Pancreas/Biliary, in full.

The CAPS Consortium recommends pancreatic surveillance for selected high-risk individuals to detect stage I (T1N0M0, margin-negative resectable) pancreatic cancer and high-grade precursors (PanIN-3, IPMN with high-grade dysplasia); it should ideally be performed in a research setting by a multidisciplinary team at a center with appropriate expertise. Candidate groups and their affected-relative requirements: Peutz-Jeghers/STK11 carriers regardless of family history; CDKN2A carriers regardless of family history (surveillance regardless of family history reached 77% agreement, still meeting the guideline's ≥75% consensus threshold as a Grade 1 'definitely do it' recommendation, while surveillance in those with at least one affected first-degree relative reached stronger 99% agreement); BRCA2 carriers with at least one affected FDR or at least two affected relatives of any degree; ATM, PALB2, and Lynch (MLH1/MSH2/MSH6) carriers only if at least one affected FDR; BRCA1 with an affected FDR did NOT reach consensus; hereditary pancreatitis was an area of disagreement (no consensus on whether or how to surveil); and familial pancreatic cancer kindreds, an individual with at least one affected FDR who in turn has an affected FDR, qualify on pedigree alone without an identified germline variant. Germline testing and genetic counseling should be considered for those eligible for surveillance but are not an absolute prerequisite. Start ages (exact age often did not reach consensus): CDKN2A at age 40; Peutz-Jeghers at least by age 40, or 10 years younger than the youngest affected relative; hereditary pancreatitis/PRSS1 at age 40 or 20 years after the first attack; BRCA2/ATM/PALB2/BRCA1/Lynch carriers at age 45 or 50, or 10 years younger than the youngest affected relative; familial pancreatic cancer kindreds at age 50 or 55, or 10 years younger than the youngest affected relative (experts split between 50 and 55). New-onset diabetes in a high-risk individual should trigger screening regardless of age. Modalities: both baseline and follow-up surveillance use EUS and MRI/MRCP, alternated (consensus that both are used, but NO consensus on if or how to alternate them); CT is reserved for individuals who cannot undergo MRI/EUS or when a solid lesion is detected; CA19-9 is an additional test only when imaging shows worrisome features; routine fasting glucose and/or HbA1c testing is advised. Interval: in the absence of pancreatic abnormalities, or with only low-risk findings such as pancreatic lobulation, cysts without worrisome features, or a <1 cm non-functioning neuroendocrine tumor, continue 12-monthly imaging. Concerning findings: a newly detected solid lesion of uncertain significance should be re-imaged at 3 months (3-6 months for CDKN2A carriers); EUS-FNA is indicated for solid lesions ≥5 mm, cystic lesions with worrisome features (mural nodule, solid component, duct dilation), or a main-pancreatic-duct stricture without a mass. Surgical resection, performed at a specialty center as an oncologic/radical resection, is indicated for a solid lesion (≥5 mm; resection regardless of size did not reach consensus), or an IPMN with a mural nodule, an enhancing solid component, symptoms (pancreatitis/jaundice/pain), or a main pancreatic duct ≥10 mm. Surveillance of average-risk individuals is not recommended.

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.

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).

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.

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.

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).

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).