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Leon Petrażycki's concept of legal policy, based on the author's original assumptions, focuses on the social and economic legal actions aiming to the general social prosperity. Legal policy was strictly connected with the idea of the real acceptance of the law, understood by the author as a specific socio-psychic mental state, approved in an individual experience and confirmed in a social practice. Petrażycki was the first law theorist who clearly emphasised the meaning of multiplicity of legal sources and economical nature of law, as well as the necessity to acknowledge various languages and local cultures in its contents. This concept, developed much ahead-of-its-time in the ideas of Leon Petrazycki, contains a lot of solutions which are convergent with one of the most important European policies - EU cohesion policy. The objectives, assumptions and sources of cohesion policy, located at the junction of traditionally understood law-making, application of law and social and economic politics, are surprisingly similar to Petrażycki's program. The author focuses on the subject of these relations.

Abstract Background Breast cancers are phenotypically and genotypically heterogeneous tumors containing multiple cancer cell populations with various metastatic potential. Aggressive tumor cell subpopulations might more easily be captured in lymph nodes metastases (LNM) than in primary tumors (PT). We evaluated mRNA and protein levels of master EMT regulators: TWIST1, SNAIL and SLUG, protein levels of EMT-related markers: E-cadherin, vimentin, and expression of classical breast cancer receptors: HER2, ER and PgR in PT and corresponding LNM. The results were correlated with clinicopathological data and patients outcomes. Methods Formalin-fixed paraffin-embedded samples from PT and matched LNM from 42 stage II-III breast cancer patients were examined. Expression of TWIST1, SNAIL and SLUG was measured by reverse-transcription quantitative PCR. Protein expression was examined by immunohistochemistry on tissue microarrays. Kaplan-Meier curves for disease-free survival (DFS) and overall survival (OS) were compared using F-Cox test. Hazard ratios (HRs) with 95% confidence intervals (95% CI) were computed using Cox regression analysis. Results On average, mRNA expression of TWIST1, SNAIL and SLUG was significantly higher in LNM compared to PT (P TWIST1 and SNAIL in LNM was associated with shorter OS (P = 0.04 and P = 0.02, respectively) and DFS (P = 0.02 and P = 0.01, respectively), whereas their expression in PT had no prognostic impact. Negative-to-positive switch of SNAIL protein correlated with decreased OS and DFS (HR = 4.6; 1.1-18.7; P = 0.03 and HR = 3.8; 1.0-48.7; P = 0.05, respectively). Conclusions LNM are enriched in cells with more aggressive phenotype, marked by elevated levels of EMT regulators. High expression of TWIST1 and SNAIL in LNM, as well as negative-to-positive conversion of SNAIL confer worse prognosis, confirming the correlation of EMT with aggressive disease behavior. Thus, molecular profiling of LNM may be used as surrogate marker for aggressiveness and metastatic potential of PT.

Methylene blue is a fluorescent dye discovered in 1876 and has since been used in different scientific fields. Only recently has methylene blue been used for intraoperative fluorescent imaging. Here, the authors review the emerging role of methylene blue, not only as a dye used in clinical practice, but also as a fluorophore in a surgical setting. We discuss the promising potential of methylene blue together with the challenges and limitations among specific surgical techniques. A literature review of PubMed and Medline was conducted based on the historical, current and future usage of methylene blue within the field of medicine. We reviewed not only the current usage of methylene blue, but we also tried to grasp its' function as a fluorophore in five main domains. These domains include the near-infrared imaging visualization of ureters, parathyroid gland identification, pancreatic tumors imaging, detection of breast cancer tumor margins, as well as breast cancer sentinel node biopsy. Methylene blue is used in countless clinical procedures with a relatively low risk for patients. Usage of its fluorescent properties is still at an early stage and more pre-clinical, as well as clinical research, must be performed to fully understand its potentials and limitations.

Background and Objectives: Surgical site infection (SSI) is a significant complication of non-reconstructive and reconstructive breast surgery. This study aimed to assess SSI after breast surgery over five years in a single center in Poland. The microorganisms responsible for SSI and their antibiotic susceptibilities were determined. Materials and Methods: Data from 2129 patients acquired over five years postoperatively by the Department of Surgical Oncology, Medical University of Gdansk in Poland were analyzed. Results: SSI was diagnosed in 132 patients (6.2%) and was an early infection in most cases (65.2%). The incidence of SSI was highest in patients who underwent subcutaneous amputation with simultaneous reconstruction using an artificial prosthesis (14.6%), and breast reconstruction via the transverse rectus abdominis muscle (TRAM) flap method (14.3%). Gram-positive bacteria were responsible for SSI in most cases (72.1%), and these were mainly Staphylococcus strains (53.6%). These strains were 100% susceptible to all beta-lactam antibiotics (except penicillin) but were less susceptible to macrolides and lincosamides. Conclusions: SSI is a serious problem, and attention should be focused on its prevention. Reconstruction using an artificial prosthesis or via the TRAM flap method is connected to increased SSI incidence. Further studies are required to prevent SSI following breast surgery.

Introduction: Ductoscopy is a low invasive method enabling the diagnostics of intraductal proliferative lesions in breasts. Fiberoptic ductoscopy (FDS) is important in the diagnosis of patients with pathological nipple discharge. There are attempts to apply FDS in patients with breast cancer without the presence of nipple discharge., Aim: To assess fiberoptic ductoscopy in the diagnostics of breast neoplasms., Material and Methods: The material was composed of a group of 164 patients treated for intraductal proliferative lesions in breasts. In the analyzed group of patients, FDS was conducted in 128 patients with pathological nipple discharge and 36 patients with the presence of breast cancer. The analyzed period was divided into three sub-periods. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of FDS examination verified by post-operative histopathological examination were analyzed. The safety of the method was also assessed, taking into consideration the complications., Results: An increasing number of successful ductoscopies together with the number of performed FDS examinations was noted. There were statistically significant differences in the percentage of successful cannulations in relation to the number of performed FDS examinations in the three subsequent stages of the project (p = 0.011). The duration of FDS examination in the third period was reduced in comparison with the first and second period (p < 0.001). Sensitivity of fiberoptic ductoscopy is 68.1%, specificity 77.3% and PPV 90.4%, but NPV is 44.1%., Conclusions: The introduction of fiberoptic ductoscopy in our clinic has contributed to the widening of the diagnostic possibilities of small intraductal lesions of the mammary gland.

Introduction: The aim of the work was to analyze the impact of selected factors on the incidence of seroma formation in breast cancer patients undergoing mastectomy., Material and Methods: One hundred and fifty breast cancer patients were prospectively enrolled in the study. All patients had mastectomy performed using the same operative technique with electrocoagulation. The amount of seroma formed after surgery and its duration were correlated with selected demographic, clinical and pathological parameters., Results: The cumulative total seroma volume collected by the end of treatment was higher and the overall time of seroma treatment was longer in patients over the age of 60 years (p = 0.001 and p = 0.001 respectively). Duration of seroma was significantly longer in obese patients (p = 0.036). The cumulative total seroma volume collected by the end of treatment was higher and the overall time of seroma treatment was longer in patients who had over 130 ml of lymph drained during the first 24 postoperative hours (p < 0.001 and p = 0.001 respectively). Additionally, longer duration of seroma was observed in patients with pathological stage I and II according to TNM-UICC (p = 0.042) and in patients with ≥ 1200 g weight resected of mammary gland (p = 0.05)., Conclusions: Age and obesity are important prognostic factors influencing seroma formation in breast cancer patients undergoing mastectomy. The amount of lymph formed during first postoperative day may have predictive value in assessing cumulative total seroma volume collected during treatment and its overall duration.

Background: Previous studies showed the prognostic and predictive impact of human epidermal growth factor receptor 2 (HER-2) gene alterations analyzed separately and jointly with topoisomerase II α (TOP2A) gene alterations; however, the role of TOP2A gene abnormalities alone has not been thoroughly investigated. Additionally, TOP2A aberrations were typically studied in HER-2-positive (HER-2(+)) tumors because these genes are frequently coamplified. Therefore, the knowledge concerning the impact of TOP2A abnormalities in HER-2-negative (HER-2(-)) patients is scarce. This study aimed to investigate the clinical significance of TOP2A anomalies in breast cancer patients with HER-2(-) and HER-2(+) tumors., Materials and Methods: Snap-frozen tumor samples from 322 consecutive stage I-III breast cancer patients were analyzed for TOP2A gene dosage using quantitative real-time PCR (qPCR)., Results: A high TOP2A gene dosage was found in 94 tumors (29%)-32% and 27% of HER-2(+) and HER-2(-) tumors, respectively. The mean TOP2A gene dosages in the HER-2(+) and HER-2(-) groups were 1.49 ± 1.03 and 1.09 ± 0.35, respectively. High TOP2A gene dosage had an inverse prognostic impact in terms of shorter disease-free survival (DFS) and overall survival (OS) times in the entire group and in both the HER-2(-) and HER-2(+) subgroups. The unfavorable prognostic impact of TOP2A gene dosage was maintained in the multivariate Cox regression analysis in the entire group and in HER-2(-) patients., Conclusions: A high gene dosage of TOP2A determined using qPCR occurs frequently both in HER-2(+) and HER-2(-) tumors and has a strong adverse prognostic impact.

Background: In this prospective, randomized, placebo-controlled, double-blinded clinical trial we tested the hypothesis that preemptive analgesia with bupivacaine applied in the area of the surgical incision in patients undergoing mastectomy for breast cancer would reduce post-operative acute pain and would reduce the amount of analgesics used during surgery and in the post-operative period., Material/methods: Participants were assigned into 1 of 2 groups--with bupivacaine applied in the area of surgical incision or with placebo. We assessed the intraoperative consumption of fentanyl, the postoperative consumption of morphine delivered using a PCA method, and the subjective pain intensity according to VAS score reported by patients in the early post-operative period., Results: Out of 121 consecutive cases qualified for mastectomy, 112 women were allocated randomly to 1 of 2 groups--group A (bupivacaine) and group B (placebo). The final study group comprised 106 breast cancer cases. Between the groups, a statistically significant difference was observed with respect to: lower fentanyl consumption during surgery (p = 0.011), lower morphine (delivered by means of a PCA) consumption between the 4-12th postoperative hours (p = 0.02) and significantly lower pain intensity assessed according to VAS score at the 4th and 12th hours after surgery (p = 0.004 and p = 0.02 respectively) for the group A patients., Conclusions: Preemptive analgesia application in the form of infiltration of the area of planned surgical incisions with bupivacaine in breast cancer patients undergoing mastectomy decreases post-operative pain sensation, limits the amount of fentanyl used during surgery, and reduces the demand for opiates in the hours soon after surgery.

Background: Although studies comparing the surgical treatment of gastric carcinoma in Japan and Western industrialized countries have revealed differing survival rates, no studies to date have been performed comparing Western and Eastern Europe. This study aimed to compare demographics and surgical practice as well as the related prognostic impact on gastric cancer patients treated in Poland and Germany., Methods: This retrospective study included gastric cancer patients treated between 1999 and 2004 by surgical departments in Gdansk (Poland) and Cologne (Germany). Univariate and multivariate analyses of demographic, histopathological, surgical, and prognostic data were performed., Results: Included were 117 patients from Gdansk and 130 patients from Cologne. The Cologne patients showed higher incidence rates of serious comorbidity, pT1 cancer, and distant metastasis than those from Gdansk. Indications for and frequency of selected surgical procedures differed significantly. D2-lymphadenectomy was performed in 89% of the Cologne patients, while D1-lymphadenectomy was done for 85% of the Gdansk patients. Univariate analysis yielded a 5-year survival rate of 28.3% for the Gdansk patients, and 40.3% for the Cologne patients (p = 0.056). Independent prognostic factors were pT category (p = 0.002), pN category (p < 0.001), pM category (p = 0.027), residual tumor (R) category (p = 0.004), age (p = 0.012), and number of resected lymph nodes (p = 0.005)., Conclusions: Significant differences of clinical and surgical parameters exist between gastric cancer patients treated in Poland and Germany. In addition to established independent prognostic factors, we found that survival improved with each additionally resected lymph node.

We describe simultaneous surgery performed on a 71-year-old woman with critical aortic stenosis and gastric cancer that were diagnosed at the same time. The patient qualified for simultaneous surgery for both these diseases. Good early outcome was achieved. There is a lack of standards for treatment of patients with coexistence of two life-threatening conditions. We discuss surgical tactics and potential benefits of such management.

Purpose: The aim of this work is to compare selected parameters of implants and natural dose volume histograms for two techniques of interstitial pulsed dose rate brachytherapy (PDR BT) as a boost to the tumour bed in breast-conserving therapy (BCT)., Material and Methods: Data of T 1-3 N 0-2 M 0 breast cancer patients who underwent BCT with BT boost between 05.2002 and 12.2008 were analysed. Ninety two patients were implanted with rigid tubes after breast irradiation (group A) and 96 had a peri-operative BT with an intra-operative flexible tube placement and subsequent whole breast radiotherapy (group B). In both groups PDR BT of 15 Gy (1 Gy/pulse/h) was administered based on Paris system rules, and volume optimization using BT planning system PLATO., Results: Three-plane implant was used in 62% and 8% of patients in group A and B, respectively, and two-plane implant in 38% of group A and in 84% of group B, with a median of 11 and 9 tubes respectively. The average volume for the prescribed dose (V 100 ) was 42.0 ± 25.4 cc (group A) and 34.1 ± 19.7 cc (group B), respectively (p = 0.017). The individual V 50 and V 200 were similar. Quality index (QI) was not impacted by the technique of BT (mean QI was 1.80 ± 0.10 and 1.75 ± 0.46 for the groups A and B, respectively). Uniformity index (UI) in respective groups was 1.60 ± 0.10 and 1.52 ± 0.21 (p = 0.001)., Conclusions: Implant volume encompassed by prescribed dose was significantly lower with intra-operative plastic tubes placement. In respect to the QI, these two BT techniques were comparable. The target volume coverage by the dose distribution as defined by UI was better for rigid tubes.

Background: Hormone replacement therapy (HT) is known to increase the risk of breast cancer in healthy women, but its effect on breast cancer risk in breast cancer survivors is less clear. The randomized HABITS study, which compared HT for menopausal symptoms with best management without hormones among women with previously treated breast cancer, was stopped early due to suspicions of an increased risk of new breast cancer events following HT. We present results after extended follow-up., Methods: HABITS was a randomized, non-placebo-controlled noninferiority trial that aimed to be at a power of 80% to detect a 36% increase in the hazard ratio (HR) for a new breast cancer event following HT. Cox models were used to estimate relative risks of a breast cancer event, the maximum likelihood method was used to calculate 95% confidence intervals (CIs), and chi(2) tests were used to assess statistical significance, with all P values based on two-sided tests. The absolute risk of a new breast cancer event was estimated with the cumulative incidence function. Most patients who received HT were prescribed continuous combined or sequential estradiol hemihydrate and norethisterone., Results: Of the 447 women randomly assigned, 442 could be followed for a median of 4 years. Thirty-nine of the 221 women in the HT arm and 17 of the 221 women in the control arm experienced a new breast cancer event (HR = 2.4, 95% CI = 1.3 to 4.2). Cumulative incidences at 5 years were 22.2% in the HT arm and 8.0% in the control arm. By the end of follow-up, six women in the HT arm had died of breast cancer and six were alive with distant metastases. In the control arm, five women had died of breast cancer and four had metastatic breast cancer (P = .51, log-rank test)., Conclusion: After extended follow-up, there was a clinically and statistically significant increased risk of a new breast cancer event in survivors who took HT.

The PDC (pyruvate dehydrogenase complex) is strongly inhibited by phosphorylation during starvation to conserve substrates for gluconeogenesis. The role of PDHK4 (pyruvate dehydrogenase kinase isoenzyme 4) in regulation of PDC by this mechanism was investigated with PDHK4-/- mice (homozygous PDHK4 knockout mice). Starvation lowers blood glucose more in mice lacking PDHK4 than in wild-type mice. The activity state of PDC (percentage dephosphorylated and active) is greater in kidney, gastrocnemius muscle, diaphragm and heart but not in the liver of starved PDHK4-/- mice. Intermediates of the gluconeogenic pathway are lower in concentration in the liver of starved PDHK4-/- mice, consistent with a lower rate of gluconeogenesis due to a substrate supply limitation. The concentration of gluconeogenic substrates is lower in the blood of starved PDHK4-/- mice, consistent with reduced formation in peripheral tissues. Isolated diaphragms from starved PDHK4-/- mice accumulate less lactate and pyruvate because of a faster rate of pyruvate oxidation and a reduced rate of glycolysis. BCAAs (branched chain amino acids) are higher in the blood in starved PDHK4-/- mice, consistent with lower blood alanine levels and the importance of BCAAs as a source of amino groups for alanine formation. Non-esterified fatty acids are also elevated more in the blood of starved PDHK4-/- mice, consistent with lower rates of fatty acid oxidation due to increased rates of glucose and pyruvate oxidation due to greater PDC activity. Up-regulation of PDHK4 in tissues other than the liver is clearly important during starvation for regulation of PDC activity and glucose homoeostasis.

This study investigated whether conditions known to alter the activity and phosphorylation state of the pyruvate dehydrogenase complex have specific effects on the levels of isoenzymes of pyruvate dehydrogenase kinase (PDK) in rat heart. Immunoblot analysis revealed a remarkable increase in the amount of PDK4 in the hearts of rats that had been starved or rendered diabetic with streptozotocin. Re-feeding of starved rats and insulin treatment of diabetic rats very effectively reversed the increase in PDK4 protein and restored PDK enzyme activity to levels of chow-fed control rats. Starvation and diabetes also markedly increased the abundance of PDK4 mRNA, and re-feeding and insulin treatment reduced levels of the message to that of controls. In contrast with the findings for PDK4, little or no changes in the amounts of PDK1 and PDK2 protein and the abundance of their messages occurred in response to starvation and diabetes. The observed shift in the relative abundance of PDK isoenzymes probably explains previous studies of the effects of starvation and diabetes on heart PDK activity. The results indicate that control of the amount of PDK4 is important in long-term regulation of the activity of the pyruvate dehydrogenase complex in rat heart.

The objective of this study was to assess the essential fatty acid status of patients with anorexia nervosa. Blood was collected from eight fasting female anorexia nervosa patients with a mean of 81% ideal body weight. Fatty acid composition of phospholipids, nonesterified fatty acids, triglycerides and cholesteryl esters of plasma were determined by capillary gas chromatography to indicate polyunsaturated fatty acids status compared with 19 healthy female adults < 25 y old. Subjects with anorexia nervosa showed polyunsaturated fatty acid deficiencies in plasma phospholipids different from simple nutritional essential fatty acid deficiency or chronic malnutrition. The phospholipid profile showed significantly lower (n-6) and (n-3) elongation and desaturation products, and elevated short-chain saturated, short-chain monounsaturated, branched-chain and odd-chain fatty acids. These elevations indicate enhancement of biosynthesis of alternative fatty acids that only partially compensated for the loss of polyunsaturated fatty acids in providing membrane "fluidity." Calculated mean melting point of the fatty acids of phospholipids in patients with anorexia nervosa was elevated 7.7 degrees C above normal values. These results demonstrate that patients with anorexia nervosa have deficiencies of selected essential fatty acids, compensatory changes in nonessential fatty acids and decreased fluidity of plasma lipids.