Differences in Outcomes Between Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Breast Cancer Patients in Upper Middle-Income versus High-Income Countries: A Retrospective Study from 4 Oncology Centers.

BACKGROUND Therapeutic options for human epidermal growth factor 2 (HER2)-positive metastatic breast cancer (mBC) are developing rapidly. This study aimed to determine the differences in the survival outcomes of patients with HER2-positive mBC in relation to access to anti-HER therapy at 3 oncology centers in upper-middle-income countries (UMICs) and 1 oncology center in a high-income country (HIC). MATERIAL AND METHODS We retrospectively identified 42 patients from Croatia (HIC), 71 patients from Serbia (UMIC), and 57 from Bosnia and Herzegovina (UMIC) diagnosed with HER2-positive mBC who were treated between January 2015 and December 2020. The pathohistological features of the tumors were obtained from the pathological findings, which were made according to standard procedures for each center. Patients were treated depending on the availability of therapy, which differed for centers in different countries. We evaluated disease-free survival, progression-free survival, and overall survival (OS) based on the availability of first- and second-line anti-HER2 therapy in UMICs vs HIC. RESULTS OS in first-line therapy was better in patients treated with dual HER2 blockade than in patients treated without dual HER2 blockade, P<0.001. OS in second-line therapy was significantly better in patients treated with trastuzumab emtansine than in patients treated with other reported regimens, P=0.004. CONCLUSIONS Results of our study showed superior survival among patients who were treated with dual first-line HER2 therapy as well as second-line trastuzumab emtansine therapy than in those patients in other centers where these drugs were not available. Raising awareness about this could help improve the situation.

Acceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology Clinic of University Clinical Hospital Mostar, Bosnia and Herzegovina: A Cross-Sectional Study.

BACKGROUND The pandemic of Coronavirus infectious disease 2019 (COVID-19) poses a major public health challenge, and an effective vaccine is the potential mechanism to resolve this specific situation. The present study aimed to evaluate acceptance of COVID-19 vaccination among patients attending the Oncology Clinic of University Clinical Hospital Mostar. MATERIAL AND METHODS This cross-sectional observational study enrolled 364 patients with cancer from the Oncology Clinic of University Clinical Hospital Mostar during February 2021. Data were collected using a questionnaire that captured general information about the participants and their attitudes toward COVID-19 vaccination. RESULTS Of the participants, 41.8% answered "Yes" when asked if they would take the vaccine once it becomes available, 37.6% answered "Not sure", and 20.6% answered "No". For patients in favor of vaccination, the main reasons reported were fear of getting sick (77.6%), the desire to contribute to herd immunity (57.8%), and trusting the recommendations of health professionals (57.2%). The main reasons for the patients' vaccination -refusal/indecision were doubts about the results from clinical trials of COVID-19 vaccines (49.1%), concerns about adverse effects (24.5%), and confusion about the various vaccine options (19.8%). The majority of participants (82.4%) stated that recommendation by their oncologist could influence their decision about vaccination. Of the participants who indicated unwillingness (refusal or indecision) to be vaccinated against COVID-19, 65.3% stated that recommendation by their oncologist could influence their decision about vaccination. CONCLUSIONS The findings from the present study showed most patients had refused or were indecisive regarding immunization with COVID-19 vaccine. Increasing physician awareness of this situation may result in higher rates of vaccination.

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.

The Role of Family Physicians in the Prevention and Early Detection of Cancer in Herzegovina-Neretva and West-Herzegovina Canton.

BACKGROUND: This study aimed to investigate and analyze the role of general practitioners/family physicians (GPs/FPs) in counseling and encouraging early cancer prevention, their perception of value systems towards health and disease (especially malignant diseases), knowledge and experience with the national and local cancer early detection program. SUBJECTS AND METHODS: A cross-sectional observational study included 38 GPs/FPs from nine municipalities in the Hercegovina-Neretva and West Herzegovina canton. Data were collected by using an Individual questionnaire for all GPs/FPs which was prepared according to the Questionnaire for family physicians on implementing the Cancer Control Program, which is used in Croatia. RESULTS: Statistical analysis showed that most GPs/FPs carried out activities on primary cancer prevention (educating patients about smoking, alcohol, diet, physical activity, cancer education, and screening). The majority of respondents stated that it was not profitable to do screening for lung cancer and stomach cancer. Most GPs/FPs (73.7%) recommended mammography to women individually, sporadically, according to individual risk assessment. CONCLUSIONS: The scientific contribution and the results of this work can be applied in practice in local communities. Given its position in the health system, ongoing contact with the population that elected it, and its impact on the local community in which it operates, GP/FP plays an important role in the prevention of disease. Integration of preventive activities into the daily work of the doctor plays the most important role in achieving excellent results. Family medicine is primarily focused on primary and secondary prevention, which is carried out through a continuous approach and long-term management of patients.

The Use of Complementary and Alternative Medicine among Cancer Patients Undergoing Conventional Treatment: A Single-Centre Experience.

BACKGROUND: The alternative medicine is increasingly accepted by modern man. People realize that healing based on natural methods is much more affordable and not more aggressive than taking potent drugs of synthetic origin. The aim of this study was to collect data on the use of complementary agents and alternative medicine in cancer patients treated at the Oncology Clinic of the University Clinical Hospital in Mostar. SUBJECTS AND METHODS: We conducted a cross-sectional study that included 100 patients. Data were collected from a questionnaire compiled for this research, which comprised two groups of questions. The first group examined the sociodemographic characteristics of the respondents, and the second the modalities of using Complementary and Alternative Medicine (CAM), and health and conceptual reasons for use. RESULTS: A total of 72 patients (72.0%) had used a CAM during their anticancer treatment. Only 23% of patients had used CAM before the diagnosis of cancer. Among them, 26 (36.1%) previously discussed the topic with their oncologist. CAMs ranged from herbal medicine (58.3%), cannabinoid oil (19.4%) and different vitamins and minerals (22.2%). CAMs were mainly used to improve the health (40.3%). Among patients who used CAM only 25% find it financially demanding, 90.3% of patients were satisfied with effects of CAMs, and 78.1% would recommend it to other cancer patients. CONCLUSION: Our data showed that in our region, many patients used complementary and alternative methods of treatment. These results are very important because they provide information and give a clearer picture of the use of CAM among cancer patients and, accordingly, the right approach of the health practitioners to the patient, leading to optimized cancer therapy and increased safety.

Tumour Size Distribution of Invasive Breast Cancer in a One-Year Period: Case Study Herzegovina.

BACKGROUND: To analyse the early stage breast cancer tumour size distribution as an important prognostic factor among the female patients within our local geographic region of Herzegovina. SUBJECTS AND METHODS: This cross-sectional retrospective study included 379 patients who were treated in 2017 at the Oncology Clinic, University Clinical Hospital Mostar. The patients were divided into two groups based on their primary tumour size: early (≤2 cm) and late (>2 cm) stage groups. RESULTS: The number of patients tested for advanced stage tumours surpassing 2 cm was statistically higher (χ2=106,325; p<0.001). 39.32% (N=149) of the patients presented with tumours ≤2 cm (T1) and 52.24% (N=198) of the total number of the patients presented with tumours >2 cm but ≤5 cm in greatest dimension (T2). The patients' knowledge about breast cancer, availability and adherence of mammography did not show any statistically significant difference with regard to tumour size, while the number of patients with smaller tumours who indicated that they underwent regular mammography was statistically significantly higher (χ2=13,629; p<0.003). CONCLUSIONS: Our data shows that in our region, more women with a diagnosis of breast cancer presented with a larger tumor size. Although there was no statistically significant difference with regard to prior knowledge about breast cancer and availability to mammography, this may be due to a small sample size. Our region does not have a screening mammogram program and this data suggests that the implementation of such a program may improve adherence to existing mammography guidelines which might capture tumors at a smaller size and hence an earlier stage.

Workplace Stress in the University Clinical Settings: Comparison between the Cardiac Unit snd Emergency Center Medical Staff.

BACKGROUND: Stress at work is a specific type of stress arising from the work environment. Stress of the medical staff has been investigated in recent years by the medical institutions of different countries. The aim of this study was to examine the stress levels in medical staff of Department of Cardiac Surgery and Center of emergency medicine (CEM) in the Clinical settings, and to compare them. SUBJECTS AND METHODS: We conducted a cross-sectional study which included 55 patients between 21 and 50 years of age. The study group consisted of 30 employees from the Department of Cardiac Surgery of Mostar University Clinical Hospital, while the control group comprised 25 employees from the CEM. Research instruments were the Occupational Stress Questionnaire for Hospital Health Care Workers (OSQ-HHCW), General Health Questionnaire (GHQ 28) and a Stress MGMT-TEST A. RESULTS: The subjects from the control group had significantly higher stress experience in "bombing" with new information (p=0.028), unavailability of literature (p=0.039), poor communication with superiors (p<0.001), conflicts with patients (p=0.042) and inappropriate public criticism (p=0.007). The highest stress level showed F1 group of stressors, concerning the organization of work and funding. CEM employees had statistically significantly higher level of stress on public criticism and lawsuits compared to the study group (p=0.013), as well as higher score on the anxiety/insomnia subscale (p<0.001), social dysfunction scale (p=0.002) and on the depression subscale (p<0.001). CONCLUSIONS: Stressors from the group of organizational factors have proven to be the most common stressors in both groups. However, in some areas within the impact of workplace stress, CEM employees had significantly greater vulnerability compared to employees of the Department of cardiac surgery. Further studies are needed to establish the frequency and intensity of stress among health professionals, and to clearly determine the risk factors for its development.

GENDER DIFFERENCES IN NEURODEVELOPMENTAL OUTCOMES AMONG FULL-TERM INFANTS WITH INTRAVENTRICULAR HEMORRHAGE.

Intraventricular hemorrhage (IVH) is usually associated with premature infants; however, it has been estimated to occur in up to 5% of infants born at term and may be associated with different prenatal, perinatal and postnatal risk factors. The present retrospective study included toddlers aged 13-24 months, born at term (≥36 weeks), referred to the Department of Rheumatology, Physical Medicine and Rehabilitation in Zagreb, Croatia, because they had at least two risk factors for neurodevelopmental delay. A total of 63 patients without hemorrhage were control subjects, while 103 case patients were children with IVH. The ordinal logistic regression revealed that neurodevelopmental outcome in term infants was associated with IVH grade (p<0.05). Although more boys than girls suffered from severe IVH (grades III and IV), there were no statistically significant gender differences in the distribution of IVH or in neurodevelopmental outcomes (p>0.05).

Clinical Significance and Expression Pattern of RIP5 and VGLL4 in Clear Cell Renal Cell Carcinoma Patients Treated with Sunitinib.

While clear cell renal cell carcinoma (ccRCC) is curable, advanced metastatic (mRCC) remains a clinical challenge. We analyzed clinical, pathohistological, and molecular data (Receptor Interacting Protein 5-RIP5 and Vestigial Like Family Member 4-VGLL4 expression) of 55 mRCC patients treated with first-line treatment with sunitinib. The trend of linear increase in the protein expression of RIP5 was observed with the progression of tumor grade. Overall, 80% of RIP5-positive cells were in the control kidneys and high-grade mRCC. On the contrary, RIP5 displayed low expression in grade 2 mRCC (5.63%). The trend of linear decrease in the expression of VGLL4 was observed with the progression of tumor grade. The highest protein expression of VGLL4 was observed in grade 2 (87.82%) in comparison to grade 3 and 4 and control. High expression of RIP5 mRNA was associated with longer first-line overall survival and longer progression-free survival in mRCC. In addition, a high VGLL4 mRNA expression showed better overall survival in patients with ccRCC. In conclusion, high mRNA expression of RIP5 and VGLL4 are important markers of better survival rates in mRCC patients.

Co-administration of pazopanib and enteral nutrition with omega-3 fatty acids as a safety issue in a patient treated for metastatic clear cell renal cancer: A case report.

Pazopanib is an oral multitargeting tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptors (VEGFRs), approved as the first-line treatment of metastatic renal cell carcinoma (mRCC) and soft tissue sarcoma (STS) at a fixed dose of 800 mg daily taken fasted. Potential drug-meal interactions and adverse events (AEs) may lack recognition and the related data in literature. We report one case of stomatitis/oral mucositis associated with pazopanib administrated with an oral nutritional supplement enriched with omega-3 fatty acids. The 50-year-old patient with mRCC started pazopanib treatment at standard doses of 800 mg daily as first-line therapy for mRCC, and after a few days, he developed stomatitis. Co-administration of pazopanib with high-fat meals could increase the solubility of highly lipophilic pazopanib, increasing its plasma pazopanib area under the curve (AUC), and maximum concentration (Cmax) above optimal therapeutic level can consequently lead to increased frequency/grade of AEs.

Prognostic and predictive significance of VEGF, CD31, and Ang-1 in patients with metastatic clear cell renal cell carcinoma treated with first-line sunitinib.

The most common type of renal cell carcinoma (RCC) is clear cell renal cell carcinoma (ccRCC), which has a high metastatic potential. Even though the International Metastatic RCC Database Consortium (IMDC) risk model is conventionally utilized for selection and stratification of patients with metastatic RCC (mRCC), there remains an unmet demand for novel prognostic and predictive markers. The goal of this study was to analyze the expression of Vascular endothelial growth factor (VEGF), Cluster of Differentiation 31 (CD31) to determine microvessel density, and Angiopoietin-1 (Ang-1) in primary kidney tumors, as well as their predictive and prognostic value in patients with metastatic ccRCC (mccRCC) who were treated with first-line sunitinib. The study included 35 mccRCC patients who were treated with first-line sunitinib in period between 2009 and 2019. Immunofluorescence was used to examine biomarker expression in tissue specimens of the primary tumor and surrounding normal kidney tissue. Median disease-free survival (DFS) was longer in patients with negative and low tumor VEGF score than in patients with medium tumor VEGF score (p=0.02). Those with low tumor CD31 expression had a longer median DFS than patients with high tumor CD31 expression (p=0.019). There was no correlation between Ang-1 expression and DFS. The expression of biomarkers in normal kidney tissue was significantly lower than in tumor tissue (p<0.001). In conclusion, higher VEGF scores and greater CD31 expression were associated with longer DFS, but neither of these biomarkers correlated with progression-free survival or overall survival.

Concomitant Chemoradiotherapy Using Carboplatin and Etoposide-induced Cutaneous Vasculitis in a Patient with Small Cell Lung Cancer.

Drug-induced vasculitis occurs after drug exposure and consequent inflammation of small blood vessels which can lead to damage of affected tissue. Rare cases of drug-induced vasculitis during chemotherapy or concomitant chemoradiotherapy have been described in the literature. Our patient was diagnosed with stage IIIA (cT4N1M0) small cell lung cancer (SCLC). Four weeks after the application of the second cycle carboplatin and etoposide (CE) chemotherapy, the patient developed cutaneous vasculitis and rash on the lower extremities. CE chemotherapy was discontinued and symptomatic therapy with methylprednisolone was administered. On prescribed corticosteroid therapy, there was an improvement in local finding. After completion of chemoradiotherapy, the patient continued treatment with four cycles of consolidation chemotherapy with cisplatin (six cycles of chemotherapy in total). Clinical examination verified further regression of the cutaneous vasculitis. Elective radiotherapy of the brain was performed after completion of consolidation chemotherapy treatment. The patient was clinically monitored until disease relapse. Subsequent lines of chemotherapy for platinum-resistant disease were administered. The patient died seventeen months after diagnosis of SCLC. To our knowledge, this is the first described case of a patient who developed vasculitis of lower extremities during concomitant administration of radiotherapy and CE chemotherapy as a part of the primary treatment for SCLC.

Metastatic Malignant Melanoma Causing Small Bowel Intussusception: A Case Report with 4-year Follow-up.

Primary mucosal malignant melanoma of the small bowel is extremely rare. The small bowel is mostly affected by metastases of the primary malignant melanoma of the skin. Bowel obstruction is a rare complication of metastatic melanoma. We present a case of small bowel obstruction in a 49-year-old man with history of skin malignant melanoma. A segmental resection of the ileum with termino-terminal anastomosis was performed. Pathohistological examination showed metastatic melanoma. After 4 years of follow-up, the patient is still free of the disease.

Rare Human Epidermal Growth Factor Receptor 2 (HER-2)-Positive Neuroendocrine Carcinoma of the Breast: A Case Report with 9-Year Follow-up.

BACKGROUND Neuroendocrine carcinoma of the breast (NECB) is very rare, accounting for 0.1% of all breast tumors and less than 1% of all neuroendocrine tumors. Most NECBs are hormone receptor-positive and human epidermal growth factor receptor 2 (HER-2)-negative and more than 50% are the luminal B subtype. Because prospective studies of NECB are lacking, treatment is the same as for other breast tumors. CASE REPORT A 70-year-old woman was diagnosed with NECB in February 2011. She underwent radical right mastectomy and right axillary node dissection. Final histopathological examination revealed NECB with positive axillary nodes (N1). The tumor cells were 100% positive for estrogen receptors and 10% positive for progesterone receptors. The HER-2 status was 3+. According to the Tumor, Node, Metastasis (TNM) Classification of Malignant Tumors, the pathologic stage was IIB - pT2pN1cM0. The histologic grade was 2 and the Ki-67 proliferation index was 5.7%. The patient received adjuvant chemotherapy, radiation therapy, IV trastuzumab, and endocrine therapy. After 9 years of follow-up, she remains disease-free. CONCLUSIONS As far as we know, this is only the second report describing treatment of HER-2-positive NECB with trastuzumab. A literature review shows that it is the first report of treatment of HER-2-positive primary NECB with adjuvant trastuzumab. In similar cases, long-term follow-up is recommended because of the potential for multiple metastases of NECB even years after completion of adjuvant therapy.

The Usage of Hypoallergenic Cosmetics in Patients with Atopic Dermatitis.

The aim of this study was to investigate how many patients with atopic dermatitis applied hypoallergenic cosmetics compared with topical corticosteroids. The study included 41 patients with atopic dermatitis (AD) who were treated from June 1 to July 1, 2017 at the Department of Dermatology and Venerology, Clinical Hospital Mostar. According to the data analyzed, 46.34% of patients used hypoallergenic cosmetics while 24.39% used them periodically. 32.7% patients used topical corticosteroids and 17.07 % used them periodically. 19.51 % of the patients with atopic dermatitis used alternative products, while 17.07% used them periodically. Out of the total number of patients, most of the patients used neutral products. 78.05% used neutral cosmetic products, and 19.51 % used them periodically. 65.85 % patients used sunscreens and 24.40 % used them periodically. The majority of patients used neutral cosmetic products and sunscreens. There was no statistically significant difference in the frequency of the use hypoallergenic cosmetics compared with topical corticosteroids (χ2 = 1.802; df = 2; P=0.405). Women used sunscreens more often (χ2 = 16,02; df = 1; p = <0,05).

DRAWING SKILLS IN CHILDREN WITH NEURODEVELOPMENTAL DELAY AGED 2-5 YEARS.

In typically developing children, drawing development occurs in stages from uncontrolled strokes to complex drawing. In this study, we examined drawing development in children with neurodevelopmental delay (NDD). In order to do so, we observed the influence of age, intraventricular hemorrhage (IVH) and gender on the development of drawing skills. The sample consisted of 52 children with NDD, aged 2 years and 6 months to 5 years. All children were hospitalized for multidisciplinary team monitoring and developmental support. The evaluation of drawing development was administered by giving each child a blank A4 paper and the instruction to draw anything they wanted. All of the drawings were scored satisfactory or unsatisfactory. Descriptive statistics was employed on all relevant data to show results in frequencies and percentages. In order to determine differences between groups, the χ2-test was administered. The results showed greatest difference in drawing in children aged from 3 years to 3 years and 11 months. Children with lower IVH had better drawing scores than children with higher IVH levels. According to gender dissimilarities, a difference was found showing girls to have better drawing skills than boys. All study results pointed to the importance of early rehabilitation and continuous structured work with children with NDD.