Background: Surgery still represents the gold standard of treatment for resectable pancreatic ductal adenocarcinoma (PDAC). Neoadjuvant treatments (NAT), currently proposed for borderline and locally advanced PDACs, are gaining momentum even in resectable tumors due to the recent interesting concept of “biological resectability”. In this scenario, CA 19.9 is having increasing importance in preoperative staging and in the choice of therapeutic strategies. We aimed to assess the state of the art and to highlight the future perspectives of CA 19.9 use in the management of patients with resectable pancreatic cancer. Methods: A PubMed database search of articles published up to December 2021 has been carried out. Results: Elevated pre-operative levels of CA 19.9 have been associated with reduced overall survival, nodal involvement, and margin status positivity after surgery. These abilities of CA 19.9 increase when combined with radiological or different biological criteria. Unfortunately, due to strong limitations of previously published articles, CA 19.9 alone cannot be yet considered as a key player in resectable pancreatic cancer patient management. Conclusion: The potential of CA 19.9 must be fully explored in order to standardize its role in the “biological staging” of patients with resectable pancreatic cancer.

Background: Poor prognosis of pancreatic ductal adenocarcinoma (PDAC) is mainly due to the lack of effective early-stage detection strategies. Even though the link between inflammation and PDAC has been demonstrated and inflammatory biomarkers proved their efficacy in predicting several tumours, to date they have a role only in assessing PDAC prognosis. Recently, the studies of interactions between nanosystems and easily collectable biological fluids, alone or coupled with standard laboratory tests, have proven useful in facilitating PDAC diagnosis. Notably, tests based on magnetic levitation (MagLev) of biocoronated nanosystems have demonstrated high diagnostic accuracy in compliance with the criteria stated by WHO. Herein, the author developed a synergistic analysis that combines a user-friendly MagLev-based approach and common inflammatory biomarkers for discriminating PDAC subjects from healthy ones. Materials and Methods: Plasma samples from 24 PDAC subjects and 22 non-oncological patients have been collected and let to interact with graphene oxide nanosheets. Biomolecular corona formed around graphene oxide nanosheets have been immersed in a Maglev platform to study the levitation profiles. Inflammatory biomarkers such as neutrophil-to-lymphocyte ratio (NLR), derived-NLR (dNLR), and platelet to lymphocyte ratio have been calculated and combined with results obtained by the MagLev platform. Results: MagLev profiles resulted significantly different between non-oncological patients and PDAC and allowed to identify a MagLev fingerprint for PDAC. Four inflammatory markers were significantly higher in PDAC subjects: neutrophils (P=0.04), NLR (P=4.7 ×10⁻⁶), dNLR (P=2.7 ×10⁻⁵), and platelet to lymphocyte ratio (P=0.002). Lymphocytes were appreciably lower in PDACs (P=2.6 ×10⁻⁶). Combining the MagLev fingerprint with dNLR and NLR returned global discrimination accuracy for PDAC of 95.7% and 91.3%, respectively. Conclusions: The multiplexed approach discriminated PDAC patients from healthy volunteers in up to 95% of cases. If further confirmed in larger-cohort studies, this approach may be used for PDAC detection.

Pancreatic ductal adenocarcinoma (PDAC) represents an unmet medical need. Difficult/late diagnosis as well as the poor efficacy and high toxicity of chemotherapeutic drugs result in dismal prognosis. With the aim of improving the treatment outcome of PDAC, we tested the effect of combining Gemcitabine with a novel single chain bispecific antibody (scDb) targeting the cancer-specific hERG1/β1 integrin complex. First, using the scDb (scDb-hERG1-β1) in immunohistochemistry (IHC), Western blot (WB) analysis and immunofluorescence (IF), we confirmed the presence of the hERG1/β1 integrin complex in primary PDAC samples and PDAC cell lines. Combining Gemcitabine with scDb-hERG1-β1 improved its cytotoxicity on all PDAC cells tested in vitro. We also tested the combination treatment in vivo, using an orthotopic xenograft mouse model involving ultrasound-guided injection of PDAC cells. We first demonstrated good penetration of the scDb-hERG1-β1 conjugated with indocyanine green (ICG) into tumour masses by photoacoustic (PA) imaging. Next, we tested the effects of the combination at either therapeutic or sub-optimal doses of Gemcitabine (25 or 5 mg/kg, respectively). The combination of scDb-hERG1-β1 and sub-optimal doses of Gemcitabine reduced the tumour masses to the same extent as the therapeutic doses of Gemcitabine administrated alone; yielded increased survival; and was accompanied by minimised side effects (toxicity). These data pave the way for a novel therapeutic approach to PDAC, based on the combination of low doses of a chemotherapeutic drug (to minimize adverse side effects and the onset of resistance) and the novel scDb-hERG1-β1 targeting the hERG1/β1 integrin complex as neoantigen.

Introduction: Lymph-nodal involvement (N+) represents an adverse prognostic factor after pancreatoduodenectomy (PD) for pancreatic adenocarcinoma (PDAC). Preoperative diagnostic and staging modalities lack sensitivity for identifying N+. This study aimed to investigate preoperative carbohydrate antigen 19.9 (CA 19.9) in predicting the N+ stage in resectable-PDAC (R-PDAC). Methods: Patients included in a multi-institutional retrospective database of PDs performed for R-PDAC from January 2000 to June 2021 were analysed. A preoperative laboratory value of CA 19.9 greater than 37 U/l was used in univariate and multivariate logistic regression analysis to determine a possible association with N+. Additionally, different cut-offs of CA 19.9 related to the preoperative clinical T (cT) stage was assessed to evaluate the risk of N+. Results: A total of 2034 PDs from thirteen centres were included in the study. CA 19.9 greater than 37 U/l was significantly associated with higher N+ at univariate and multivariate analysis (P<0.001). CA 19.9 levels greater than 37 U/l were associated with N+ in 75.9%, 81.3%, and 85.7% of patients, respectively, in cT1, cT2, and cT3 tumours and with higher cut-off values for all cT stages. Conclusion: Lymph-nodal involvement is strongly related to preoperative CA 19.9 levels. Specially in patients staged as cT3 the CA 19.9 could represent a valid and easy tool to suspect nodal involvement. Due to these findings, R-PDAC patients with elevated CA 19.9 values should be considered in a more biologically advanced stage.

Antimicrobial resistance is an escalating global threat that undermines the efficacy of modern antibiotics and places a substantial economic burden on healthcare systems—costing Europe alone over EUR 11.7 billion each year due to rising medical expenses and productivity losses. While genomics and transcriptomics have significantly advanced our understanding of the genetic foundations of resistance, they often fail to capture the dynamic, real-time adaptations that enable bacterial survival. Proteomics, particularly mass spectrometry-based strategies, bridges this gap by uncovering the functional protein-level changes that drive resistance, persistence, and tolerance under antibiotic pressure. In this review, we examine how proteomic approaches provide new insights into resistance mechanisms across various antibiotic classes, with a particular focus on β-lactams, aminoglycosides, and fluoroquinolones, highlighting clinically relevant pathogens, especially members of the ESKAPE group. Finally, we examine future directions, including the integration of proteomics with other omic technologies and the growing role of artificial intelligence in resistance prediction, paving the way for more predictive, personalized, and effective solutions to combat antimicrobial resistance.

Background: Pancreatic ductal adenocarcinoma (PDAC) represents a challenging disease for the surgeon, oncologist, and radiation oncologist in both diagnostic and therapeutic settings. Surgery is currently the gold standard treatment, but the role of neoadjuvant treatment (NAD) is constantly evolving and gaining importance in resectable PDACs. The aim of this narrative review is to report the state of the art and future perspectives of neoadjuvant therapy in patients with PDAC. Methods: A PubMed database search of articles published up to September 2022 was carried out. Results: Many studies showed that FOLFIRINOX or Gemcitabine-nab-paclitaxel in a neoadjuvant setting had a relevant impact on overall survival (OS) for patients with locally advanced and borderline resectable PDAC without increasing post-operative complications. To date, there have not been many published multicentre randomised trials comparing upfront surgery with NAD in resectable PDAC patients, but the results obtained are promising. NAD in resectable PDAC showed long-term effective benefits in terms of median OS (5-year OS rate 20.5% in NAD group vs. 6.5% in upfront surgery). NAD could play a role in the treatment of micro-metastatic disease and lymph nodal involvement. In this scenario, given the low sensitivity and specificity for lymph-node metastases of radiological investigations, CA 19-9 could be an additional tool in the decision-making process. Conclusions: The future challenge could be to identify only selected patients who will really benefit from upfront surgery despite a combination of NAD and surgery.