The importance of sentinel lymph node biopsy following neoadjuvant chemotherapy in patients with breast cancer: prospective multicentre trial.

INTRODUCTION: The role of sentinel lymph node biopsy (SLNB) in patients with breast cancer after neoadjuvant chemotherapy (NAC) is currently under discussion. The aim of our study was to determine the false negativity rate (FNR) of SLNB, the accuracy of ultrasound examination in the evaluation of the status of lymph nodes and the accuracy of perioperative cryobiopsy of the sentinel lymph node (SLN). METHODS: Prospective multicentre study, which took place in years 20182020 at three centres in the Czech Republic. A total of 59 patients were evaluated. RESULTS: The FNR of SLNB in the group of patients with cN1 before NAC and ycN0 after NAC was 12.5%. The FNR of perioperative histological examination of the SLN was 38.5%. The FNR of ultrasound examination of axillary lymph nodes in patients after NAC was 35.5%, and the false positivity rate was 16.7%. The incidence of inflammatory complications in our cohort was 3.3%. CONCLUSION: The FNR of SLNB in the group of patients with cN1 before NAC and ycN0 after NAC exceeds the tolerable limit of 10%. The FNR of perioperative histological examination of the SLN is high; definitive histological examination of the SLN may change the original diagnostic-therapeutic plan. Ultrasound examination of the axillary lymph nodes in patients after NAC is a method with high false negativity and positivity and may not correspond with the perioperative finding. The incidence of inflammatory complications in our cohort in patients after NAC is comparable to literature data on the frequency of complications in patients without NAC.

Granulomatous mastitis treatment options and our experience.

Granulomatous mastitis (GM) is a rare benign inflammatory disease of the breast, first described by Kessler and Wolloch in 1972. Clinically, it can present as unilateral, sometimes painful, increasing breast resistance, or as a hard, irregular mass. Sonography is the most useful diagnostic method for GM evaluation. The only method for definitive diagnosis is the use of biopsy. In histological findings, GM is characterized by non-caseifying granulomas, often associated with microabscess and fistula formation. There is considerable heterogeneity in treatment options; this may explain the high recurrence rate which is close to 50%. Such a high recurrence rate is alarming and proves that current treatments are suboptimal. Two treatment options are discussed worldwide: conservative strategies involving drug therapy with corticosteroids versus a surgical approach involving partial or total mastectomy. All conservative treatment options are associated with a high risk of recurrence, and most patients require surgery in the end. Thorough excision of inflammatory tissue is crucial for successful treatment while negative surgical margins are associated with a low recurrence rate. The surgical approach to GM requires sufficient radicality and presumes knowledge in the field of reconstructive breast surgery, similarly to oncosurgical breast conservation operations. However, alternatives to GM treatment with oral steroids may be acceptable for patients concerned about surgery. This article presents six case reports of patients treated at our department.

Sebaceous carcinoma of the breast area a case report.

INTRODUCTION: Sebaceous carcinoma is a rare malignant tumor of the sebaceous glands. Sebaceous carcinoma occurs mainly in the head and neck region, rarely in trunk.  Case report: We present a case report of 63-year-old patient, operated on for sebaceous carcinoma in the right breast area. The patient underwent radical surgery, removal of the tumor with the skin, subcutaneous tissue, and the large pectoral muscle. The patient is in good clinical condition eight months after the surgery. She is being constantly monitored and so far, there are neither signs of local recurrence nor tumor progression.  Conclusion: Patients with rare tumors should be treated comprehensively with subsequent lifelong dispensarisation in specialized centers. Multidisciplinary medical teams are able to eruditely diagnose, recognize, treat and dispense patients.

[Breast angiosarcoma induced by radiotherapy - surgical treatment options and review of literature]. / Radiací indukovaný (postiradiacní) angiosarkom prsu - moznosti chirurgické lécby a prehled literatury.

INTRODUCTION: Radiation-induced angiosarcoma is a rare but very aggressive tumour. The highest risk of sarcoma development is in patients after breast-conserving surgery.Case 1: The 66 years old patient underwent radical mastectomy with axillary dissection because of ductal carcinoma with consequent radiotherapy, chemotherapy and hormonal therapy. After 6 years, high-grade angiosarcoma was diagnosed and resected with negative resection margins. Within subsequent 24 months, additional three radical re-excisions were performed because of repeated sarcoma recurrence. 29 months from the diagnosis of the first sarcoma, another radical re-excision was performed, this time with positive resection margins and with consequent disease progression. The patient died three years after the first angiosarcoma diagnosis.Case 2: The 68 years old patient underwent breast-conserving surgery with axillary dissection because of ductal carcinoma and radiotherapy. Breast colour changes were observed 6 years later; radical mastectomy was performed after additional 16 months due to locally advanced angiosarcoma. Given positive resection margin, radical re-excision with musculocutaneous musculus latissimus dorsi flap was done. 24 months later, a small sarcoma recurrence was detected near the upper resection margin, which was managed by radical re-excision. 52 months after radical operation, a metastasis was diagnosed by means of PET/CT in the contralateral axilla. Radical axillary dissection was performed (two metastases were found in axillary lymph nodes). According to follow-up, the patient has been free of any recurrence for 66 months from the radical surgery. CONCLUSION: Recommendations regarding the management of radiotherapy induced breast angiosarcoma are very vague due to limited evidence. Radical surgical excision with negative resection margins (potentially with complementary flap reconstruction) presents the fundamental approach to breast angiosarcoma.Key words: radiation-induced angiosarcoma - breast cancer - surgery.

Beyond thermoregulation: metabolic function of cetacean blubber in migrating bowhead and beluga whales.

The processes of lipid deposition and utilization, via the gene leptin (Lep), are poorly understood in taxa with varying degrees of adipose storage. This study examines how these systems may have adapted in marine aquatic environments inhabited by cetaceans. Bowhead (Balaena mysticetus) and beluga whales (Delphinapterus leucas) are ideal study animals-they possess large subcutaneous adipose stores (blubber) and undergo bi-annual migrations concurrent with variations in food availability. To answer long-standing questions regarding how (or if) energy and lipid utilization adapted to aquatic stressors, we quantified variations in gene transcripts critical to lipid metabolism related to season, age, and blubber depth. We predicted leptin tertiary structure conservation and assessed inter-specific variations in Lep transcript numbers between bowheads and other mammals. Our study is the first to identify seasonal and age-related variations in Lep and lipolysis in these cetaceans. While Lep transcripts and protein oscillate with season in adult bowheads reminiscent of hibernating mammals, transcript levels reach up to 10 times higher in bowheads than any other mammal. Data from immature bowheads are consistent with the hypothesis that short baleen inhibits efficient feeding. Lipolysis transcripts also indicate young Fall bowheads and those sampled during Spring months limit energy utilization. These novel data from rarely examined species expand the existing knowledge and offer unique insight into how the regulation of Lep and lipolysis has adapted to permit seasonal deposition and maintain vital blubber stores.

Chromosome Y genetic variants: impact in animal models and on human disease.

Chromosome Y (chrY) variation has been associated with many complex diseases ranging from cancer to cardiovascular disorders. Functional roles of chrY genes outside of testes are suggested by the fact that they are broadly expressed in many other tissues and correspond to regulators of basic cellular functions (such as transcription, translation, and protein stability). However, the unique genetic properties of chrY (including the lack of meiotic crossover and the presence of numerous highly repetitive sequences) have made the identification of causal variants very difficult. Despite the prior lack of reliable sequences and/or data on genetic polymorphisms, earlier studies with animal chrY consomic strains have made it possible to narrow down the phenotypic contributions of chrY. Some of the evidence so far indicates that chrY gene variants associate with regulatory changes in the expression of other autosomal genes, in part via epigenetic effects. In humans, a limited number of studies have shown associations between chrY haplotypes and disease traits. However, recent sequencing efforts have made it possible to greatly increase the identification of genetic variants on chrY, which promises that future association of chrY with disease traits will be further refined. Continuing studies (both in humans and in animal models) will be critical to help explain the many sex-biased disease states in human that are contributed to not only by the classical sex steroid hormones, but also by chrY genetics.

[Anatomic-surgical study of intercostobrachial nerve (ICBN) course in axilla during I. and II. level of axilla clearance in breast cancer and malignant melanoma]. / Anatomicko-chirurgická studie prubehu interkostobrachiálních nervu (ICBN) v axile pri exenteraci I. a II. etáze axily u karcinomu prsu a maligního melanomu.

INTRODUCTION: The aim of this paper is to offer results of anatomic study of axillary course of intercostobrachial nerve (ICBN) and the effort of its saving in primary axilla clearance (PE), secondary clearance (SE) after previous positive sentinel nodes detection (SLN) and in re-clearance (RE) after previous axilla clearance in breast cancer and malignant melanoma. The correlation between possibility of ICBN saving and anatomic variant of ICBN and type of previous surgery was observed. MATERIAL AND METHODS: A total of 113 surgeries with the effort of description and preservation of ICBN were done between September 2007 and August 2011. Patients were divided into three groups according to type of surgery: primary clearance (PE), secondary clearance (SE) and re-clearance (RE). Results have been statistically tested using licensed statistical software Statgraphics. RESULTS: ICBN was found in 107 patients (94.7%), it wasnt found in six cases. There were eight different types of ICBN branching. Two most frequent variants formed majority of cases - 87 out of 107 (81.3%). The successful preservation of intact ICBN was in 86 patients (76.1%). ICBN was interrupted or not found in 10 patients (8.8%), partial injury of ICBN branches was detected in 17 cases (15.0%). If the most frequent variant of ICBN branching was present, the nerve was not injured in 42 out of 45 cases (93.3%). Statistical testing showed that non-standard anatomical branches are associated with higher risk of perioperative injury. The risk of injury was lowest in PE (21.6%) and the highest in RE (42.9%). The difference wasnt statistically significant because of low number of re-clearance cases in our study. CONCLUSION: The anatomy of ICBN in axilla is variable. The standard variant of ICBN course is the most frequent (the trunk coming out of second intercostal space; no branches in axillary course). If other variants are present, there is significantly higher risk of perioperative injury. ICBN preservation is possible also after previous axilla clearance. Preparation is more difficult and the risk of injury is increasing with the degree of previous surgery radicality.

Leptin and leptin receptor: analysis of a structure to function relationship in interaction and evolution from humans to fish.

Leptin is a circulating protein which regulates dietary intake through binding the leptin receptor. Numerous labs have used known structures and mutagenesis to study this binding process in common animal models (human, mouse and rat). Understanding this binding process in other vertebrate species will allow for a better understanding of leptin and leptin receptor function. The binding site between leptin and leptin receptor is highly conserved in mammals as confirmed through sequence alignments mapped onto structures of both leptin and leptin receptor. More variation in this interaction is found in lizard and frog sequences. Using our models, we show that the avian leptin sequences have far less variation in the binding site than does the leptin receptor. This analysis further suggests that avian leptins are artifactual. In fish, gene duplication events have led to the expression of multiple leptin proteins. These multiple leptin proteins have variation in the regions interacting with leptin receptor. In zebrafish and the Japanese rice fish, we propose that leptin A has a higher binding energy than does B. Differing binding energies are evidence of either divergent functions, different binding confirmations, or other protein partners of leptin B.

[Predictive factors for non-sentinel lymph nodes affection in breast carcinoma--outcomes of a Czech multicenter study of sentinel lymph nodes]. / Prediktivní faktory postizení nonsentinelových uzlin u karcinomu prsu--závery ceské multicentrické studie sentinelových uzlin.

BACKGROUND: The aim of the study was to assess positivity nonsentinel lymph nodes in patients with macro, micro and submicrometastases in sentinel lymph nodes and find predictive factors of positivity nonsentinel lymph nodes. Study was conducted at the Department of Surgery in Pardubice, Pilsen, Ostrava and Zlín. MATERIAL AND METHODS: Sentinel lymph nodes were assessed based on standards of Czech Pathological Society. Detection of sentinel lymph nodes was performed based on radionavigation or combination of radionavigation and blue dye method. RESULTS: In group N1 (macrometastases) there was found positivity of nonsentinel lymph nodes in 50% (45 from 90 patients). In group N1 Mi (micrometastases) there was found positivity of nonsentinel lymph nodes in 26.7% (16 from 60 patients). In group NO I+ (sub-micrometastases) there was found positivity of nonsentinel lymph nodes in 6.7% (1 from 15 patients). Predictive factors were size of metastasis, number of positive sentinel lymph nodes and grading. Size of tumor was not found to be a predictive factor of positivity nonsentinel lymph nodes. DISCUSSION: High positivity of nonsentinel lymph nodes in pacients with macro and micrometastases in sentinel lymph nodes advocates to perform axillary lymph nodes dissection. Due to small number of patients with submicrometastases it is not possible to assess if axillary dissection is necessary or not. Predictive factors of positivity of nonsentinel lymph nodes are size of metastasis in sentinel lymph nodes, number of positive sentinel lymph nodes and grading. Size of tumor was not found to be a predictive factor due to small tumors in the study. In spite of this it is necessary to consider it like a predictive factor of positivity nonsentinel lymph nodes. CONCLUSION: In patients with macro and micrometastases it is necessary to perform axillary dissection. In patients with submicrometastases in sentinel lymph nodes it is necessary to consider predictive factors.

Elementary excitations at magnetic surfaces and their spin dependence.

The elementary surface excitations are studied by spin-polarized electron energy loss spectroscopy on a prototype oxide surface [an oxygen passivated Fe(001)-p(1×1) surface], where the various excitations coexist. For the first time, the surface phonons and magnons are measured simultaneously and are distinguished based on their different spin nature. The dispersion relation of all excitations is probed over the entire Brillouin zone. The different phonon modes observed in our experiment are described by means of ab initio calculations.

Asymmetric spin-wave dispersion on Fe(110): direct evidence of the Dzyaloshinskii-Moriya interaction.

The influence of the Dzyaloshinskii-Moriya interaction on the spin-wave dispersion in an Fe double layer grown on W(110) is measured for the first time. It is demonstrated that the Dzyaloshinskii-Moriya interaction breaks the degeneracy of spin waves and leads to an asymmetric spin-wave dispersion relation. An extended Heisenberg spin Hamiltonian is employed to obtain the longitudinal component of the Dzyaloshinskii-Moriya vectors from the experimentally measured energy asymmetry.

Silent pulmonary embolism in a patient with acute myocardial infarction and type B acute aortic dissection - a case report.

A 69-year-old man while being treated for type B aortic dissection was also found to have acute myocardial infarction. The patient initially was treated conservatively. Prophylactic anticoagulant treatment of potential thrombosis was not given because of aortic dissection. Stent-graft implantation to the thoracic aorta was considered at the time. Unexpectedly, elective computer tomography (CT), revealed 2 large thrombi at the bifurcation of the pulmonary trunk. The patient did not show any symptoms of pulmonary embolism. Heparin therapy was initiated immediately. The patient responded well to the therapy and on transesophageal echocardiography and subsequent CT no embolic material was found. Since that time, the patient is receiving oral anticoagulation. The case we present raises the question of anticoagulation prophylaxis in the presence of aortic dissection in bedridden patients. Failure to use such therapy in our patient could have resulted in an unfavorable clinical outcome.

Magnons in a ferromagnetic monolayer.

We report the first observation of high wave vector magnon excitations in a ferromagnetic monolayer. Using spin-polarized electron energy loss spectroscopy, we observed the magnon dispersion in one atomic layer (ML) of Fe on W(110) at 120 K. The magnon energies are small in comparison to the bulk and surface Fe(110) excitations. We find an exchange parameter and magnetic anisotropy similar to that from static measurements. Our results are in sharp contrast to theoretical calculations, indicating that the present understanding of magnetism of the ML Fe requires considerable revision.

Large wave vector spin waves and dispersion in two monolayer fe on w(110).

We present the first surface spin-wave (SW) dispersion measurements up to the surface Brillouin zone boundary of a two monolayer Fe film on W(110) by using spin-polarized electron energy loss spectroscopy. Pronounced features of SW peaks are observed in the spectra at room temperature. We found that the SW energies in the Fe film are strongly reduced compared to spin waves in bulk Fe and to theoretical predictions. Our results suggest that this reduction is caused by the reduction of exchange interaction within the 2 ML Fe on W(110) as compared to bulk Fe.

PML protein expression in hereditary and sporadic breast cancer.

The PML protein is concentrated in the PML nuclear bodies. Downregulation of the PML protein has been described in various types of cancer and is in accordance with the fact that dysqualification of tumor suppressive functions of the PML protein might promote cancer development. Various differences have been described between sporadic breast cancer and that associated with BRCA1 and BRCA2 gene mutations. Expression of the PML protein has not been studied yet. The aim of this study was to determine if there is any difference in PML protein expression in breast cancer of BRCA1 and BRCA2 gene mutation carriers compared to sporadic breast cancer and if the PML protein can be used as a prognostic marker. There were 47 breast cancer samples included, 14 and 10 from BRCA1 and BRCA2 germline mutation carriers, respectively, and 23 from patients without a BRCA1/BRCA2 germline mutation. Immunofluorescence staining was used. Downregulation of PML protein expression was found in 2 of 14 (14%), 3 of 10 (30%) and 15 of 47 (31%) cases of breast cancer samples from BRCA1, BRCA2 and no BRCA1/BRCA2 mutation carriers, respectively (p(BRCA1) = 0.019; p(BRCA2) = 0.111). There was no correlation between PML protein expression and age, histological types, estrogen and progesterone receptor, c-erbB-2 and PCNA expression, TNM classification, disease-free and overall survival. In conclusion, the PML protein is downregulated in approximately 30% of breast cancers cases. Downregulation of PML protein expression was significantly less frequent in BRCA1 mutation carriers compared to sporadic cases. No correlation was found between PML protein expression and any of the other clinical and laboratory characteristics.

Plasma adiponectin and E-selectin concentrations in patients with coronary heart disease and newly diagnosed disturbances of glucose metabolism.

PURPOSE: Adiponectin is a fat derived hormone, which enhances insulin sensitivity. In experimental studies adiponectin was shown to have antiatherogenic properties by suppressing endothelial expression of adhesion molecules. Therefore, the aim of the study was to evaluate plasma adiponectin and E-selectin concentrations in patients with coronary artery disease and impaired glucose metabolism and evaluation of their relationship with selected anthropometric, biochemical and clinical parameters. MATERIAL AND METHODS: The study group consisted of 62 patients with coronary heart disease, without previous diagnosis of diabetes mellitus (mean age 48.6 +/- 6.0 years; mean BMI 28.6 +/- 3.13 kg/m2). In the studied group the OGTT with glucose and insulin estimation was performed and insulin resistance index (HOMA-IR) was calculated. In the fasting state, the plasma adiponectin, soluble form of E-selectin, HbA1c and lipid parameters were estimated. RESULTS: Adiponectin concentration was not different in patients with type 2 diabetes mellitus and impaired glucose tolerance (n = 36) in comparison to the group with normal glucose tolerance (n = 26). There was also no difference in adiponectin concentration in relation to atherosclerosis progression. There was no significant correlation between adiponectin and calculated insulin resistance index, while there was marked inverse correlation between adiponectin and BMI (r = -0.30; p = 0.018), body weight (r = -0.33; p = 0.008), E-selectin (r = -0.263; p = 0.039), TG concentration (r = -0.27; p = 0.036), duration of coronary heart disease (r = -0.33; p = 0.009) and borderline significance with ejection fraction (r = -0.268; p = 0.06). CONCLUSIONS: Our study supports the hypothesis that adiponectin could be recognised as a protective protein for the development of atherosclerosis.

Magnetic anisotropies and coupling mechanisms in Fe/Mo(110) nanostripes.

Using low-temperature (5 K) spin-polarized scanning tunneling microscopy, we have studied the morphology and magnetic properties of monolayer (ML) and double layer (DL) thick Fe nanowires grown by step flow on a Mo(110) single crystal. Magnetic contrast has been obtained using tungsten tips covered by Au/Co thin films. We find that the DL Fe nanowires, similarly to ML Fe nanowires, are perpendicularly magnetized. Because of the dipolar coupling, separated DL Fe nanowires are antiferromagnetically coupled. DL wires that are touching at step edges are ferromagnetically ordered due to direct exchange coupling. We measured the widths of the magnetic domain walls in the ML and DL Fe nanowires. The domain wall width increases with the thickness of Fe.