Simple Summary This study explores hypoxia-inducible factors (HIFs) in glioblastoma development, progression, and treatment. Reviewing 104 relevant studies, it highlights diverse global contributions, with China leading at 23.1%. The most productive year was 2019, contributing 11.5% of the studies. Key factors studied included HIF1α, HIF2α, osteopontin, and cavolin-1, involving pathways such as GLUT1, GLUT3, VEGF, PI3K-Akt-mTOR, and ROS. HIF expression correlates with glioblastoma progression, survival, neovascularization, glucose metabolism, migration, and invasion. Overcoming treatment resistance and the lack of biomarkers is crucial for integrating HIF-related therapies into glioblastoma treatment to improve patient outcomes. Abstract 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.

Aim: The primary aim of the study was to determine the incidence of testicular neoplasms in the Zenica-Doboj Canton (ZDC) region for the period from 2019 to 2021. Also, the study aimed to examine the age structure of the affected population, the frequency of testicular neoplasms in all the ZDC cities and municipalities, and the pathohistological characteristics of neoplasms. Material and methods: The study was conducted at the Oncology and Radiotherapy Department of the Zenica Cantonal Hospital. The study period refers to the time interval from January 2019 to December 2021. The study included 37 patients with a verified diagnosis of testicular neoplasm. Results: Arithmetic mean of patients’ age was 33.49 years, while the standard deviation was 12.59. Most respondents, accounting for 40.5%, were aged 26-35 years. The incidence of testicular neoplasms in the ZDC region was 4.2/100,000 per - sons in 2019, 3.08/100,000 persons in 2020, and 3.10/100,000 persons in 2021. Most diagnosed neoplasms (48.6%) were the myxoid type germ cell originating tumors. Conclusion: The incidence of testicular neoplasms in the ZDC was 4.2/100,000 persons in 2019, 3.08/100,000 persons in 2020, and 3.10/100,000 persons in 2021.

Breast cancer is the most common cancer among women. In Bosnia and Herzegovina (BiH), 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 BiH 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 BiH. 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 BiH 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.

Abstract 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.

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.

SUMMARY 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.

O bjective − To analyse the results of the surgical treatment of myelomeningocele in the Zenica Cantonal Hospital in a five-year period. P atients and methods − This retrospective study included 10 patients with myelomeningocele, surgically treated at the Department of Neurosurgery, Zenica Cantonal Hospital, in the 2011-2016 period. Patients were assessed based on their history, symptoms and neurological state. In all cases we performed a detailed neurological examination and craniospinal Magnetic Resonance Imaging. In most cases we performed surgery within the first 72 hours after birth. In three patients we did not perform early surgery because the parents did not give consent for the operation in this period. All patients were hospitalized at the Department of Paediatrics, Zenica Cantonal Hospital. The patients were followed up by a neurosurgeon, a paediatric surgeon and a paediatrician. R esults − In our research, the incidence of myelomeningoceles in females and males was equal. In most cases the surgery is the most devastating congenital malformation compatible with survival. Newborns with late antenatal diagnosis must undergo surgery as soon as possible, preferably within 24-72 hours. Despite limited resources and conditions we documented a significant recovery in most patients. Conclusion − Myelomeningocele is the most devastating congenital malformation compatible with survival. Newborns with late antenatal diagnosis must undergo surgery as soon as possible, preferably within 24-72 hours. Despite limited resources and conditions we documented significant recovery in most patients.

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).

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.

Abstract In this case, we have presented a 55-year old patient with dysuria and bloody urine. He was hospitalized at the Urology Department of County Zenica Hospital due to obstructive uropathy. Diagnostics showed the cause is a large bleeding mass in prostatic part of urethra. After cystectomy, immunohistochemistry revealed urachal adenocarcinoma, rare type of urogenital carcinomas, presented only in 5% of all cancer types. He was treated with dual modality, chemotherapy and radiotherapy

Objective – We report an unusual case of split cord malformation (SCM) associated with open spinal dysraphism and other anomalies of the central nervous system. Case report – A male newborn was admitted to the Pediatric Intensive Care Unit immediately after birth by Caesarean delivery. Clinical examination and diagnostics (MRI) showed open spinal dysraphism in the distal part of the spine (level L5 and S1), split cord malformation type I which separated two hemicords, tethered cord and syringomyelia. Two days after birth microneurosurgery was performed. Cranial and cervical MRI showed Chiari I and corpus callosum hypoplasia. There was no hydrocephalus. Preoperatively the patient had paraparesis and discretely moved his left foot. MRI showed a dilated bladder so he may have had urinary retention. The postoperative recovery was satisfactory. The patient did not have any additional neurological deficit. The patient was followed up by a neurosurgeon, pediatric surgeon, pediatrician and physiatrist. Control MRI scans showed significant regression of the syrinx and some ascensus of the medulla. About 18 months after operation the patient had discrete paresis of the left foot. Conclusion – Complex spina bifida is an extremely rare condition. In this paper we describe this interesting case of complex spina bifida: a split cord malformation characterized by atypical bony morphology with a dural fold into the bone septum.

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Objective – To analyze the clinical and histological characteristics, as well as to evaluate the results of surgical treatment of pediatric neuroepithelial tumors. Patients and methods – A retrospective study was conducted, including 40 pediatric patients surgically treated at the Clinic of Neurosurgery, University Clinical Hospital Tuzla in the period 2002-2012. During the study we formed groups and the analysis was conducted by age, gender, clinical signs, histopathologic types and type of surgical treatment. The results are presented in tables and expressed by relative values. Results – Neuroepithlial tumors are more common in male patients. There was no statistically significant difference in distribution of neuroepithelial tumors (I‡2=0.400; p=0.527) related to supratentorial and infratentorial localization. Infratentorial neuroepithelial tumors are most common at a younger age (F=6.516; p=0.015). Increased intracranial pressure and seizures are the most common initial presentation of neuroepithelial tumors (I‡2=0.022; p=0.882). There was no statistically significant difference between types of surgical resection and localization of the tumor. Usually we performed total resection (I‡2=0.246; p=0.620). There was a statistically significant difference in tumor grade regarding supratentorial and infratentorial localizations (p=0.013). Infratentorial tumors are higher grade (I‡2=5.495; p=0.019). Conclusion – The most common initial presentations of neuroepithelial tumors are increased intracranial pressure and seizures. Infratentorial tumors are higher grade. The most common initial treatment of neuroepithelial tumors is radical surgical resection.