Pancreas/Biliary, in full.

Kyoto 2024 (IAP) applies a single HRS/WF risk-stratification algorithm to all IPMN, including main-duct and mixed types. Workup uses a combination of MDCT, MRI/MRCP, and EUS plus blood tests (tumor markers, HbA1c) per institutional policy, the guideline considers MDCT, MRI, and EUS equivalent for diagnosis rather than designating MRI/MRCP as the single preferred initial modality; new in 2024, EUS imaging and EUS-FNA cytology are folded into the HRS/WF assessment when EUS is performed. High-risk stigmata (HRS): (1) obstructive jaundice in a patient with a cystic lesion of the pancreatic head, (2) enhancing mural nodule >=5 mm or a solid component, (3) main pancreatic duct >=10 mm, and (4) suspicious or positive cytology if EUS-FNA was done. Worrisome features (WF): (1) acute pancreatitis, (2) elevated CA19-9 (>37 U/mL), (3) new-onset or acute exacerbation of diabetes within the past year, (4) cyst >=30 mm, (5) enhancing mural nodule <5 mm, (6) thickened/enhancing cyst walls, (7) MPD >=5 and <10 mm, (8) abrupt change in duct caliber with distal parenchymal atrophy, (9) lymphadenopathy, and (10) cyst growth rate >=2.5 mm/year. Importantly, Kyoto deliberately keeps the 'HRS/WF' framing rather than 'absolute/relative indication': the operative decision is a careful multidisciplinary judgment weighing the degree of suspicion for high-grade dysplasia/invasive carcinoma AGAINST the patient's general condition, comorbidity, life expectancy, and preference, HRS should trigger consideration of resection, not automatic resection, and WF should prompt EUS and multidisciplinary evaluation, with EUS-FNA cytology/molecular sampling reserved for cases in which its results would actually alter management (per Kyoto, the indication for cyst-fluid sampling by EUS-FNA is limited to when further management will be altered according to the results, and FNA should not be performed when HRS is already obvious on MDCT/MRI and surgery is otherwise indicated). MD-IPMN and mixed IPMN are managed by the SAME algorithm, with the surgical decision driven by suspicion for invasive carcinoma and the goal of a negative margin, not by main-duct involvement alone. Non-resected BD-IPMN enters size-stratified surveillance: <20 mm, at 6 months once, then every 18 months if stable; 20 to <30 mm, every 6 months x2, then every 12 months if stable; >=30 mm, every 6 months. On discontinuing surveillance, Kyoto offers TWO options for small unchanged BD-IPMN ('stop surveillance' vs 'continue surveillance' because of possible concomitant pancreatic ductal adenocarcinoma): surveillance MAY be discontinued for cysts <20 mm with no morphological change and no worrisome features after 5 years, with consideration of patient condition and life expectancy, and SHOULD be discontinued for patients unfit for surgery or with life expectancy <10 years, but this discontinuation guidance may not apply to younger patients, and cumulative concomitant-PDAC risk continues to accrue (reported 2.2%, 4.6%, 7.4% at 5, 10, 15 years in one Japanese BD-IPMN cohort), so continued surveillance remains a legitimate alternative. After resection of non-invasive IPMN the pancreatic remnant carries increased risk and warrants long-term surveillance as long as the patient remains fit for further intervention (roughly yearly imaging without additional risk factors, every 6 months with higher-risk features); after total pancreatectomy for non-invasive disease, IPMN-specific surveillance may stop if uneventful over 5 years. (Kyoto 2024 addresses IPMN specifically; the 'all presumed MCNs are resected' rule and the family-history/germline CAPS pathway in the current entry come from other guidelines and are not part of this document.)

Distinguish benign from malignant biliary strictures using cross-sectional imaging (MRI/MRCP preferred over contrast-enhanced CT) plus laboratory tests, interpreting CA19-9 after biliary decompression and never relying on tumor markers alone; check serum IgG4 when IgG4-related sclerosing cholangitis is suspected (HISORt criteria). Per the ESGE 2024 diagnostic work-up guideline, tissue-acquisition strategy now branches by stricture location rather than following one linear sequence: for DISTAL extrahepatic strictures with jaundice and no pancreatic mass, combined same-session EUS-guided tissue acquisition (EUS-TA, end-cutting FNB needle) plus ERCP-based tissue acquisition (standard brush cytology plus fluoroscopy-guided biopsy) is the strongly preferred first-line approach; for PERIHILAR strictures, obtain brush cytology plus fluoroscopy-guided biopsy at index ERCP, escalate indeterminate strictures to cholangioscopy-guided biopsy (with intraductal ultrasound/confocal laser endomicroscopy selectively), and reserve EUS-TA for cases where ERCP-based sampling is insufficient and curative resection is not feasible and/or extraluminal disease is accessible; escalate any positive or indeterminate feature to multidisciplinary tumor board. Manage benign anastomotic and chronic-pancreatitis strictures with a fully-covered self-expanding metal stent for 6-12 months (multiple plastic stents when FCSEMS is contraindicated, hepaticojejunostomy if refractory). Treat cholangitis with biliary obstruction as an indication for urgent biliary drainage, but do not instrument every obstructed sector: for hilar or multisegmental strictures (Bismuth II-IV), ESGE suggests draining ≥50% of the liver volume and avoiding opacification of biliary ducts that will not be drained (weak recommendation, low-quality evidence), because post-ERCP cholangitis frequently complicates injection of obstructed ducts that are not subsequently drained, whereas drainage of >50% of liver volume is associated with less cholangitis and longer survival; ESGE suggests antibiotic prophylaxis before biliary stenting in selected patients (e.g., immunocompromised patients, expected incomplete biliary drainage; weak recommendation, moderate-quality evidence), with a full antibiotic course if adequate drainage is not achieved during the procedure. Direct etiology-specific care for Strasberg bile-duct injuries, post-transplant strictures (ASGE 2023: ERCP preferred over PTBD, covered SEMS preferred over multiple plastic stents), IgG4-sclerosing cholangitis, Mirizzi syndrome, and choledochal cysts.

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.