OBJECTIVE To report two additional cases of glycogen-rich clear cell carcinoma (GRCC) of the breast - detailing their clinicopathologic features, immunophenotypes, and follow-up - and to provide an updated literature review since 2020. CASE REPORTS Two patients (66 and 52 years old) had GRCC confirmed morphologically and histochemically. Case 1 was ER-positive/HER2- positive (luminal B/HER2-positive) and was managed with surgery, followed by adjuvant chemotherapy, endocrine therapy, and anti-HER2 therapy (trastuzumab). Case 2 was triple-negative and received neoadjuvant chemoimmunotherapy (pembrolizumab- based) with marked pathologic tumor regression at resection. Both patients were disease-free at one and 12 months, respectively. CONCLUSIONS GRCC is heterogeneous and should not be regarded as a single clinicopathologic entity within invasive breast carcinoma of no special type or assumed to have a uniform prognosis. Management should be biomarker-guided, as illustrated by these cases. The role of targeted and immune therapies in GRCC warrants multi-institutional studies.

Symptomatic Meckel’s diverticulum (MD) has various clinical presentations and can be easily misdiagnosed. This multicenter study examines the clinical characteristics, management, and outcomes of patients across five academic pediatric surgery centers in Bosnia & Herzegovina and Serbia. We retrospectively included all pediatric patients (< 18 years) who were surgically and histopathologically confirmed to have symptomatic MD between 2011 and 2020. Demographics, clinical and radiological features, surgical treatment approaches, histopathologic findings, and outcomes were collected and analyzed. Among 151 patients (80.1% male), the median age was 6.7 years (IQR 1.5–10.8). Presentations included intestinal obstruction (38.4%), GI bleeding (37.8%), and peritonitis (23.8%); 63.6% had multiple symptoms. A technetium-99 m scan was positive in 80.7% of bleeding cases. Laparotomy was performed in 72.2%, laparoscopy in 23.2%, and conversion in 4.6%. Partial small bowel resection was required in 80.8%, versus diverticulectomy in 19.2% (p < 0.001). Ectopic mucosa was found in 55.6% (gastric 48.3%, pancreatic 2.6%, both 4.6%; p = 0.05), significantly more common in males (p < 0.001). Postoperative complications occurred in 3.2%, with no mortality. Symptomatic MD displays highly variable clinical presentations. It is often underdiagnosed preoperatively, particularly without GI bleeding, emphasizing the need for high clinical suspicion and tailored surgical approaches.

ABSTRACT Purpose Acinic cell carcinoma (ACC) of the breast is a very rare, primary salivary gland‐type breast malignancy, with ~100 reported cases in the literature. Limited information about the clinical features and outcomes of patients with ACC is available. Methods We utilized the Surveillance, Epidemiology, and End Results (SEER) database to identify ACC patients. For comparison, we also examined a cohort of invasive breast carcinomas of no special type (NST). Results Thirty ACC patients were identified among the more than 248 000 invasive breast carcinoma NST patients. ACCs were predominantly grade 3 carcinomas (44%) and were diagnosed at an earlier stage (67%). Hormone receptor (HR) and HER2 status data were available for only 13 patients, revealing molecular heterogeneity: HR−/HER2− (four patients), HR−/HER2+ (two patients), HR+/HER2− (four patients), and HR+/HER2+ (three patients). The median survival time for ACC patients was 19 months vs. 48 months for NST patients (p < 0.001). A complete‐case approach was utilized for the adjusted analyses, restricting the sample to 46 257 patients without missing data on all relevant covariates. The adjusted Kaplan–Meier analysis indicated a more pronounced decline in survival probabilities among patients with ACC compared to those with NST, with the number at risk in the ACC group diminishing to four patients by the 30‐month mark. In contrast, NST patients exhibited a more gradual decrease. In the multivariable Cox regression, which adjusted for age, TNM stage, HR/HER2, and chemotherapy, ACC histology was correlated with a 1.69‐fold increase in the hazard of death (HR: 1.69; 95% CI: 0.63–4.56), although this result was not statistically significant. Age and advanced stage continued to be strong predictors of poor survival, and the inclusion of an age–time interaction enhanced the model fit. Conclusion Acinic cell carcinoma of the breast is a very rare primary breast malignancy. Our study indicates potentially aggressive clinical behavior in mammary ACC; however, findings must be interpreted cautiously given inherent SEER limitations, especially regarding histologic and molecular subtyping accuracy. Further centralized studies are urgently needed for the accurate characterization of this rare entity.

Objective This study aimed to evaluate the functional status of the urethra using uroflowmetry before surgery, as well as three and six months postoperatively in cases of distal hypospadias. Material and Methods Thirty-nine consecutive patients who underwent surgery for distal hypospadias (hypospadias group) between 2016 and 2019 were prospectively included as part of this study. The control group consisted of 40 patients with a normal urethra who underwent surgery due to conditions other than hypospadias (phimosis, undescended testis, hernia). Uroflowmetry was performed preoperatively in these patients. Postoperative uroflowmetry was performed at three and six months following hypospadias surgery. Uroflowmetric results [maximum flow rate (Qmax), average flow rate (Qave), voided volume, void duration, flow start time, time to maximum urine flow rate, post-void residual urine, flow curve] were compared between the groups. Results The mean age for the patients with distal hypospadias was 35.9±29.6 months and 40.8±26.1 months for the control group. Pre- and postoperative Qmax values (three and six months after surgery) were 6.9 mL/s (0.1-15), 6.4 (0.2-14), and 7.5 (2.5-15). Qave values were preoperatively 4.0 (0.1-12.1), 3.8 (0.3-8.1), and 4.7 (1.0-11.1) mL/s three and six months after surgery, respectively. Bell-type flow was the most frequent uroflow flow curve in the preoperative hypospadias and control groups (95% and 66.6%, respectively). Postoperatively, bell-type flow remained the most common pattern, while a significant reduction in plateau-type flow was observed. Four boys (10.3%) had symptoms of obstruction. Conclusion Surgery improved urination dynamics and partial urethral obstruction of hypospadias cases that were present from the baseline. The urinary flow rates improve over time as the reconstructed neourethra regains functionality six months after the tubularized incised plate procedure.

Small-cell lung cancer (SCLC) is a tobacco-associated neuroendocrine tumor comprising ~15% of lung cancers (~150,000 cases/year). For decades, outcomes stagnated: most patients present with extensive-stage disease, screening rarely detects early tumors, surgery is seldom feasible, and platinum-etoposide remained the first-line standard with median overall survival (OS) <12 months. Radiotherapy (including consolidative thoracic RT) and prophylactic cranial irradiation or MRI surveillance offered incremental gains. Two shifts have begun to change the field. First, four transcriptional subtypes (SCLC-A, -N, -P, and inflammatory SCLC-I) support a more personalized approach, with SCLC-I appearing more responsive to immune checkpoint inhibitors (ICI). Second, adding atezolizumab or durvalumab to chemotherapy in extensive-stage SCLC produced a modest median OS gain but, crucially, a tail of long-term survivors. Subsequent trials extended these advances: IMforte suggested benefit from lurbinectedin maintenance with atezolizumab in ES-SCLC, and ADRIATIC demonstrated a landmark OS improvement (~22 months) with durvalumab consolidation after concurrent chemoradiotherapy in limited-stage SCLC. Targeted strategies are now emerging. Delta-like ligand 3 (DLL3), overexpressed in >80% of SCLC, enables T-cell-redirecting therapy: the bispecific T-cell engager tarlatamab improved OS to 13.6 vs 8.3 months over standard second-line chemotherapy, with manageable cytokine release syndrome and occasional ICANS. B7 homolog 3 (B7-H3, CD276), uniformly expressed across SCLC subtypes and linked to poor prognosis, is another compelling target: the antibody-drug conjugate ifinatamab deruxtecan achieved a 54.8% response rate and meaningful survival in heavily pretreated patients, earning FDA Breakthrough designation. Together, DLL3- and B7-H3-directed therapies (with additional ADCs against Trop-2 and SEZ6 in development) are redefining second-line and later care. Key next steps include optimizing sequencing/combination strategies, managing BiTE-specific toxicities, and developing predictive biomarkers. After decades of futility, SCLC is transitioning from uniform chemotherapy to a precision-medicine paradigm with cautious optimism.

Introduction Small cell lung cancer (SCLC) is a highly aggressive subtype of lung cancer that accounts for approximately 15% of all lung cancers. Despite advancements in treatment, real-world clinical practice in developing countries often reveals less favorable outcomes than those observed in randomized clinical trials. Material and methods A retrospective analysis was conducted on all patients with extensive-stage SCLC (ES-SCLC) diagnosed or treated at a single center in Bosnia and Herzego-vina. Medical and electronic health records were reviewed to collect data on patients diagnosed with ES-SCLC between 2013 and 2023. The analysis included patient demographics, clinical characteristics, treatment outcomes, and adverse events. Results Ninety-four patients with ES-SCLC were included in the study. Of these, 89.4% were prescribed first-line treatment, and 63.8% received first- line chemotherapy based on cisplatin and etoposide. The median progression- free survival in patients treated with first-line ES-SCLC was five months, with a response rate of 57.5%. The median overall survival of patients treated with first-line chemotherapy in our study was seven months. The most common side effect was hematologic toxicity. Conclusions Our results showed that the outcomes of patients with ES-SCLC in real clinical practice are poor. Further studies of real-world treatment outcomes are essential to validate the findings from randomized controlled trials. Ongoing research is needed to explore strategies for improving outcomes and addressing the unmet needs of patients with ES-SCLC.

Background/Objectives: This study aimed to evaluate the diagnostic and prognostic utility of B7-H3 expression in differentiating low-grade gliomas (LGGs) from high-grade gliomas (HGGs) and to examine its association with clinical outcomes. Methods: This retrospective study included 99 patients with histopathologically confirmed gliomas (42 LGGs and 57 HGGs). B7-H3 expression was assessed using immunohistochemistry and scored by immunoreactive score (IRS). Results: B7-H3 expression was significantly higher in HGG compared to LGG (p < 0.001). The total IRS (B7-H3 A × B) demonstrated strong discriminative power (AUC = 0.816). High B7-H3 expression independently predicted disease progression (OR = 4.9, 95% CI: 2.4–10.1; p < 0.001) and was associated with IDH wild-type status and elevated Ki-67 index. Patients with high B7-H3 had significantly shorter overall survival (median 6 months vs. 42 months) and progression-free survival (median 3 months vs. 25 months) (both p < 0.001). Cox regression confirmed high B7-H3 as an independent predictor of mortality (HR = 2.9, 95% CI: 1.7–4.7; p < 0.001) and progression (HR = 2.6, 95% CI: 1.6–4.2; p < 0.001). Conclusions: B7-H3 expression is a reliable biomarker for distinguishing HGG from LGG and is independently associated with worse survival outcomes. Its assessment may aid in glioma classification and prognostication.

A systematic review with meta-analysis (SRMA) represents the pinnacle of evidence, but its validity depends on methodological rigor. This narrative review synthesizes recommendations from major reporting frameworks—Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 (PRISMA-2020), Meta-Analysis of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Overviews of Reviews (PRIOR)—into a concise checklist for peer reviewers. The checklist addresses common sources of bias that often escape editorial assessment. Initially, it outlines how reviewers should assess the rationale for an SRMA by identifying existing syntheses on the same topic and determining whether the new work provides substantive novelty or a significant update. Best practices are summarized for protocol registration, comprehensive search strategies, study selection and data extraction, risk-of-bias evaluation, and context-appropriate statistical modeling, with a specific focus on heterogeneity, small-study effects, and data transparency. Case examples highlight frequent pitfalls, such as unjustified pooling of heterogeneous designs and selective outcome reporting. Guidance is also provided for formulating balanced, actionable review comments that enhance methodological integrity without extending editorial timelines. This checklist equips editors and reviewers with a structured tool for systematic appraisal across clinical disciplines, ultimately improving the reliability, reproducibility, and clinical utility of future SRMAs.

The scientific community is continually evolving, driven by advancements, shifting priorities, and growing demands for global dissemination of knowledge. A clear example of successfully adapting to these demands is the transition from the Bosnian Journal of Basic Medical Sciences (BJBMS) to Biomolecules and Biomedicine (BB) in 2023. This strategic move symbolizes a significant step forward, expanding the journal's global reach and scientific scope.

Introduction: Tumor-infiltrating lymphocytes (TIL) are linked to responses to chemotherapy and immunotherapy and clinical outcomes, especially in high-risk breast carcinomas. MammaPrint® (MP) and BluePrint® (BP) are genomic tests designed to provide risk stratification and molecular classification for early-stage hormone receptor (HR)-positive breast carcinomas, which could include tumors with HER2-low expression. We investigated correlations between TIL measurements, HER2 status, and MP/BP assays in early-stage HR-positive breast carcinomas. Materials and Methods: 167 early-stage HR-positive breast carcinomas with known MP/BP risk categorization were evaluated for TIL using whole slide scanned images according to the International TILs Working Group 2014 guidelines. HER2-low breast cancers were identified by IHC scores of 1+ and 2+ without HER2 amplification. A subset of high-TIL, high-risk cases underwent TSO500 (Illumina) next-generation sequencing (NGS). Results: The patients had a mean age of 51 years, ranging from 26 to 75 years. Among the profiled cases, 97% were either luminal A (96/167) or luminal B (66/167) breast carcinomas, with only five cases classified as HER2-enriched (n = 2) or basal-like (n = 3) carcinomas. Tumor grade was strongly associated with recurrence risk (p<0.001). The prevalence of the HER2-low phenotype was 65%, including 46/69 (67%) high-risk cases. TIL levels ranged from 0 to 70% and were low (≤10%) in the majority (75%) of cases in the cohort. However, high TIL levels were more frequently observed in cases with high recurrence risk (56% vs. 39%, p = 0.03). Additionally, TIL-enriched high-recurrence risk carcinomas contained targetable genomic alterations, including PIK3CA, BRCA1, BRCA2, and HER2 mutations. Conclusions: TIL levels are higher in early-stage HR-positive breast carcinomas with a high recurrence risk. These tumors also harbor targetable genomic alterations, suggesting that TIL measurement and genomic profiling could enhance risk stratification and identify patients who might benefit from targeted therapies. Her-2 low expression in high-risk patients provides a consideration for including novel ADC therapies in this subset of patients. Citation Format: Zoran Gatalica, Inga Rose, Faruk Skenderi, Nataliya Kuzmova, Semir Beslija, Timur Ceric, Inga Marijanovic, Ilir Kurtishi, Semir Vranic. High Tumor-Infiltrating Lymphocyte Levels Correlate with High MammaPrint® Recurrence Risk in Early-Stage Breast Carcinomas [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P1-11-17.

Background/Aim: Rheumatoid arthritis (RA) is an autoimmune inflammatory disease, characterized by the production of numerous pro-inflammatory cytokines, such as tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), which lead to pathophysiological changes in innate and acquired immunity. The existing evidence shows that pro-inflammatory cytokines in rheumatoid arthritis impact monoaminergic neurotransmission, neurotropic factors, and synaptic activity, which may lead to the development of depression. Materials and Methods: In our study, we explored the association between TNF-α and IL-6, disease activity, and the degree of depression in patients with RA. The association between TNF-α and IL-6 and the Beck and Hamilton depression scales was analyzed in a group of 116 RA patients with depression. We investigated the same correlation in 45 patients with primary depression who represented the control group. Results: A Spearman test showed that IL-6 levels had a positive association with the Beck and Hamilton scales (p < 0.05) and that TNF-α had a positive association with the Hamilton scale (p < 0.05). Also, the Hamilton depression scale was the more sensitive scale in the detection of depressive symptoms. Conclusions: Our study indicates that elevated values of pro-inflammatory cytokines are associated with the degree of depression in patients with RA. Future preclinical and clinical studies will contribute to a better understanding of the pathophysiological mechanism of depression in patients with RA and may serve as the basis for new treatment modalities. By detecting depression promptly, with the help of the HAM-D as the more sensitive scale, we could influence the future modality of treatment, and with a multidisciplinary approach, we could ensure an improvement in the quality of life of patients with RA.

Despite the well-established role of human papillomavirus (HPV) as the primary cause of cervical cancer (CC) and the existence of an effective HPV vaccine, over half a million women are diagnosed with CC globally each year, with more than half of them dying from the disease. Immunotherapy has rapidly become a cornerstone of cancer treatment, offering substantial improvements in survival rates and reducing treatment-related side effects compared to traditional therapies. For the past 25 years, chemoradiotherapy (CRT) has been the standard treatment for locally advanced CC (LACC). However, while adjuvant chemotherapy has failed to improve outcomes in LACC, the integration of neoadjuvant chemotherapy (NACT) with CRT, as well as chemoimmunoradiotherapy followed by consolidation immunotherapy, has transformed treatment strategies, demonstrating superior efficacy compared to CRT alone. In the first-line treatment of CC, adding pembrolizumab to platinum-based chemotherapy, either with or without bevacizumab, has significantly improved outcomes compared to platinum-based chemotherapy and bevacizumab alone. This review explores the current landscape of immunotherapy and biomarker advancements in CC. Furthermore, we discuss promising future directions, including the potential of personalized immunotherapy approaches and novel combination therapies to further enhance treatment efficacy and improve prognoses for patients with CC.

Abstract Basal cell carcinoma (BCC) is the most common type of skin cancer that usually appears in sun-exposed body regions such as the head, trunk, and extremities. There are four main clinicopathological subtypes of BCC: nodular, superficial, morpheaform, and fibroepithelial. BCC’s molecular basis includes inherited genetic susceptibility and somatic mutations, often induced by exposure to UV radiation. The aberrant activation of the hedgehog (Hh) signalling pathway, caused by mutations in the Hh components, plays a central role in the molecular pathogenesis of this carcinoma. This led to the development of Hh signalling pathway inhibitors as a new treatment option for patients with advanced disease. In this review, we summarise BCC’s clinical presentation and histopathology and present knowledge on the most studied Hh signalling inhibitors, vismodegib and sonidegib, and other inhibitors of this signalling, such as itraconazole, patidegib, taladegib, and arsenic trioxide, in the treatment of BCC. We also present the most common Hh signalling inhibitor adverse events and their management options, which could improve patients’ quality of life during treatment.