Pancreatic ductal adenocarcinoma (PDAC) remains a formidable malignancy with rising incidence and dismal long-term survival, largely due to late-stage presentation and intrinsic resistance to therapy. Recent advances in the multidisciplinary management of PDAC have reshaped treatment paradigms across disease stages. For localized disease, innovations in surgical techniques and the adoption of neoadjuvant strategies have improved resection rates and survival outcomes. In metastatic settings, multiagent chemotherapy regimens and precision therapies targeting BRCA mutations and rare gene fusions are expanding treatment options. Immunotherapeutic modalities, including checkpoint inhibitors, adoptive cell therapies, and mRNA vaccines, show emerging promise despite PDAC’s traditionally immunosuppressive microenvironment. This review synthesizes the current evidence on established therapies and critically evaluates novel and investigational approaches poised to redefine the therapeutic landscape of pancreatic cancer.

Immunotherapy has emerged as a transformative approach in gastrointestinal (GI) cancers, addressing historically poor survival rates in advanced-stage disease. Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis demonstrate remarkable efficacy in colorectal cancer with deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H), exemplified by trials like NICHE-2 achieving exceptional pathological response rates. However, significant limitations persist, including resistance in some dMMR/MSI-H tumors, minimal efficacy in proficient mismatch repair (pMMR) tumors, and low overall response rates across most GI malignancies due to tumor heterogeneity and immune evasion mechanisms. Predictive biomarkers such as tumor mutational burden (TMB) and PD-L1 expression are crucial for optimizing patient selection, while hypermutated pMMR tumors with POLE mutations represent emerging therapeutic opportunities. In pancreatic adenocarcinoma, where survival remains dismal, combination strategies with chemotherapy and novel approaches like cancer vaccines show promise but lack transformative breakthroughs. Esophagogastric cancers benefit from ICIs combined with chemotherapy, particularly in MSI-H and HER2-positive tumors, while hepatocellular carcinoma has achieved significant progress with combinations like atezolizumab–bevacizumab and durvalumab–tremelimumab surpassing traditional therapies. Biliary tract cancers show modest improvements with durvalumab–chemotherapy combinations. Despite these advances, immunotherapy faces substantial challenges including immune-related adverse events, acquired resistance through cancer immunoediting, and the need for biomarker-driven approaches to overcome tumor microenvironment barriers. This review discusses key clinical trials, therapeutic progress, and emerging modalities including CAR T-cell therapies and combination strategies, emphasizing the critical need to address resistance mechanisms and refine precision medicine approaches to fully realize immunotherapy’s potential in GI malignancies.

Background: Type 2 diabetes mellitus (T2DM) is increasingly seen as a chronic inflammatory state, with the neutrophil‐to‐lymphocyte ratio (NLR) studied as a new biomarker of systemic inflammation. Evidence links NLR to glycemic control, but its consistency and strength vary. This review summarizes data on NLR's relationship with glycemic indicators, such as hemoglobin A1c (HbA1c), across different T2DM glycemic states. Methods: A systematic literature search was carried out in PubMed/MEDLINE, Scopus, Web of Science, and Embase through November 2025 to find studies that reported both NLR and glycemic control indicators in adults with T2DM. Data were systematically extracted based on predefined criteria. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were combined using random‐effects models. Heterogeneity was measured using the I² statistic, and robustness was assessed using sensitivity analyses. Publication bias was investigated using Begg's and Egger's tests, trim‐and‐fill analysis, and funnel plot examination. All statistical analyses were conducted using STATA 18 (StataCorp, College Station, TX, USA). Results: The meta‐analysis consisted of 27 studies (37 comparisons) with a total of 48,714 individuals from 11 nations. NLR demonstrated a stepwise gradient with deteriorating glycemic control: poorly controlled T2DM (HbA1c > 7%) had higher NLR than well‐controlled T2DM (HbA1c ≤ 7%) ( p < 0.001), prediabetes (HbA1c 5.7–6.4%) ( p < 0.001), and normoglycemia (HbA1c ≤ 5.7%) ( p = 0.037). Conclusions: NLR rises progressively with deteriorating glycemic control and is markedly raised in poorly controlled T2DM. These observations endorse NLR as an inexpensive, widely available inflammatory biomarker that can augment conventional glycemic measures in the clinical setting.

IgG4-related disease (IgG4-RD) is a systemic fibro-inflammatory condition characterized by elevated IgG4 serum levels and tissue infiltration by IgG4-positive plasma cells. While often presenting with organ-specific involvement, such as sialadenitis or pancreatitis, its rheumatologic manifestations are rare and poorly understood. IgG4-RD often overlaps with autoimmune diseases such as rheumatoid arthritis (RA), posing a diagnostic challenge, particularly in seronegative presentations. We report a 48-year-old male presenting with progressive symmetrical polyarthritis mimicking rheumatoid arthritis. Laboratory findings showed elevated serum IgG4 levels and inflammatory markers, while autoantibodies (RF, ACPA, ANA, ANCA) were negative. A biopsy of a submandibular gland revealed dense lymphoplasmacytic infiltrates + fibrosis and IgG4-positive plasma cells, confirming the diagnosis of IgG4-RD. The patient responded well to a combination of glucocorticoids and methotrexate, with complete symptom resolution within one month and normalization of inflammatory markers.The therapeutic response observed in this case demonstrates the effectiveness of immunosuppression therapy in IgG4-RD management, while emphasizing the need for long-term follow-up. This case underscores the diagnostic challenges in recognizing arthritis in a patient with biopsy-confirmed IgG4-related sialadenitis particularly when seronegative rheumatoid arthritis (RA) remains a plausible differential diagnosis.The overlapping clinical features and shared treatment responses make it challenging to attribute the arthritis to a single etiology.This report emphasizes the importance of considering IgG4-RD in the differential diagnosis of atypical arthritis presentations, particularly in patients with systemic manifestations. Histopathological confirmation, supported by clinical and serological evaluation, remains pivotal in guiding diagnosis and management. Long-term follow-up is essential to monitor for evolving features, including the potential development of overlapping conditions, and to ensure optimal treatment outcomes. Early recognition and tailored interventions are critical to preventing complications and improving patient quality of life. IgG4-related disease (IgG4-RD) must be considered in the differential diagnosis of seronegative arthritis, especially when systemic symptoms or organ involvement are present. This case underscores the growing recognition of IgG4-RD in rheumatologic practice and the importance of a multidisciplinary approach to diagnosis and management. Clinicians should maintain heightened awareness of the overlap between IgG4-RD and rheumatoid arthritis (RA), advocating for the integration of histopathology, imaging, and serological testing to ensure accurate diagnosis. Additionally, long-term follow-up is essential to monitor disease progression, recurrence, development of new symptoms, and treatment response, ultimately enhancing patient care and outcomes.

Background : Metabolic syndrome (MetS) is a significant global health burden and a known risk factor of cardiovascular disease and diabetes. Growing evidence also links MetS to cancer development, likely via chronic inflammation, insulin resistance, and hormone disruption. However, its association with laryngeal cancer remains largely unclear and underexplored. Methods: For this review, we thoroughly searched PubMed/MEDLINE, Scopus, and Web of Science for observational studies investigating associations of MetS with laryngeal or head and neck cancers (HNCs) until 1 August 2025. Five large population-based studies were found to meet inclusion criteria, and risk of bias was assessed using the Joanna Briggs Institute checklist (JBI). Results: Three Korean cohort studies consistently found that MetS increased the risk of laryngeal cancer (HR 1.13–1.32), independent of smoking and alcohol use. Hypertension and hyperglycemia were the most consistent components associated with increased risk, and chronic MetS conferred the highest hazard. In contrast, analyses from the UK Biobank (HNC) and SEER-Medicare (HNSCC) cohorts showed null and inverse associations, respectively. Additional findings included dose–response effects with increasing MetS components, U-shaped associations for HDL-C and waist circumference and increased risk associated with elevated C-reactive protein. Conclusions: Current evidence suggests a possible association between MetS and risk of laryngeal cancer, although the direction and strength of effect vary across populations. Findings from Korean cohorts provide consistent signals of increased risk, whereas Western datasets have not replicated this pattern. Overall, the certainty of evidence is low to moderate, warranting cautious interpretation and further validation in diverse populations before inferring causality.

Background and Aims: Circulating tumor DNA (ctDNA) has emerged as a promising biomarker of tumor burden and minimal residual disease. As total neoadjuvant therapy (TNT) increasingly supports organ‐preserving strategies in locally advanced rectal cancer (LARC), reliable markers of treatment response are needed. This review evaluates the prognostic and predictive value of ctDNA in this setting. Methods: Following PRISMA guidelines, we systematically reviewed studies across PubMed/MEDLINE, Web of Science, Cochrane and Google Scholar evaluating ctDNA during or after TNT in LARC reporting treatment‐response or survival outcomes. Results: Seven studies met inclusion criteria. Baseline ctDNA detection was near‐universal (83–100%) but lacked discriminatory value. ctDNA declined progressively during TNT, with post‐TNT negativity correlating with clinical or pathological complete response ( p = 0.007–0.038). Persistent positivity predicted residual disease and inferior survival (DFS HR 4.03; OS HR 23.0), with presurgical ctDNA in GEMCAD showing preferential association with hepatic recurrence suggesting a marker of systemic rather than locoregional disease. Post‐TNT ctDNA demonstrated high specificity but low sensitivity (23%–45%) for residual disease, and preceded clinical recurrence detection by weeks to months. Conclusions: ctDNA clearance at the end of TNT may represent a biologically meaningful marker of treatment response and recurrence risk. However, current data derive from small, heterogeneous cohorts with variable assay platforms and sampling schedules, and ctDNA's limited sensitivity precludes its use as a standalone tool for non‐operative management selection.