Surgical solution of the extensive post-radiation defect developped 33 years after radiotherapy for breast carcinoma case report.

INTRODUCTION: Damage of the skin and its underlying structures is a common side effect of radiotherapy. These conditions limit further treatment and dealing with these complications is a routine practice of clinical oncologist. The majority of the complications are immediate, with a perspective of healing ad integrum within a few weeks. Less frequently, but sometimes with severe manifestations, chronic toxicity occurs belatedly after months, or even many years after irradiation, in form of post-radiation ulcer, for instance with potential of secondary malignant transformation. Regarding surgery, it might be one of the most challenging chronic wounds to treat. In extreme cases, extensive resection of the entire affected area is needed, inevitably ending with demanding reconstruction of the resulting defect. CASE REPORT: This case report presents a female patient with rapidly progressive post-radiation chest wall defect 33 years after the irradiation, when relatively insignificant skin injury occured. Prior to this sudden deterioration, only long-term, non-progressive changes, without a cutaneous defect, were described during the dispensarisation. After a protracted outpatient treatment with unsatisfactory results, when the patient repeatedly refused mastectomy, the condition inevitably led to the complex surgical procedure with necessary cooperation of breast, plastic and thoracic surgeons. CONCLUSION: Although changes of the similar severity rarely occur even after many years following the treatment, we havent found such a dramatic change of the patients condition three decades after the therapy with urgency of this type of complex,  surgical intervention in current literature.

The Anti-apoptotic Mechanism of Metformin Against Apoptosis Induced by Ionizing Radiation in Human Peripheral Blood Mononuclear Cells.

BACKGROUND: In a previous article, we showed that metformin (MET) can reduce ionizing radiation (IR) induced apoptosis in human peripheral blood mononuclear cells. However, the anti-apoptotic mechanism of MET against IR remains unclear. The present study attempts to investigate the mechanism of action of MET in limiting X-ray induced apoptosis in human peripheral blood mononuclear cells. MATERIAL AND METHODS: Mononuclear cells were treated with MET for 2 hours and irradiated with 6 MV X-rays. The gene expression levels of BAX, CASP3 and BCL2 were determined 24 hours post irradiation using real time quantitative polymerase chain reaction (qPCR) technique. Furthermore, the protein levels of BAX, CASP3 and BCL2 were analyzed by Western blotting assay. RESULTS: Radiation exposure increased the expressions of BAX and CASP3 genes, and decreased the expression of BCL2 gene in mononuclear cells. Conversely, an increase in BCL2 gene expression along with a decrease in BAX and CASP3 genes expression was observed in MET plus irradiated mononuclear cells. It was found that radiation increased BAX/BCL2 ratio, while MET pretreatment reduced these ratios. Also, treatment with MET without irradiation did not change the expressions of BAX, CASP3 and BCL2 genes. On the other hand, downregulated expression of BCL2 protein and upregulated expressions of BAX and CASP3 proteins were found in 2 Gy irradiated mononuclear cells, while pretreatment with MET significantly reversed this tendency. CONCLUSION: These results suggest that MET can protect mononuclear cells against apoptosis induced by IR through induction of cellular anti-apoptotic signaling.Key words: ionizing radiation - metformin - apoptosis - genes - proteins - blood cells.

[Lymphoedema Following Regional Lymph Node Surgery for Breast Cancer]. / Lymfedém po operacích na spádových lymfatických uzlinách pro karcinom prsu.

BACKGROUND: The treatment of breast cancer is based on the multimodal principle and surgery of regional lymph nodes is an inseparable part of this. Indication criteria are changing constantly folowing advances in other modalities. It is necessary to consider not only the diagnostic or therapeutic benefit but also to take into account adverse effects. Previous studies have demonstrated that axillary dissection (ALND) is burdened by a high frequency of chronic lymphoedema of the arm or chest wall; however, a considerable percentage of patients may also suffer from lymphoedema after sentinel lymph node biopsy (SLNB). AIM: This paper focuses on the pathophysiology of lymphoedema, its potential predictive factors, and its complications. Furthermore, it presents an overview of published studies comparing the incidences of lymphoedema after current axillary surgery for breast cancer together with current trends designed to radically reduce the number of these operations. It also briefly refers to the possibilities of implementing preventive or therapeutic operations for lymphoedema. CONCLUSIONS: Both ALND and SLNB are burdened by a clinically significant risk of lymphoedema. This risk is more serious after ALND. In the medium term, approximately 7-59% of operated patients suffer from lymphoedema. The incidence of lymphoedema after SLNB, considered a very gentle method, is also not negligible (0-14%). As the number of patients surviving breast cancer treatment continues to increase, monitoring the undesirable effects of axillary surgery over the long term will become more important. The results of published studies support research into treatment methods that have the potential to reduce the radicality of axillary surgery while preserving or improving total medical effectiveness.Key words: breast neoplasms - sentinel lymph node biopsy - axillary dissection - adverse effects - breast cancer lymphedemaThis work was supported by the grants MEYS - NPS I - LO1413 and MH CZ - DRO (MMCI, 00209- 805).The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 7. 11. 2016Accepted: 5. 12. 2016.

[SentiMag--the magnetic detection system of sentinel lymph nodes in breast cancer]. / Magnetická detekce sentinelových uzlin u karcinomu prsu metodou SentiMag.

INTRODUCTION: The aim of this study was to assess the feasibility of the new detection system of sentinel lymph nodes in breast cancer (SentiMag) and to compare its use to the standard method of detection with a radioisotope and a gamma-probe. METHODS: Twenty breast cancer patients scheduled for sentinel lymph node biopsy underwent standard lymphatic mapping with a radioisotope and also with the Sienna+ tracer. During the surgery, sentinel lymph nodes were identified preferably with the SentiMag system. The gamma-probe was used only at the end of the surgery to verify whether all sentinel lymph nodes had been harvested. RESULTS: The sentinel lymph node was detected in all cases. Both methods agreed in 18 cases, i.e. the lymph node with the highest magnetic value ex vivo was the same node as the one with the highest radioactivity. A metastasis in the sentinel lymph node was found in three patients. It is very likely that with the sole use of the SentiMag system, the results would have been identical to those of using the standard method with a radioisotope and the gamma-probe. CONCLUSION: The new magnetic detection method of sentinel lymph nodes (SentiMag) is feasible and clinically comparable to the gold standard method of detection with a radioisotope and the gamma-probe in patients with breast cancer. The new method could find its use not only in hospitals where the department of nuclear medicine is not available but in all hospitals performing sentinel lymph node biopsies in breast cancer and possibly other types of cancer.

[Association of microsatellite loci alleles of the group-5 chromosomes with frost resistance of winter wheat].

Analysis of frost resistance and microsatellite analysis of the group-5 chromosomes were performed on parental varieties and recombinant-inbred lines F7 Luzanovka odesskaya/Odesskaya krasnokolosaya. Allelic differences for Xcfd7-5B Xwmc415-5B and Xgwm 182-5D microsatellite loci were associated with the level of frost resistance of the lines.

[QTL marking of duration of the period up to winter wheat heading].

Duration of the period up to heading of 107 winter wheat cultivars of different origin has been studied. The most contrast for analyzed character cultivars, as well as F2 Omskaya ozimaya/Numbu Komugi individual plants were investigated with SSR-PCR methods to reveal DNA-markers for QTL of heading temps. Two loci Xgwm512 and Xgwm429 have been revealed to explain 19.3% (part of influence of the first locus--8.9%, of the second 10.4%) differences induration of the period up to heading of the F2 individuals in field conditions.

[Gastrointestinal metastases of malignant melanoma]. / Gastrointestinální metastázy maligního melanomu.

INTRODUCTION: Malignant melanomas are aggressive malignant tumors with major potential for the development of distant metastases. The authors present five case reviews of melanoma intestinal metastases, which were managed surgically. BASE REVIEW 1: A male, 65 y.o.a, underwent planned resection of the small intestine infiltrated with metastases 19 months after he was diagnosed with skin melanoma. During his follow up period, he died of complications of cerebral metastases of the tumor. BASE REVIEW 2: A female, 34 y.o.a, 5 months after the first occurrence of signs of the disease, which included neurological symptoms resulting from a brain metastasis. She was urgently operated for ileus, caused by a jejunal metastis of the tumor. The patient died following dissemination of the primary tumor 2 months after her abdominal procedure. BASE REVIEW 3: A female, 30 y.o.a. 52 months after removal of her skin melanoma, she was urgenty operated for ileus, caused by a jejunal metastasis of the tumor. She had no postoperative complications. BASE REVIEW 4: A female, 68 y.o.a, 26 months after being diagnosed with skin melanoma, underwent planned abdominal revision for multiple intestinal metastases. She died of massive pulmonary embolization on the postoperative Day 6. BASE REVIEW 5: A male, 76 y.o.a, underwent resection of a sigmoid metastasis 72 months after his skin melanoma excision. Further course of the disease shows no signs of the primary disease recurrence, the patient is surviving 153 months after the primary diagnosis establishment, 59 months after the distant large intestinal metastasis resection. DISCUSSION: The authors present literature overview, assessing contribution of surgery in the management of malignant melanomas with GIT metastases. The literature data show that complete resections of all GIT metastatic melanoma foci result in the mean survival time prolongation in selected patients.

[Accuracy of preoperative establishment of invasive breast carcinoma size using ultrasound and mammography]. / Presnost predoperacního stanovení velikosti invazivního mamárního karcinomu ultrasonografií a mamografií.

INTRODUCTION: Accurate preoperative assessment of breast cancer size is important for choosing appropriate surgical treatment. Mammography and ultrasonography are the most widely used breast imaging techniques. The aim of this study was to compare the tumour size measured by these two modalities with the pathological size of native specimen. METHODS AND SUBJECTS: From 2001 to 2007, a retrospective review was conducted of 299 patients operated on at Masaryk Memorial Cancer Institute for the diagnosis of invasive breast carcinoma detected on ultrasonography or mammography as a nucleus shadow lesion where the preoperative size was estimated. Pearson's correlation to pathological size was tested and the mean deviation was analysed in the whole group of patients as well as in subgroups defined by pathological size (pT), histogical type and grading. RESULTS: Ultrasonography was accurate in determination of the tumour size (i.e. within the deviation of 5mm) in 195 patients (74%), it underestimated in 45 cases (17%) and overestimated in 24 cases (9%). Pearson's correlation coefficient (r) was 0.610 and mean deviation minus 0.115 cm. Mammography estimated accurate results in 162 patients (81%), the size was underestimated in 14 cases (7%) and overestimated in 25 (12%). Pearson's correlation coefficient (r) was 0,645 and mean deviation 0.08 cm. Generally lower accuracy in assessing the size was noted in lobular carcinomas. CONCLUSIONS: Despite some limitations of our study, we can resume that in most cases (approximately 75%) the size assessment of invasive tumour lesion by both ultrasound and mammography is relatively reliable within the deviation of 5mm from the pathological size. But there's still been some portion of cases remaining where the estimation is not accurate, therefore we are not completely able to avoid redundant removal of tissue or, on contrary, demand of consecutive operations due to positive resection margins.

[Male breast cancer--our experience]. / Karcminom prsu u muzu--nase zkusenosti.

INTRODUCTION AND AIM: Male breast cancer (MBC) is a rare disease which represents only about 0.2% of all cancers. The ratio of female to male breast cancer is approximately 100:1. In this study, we review our experience with diagnosis, surgical treatment, and overall management of patients with MBC. METHODS: Overall, 5384 breast cancer patients underwent surgery in Masaryk Memorial Cancer Institute, Brno, Czech Republic during the period of 2001 to 2009. Among these, seventeen were men. In these patients, data on incidence, clinical symptoms, diagnostic procedures, types of surgical resection, histopathology, adjuvant systematic therapy, genetic investigation and therapeutic results were retrospectively reviewed from their medical records. RESULTS: None of the patients have distant metastases at the time of surgery. In sixteen cases an invasive cancer was histopathologically diagnosed, one patient had ductal carcinoma in situ (DCIS). Eight patients exhibited locally advanced stage of the disease (IIIB). All patients were primarily treated surgically; in no case neoadjuvant therapy was recommended. From the five patients operated primarily elsewhere, four underwent completion of modified radical mastectomy (RAME) at our institution and one patient underwent subcutaneous (nipple-sparing) mastectomy without the surgery on lymph nodes. Twelve patients were primarily diagnosed and operated at our institution. Ten of these were scheduled for RAME, one patient was recommended total mastectomy with sentinel lymph node biopsy, and one patient underwent total mastectomy without surgery on regional lymph nodes. Adjuvant therapy overall comprised radiotherapy, chemotherapy, hormonal therapy, and biological therapy. Investigation of BRCA genes was suggested in nine patients, but the results of only four of them are available to date. Two patients exhibited a mutation in BRCA genes. One mutation is explicitly pathogenic; another case represents variation with unknown clinical effect. Twelve patients of the cohort are in complete remission, two are alive with distant metastases and three died (two on cancer, one on cardiovascular disease). CONCLUSION: Our study should point out a rare form of mammary tumors--male breast cancer. There are some particular differences between male and female breast cancer though the overall clinical management of both is generally similar. There is a necessity of appropriate health education to prevent late diagnosis of breast cancer in men. Genetic testing should be recommended to every male patient with this disease.

[Identification and characteristics of the 1R (1B) bread wheat substitution strains].

The 1R (1B) chromosome substitution has been identified at two introgression bread wheat stocks derived from the cross between an octoploid triticale and durum wheat. The substitution is marked by original alleles of the secaline coding loci Sec1 and Sec2. At rather low level of chromosome pairing, high winter-hardiness and frost resistance, and yield productivity both in favorable and in unfavorable years the stocks are differentiated for these traits.

Interferon-alpha treatment may negatively influence disease progression in melanoma patients by hyperactivation of STAT3 protein.

Interferon-alpha (IFN-alpha) is an important drug used in anti-melanoma therapy. However, metastases eventually reappear in almost 60% of melanoma patients, who have received adjuvant cytokine therapy suggesting that IFN-alpha can paradoxically promote disease progression in some cases, at least. In this study, we have investigated the possibility that a growth-promoting STAT3 protein might be activated by interferon-alpha in melanoma cells. We examined 24 primary cultures established from node metastases of melanoma patients who were monitored in a 5-year clinical follow-up. The patients differed in the course of disease and survival end-points. Using Western blot analyses, we show that interferon-alpha stimulated STAT3 phosphorylation at tyrosine (Y705) residue in 17% of cases. These over-reactive cell populations originated from patients who had the shortest disease-free intervals. A significant correlation was obtained between the length of survival end-points and a lack of STAT3 activation by IFN-alpha. No STAT3 induction was observed in normal melanocytes. The STAT1 activation at tyrosine (Y701) occurred at a similar frequency as that of STAT3 (17%) albeit in different patients, no clear correlation with the clinical status could be made. The interferon-alpha/beta receptors (IRFARs) were expressed irrespective to the signal transducers and activators of transcription (STATs) inducibility suggesting that signalling defects occur downstream from IRFAR. We propose that in some cases the application of IFN-alpha could increase the probability of disease progression via overactive STAT3. The tests for STAT3 inducibility prior to cytokine immunotherapy in the clinic are therefore warranted.

[Visibility in ultrasonography as the strongest invasion predictor in ductal carcinoma in situ in a retrospective study]. / Viditelnost na ultrasonografii jako nejsilnejsí prediktor invazivity u duktálních karcinomu in situ v retrospektivní studii.

BACKGROUND: Detection of ductal carcinoma in situ (DCIS) of the breast has markedly increased since the introduction of screening mammography. Current management of this preinvasive lesion comprises complete margin-free resection of the tumour. Lymph node staging is still not indicated as a standard procedure but we can find published cases of pure DCIS with lymph node involvement as well as a high proportion of invasive carcinomas in the final histopathology. The aim of this study was to determine the proportion of invasive tumours in our group of patients operated on for DCIS, to analyse the predictive factors of invasion and to assess the frequency of lymph node metastases. DESIGN AND SUBJECTS: From 2006 to 2008, a retrospective review was conducted of 179 patients operated on at Masaryk Memorial Cancer Institute for the initial diagnosis of DCIS carried out by core-needle biopsy; in 117 of them, regional lymph node staging was performed. METHODS AND RESULTS: In the final histopathological results, an invasive lesion was found in 34% of cases. The expected predictive factors of invasion were statistically analysed by Fisher's exact and Chi-square test. Preoperative ultrasound-guided core-needle biopsy (p = 0.014) related to ultrasound detection of the lesion (p = 0.023) was shown to be the statistically most significant predictive factor. Mammographic character (p = 0.105) or size (p = 0.077), histopathological grade (p = 0.104), multifocality (p = 0.544) and age (p = 0.212) did not show any statistical significance. Lymph node metastases were detected in fewer than 10% of cases of invasive carcinoma. There was no detection of lymph node involvement in pure DCIS. CONCLUSIONS: We recommend performing primary sentinel node biopsy in DCIS unambiguously detected by ultrasound and in patients treated by total mastectomy where, in the case of invasive carcinoma, subsequent identification of the sentinel node would be difficult.

[Sentinel node biopsy and possibilities of use in current surgical oncology]. / Sentinelová biopsie a moznosti vyuzití v soucasné onkochirurgii.

Sentinel node biopsy originally developed for melanoma has gradually extended into further fields of surgical oncology. It became a standard procedure in melanoma and breast cancer, it appears to be a very helpful method in colorectal cancer. The possibilities of use are tested throughout all of surgical oncology in gastrointestinal, urological and gynecological tumors. It's importance can be displayed even in head and neck tumor, intrathoracical tumors and in thyroid cancer.

[Therapeutic approaches for breast carcinoma]. / Lécebné postupy u karcinomu prsu.

With increasing incidence of breast cancer its prevalence also increases. Improvement of therapeutic approaches recently introduced led to improved treatment outcomes. The introduction of taxanes into the adjuvant treatment prolongs the overall survival (OS) of the patients. Third generation of aromatase inhibitors appear better than tamoxifen in the adjuvant treatment of postmenopausal women. New anticancer drugs in combination with bevacizumab and trastuzumab have brought new possibilities in treatment of patients with metastatic breast cancer: their use apparently increases the rate of treatment response and overall survival.

Defective IFNα/γ-induced STAT3 protein activation in human malignant melanoma cells.

Signal transducer and activator of transcription 3 (STAT3) protein has been documented as a significant mediator of interferon (IFN) signaling. Physiological STAT3 phosphorylation involves tyrosine (Y705) and serine (S727) activation. Impairment of STAT3 protein levels and/or of STAT3 phosphorylation after IFN treatment has been found in many pathological conditions such as cancer, immunopathy and inflammatory disease. To analyze tumor-associated defective STAT3 response to IFNs, the induction of S727 and Y705 STAT3 activation after IFN exposure was evaluated in 18 human malignant melanoma cell lines and 68 primary cell cultures established from the lymph node metastases of melanoma patients. STAT3 expression and STAT3 phosphorylated forms were assayed by Western blot analysis employing specific STAT3 antibodies. All melanoma cell lines as well as samples derived from metastatic melanoma patients expressed STAT3 with variable signal intensities depending on the appropriate cell type. Significantly altered IFNγ-induced S727 STAT3 activation was found in both experimental models, with on average 94.1% of patients detected to be non-responders in lymph node cell cultures and 83.3% in melanoma cell lines. Moreover, a deficiency in IFNα-induced S727 induction was detected in 88.9% of melanoma cell lines. Defects in Y705 STAT3 phosphorylation were determined in clinical material (61.8% after IFNγ exposure) as well as in melanoma cell lines (absence of response to IFNα/γ in 83.3 and 55.5%, respectively). Our data clearly confirm STAT3 pathophysiological perturbances in human malignant melanoma cells. Depending on the induction of STAT3-activated phosphoforms by IFNs, three categories of melanoma cells were identified: a) phosphorylation on both the S727 and Y705 amino acid residues; b) STAT3 activation on Y705 only; c) phosphorylation at neither S727 nor Y705. The significance of in vitro STAT3 activation for predicting patient response to immunotherapy will be examined in a prospective clinical study by our group.