Changing the role of pCR in breast cancer treatment - an unjustifiable interpretation of a good prognostic factor as a "factor for a good prognosis".

Pathologic complete response (pCR) after neoadjuvant systemic therapy (NAST) of early breast cancer (EBC) has been recognized as a good prognostic factor in the treatment of breast cancer because of its significant correlation with long-term disease outcome. Based on this correlation, pCR has been accepted by health authorities (FDA, EMA) as a surrogate endpoint in clinical trials for accelerated drug approval. Moreover, in recent years, we have observed a tendency to treat pCR in routine clinical practice as a primary therapeutic target rather than just one of the pieces of information obtained from clinical trials. These trends in routine clinical practice are the result of recommendations in treatment guidelines, such as the ESMO recommendation "…to deliver all planned (neoadjuvant) treatment without unnecessary breaks, i.e. without dividing it into preoperative and postoperative periods, irrespective of the magnitude of tumor response", because "…this will increase the probability of achieving pCR, which is a proven factor for a good prognosis…". We hypothesize that the above recommendations and trends in routine clinical practice are the consequences of misunderstanding regarding the concept of pCR, which has led to a shift in its importance from a prognostic factor to a desired treatment outcome. The origin of this misunderstanding could be a strong subconscious incentive to achieve pCR, as patients who achieved pCR after NAST had a better long-term outcome compared with those who did not. In this paper, we attempt to prove our hypothesis. We performed a comprehensive analysis of the therapeutic effects of NAST and adjuvant systemic therapy (AST) in EBC to determine whether pCR, as a phenomenon that can only be achieved at NAST, improves prognosis per se. We used published papers as a source of data, which had a decisive influence on the formation of the modern attitude towards EBC therapy. We were unable to find any evidence supporting the use of pCR as a desired therapeutic goal because NAST (reinforced by pCR) was never demonstrated to be superior to AST in any context.

DO THE GUIDELINES GUIDE THE BELGRADE EMERGENCY MEDICAL SERVICE PHYSICIANS THROUGH THE MANAGEMENT OF ACUTE ST-ELEVATION MYOCARDIAL INFARCTION?

The aim of the study was to assess whether current guidelines for diagnosis and treatment of acute ST-elevation myocardial infarction (STEMI) in daily clinical practice are adequately applied in the Belgrade Emergency Medical Service (EMS). A retrospective research included 2,982 STEMI patients who were cared for by EMS teams. Therapy consisting of morphine, oxygen, nitroglycerin and aspirin (MONA) was applied. Dual antiaggregation therapy (aspirin 325 mg + ticagrelor 180 mg or clopidogrel 600 mg) was administered to patients with primary percutaneous coronary intervention (PCI) indicated. With electrocardiographic monitoring included, the patients were transported directly to PCI unit with announcement of the arrival. Response times I-V were measured. There was an increasing trend in the number of STEMI patients. A rapid increase in the use of dual antiaggregation therapy (MONA and clopidogrel or MONA and ticagrelor) was reported from year to year, as well as a dramatic increase in the use of ticagrelor compared to clopidogrel. The time from receiving the call to the arrival on the scene was 13.72 minutes, and the time from receiving the call to hospital arrival was 52.83 minutes. Our physicians care for STEMI patients in accordance with the current international and local recommendations.

Possible role of lead in breast cancer - a case-control study.

Numerous risk factors have been associated with breast cancer (BC), exposure to metalloestrogen, like lead, being such. Since lead involvement in BC is still equivocal, we focused on lead levels in three compartments of BC patients, blood, healthy, and malignant tissues. Also, as the cholesterol role in cancer development was recognized at the beginning of the twentieth century and led to involvement in lipid profile impairment, we further extend our research on lipid profile and enzymes responsible for maintaining lipid balance in BC patients. Fifty-five women diagnosed with BC were enrolled in the study. Forty-one healthy women represented the control group. Lead levels in blood, healthy surrounding and malignant tissue, and lipid profile parameters in serum, were determined. Higher lead levels were obtained in surrounding healthy tissue samples compared to cancerous tissue samples, while blood lead levels of BC women did not differ significantly from the control group. The altered lipid profile scheme in women diagnosed with breast cancer contained significantly higher triglycerides levels (P < 0.001). Moreover, logistic regression analysis revealed triglycerides as a significant predictor of BC (OR = 2.6; P < 0.01). Although statistical significance was missing for lower paraoxonase-1 (PON-1) activities observed in BC women, multivariate logistic regression singled out PON-1 activities as significant BC predictors. The result of the present study further indicated oxidative status imbalance and tissue levels bioelements perturbation. Obtained results in the present study propose possible lead involvement in BC onset accompanied with bioelements redistribution and oxidative stress occurrence.

Cadmium tissue level in women diagnosed with breast cancer - A case control study.

Breast cancer is at the forefront of female malignancy and the leading cause of cancer death among women. Gender, age, hormone therapy, smoking, exposure to endocrine disruptors and family history are significant breast cancer risk factors according to epidemiological data. Considering metalloestrogenic Cd property and a plethora of research work on hormone involvement in breast cancer the study aimed to determine Cd concentration in three compartments of breast cancer patients in relation to their blood hormone status. Further, as oxidative stress is a critical mechanism of Cd toxicity, the objective of this study was to determine potential changes in oxidative status homeostasis. The study enrolled 55 patients with breast cancer diagnosis and 41 healthy women with benign breast changes. Concentration of Cd was determined using graphite furnace atomic absorption spectrometry. Cadmium concentration in tumor tissue was significantly higher than control and almost four times higher than Cd concentration in the healthy surrounding tissue. Strong positive correlation was observed between Cd concentrations in changed breast tissue and FSH and LH levels, while the correlation was negative with estradiol level. Cancer patients had significantly increased blood total antioxidative status while total oxidative status did not significantly differ between study groups. The study revealed Cd implication in breast cancer onset following a significant odd ratio for Cd levels in changed tissue samples. Moreover, presented data confirmed sex hormone and oxidative status imbalance caused by Cd presence, closely related to cancer development.

Intraoperative ultrasound in breast cancer surgery-from localization of non-palpable tumors to objectively measurable excision.

BACKGROUND: The utilization of intraoperative ultrasound (IOUS) in breast cancer surgery is a relatively new concept in surgical oncology. Over the last few decades, the field of breast cancer surgery has been striving for a more rational approach, directing its efforts towards removing the tumor entirely yet sparing tissue and structures not infiltrated by tumor cells. Further progress in objectivity and optimization of breast cancer excision is possible if we make the tumor and surrounding tissue visible and measurable in real time, during the course of the operation; IOUS seems to be the optimal solution to this complex requirement. IOUS was introduced into clinical practice as a device for visualization of non-palpable tumors, and compared to wire-guided localization (WGL), IOUS was always at least a viable, or much better alternative, in terms of both precision in identification and resection and for patients' and surgeons' comfort. In recent years, intraoperative ultrasound has been used in the surgery of palpable tumors to optimize resection procedures and overcome the disadvantages of classic palpation guided surgery. OBJECTIVE: The aim of this review is to show the role of IOUS in contemporary breast cancer surgery and its changes over time. METHODS: A PubMed database comprehensive search was conducted to identify all relevant articles according to assigned key words. CONCLUSION: Over time, the use of IOUS has been transformed from being the means of localizing non-palpable lesions to an instrument yielding a reduced number of positive resection margins, with a smaller volume of healthy breast tissue excided around tumor, by making the excision of the tumor optimal and objectively measurable.

Lymph nodes behind the axillary neurovascular bundle: case report and cadaveric study of frequency and distribution.

Axillary clearance was undertaken in a 58-year-old male with massive lymph node enlargement caused by melanoma from an unknown primary site. We discovered a group of metastatic lymph nodes behind the axillary neurovascular bundle. This group of nodes (retro-axillary lymph nodes) could represent an extension of the subscapular group, or the seventh group of axillary lymphoid nodes. They were successfully removed using an ad hoc surgical technique, and the subsequent findings are presented herein. To check the frequency of these lymph nodes in this area, we conducted a study on 15 cadavers (30 armpits). The technique of cadaveric sampling is described. Retro-axillary tissue was histologically processed to determine the number of lymph nodes present. It was found that lymph nodes were present in the defined area in 18 of the 30 (60 %) armpits explored. We recommend assessment of the retro-axillary space during surgery entailing massive axillary lymph node involvement.

Optimization of breast cancer excision by intraoperative ultrasound and marking needle - technique description and feasibility.

BACKGROUND: We present a surgical technique and the preliminary results of breast cancer excision after insertion of a specially constructed marking needle into the tumor, controlled by intraoperative ultrasound. Resection margins were projected in six directions by ultrasound measurements, determined in relation to the needle, and resection was done in accordance with those measurements. The main objective was to obtain resection margins similar (equal) to those projected by intraoperative ultrasound (10 mm). METHODS: Detailed description of the technique is given. Thirty-two female patients undergoing breast-conserving surgery, up to 30 mm in diameter, for palpable and non-palpable invasive breast cancer, were operated on using this technique. Its feasibility was tested by analyzing the success (rate) of needle placement in the tumor, the measurements executed, and the performance of the excision. RESULTS: All stages of the technique were successfully performed to completion on all 32 patients. The procedure of needle placement and ultrasound measurement of distances took 11 min on average (between 6 and 20 min). The average distance of the tumor margin from the resection margin was 12.9 mm (2 to 30 mm, 95% confidence interval [11.9, 14.06]). There was one patient with a positive resection margin (3%). CONCLUSIONS: The technique of excising palpable and non-palpable breast cancer by intraoperative ultrasound and an especially constructed marking needle is feasible and comfortable to perform. Preliminary results imply that resection volume can be rationalized, with the same or better oncological safety.