Preoperative Plasma miRNA Levels Predict Prognosis in Early-stage Malignant Melanoma.

BACKGROUND/AIM: Non-invasive circulating tumor biomarkers in liquid biopsy, such as microRNAs (miRNA), provide for better personalization of treatment strategies. The aim of our study was to assess the prognosis of patients with melanoma undergoing tumor resection with curative intent based on analysis of selected circulating miRNAs. PATIENTS AND METHODS: A total of 22 patients with stage I to III melanoma were enrolled into this prospective study. Plasma samples were obtained pre-surgery and early post-surgery from peripheral blood draws. A panel of 23 candidate miRNAs was designed and expression of miRNAs were analyzed by reverse transcription-quantitative polymerase chain reaction with exogenous reference control cel-miR-39-3p. RESULTS: Higher preoperative expression levels of miR-99a (p=0.008), miR-320 (p=0.009), miR-1908 (p=0.001), miR-494 (p=0.018) and miR-4487 (p=0.048) were associated with a shorter disease-free interval. Similarly, higher preoperative plasma levels of miR-99a (p=0.017), miR-221 (p=0.026), miR-320 (p=0.016), miR-494 (p=0.009), miR-1260 (p=0.026) and miR-1908 (p=0.024) were associated with worse overall survival. No significant differences between pre- and postoperative plasma miRNA levels were observed. CONCLUSION: Liquid biopsy is a minimally-invasive approach which can lead to a better understanding of cancer behavior and offers the possibility of precise patient prognosis, allowing selection of the most appropriate treatment. Our study showed that preoperative plasma levels of miR-99a, miR-221, miR-320, miR-494, miR-1908 and miR-4487 were associated with disease-free interval and overall survival of patients with early-stage melanoma. This approach may help in decision-making about the appropriateness of modern adjuvant treatment administration in patients with resectable melanoma.

Prognostic Factors After Surgical Treatment of Liver Metastases from Breast Cancer - 19 Years of Experience.

BACKGROUND/AIM: The aim of this study was to determine the importance of surgical treatment, utility of hormone receptor status and selected biomarkers in the prognosis of patients with liver metastases from breast cancer (BCLM). PATIENTS AND METHODS: Thirty female underwent surgery for BCLM between 1/2000 and 1/2019. RESULTS: The type of surgery (resection/radiofrequency ablation) had no impact on overall survival (OS) - (p=0.894). Having more than one BCLM (p=0.003), expression of human epidermal receptor 2 in metastases (p=0.034), as well as an elevated presurgical level of carbohydrate antigen 19-9 (p=0.017) and postsurgical thymidine kinase (p=0.034) were negative prognostics factor for recurrence-free survival. The factors affecting OS included the number of liver procedures (p=0.021), the degree of proliferative activity (p=0.008) and elevated postsurgical carcinoembryonic antigen level (p=0.038). CONCLUSION: The type of surgery had no impact on OS. Markers and hormonal status of liver metastases are important factors affecting prognosis.

Serious Complications of Intraosseous Access during Infant Resuscitation.

We report on a 2.5-month-old infant with ischemia of the left leg and compartment following intraosseous needle application during resuscitation. Unfortunately, this event led to major limb amputation. The cause, mechanism, and prevention of this severe complication are discussed in this article.

Long-term hormonal therapy resulting in breast cancer in female-to-male transsexual: Case report.

RATIONALE: Testosterone is important for the development of secondary sexual characteristics in female-to-male transsexuals. On the contrary, it can increase the risk of breast cancer. PATIENT CONCERNS: We present a rare case of breast cancer in female-to-male transsexual patient after long-term hormonal therapy. DIAGNOSIS: Breast cancer in female-to-male transsexual patient. INTERVENTIONS: The patient underwent mastectomy and chemotherapy. OUTCOMES: The patient had local recurrence of the disease and he underwent re-excision, radiotherapy and the tamoxifen treatment. After this treatment, the patient is in the remission from the disease. LESSONS: Breast cancer in transsexuals appears to be rare. However, there is a potential risk that testosterone exposure can increase the risk of developing breast cancer by the stimulation of breast tissue. There is limited published literature on the risk of breast cancer in transsexual patients.

Portal Vein Embolization (PVE) Versus PVE with Haematopoietic Stem Cell Application in Patients with Primarily Non-resectable Colorectal Liver Metastases.

BACKGROUND: Portal vein embolization (PVE) and PVE with autologous mesenchymal stem cell application (PVE-MSC) increases future liver remnant volume (FLRV). The aim of this study was to compare both methods from the aspect of FLRV growth, progression of colorectal liver metastases (CLM), CLM resectability and long-term results. PATIENTS AND METHODS: Fifty-five patients with CLM and insufficient FLRV were included in the study. FLVR growth and CLM volume were evaluated using computed tomography. Liver resection was performed in patients with FLVR >30% of total liver volume. RESULTS: In the PVE (N=27) group, FLRV growth was observed in 23 patients (85.2%) and in 100% of patients in the PVE-MSC (N=28) group (p<0.05). The rapidity of FLRV and CLM growth did not differ between groups. R0 resection was performed in 14 (51.8%) and 24 (85.7%) patients from the PVE and PVE-MSC (p<0.02) groups, respectively. The 3-year overall and progression-free survival rates were 85.75% and 9.3% in the PVE group and 68.7% and 17.1% in the PVE-MSC group, respectively (p<0.67 and p<0.84, respectively). CONCLUSION: PVE-MSC allows for more effective growth of FLRV and resectability of CLM compared to PVE. The two methods do not differ in their long-term results.

OPG, OPN, EGF and VEGF Levels at Individual Breslow Score Stages in Malignant Melanoma.

BACKGROUND/AIM: Melanoma represents one of the most aggressive forms of cancer. With the rapid increases in the incidence of melanoma in the United States, Australia and Europe over the last decades, melanoma has been considered an epidemic cancer in these areas. The aim of our study was to evaluate the utility of osteoprotegerin (OPG), osteopontin (OPN), epidermal growth factor (EGF) and vascular endothelial growth factor VEGF for the diagnosis and prognosis of melanoma. PATIENTS AND METHODS: Overall, 322 individuals were assessed: 183 melanoma patients and 139 healthy individuals. Melanoma patients were divided into four subgroups according to the Breslow score. OPN, OPG, EGF, and VEGF were determined in each plasma sample. RESULTS: The serum levels of the following biomarkers were statistically significantly higher in the melanoma group compared to the control group: OPG and, OPN (p<0.0001), EGF (p=0.0379). In the first stage, OPG (p=0.0236) and OPN (p=0.0327) showed a statistically significant increase. Concerning positive and negative sentinel node metastases a statistically significant change was observed in: OPN (p<0.0001), EGF (p=0.0114), VEGF (p=0.0114). CONCLUSION: OPG and OPN are promising biomarkers of early-stage melanoma. EGF and VEGF appear to be prognostic biomarkers.

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.

Advances in Experimental Targeted Therapy and Immunotherapy for Patients with Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) represents the most malignant primary brain tumor in adults with generally dismal prognosis, early clinical deterioration and high mortality. GBM is extremely invasive, characterized by intense and aberrant vascularization and high resistance to multimodal treatment. Standard therapy (surgery, radiotherapy and chemotherapy with temozolomide) has very limited effectiveness, with median overall survival of patients no longer than 15 months. Progress in genetics and epigenetics of GBM over the past decade has revealed various aberrations in cellular signaling pathways, the tumor microenvironment, and pathological angiogenesis. A number of targeted anticancer drugs, such as small-molecule kinase inhibitors and monoclonal antibodies, have been evaluated in clinical trials with newly-diagnosed, as well as recurrent GBM. Unfortunately, to date, only a single anti-angiogenic agent, bevacizumab, has been approved for the treatment of recurrent GBM in the USA and Canada. The novel possibilities of cancer immunotherapy, especially immune checkpoint inhibitors, are being evaluated in clinical trials of patients with GBM. The most recent clinical experiences with targeted therapy as well as immunotherapy of GBM are given in this review. The relative lack of success of some of these approaches recently revealed in well-designed randomized clinical trials is also discussed.

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.

Evaluation of IL-2, IL-6, IL-8 and IL-10 in Malignant Melanoma Diagnostics.

AIM: The aim of the present study was to evaluate the usefulness of four interleukins (IL-2, IL-6, IL-8 and IL-10) for melanoma detection and correlate these interleukins with sentinel node metastasis positivity. PATIENTS AND METHODS: A group of 236 persons was assessed: 175 patients with melanomas and 61 healthy persons. Melanoma patients were divided to four groups according to Breslow score. We determined IL-2, IL-6, IL-8 and IL-10 in each plasma sample. Interleukin plasma levels were assayed using a Human Cytokine Milliplex Map kit. Measurements were performed using the Bio-Plex MAGPIX Multiplex Reader. Plasma samples were collected prior to surgery or any other form of treatment. All melanoma diagnoses were histologically verified. RESULTS: We compared interleukin plasma levels in the healthy group and plasma levels in each Breslow score stage. In the first Breslow score stage, IL-2 (p<0.0001), IL-6 (p=0.0004) and IL-10 (p<0.0001) were positive. In the second Breslow score, stage IL-2 (p<0.0001), IL-6 (p<0.0001), IL-8 (p=0.0017) and IL-10 (p<0.0001) were positive. By comparing the group of positive and negative sentinel node metastasis, we observed a statistically significant difference in two interleukins: The median of IL-2 levels in the negative group was 5.88 pg/ml compared to 32.57 pg/ml in the positive group (p=0.0005). The median of IL-6 levels in the negative group was 4.80 pg/ml compared to 32.02 pg/ml in the positive group (p=0.0048). CONCLUSION: Interleukins IL-2, IL-6 and IL-10 are promising biomarkers of early-stage melanoma. IL-2 and IL-6 appear to be prognostic biomarkers.

Portal vein embolisation with application of haematopoietic stem cells in patients with primarily or non-resectable colorectal liver metastases.

BACKGROUND: Insufficient future liver remnant volume (FLRV) is the main cause of low resectability of liver metastases from colorectal cancer (CLMs). One option for enhancing FLVR growth is the use of portal vein embolisation (PVE) with the application of autologous haematopoietic stem cells (HSCs). PATIENTS AND METHODS: PVE with the application of HSCs was used in 11 patients (group 1) with primarily non-resectable CLMs due to insufficient FLRV without signs of extrahepatic metastases. The control group (group 2) consisted of 14 patients in whom only PVE was performed. We evaluated the product quality, FLRV growth, CLM volume, median survival and progression-free survival (PFS). RESULTS: Product quality was achieved in all collections. In all group-I patients, sufficient FLRV growth occurred within three weeks. In the first and second weeks, FLRV increased optimally in most patients (p<0.006). In 13 out of the 14 group-2 patients, optimum FLVR growth was observed within three weeks following PVE (p<0.002). More rapid FLVR growth was observed in group 1 patients (p<0.01). CLM volume was significantly increased in both the group-2 (p<0.0005) and group-1 (p<0.008) patients at the time of liver resection. There was no significant difference in the growth of the CLM volume between the groups (p<0.18). The median survival was 7.3 and 6.8 months for group 1 and 2 patients, respectively, and the two-year PFS was 28% and 22% (p<0.18), respectively. CONCLUSION: PVE with HSC application is a promising method for effectively stimulating FLRV growth in patients with primarily non-resectable CLMs.

Evaluation of IGF1 serum levels in malignant melanoma and healthy subjects.

BACKGROUND/AIM: There were two aims in the present study. The first was to evaluate the usefulness of insulin-like growth factor 1 (IGF1) for melanoma detection. The second was to correlate changes of serum levels of IGF1 with the Breslow score and sentinel node metastasis positivity. PATIENTS AND METHODS: We examined a group of 216 cases, 77 patients with melanomas and 139 healthy probands. We determined the serum IGF1 levels of each patient using an IRMA radioisotope IGF1 assay kit. Serum samples were collected prior to surgery or any other form of treatment. All melanoma diagnoses were histologically verified. RESULTS AND DISCUSSION: Based on the statistical evaluation between the melanoma group and group of healthy individuals, we observed statistically significant differences in IGF1 serum levels. The median IGF1 levels in the melanoma group was 154.1 ng/ml compared to 111.2 ng/ml in the group of healthy individuals (p=0.0036). The changes of the IGF1 levels related to the Breslow score categories were statistically significant (p=0.0027). Lastly, we compared the results between the positive and negative metastatic affection of the sentinel nodes. The median IGF1 levels in the negative group was 173.5 ng/ml compared to 205.8 ng/ml in the positive group. This difference was statistically significant (p=0.0407). CONCLUSION: Serum levels of IGF1 were significantly higher in patients diagnosed with melanoma compared to the healthy control group. The changes of the IGF1 levels related to the Breslow score categories were statistically significant. Serum levels of IGF1 were significantly higher in the group with the positive metastatic affection of the sentinel nodes than in negative patients.

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.

[Deferred breast reconstruction - soul surgery?]. / Odlozené rekonstrukce prsu - chirurgie duse?

BACKGROUND: The loss or mutilation of a breast as a result of surgical treatment of neoplastic disease always represents a negative impact on a woman's psyche and negatively influences the quality of the woman's remaining life. The goal of our work was to implement deferred breast reconstruction into routine practice and the objectification of the influence of reconstruction on bodily integrity, quality of life, and the feeling of satisfaction in women. METHODS AND RESULTS: Women in remission from neoplastic disease after a radical mastectomy were indicated for breast reconstruction. Between January 2002 and December 2011 deferred breast reconstruction was carried out 174 × on 163 women, with an average age of 49.2 and an age range of 29-67 years. The most frequently used reconstruction method was a simple gel augmentation of the breast or a Becker expander/implant - 51 (29.3%) and 37 (21.3%), or in combination with a lateral thoracodorsal flap (31; 17.8% and 47; 27%); reconstruction using a free DIEP flap was carried out 7 × (4%). Complications occurred in 19 operations (10.9%) with a dominance of inflammation and pericapsular fibrosis, in a subjective analysis, satisfaction with the results prevailed, along with an increased quality of life after reconstruction. CONCLUSION: A growing number of deferred breast reconstructions, women's satisfaction with the results, the positive influence of renewed bodily integrity on the feeling of life satisfaction and the quality of life have elevated breast reconstructions to a qualitatively higher level.

Spectrum of cutaneous and soft tissue lesions in two Carney complex patients-adnexal induction versus authentic adnexal neoplasms.

Two unusual Carney complex patients are described. In one of them, several cutaneous biopsies revealed myxoid lesions that were rather more close to authentic adnexal neoplasms with myxoid stroma than to a "myxoma with an epithelial component." These included lesions resembling trichofolliculoma, infundibular cyst, and trichodiscoma. Additionally, 1 soft tissue myxoma was unique in the sense that it greatly resembled a cardiac myxoma, begging the question whether this could represent an embolus from the patient's cardiac myxoma. Given the large size and complexity and heterogeneity of the cutaneous lesions, the authors suggest that these may represent authentic cutaneous neoplasms accompanied by myxoid stroma and not adnexal elements induced by the stroma. However, the latter mechanism is well recognized and demonstrated by our second patient in whom adnexal-type elements in the cutaneous lesion were clearly induced by the myxoid stroma but were unusually complex by manifesting panfollicular and also sebaceous differentiation.

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.