Pancreatic ductal adenocarcinoma (PDAC) is associated with intratumoral microbiota changes. However, defining the normal pancreatic microbial composition remains a challenge. Herein, we tested the hypothesis that the microbial profiling of normal pancreatic tissue from healthy organ donors (HC) could help in determining the signature of microbiota in PDAC. Matched pairs of tumor and normal tissues from PDAC patients (n = 32) and normal pancreatic tissues from HC (n = 17) were analyzed by 16S rRNA gene sequencing. Dissimilarities in all the beta metrics emerged in both normal samples and tumor samples, compared to HC (Bray–Curtis dissimilarity and Jaccard distance: p = 0.002; weighted UniFrac distances: p = 0.42 and p = 0.012, respectively; unweighted UniFrac distance: p = 0.009); a trend toward a lower Faith’s phylogenetic distance was found at the tumor level vs. HC (p = 0.08). Within PDAC, a lower Faith’s phylogenetic distance (p = 0.003) and a significant unweighted UniFrac distance (p = 0.024) were observed in tumor samples vs. normal samples. We noted the presence of a decreased abundance of bacteria with potential beneficial effects (Jeotgalicoccus) and anticancer activity (Acinetobacter_guillouiae) in PDAC vs. HC; bacteria involved in immune homeostasis and suppression of tumor progression (Streptococcus_salivarius, Sphingomonas) were reduced, and those implicated in tumor initiation and development (Methylobacterium-Methylorubrum, g_Delftia) were enhanced in tumor samples vs. normal samples. Metagenomic functions involved in fatty acid synthesis were reduced in normal samples compared to HC, while peptidoglycan biosynthesis IV and L-rhamnose degradation were more abundant in tumor samples vs. normal samples. Future prospective studies on larger populations, also including patients in advanced tumor stages and considering all potential existing confounding factors, as well as further functional investigations, are needed to prove the role of microbiota-mediated pathogenicity in PDAC.

Background: Enhanced Recovery After Surgery (ERAS) pathways have become the standard of care in elective colorectal surgery. However, implementation remains heterogeneous across institutions, and the relative contribution of ERAS pathways and minimally invasive surgery to improved postoperative outcomes remains uncertain. This study evaluated the association between ERAS implementation and short-term outcomes in two university-affiliated colorectal units with different levels of ERAS adoption. Methods: A retrospective bi-centre observational study was conducted, and comprised 802 consecutive patients who underwent elective colorectal resection between January 2016 and December 2024. Patients managed according to a standardized ERAS pathway (Group 1, n = 406) were compared with patients who received conventional perioperative care (Group 2, n = 396). Primary endpoints included postoperative morbidity, anastomotic leakage, and length of hospital stay (LOS). Secondary endpoints included mortality, readmission, postoperative complications, and hospitalization-related costs. Multivariable logistic regression was performed, adjusting for age, sex, ASA score, tumour stage, and tumour location. Results: Baseline demographic characteristics were largely comparable between groups, although patients in the conventional care group had a higher proportion of ASA III–IV status. Overall postoperative morbidity was significantly lower in the ERAS cohort (8.6% vs. 20.9%, p < 0.001), together with a lower incidence of anastomotic leakage (1.2% vs. 4.5%, p < 0.001). Median LOS was reduced from 9 to 8 days overall and, among patients who underwent laparoscopic surgery, from 6 to 4 days (p = 0.010). After multivariable adjustment, conventional perioperative management remained independently associated with higher postoperative morbidity (OR 2.62, 95% CI 1.60–4.09; p < 0.001) and anastomotic leakage (OR 1.92, 95% CI 1.01–4.98; p = 0.048). Mortality, surgical site infections, intra-abdominal abscesses, and other postoperative complications were comparable between groups. Based on regional reimbursement tariffs, ERAS implementation was associated with an estimated annual reduction of 567 hospital bed-days. Conclusions: Implementation of a standardized ERAS pathway was associated with reduced postoperative morbidity, lower anastomotic leakage rates, and shorter hospital stay after elective colorectal surgery. These benefits persisted after adjustment for major clinical confounders, supporting the effectiveness of standardized perioperative care. The greatest reduction in hospital stay was observed when ERAS was combined with minimally invasive surgery, emphasizing the complementary role of these strategies in optimizing postoperative recovery.