Introduction: Oxidative stress and lipid peroxidation are pointed as possible factors in the development of colorectal cancer (CRC). The aim of this study was to assess the serum malondialdehyde (MDA) and non-enzymatic antioxidants concentration (albumin, bilirubin, uric acid, and ferritin) and their relation with the stage and histopathologic size (pT) of CRC. Methods: One hundred and twenty patients with clinically and histopathologically confirmed CRC and the need for surgical treatment were included in a cross-sectional study. All patients were divided into groups according to the disease stage and depth of tumor invasion. The control group included 30 subjects with no signs of malignant and inflammatory bowel disease. The patients and controls did not receive vitamin supplementation. Peripheral venous blood was sampled before the surgical treatment of CRC patients and on the day of the examination of control subjects for determination of serum MDA and the concentration of the non-enzymatic antioxidants. Results: The serum levels of MDA were progressively increased in CRC patients with the highest level in the fourth stage of disease and pT4 group. Ferritin levels increased significantly with the CRC stage and decreased with the depth of bowel wall invasion. Serum albumin concentration significantly decreased with increasing stage and increasing depth of tumor invasion of the intestinal wall, while serum bilirubin level showed no change compared to the control group. Serum uric acid concentration was significantly higher in CRC patients, but no difference was observed with CRC progression. It was confirmed that serum albumin significantly negatively correlated with the CRC stage (rho = −0.649, p < 0.001), while serum MDA significantly positively correlated with the CRC stage (rho = 0.750, p < 0.001). Conclusion: These results indicate that serum MDA concentrations are related to the progression of CRC, to which the imbalance in non-enzymatic antioxidants also contributes.

Abstract Background An optimal adjuvant treatment of HER2 positive breast cancer includes the initiation of trastuzumab within 6 months after the surgery. However, due to limited resources and waiting lists, this timeframe is often exceeded in developing countries. We previously reported short-term outcomes of a time-optimal versus delayed postoperative initiation of trastuzumab in women with HER2 positive, non-metastatic, neoadjuvant naive breast cancer. Here, we report an extended follow-up, summarizing outcomes of our cohorts. Methods We included 223 consecutive women with surgically treated, non-metastatic, neoadjuvant naive, HER2 positive breast cancer from 2009 to 2011, from four institutions in Bosnia and Herzegovina. Patients were assigned to a time-optimal group (TOG), or a delayed group 1 (DG1), or a delayed group 2 (DG2), depending on whether their adjuvant trastuzumab was initiated 6 months, or 6-12 months, or more than 12 months after the surgery, respectively. A cut-off point for the follow-up was January 2019. We compared clinical outcomes between the groups, taking into account lymph node status. Results The patient’s median age was 55 (range 27-80) years. Mean follow-up period was 67 (range 4-109) months. Node-negative disease was found in 38.6% patients overall. 37% (TOG) patients received trastuzumab within 6 months, while 41% (DG1) received it within 6-12, and 22% (DG2) more than 12 months after their surgery. A higher number of node negative patients was found in the DG2 group compared to the TOG and DG1 groups (48%, 35%, and 36% respectively). 5-year DFS rate was 70.73% (TOG), 67.03% (DG1), and 62.00% (DG2). The OS rate was 78.05% (TOG), 75.82% (DG1), and 74.00% (DG2). Conclusions From the above, a conclusion can be made that patients with time-optimal initiation of adjuvant trastuzumab therapy had a higher 5-year DFS and OS rate compared to the delayed treatment initiation groups. Results of the DG1 and the DG2 group indicate that trastuzumab therapy shows a persistent benefit even if administered with a delay. Higher DFS and OS rates in the DG2 group could be explained by a higher number of node-negative low-risk, patients in this group. Legal entity responsible for the study The authors. Funding Roche. Disclosure S. Beslija: Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Novartis; Advisory / Consultancy: MSD; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer. T. Ceric: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: MSD; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Novartis. B. Hasanbegovic: Advisory / Consultancy: Roche. A. Pasic: Advisory / Consultancy: Merck; Advisory / Consultancy: Sanofi. All other authors have declared no conflicts of interest.

Introduction: Beneficial effect of local administration of lysozyme in patients with recurrent aphthous stomatitis was demonstrated, but there are no published studies focused on treatment of chemotherapy or radiotherapy induced oral mucositis with lysozyme. Aim: The aim of this study was to compare efficacy and safety of Lysobact Complete spray (lysozyme, cetylpyridinium, and lidocaine) and compounded medication for local use in the treatment of radio- and chemo-therapy induced oral mucositis. Patients and Methods: This observational, phase IV study was designed as prospective cohort investigation, and conducted at two sites, Clinical Hospital Zenica and University Clinical Center Tuzla, Bosnia & Herzegovina, from August to November, 2018. The patients with oral mucositis after radio- or chemo-therapy were treated by either registered lysozyme-based or compounded medication (standardized and bicarbonate-based) for 21 days. Results: Both lysozyme-based (Lysobact Complete Spray) spray (lysozyme, cetylpyridinium and lidocaine) and compounded medication for local use were effective in local treatment of chemotherapy and radiotherapy-induced oral mucositis. However, lysozyme-based preparation was more effective, since signs of inflammation, number of oral ulcers and intensity of pain during eating and speaking withdrew to a greater extent than with highly variable compounded medication for local use. No adverse events were recorded in both treatment arms. Conclusions: Locally administered spray with fixed combination of lysozyme, cetylpyridinium and lidocaine (Lysobact Complete Spray) is very efficient and completely safe treatment of both radiotherapy and chemotherapy-induced oral mucositis.

Aim To compare the effect of neoadjuvant chemotherapy based on taxane and/or anthracycline to the extent of an objective response in female patients with unresectable breast cancer with evaluation of the toxic profile of applied chemotherapy. Methods One hundred patients with histologically verified breast cancer, treated with neoadjuvant chemotherapy were divided into two groups: a study group A (50 patients), who had received 4 to 6 cycles of taxane-based chemotherapy, and control group B (50 patients), who had received 4 to 6 cycles of anthracyclines-based chemotherapy. Pathohistological response was evaluated after tumour excision and axillary resection at the end of chemotherapy and it was defined as pathologic complete (pCR), partial (pPR), or no response (pNR). Toxic effects were evaluated and quantified by the Common Terminology Criteria for Adverse Events v4.0. Results After neoadjuvant chemotherapy, 8% of patients in the group A achieved pCR, 54% achieved pPR, while 38% of patients had no tumour response to applied chemotherapy. In the group B pCR was achieved in 6%, pPR in 42% of patients, while 51% of patients were pNR to the administered chemotherapy. Significant reduction of tumour mass was achieved in the group of patients treated with taxanes: 20.00 (7.75-30.25) vs. 13.50 (6.00-25.00) mm (p=0.024). Toxicity of chemotherapy in group A and group B was within the limits of grade 2. Conclusion The addition of taxane to anthracycline-based neoadjuvant chemotherapy in patients with breast cancer resulted in a significant reduction in tumour mass compared to the group of patients treated with anthracyclines, but without increasing the overall side effects.

SUMMARY – The purpose of the study was to assess the level of serum malondialdehyde (MDA) concentration and its association with the stage and histopathologic sizes of colorectal cancer (CRC). One hundred and two patients having undergone surgical treatment of CRC between January 2014 and December 2015 were included in this cross-sectional study. The patients were divided into four groups (stage I-IV) according to the TNM classification. Control group included 30 subjects with no signs of malignancy and inflammatory diseases. In each patient, preoperative blood samples were obtained for determination of MDA concentration by ELISA immunoassay. Serum levels of MDA were progressively increased in patients with CRC, reaching the highest value in the fourth stage of CRC. Serum concentrations of MDA were significantly higher in pT4 group as compared with pT3 and pT2 groups of CRC patients (p<0.01). Significantly higher levels of MDA were found in the N1 and N2 groups of CRC patients as compared with N0 group, as well as in patients with metastatic disease as compared with those without metastasis (p<0.001). In conclusion, the progression of CRC is associated with a significant increase in serum MDA levels.

Background Tumor development and growth are driven in many cases by inflammatory cells, which can produce cytokines and other factors that can stimulate the development of the malignant process. The aim of this study was to evaluate interleukin-6 (IL-6), C-reactive protein (CRP), matrix metalloproteinase-9 (MMP-9), serum levels in patients with colorectal cancer (CRC), and their association with the stage of CRC. Methods IL-6, MMP-9, and CRP serum levels were measured in 75 patients with CRC just before surgical treatment, as well as in 20 healthy individuals as controls. Surgically obtained tissue material was subjected to pathological analysis. Results Significant increase in CRP and IL-6 serum concentration is associated with increasing stage of CRC (p <0.05), where MMP-9 serum level was significantly higher in stages III and IV compared to the stage II CRC. Significant correlation was found between IL-6 and MMP-9 serum levels (rho=0.478; p <0.001) as well as between IL-6 and CRP serum levels (rho=0.720; p <0.001) and between MMP-9 and CRP serum levels (rho=0.379; p <0.001). Serum levels of MMP-9 and CRP have been shown to be independent predictors of the CRC stage. Conclusion Combined quantification of IL-6, MMP-9, and CRP serum levels seems to be a reliable index of inflammation-related processes during colorectal carcinogenesis.

Aim To determine the serum levels of matrix metalloproteinase 9 (MMP-9) concentration and their association with the stage and histopathologic sizes of colorectal cancer (CRC). Methods One hundred and two patients with clinically diagnosed and histologically confirmed colorectal cancer ready for surgical treatment were included in the study. In each patient, preoperative peripheral venous blood samples were taken for determination of the concentration of MMP-9 using ELISA immunoassay test. Resected tumour specimens were studied pathologically according to the criteria of the TNM classification. All patients were divided into groups according to the TNM classification. The control group presented 30 subjects of the appropriate age and gender with no family history of cancer, clinical signs of malignancy or inflammatory bowel disease. Results The serum levels of MMP-9 were progressively increased in patients with CRC reaching the highest value in the fourth stage of CRC. It was also confirmed that the serum concentrations of MMP-9 were significantly higher in patients with pericolonic lymph nodes involvement compared to the patients with no involvement of lymph nodes, 456.4 (445.9-464.7) ng/mL vs. 438.4 (418.4-447.8) ng/mL (p<0.001). Significantly higher serum levels of MMP-9 were found in the patients with metastatic CRC, 458.5 (452.0-468.1) ng/mL compared with the CRC patients without metastasis, 445.8 (436.9-456.5) ng/mL (p<0.001). Conclusion It was confirmed that serum concentration of MMP-9 presented the significant independent risk factors for the progression of CRC.

Goal: The goal of this study was the determination of the effects in treatment of early stage (<IIB) and locally advanced stages (≥IIB) of uterine cervical carcinoma by using MRI. Material and Methods: The study was a prospective, comparative, analytical, and observational and included 74 patients with cervical cancer (PH confirmed). All 74 patients have initially gone through the pre-therapeutic MRI to determine the tumour FIGO stage. At a renewal of the initial MRI findings, patients were divided into two study groups: group A and group B. Group A consisted from 39 patients with early-stage cervical carcinoma (<IIB) and group B comprised from 35 patients with locally advanced stage (≥IIB). Postterapeutic MRI control, were perfomed in both group (A and B). Further MRI examinations were set for the patients from both groups. Results: An analysis of treatment outcomes in group A showed that most patients had no local recurrence or residuum disease in 89.7%, while local recurrence was observed in only 10.3% cases. An analysis of treatment outcomes in group B showed that most patients had complete regression after local chemoradiotherapy in 68.8%, while 25.7% of patients had local progression of the disease, while the 5.7% cases recorded partial local tumour regression(p<0.05). It has been shown that a complete local regression was more frequent in the case of squamous cell carcinoma in 74.2% vs 25% in adenocarcinoma cases. Also local and partial regression was observed more frequently in the case of squamous cell carcinoma in 6.5% compared to 0% in adenocarcinoma, while progression was more common in adenocarcinoma at 75% compared to 19.4% for squamous cell (p<0.05). MRI results showed positive outcome of treatment group A and B in our study, showed a statistically significant difference in favour of group A (89.7%) compared to group B 68.8% (p<0.05). Conclusion: The results obtained from our studies show that early stage cervical cancer (<IIB) shows a better outcome in treatment of advanced stages (≥IIB). In the treatment of advanced stages (≥IIB), concomitant radio chemotherapy shows significant results in terms of complete tumour regression, especially in squamous cell type of cervical cancer.

Objective: Expenditures for drugs are increasingly burdening already insufficient funds for health protection. This is especially evident in less developed European countries such as Bosnia and Herzegovina. The question is whether such analyses can help save funds for financing treatment for diseases, with an emphasis on a more rational choice of drug for appropriate indication, whereby clinical complications of hypertension would be prevented and patients would have quality of their lives improved. Aim: Focus of research has been set on analysis of use of antihypertensive drugs in Bosnia and Herzegovina in the time-period January 2013–March 2015. Use of all drugs for treatment of hypertension in that time-period in the country has been shown in an unbiased manner. Methods: The study is designed as retrospective-prospective comparative research of use of antihypertensive drugs in BiH in a certain time-period. Data are collected from relevant drug utilisation database which has been established in Bosnia and Herzegovina since 2013. Results: We have calculated financial expenditure for prescribed antihypertensives in the time- period of 2013, 2014 and Q1 2015. Use of antihypertensives at the country level for this time-period is BAM 200,242,218. At the country level, physicians are most often opting for combination therapy: ACE inhibitors + diuretics (20.2%) and ACE inhibitors + Ca channel antagonists (18.0%). Conclusion: In this research, it has been shown that modern drugs are used for treatment of hypertension in Bosnia and Herzegovina. These drugs are used in the same order as they are prescribed in developed countries.