Anıl Aysal Ağalar

Background/Objectives: While perioperative chemotherapy is standard for locally advanced gastric cancer, no baseline blood marker reliably identifies which patients will respond to treatment. In this retrospective study, we compared eleven inflammatory and nutritional indices against pathological response and survival using data collected between 2020 and 2025. Methods: We analyzed 130 patients with gastric adenocarcinoma receiving perioperative systemic therapy at two centers. Eleven indices—the neutrophil-to-lymphocyte ratio (NLR), systemic immune–inflammation index (SII), Prognostic Nutritional Index (PNI), and eight further indices defined—were assessed against the Mandard tumor regression grade (TRG), overall survival (OS), and disease-free survival (DFS). Results: The median age was 63 years, and the median follow-up was 22.1 months from diagnosis. A Mandard TRG was assigned in 123 patients, 32 of whom achieved a major pathological response (TRG 1–2). The PNI had the highest point estimate of discrimination for major pathological response (AUC 0.618, 95% CI 0.490–0.746; p = 0.070), but its area under the curve did not differ significantly from that of any other index (all p ≥ 0.18), and bootstrap validation incorporating index selection and threshold derivation yielded an optimism-corrected AUC of 0.567. While PNI ≥ 53 was nominally associated with TRG 1–2 (OR 3.823, 95% CI 1.503–9.722; p = 0.005), no association survived correction for multiple comparisons, and the PNI was selected as the best-performing index in only 49% of bootstrap resamples. No index showed a statistically significant association with overall survival, and the event count is insufficient to establish the presence or absence of an association. Conclusions: None of the eleven baseline blood-based indices demonstrated statistically robust or clinically useful discrimination for major pathological response, and none were associated with survival. Although the PNI represented the most promising exploratory signal, its apparent advantage was not statistically distinguishable from the other indices and did not survive internal validation. The threshold of approximately 53 should be regarded as hypothesis-generating only.

Background and Objectives: The MATTERHORN study demonstrated that adding durvalumab to perioperative FLOT improves survival in resectable gastric cancer. As immunotherapy enters routine practice, precise patient stratification becomes critical. This study examines whether baseline blood-based inflammatory markers can predict pathological response and long-term outcomes. Materials and Methods: We retrospectively analyzed 130 patients with gastric adenocarcinoma receiving perioperative systemic treatment. Nine inflammatory and nutritional indices (NLR, MLR, NMR, SII, SIRI, HALP, ALBI, PALBI, and PNI) were assessed against Mandard Tumor Regression Grade (TRG), overall survival (OS), and disease-free survival (DFS). Results: Median age was 63 years (range 28–83); median follow-up was 22.2 months. Of all markers assessed, only PNI was significantly associated with major pathological response (TRG 1–2) and DFS on univariable analysis. Multivariable logistic regression identified PNI ≥ 53.125 as the sole independent predictor of TRG 1–2 (OR 4.200, 95% CI 1.631–10.820; p = 0.003). Completing perioperative treatment independently predicted DFS, while post-treatment nodal stage (ypN) and treatment completion independently predicted OS. Optimal cut-offs were PNI ≥ 53.125 for major response (sensitivity 57.1%, specificity 73.6%) and PNI ≤ 48.475 for recurrence risk (sensitivity 59.4%, specificity 68.7%). Conclusions: Among all markers evaluated, PNI showed the most consistent associations with treatment response and survival, and was the only independent predictor of major pathological response. The proposed cut-off values offer a practical, cost-effective approach to patient stratification—helping identify those who may need intensified treatment or closer postoperative surveillance.

Background and Objectives: This study aimed to evaluate and compare the early postoperative outcomes of patients who underwent pancreaticoduodenectomy (PD) with total mesopancreatic excision (TMpE) versus conventional pancreaticoduodenectomy (Co-PD) for pancreatic head ductal adenocarcinoma (PDAC). Materials and Methods: Patients who underwent PD for pancreatic head cancer between January 2021 and December 2024 in our clinic and had a pathological diagnosis of PDAC were included. Patients were stratified into two groups according to the surgical technique performed (TMpE-PD vs. Co-PD). Demographic characteristics and early postoperative clinicopathological data were compared between the groups. Results: A total of 41 patients were included: 17 (41.5%) underwent TMpE-PD and 24 (58.5%) underwent Co-PD. Demographic and clinicopathological parameters were comparable between the groups. Although not statistically significant, the TMpE-PD group demonstrated higher R0 resection rates (58.8% vs. 45.8%; p = 0.412) and greater lymph node yield (33.9 vs. 29.1; p = 0.757) compared to the Co-PD group. Overall postoperative complications were more frequent in the TMpE-PD group (82.4% vs. 63.4%; p = 0.034). A smaller pancreatic duct diameter was associated with an increased risk of postoperative complications in both groups, approaching statistical significance (p = 0.053). Multivariable logistic regression analysis revealed that the surgical technique was not an independent risk factor for postoperative complications (OR: 0.64; 95% CI: 0.14–2.83; p = 0.56). No direct correlation was found between resection margin status (R0 vs. R1) and the development of postoperative complications. Conclusions: TMpE demonstrated non-significant trends toward higher R0 resection rates and greater lymph node yield compared with conventional PD. These findings suggest possible oncological benefits without significantly increasing perioperative morbidity.

Research groups have identified 4 groups [polymerase epsilon (POLE) mutant, mismatch repair-deficient, p53-abnormal, and no specific molecular profile)] reflecting the Tumor Cancer Genomic Atlas Research Network subgroups in endometrial carcinomas, improving the clinical applicability of molecular classification. We have analyzed the histopathologic and prognostic characteristics of our cases based on the ProMisE classification, supported by growing data on recommended treatment regimens. The study included 118 cases of endometrial carcinoma diagnosed between 2016 and 2020, which underwent mismatch repair and p53 immunohistochemistry. Next-generation sequencing was performed for POLE mutation analysis, dividing the cases into 4 subgroups. The histopathologic and clinical characteristics of these groups were then analyzed statistically. Four cases(3.4%) were classified as POLE mutant, 31 (26.3%) as mismatch repair-deficient, 22 (18.6%) as p53 mutant, and 61 (51.7%) as no specific molecular profile. We categorized 118 patients with endometrial carcinoma into low (n=43), intermediate (n=28), high-intermediate (n=21), high (n=22), and advanced metastatic (n=4) risk groups regardless of the molecular subtypes of their disease. When we reclassified all cases according to the molecular subtypes of endometrial carcinoma only the risk group of 3 (2.5%) cases changed. Using the new algorithm we designed, after narrowing down the number of patients, the microcystic, elongated, and fragmented pattern of invasion was revealed as an independent prognostic factor that reduces overall survival time (hazard ratio: 16.395, 95% CI: 2.140–125.606, P=0.007). In conclusion, using the new algorithm we have designed, and by identifying patients for whom molecular classification could alter risk groups, we observed that molecular tests can be utilized more efficiently in populations with limited economic resources and, in doing so, we discovered a new morphologic marker with prognostic significance.