with early-stage breast cancer.

May CTC technologies promote better cancer management?

In the case of cancer, death is usually not due to the primary tumor itself but due to dissemination. Analysis of the circulating tumor cells (CTCs), i.e., cells responsible for a formation of metastases, should provide information useful for the management of cancer patients, fulfilling the objectives of predictive, preventive, and personalized medicine (PPPM). Despite promising results, the decisions on stage of disease and how to guide the adjuvant treatment still do not include results of CTC assessment. We want to describe two major reasons why the recent diagnostic value of CTC analysis is not sufficient for clinical use. The first reason arises from the biological nature of the tumor itself and the second reason is associated with an interdisciplinary status of CTC diagnostics in the sense that it is neither a theme purely for pathologists nor for haemato-oncologists nor clinical biochemists. We anticipate that there are at least three areas where CTCs can be useful for clinical practice. The first is monitoring of treatment efficacy of cancer patients. The second is a molecular characterization of captured CTCs for targeted treatment, and the third is a cultivation of captured CTCs for drug sensitivity testing. All of these approaches allow researchers recognize and respond to changes of phenotype of cancer cells during disease progression and introduce PPPM into clinical practice.

Surgery for breast cancer liver metastases - factors determining results.

BACKGROUND/AIM: The results of the surgical treatment of liver metastases from breast cancer (BCLMs) may be determined by various factors. The aim of the present study was to specify the risk factors for surgical treatment of BCLM. PATIENTS AND METHODS: Twenty-four female patients with BCLMs were treated with liver resection or radiofrequency ablation (RFA). We evaluated the effects of patient age, time interval between the breast cancer and BCLM surgery, the type of surgical procedure, histopathological findings of the primary tumor, the number and overall diameter of BCLMs, the presence of resectable extra-hepatic metastases, and local tumor recurrence after breast cancer surgery on patients' overall (OS) and progression-free survival (PFS). RESULTS: Age <50 years and shorter interval between breast and liver surgery were risk factors for poorer OS (p<0.02 and p<0.01, respectively) and for PFS (p<0.01 and p<0.01, respectively). The presence of extra-hepatic metastases was a risk factor for OS (p<0.005). An overall diameter of BCLM ≥3.5 cm and a negative status of both estrogen (ER) and progesterone receptors (PR) in the primary tumor were risk factors for poorer PFS (p<0.009 and p<0.0003, respectively). CONCLUSION: The risk factors for surgery for BCLMs are age <50 years, the presence of extra-hepatic metastases, hormone receptor negativity of the primary tumor and an overall BCLM diameter ≥3.5 cm.

Prognostic importance of some clinical and therapeutic factors for the effect of portal vein embolization in patients with primarily inoperable colorectal liver metastases.

INTRODUCTION: Portal vein embolization (PVE) may increase the resectability of liver metastases. However, the problem of PVE is insufficient growth of the liver or tumor progression in some patients. The aim of this study was to evaluate the significance of commonly available clinical factors for the result of PVE. MATERIAL AND METHODS: Portal vein embolization was performed in 38 patients with colorectal liver metastases. Effects of age, gender, time between PVE and liver resection, oncological therapy after PVE, indocyanine green retention rate test, synchronous, metachronous and extrahepatic metastases, liver volume before and after PVE, increase of liver volume after PVE and the quality of liver parenchyma before PVE on the result of PVE were evaluated. RESULTS: Liver resection was performed in 23 (62.2%) patients within 1.3 ±0.4 months after PVE. Tumor progression occurred in 9 (23.7%) patients and 6 (15.8%) patients had insufficient liver hypertrophy. Significant clinical factors of PVE failure were number of liver metastases (cut-off - 4; odds ratio - 4.7; p < 0.03), liver volume after PVE (cut-off 1000 cm(3); odds ratio - 5.1; p < 0.02), growth of liver volume after PVE (cut-off 150 cm(3); odds ratio - 18.7; p < 0.002), oncological therapy administered concomitantly with PVE (p < 0.003). CONCLUSIONS: Negative clinical factors of resectability of colorectal cancer liver metastases after PVE included more than four liver metastases, liver volume after PVE < 1000 cm(3), growth of the contralateral lobe by less than 150 cm(3) and concurrent oncological therapy.

Non-colorectal liver metastases: surgical treatment options.

BACKGROUND/AIMS: Due to different biological characteristics of non-colorectal liver metastasizes (NCLM), surgical treatment, especially it´s long term results, is a topic of discussion. The aim of the study was to evaluate the single center experience with surgical treatment of NCLM. METHODOLOGY: Seventy two patients were prospectively included. The average length of time after the primary surgery was 3.9 years (0-8.5 years). RFA prevailed -50 patients (69.4%), resection presenting 30.6%. Preoperative chemotherapeutical downstaging or portal vein embolization was performed on 12 patients (16.7%). Resectable or radiofrequency ablation (RFA) treatable extrahepatic metastasizes were removed in 26 patients (36.1%). RESULTS: One, three and five years patient survival after the liver resection or RFA was 88.6, 72.5 and 36.9%. The best survival rate was in patients with carcinoid (5 years-100%), breast cancer (5 years-33.8%), renal carcinoma (3 years-44.4% ) and gynecological tumors metastasizes (2 years-72.9%). With regards to long-term survival of patients, we did not find any statistically significant difference between RFA and resection. Patients with extrahepatic metastasizes had worse prognosis (p<0.01). CONCLUSIONS: Liver resection and RFA in NCLM have an unambiguous place in multi-modal curative strategy. The decision for surgical treatment of patients suffering from NCLM, is strictly individual with the aim of achieving qualitative long-term survival.

Growth factors and breast tumors, comparison of selected growth factors with traditional tumor markers.

BACKGROUND: The first aim of this project was to study new possibilities for distinguishing benign from malignant tumors using growth factors and to compare them with the traditional tumor markers Carcinoembryonic antigen (CEA) and Cancer antigen 15-3 (CA15-3) for breast tumors. The second aim was to make a comparison of CEA, CA 15-3, Insulin-like growth factor I (IGF1), Insulin-like growth factor-binding protein 3 (IGFBP3), Hepatocyte growth factor (HGF) and Epidermal growth factor (EGF) for individual stages of cancer. PATIENTS AND METHODS: Our group of patients consisted of 110 females, 89 with breast cancer and 21 with benign breast tumors (fibroadenomas). Serum levels of CEA and CA 15-3 were measured using a DxI instrument. Serum levels of IGF1 and IGFBP3 were measured using IRMA radioisotope assay kits. HGF and EGF were measured using an xMAP Luminex multiplex panel. Serum samples were collected prior to surgery and those of the two groups of patients were compared (malign vs. benign). Patients with diabetes mellitus were excluded from this project. RESULTS AND DISCUSSION: Comparing the individual parameters of serum levels between the two groups of patients (malignant vs. benign) only HGF was found to show a statistically significant difference. The mean of HGF in patients with malignant diseases prior to surgery was 3370 pg/ml compared to 1799 pg/ml in benign tumors with p=0.0016. We found significantly lower serum values of IGF1 at stage III in comparison to stages I and II: mean values: at stage I=181 ng/ml, at stage II=182 ng/ml and at stage III=70 ng/ml; stage III vs. stage II, p=0.0167. CONCLUSION: Tumor markers are currently used for therapy monitoring in cancer patients as one of the indicators of successful therapy. Our findings correspond to existing literature. IGF1 and its binding protein IGFBP3 cannot be used to distinguish between malignant and benign tumor. HGF is considered to be a marker of progression and of the aggressiveness of breast cancer; our data fully corresponds to this. Based on our data, this marker could potentially be used as an additional tool for the differentiation between benign and malignant tumor.

Vitamin D in colorectal, breast, prostate and lung cancer: a pilot study.

BACKGROUND: Many studies have demonstrated the relationship between vitamin D and cancer of many different sites, including of the breast, colorectum, prostate and lung. Most epidemiological studies have assessed the effects of dietary intake only, although endogenous production after sun exposure is the main source of vitamin D. The aim of our pilot study was to study serum levels of vitamin D in general population and in patients with different type of cancer. PATIENTS AND METHODS: The control group consisted of 214 healthy individuals. Pathological groups of patients included 170 patients with different cancer types (28 patients with prostate cancer, 43 patients with breast cancer, 49 patients with colorectal cancer and 50 patients with lung cancer). All of the patients were enrolled in the early clinical stage of cancer up to clinical stage III. Advanced stages were not included into the study. Vitamin D serum levels were measured using ECLIA Roche method. RESULTS: All the results for serum vitamin D from pathological groups were significantly lower compared to the levels of the control group. All the cancer types had a high incidence rate of very low serum levels of vitamin D. Lung cancer had the highest incidence rate of very low vitamin D serum levels. CONCLUSION: We found a high incidence of hypovitaminosis D in cancer patients compared to a healthy control group among a Czech population. This incidence rate is higher in comparison to data found in literature from the other parts of the world. Based on the data from this study, a large epidemiological study monitoring vitamin D serum levels in the healthy population and in cancer patients in the Czech Republic has been already proposed.

Predictive value of serum biomarkers in patients after portal vein embolization (PVE): a pilot study.

BACKGROUND/AIM: Insufficient growth of the liver or tumor progression is an important issue of portal vein embolization (PVE) in some patients. This study evaluated the predictive value of serum biomarkers for liver hypertrophy and tumor progression after PVE. PATIENTS AND METHODS: Serum levels of tumor markers, growth factors and cytokines were determined in 40 patients with malignant liver tumors in the pre- and post-PVE period. The values were compared with contralateral liver hypertrophy and tumor progression. RESULTS: Liver tissue hypertrophy occurred in 26 (65%), tumor progression in 11 (27.5%) and insufficient liver hypertrophy in 3 (7.5%) of the patients. The significant predictive biomarkers of PVE included serum TPA levels, monototal, IGF-BP3, IGF1, TGF-α, EGF, HGF, VEGF, TNFa and IL-10 before PVE; and TK, TPA, monototal, IGF-BP3, TGFa and IL-8 over the course of 28 days after PVE. CONCLUSION: Certain serum biomarkers have an important predictive value for the result of PVE.