Pancreas/Biliary, in full.

Kyoto 2024 (IAP) is still the core algorithm for IPMN, and nothing in it has changed. MD-, mixed- and BD-IPMN all go through one HRS/WF algorithm. MDCT, MRI/MRCP and EUS are treated as equivalent for diagnosis, with tumor markers and HbA1c added. Since 2024, EUS imaging and EUS-FNA cytology count toward HRS/WF when EUS is done. High-risk stigmata are: obstructive jaundice with a head cyst; an enhancing mural nodule >=5 mm or a solid component; MPD >=10 mm; or suspicious/positive cytology. Worrisome features are: pancreatitis; CA19-9 >37 U/mL; new-onset or worsening diabetes within 1 year; cyst >=30 mm; enhancing mural nodule <5 mm; thickened or enhancing cyst wall; MPD 5-9 mm; abrupt change in duct caliber with distal atrophy; lymphadenopathy; or growth >=2.5 mm/year. HRS should prompt consideration of resection, weighed against fitness and life expectancy; it does not mean automatic surgery. WF should prompt EUS and multidisciplinary review. EUS-FNA is used only when its result would change management. Surveillance of non-resected BD-IPMN depends on size: <20 mm at 6 months, then every 18 months; 20 to <30 mm every 6 months twice, then every 12 months; >=30 mm every 6 months. Under Kyoto, surveillance may stop for cysts <20 mm with no change and no WF after 5 years, and should stop if the patient is unfit for surgery or life expectancy is <10 years. Continued surveillance remains an option because the risk of a separate pancreatic cancer keeps accumulating. NEW in 2026: an AGA Clinical Practice Update (Das, Serper, Vege; expert opinion, not formally graded) adds stopping rules by age and comorbidity for any pancreatic cystic lesion. (1) At any age, patients with significant comorbidity (age-adjusted Charlson index >=3-5) and an incidental, especially low-risk, cyst should be counseled against routine surveillance. (2) Over 65, cysts <=15 mm stable for 5 years with no WF/HRS should be considered for stopping after shared decision-making. 'Stable' means growth under 3 mm/year and under 6 mm over 2 years. (3) Over 75, cysts <30 mm stable for 5 years with no WF/HRS call for a discussion of whether surveillance is worth continuing, and it may stop if the patient accepts the small residual risk. (4) If comorbidity develops that rules out surgery, stopping should be discussed, even when WF/HRS were found earlier, provided there is no evidence of HGD or cancer. (5) After resection with no HGD or cancer, the remnant follows the same rules, counting surveillance time before surgery, and stopping is discussed after 5 years of stability. (6) After resection with HGD, MRI/MRCP every 6 months for 2 years and then yearly while the patient can still have a completion pancreatectomy. If invasive cancer was found, the remnant follows oncology guidelines. In both cases, stopping is discussed with oncology after 5 years of remnant stability with no WF/HRS. The resect-all-MCNs rule and the familial/germline (CAPS) screening pathway come from other guidelines, not from either of these documents.

Diagnosis is unchanged and still follows the separate ESGE diagnostic guideline (Endoscopy 2025;57:166-185). Start with MRI/MRCP plus laboratory tests, read CA19-9 only after decompression, and check IgG4 when IgG4-related sclerosing cholangitis is suspected. For distal extrahepatic strictures with no pancreatic mass, do combined same-session EUS-guided tissue acquisition plus ERCP brushing and biopsy. For perihilar strictures, sample by ERCP first and move to cholangioscopy-guided biopsy if the result is indeterminate. Do not place an uncovered SEMS (USEMS) until malignancy is confirmed. Management now follows the 2026 ESGE biliary stricture management guideline, which replaces the 2018 stenting guideline and brings it into line with the 2022 therapeutic EUS guideline. Benign: post-cholecystectomy strictures get temporary multiple plastic stents (MPSs), exchanged every 3-4 months with as many stents as possible, for about 12 months. A fully covered SEMS (FCSEMS) is an option only if the stricture is more than 2 cm below the hepatic confluence or the patient will not comply with repeated ERCPs. Anastomotic strictures after liver transplant get MPSs, or a temporary FCSEMS if more than 2 cm below the confluence. Nonanastomotic post-transplant strictures that can be treated endoscopically get MPSs plus balloon dilation if needed. Chronic pancreatitis strictures get a temporary 8-10 mm FCSEMS for 6-12 months. High-grade PSC strictures get balloon dilation alone, with no stent, because stenting adds no benefit and may add adverse events. Endotherapy is indicated for a benign stricture with liver tests raised for more than 1 month and/or cholangitis. Malignant distal: drain before surgery only selectively (cholangitis, severe jaundice or pruritus, delayed surgery). When drainage is needed before surgery or neoadjuvant therapy, or for palliation, place a 10-mm SEMS endoscopically. Endoscopic drainage is preferred over surgery or PTBD for inoperable obstruction. Malignant hilar: manage in high-volume centres with a hepatobiliary multidisciplinary team (MDT). ERCP is preferred over PTBD for preoperative drainage. Palliate Bismuth I-II with ERCP. For Bismuth III-IV, ERCP or ERCP combined with EUS-guided drainage (EUS-BD) is preferred over primary PTBD, with PTBD as a complement if needed. For proven Bismuth II-IV, aim to drain more than 50%, ideally 70% or more, of the viable nonatrophic liver volume using several routes as needed. Use plastic stents when the drainage strategy is undefined or the centre is not expert. USEMS are for expert centres when the diagnosis is proven, the tumour is unresectable, and complete drainage is predicted. After failed or unfeasible ERCP, EUS-BD is recommended over PTBD. Use hepaticogastrostomy (EUS-HGS) if there is a duodenal stricture, and EUS-HGS or choledochoduodenostomy (EUS-CDS) if there is not. PTBD is used if EUS-BD fails. In surgically altered anatomy, benign disease gets enteroscopy-assisted ERCP first; malignant disease gets enteroscopy-assisted ERCP or EUS-BD. Give antibiotics before ERCP in selected cases: predicted incomplete drainage, hilar strictures, immunocompromised patients, PSC, cholangioscopy. This follows the ESGE ERCP-adverse-events guideline. Etiology-specific care (Strasberg injuries, IgG4-SC, Mirizzi, choledochal cysts) is unchanged.

Evaluate suspected pancreatic adenocarcinoma with a dedicated pancreatic-protocol (multiphasic, contrast-enhanced) CT of the abdomen as the preferred imaging for diagnosis and staging (MRI/MRCP is an acceptable alternative); PET/CT may be added after, never as a substitute for, protocol CT/MRI in higher-risk situations. Obtain tissue confirmation, preferably by EUS-guided FNA/FNB with core biopsy where feasible; biopsy is generally required before neoadjuvant or palliative therapy, whereas patients with clearly resectable disease may proceed to surgery without preoperative biopsy. Measure baseline CA 19-9 (interpret after biliary decompression / with normal bilirubin; it can be falsely low in Lewis-antigen-negative patients and falsely elevated with cholestasis). Offer GERMLINE testing for inherited susceptibility to EVERY patient with confirmed pancreatic adenocarcinoma regardless of family history, using a comprehensive multi-gene panel; separately, for patients with locally advanced or metastatic disease who are candidates for anti-cancer therapy, obtain TUMOR/SOMATIC molecular profiling (broad NGS; RNA-based assays improve fusion detection; cell-free/liquid biopsy if tissue is insufficient). Assign resectability, resectable, borderline resectable, locally advanced (unresectable), or metastatic, by multidisciplinary review, ideally at a high-volume center. RESECTABLE disease: upfront resection (pancreaticoduodenectomy for head/uncinate; distal pancreatectomy ± splenectomy for body/tail) followed by adjuvant therapy, or neoadjuvant therapy in selected high-risk patients; preferred adjuvant regimen is modified FOLFIRINOX in patients able to tolerate it, ideally begun within 12 weeks of surgery, for a total of ~6 months of perioperative systemic therapy. BORDERLINE RESECTABLE and LOCALLY ADVANCED disease: neoadjuvant systemic therapy, with or without subsequent chemoradiation/RT, then restaging and reassessment for resection. METASTATIC disease by performance status: good PS (ECOG 0-1, adequate organ function), first-line FOLFIRINOX/modified FOLFIRINOX, NALIRIFOX, or gemcitabine + nab-paclitaxel, with clinical trial preferred; after ~4-6 months without progression, transition to a maintenance strategy (including olaparib for germline BRCA1/2 carriers who have NOT progressed on first-line platinum-based therapy), a clinical trial, or a treatment break; intermediate PS (ECOG 2), clinical trial preferred, otherwise less-intensive first-line therapy (preferred gemcitabine + nab-paclitaxel [category 1], or single-agent gemcitabine or capecitabine, or FOLFOX/FOLFIRI/CapeOx), since the intensive triplets (FOLFIRINOX/modified FOLFIRINOX and NALIRIFOX) are limited to ECOG 0-1 and are generally not appropriate at ECOG 2, with the same maintenance-versus-progression reassessment applied after ~4-6 months without progression; poor PS (ECOG 3-4), palliative/best supportive care, with single-agent chemotherapy or a biomarker-directed agent only if clinically appropriate. Treat by molecular target wherever an actionable alteration is present, across lines: pembrolizumab (or dostarlimab) for MSI-H/dMMR and pembrolizumab for TMB-H, olaparib for germline BRCA1/2 (maintenance after platinum), larotrectinib/entrectinib for NTRK fusions, selpercatinib for RET fusions, dabrafenib + trametinib for BRAF V600E, erdafitinib for FGFR2 alterations, fam-trastuzumab deruxtecan for HER2-positive disease, zenocutuzumab for NRG1 fusion-positive disease, and (in recent NCCN versions) KRAS G12C inhibitors (adagrasib/sotorasib), several of these after prior systemic therapy. Integrate supportive care throughout: relieve obstructive jaundice with an endoscopic self-expanding metal stent in non-operative or neoadjuvant pathways, but do NOT perform routine preoperative biliary drainage before planned upfront resection; treat exocrine insufficiency with pancreatic enzyme replacement titrated to symptoms (common starting dose ~40,000-50,000 units of lipase with main meals, roughly half with snacks, increased as needed); manage refractory pain with celiac plexus neurolysis or palliative RT; relieve gastric outlet obstruction with surgical or EUS-guided gastrojejunostomy (or enteral stenting); and provide VTE prophylaxis, nutritional support, and early palliative care.