Use of the Depression, Anxiety and Stress Scale (DASS-21) Questionnaire to Assess Levels of Depression, Anxiety, and Stress in Healthcare and Administrative Staff in 5 Oncology Institutions in Bosnia and Herzegovina During the 2020 COVID-19 Pandemic.

BACKGROUND Providing oncology services during a pandemic can contribute to mental health challenges among healthcare workers. The present study aimed to evaluate the levels of depression, anxiety, and stress in healthcare and administrative staff in 5 oncology institutions in Bosnia and Herzegovina (BiH) in 2020 during the coronavirus disease 2019 (COVID-19) pandemic using the Depression, Anxiety and Stress Scale (DASS-21) questionnaire. MATERIAL AND METHODS A cross-sectional observational study enrolled 175 healthcare and administrative workers from 5 oncology institutions in BiH during December 2020. Data were collected using a questionnaire that captured general information about the participants and a DASS-21 questionnaire. RESULTS Statistical analysis revealed a statistically significant difference in the levels of depression, anxiety, and stress (P=0.003, P=0.011, and P=0.022, respectively) among participants with comorbidities connected with increased risk of severe illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) compared with participants without comorbidities. There was also a statistically significant difference in the levels of stress among participants from different cities (P=0.031). Supplement intake and educational level were significantly related (P=0.012). High levels of stress and anxiety were accompanied by high levels of depression among participants (P<0.01). CONCLUSIONS The findings from the present study showed that the COVID-19 pandemic has had an effect on depression, anxiety, and stress levels in oncology staff in BiH. Monitoring these levels and providing interventions and support to oncology staff are increasingly important for their wellbeing and retention at a time of global crisis in healthcare.

CORRELATION OF PERITUMORAL BRAIN EDEMA WITH MORPHOLOGICAL CHARACTERISTICS AND KI67 PROLIFERATIVE INDEX IN RESECTED INTRACRANIAL MENINGIOMAS.

The aim of the study was to analyze correlation between morphological characteristics of intracranial meningiomas and Ki67 labeling index (Ki67 LI), and their influence on peritumoral brain edema (PTBE). There were 41 consecutive patients with intracranial meningiomas surgically treated at the Department of Neurosurgery, Zenica Cantonal Hospital, Zenica, Bosnia and Herzegovina, during the period from January 2010 to December 2015. We reviewed clinical data including patient age, gender, magnetic resonance imaging (MRI) characteristics of the tumor and peritumoral edema, tumor margins, intraoperative characteristics, histopathologic grade and Ki67 LI. In all cases, follow up MRI was obtained at about three months after resection and PTBE was analyzed. Our research showed the tumor volume, tumor margins, and intraoperative signs of arachnoidal and pial invasion to be associated with PTBE in intracranial meningiomas. Ki67 LI expression correlated with PTBE. This study showed the resolution of PTBE to depend on invasive behavior of meningioma and KI67 LI. PTBE, pial/cortical and arachnoidal invasion significantly influence the extent of surgical resection.

Understanding the Significance of Hypoxia-Inducible Factors (HIFs) in Glioblastoma: A Systematic Review.

BACKGROUND: The study aims to investigate the role of hypoxia-inducible factors (HIFs) in the development, progression, and therapeutic potential of glioblastomas. METHODOLOGY: The study, following PRISMA guidelines, systematically examined hypoxia and HIFs in glioblastoma using MEDLINE (PubMed), Web of Science, and Scopus. A total of 104 relevant studies underwent data extraction. RESULTS: Among the 104 studies, global contributions were diverse, with China leading at 23.1%. The most productive year was 2019, accounting for 11.5%. Hypoxia-inducible factor 1 alpha (HIF1α) was frequently studied, followed by hypoxia-inducible factor 2 alpha (HIF2α), osteopontin, and cavolin-1. Commonly associated factors and pathways include glucose transporter 1 (GLUT1) and glucose transporter 3 (GLUT3) receptors, vascular endothelial growth factor (VEGF), phosphoinositide 3-kinase (PI3K)-Akt-mechanistic target of rapamycin (mTOR) pathway, and reactive oxygen species (ROS). HIF expression correlates with various glioblastoma hallmarks, including progression, survival, neovascularization, glucose metabolism, migration, and invasion. CONCLUSION: Overcoming challenges such as treatment resistance and the absence of biomarkers is critical for the effective integration of HIF-related therapies into the treatment of glioblastoma with the aim of optimizing patient outcomes.

Guidelines for breast cancer management in Bosnia and Herzegovina.

Breast cancer is the most common cancer among women. In Bosnia and Herzegovina, accurate data on the status of breast cancer are lacking due to the absence of a central registry. Multiple international guidelines imply that institutions that monitor breast cancer patients should have optimal therapeutic options for treatment. In addition, there have been several international consensus guidelines written on the management of breast cancer. Application of consensus guidelines has previously been demonstrated to have a positive influence on breast cancer care. The importance of specialty breast centers has previously been reported. As part of the 2021 Bosnian-Herzegovinian American Academy of Arts and Sciences (BHAAAS) conference in Mostar, a round table of multidisciplinary specialists from Bosnia and Herzegovina and the diaspora was held. All were either members of BHAAAS or regularly participate in collaborative projects. The focus of the consortium was to write the first multidisciplinary guidelines for the general management of breast cancer in Bosnia and Herzegovina. Guidelines were developed for each area of breast cancer treatment and management. These guidelines will serve as a resource for practitioners managing breast cancer in the Bosnia and Herzegovina region. This might also be of benefit to the ministry of health and any future investors interested in developing breast cancer care policies in this region of the world.

Analysis of chemotherapy and molecular therapy efficiency in advanced or metastatic non-small cell lung cancer.

AIM: To compare a benefit of chemiotherapeutic protocols docetaxel with Tarceva molecular therapy in advanced or metastatic non-small cell lung cancer (NSCLC). Primary endpoint-OS (overall survival), toxicity, secondary endpoint-quality of life. PATIENTS AND METHODS: In this retrospective and -prospective study a total of 63 patients (two groups--30+33 patients) were analysed and treated for advanced or metastatic NSCLC during the period 2008-2010. One group was treated with molecular therapy Tarceva oral, and the other group was treated with chemiotherapy docetaxel monotherapy every three weeks. The chemotherapy was administered intravenously. Monitoring parameters included overall survival and toxicity. RESULTS: Statistical differencet was registered in histology type, total toxicity and total survival. Adenocarcinom occured as a more often pathohistologic type in both groups of patients (Tarceva 57, 6% vs. Docetaxel 83, 3%). The chemiotherapeutic protocol, Docetaxel monotherapy, demonstrated higher total toxicity than Tarceva molecular therapy (hematological toxicity grade II 69.0% Docetaxel vs. 12.5% Tarceva). Tarceva molecular therapy demonstrated longer overall survival (OS) than Docetaxel (Tarceva 26, 4 months vs. Docetaxel 15, 5 months). CONCLUSION: In this investigation of two groups of patients the molecular therapy Tarceva was showed better efficiency and toxicity profile. Preferred regimen could be molecular therapy Tarceva.

The Oncology Association of Bosnia and Herzegovina's recommendations for fertility preservation in oncologic patients.

Malignancy is one of the major public health problems in Bosnia and Herzegovina. Along with breakthroughs in specific oncological therapy, improving the quality of life of cancer patients and management of therapy-induced side effects need to be recognized as a priority in the comprehensive cancer patient care. Fertility loss after cancer treatment is a field requiring special attention due to its various consequences on patients themselves.  Although oncofertility is well-recognized area of oncology, low- to middle-income countries are facing issues with its implementation in everyday practice. Increased awareness about fertility preservation is of high priority for all specialists who participate in the medical care of cancer patients. The absence of a systemic solution and lack of expertise led to the founding of Fertility Preservation Working Group of the Oncology Association of Bosnia and Herzegovina. We have made recommendationsas an expert consensus with the ultimate goal of making the first step towards enhancement of oncofertility implementation in Bosnia and Herzegovina.

2020 consensus guideline for optimal approach to the diagnosis and treatment of HER2-positive breast cancer in Bosnia and Herzegovina.

The HERe2Cure project, which involved a group of breast cancer experts, members of multidisciplinary tumor boards from healthcare institutions in Bosnia and Herzegovina, was initiated with the aim of defining an optimal approach to the diagnosis and treatment of HER2 positive breast cancer. After individual multidisciplinary consensus meetings were held in all oncology centers in Bosnia and Herzegovina, a final consensus meeting was held in order to reconcile the final conclusions discussed in individual meetings. Guidelines were adopted by consensus, based on the presentations and suggestions of experts, which were first discussed in a panel discussion and then agreed electronically between all the authors mentioned. The conclusions of the panel discussion represent the consensus of experts in the field of breast cancer diagnosis and treatment in Bosnia and Herzegovina. The objectives of the guidelines include the standardization, harmonization and optimization of the procedures for the diagnosis, treatment and monitoring of patients with HER2-positive breast cancer, all of which should lead to an improvement in the quality of health care of mentioned patients. The initial treatment plan for patients with HER2-positive breast cancer must be made by a multidisciplinary tumor board comprised of at least: a medical oncologist, a pathologist, a radiologist, a surgeon, and a radiation oncologist/radiotherapist.

Efficacy and Safety of Lysozyme, Cetylpyridinium and Lidocaine Fixed Combination for Treatment of Chemotherapy- and Radiotherapy-Induced Oral Mucositis: a Pilot Study.

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.

Efficacy and safety of local lysozyme treatment in patients with oral mucositis after chemotherapy and radiotherapy.

This observational clinical study was composed of two substudies: a non-comparative one (n = 166), testing only lysozyme-based compounds (LBCs), and a comparative substudy (n = 275), testing both LBCs and bicarbonate-based local compounds (BBCs) on the healing of oral mucositis during radio- or chemotherapy. The density of ulcerations has decreased significantly after the treatment with lysozyme in both substudies. The density of ulcerations in the radiotherapy group was lower in patients treated with LBCs compared to patients treated with BBCs (p < 0.001). In the chemotherapy group, reduction of ulceration density was similar with both LBCs and BBCs. The LBCs reduced pain intensity during the intake of solid food and speech more than BBCs in both patient cohorts (p < 0.05). In the radiotherapy cohort, pain intensity when consuming liquid foods was reduced more with LBCs than with BBCs (p < 0.05). No adverse events were recorded. This study demonstrates the advantages of treating oral mucositis during radiotherapy or chemo-therapy with LBCs.

Significance of diffusion weighted imaging (DWI) as an improving factor in contrast enhanced magnetic resonance imaging (MRI) enterography in evaluation of patients with Crohn's disease.

Aim To determine capabilities and potential of contrast enhanced magnetic resonance imaging (MRI) enterography in order to establish the diagnosis and to evaluate severity and activity of intestinal inflammation. Methods Fifty-five patients with suspicion for presence of Crohn's disease were evaluated. All patients underwent contrast enhanced MRI enterography and diffusion weighted imaging (DWI), and subsequently endoscopic examination or surgical treatment. Four parameters were analysed: thickening of the bowel wall, and presence of abscess, fistula and lymphadenopathy. Results Comparing results of DWI and contrast enhanced MRI enterography a significant difference between results given through diffusion and histopathological test was found, e.g. a significant difference between results obtained through diffusion and MRI enterography was found. MRI enterography sensitiveness for bowel wall thickening was 97.7% and specificity 70%, whilst DWI sensitivity for bowel wall thickening was 84% and specificity 100%. The diagnostics of abscess and fistula showed no significant difference between DWI and MRI, while in lymphadenopathy significant difference between contrast enhanced MRI enterography and DWI was found. Conclusion Contrast enhanced MRI enterography in combination with DWI allows for excellent evaluation of disease activity, but also problems or complications following it. The examination can be repeated, controlled, and it can contribute to monitoring of patients with this disease.

Spontaneous brain and arachnoid herniation into the dural venous sinuses: a rare anatomic variation or clinical entity?

Aim To investigate the presence, type and distribution of spontaneous brain and arachnoid herniation into the dural venous sinuses as well as a clinical significance of these herniations. Methods This retrospective - prospective, non-randomised anatomical and clinical study included 990 patients who were referred to Magnetic Resonance Imaging at the Department of Radiology of the Cantonal Hospital in Zenica in the period from January to December 2016. The T1 and T2 sequences in axial, sagittal, and coronary section were used for brain or arachnoid herniation analysis. In all patients with intra-sinusal herniation health records were analysed and symptoms and reasons to refer for MRI examination were evaluated . Results In 26 (2.6%) patients (19 females; 73.08%) the arachnoid or brain herniation was found. Average age of patients was 40.269±16.496 years. Arachnoid herniation was presented in 15 (57.69%) and brain herniation in 11 (42.31%) patients. Statistical significance in relation to type of herniation was not found (p=11.070). Statistical significance between the symptoms and localisation of herniation (except for nausea and vomiting and posterior fossa herniations) (p=0.05) as well us between symptoms and type of herniation was not found (p>0.05). Conclusion The results suggest that there is a possibility of interconnection between arachnoid or/and brain herniations and some clinical symptoms such as nausea and vomiting.

COST OF FEBRILE NEUTROPENIA TREATMENT IN BOSNIA AND HERZEGOVINA.

Febrile neutropenia is common chemotherapy complication significantly impacting patient's outcomes, quality of life and costs, too. Febrile neutropenia (FN) often leads to hospitalization, the need for intravenous antibiotics and use of granulocyte colony-stimulating factors (GCSF) in order to avoid its complications. Cost of febrile neutropenia is well described in literature, but no study has been performed in Bosnia and Herzegovina. We have conducted observational cohort study with aim to describe and present costs of FN treatment from payers' (provider's) perspective. Only direct medical costs from one middle-sized oncology Clinic in Bosnia and Herzegovina database have been included and presented. We found that overall cost in five months period (January-May 2015) were almost 30.000 euros, or 1.0035 euro per episode/patient in average. The highest cost are allocated to hospitalization (40%), followed by GCSF (36%), while rest of costs are generated by laboratory tests performed and drug application. Proportion of costs is in line with other published studies even with huge differences in absolute values, mainly to low prices of services in Bosnia and Herzegovina. This was the first study on costs of chemotherapy induced FN in Bosnia and Herzegovina suggesting that significant costs are inquired by this conditions and that further research should be performed including larger patient population and other clinical oncology data, including pharmacoeconomic analysis.

Impact of timing on surgical outcome in patients with cauda equina syndrome caused by lumbar disc herniation.

Aim To analyze the relationship between timing of surgery and outcome in patients with cauda equina syndrome caused by lumbar disc herniation. Methods A retrospective, non-randomized clinical study included 25 consecutive patients with cauda equina syndrome (CES) caused by lumbar disc herniation. All patients were operated within 24 hours after hospitalization at the Department of Neurosurgery, Cantonal Hospital Zenica, Bosnia and Herzegovina, between January 2000 and December 2010. All patients were evaluated before surgery on the basis of complete history, neurological examination and neuroimaging evaluations using CT (computed tomography)and MRI (magnetic resonance imaging). Results Statistically significant difference between preoperative and postoperative bladder (p=0.05) and bowel (p=0.05) function was found. A significant number of patients had bladder and bowel recovery after surgery, nine (36%) and 11 (44%), respectively. Significant recovery of muscle strength was noted with complete recovery(5/5) in 12 (48%) and partial recovery in 13 (52%) patients. Complete sensory recovery was noted in 16 (64%), incomplete in four (16%), and in five (20%) patients there were no changes. Most commonly, patients with complete sensory recovery were operated within 48 hours of symptom onset. In most patients early surgery was associated with better outcome. Conclusion This research showed that early decompression correlated with better outcome. Patients with cauda equina syndrome must be cleared for surgery in optimal conditions and, if it possible within optimal timing for recovery (within 48 hours).

Therapeutic efficacy and toxicity of bolus application of chemotherapy protocol in the treatment of metastatic colorectal cancer.

AIM: To compare efficacy and toxicity of bolus application of chemotherapy protocol, oxaliplatin, fluorouracil (bolus), leucovorin (folfox) between two groups of patients in the therapy of metastatic colorectal carcinoma (mCRC). METHODS: A total of 63 patients were treated for mCRC in the period January 2009 - January 2010 at the Department of Oncology of the Cantonal Hospital Zenica, Bosnia and Herzegovina (first group, 30 patients) and at the Department of Oncology of the Clinical Hospital Centre Bezanijska kosa in Belgrade, Serbia, in the period January 2005 - January 2006 (second group, 33 patients). The patients were treated according the same protocol, i.v. bolus infusion, but in different day intervals (D), 1, 8, 15/28 days or D1-D5/28 days, respectively. In all patients the following factors were analyzed: tumor response, overall survival (OS), progression free survival, hematological and non-hematological toxicity . RESULTS: Colon was the primary localization in almost two thirds of patients. There was no statistically significant difference between the groups according to the age, hematological and non-hematological toxicity, as well as in achieved OS. Progression free survival expressed in months was in average 5 months though with a large range between minimal and maximal survival time. CONCLUSION: Both groups have shown equivalent efficacy to applied chemotherapy protocols. Overall survival in the two groups matched data from the literature. Further research should confirm success of the combination of chemotherapy protocols and their combination with the biological therapy.

Atypical localization of lung cancer located in lobus v. azygos.

Lobus v. azygos (lobe of the azygos vein, azygos lobe) is an accessory lobe of the right upper lobe of the lung that corresponds to the anatomical variety. The presence of expansive lesions in it represents unusual radiographic findings. This paper presents the case of a patient with an extensive expansion process in azygos lobe, radiologically diagnosed by standard radiography (X-ray) and Multislice Computed Tomography Scan (MSCT). The process was subsequently treated surgically and confirmed histologically as a non-small-cell lung adenocarcinoma.

[Chronic epidural haematoma mimicking meningioma]. / Hronicni epiduralni hematom dijagnosticiran kao meningeom.

The study presents a rare case of organised chronic epidural haematoma that imitated a meningioma. A patient was admitted to the Department of Neurology of the Cantonal Hospital Zenica due to loss of consciousness and right hemiparesis. Non-contrast Computed Tomography (CT) scan had shown an expansive intracranial process in the left parietal region which was radiologically diagnosed as a meningioma. During the operation a linear skull fracture and organised chronic epidural haematoma were found.

[Endometrial cancer associated with an increase of CA 15 3 and CA 125 in tamoxifen treated patients with breast cancer]. / Endometrijalni karcinom povezan s porastom CA15_3 i CA 125 u bolesnice s karcinomom dojke lijecene tamoksifenom.

The study presents a case of endometrial cancer in a breast cancer patient treated with tamoxifen. The disease occured with elevated values of CA 125 and CA 15_3 tumour markers without any other signs. Additional diagnostic analyses were performed showing a "de novo" endometrial cancer rather than metastatic breast cancer. The patient underwent surgery and radiotherapy. Thereafter, the values of tumour markers were in the reference values.

Analysis of chemiotherapeutic protocols efficiency in therapy of advanced non small cell lung cancer.

AIM: To confirm the efficiency and toxicity of two chemiotherapeutic protocols- Cisplatin Gemcitabin (CDDP, Gemcitabin) and Cisplatin, Vinorelbin (CDDP, Vinorelbin) in advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Retrospectively were analyzed and treated a total of 60 patients (two groups with 30 patients) for advanced or metastatic NSCLC during the period from January 2005 to January 2007. The patients were treated with chemiotherapeutic protocols CDDP, Vinorelbin and CDDP, Gemcitabin for four weeks. The chemiotherapy was administered intravenously. RESULTS: Although registered response rates were a bit lower than in previously published trials, they were not significantly different in two arms (26% vs. 15%) (p = 0.485). Statistically different were therapeutic responses in SD (CDDP, Vinorelbin 44% vs. CDDP, Gemcitabin 93,3%) (P < 0.001) and OS (CDDP, Vinorelbin 10.83% vs. CDDP, Gemcitabin 21.00%) (p < 0.05). Cisplatin, Vinorelbin regimen has shown a higher hematologic (9% vs. 7%), and total toxicities (p = 0.0029). CONCLUSION: In this investigation of two groups of patients, Cisplatin, Gemcitabin regimen has shown better efficiency and toxicity profile. Preferred regimen could be Cisplatin, Gemcitabin.