The lymphatic system plays a central role in lipid absorption by transporting triglyceride-rich particles called chylomicrons (CMs) from the small intestine to the systemic circulation. However, the molecular mechanism by which CMs get into the intestinal lymphatics is unknown. Here, we demonstrated that GPR182, an atypical chemokine receptor in lymphatic endothelial cells, mediates dietary fat absorption. GPR182-KO mice exhibited a selective increase in circulating high-density lipoproteins and are resistant to diet-induced obesity. GPR182 ablation in mice led to poor lipid absorption and thereby a delay in growth during development. GPR182 broadly interacted with and transported lipoproteins. Transmission electron microscopy analysis revealed that, mechanistically, loss of GPR182 prevented CMs from entering the lacteal lumen of the small intestine. Consistent with this, GPR182 blockade with mAbs protected mice from diet-induced obesity and treated existing obesity. Together, our study identifies GPR182 as a lipoprotein receptor that mediates dietary fat absorption and supports GPR182 blockade as a feasible approach to treating obesity and related disorders.

BACKGROUND:Pancreatic surgeries carry high post-discharge complication and readmission rates, often due to delayed recognition of symptoms. This study evaluates feasibility of an application-based patient-reported symptoms system following hospital discharge to track recovery after major oncologic surgery. METHODS:A QI initiative was launched in an academic setting for pancreatic surgery patients, recruiting patients to participate in a real-time symptom monitoring program via a smartphone application. Daily surveys for 2 weeks following discharge assessed 10 symptoms potentially signaling complications. Recovery trajectory was tracked, with algorithmically triggered alerts to Virtual Health Center (VHC) using pre-specified thresholds. Alerts prompted tiered response from VHC technician to nurse or physician, who contacted the patient for symptom verification, intervention, or escalation to the surgical team. After program completion, patients evaluated satisfaction with the application/survey and VHC, using a 0-10 scale, 10 indicating maximum satisfaction. RESULTS:Between August 2023 and February 2024, 21 patients were enrolled to the program at pre-operative visit. Thirteen patients have successfully completed the program, 5 await surgery/discharge, 3 did not participate after discharge. Whipple procedure was most common-8 (61.5%). Median days for patients to enroll after discharge was 1 (0.5-1.5 IQR) and median number of days in program was 14 (13.5-14.5 IQR). On average, patients responded to 81.5% of surveys (11.9 out of 14.6). Alerts to VHC were triggered 138 times, requiring escalation to VHC physician 11 times. Median post-program patient satisfaction was 10/10 (IQR, 7.5-10) with the application/survey and 10/10 (IQR, 10-10) with the VHC. CONCLUSION:The study suggests the feasibility of an application-based system for real-time monitoring of patient-reported symptoms after pancreatic surgery, demonstrating promising early levels of patient compliance and satisfaction.

Background/Objectives. Lymph Node Ratio (LNR) is increasingly recognized as an important prognostic factor in various cancer types, with the potential to enhance patient stratification for intrahepatic (ICC) and extrahepatic (ECC) cholangiocarcinoma. The study aimed to assess the impact of LNR on survival in surgically resected patients with ICC and ECC. Methods. This was a retrospective analysis of National Cancer Database (2004–2020) included ICC and ECC (excluding distal bile duct) patients who underwent primary site resection with adequate lymphadenectomy (≥4 LNs excised). Exclusions comprised age < 18 years, distant metastasis, or incomplete key data. LNR was calculated as the ratio of positive LNs to total examined LNs. Survival probabilities were estimated using Kaplan–Meier analysis and Cox regression. Results. The inclusion criteria were met by 954 patients with ICC and 1607 patients with ECC. In patients with ICC, the median OS time was 62.7 months in LNR0 group, 40.8 months in LNR < 30%, and 25.2 months in LNR ≥ 30% (p < 0.001). In ICC, 3-year OS was 69.3%, 54.6%, and 34% for LNR 0, LNR < 30%, and LNR ≥ 30%, respectively (p < 0.05). When adjusted for age, sex, Charlson–Deyo score, histology, surgical margins, chemo- and radiotherapy using Cox regression, LNR < 30% and LNR ≥ 30% were associated with worse OS in patients with ICC (HR 2.1 (95% CI 1.6–2.7) and HR 2.94 (95% CI 2.3–3.8)) and ECC (HR 2.1 (95% CI 1.8–2.5) and HR 3 (95% CI 2.4–3.7)). Conclusions. It is well-known that LN-negative patients have significantly better survival than LN-positive patients with ICC and ECC. This study strongly demonstrates that survival prognosis can be further stratified based on LNR for ICC and ECC patients and that it is not simply a binary factor.

BACKGROUND:The effectiveness and preferred reconstruction methods of pancreatectomy associated with vein resection (PAVR) for pancreatic cancer, especially for the extensive portal vein/superior mesenteric vein (PV/SMV) resections (more than 4 cm), are still subjects of debate. The aim of this study is to evaluate the safety and feasibility of PAVR by analyzing data from two large institutions from different regions. METHODS:From 2008 to 2018, we identified consecutive series of patients with pancreatic cancer who underwent PAVR at Karolinska University Hospital (KUH), Sweden, and Cancer Institute Hospital, Japanese Foundation of Cancer Research (JFCR), Japan. Both institutions adopted the artery-first approach to enhance surgical precision. This study compared the short- and long-term outcomes, vein resection types, and reconstruction methods between the two centers. RESULTS:A total of 506 patients who underwent PAVR were identified, 211 patients were from KUH and 295 patients were from JFCR. A higher incidence of total pancreatectomy was identified at KUH (24.6 % vs 0.3 %). There were no significant differences in intraoperative estimated blood loss (KUH: 630 ml, JFCR: 600 ml), severe complications rate (8.5 %, 5.1 %), and mortality (2.4 %, 0.7 %). Primary end-to-end anastomosis was primarily performed even if the length of PV/SMV resection was 5 cm or more and achieved successfully with acceptable patency (No thrombus rate: overall cases, 98.0 %; 5 cm or more, 93.5 %). CONCLUSIONS:We report favorable outcomes of PAVR for pancreatic cancer from two high-volume centers in the east and west. Primary end-to-end anastomosis was safe and feasible even if the length of PV/SMV resection was 5 cm or more.

The incidence of hepatocellular carcinoma (HCC) has been steadily rising, underscoring the need for a clear, stage-specific treatment approach. The Barcelona Clinic Liver Cancer (BCLC) staging system remains the most widely used framework for classifying HCC and guiding therapy. Among its classifications, the intermediate stage (BCLC-B) encompasses a highly heterogeneous patient population, with varying degrees of tumor burden and liver function. Traditionally, transarterial chemoembolization has been the standard treatment for this stage, based on earlier evidence. However, recent studies suggest that a subset of BCLC-B patients-particularly those with localized disease-may benefit more from liver resection. This review summarizes current treatment paradigms for BCLC-B HCC, explores emerging subclassifications within this group, and highlights evolving guidelines that support the selective use of surgery in appropriately chosen patients.

INTRODUCTION:Solid pseudopapillary neoplasm (SPN) comprises 2% of pancreatic tumors. We aimed to examine the clinical characteristics, management, and outcomes of SPN in children and adults using US-based national cancer registry data. METHODS:In this retrospective National Cancer Database analysis, children (<18 y) and adults (≥18 y) with SPN were included (2004-2020). RESULTS:A total of 1325 patients (231 children, 1094 adults) with SPN were identified. There were no differences between groups regarding tumor size, metastasis, or stage. Most patients in both groups underwent surgical treatment (96.5% versus 92.1%, P = 0.056), whereas a smaller proportion of children received chemotherapy compared to adults (0.9% versus 4.2%, P = 0.01). The 10-year overall survival rate was 99.1% in children versus 88.0% in adults. In multivariable Cox regression, when adjusted for tumor location and receipt of chemotherapy and radiation, adulthood (hazard ratio [HR]: 5.32, 95% confidence interval [95% CI]: 1.26-22.49, P = 0.02), Charlson-Deyo score ≥2 (HR: 3.04, 95% CI: 1.21-7.63, P = 0.02) compared to 0, stage II (HR: 2.48, 95% CI: 1.27-4.82, P = 0.008), stage III (HR: 6.82, 95% CI: 1.50-31.02, P = 0.01), and stage IV (HR: 5.94, 95% CI: 2.49-14.16, P < 0.001) compared to stage I were associated with an increased risk of mortality, whereas Hispanic compared to White patients (HR: 0.44, 95% CI: 0.21-0.95, P = 0.04) and surgically treated patients had a decreased risk of mortality (HR: 0.10, 95% CI: 0.05-0.21, P < 0.001). CONCLUSIONS:Despite similar stage presentation, children with SPN exhibit prolonged survival compared to adults. Most patients underwent surgical treatment, whereas children were less likely to undergo chemotherapy than adults.

Postoperative delirium is a frequent and serious neurocognitive complication in older surgical patients, characterized by acute impairments in attention, awareness, and cognition. It is associated with increased morbidity, prolonged hospitalization, and persistent cognitive decline. In this narrative review, we synthesize translational research on biological mechanisms underlying delirium and emerging targeted interventions. We conducted a comprehensive search of major biomedical databases, with no date restrictions but prioritizing publications from 2018 to 2025. The multifactorial pathophysiology involves dysregulated cholinergic and dopaminergic signaling, systemic and neuroinflammation, oxidative stress, and metabolic disturbances. Pre-existing cognitive impairment and frailty emerge as key clinical risk factors linked to these mechanisms. Aged rodent models replicate delirium-like cognitive deficits and validate mechanistic pathways, while human neuroimaging studies demonstrate disrupted functional connectivity in attentional and consciousness networks. Genomic and proteomic analyses have identified candidate biomarkers for early detection and risk stratification, and genetic variants associated with inflammation and neurodegeneration contribute to individual vulnerability. Emerging therapies targeting inflammation, microglial activation, mitochondrial function, and neurotransmitter balance show promise in preclinical studies, although clinical trials report mixed results. We advocate integrating basic science with clinical care through thorough preoperative assessment, multicomponent non-pharmacological strategies, and mechanism-based preventive measures to reduce the burden of postoperative delirium.

Objective: To investigate whether tangential versus segmental portomesenteric venous resection (PVR) impacts surgical and oncological outcome in patients undergoing pancreatoduodenectomy for pancreatic cancer with portomesenteric vein (PMV) involvement. Summary Background Data: Current comparative studies on tangential versus segmental PVR as part of pancreatoduodenectomy for pancreatic cancer include all degrees of PMV involvement, including cases where tangential PVR may not be a feasible approach, limiting the clinical applicability. Methods: International retrospective study in 10 centers from 5 countries, including all consecutive patients after pancreatoduodenectomy with PVR for pancreatic cancer with ≤180° PMV involvement on cross-sectional imaging at diagnosis (2014-2020). Cox and logistic regression analyses were performed to investigate the association of tangential versus segmental PVR with overall survival (OS) from surgery, recurrence-free survival (RFS), locoregional recurrence, and in-hospital/30-day major morbidity, adjusting for potential confounders. Results: Overall, 357 patients who underwent pancreatoduodenectomy with PVR were included (42% tangential PVR, 58% segmental PVR). The adjusted risk for in-hospital/30-day major morbidity was 23% (95%CI, 17-32) after tangential and 23% (95%CI, 17-30) after segmental PVR (P=0.98). After adjusting for confounders, PVR type was not associated with OS (HR=0.94 [95%CI, 0.69-1.30]), RFS (HR=0.94 [95% CI, 0.69 to 1.28), and locoregional recurrence (OR=0.76 [95%CI, 0.40-1.46]). Conclusions: In patients undergoing pancreatoduodenectomy for pancreatic cancer with ≤180° PMV involvement, the type of PVR (i.e., tangential vs. segmental) was not associated with differences in surgical and oncological outcome. This suggest that if both procedures are technically feasible, surgeons can choose the type of PVR based on their preference.

BACKGROUND:Radiologic occult metastatic disease (ROMD) in patients with pancreatic ductal adenocarcinoma (PDAC) who undergo contemporary neoadjuvant chemotherapy (NAC) has not been well studied. This study sought to analyze the incidence, risk factors, and oncologic outcomes for patients who underwent the NAC approach for PDAC. METHODS:A retrospective review analyzed a prospectively maintained database of patients who had potentially resectable PDAC treated with NAC and were offered pancreatectomy at our institution from 2011 to 2022. Multivariable regression analysis was performed to assess risk factors associated with ROMD. Kaplan-Meier curves with log-rank analyses were generated to estimate time-to-event end points. RESULTS:The study enrolled 366 patients. Upfront and borderline resectable anatomic staging comprised 80% of the cohort, whereas 20% had locally advanced disease. The most common NAC regimen was FOLFIRINOX (n = 274, 75%). For 55 patients (15%) who harbored ROMD, the most common site was liver-only metastases (n = 33, 60%). The independent risk factors for ROMD were increasing CA19-9 levels during NAC (odds ratio [OR], 7.01; confidence interval [CI], 1.97-24.96; p = 0.008), indeterminate liver lesions (OR, 2.19; CI, 1.09-4.39; p = 0.028), and enlarged para-aortic lymph nodes (OR, 6.87; CI, 2.07-22.74; p = 0.002) on preoperative cross-sectional imaging. Receipt of palliative chemotherapy (p < 0.001) and eventual formal pancreatectomy (p = 0.04) were associated with survival benefit in the log-rank analysis. The median overall survival (OS) of the patients with ROMD was nearly 15 months from the initial diagnosis, with radiologic evidence of metastases occurring after a median of 2 months. CONCLUSIONS:Radiologic occult metastatic disease remains a clinical challenge associated with poor outcomes for patients who have PDAC treated with multi-agent NAC.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with poor long-term survival despite advances in surgical techniques, systemic therapies, and perioperative management. High rates of systemic recurrence following curative-intent resection suggest that many patients harbor minimal residual disease (MRD), microscopic tumor burden that persists postoperatively and remains undetectable by conventional diagnostic tools. Recent advances in liquid biopsy technologies, particularly circulating tumor DNA (ctDNA) analysis, alongside detailed characterization of the PDAC mutational landscape, offer a promising non-invasive approach for MRD detection. Emerging evidence indicates that MRD status can serve as a sensitive prognostic biomarker, identify patients at high risk of relapse, and guide personalized perioperative therapy, including optimization of adjuvant treatment. This review summarizes current knowledge on the biology and detection of MRD in PDAC, its implications for perioperative risk stratification and treatment decision-making, and discusses future directions for integrating MRD assessment into clinical practice to enable more precise, individualized patient management.

Objective Ampullary neoplastic lesions can be resected by endoscopic papillectomy (EP) or transduodenal surgical ampullectomy (TSA) while pancreaticoduodenectomy is reserved for more advanced lesions. We present the largest retrospective comparative study analysing EP and TSA. Design Of all patients in the database, lesions with prior interventions, benign histology advanced malignancy (T2 and more), patients with hereditary syndromes and those undergoing pancreatoduodenectomy were excluded. All remaining cases as well as a subgroup of them, after propensity-matching (nearest-neighbour-method) based on age, gender, anthropometrics, comorbidities, size and histological subtype, were analysed. The median follow-up was 21 months (IQR 10-47) after the primary intervention. Primary outcomes were rates of complete resection (R0) and complications. Groups were compared by Fisher's exact or chi(2) test, Mann-Whitney-U-test and log-rank test for survival. Results Of 1673 patients in the database, 1422 underwent EP and 251 TSA. Of them, 23.2% were excluded for missing or inconclusive data and 19.8% of patients for prior interventions or hereditary syndromes. Final histology showed in 24.2% of EP and 14.8% of TSA patients a histology other than adenoma or adenocarcinoma while advanced cancers were recorded in 10.9% of EP and 36.6% of TSA patients. Finally, 569 EP and 63 TSA were included in the overall analysis, with a higher rate of more advanced cases and higher R0 resection rates in the TSA groups (90.5% vs 73.1%; p<0.01), with additional ablation in the EP group in 14.4%. Severe adverse event rates were 3.2% (TSA) vs 1.9% (EP). Recurrence after histological R0 resection was 16% (EP) vs 3.2% (TSA; p=0.01), and additional therapy for R1 resection was applied in 67% of the 159 cases. Propensity-score-based matching identified 62 pairs of EP/TSA patients with comparable baseline patient and lesion characteristics. The initial R0-rate was 72.6% (EP) compared with 90.3% (TSA, p=0.02) with recurrences found in 8% (EP) vs 3.2% (TSA; p=0.07); reinterventions were more frequent in the EP group. Overall survival was comparable. Conclusions The rate of patients with poor indications due to non-neoplastic disease or advanced cancer is still high for both EP and TSA; multiple retreatments were necessary for EP. Although EP can be considered an appropriate primary therapy for certain ampullary adenomas, case selection for both therapies (especially with regard to the best step-up approach) should be studied further.

Pancreatic neuroendocrine tumors (PanNETs) are rare malignancies of the pancreas, but their incidence is steadily increasing. Standard therapy with antiangiogenic inhibitors, including sunitinib, has shown clinical benefit for advanced PanNETs; however, its long-term effectiveness is limited due to the development of resistance. In this study, we demonstrate that targeting the CD93-IGFBP7 axis enhances the efficacy of sunitinib by normalizing tumor vasculature in PanNETs. Both CD93 and its ligand IGFBP7 are enriched in the tumor microenvironment (TME) of PanNETs. Disrupting the CD93/IGFBP7 interaction with monoclonal antibodies (mAbs) in RIP1-Tag2 mice normalizes tumor vasculature to inhibit tumor progression and metastasis. Combining anti-CD93 mAb and sunitinib synergistically slows tumor growth and improves survival. Mechanistically, CD93 blockade mitigates sunitinib-induced tumor hypoxia and invasiveness, preventing the upregulation of proangiogenic factors. Critically, anti-CD93 mAb treatment prolongs survival in RIP1-Tag2 mice with late-stage, sunitinib-resistant PanNETs. Our results support CD93 blockade as a promising therapeutic approach for advanced PanNETs.