Pancreas/Biliary, in full.

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.

Diagnose acute pancreatitis (AP) by the Atlanta criteria (2 of 3: characteristic epigastric/LUQ pain, lipase or amylase >3x ULN [lipase preferred for specificity/duration], or characteristic imaging). ACG 2024 stratifies severity risk using SIRS on admission plus bedside risk factors, rising/elevated BUN, rising/elevated hematocrit (>44), obesity (BMI>30), extrapancreatic fluid collections/pleural effusion/infiltrates, altered mental status, and older age/comorbidities, rather than mandating a formal BISAP or APACHE II composite score. Give moderately aggressive lactated Ringer's, most important in the first 6-12 hours, reassessing volume status/BUN/HCT at 6 hours (further aggressive hydration has little added benefit after 24-48h). Start oral low-fat solid food within 24-48h as tolerated in mild disease; if enteral feeding is needed for moderately severe/severe disease, prefer nasogastric over nasojejunal with small-peptide/medium-chain-triglyceride formula and continuous (not bolus/cyclic) feeding; avoid parenteral nutrition if possible. Do not give prophylactic antibiotics, even in severe disease or sterile necrosis; reserve antibiotics for suspected infected necrosis (typically arising 10-14 days in), and choose agents that penetrate pancreatic necrosis while together covering both gut-derived gram-negative enterics and anaerobes, a carbapenem supplies this as monotherapy, whereas a fluoroquinolone or a third-or-higher-generation cephalosporin must be combined with metronidazole; metronidazole alone (anaerobic cover only), or a cephalosporin or a quinolone alone, does not adequately treat infected necrosis. Perform cholecystectomy preferably before discharge for mild acute biliary pancreatitis, and after a second unexplained AP episode even without identified gallstones; reserve ERCP within 24h for AP complicated by cholangitis, with rectal indomethacin +/- pancreatic duct stent and periprocedural hydration to reduce post-ERCP pancreatitis risk. Check triglycerides when gallstones/alcohol are absent (>1000 mg/dL supports a hypertriglyceridemia etiology). For stable pancreatic necrosis, defer surgical, radiological, or endoscopic intervention 4-6 weeks to allow walling-off (step-up approach).

Do not diagnose acute pancreatitis (AP) from an elevated lipase alone. ACG establishes the diagnosis by identification of 2 of the 3 following criteria: (i) abdominal pain consistent with the disease, (ii) serum amylase and/or lipase greater than 3 times the upper limit of normal, and/or (iii) characteristic findings on abdominal imaging. Serum lipase is the preferred enzyme; serum amylase alone cannot be used reliably because of limitations in sensitivity and negative predictive value. The guideline states explicitly that some patients without AP will have elevated amylase and/or lipase, sometimes greater than 3 times normal, and that in the absence of abdominal pain consistent with the disease, elevations of amylase and lipase do not predict the development of AP. The 3 times threshold is qualified, not absolute: although most studies show diagnostic efficacy at greater than 3 to 5 times the upper limit of normal, a cutoff greater than 3 to 5 times may be needed especially in some patient groups such as diabetic patients, a Japanese consensus conference could not reach consensus on appropriate upper limits of normal, and clinicians must consider the clinical condition of the patient when evaluating amylase and lipase elevations. Pain quality is a stated discriminator: AP pain is typically epigastric or left upper quadrant, usually constant with radiation to the back, chest, or flanks, though this description is nonspecific and intensity is variable; pain described as dull, colicky, or located in the lower abdominal region is not consistent with AP and suggests an alternative etiology. Intensity and location of pain do not correlate with severity. When doubt about the diagnosis of AP exists, abdominal imaging may assist, and contrast-enhanced CT provides more than 90 percent sensitivity and specificity; however the guideline's Diagnosis key concept is that early or at-admission routine CT should NOT be performed to determine severity and should be reserved for patients in whom the diagnosis is unclear or who fail to improve clinically within the first 48 to 72 hours after hospital admission and intravenous hydration. Lipase is also found to be elevated in a variety of nonpancreatic diseases; the specific non-pancreatitis causes the document enumerates (given for amylase) are macroamylasemia, decreased glomerular filtration rate, diseases of the salivary glands, and extrapancreatic abdominal diseases associated with inflammation including acute appendicitis, cholecystitis, intestinal obstruction or ischemia, peptic ulcer, and gynecological diseases. Once the diagnosis of AP is established there is no reason to follow serum amylase or lipase, because there is no relationship to severity, prognosis, or the decision to refeed or discharge the patient. Separately, as an etiology key concept, in patients older than 40 years in whom an etiology is not established, a pancreatic tumor should be considered as a possible cause of AP.

Identify candidates for bile acid diarrhea (BAD) among patients with chronic diarrhea by RISK FACTORS, prior terminal ileal resection, cholecystectomy, or abdominal radiotherapy (strong recommendation, very low certainty); do NOT rely on symptom presentation alone to identify BAD (conditional, very low certainty). Diagnose by testing rather than by treating. In chronic diarrhea, IBS-D, and functional diarrhea, test with SeHCAT where available (conditional, very low certainty) or with a 7-alpha-hydroxy-4-cholesten-3-one (C4) assay (conditional, very low certainty). In small-intestinal Crohn's disease without active inflammation and persistent diarrhea, the guideline recommends SeHCAT specifically (conditional, very low certainty); the C4-assay recommendation is confined to the chronic diarrhea, IBS-D, and functional diarrhea population and is not extended to this Crohn's group. The guideline explicitly SUGGESTS AGAINST empiric bile acid sequestrant therapy in preference to SeHCAT testing (conditional, very low certainty), an empiric trial is a fallback where testing is unavailable, not a co-equal diagnostic strategy. Treat remediable contributing causes (active Crohn's disease, microscopic colitis, SIBO) alongside BAD (conditional, very low certainty). For induction, use cholestyramine over no treatment (conditional, very low certainty) and cholestyramine over other sequestrants as INITIAL therapy (conditional, very low certainty), switching to an alternate sequestrant when cholestyramine is poorly tolerated (conditional, low certainty). Dose cholestyramine from 2-4 g/day titrated to response (range up to 4-24 g/day); colestipol from 1 g twice daily increasing by 1 g/day every other day; colesevelam 625 mg two tablets three times daily (3.75 g/day). Gradual daily dose titration should be used to minimize side effects (good practice statement). SUGGEST AGAINST sequestrants in patients with extensive ileal Crohn's disease or ileal resection (historically >100 cm) because of steatorrhea risk (conditional, very low certainty), evaluate case by case; use alternative antidiarrheal agents in patients who cannot tolerate sequestrants (conditional, very low certainty). For maintenance, try intermittent, on-demand dosing after initial response (conditional, very low certainty) and use the lowest dose needed to control symptoms (good practice statement). Review concurrent medications (good practice statement): per Health Canada labeling, take other drugs at least 1 hour before or 4-6 hours after the sequestrant (a 3-hour window may suffice based on gastric-emptying data); interacting drugs include thyroid preparations, warfarin, and digoxin, with colesevelam having lower interaction potential. Re-investigate diagnostically if symptoms worsen despite stable sequestrant therapy (good practice statement). The guideline makes NO RECOMMENDATION for or against measuring fat-soluble vitamin levels at baseline or annually (very low certainty); product labels advise supplementing vitamins A, D and K only if a deficiency occurs. Note that 16 of the 17 recommendations are conditional and most rest on very low certainty evidence.