Pancreas/Biliary, in full.

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).

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.

Perform HCC surveillance in adults with cirrhosis of any etiology who are able to benefit from HCC treatment, accordingly, do not enroll patients with Child-Turcotte-Pugh class C cirrhosis unless they are candidates for (or listed for) liver transplantation, and do not surveil those with life-limiting comorbidity (life expectancy <1-2 years) that transplantation cannot remedy, and in select non-cirrhotic chronic HBV carriers at elevated risk (e.g., active hepatitis/high viral load, family history of HCC, African/African-American ancestry, Asian men >40 and Asian women >50; AASLD references risk scores such as PAGE-B but stops short of mandating a specific numeric cutoff). Surveillance is abdominal ultrasound PLUS serum AFP at ~6-month (semiannual) intervals, a change from prior AASLD guidance, which had left AFP optional (Strong recommendation). Pursue diagnostic evaluation for an AFP ≥20 ng/mL or for a rising AFP, defined as a doubling of AFP or an increase on two consecutive tests even if the absolute value is <20 ng/mL. Any suspicious ultrasound observation ≥1 cm, or an inadequate/limited ultrasound, should be evaluated with multiphasic contrast-enhanced CT or MRI interpreted with CT/MRI LI-RADS. AASLD 2023 stages confirmed HCC using the BCLC framework and links stage to therapy (curative resection, ablation, or transplantation within Milan criteria for very-early/early disease; TACE and other locoregional therapy for intermediate disease; systemic therapy for advanced disease). Its first-line systemic options for advanced HCC with preserved liver function (Child-Pugh A) are atezolizumab+bevacizumab OR durvalumab+tremelimumab (STRIDE) as preferred, with sorafenib, lenvatinib, or durvalumab monotherapy as alternatives when the preferred combinations are contraindicated. After potentially curative therapy, continue surveillance for recurrence given high recurrence risk (AASLD monitors with cross-sectional contrast-enhanced imaging, not ultrasound, in the early post-treatment period).

Confirm chronic pancreatitis on CROSS-SECTIONAL IMAGING, CT for late calcific disease, MRI/MRCP (with secretin where available) for earlier ductal and parenchymal change, EUS an acceptable alternative; per ACG 2020, "Diagnosis is made usually on cross-sectional imaging, with modalities such as endoscopic ultrasonography and pancreatic function tests playing a secondary role". Fecal elastase does NOT confirm chronic pancreatitis: it is a test of exocrine FUNCTION and is the appropriate initial test for the exocrine pancreatic insufficiency (EPI) that chronic pancreatitis causes, a consequence of the disease, not the diagnosis of it. A normal fecal elastase does not exclude chronic pancreatitis and a low one does not establish it. Per AGA 2023, fecal elastase must be run on a semi-solid or solid stool specimen; below 100 mcg/g is good evidence of EPI and 100-200 mcg/g is indeterminate (below 200 mcg/g is the cutoff commonly used to screen). Then manage with smoking and alcohol cessation, PERT for exocrine insufficiency titrated to symptoms, fat-soluble vitamin and bone surveillance, and individualized type 3c diabetes control, considering insulin early in patients with marked hyperglycemia or symptoms of insulin deficiency. Treat pain with a stepwise ladder from scheduled acetaminophen and neuromodulators to EUS-guided celiac plexus block and endoscopic/surgical intervention, referring early for surgery per ESCAPE 2020 in candidates with main pancreatic duct obstruction. Screen for PDAC per lifetime risk and pursue etiologic workup via TIGAR-O v2, including genetic testing and autoimmune pancreatitis evaluation.

Stage cholangiocarcinoma with multiphasic MRI/MRCP plus CT chest/abdomen/pelvis, obtain tissue via ERCP brush cytology with FISH, cholangioscopy-directed biopsy, or EUS-FNA (avoiding primary perihilar tumor sampling if liver transplant is being considered due to theoretical seeding risk), and manage through a multidisciplinary tumor board with treatment stratified by tumor location: resect (anatomic hepatectomy for intrahepatic, hemihepatectomy with bile duct resection for perihilar, Whipple for distal) with adjuvant capecitabine (category 1, per BILCAP) when resectable. For unresectable or metastatic disease, first-line systemic therapy is gemcitabine plus cisplatin combined with a PD-L1/PD-1 checkpoint inhibitor, either durvalumab (TOPAZ-1) or pembrolizumab (KEYNOTE-966), both listed as category 1 preferred options by NCCN; comprehensive molecular/genomic profiling is recommended for all unresectable/metastatic candidates for systemic therapy to identify actionable targets (e.g., FGFR2 fusions, IDH1 mutations, HER2 amplification) for later-line therapy. Selected unresectable early-stage perihilar tumors may undergo neoadjuvant chemoradiation and liver transplant per the Mayo Clinic protocol at experienced centers, and jaundice or cholangitis is managed with biliary drainage (ERCP preferred over PTC).