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Semir Vranić

Društvene mreže:

Zoran Gatalica, I. Rose, S. Vranić

A commercial biorepository of tumor samples with associated clinical data is crucial for discovering and validating biomarkers and advancing all stages of cancer research. Although oncogenic fusions are highly specific and attractive drug targets, the progress is limited by their diversity and low (1-4%) prevalence in solid tumors, outside prostate adenocarcinoma (>30% with a characteristic TMPRSS2::ERG fusion). Systematic, cost effective evaluation of banked tumor samples for the oncogenic fusions could accelerate such research efforts. We examined formalin-fixed paraffin-embedded tumor samples from a commercial biorepository (Reference Medicine, Phoenix, AZ) using a workflow which included expert pathology review, whole slide scanning, construction of multi-tumor tissue microarrays (TMA) immunohistochemistry (IHC) and genomic profiling with commercially available next generation sequencing (NGS) panels. More than 500 tumors were reviewed by board-certified pathologists; selected cases were then cored for TMAs. Immunohistochemistry for ALK and ROS1 proteins' expression were performed on TMAs. IHC for ALK and ROS1 identified two positive cases, one for ROS1 and one for ALK. Thirty eight tumors underwent NGS and both IHC-positive cases were confirmed to harbor gene fusions (EML4::ALK and EZR::ROS1, respectively). All other cases were fusion-negative, concordant with the IHC result. Properly characterized tissue samples are essential for image analysis, biomarker detection and genomic profiling. Rigorous pathologic review helps avoid archiving of poorly preserved samples. IHC screening of TMAs provides a cost-effective approach for identification of fusion events, particularly in non-small cell lung carcinomas, while preserving material for multiple downstream applications. Zoran Gatalica, Inga Rose, Semir Vranic. Detection of fusion oncogenes in routinely collected biorepository samples [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Fusion-Positive Cancer: From Discovery to Therapy; 2026 Jan 13-15; Philadelphia PA. Philadelphia (PA): AACR; Cancer Res 2026;86(1_Suppl):Abstract nr A005.

Krešimir Tomić, S. Vranić

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer mortality worldwide; however, precision oncology has fundamentally transformed its treatment landscape. In 2025, seven approvals by the U.S. Food and Drug Administration (FDA) further accelerated biomarker-driven care across critical molecular subsets. These include MET-directed and trophoblast cell-surface antigen-2 (TROP-2) antibody-drug conjugates (ADCs), expanded strategies targeting epidermal growth factor receptor (EGFR), notably those addressing exon 20 insertion mutations, a ROS proto-oncogene 1 (ROS1) inhibitor, and various human epidermal growth factor receptor 2 (HER2) options that encompass both tumor-agnostic and mutation-selected approaches. These advancements underscore the necessity for integrated diagnostics-such as next-generation sequencing (NGS), fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC)-while also emphasizing ongoing challenges in biomarker selection, therapeutic sequencing, and equitable global implementation.

We report an infrequent case of a full-term male neonate presenting with a large congenital hernia of the umbilical cord (6 cm × 6 cm) containing only the entire left lobe of the liver. Prenatal ultrasonography suggested an omphalocele; however, the definitive postnatal diagnosis was established based on the presence of a narrow rim of normal skin encircling the umbilical ring and the proximal umbilical cord. Primary closure of the fascial defect was achieved successfully, with no intraoperative or postoperative complications observed. The patient recovered well postoperatively and was discharged in stable condition. Accurate differentiation from an omphalocele is crucial for appropriate management. Unlike omphaloceles, congenital hernias of the umbilical cord (CHUC) typically do not require extensive genetic or cardiac evaluation, and their surgical repair is generally less complex. However, awareness of atypical presentations of CHUC can aid in timely diagnosis, guide surgical planning, and improve clinical outcomes.

Jasmina Redžepagić, F. Skenderi, N. Ibišević, S. Bešlija, Timur Cerić, Zoran Gatalica, S. Vranić

Abstract 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.

Z. Zvizdic, B. Grujić, A. Jonuzi, Edin Husarić, Vlatka Martinović, Aleksandar Brkovic, Nikola Rakocevic, Amir Halilbašić, V. Lasić et al.

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.

Omar Tluli, H. Rajha, Dina Tluli, Ahmad Hamdan, G. R. Babu, Ivan Damjanov, S. Vranić

OBJECTIVES To compare the clinicopathologic features, treatment patterns, and survival outcomes of mucinous tubular and spindle cell carcinoma (MTSCC) with those of clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (PRCC). SUBJECTS AND METHODS This retrospective cohort study used SEER data from 1983 to 2022, including 461 MTSCC, 133,229 ccRCC, and 29,442 PRCC cases. Demographic, clinical, and treatment variables were analyzed using chi-square, ANOVA/Kruskal-Wallis tests, and Kaplan-Meier methods. Cox proportional hazards regression models were applied to estimate hazard ratios (HRs) for overall (OS) and disease-specific survival (DSS), adjusting for age, sex, race, stage, grade, treatment, and metastasis status. RESULTS MTSCC patients were more often female (54.9%), Black (20.6%), and aged ≥70 years (50.5%) compared to ccRCC and PRCC (P < 0.001). MTSCC had a lower incidence of distant metastasis than ccRCC (8.7% vs. 9.5%), but higher than PRCC (4.2%). Although most MTSCC patients presented with early-stage disease and underwent surgery (87.9%), they had the shortest mean survival (47.9 months) and the highest proportion of deaths within 100 months (83.5%). Kaplan-Meier analysis showed higher early mortality for MTSCC, with survival curves converging after 75 to 100 months. In adjusted models, MTSCC was associated with a nonsignificant increase in mortality compared to ccRCC (OS HR: 1.36, P = 0.422; DSS HR: 1.13, P = 0.832), while PRCC had a significantly higher DSS risk (HR: 1.24, P = 0.001). Poor survival in MTSCC was associated with older age, high-grade tumors, distant metastases, and absence of surgery. CONCLUSION MTSCC shows distinct demographic and clinical features and a paradoxically shorter survival despite early-stage presentation. Early mortality may contribute to its poorer outcomes, indicating that MTSCC is not uniformly indolent. Closer surveillance and individualized risk assessment are warranted in selected patients.

F. Skenderi, G. R. Babu, U. Glamočlija, E. Veledar, Zoran Gatalica, J. Lamovec, S. Vranić

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.

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.

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