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The choice of the anti-HER2 agent depends on country-specific availability, the specific, previously administered anti-HER2 therapy and the relapse-free interval, although there is not much published data on the use of lapatinib after progression on pertuzumab and/or T-DM1. The aim of this research is to determine efficacy of lapatinib in this setting. This research included 111 patients with metastatic HER2 positive breast cancer who received lapatinib with capecitabine at The Oncology Institute of Vojvodina. Lapatinib was given to 83 patients after trastuzumab without prior exposure to pertuzumab or T-DM1 while 28 patients received lapatinib after prior exposure to trastuzumab, pertuzumab and/or T-DM1. In order to determine efficacy of lapatinib in both groups, we measured progression free survival (PFS) and overall survival (OS), as well as by subsets: hormonal status (ER-positive and/or PR-positive tumours versus ER-negative and PR-negative tumours), the number of positive axillary lymph nodes (four or more positive axillary lymph nodes versus less than four positive axillary lymph nodes), marker of proliferation (Ki-67 ≥ 30 versus Ki-67 30), disease free interval (metastatic recurrence ≤ 1 year after initial diagnosis versus metastatic recurrence1 year after initial diagnosis or de novo metastatic disease. Median PFS was 5.6 months (95% CI 4.6-6.6) in the group of patients who received lapatinib after prior exposure to trastuzumab, pertuzumab and/or T-DM 1 and 7.4 months (95% CI 6.1-10.2) in the group of patients who received lapatinib after trastuzumab (HR, 0.79; 95% CI 0.61-0.98; P = 0.09). The patients with negative prognostic factors such as hormone receptor negativity, more than four positive axillary lymph nodes, marker of proliferation Ki 67 ≥ 30 and metastatic recurrence ≤ 1 year after initial diagnosis, had a similar PFS, regardless of receiving lapatinib after prior exposure to trastuzumab, pertuzumab and/or T-DM1 or without prior exposure. Median OS was 10.1 months (95% CI 8.6-NR) in the group that received lapatinib after exposure to trastuzumab, pertuzumab and/or T-DM1 and 16.3 months (95% CI 14.4-20.2) in the group of patients who received lapatinib after trastuzumab (HR, 0.76; 95% CI, 0.59-0.94; P = 0.04). Patients with negative prognostic factors such as hormone receptor negativity, more than four positive axillary lymph nodes and marker of proliferation Ki 67 ≥ 30, had no distinctly worse OS, regardless of receiving lapatinib after prior exposure to trastuzumab, pertuzumab and/or T-DM1 or without prior exposure. Lapatinib with capecitabine is an effective therapeutic option, especially in patients with negative prognostic factors, who have received prior chemotherapy, trastuzumab, pertuzumab, T-DM1 and remains an acceptable option for HER2 positive metastatic breast cancer until the novel drugs are approved in developing countries.

Group of symptoms due to vena cava superior obstruction is named superior vena cava syndrome. A 65-year-old female, long-standing smoker was presented with a two-week history of dry cough and facial swelling. The patient noticed a palpable mass on the right side of the neck. Computer tomography scan with contrast showed extensive, irregular, non-homogenous consolidation in the right upper lobe, involving the right hilus, surrounding the aortic arch, supra aortic branches and pleural effusion at the right side of the body. Also, ultrasound examination of supra clavicular space showed enlarged pathologic hypoehogenic lymph node without an echogenic hilum. Ultrasound guided fine needle biopsy of lymph node was performed, and cytopathology findings showed metastatic lesion from primary microcellular lung cancer, IIIC stadium, cT4N3M0. Venous angioplasty was performed showing stenosis in the superior vena cava. After balloon dilatation, the stent was placed at the site of stenosis. The patient received chemio- and radiotherapy and survival time was seven months. Superior vena cava syndrome is an urgent clinical condition, and lung cancer is the leading cause of this syndrome. Computer tomography imaging findings and endovascular stent placement are important for detection and management of the superior vena cava thrombosis.

Introduction: The development of laparoscopic colorectal surgery began in 1991. Today, laparoscopic surgery presents standard approach in the surgical treatment of malignant colon and rectal diseases. Aim: Surgical and oncological outcomes and survival rates of laparoscopic colorectal surgery at the Oncology Institute of Vojvodina. Methods: Data were collected prospectively from 66 patients undergoing laparoscopic colorectal surgery between December 2009 and December 2019. Registered data included sex, age, surgical indication and type for the procedure, indication and reason for conversion to open surgery, operative time, performing temporary or permanent stoma, intraoperative bowel perforation, pathologic TNM grade, number of harvested lymph nodes, inclusion of positive resection margin, number of postoperative days at the hospital, postoperative complications, postoperative mortality, presence of distant metastases and survival rates. Results: Laparoscopic procedures were right hemicolectomy in 11/66 (16.7%), left hemicolectomy in 1/66 (1.5%), sigmoid colectomy in 19/66 (28.8%), high anterior rectal resection in 13/66 (19.7%), low anterior rectal resection in 12/66 (18.2%), abdominoperineal amputation of the rectum in 7/66 (10.6%), colectomy in 2/66 (3%) and proctocolectomy in 1/66 (1.5%) patient. The median follow-up was 37.5 months (range 6 to 128). The total number of surviving patients was 60 (90.9%). Conclusion: This study showed that laparoscopic colorectal surgery has good clinical and oncological outcomes.

Recommendations and guidelines consider cancer patients a high-priority population for COVID-19 immunization. Vaccination process in Serbia began in January 2021 with four available vaccines. We have conducted a cross-sectional study investigating cancer patients' acceptability of anti SARS-COV2 vaccines.The study included 767 patients with solid and hematologic malignancies treated at the Oncology Institute of Vojvodina, Serbia. During July and August 2021 patients filled in an individual paper questionnaire on anti SARS-COV2 vaccination acceptance, preferences, side effects and information origin. Data on treatment phase, diagnosis and treatment was collected from electronic health records.During the first six months of vaccination campaign in Serbia 41% (320/767) of the investigated oncology patients received COVID-19 vaccines. The median age of vaccinated patients was 65 years (28-84). Most of them (75%) were in active treatment of cancer. Half of the unvaccinated patients (52%) wish to get vaccinated after the end of their cancer treatment. Around 10% of the patients definitely refused vaccination. The majority of information on COVID-19 vaccines cancer patients got from their oncologist, television and newspapers. Side effects were reported by 10.93% of the patients after the first dose and 13,31% after the second dose. No serious side effects were reported.We have confirmed that patients are reluctant of receiving vaccine due to fear of side effects, especially during the active cancer treatment. However, real-world evidence and clinical trials data have gathered enough evidence to reassure any doubts of the patients and their oncologists on safety and efficacy of anti SARS-COV2 vaccines.

Introduction. Hepatocellular carcinoma is a serious problem for patients with hemophilia. Hepatitis C virus infection is the most common comorbidity in adult patients with inherited bleeding disorders, including hemophilia. Case Report. This is a case report of a 65-year-old male patient with hemophilia A and hepatocellular carcinoma. Sorafenib treatment was initiated at a dose of 400 mg/day, after a 50% dose reduction. In order to prevent bleeding episodes, prophylactic doses of replacement plasma-derived factor VIII concentrate (40 U/kg of body weight three times a week) were introduced. Our patient received a total of ten cycles of sorafenib therapy, in good general condition, without bleeding episodes. Conclusion. Differential chemotherapy is not contraindicated in patients with inherited bleeding disorders, provided that adequate hemostasis is achieved. In such cases, a multidisciplinary approach is necessary for the management of hemophilia during systemic cancer treatment.

Introduction. This retrospective study evaluates the association between the time of chemotherapy initiation and disease free survival in regard to breast cancer subtypes and stage at diagnosis. Material and Methods. The study included a total of 1075 breast cancer patients, stages I - III, treated at Oncology Institute of Vojvodina, Serbia (from 2010 to 2012; n = 617). The gathered data included prognostic factors used in everyday practice. Patients were divided into three groups according to the interval between surgery and chemotherapy (? 30, 31 - 60, ? 61 days). Disease free survival was calculated. Results. Among the 617 patients, the 5-year disease free survival estimate was similar: 81.5%, 81.0%, 84.6% (log-rank test, p = 0.728) regarding the time of adjuvant chemotherapy initiation: ? 30 days, 31 - 60, and ? 61 days, respectively. The study showed that 85% of our breast cancer patients started adjuvant chemotherapy within 3 months after definitive surgery. In multivariate analysis, independent prognostic factors for disease free survival were nodal status and tumor size. The 5-year disease free survival estimate was 85.8% (p = 0.001) for patients with luminal- A subtype (Estrogen +, Progesterone high, human epidermal growth factor receptor 2-, Ki-67 < 20%) with a median follow-up of 62,7 months; for patients with luminal-B (Luminal B (human epidermal growth factor receptor 2 -) Estrogen +, human epidermal growth factor receptor 2-, either Ki-67 high or Progesterone low, Luminal B (human epidermal growth factor receptor +) Estrogen +, human epidermal growth factor receptor 2 +, any Ki-67, any Progesterone) 78.3% (p = 0.534) with a median follow-up of 55.9 months; for patients with triple negative breast cancer it was 73.4% with a median follow-up of 58,1 months, and for patients with human epidermal growth factor receptor 2+ it was 77.1% (p = 0.448) with a median follow-up of 55.5 months. Conclusion. Early initiation of adjuvant chemotherapy is particularly important in patients with advanced- stage breast cancer at diagnosis, and those with trastuzumab- treated triple-negative breast cancer and human epidermal growth factor receptor 2-positive tumors.

Background/Aim. Multimodal approach to locally advanced rectal cancer treatment results in better disease outcome. Preoperative chemoradiotherapy improves disease local control, reduces risk of local recurrence and in the majority of patients with complete or substantial regression of the tumors significantly improves survival rates. According to the literature data, approximately 20% of patients had achieved complete histopathological response (pCR) after neoadjuvant chemoradiation therapy. The aim of this study was to evaluate overall survival in rectal cancer patients treated with preoperative chemoradiotherapy and sphincter preserving surgery. Methods. This retrospective study included 191 patients. Patients received preoperative radiation therapy and chemotherapy-chemoradiation therapy (CRT) followed by operation that favorized sphincter preservation with total mesorectal excision (TME) from June 2000 until December 2010. Diagnosis was established according to the following algorithm: patient history, digital rectal examiantion, colonoscopy with biopsy and histopathology verification, and preoperative clinical staging. Patients with tumors located below promontorium were included in the study and patients with metastatic disease and local recurrence were excluded from the study. For tumors located below the promontorium preoperative radiotherapy was used with total dose of 50.4 Gy, divided into daily doses of 1.8 Gy, during 28 days. Chemotherapy followed radiotherapy with 5- fluorouracil and folic acid (Leucovorin?) on days 1, 2, 10, 11, 20 and 21. Six to ten weeks after neoadjuvant therapy, magnetic resonance imaging (MRI) to restage tumors and operation were performed. Results. Of all patients that received preopertive chemoradiation, 163 had radical sphincter preservig surgery and 28 patients had paliative operations. Histopathological examination of the specimens showed that the complete histopathological regression was achieved in 21.4% of the patients, downstaged was found in 63.2% of them and unchanged stage was found in 15.3% of the patients. The five-year survival rate was 63.3% and 50.5 % in the patients with pCR and patients with incomplete histopathological regression, respectively. Survival rates between two groups were not statistically significant (p > 0.05). Conclusion. The preoperative chemoradiotherapy is very important in achieving optimal clinical care for patients with locally advanced rectal cancer.

Energy efficiency has become an integral part of the projects by adoption of laws and regulations on energy efficiency in 2011. This paper presents energy rehabilitation of the primary school building 'Dobrila Stambolic' in Svrljig. Energy restoration of this building, in addition to replacement of the roof cladding and roof constructions, included the installation of thermal insulation on all facade walls of the building, replacement of windows and heating system. By applying the suggested refurbishments the building energy class rating transferred from F to D which is two classes improvement.

Introduction: In the last two decades there has been a significant progress in rectal cancer surgery. Preoperative radiotherapy, the introduction of staplers and largely improved surgical techniques have greatly contributed to better treatment outcomes, primarily by reducing the frequency of early surgical complications and the rate of local recurrence. The aim of this study was to compare operative and postoperative results in the treatment of rectal cancer between the two groups of surgeons - those who are closely engaged in colorectal surgery and those who deal with these issues sporadically. Material and Methods: A retrospective study on 146 patients who underwent rectal cancer surgery at the Institute of Oncology in the period from 01.01.2008. to 31.12.2010. Patients were divided into two groups. The first group (N1 = 101) consisted of patients operated by trained colorectal surgeons, and in the second (N2 = 45) there were patients who were operated on by surgeons without training in TME. Results: Preoperative chemoradiotherapy was received by 49 (33.56%) patients. Statistically significant difference between the two groups was noted in the duration of surgery and the need for blood transfusion during surgery. Anastomotic leakage occurred in 3 patients from N1 and in 10 patients from group N2. Seven patients (4.79%) developed local recurrence after surgical treatment. Significant differences exist in local recurrence rate and anastomotic leakage rate between compared groups. Conclusion: It is necessary to continue education and training in surgery for rectal cancer to master new technologies and surgical techniques and to improve the results of surgical treatment.

In this paper, we present a novel method for impulse noise filter construction, based on the switching scheme with two cascaded detectors and two corresponding estimators. Genetic programming as a supervised learning algorithm is employed for building two detectors with complementary characteristics. The first detector identifies the majority of noisy pixels. The second detector searches for the remaining noise missed by the first detector, usually hidden in image details or with amplitudes close to its local neighborhood. Both detectors are based on the robust estimators of location and scale-median and MAD. The filter made by the proposed method is capable of effectively suppressing all kinds of impulse noise, in contrast to many existing filters which are specialized only for a particular noise model. In addition, we propose the usage of a new impulse noise model-the mixed impulse noise, which is more realistic and harder to treat than existing impulse noise models. The proposed model is the combination of commonly used noise models: salt-and-pepper and uniform impulse noise models. Simulation results show that the proposed two-stage GP filter produces excellent results and outperforms existing state-of-the-art filters.

The problem of foreground detection in real-time video surveillance applications is addressed. Proposes is a framework, which is computationally cheap and has low memory requirements. It combines two simple processing blocks, both of which are essentially background subtraction algorithms. The main novelty of the approach is a combination of an autoregressive moving average filter with two background models having different adaptation speeds. The first model, having a lower adaptation speed, models long-term background and detects foreground objects by finding areas in the current frame which significantly differ from the proposed background model. The second model, with a higher adaptation speed, models the short-term background and is responsible for finding regions in the scene with a high foreground object activity. The final foreground detection is built by combining the outputs from these building blocks. The foreground obtained by the long-term modelling block is verified by the output of the short-term modelling block, i.e. only the objects exhibiting significant motion are detected as real foreground objects. The proposed method results in a very good foreground detection performance at a low computational cost.

Background: Beneficial effects of berries have been known from 16th century, but their antimicrobial effects have been explained scientifically only recently. The two most common aronia species are black chokeberry, Aronia melanocarpa [Michx.] Elliot and red chokeberry, Aronia arbutifolia [L.] Elliot. Purple chokeberry (Aronia prunifolia) is a hybrid of these two species. Protothecosis is a disease caused by achlorophyllous algae Prototheca species. Infections with Prototheca species are more common in veterinary medicine. The purpose of this study was to investigate the activity of Aronia prunifolia berries against Prototheca zopfii (P. zopfii) and Prototheca wickerhamii (P. wickerhamii).Materials, Methods & Results: Purple chokeberry juice was made by squeezing the fruits and evaporated to dryness. Extracts of purple aronia were obtained by maceration with ethanol 80 % (v/v) for 24 h. Prototheca zopfii was obtained from udder of cow with mastitis and Prototheca wickerhamii was isolated from human oral cavity. Total phenolic and flavonoid contents were analized using spectrophotometric methods. The chemical composition of the tested substances was determined by a high performance liquid chromatography (HPLC) method. The examination was conducted by a micro-dilution method according to the guidelines of Clinical and Laboratory Standards Institute (CLSI). Microsoft Excel program 2007 was used for statistical analysis. The antialgal activity was expressed as minimal inhibitory concentrations MIC99, MIC90 and MIC80, the lowest concentration which kills 99%, 90% and 80% of organisms, respectively. Furthermore, minimal algaecide concentration (MAC), the lowest concentration which kills 99.9% of organisms is determined, as well as break point, the lowest concentration at which there is no algal growth.Discussion: The content of ascorbic acid was twice as high in the ethanolic extract as in the juice. Content of polyphenolic compounds was high in both juice and ethanolic extract. The quantity of phenocarbonic acids in juice and ethanolic extract was relatively low. Some of them were found only in juice (ellagic, coumaric and gentisic acids) as opposed to others found only in ethanolic extract (chlorogenic acid). Flavonoids were also detected in juice and ethanolic extract. Extract was much richer in flavonoid content when compared to aronia juice. Catechin was present in concentration of 186.3 mg/ 100 g of dry matter in the aronia juice, and 680.65 mg/ 100 g of dry matter in the ethanolic extract, which was more than 3.6 times higher. Quercetin was found only in the extract. The rutin content was 12 times and the chrysin content was 2.5 times higher in the aronia extract. The biggest difference could be noted in the quantitative contents of anthocyanins, 26 times higher concentration in extract than in juice. In general, higher content of bioactive compounds could be observed in the extract than in the juice. The results showed that the ethanolic extract of aronia fruits exhibited antialgal activity against both Prototheca species, while the juice showed no antialgal activity. This difference in antialgal effect is presumably related to the high content of several groups of biocompounds, especially catechin and anthocyanins, present in the ethanolic extract, and probably their synergistic action. There is no comparable data of antialgal effects of aronia in literature.

Introduction. Carcinoma of the esophagus is in the eighth place by the frequency of malignant diseases and the sixth cause of death from cancer worldwide. It usually metastasizes to regional lymph nodes, liver, lungs, central nervous system, and bones, but metastases can appear to unusual locations such as facial skin and lips. Case report. We presented a 56- year-old man who reported to his physician because of upper lip swelling. A physical checkup of the patients also showed a lesion on the skin of the left temporal region and both lesions were biopsied. Based on the results of histopathological and immunohistochemical analyses of the samples a diagnosis of metastatic adenocarcinoma to the skin was established. Additional diagnostic procedures, including esophagogastroduodenoscopy, detected the infiltration into the distal part of esophagus, which was histopathologically confirmed as adenocarcinoma of esophagus. The results of positron emission tomography/computed tomography (PET/CT) examination showed the invasion of the disease. Because of the disease expansion, a multidisciplinary oncology team suggested chemo- and radiotherapy treatment. The patient has received 4 cycles of platinum-based chemotherapy so far. Conclusion. The physicians should always consider unusual skin lesions as the first sign of cancer spreading.

In this paper, we propose a novel method for denoising images corrupted by the mixture of the additive white Gaussian noise and the heavy tailed noise. The proposed method is based on robust statistical approach, i.e. application of M-estimators in the combination with l 1 sparse regularization technique. Thus, we perform the denoising by numerical solving of the convex optimization problem. Additionally, the developed method performs denoising adaptively in order to preserve the image details, by adjusting regularization coefficients according to the local variance. The proposed de-noising scheme produces excellent results, both objectively (in terms of PSNR and MSSIM) and subjectively and outperforms state-of-the-art filters for denoising heavy tailed noise in images.

We present a supervised learning approach for object-category specific restoration, recognition, and segmentation of images which are blurred using an unknown kernel. The novelty of this work is a multilayer graphical model which unifies the low-level vision task of restoration and the high-level vision task of recognition in a cooperative framework. The graphical model is an interconnected two-layer Markov random field. The restoration layer accounts for the compatibility between sharp and blurred images and models the association between adjacent patches in the sharp image. The recognition layer encodes the entity class and its location in the underlying scene. The potentials are represented using nonparametric kernel densities and are learnt from training data. Inference is performed using nonparametric belief propagation. Experiments demonstrate the effectiveness of our model for the restoration and recognition of blurred license plates as well as face images.

This paper presents a new method for unsupervised video segmentation based on mean shift clustering in spatio-temporal domain. The main novelties of the proposed approach are dynamic temporal adaptation of clusters due to which the segmentation evolves quickly and smoothly over time. The proposed method consists of a short initialization phase and an update phase. The proposed method significantly reduce the computation load for the mean shift clustering. In the update phase only the positions of relatively small number of cluster centers are updated and new frames are segmented based on the segmentation of previous frames. The method segments video in real-time and tracks video objects effectively.

In this paper we present a new method for joint denoising of depth and luminance images produced by time-of-flight camera. Here we assume that the sequence does not contain outlier points which can be present in the depth images. Our method first performs estimation of noise and signal covariance matrices and then performs vector denoising. Luminance image is segmented into similar contexts using k-means algorithm, which are used for calculation of covariance matrices. Denoising results are compared with the ground truth images obtained by averaging of the multiple frames of the still scene.

Object segmentation is considered as an important step in video analysis and has a wide range of practical applications. In this paper we propose a novel video segmentation method, based on a combination of watershed segmentation and mean-shift clustering. The proposed method segments video by clustering spatio-temporal data in a six-dimensional feature space, where the features are spatio-temporal coordinates and spectral attributes. The main novelty is an efficient data aggregation method employing watershed segmentation and local feature averaging. The experimental results show that the proposed algorithm significantly reduces the processing time by mean-shift algorithm and results in superior video segmentation where video objects are well defined and tracked throughout the time.