Trending Topics in Gastroenterology | GastroAGI

Peripancreatic Vascular Involvement in AIP: CGH | March 2026

Introduction Autoimmune pancreatitis (AIP) is a unique IgG4-related inflammatory disease with generally favourable outcomes following glucocorticoid therapy. However, beyond pancreatic inflammation, extension into the peripancreatic vasculature can occur, leading to venous stenosis, collateral formation, and in severe cases, gastric varices. These vascular complications remain underrecognized and are not adequately addressed in existing diagnostic guidelines, despite their potential to cause life-threatening bleeding. Problem Statement There is limited large-scale evidence on the true prevalence, clinical significance, and treatment responsiveness of peripancreatic vascular involvement in AIP. Additionally, there is no clear strategy to identify patients at risk of gastric varices or variceal rupture, leading to potential missed opportunities for early intervention. Summary This multicenter Japanese study demonstrates that peripancreatic vascular involvement is common in AIP, occurring in over 50% of patients, most frequently affecting the splenic vein. Collateral formation was observed in 40%, and gastric varices were identified in approximately 11% of those undergoing endoscopy, with rare but serious cases of variceal rupture. Importantly, glucocorticoid therapy showed excellent efficacy, reversing venous stenosis in more than 90% of cases and improving collateral circulation in the majority. Severe splenic vein involvement emerged as a key predictor of gastric varices. These findings highlight the need for routine vascular assessment in AIP and selective endoscopic screening in high-risk patients to prevent fatal complications.

NAPAN Trial in Metastatic Pancreatic Cancer: EJC/ March 2026

Introduction: Metastatic pancreatic cancer continues to carry a dismal prognosis, with limited effective options after failure of first-line gemcitabine-based therapy. Liposomal irinotecan (nal-IRI) combined with 5-fluorouracil/leucovorin (5-FU/LV) is currently an established second-line standard. However, S-1, an oral fluoropyrimidine widely used in Asian populations, has shown promising efficacy and convenience, raising the possibility of an alternative combination strategy with nal-IRI. Problem Statement and Summary: The NAPAN trial was designed to evaluate whether nal-IRI plus S-1 could outperform the current standard nal-IRI plus 5-FU/LV in second-line treatment. However, the study failed to demonstrate superiority, with shorter progression-free survival and a trend toward inferior overall survival in the S-1 arm. While toxicity profiles were comparable, no clinical advantage was observed with S-1. These findings reinforce nal-IRI plus 5-FU/LV as the standard second-line regimen and highlight the ongoing challenge of improving outcomes in metastatic pancreatic cancer beyond current chemotherapy backbones.

GOLP in High-Risk Resectable Intrahepatic Cholangiocarcinoma NEJM, March 2026

Introduction Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver cancer and carries a poor prognosis even after curative surgery. Recurrence rates exceed 50%, particularly in patients with high-risk features such as large tumours (>5 cm), vascular invasion, multifocal disease, lymph-node involvement, or elevated CA19-9. Until now, no neoadjuvant therapy has been established as standard treatment for resectable high-risk iCCA. The GOLP regimen—a combination of gemcitabine–oxaliplatin chemotherapy, lenvatinib (an anti-angiogenic agent), and the PD-1 inhibitor toripalimab—has shown encouraging activity in advanced biliary tract cancers. This phase 2–3 randomised trial evaluated whether neoadjuvant GOLP before surgery could improve outcomes in patients with resectable high-risk iCCA. Summary In this multicenter randomised trial, 178 patients with resectable high-risk intrahepatic cholangiocarcinoma were assigned to either: Neoadjuvant GOLP therapy followed by surgery and adjuvant capecitabine Upfront surgery followed by adjuvant capecitabine (control group) At a median follow-up of 16.9 months, the median event-free survival was significantly longer with neoadjuvant therapy (18.0 months) compared with the control group (8.7 months, P<0.001). Two-year overall survival was 79% in the neoadjuvant group versus 61% in the control group, suggesting a survival advantage, although the predefined statistical threshold was not met. The objective response rate to neoadjuvant therapy was approximately 55%, with major pathological response in 19% and pathological complete response in 5% of patients. Adverse events occurred in 97% of patients receiving GOLP, with grade ≥3 toxicity in 28%, mainly hematologic, but no treatment-related deaths were reported. Key Message Neoadjuvant GOLP therapy significantly improves event-free survival in patients with resectable high-risk intrahepatic cholangiocarcinoma, suggesting a promising strategy to reduce early recurrence and potentially improve long-term outcomes.

Glucose Addiction in Cholangiocarcinoma: Hepatoma Research, 2025

Introduction Cholangiocarcinoma (CCA) is the second most common primary liver cancer and is associated with poor prognosis due to late diagnosis and aggressive tumour biology. Increasing evidence links diabetes mellitus and chronic hyperglycemia with both the development and progression of CCA. Tumour cells demonstrate a strong dependence on glucose metabolism—a phenomenon termed “glucose addiction.” CCA cells frequently upregulate glucose transporters (GLUTs) and glycolytic enzymes, allowing them to utilise glucose for rapid energy generation through aerobic glycolysis (Warburg effect). Beyond energy production, glucose also fuels multiple biosynthetic and signalling pathways that support tumour proliferation, invasion, and resistance to therapy. Summary This review highlights how high glucose environments promote cholangiocarcinoma progression through metabolic and signalling mechanisms. Key mechanisms include: Enhanced glycolysis (Warburg effect): Upregulation of GLUT1, PKM2, HK2, PFK1, and LDHA increases glucose uptake and glycolytic flux, supporting rapid tumour growth. Activation of oncogenic pathways: Hyperglycemia stimulates signaling cascades such as PI3K–AKT–mTOR, HIF-1α, and MYC, which further drive tumor proliferation and metabolic reprogramming. Alternative glucose pathways: Glucose metabolites feed into the pentose phosphate pathway (PPP) and hexosamine biosynthetic pathway (HBP), generating nucleotides, lipids, and glycosylated proteins essential for cancer progression. Tumor microenvironment changes: Increased lactate production leads to acidic microenvironments, enhancing tumor invasion and immune evasion. Importantly, this metabolic dependency may represent an Achilles’ heel of CCA cells. Targeting glucose metabolism—through glycolytic inhibitors, GLUT blockade, or metabolic pathway inhibitors—offers promising therapeutic opportunities for future CCA treatment strategies.

Acute Pancreatitis to Pancreatic Damage and Diabetes: Gastroenterology | March 2026

Introduction Acute pancreatitis (AP) is often considered a self-limited illness once the acute episode resolves, with survival exceeding 95%. However, increasing evidence suggests that AP frequently initiates a cascade of long-term pancreatic complications, including recurrent acute pancreatitis (RAP), early chronic pancreatitis (ECP), chronic pancreatitis (CP), and progressive endocrine dysfunction such as prediabetes and diabetes mellitus. The Goulash-Plus study, a prospective multicenter cohort from the Hungarian Pancreatic Study Group, was designed to longitudinally track structural pancreatic changes and endocrine outcomes following AP, aiming to clarify when disease progression occurs and identify critical periods for monitoring. Summary In this ongoing prospective cohort study, 360 patients with AP were followed for four years. At baseline, most patients (74.7%) had a single AP episode without morphologic pancreatic changes. Over time, structural progression was substantial: the proportion of patients with RAP, ECP, or CP increased from 25.3% at baseline to 55.1% at 4 years. Among patients with a single AP episode initially, 35.1% developed morphologic progression. Endocrine dysfunction progressed even more dramatically. At baseline, 59% had normal glucose metabolism, but by four years, prediabetes or diabetes occurred in 76.4%, and diabetes alone increased from 13.6% to 39.2%. Notably, most progression—both structural and endocrine—occurred within the first two years after AP. These findings highlight AP as a major risk factor for chronic pancreatic disease and metabolic dysfunction, supporting structured follow-up with pancreatic imaging and glucose testing during the first two years after AP.

Metabolic Syndrome Increases Cholangiocarcinoma Risk- Hepatology Feb.26

This large population-based cohort study evaluated the relationship between metabolic syndrome (MetS) and the risk of cholangiocarcinoma (CCA), including both intrahepatic and extrahepatic subtypes. The study included nearly 4.9 million adults aged ≥40 years who underwent national health screening between 2012 and 2017, with follow-up through 2021. Over 35.9 million person-years, 6,117 cases of CCA were identified. Individuals with metabolic syndrome had a 20% higher risk of cholangiocarcinoma compared with those without MetS (adjusted HR 1.20). The increased risk was consistent across subgroups defined by age, sex, liver enzyme levels, and comorbidities. Importantly, the association applied to both intrahepatic and extrahepatic CCA. A clear dose–response relationship was observed: the more metabolic components present (central obesity, hypertension, hyperglycemia, dyslipidemia), the higher the CCA risk. Individuals with five metabolic components had a 67% increased risk compared with those without metabolic abnormalities. These findings remained robust after accounting for the competing risk of all-cause mortality. Clinical implication: Metabolic syndrome is not only a cardiovascular and hepatometabolic concern but also an independent risk factor for biliary tract malignancy. Aggressive management of metabolic risk factors may have potential implications for reducing cholangiocarcinoma incidence.

Blood-Based Early Detection for Pancreatic Cancer: Are We There Yet- Gastroenterology Feb.26

Introduction Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers, largely because it is usually diagnosed late. Individuals with familial risk, pathogenic germline variants, or pancreatic cystic disease carry a substantially higher risk and are now included in surveillance programs. Observational data suggest that surveillance improves resectability and survival, even after accounting for lead-time bias. Current guideline-endorsed surveillance relies on endoscopic ultrasound (EUS) and MRI, performed every 6–12 months. While effective, these approaches are expensive, operator-dependent, invasive, and not universally accessible—fueling intense interest in blood-based molecular early detection tests. The promise: a validated serum biomarker panel The editorial discusses a phase 2 validation study of a commercial serum-based test (PancreaSure), which combines: multiple protein biomarkers, and CA 19-9, into a locked algorithm tested in blinded samples from early-stage PDAC cases and controls drawn largely from high-risk cohorts. The test outperformed CA 19-9 alone in detecting early-stage disease and showed similar performance for stage I and II cancers—an encouraging signal for early detection. The key concern: performance in the intended-use population Despite promising headline performance, the authors urge caution for several reasons: 1) Limited representation of truly high-risk individuals Only a minority of PDAC cases in the study had genetic or familial susceptibility—the very population for whom such a test would be clinically deployed. In this subgroup, the biomarker panel did not clearly outperform CA 19-9 alone. 2) Specificity drops outside hereditary-risk settings Test specificity declined notably in participants without genetic or familial risk—particularly those with abnormal imaging or symptoms but no cancer. This raises concern about false positives if the test is used beyond its narrow intended context. 3) Key real-world confounders were excluded Conditions such as chronic pancreatitis and biliary obstruction—common in high-risk populations and known to elevate biomarkers—were excluded from controls. This limits confidence in how the test would perform in routine surveillance clinics. 4) Not yet evaluated in pancreatic cyst surveillance Patients with pancreatic cysts and worrisome features—a major surveillance group—were not included, leaving a critical evidence gap. Bigger picture: feasibility and integration Even among high-risk individuals, pancreatic cancer remains rare, and uptake of germline testing is low. This makes prospective screening trials difficult and raises fundamental questions: 1. What level of sensitivity and specificity is good enough to justify use? 2. How should biomarker testing integrate with EUS/MRI—replace them, triage them, or simply add cost and complexity? 3. Will biomarker-based screening actually reduce pancreatic cancer–specific or overall mortality? Without answers to these questions, premature adoption risks overdiagnosis, anxiety, unnecessary procedures, and added societal cost. Bottom-line interpretation: Blood-based molecular tests for early pancreatic cancer detection are scientifically promising—but not yet ready to replace or meaningfully augment imaging-based surveillance. Robust prospective studies in clearly defined high-risk populations are still needed to determine: true clinical utility, impact on outcomes, and cost-effectiveness. One-line GastroAGI takeaway Encouraging biomarker data do not yet justify changing pancreatic cancer surveillance practice.

NLR and Acute Pancreaatitis - Front Med 2026

#### Overview The neutrophil-to-lymphocyte ratio (NLR) is a simple, cost-effective biomarker derived from routine blood tests. It measures the ratio of neutrophils (a type of white blood cell involved in inflammation) to lymphocytes (white blood cells associated with immune regulation). NLR has gained attention as a potential early predictor of severity, complications, and mortality in acute pancreatitis (AP). #### Clinical Utility in Acute Pancreatitis NLR has been systematically reviewed and analysed for its role in predicting outcomes in acute pancreatitis. It is particularly useful during the first 24–48 hours after hospital admission, a critical window for risk stratification. Key findings from the systematic review include: 1. **Prediction of Severe Disease**: - Elevated NLR at admission is consistently associated with a higher likelihood of severe acute pancreatitis (SAP), which often requires intensive care. - NLR dynamics (changes over time) during day 1 and day 2 improve the ability to identify patients at risk of persistent organ failure (POF). 2. **Identification of Infectious Complications**: - NLR has shown utility in predicting infection-related complications, such as infected pancreatic necrosis (IPN), which is a serious condition requiring timely intervention. 3. **Mortality Risk**: - An admission NLR greater than 12 has been associated with in-hospital mortality, making it a valuable tool for identifying patients with a poor prognosis. 4. **Discriminative Performance**: - NLR demonstrates acceptable sensitivity and specificity for early triage decisions, making it a practical option for emergency departments. - It remains clinically useful when combined with other scoring systems (e.g., APACHE II, BISAP) or laboratory markers (e.g., procalcitonin, CRP). #### Advantages of NLR - **Accessibility**: NLR can be calculated from routine blood tests, making it readily available without additional costs or delays. - **Reproducibility**: It is a simple and reliable measurement. - **Dynamic Monitoring**: NLR can be tracked over time to assess changes in inflammatory status, which is crucial for managing acute pancreatitis. #### Limitations and Considerations - **Time-Specific Thresholds**: The predictive accuracy of NLR depends on the timing of measurement (e.g., admission, 24 hours, 48 hours). Fixed thresholds may not account for dynamic changes. - **Etiological Factors**: The performance of NLR may vary based on the underlying cause of pancreatitis (e.g., biliary pancreatitis vs. hypertriglyceridemia). - **Integration with Other Tools**: While NLR is valuable, it is most effective when used alongside validated clinical scores and other biomarkers. #### Recommendations - The use of NLR for early triage in acute pancreatitis is recommended, particularly in the first 48 hours. - Time-specific thresholds should be locally calibrated to optimize sensitivity and specificity. - Combining NLR with clinical scores and other laboratory markers (e.g., CRP, procalcitonin) can enhance decision-making accuracy. #### Systematic Review Registration The systematic review evaluating NLR in acute pancreatitis is registered with PROSPERO (CRD420251169592), ensuring transparency and methodological rigour. ### Conclusion The neutrophil-to-lymphocyte ratio (NLR) is a promising biomarker for early risk stratification in acute pancreatitis. Its ability to predict severe disease, persistent organ failure, infectious complications, and mortality makes it a valuable tool for guiding clinical decisions during the critical early phase of hospitalisation. Future studies should focus on refining thresholds, validating findings across different populations, and integrating NLR into composite predictive models.

HTG-Induced Pancreatitis

### HTG-Induced Pancreatitis: Overview and Latest Treatments **What is HTG-Induced Pancreatitis?** HTG-induced pancreatitis refers to acute pancreatitis caused by severe hypertriglyceridemia (HTG), which is an abnormally high level of triglycerides in the blood. Triglycerides are a type of fat (lipid) found in the bloodstream, and their elevation can lead to inflammation of the pancreas. Acute pancreatitis is a potentially life-threatening condition characterized by inflammation of the pancreas, causing abdominal pain, nausea, vomiting, and systemic complications. When triglyceride levels exceed 1,000 mg/dL (11.3 mmol/L) — and particularly when they surpass 2,000 mg/dL (22.6 mmol/L) — the risk of developing pancreatitis increases significantly. HTG is the third most common cause of acute pancreatitis after gallstones and alcohol. **Pathophysiology:** - In severe HTG, triglycerides in the blood are hydrolyzed by pancreatic lipase into free fatty acids (FFAs). - Excess FFAs overwhelm the pancreas's buffering capacity, leading to toxic effects on pancreatic cells, local ischemia, and inflammation. - This cascade of events results in acute pancreatitis. --- ### Risk Factors for HTG-Induced Pancreatitis: 1. **Genetic predisposition**: Familial hyperlipoproteinemia or mutations in genes like LPL, APOC2, APOA5, and GPIHBP1. 2. **Secondary causes**: Uncontrolled diabetes mellitus, obesity, metabolic syndrome, hypothyroidism, pregnancy, alcohol abuse, and certain medications (e.g., estrogens, isotretinoin, beta-blockers, or antiretrovirals). 3. **Diet**: High-fat diets can exacerbate the condition in susceptible individuals. 4. **Other factors**: Poorly controlled lipid-lowering therapy or nonadherence to treatment. --- ### Clinical Presentation: - **Symptoms**: Severe epigastric pain radiating to the back, nausea, vomiting, and abdominal tenderness. - **Lab findings**: Elevated serum triglycerides (often >1,000 mg/dL), elevated pancreatic enzymes (amylase and lipase), and evidence of systemic inflammation. - **Imaging**: Abdominal CT or MRI may reveal pancreatic inflammation, necrosis, or fluid collections. --- ### Latest Treatment Strategies for HTG-Induced Pancreatitis: - **Supportive Care**: - **Fluid resuscitation**: Aggressive intravenous (IV) fluids (e.g., lactated Ringer's solution) to maintain hemodynamic stability and prevent complications. - **Pain management**: Use of opioid analgesics (e.g., morphine or fentanyl) for severe abdominal pain. - **Nutritional support**: Early enteral feeding (via nasogastric or nasojejunal tube) is preferred over parenteral nutrition to reduce the risk of infections and improve outcomes. - **Monitoring and management of complications**: - Monitor for systemic inflammatory response syndrome (SIRS), organ failure, and local complications (e.g., necrosis, abscess, or pseudocyst). - Treat complications such as infected pancreatic necrosis with antibiotics or surgical intervention if needed. --- #### 2. **Rapid Reduction of Triglycerides:** The goal is to reduce triglyceride levels rapidly, ideally below 500 mg/dL, to mitigate ongoing pancreatic damage. - **Insulin Infusion**: - Insulin lowers triglycerides by activating lipoprotein lipase (LPL), which breaks down circulating triglycerides. - Indicated in patients with concurrent diabetes, metabolic syndrome, or hyperglycemia. - Dose: Continuous IV insulin infusion with glucose monitoring to prevent hypoglycemia. - **Plasmapheresis (Therapeutic Plasma Exchange)**: - Plasmapheresis is a procedure that removes triglyceride-rich plasma and replaces it with fresh plasma or albumin. - It is considered in severe cases with extremely high triglycerides (>2,000 mg/dL) or when there is a poor response to medical therapy. - Plasmapheresis can rapidly lower triglycerides and improve symptoms, but access to this therapy may be limited. - **Heparin**: - Low-dose unfractionated heparin can stimulate lipoprotein lipase activity and reduce triglycerides. However, its use is controversial due to the risk of bleeding and limited evidence supporting its efficacy. --- #### 3. **Lipid-Lowering Medications:** Once the acute phase is stabilized, long-term lipid-lowering therapy is initiated to prevent recurrence. - **Fibrates** (e.g., fenofibrate, gemfibrozil): - First-line agents for lowering triglycerides in patients with hypertriglyceridemia. - They reduce hepatic production of triglycerides and increase triglyceride clearance. - **Omega-3 Fatty Acids**: - High-dose omega-3 fatty acids (e.g., 2-4 g/day of EPA/DHA) can effectively lower triglycerides. - They are often used as an adjunct to fibrates or statins. - **Statins**: - While primarily used for cholesterol reduction, statins can modestly lower triglycerides and reduce cardiovascular risk. - **Niacin**: - Niacin (vitamin B3) reduces triglycerides by inhibiting hepatic triglyceride synthesis. However, its use is limited by side effects like flushing and hepatotoxicity. --- #### 4. **Management of Underlying Conditions:** - **Diabetes management**: Tight glycemic control with insulin or oral hypoglycemic agents. - **Weight loss**: Lifestyle modifications, including weight loss and exercise, can reduce triglyceride levels. - **Dietary changes**: - Low-fat diet (<15% of total calories from fat). - Avoid simple sugars, alcohol, and refined carbohydrates. - **Alcohol cessation**: Essential for patients with alcohol-related HTG. --- #### 5. **Experimental and Emerging Therapies:** - **Gene Therapy**: - Research is ongoing into gene therapies targeting mutations in genes like LPL and APOC3 to treat familial hypertriglyceridemia. - **Apolipoprotein C-III (APOC3) Inhibitors**: - Drugs like volanesorsen (an antisense oligonucleotide targeting APOC3) have shown promise in reducing triglycerides in patients with familial chylomicronemia syndrome (FCS). - **ANGPTL3 Inhibitors**: - Angiopoietin-like protein 3 (ANGPTL3) inhibitors (e.g., evinacumab) are being studied for their ability to lower triglycerides by enhancing lipoprotein lipase activity. --- ### Prognosis and Prevention: - With prompt and appropriate management, most patients recover from HTG-induced pancreatitis without long-term complications. - Preventive strategies include strict lipid control, lifestyle modifications, and adherence to medical therapy to prevent recurrence. --- ### Key Takeaways: - HTG-induced pancreatitis is a serious condition requiring rapid diagnosis and treatment. - Acute management focuses on supportive care and rapid triglyceride reduction using insulin infusions or plasmapheresis. - Long-term management involves lipid-lowering therapies, lifestyle changes, and addressing underlying causes. - Emerging therapies such as APOC3 and ANGPTL3 inhibitors hold promise for patients with severe or refractory hypertriglyceridemia.

EUS -guided Biliary Drainage in acute cholecystitis(GIE, Jan-2026)

The article discusses the efficacy and clinical durability of EUS-guided gallbladder drainage (EUS-GBD) as a treatment for acute cholecystitis in high-risk surgical patients. Acute cholecystitis, which is an inflammation of the gallbladder, is traditionally treated with surgical intervention. However, in patients who are not candidates for surgery due to high risk, EUS-GBD has emerged as a reliable alternative. This minimally invasive procedure has been supported by recent guidelines over percutaneous transhepatic gallbladder drainage (PTGBD) in such cases. The study systematically analyzed data from 18 studies, including 701 patients, with follow-up periods exceeding 1 year. The technical success rate of EUS-GBD was 95.8%, and the clinical success rate was 94.3%. Recurrence of cholecystitis was low (4.2%), while readmission rates were 19% and reintervention rates were 6%. Stent patency was observed for an average of 418.8 days, and the need for repeat endoscopy due to stent obstruction or occlusion was minimal (2.9%). Overall, the procedure showed a low rate of adverse events. In conclusion, EUS-GBD is a technically effective, clinically durable, and safe treatment for acute cholecystitis in high-risk patients, offering a viable alternative to traditional surgical approaches with sustained long-term outcomes.