The week in GI, filtered to what is worth knowing.

Confirm ulcerative colitis with endoscopy showing continuous colonic inflammation from the rectum plus histology, after excluding infection with two-step CDI testing. Treat mild-moderate disease with 5-ASA by route and extent (suppository for proctitis, enema for left-sided, oral plus rectal for extensive); if 5-ASA fails, treat as moderate-to-severe rather than stepping up gradually. Position advanced therapy by EFFICACY TIER, not by an anti-TNF-first rule. Advanced-therapy-naive, higher efficacy: infliximab, vedolizumab, ozanimod, etrasimod, upadacitinib, risankizumab, guselkumab; intermediate: golimumab, ustekinumab, tofacitinib, filgotinib, mirikizumab; lower: adalimumab. PREVIOUSLY TNF-EXPOSED, higher efficacy: tofacitinib, upadacitinib, ustekinumab; lower: adalimumab, vedolizumab, ozanimod, etrasimod - S1P modulators are weakest in exactly this group. Do not cycle within the anti-TNF class after primary non-response; switch mechanism. Apply treat-to-target (STRIDE-II) to endoscopic improvement (MES 0-1). Screen for acute severe UC by Truelove-Witts and admit for IV steroids. Begin CRC surveillance 8-10 years after DIAGNOSIS for extensive or left-sided disease; isolated proctitis follows average-risk screening.

DIAGNOSIS: Use fecal calprotectin (cutoff >50-100 μg/g) to differentiate inflammatory from noninflammatory disease OF THE COLON (strong, moderate). Ileocolonoscopy with biopsies for suspected CD; biopsy uninvolved mucosa to define histologic extent; small bowel imaging is part of the initial workup (key concepts, ungraded). CT enterography is comparable to MR enterography for small bowel detection; MRE should be used PREFERENTIALLY in patients younger than 35 years and where serial examinations are likely, because of radiation avoidance, MRE is not a blanket first choice. Intestinal ultrasound is a radiation-free ADJUNCT to diagnosis and to monitoring treatment response (key concept, ungraded, not a graded recommendation). Perform routine endoscopic CRC surveillance in Crohn's colitis (strong, moderate). MILD-TO-MODERATE / LOWER PROGRESSION RISK: Recommend AGAINST oral mesalamine for induction or maintenance (strong, moderate); sulfasalazine should be considered ONLY for symptomatic mild COLONIC CD (key concept). Controlled ileal-release budesonide 9 mg daily for induction of symptomatic remission in mildly-to-moderately active ileocecal CD (strong, moderate), but recommend AGAINST ileal-release budesonide for MAINTENANCE (strong, low). MODERATE-TO-SEVERE / HIGHER RISK: SUGGEST AGAINST requiring failure of conventional therapy before initiating advanced therapy (conditional, LOW, a permission to skip step-up, not a mandate to start advanced therapy upfront). Oral corticosteroids for short-term induction only (strong, low). Recommend AGAINST azathioprine 1.5-2.5 mg/kg/d and 6-mercaptopurine 0.75-1.5 mg/kg/d for INDUCTION (strong, moderate), but SUGGEST the same agents and doses for MAINTENANCE after corticosteroid-induced remission (conditional, low). Check TPMT before starting azathioprine/6-MP (strong, low); measure NUDT15 variants in patients of East Asian ancestry and TPMT variants in all patients prior to thiopurine initiation (strong, moderate). Methotrexate up to 25 mg weekly IM/SC for maintenance after corticosteroid induction (conditional, low). Anti-TNF agents (IV infliximab, SC adalimumab, SC certolizumab pegol) for induction and maintenance (strong, moderate). Recommend COMBINATION IV infliximab + thiopurine over either agent alone in patients naive to both (strong, moderate). Vedolizumab IV for induction and maintenance of symptomatic remission (strong, moderate). Ustekinumab (strong, moderate); risankizumab (strong, moderate), and risankizumab over ustekinumab in prior anti-TNF exposure (conditional, low); mirikizumab (strong, moderate); guselkumab IV-then-SC or all-SC (strong, moderate). Upadacitinib for induction and maintenance in patients PREVIOUSLY EXPOSED TO ANTI-TNF (strong, moderate), the ACG does not endorse it as a first-line biologic-naive option. SC infliximab and SC vedolizumab are maintenance options in responders to IV induction (strong, moderate). PERIANAL FISTULIZING: infliximab for induction (strong, moderate); adalimumab (conditional, low); antibiotics added to infliximab or adalimumab (conditional, very low); vedolizumab, ustekinumab, upadacitinib each (conditional, VERY LOW). Drain perianal abscesses and place setons before escalating advanced therapy (key concept). POST-OPERATIVE: endoscopic assessment at 6-12 months after surgically induced remission over no monitoring (conditional, moderate); in LOW post-op recurrence risk, continued observation rather than immediate medical therapy (conditional, very low); imidazole antibiotics (metronidazole) 1-2 g/d after small intestinal resection (conditional, low); in HIGH-risk CD, anti-TNF to prevent endoscopic recurrence (STRONG, moderate) and vedolizumab (CONDITIONAL, low), these two are not co-equal. SURGERY/ABSCESS: intra-abdominal abscess >2 cm should be treated with antibiotics plus a drainage procedure, and immunosuppression HELD until drainage is achieved (conditional, low). DISEASE MODIFIERS: counsel active smokers to quit; use NSAIDs with caution; assess stress, depression and anxiety as part of comprehensive care (key concepts).

Confirm ulcerative colitis with endoscopy showing continuous colonic inflammation from the rectum plus histology, after excluding infection with two-step CDI testing. Treat mild-moderate disease with 5-ASA by route and extent (suppository for proctitis, enema for left-sided, oral plus rectal for extensive); if 5-ASA fails, treat as moderate-to-severe rather than stepping up gradually. Position advanced therapy by EFFICACY TIER, not by an anti-TNF-first rule. Advanced-therapy-naive, higher efficacy: infliximab, vedolizumab, ozanimod, etrasimod, upadacitinib, risankizumab, guselkumab; intermediate: golimumab, ustekinumab, tofacitinib, filgotinib, mirikizumab; lower: adalimumab. PREVIOUSLY TNF-EXPOSED, higher efficacy: tofacitinib, upadacitinib, ustekinumab; lower: adalimumab, vedolizumab, ozanimod, etrasimod - S1P modulators are weakest in exactly this group. Do not cycle within the anti-TNF class after primary non-response; switch mechanism. Apply treat-to-target (STRIDE-II) to endoscopic improvement (MES 0-1). Screen for acute severe UC by Truelove-Witts and admit for IV steroids. Begin CRC surveillance 8-10 years after DIAGNOSIS for extensive or left-sided disease; isolated proctitis follows average-risk screening.

Diagnose MASLD by hepatic steatosis on imaging (or biopsy) plus at least one cardiometabolic criterion and exclusion of competing etiologies (significant alcohol use, other liver disease), then risk-stratify fibrosis using a sequential non-invasive approach: FIB-4 first, followed by a second-line imaging-based test (VCTE, MRE, or ELF) for indeterminate/high-risk FIB-4, with liver biopsy reserved for discordant or unclear cases. Lifestyle modification (≥7-10% weight loss, Mediterranean diet, exercise) remains the foundation for all patients. For adults with MASH and F2-F3 fibrosis identified by non-invasive tests (VCTE 8-15 kPa, MRE 3.1-4.4 kPa, or ELF 9.2-10.5) rather than biopsy, AASLD now gives dedicated, updated practice guidance on both FDA-approved pharmacotherapies: resmetirom (Oct 2024 update) and semaglutide 2.4mg/week subcutaneous (Nov 2025 update, following August 2025 accelerated FDA approval based on ESSENCE trial data: 62.9% vs 34.3% MASH resolution without fibrosis worsening; 36.8% vs 22.4% ≥1-stage fibrosis improvement). Pioglitazone or vitamin E remain options per the 2023 base guidance. Manage cardiometabolic risk with statins for ASCVD reduction plus glycemic and blood-pressure control; for semaglutide specifically, routine hepatic panels are recommended only as clinically indicated (no discontinuations for LFT elevation in ESSENCE), with monitoring for GI adverse effects and rare risks (AKI, gallbladder disease, pancreatitis, thyroid C-cell tumors, retinopathy progression, lean mass loss). HCC surveillance with ultrasound and AFP every 6 months remains indicated only if cirrhosis is present.

Manage portal hypertension without cirrhosis by confirming portal hypertensive features while excluding cirrhosis (liver biopsy is the gold standard), then performing a comprehensive etiology workup (drug history, MPN/thrombophilia/PNH screen, autoimmune, CVID, HIV, schistosomiasis). Treat portal hypertension complications the same as cirrhosis, variceal prophylaxis with NSBB (carvedilol preferred) or EVL, TIPS for refractory or recurrent bleeding, and address the underlying cause by discontinuing offending drugs and treating the specific etiology. For concurrent portal vein thrombosis, anticoagulation decisions should be individualized based on thrombus acuity (recent vs. chronic), bleeding risk, and underlying etiology; liver transplantation is reserved for refractory complications, and HCC surveillance is not routine without cirrhosis.

ACG 2025 makes 19 GRADE-rated statements plus non-graded key concepts. DIAGNOSIS: EoE is diagnosed by symptoms of esophageal dysfunction plus at least 15 eos/hpf in at least 1 hpf on esophageal biopsy, after evaluating for non-EoE disorders that cause or potentially contribute to esophageal eosinophilia (strong recommendation, low-quality evidence). A PPI trial is NOT a diagnostic criterion and the term PPI-REE is abandoned; PPIs are positioned purely as a treatment. Obtain at least 6 esophageal biopsies from at least 2 esophageal levels (e.g., proximal/mid and distal), targeting endoscopic findings if possible (strong, low). Use a systematic endoscopic scoring system such as the EoE Endoscopic Reference Score (EREFS) at every endoscopy (strong, low). Quantify eosinophil counts, not merely report them as above threshold, on biopsies from every endoscopy performed for EoE (strong, low), since serial counts gauge anti-inflammatory effect; the guideline notes eosinophil density (~60 eos/mm2) may be preferable for cross-setting comparison but that this has not yet been adopted in practice. Key concept: perform the diagnostic endoscopy off treatment (no dietary restriction and no PPI) to maximize diagnostic sensitivity. TREATMENT, the three anti-inflammatory options do NOT carry equal recommendation strength: swallowed topical steroids are recommended (STRONG, moderate evidence); PPIs are suggested (CONDITIONAL, low); empiric food elimination diet is suggested (CONDITIONAL, low). Because the field lacks comparative efficacy trials, the guideline states the choice among them is individualized to disease characteristics and patient preference within a shared decision-making framework, and advises that a single anti-inflammatory therapy be selected initially. Either fluticasone propionate or budesonide is a reasonable initial topical steroid (conditional, low); options include the FDA-approved budesonide oral suspension, the EMA-approved budesonide orodispersible tablet, and off-label asthma preparations adapted for esophageal delivery. Administer topical steroids after meals or at bedtime with nothing to eat or drink for 30-60 minutes to maximize esophageal dwell time; in young children prefer a slurry/suspension over an inhaler device. Dosing (Table 6): high-dose PPI, adults, double the approved reflux dose per day (e.g., omeprazole 20 mg twice daily or 40 mg daily or PPI equivalent); children, 2 mg/kg/day (or 1 mg/kg twice daily). Budesonide, adults 2-4 mg/day, divisible twice daily (approved budesonide oral suspension dosing is 2 mg twice daily); children 1-2 mg/day by age/height/weight. Fluticasone, adults 1,760 mcg/day in divided doses; children 110-880 mcg/day in divided doses. Currently available allergy testing (skin prick, patch, or serum Ig panels) is NOT suggested to direct elimination diets (conditional, very low). Providers MAY consider starting with a less-restrictive empiric elimination (1FED or 2FED) as the initial diet choice, incorporating patient preference through shared decision-making, and should collaborate with a dietician or nutritionist; after an initial dietary response a structured food reintroduction process is advised, with endoscopy and biopsy after each food reintroduced, because symptoms alone must not be used to determine food triggers. BIOLOGICS: dupilumab is suggested for EoE in individuals 12 years of age or older who are nonresponsive to PPI therapy (conditional, moderate) and, as a separate statement, for pediatric patients aged 1-11 years weighing at least 15 kg who are nonresponsive to PPI therapy (conditional, low). Dosing: 15 to <30 kg, 200 mg subcutaneously every other week; 30 to <40 kg, 300 mg subcutaneously every other week; >=40 kg, 300 mg subcutaneously weekly. Key concept: use dupilumab as step-up therapy in difficult-to-treat patients, and consider it in patients with multiple atopic conditions that would independently meet requirements for its use; the guideline explicitly states its position in the treatment algorithm is still being determined. No recommendation can be made for or against cendakimab, benralizumab, lirentelimab, mepolizumab, or reslizumab. Omalizumab is suggested AGAINST (conditional, low), as are cromolyn and montelukast (conditional, very low). DILATION: endoscopic dilation is suggested as an ADJUNCT to medical therapy for esophageal strictures causing dysphagia (conditional, low). Dilation alone does not affect underlying inflammatory disease activity, so in fibrostenotic EoE it should occur in conjunction with effective medical or dietary anti-inflammatory therapy. Use a start-low-and-go-slow approach: begin with a dilator size that may underestimate esophageal caliber, relook after dilation, and work to larger sizes until a mucosal disruption ('dilation effect') or the target diameter is reached. In adults and adolescents, a goal luminal diameter that relieves dysphagia and food impaction, typically at least 16 mm, should be achieved over one or more sessions, depending on initial luminal caliber and the effect observed during dilation. Dilation technique may be chosen by stricture characteristics and endoscopist preference. MAINTENANCE: continuation of EFFECTIVE dietary or pharmacologic therapy is advised to prevent recurrence of symptoms, histologic inflammation, and endoscopic abnormalities, notably graded STRONG despite low-quality evidence, because disease activity almost universally recurs when treatment is stopped. For patients on pharmacologic treatment, providers should consider identifying the lowest effective dose for long-term use, with any dose-reduction decision individualized. MONITORING AND RESPONSE: evaluate treatment response with symptomatic AND endoscopic AND histologic outcomes (strong, low); providers are advised NOT to monitor symptoms alone, since symptoms do not strongly correlate with endoscopic or histologic disease activity. Perform endoscopy to assess response 8-12 weeks after starting a new therapy such as PPI, topical steroid, or food elimination diet; for dupilumab the assessment interval may range from 12 to 24 weeks based on clinical trial findings. Providers MAY consider using a histologic response threshold of <15 eos/hpf, with the improvement in eosinophil count interpreted in the context of other histologic features, endoscopic findings, and symptoms, the guideline frames this as a 'may consider' key concept rather than a fixed target. Follow-up should be individualized and at shorter intervals for patients with complications (food impaction, perforation, strictures requiring dilation, malnutrition); repeat endoscopy after any treatment change such as dose reduction; care gaps of 2 years or more are associated with progression to fibrostenosis. PEDIATRIC-SPECIFIC: in children with EoE and dysphagia, an esophagram is suggested to evaluate fibrostenotic disease (conditional, very low); evaluation by a feeding therapist and/or dietician is suggested as an adjunctive intervention in children with feeding dysfunction (conditional, very low); growth, development including eating skills, and nutrition are treatment goals in children in addition to symptomatic, endoscopic, and histologic goals.

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).

Risk-stratify suspected choledocholithiasis (high >50%, intermediate 10-50%, low <10% probability). HIGH-risk criteria, any of which should directly prompt ERCP: (1) CBD stone on ultrasound or cross-sectional imaging; (2) ascending cholangitis; (3) total bilirubin >4 mg/dL AND dilated CBD (>6 mm in adults with gallbladder in situ, >8 mm after cholecystectomy). Gallstone pancreatitis was deliberately REMOVED as a high-risk criterion in the 2019 revision. INTERMEDIATE risk (abnormal liver biochemical tests, age >55 y, or bile-duct dilation on imaging): the panel suggests confirmation with either EUS or MRCP (conditional recommendation, low-quality evidence; choice by patient preference, local expertise, availability), laparoscopic intraoperative cholangiography (IOC) or intraoperative US are equally sanctioned alternatives. LOW risk: cholecystectomy with or without IOC/intraoperative US if indicated for symptomatic cholelithiasis; no ERCP and no mandatory advanced biliary imaging. In gallstone pancreatitis WITHOUT cholangitis or biliary obstruction/choledocholithiasis, the panel recommends AGAINST urgent (<48 h) ERCP (strong recommendation, low-quality evidence). Same-admission cholecystectomy is recommended for patients with MILD gallstone pancreatitis (consensus, PONCHO-based); ERCP with prophylactic sphincterotomy should not be used as an alternative to cholecystectomy unless surgery is absolutely contraindicated (e.g., recurrent pancreatitis in end-stage liver disease). For large bile-duct stones, the panel suggests endoscopic sphincterotomy followed by large-balloon dilation (ES-LBD) rather than sphincterotomy alone (conditional, moderate); for large AND difficult stones, it suggests intraductal therapy (cholangioscopy-guided EHL or laser lithotripsy) or conventional therapy with papillary dilation, chosen by local expertise, cost, and patient/physician preference (conditional, very low). Timing versus cholecystectomy: pre- or postoperative ERCP or laparoscopic bile-duct clearance for patients at high risk or with positive IOC, depending on local surgical and endoscopic expertise (consensus).

For acute variceal hemorrhage in cirrhosis, resuscitate conservatively with a restrictive RBC transfusion strategy targeting hemoglobin 7-8 g/dL, start a vasoactive agent as soon as bleeding is suspected and before endoscopy (terlipressin, somatostatin, or octreotide; octreotide is the agent available for this indication in US practice) and continue it 2-5 days, and give empiric IV ceftriaxone 1 g every 24 hours in patients with advanced cirrhosis. Perform upper endoscopy within 12 hours of presentation once resuscitated, or as soon as safely possible if the patient is unstable, with band ligation for esophageal varices and for GOV1 (which is treated as an esophageal varix); cardiofundal varices (GOV2 and IGV1) are treated with cyanoacrylate injection, with EUS-guided coil placement with or without cyanoacrylate increasingly used as first-line where expertise exists, and TIPS or BRTO as alternatives or salvage. PPIs started empirically should be stopped immediately after endoscopy unless there is a separate strict indication. Evaluate every patient at presentation for pre-emptive (early) TIPS with a PTFE-covered stent, placed within 72 hours and ideally within 24 hours, in high-risk patients defined as Child-Pugh class C with score under 14 (that is, 10-13) or Child-Pugh class B with score above 7 who have active bleeding at initial endoscopy despite vasoactive drugs; the decision is individualized and multidisciplinary, weighing age, frailty, comorbidity, heart failure, HCC, portal vein thrombosis, and transplant candidacy. For uncontrolled bleeding, a self-expanding covered esophageal metal stent is as effective as balloon tamponade and is the safer option; both are a bridge to definitive therapy (PTFE-covered TIPS) and neither is definitive therapy. Balloon tamponade must NOT be left in place for more than 24 hours, 24 hours is the ceiling, not a range: Baveno VI states it "should only be used in refractory oesophageal bleeding, as a temporary bridge (for a maximum of 24 h) with intensive care monitoring and considering intubation, until definitive treatment can be instituted", because severe esophageal injury/necrosis, perforation and aspiration rise sharply beyond that point. The 72-hour figure in this standard belongs to the pre-emptive TIPS window and must not be read as a permissible tamponade duration. Secondary prophylaxis is mandatory in all survivors and is combination therapy: a nonselective beta-blocker, either a traditional NSBB (propranolol or nadolol) or carvedilol, which Baveno VII endorses as an equivalent rather than clearly superior option in this specific indication, plus serial EVL every 2 to 8 weeks until variceal eradication, with surveillance endoscopy thereafter. TIPS is the treatment of choice for patients who rebleed despite NSBB plus EVL.

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).

For average-risk adults, colorectal cancer screening is routine from age 45-75 (2021 update lowered the start age from 50 to 45; USPSTF/USMSTF/ACS concordant). For ages 76-85, the decision to start or continue is individualized, based on shared decision-making that weighs prior screening history, comorbidity, life expectancy, CRC risk, and patient preference (USPSTF Grade C). Screening is not recommended/offered at age 86 or older. The specific USMSTF criterion for stopping in previously well-screened patients is: individuals up to date with screening who have negative prior screening (particularly high-quality colonoscopy) should consider stopping at age 75 OR when life expectancy is less than 10 years, not 5 years. Individuals without adequate prior screening may be considered for screening up to age 85 depending on age and comorbidities. New alarm symptoms (iron deficiency anemia, GI bleeding, change in bowel habits, weight loss) always warrant workup regardless of age or screening status; this remains sound general practice though it is not a specific guideline citation.

DIAGNOSIS: Diagnosis of BE requires intestinal metaplasia in the tubular esophagus (conditional, very-low certainty) AND columnar mucosa of at least 1 cm (conditional, low). Patients with a normal-appearing Z line, or a Z line with <1 cm proximal displacement from the top of the gastric folds and no visible lesion, should NOT undergo routine biopsy. At screening endoscopy with findings consistent with possible BE, obtain at least 8 biopsies, following the Seattle protocol (4-quadrant biopsies every 1-2 cm plus targeted sampling of any visible lesion) for segments longer than 4 cm (conditional, low). The at-least-8-biopsy minimum applies to all screening exams regardless of segment length and is NOT waived for shorter (<=4 cm) segments; when a short segment - typically 1-2 cm, e.g. a single tongue - will not physically support 8 biopsies, obtain at least 4 biopsies per cm of circumferential BE and 1 biopsy per cm of tongues of BE, so that short segments are still adequately sampled and dysplasia or cancer is not missed. Dysplasia of any grade must be confirmed by a SECOND pathologist with expertise in GI pathology (STRONG, low). SURVEILLANCE: Use both high-definition white-light endoscopy AND chromoendoscopy (STRONG, moderate) with a structured biopsy protocol (STRONG, low). Intervals are dictated by degree of dysplasia (conditional, very-low) and by segment length (STRONG, moderate): nondysplastic BE <3 cm - EGD every 5 years; nondysplastic BE >=3 cm - EGD every 3 years. Indefinite for dysplasia (confirmed by a second pathologist), any length - escalate to twice-daily PPI and repeat EGD within 6 months; if still indefinite, EGD annually; if downgraded/upgraded, follow the NDBE or LGD algorithm. Confirmed LGD opting for surveillance - EGD at 6 months, at 12 months from diagnosis, then annually, sampling with 4-quadrant biopsies every 1 cm. MEDICAL: At least once-daily PPI in patients with BE without allergy or other contraindication to PPI use (conditional, VERY-LOW certainty); higher/twice-daily dosing is reserved for those who need it for symptom control, as the incremental antineoplastic benefit of dose escalation is unclear. Suggest AGAINST antireflux surgery as an antineoplastic measure (conditional, low). No recommendation could be made on aspirin plus PPI chemoprevention, on WATS-3D, or on p53 IHC/TissueCypher. ENDOSCOPIC THERAPY: For BE with HGD or intramucosal carcinoma (T1a), EET is recommended over ESOPHAGECTOMY (STRONG, moderate). For confirmed LGD, endoscopic therapy is SUGGESTED to reduce progression to HGD/EAC, with endoscopic surveillance of confirmed LGD explicitly retained as an ACCEPTABLE ALTERNATIVE (conditional, moderate) - this is a shared-decision-making choice, not a mandate. Resect all visible lesions endoscopically BEFORE ablation of the residual segment (conditional, very-low); RFA is the preferred ablative modality; goal is complete eradication of intestinal metaplasia. EET should be performed at high-volume centers (conditional, very-low). T1b (submucosal) cancer: the default is surgical referral for esophagectomy, BUT EET may be considered for sm1 disease (invasion into the upper third of the submucosa, depth <500 micrometers) with low-risk features - well differentiated, <2 cm, no lymphovascular invasion, negative deep margin. Patients with high-risk histology are best treated with esophagectomy unless they are poor surgical candidates, for whom multidisciplinary discussion of alternatives such as ADJUVANT chemoradiation may be appropriate. POST-EET: An endoscopic surveillance program is recommended after successful EET (STRONG, moderate), with intervals set by the BASELINE degree of dysplasia: baseline LGD - 1 year, 3 years, then every 2 years; baseline HGD or T1a - 3, 6, and 12 months, then annually.

Begin evaluation of abdominal pain with a rapid risk assessment: identify hemodynamic instability, signs of peritonitis, or pain out of proportion to examination findings, these patients need urgent resuscitation or surgical evaluation. Pursue specific life-threatening causes (ruptured AAA, aortic dissection, mesenteric ischemia, ectopic pregnancy, myocardial ischemia) when presentation and risk factors raise suspicion for them, rather than as a universal rule-out before assigning a GI cause. In stable patients, apply a localization-driven differential (RUQ/epigastric/LUQ/RLQ/LLQ/diffuse/periumbilical/suprapubic) with stepwise workup: history and exam with red flags (fever, protracted vomiting, syncope/presyncope, GI blood loss), labs (CBC, CRP, hepatobiliary markers, electrolytes/creatinine/glucose, urinalysis, lipase; pregnancy test in all premenopausal women, including those using reliable contraception; lactate when sepsis or mesenteric ischemia is suspected, may be normal early; ECG/troponin when a cardiac cause is suspected), imaging by location (ultrasound first for RUQ pain; CT with IV contrast for RLQ, LLQ, and generalized pain; CTA when mesenteric ischemia is suspected; in pregnancy, ultrasound first with MRI when ultrasound is inconclusive), then endoscopy and specialty referral by suspicion.