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Öğe Appendiceal Collision Tumors: An Institutional Case Series and Systematic Review of the Histologic Spectrum, Clinical Outcomes, and Management Strategies(Mdpi, 2025) Issin, Gizem; Demir, Fatih; Cagatay, Diren Vuslat; Guvendir, Irem; Simsek, Hasan Aktug; Zemheri, Itir EbruBackground/Objectives: Appendiceal collision tumors (ACTs), defined by the coexistence of two or more histologically distinct neoplastic components within the appendix, are rare entities. We aimed to characterize their clinicopathologic features, management strategies, and outcomes by integrating an institutional case series with a systematic review of the literature. Methods: We retrospectively identified ACTs diagnosed at our institution and performed a PRISMA 2020-guided search of PubMed, Scopus, and Web of Science databases through May 2025 for case reports and case series. Two reviewers screened studies and extracted data on presentation, histologic composition, treatment, approaches and outcomes. Results: ACTs accounted for 4% of appendiceal tumors in our institution, all combining a neuroendocrine neoplasm (NEN) with a low-grade appendiceal mucinous neoplasm. The literature search identified 69 ACTs from 33 studies; pooled with our cases, 74 patients were evaluated. The most common pairings were NEN-appendiceal mucinous neoplasm (53%) and NEN-adenocarcinoma (26%), while three-component tumors were rare (n = 2). Early-stage tumors (pTis-pT1) were uniformly managed with appendectomy or limited resection, in line with established stage-based management algorithms for appendiceal neoplasms. Advanced-stage tumors (pT3-pT4) were treated according to the biologically dominant component, frequently with colectomy and, in high-risk mucinous disease, cytoreductive approaches. Across stages, outcomes appeared to be driven by the non-neuroendocrine component; a coexisting low-grade NEN did not independently confer worse prognosis. In ACTs with an adenocarcinoma component, goblet cell morphology was common, and outcomes appeared similar to those reported for non-collision appendiceal adenocarcinoma. Conclusions: ACTs represent a heterogeneous group in which prognosis is dictated by the non-neuroendocrine component and tumor stage. Low-grade NEN components appear biologically indolent, whereas adenocarcinoma and high-risk mucinous components have been observed to exhibit behavior similar to their solitary counterparts.Öğe Clinicopathologic Features and Prognostic Significance of Immunohistochemistry and In Situ Hybridization Based Molecular Classification in Gastric Carcinoma(Begell House Inc, 2023) Issin, Gizem; Sayar, Ilyas; Demir, Fatih; Bakkaloglu, Irem Guvendir; Gamsizkan, Mehmet; Yildiz, Zeliha; Yilmaz, IsmailBackground/Aim: Gastric carcinoma (GC) is a highly heterogeneous disease with many subtypes that have different morphologic and molecular characteristics. In the current study, we analyzed immunohistochemical (IHC) and in situ hybridization (ISH) features of GCs and evaluated their association with prognosis and clinicopathological features. Materials and Methods: Three hundred cases analyzed by IHC and ISH for microsatellite stability, p53, e-cadherin, HER2, PD-L1 expression, and Epstein-Barr virus (EBV) status. Cases were classified into five subgroups based on expression profile. The relationships between subgroups, clinicopathological features, and survival were determined. Results: Ten ( 3.3%) cases were classified as EBV-associated, 45 (15%) as microsatellite instable (MSI), 73 (24.3%) as EBV-/ microsatellite-stable (MSS)/epithelial-mesenchymal-transformation (EMT)-like, 75 (25%) as EBV-/MSS/ non-EMT-like/p53+, and 97 (32.3%) as EBV-/MSS/non-EMT-like/ p53-. The MSI subtype had the best overall survival (OS). In contrast, the EBV-/MSS/EMT-like subtype had the poorest OS. The MSI subtype was also related with old age of the patient and antrum-corpus localized tumors, whereas the EBV-/MSS/EMT-like was associated with young age, larger tumor size, and advanced stage presentation. PD-L1 positivity is highly correlated with MSI and EBV-associated subtypes. Conclusion: Our data demonstrated a link between IHC/ISH characteristics of GC and clinical outcomes. IHC/ISH based molecular classification may be helpful in predicting the survival.Öğe Columnar cell variant of papillary thyroid carcinoma in an adolescent: a comprehensive histopathological, immunohistochemical, and molecular analysis(Editura Acad Romane, 2025) Issin, Gizem; Demir, Fatih; Cagatay, Diren Vuslat; Yilmaz, IsmailThe columnar cell variant (CCV) of papillary thyroid carcinoma (PTC) is a rare histological subtype with distinct morphological and immunohistochemical (IHC) features, which can present diagnostic challenges. We report a case of a 13-year-old girl diagnosed with CCV of PTC (CCV-PTC) following a total thyroidectomy for a solitary thyroid nodule. Histopathological (HP) examination revealed aggressive features, including vascular invasion and extrathyroidal extension. However, no metastases or recurrences were observed during six years of follow-up. This case report provides a comprehensive analysis of a rare CCV-PTC in an adolescent, focusing on its HP, IHC, and molecular characteristics. It also discusses diagnostic pitfalls and differential diagnoses that should be considered.Öğe Comparison of topical hypericum perforatum and metformin effectiveness in wound healing in streptozotocin-induced diabetic rats(Frontiers Media Sa, 2025) Turhan, Banu; Saglam, Sonmez; Yucel, Mucahit Osman; Dalaslan, Rasit Emin; Sungur, Mehmet Ali; Demir, Fatih; Arican, MehmetPurpose: Our study aimed to assess and compare the effectiveness of topically applied Hypericum perforatum (HP) and metformin on wound healing in diabetic rats. Methods: Thirty-two male Wistar rats (8-10 weeks old, 250 +/- 50g) were divided into four groups of eight rats each: Control, Diabetes mellitus (DM), Metformin (Met), and HP. Diabetes was induced in all experimental rats except the control group using streptozotocin (STZ) (60mg/kg, intraperitoneal). A full-thickness skin defect was created in all rats. Two milliliters (ml) of sterile saline were administered to the Control and DM groups, two ml of metformin (10% gel, topical) to the Met group, and two ml of HP (olive oil extract) to the HP group, repeated every 24 hours for 14 days. The condition of the lesions was monitored on days 0, 3, 7, 10, and 14, and the extent of contraction and granulation tissue formation was documented. At the 14(th) day, the lesioned areas were examined histopathologically and immunohistochemically. Results: The baseline characteristics of the rats before the study showed no significant differences between the groups (p>0.05). The HP group had the smallest final wound size and the highest wound contraction percentages from day 0 to 14 (p<0.001 for both). There was no statistically significant difference among the groups in the collagen index (p=0.118). The fibroblast density scores in the DM group were significantly lower than those in the other groups (p=0.004). The hypertrophic index values of the HP group were the highest compared to the other groups (p=0.003). Although the HP and control groups exhibited higher TGF-beta percentages and H scores than the other groups, these differences were not statistically significant (p=0.660 and p=0.647). Conclusion: Topically applied HP in uncontrolled DM rats improved wound healing scores more than the non-diabetic controls. Metformin also significantly enhanced healing in DM rats, with results comparable to controls. Since HP and metformin are easily accessible, further research could lead to cost-effective treatments for wound healing issues in DM patients.Öğe The effect of peripheral dopamine on fracture healing: an experimental study in a rat model(Bmc, 2025) Yucel, Mucahid Osman; Dalaslan, Rasit Emin; Saglam, Sonmez; Arican, Mehmet; Karaduman, Zekeriya Okan; Turhan, Banu; Demir, FatihBackgroundDopamine is a versatile biomolecule that functions as a neurotransmitter, hormone, and immune modulator in the body. Although some anabolic effects of dopamine on bone tissue have been described in the literature, its influence on the complex processes involved in fracture healing remains unclear. This study aimed to evaluate the effects of dopamine on bone healing at the peripheral level.MethodsThirty-six male Wistar albino rats were randomly assigned to two groups: a control group with no treatment and a dopamine group that received 12 mg/kg levodopa twice daily via oral gavage following surgery. A standardized femoral fracture was induced under anesthesia in all the rats, which were then fixed with an intramedullary Kirschner wire. Each group consisted of 18 rats, and six rats from each group were randomly sacrificed on postoperative days 15, 30, and 45. The harvested femurs were first evaluated radiologically, followed by biomechanical analysis via a three-point bending test, and finally subjected to histopathological examination.ResultsNo significant differences were observed between the groups on days 15 and 30. However, on day 45, histopathological scores were significantly lower in the dopamine group (p = 0.015), and biomechanical strength was also lower (p = 0.004). Radiological scores were not significantly different between the groups at any time point.ConclusionDespite the known anabolic effects of dopamine on bone cells, it may adversely affect fracture healing. The negative impact of dopamine on bone union could be attributed to the multifactorial and complex nature of fracture healing, the dynamics of inflammatory processes, and the cumulative effects of various dopamine receptor subtypes.Öğe EZH2 expression in colorectal carcinoma: an evaluation of clinicopathological and prognostic value(Springer, 2025) Cagatay, Diren Vuslat; Balci, Mecdi Gurhan; Issin, Gizem; Demir, FatihBackgroundEnhancer of zeste homolog 2 (EZH2), the catalytic subunit of Polycomb Repressive Complex 2, catalyzes trimethylation of histone H3 lysine 27 and has been implicated in tumor progression.AimOur study aims to assess the relationship between EZH2 expression and clinicopathologic data, and survival in colorectal carcinomas (CRC).Materials and methodsEZH2 immunohistochemistry was performed on tumor blocks from 124 CRC patients. Based on H-scores, cases were stratified into low- and high-expression groups. EZH2 status was correlated with demographic, clinical, and pathologic features, and overall survival was analyzed with the Kaplan-Meier method and log-rank test.ResultsA total of 124 cases of CRC; 12 (9.7%) cases were classified as low EZH2 expression, and 112 (90.3%) cases were classified as high EZH2 expression. A significant association was found between EZH2 expression and microsatellite stability. High EZH2 expression was significantly enriched in microsatellite-stable tumors (p = 0.007) and in left-sided lesions (p = 0.049). No significant associations were detected with sex, stage, grade, lymph-node status, or vascular invasion. Kaplan-Meier analysis revealed no difference in overall survival between low- and high-EZH2 groups (log-rank p = 0.47; hazard ratio = 1.13, 95% CI 0.45-2.85). EZH2 staining was uniformly strong in normal mucosa and adenomas, mirroring the high expression observed in most CRCs.ConclusionsEZH2 is highly expressed across the normal-adenoma-carcinoma sequence and, in our cohort, was not linked to overall survival or to most clinicopathologic parameters in CRC. The lower expression observed in a subset of MSI-H tumors warrants further investigation; present evidence remains insufficient to establish EZH2 as an independent prognostic biomarker.Öğe Macroscopic growth patterns and their molecular implications in gastric carcinoma: toward risk stratification via borrmann classification(Bmc, 2025) Issin, Gizem; Demir, Fatih; Cagatay, Diren Vuslat; Bakkaloglu, Irem Guvendir; Gamsizkan, Mehmet; Yildiz, Zeliha; Gunal, ArmaganGastric carcinoma (GC) is a heterogeneous disease with diverse histopathological and molecular features. The Borrmann classification, which reflects the macroscopic growth pattern, has potential value in correlating with molecular characteristics and predicting disease extent and prognosis. However, its relationship with GC molecular subtypes remains incompletely defined. In the present study, we attempted to assess the relationship between Borrmann classification and clinical, pathological, and molecular findings in GC, as well as its impact on overall survival. Material and methods A retrospective analysis was conducted on 255 patients who underwent surgery for GC between January 2012 and 2021. Cases were classified into types I, II, III, and IV, according to the Borrmann classification. Clinical data, tumor characteristics, molecular marker expression status, and survival data were analyzed in relation to the Borrmann classification. Result The most common macroscopic growth pattern was Borrmann type III (38.8%). Type IV tumors were associated with younger patients, larger size, epithelial-mesenchymal transition-related molecular subtype, diffuse histology, and a higher incidence of peritoneal dissemination. In contrast, type I tumors were more frequently diagnosed at earlier stages and demonstrated well-differentiated morphology, frequent HER2 positivity, and p53 mutant expression. Kaplan-Meier analysis demonstrated clear survival differences among Borrmann types, with type I tumors showing the most favorable outcomes (median 82.2 months) and type IV tumors the poorest (median 34.6 months; log-rank p < 0.001). When adjusted for covariates in the multivariate Cox model, only age, Borrmann type III (compared to type I) and advanced nodal status (pN0 compared to pN2-3) were found to be independent prognostic indicators. Advanced age was consistently associated with reduced survival time, type III tumors resulted in more than a twofold increase in mortality risk, and higher nodal stages were strongly linked to poor outcomes. Conclusion The Borrmann classification showed associations with molecular and pathological features of GC, and survival varied among types, suggesting potential utility for prognostic assessment prior to surgery.Öğe The effects of liraglutide and metformin treatment on fracture healing in partially insulinopenic diabetic rats(Frontiers Media Sa, 2025) Turhan, Banu; Saglam, Sonmez; Yucel, Mucahit Osman; Dalaslan, Rasit Emin; Sungur, Mehmet Ali; Demir, Fatih; Arican, MehmetPurpose Although Metformin has been studied, the comparative or synergistic effect with GLP-1 agonists like Liraglutide on fracture healing remains poorly characterized. This study aimed to evaluate the impact of metformin, liraglutide, and their combination on fracture healing in a rat model of partially insulinopenic diabetes mellitus (DM). Methods Sixty male Wistar rats (10-14 weeks old, 350 +/- 50g) were divided into five groups of twelve rats each: Control, DM, Met (Metformin), L (Liraglutide), and Met+L. Partially insulinopenic DM was induced in all experimental rats except the control group using streptozotocin (STZ) and nicotinamide (NA) combination. A femoral fracture was created, and a Kirschner wire was inserted retrogradely into the femoral canal. Liraglutide was injected subcutaneously at a daily dose of 0.6 mg/kg into the rats in the L and Met+L groups, and oral metformin was administered to the rats in the Met and Met+L groups daily at a dose of 180 mg/kg. On the 15th, 30th, and 45th days, four rats from each group were selected randomly and euthanized, and the femurs were examined radiographically, biomechanically, and histopathologically. Results The baseline characteristics of the rats before the study showed no significant differences between the groups (p>0.05). Biomechanical test results showed a significant main effect of group (p<0.001), indicating that overall Newton values varied across groups. Additionally, a significant main effect of experimental day was found (p<0.001), suggesting that Newton values changed across days regardless of group. Histopathological scores showed a statistically significant difference between the groups on the 15th day, with the L group having 75% scoring 7 (p=0.047), and on the 45th day, with the L and Met+L groups both having 75% scoring 9 (p=0.036). Conversely, no significant difference was found in radiological scores between the groups on the 15th day (p=0.934), 30th day (p=0.649), and 45th day (p=0.502) of the experiment. Conclusion Both metformin and liraglutide improve fracture healing in a partially insulinopenic diabetic rat model, and these findings suggest that liraglutide may offer a superior therapeutic advantage over metformin in accelerating fracture repair in patients with diabetes.Öğe Time-dependent effects of topical mucopolysaccharide polysulfate and silver sulfadiazine on wound healing in a rat excisional wound model(Turkish Joint Diseases Foundation, 2026) Dalaslan, Rasit Emin; Yucel, Mucahid Osman; Saglam, Sonmez; Arican, Mehmet; Karaduman, Zekeriya Okan; Demir, Fatih; Toker, MustafaObjectives: This study aims to evaluate the effects of topical creams containing mucopolysaccharide polysulfate (MPS) on wound healing using an experimental wound model. Materials and methods: Standard full-thickness skin defects were created in 32 Wistar rats and monitored for 14 days under four different topical treatment protocols: Control (Group 1, n = 8), Hirudoid (Group 2, n = 8), Silverdin (Group 3, n = 8), and Hirudoid + Silverdin (Group 4, n = 8). Wound closure rates were quantified through photographic analysis, while histological and immunohistochemical healing characteristics were assessed using the Structure, Presence of Cells, Organization, and Tissue Integration (SPOT) score, additional histological indices, and the transforming growth factor-beta 1 (TGF-beta 1) H-score. Intergroup differences were analyzed using appropriate non-parametric statistical tests. Results: On Day 3, wound closure rates were higher in the Hirudoid, Silverdin, and Hirudoid + Silverdin groups compared to the control group (p < 0.01). By Day 14, this difference sustained only in the Silverdin and Hirudoid + Silverdin groups, indicating that the early advantage observed with Hirudoid alone was not maintained over time (p < 0.01). No significant differences in the general histological parameters were observed among the groups (p > 0.05). However, the TGF-beta 1 H-score was lower in the Silverdin group than in the control and Hirudoid groups (p < 0.01). Conclusion: Our study results suggest that MPS may accelerate early wound closure, but does not significantly improve wound closure in later stages, and its combination with silver sulfadiazine offers no additional benefit compared to silver sulfadiazine alone.
