Pancreas/Biliary, in full.

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).

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).