Background and Objectives: A recent clinical trial has demonstrated that breast cancer with low-HER2 expression levels responds to trastuzumab deruxtecan treatment. This has prompted a re-evaluation of HER2-targeted therapies in the HER2-negative group. Further research is required in the form of more detailed information about HER2-negative breast cancers with HER2-null, HER2-ultralow, and HER2-low subgroups. This study represents a novel approach to this field. Materials and Methods: HER2-negative breast cancer patients were classified into three groups as HER2-null, HER2-ultralow, and HER2-low. A comparison of clinicopathological features was analyzed retrospectively. Results: Of 722 patients, 22.3% were HER2-null, 23.7% were HER2-ultralow, 54.0% were HER2-low. While two-thirds of all the patients were evaluated as having T2 tumors, T4 tumors constituted 2.4%. Among HER2-negative cases, 11.8% were triple-negative and 88.2% were hormone-positive. The mean tumor diameter was 0.57 cm larger in the HER2-ultralow group than in the HER2-null group and 0.34 cm larger in the HER2-low group than in the HER2-null group. HER2-null tumors tend to be smaller. The HER2-low group was more likely to relapse than the HER2-null group. There were no significant differences in the distribution of hormone positivity or negativity (TNBC) among the groups; they accounted for 89.2% and 10.8% of all cases, respectively. Conclusions: HER2-negative breast cancer is a heterogeneous disease and deserves a detailed review in terms of diagnosis and treatment. HER2-ultralow tumors are larger in size and have a prognosis comparable to HER2-null tumors. HER2-low tumors tend to recur much more frequently and with poorer outcomes. In this field, new therapeutic approaches may result in better outcomes.

(1) Background: Metastatic L-type sarcomas (liposarcoma and leiomyosarcoma) are rare and have a poor prognosis. Trabectedin is an effective agent that can be used after anthracyclines. This study was designed to evaluate the real-life effectiveness and safety of trabectedin. (2) Methods: A retrospective multicenter study was conducted on patients who were treated with trabectedin for metastatic L-type sarcomas at ten tertiary oncology centers between 2015 and 2023. The objective response rate (ORR), disease control rate (DCR), time to treatment failure (TTF), and overall survival (OS) were evaluated in the cohort. Cox regression analysis was used to determine prognostic factors for survival. (3) Results: A total of 98 patients (52% liposarcoma and 48% leiomyosarcoma) were included in the study. The median treatment line was three (range: 1 to 6). Thirteen patients (13.3%) underwent local treatment due to oligoprogression, and dose reduction was required in seventeen patients (17.3%) due to toxicity. The ORR and DCR were 16% and 42%, respectively. The median TTF was 3 months, and the median OS was 10 months. In univariate analysis, a significantly longer median TTF was observed in patients who underwent local treatment (p = 0.008), obtained objective responses (p < 0.001), and underwent dose reduction (p = 0.002). No statistical differences were observed according to the histologic subtype and metastatic site. In the multivariate analysis for OS, it was found that obtaining an objective response was a good prognostic factor (p = 0.003), while the presence of liver metastases was associated with a poor prognosis (p = 0.016). (4) Conclusion: Trabectedin is a suitable option for L-type sarcoma after doxorubicin-based treatments. Survival was not worse in patients who underwent dose reduction. The use of local therapies simultaneously with trabectedin can be effective.

SUMMARY INTRODUCTION Celiac disease (CeD) is an autoimmune disease that can be delayed in diagnosis due to the presence of atypical and asymptomatic cases in adulthood. Herein we aimed to study the frequency of CeD and evaluate whether magnified endoscopy and magnified/FICE (flexible spectral imaging color enhancement) techniques contribute to the diagnosis in patients with serum iron and vitamin B12 deficiency. METHODS We evaluated 50 adult patients (10 males and 40 females) who had serum iron and vitamin B12 deficiency, prospectively. All the patients had undergone upper gastrointestinal system endoscopy by the same endoscopist. The second part of the duodenum was evaluated with white light, magnified, and magnified/FICE endoscopy. Biopsy specimens were evaluated by the same pathologist. The specimens diagnosed as CeD were classified according to the Modified Marsh-Oberhuber criteria. RESULTS 10 of 50 patients (20%) were diagnosed as CeD. The average age was 41±11 years (20-67 years). Thirty percent of CeD diagnosed patients had typical CeD symptoms. Six of 10 patients (60%) who were diagnosed as CeD had typical endoscopic images under white lighted endoscopy. All of these 10 patients (100%) showed villous irregularity, partial villous atrophy, or total villous atrophy consistent with CeD with magnified and magnified/FICE endoscopy. CONCLUSION The practical use of magnified/FICE endoscopy allows us to differentiate mucosal abnormalities of the duodenum and minimize false-negative results that indicate normal mucosal findings with conventional endoscopy.

Background: Germline alterations in DNA damage repair (DDR) genes represent a clinically important subset of prostate cancer (PCa), but real-world data from Middle Eastern and Turkish populations remain limited. We evaluated the prevalence and clinicopathologic associations of germline DDR variants in a single-center Turkish cohort. Methods: We retrospectively analyzed 122 men with histologically confirmed PCa who underwent germline multigene panel testing. Variants were classified according to ACMG/ClinVar criteria. Patients were grouped as pathogenic/likely pathogenic (P/LP), variants of uncertain significance (VUS), or variant-negative. Patients were grouped as variant-positive (P/LP or VUS/uncategorized) or clinically actionable variant–negative (benign/likely benign or no variant detected). Group comparisons used t-tests, chi-square or Fisher’s exact tests as appropriate. Results: The median age at diagnosis was 65.2 years (mean 64.6 ± 8.78). Overall, 37 patients (30.3%) carried at least one germline variant, including 12 (9.8%) with P/LP alterations and 24 (19.7%) with VUS; one patient (0.8%) harbored an uncategorized variant. The most frequently affected genes were CHEK2 (n = 8), BRCA1 (n = 6), BRCA2 (n = 6), ATM (n = 5), and APC (n = 4). Variant-positive status increased from 10.8% in ISUP 1–2 to 21.6% in ISUP 3 and 76.0% in ISUP 4–5, although this trend was not statistically significant (p = 0.391). Mean age at diagnosis and the prevalence of metastatic disease did not differ between variant-positive and clinically actionable variant–negative patients (64.2 vs. 65.7 years, p = 0.390; 66.7% vs. 64.6%, p = 0.842). Truncating DDR variants (RAD50, BRCA2, MSH3, NBN, CHEK2, ATM) occurred predominantly in ISUP 4–5 tumors. Conclusions: Germline DDR alterations—most notably in BRCA2, CHEK2, and ATM—were present in a substantial subset of Turkish men with PCa and showed a non-significant trend toward clustering in higher-grade disease. The high prevalence of VUS reflects limited genomic annotation in under-represented populations and underscores the need for longitudinal reinterpretation. These data support the clinical value of incorporating germline DDR testing into risk assessment and familial counseling, while larger cohorts integrating somatic profiling are needed to refine genotype–phenotype associations.

Background: Parotid gland tumors pose diagnostic and surgical challenges due to their histological heterogeneity and proximity to the facial nerve. This study aimed to evaluate clinicopathological features and postoperative outcomes with a specific focus on facial nerve function in patients undergoing parotidectomy. Methods: This retrospective study included 314 patients who underwent parotidectomy between 2008 and 2024 at a tertiary center. Demographic data, tumor histology, and postoperative complications—particularly facial nerve paralysis within the first three months—were analyzed. Histopathological features including capsular, perineural, and lymphovascular invasion were also assessed. Results: Of all cases, 79% were benign, 14.6% malignant, and 6.4% non-neoplastic. Pleomorphic adenoma and Warthin tumor were the most common benign entities, while mucoepidermoid carcinoma was the most frequent malignancy. Malignant tumors were associated with higher rates of positive surgical margins (44.2% vs. 12.5%, p < 0.001), capsular invasion (25% vs. 7%, p < 0.001), and tumor necrosis (22% vs. <1%, p < 0.001). Facial paralysis occurred in 4.4% of patients, largely transient and significantly associated with malignant tumors (p < 0.001) and extensive lymph node dissection (p < 0.001). Capsular invasion and necrosis were rare in benign lesions but still observed, especially in pleomorphic adenoma. Conclusions: Histopathologic aggressiveness markers were associated with malignant disease and postoperative facial nerve dysfunction. These findings support a risk-stratified approach to follow-up: all patients undergo universal early assessment at two weeks and three months, after which surveillance intensity may be individualized according to histopathologic features—such as necrosis, perineural invasion, capsular invasion, or positive margins.