Endoscopy, in full.

For suspected ICI colitis, exclude infectious causes of diarrhea (including C. difficile) before treating. In grade 2 or higher colitis/diarrhea, early stool inflammatory markers (lactoferrin, calprotectin) may help stratify patients for endoscopy, and endoscopic confirmation of the diagnosis and severity should be considered before starting high-dose systemic glucocorticoids; abdominal imaging is reserved for dominant pain, fever, or bleeding and should not be done routinely for diarrhea alone. The AGA cautions that no validated severity index for ICI colitis exists and that symptoms correlate poorly with endoscopic, radiologic, and treatment-response severity, and that rapid progression over days can occur, particularly with ipilimumab. ICI colitis typically responds to high-dose systemic glucocorticoids at 0.5-2 mg/kg prednisone-equivalent daily tapered over 4-6 weeks (the AGA explicitly notes these doses and schedules have not been rigorously examined). If there is no improvement after 2-3 days, add infliximab or vedolizumab while continuing glucocorticoids; both are reasonable options for glucocorticoid-refractory colitis. Budesonide is ineffective as prophylaxis and is not a standard treatment for ICI colitis, it is reserved for ICI-associated microscopic colitis. Retreatment with immunotherapy is possible under select conditions. For hepatitis, obtain baseline liver chemistries (total bilirubin, alkaline phosphatase, AST, ALT) and HBV serologies before ICI; grade by CTCAE and manage as follows: grade 1 (AST/ALT 1-3x ULN or bilirubin 1-1.5x ULN), monitor liver chemistries 1-2 times weekly; grade 2 (AST/ALT >3-5x ULN or bilirubin >1.5-3x ULN), hold ICI until resolution to grade 1, and if symptomatic give prednisone 0.5-1.0 mg/kg/d or equivalent; grade 3 (AST/ALT >5-20x ULN or bilirubin >3-10x ULN), discontinue ICI and start methylprednisolone 1-2 mg/kg/d or equivalent; grade 4 (AST/ALT >20x ULN or bilirubin >10x ULN or hepatic decompensation), permanently discontinue ICI and start methylprednisolone 2 mg/kg/d. For ICI hepatitis that does not adequately improve after 3-5 days of high-dose glucocorticoids, escalate to a second-line immunosuppressant, mycophenolate mofetil (with azathioprine as an accepted alternative), while continuing glucocorticoids; infliximab is not recommended for ICI hepatitis because of its potential for hepatotoxicity. Evaluate all ICI-related liver-chemistry elevations for alternate etiologies (consider liver biopsy), and obtain biliary imaging when alkaline phosphatase and/or bilirubin are elevated.

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.

ESGE 2021 gates everything on proven adenoma. ESGE recommends AGAINST diagnostic/therapeutic papillectomy when adenoma has not been proven (strong, low), and recommends histological confirmation by endoscopic biopsies in the case of low-grade-dysplasia adenoma before initiating any treatment (strong, low). Assessment uses a side-viewing endoscope when an ampullary tumor is suspected (strong, moderate); the cap-assisted method is suggested only when the papilla is not seen on forward-viewing endoscopy (weak, moderate); high-resolution virtual chromoendoscopy is suggested for diagnosis and staging (weak, low). Staging is EUS plus abdominal MRCP (strong, low); IDUS is suggested only in selected patients, with routine use balanced against training, cost and pancreatitis risk (weak, low). ESGE suggests that IHC, K-ras and p53 evaluation, PCR, and microsatellite instability testing should NOT routinely be applied to ampullary tumor biopsies to inform prognosis or potential treatment response (weak, low). TREATMENT: ESGE recommends endoscopic papillectomy for ampullary adenoma without intraductal extension (strong, moderate), and en bloc resection of adenomas up to 20-30 mm to achieve R0 (strong, low). Technique is direct snare resection WITHOUT submucosal injection (strong, moderate) - but submucosal injection IS recommended before EMR of the extrapapillary duodenal-wall component of a laterally spreading ampullary tumor (strong, moderate); LST-p can be managed endoscopically, accepting higher intraprocedural and delayed bleeding risk (strong, low). ESGE suggests avoiding any biliary, pancreatic or biductal sphincterotomy prior to papillectomy (weak, very low) and suggests endocut current (weak, low). PROPHYLAXIS: prophylactic pancreatic duct stenting is recommended to reduce post-papillectomy pancreatitis (strong, moderate); ESGE suggests routine rectal administration of 100 mg diclofenac or indomethacin immediately before papillectomy in all patients without NSAID contraindication (weak, low); if PD stenting is not possible, high-volume lactated Ringer's hydration is suggested (weak, low). Prophylactic hemostasis is individualized (strong, very low). SURGERY: ESGE only SUGGESTS considering surgical treatment when endoscopic resection is not feasible for technical reasons (e.g. periampullary diverticulum, size >4 cm) and in the case of intraductal involvement of >20 mm - and surveillance thereafter is still mandatory (weak, low). For adenoma with intraductal extension of 20 mm or less, ESGE suggests complementary techniques in expert centers (thermal ablation by cystotome, or RFA) with temporary biliary stenting (weak, low). For malignancy, ESGE recommends pancreaticoduodenectomy including lymphadenectomy for ampullary lesions of stage T1 or higher, including when pathology after endoscopic papillectomy or surgical ampullectomy reveals T1 adenocarcinoma (strong, low); for Tis ampullary cancer, transduodenal ampullectomy or endoscopic papillectomy may be considered sufficient when final pathology shows no residual disease (strong, low). BILIARY DRAINAGE: ESGE recommends against routine preoperative biliary drainage in surgically eligible ampullary cancer, reserving it for cholangitis, severe symptomatic jaundice (e.g. intense pruritus), delayed surgery, or before neoadjuvant chemotherapy in jaundiced patients (strong, moderate); when required, endoscopic SEMS insertion (strong, moderate); ERCP with SEMS in palliative settings (strong, high). FOLLOW-UP: long-term monitoring after endoscopic papillectomy or surgical ampullectomy by duodenoscopy with biopsies of the scar and of any abnormal area, within the first 3 months, at 6 and 12 months, and yearly thereafter for at least 5 years (strong, low). On recurrence, assess local extent with endoscopy plus biopsies, EUS and MRCP before any treatment (strong, low); benign residual or recurrent lesions may be managed endoscopically including APC and EMR (weak, low).

After polyp removal, assign the next colonoscopy surveillance interval using USMSTF 2020 based on polyp number, size, and histology (e.g., 1-2 tubular adenomas <10 mm 7-10 years; 3-4 tubular adenomas <10 mm 3-5 years; 5-10 tubular adenomas <10 mm, any adenoma ≥10 mm, or adenoma with tubulovillous/villous histology or high-grade dysplasia 3 years; >10 adenomas 1 year with polyposis evaluation; and for serrated polyps, 1-2 sessile serrated lesions <10 mm 5-10 years, 3-4 sessile serrated lesions <10 mm or a hyperplastic polyp ≥10 mm 3-5 years, and a sessile serrated lesion ≥10 mm or with dysplasia or a traditional serrated adenoma 3 years), and apply the shortest interval indicated when findings are mixed. Confirm complete resection and adequate prep before applying an interval, and use site-check/tumor-board pathways for piecemeal resection and malignant (T1) polyps. Refer for genetic evaluation when Lynch, FAP/AFAP/MAP, or serrated polyposis syndrome criteria are met.

For right upper quadrant pain, characterize the pattern (acute vs chronic, post-meal vs unrelated, with vs without fever/jaundice) and triage acute red-flag presentations (Murphy sign, Charcot's triad, painless jaundice with weight loss, pregnancy with LFT/coagulation derangement) to the ED. Obtain labs (CBC, CMP with LFTs, lipase, urinalysis, pregnancy test in reproductive-age women) and RUQ ultrasound as first imaging, then direct further workup by ultrasound findings, cholecystectomy for acute cholecystitis, MRCP for suspected choledocholithiasis based on risk stratification (e.g., high-risk criteria including CBD dilation >6 mm, bilirubin >4 mg/dL, or gallstone pancreatitis), CCK-HIDA/GBEF for acalculous functional gallbladder disorder, and cross-sectional imaging for liver masses or other pathology.