Endoscopy, in full.

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).

WORKUP (NCCN ESOPH-1): H&P; EGD with biopsy; chest/abdomen CT with oral and IV contrast; pelvis CT with contrast ONLY as clinically indicated; FDG-PET/CT (skull base to mid-thigh) if no evidence of M1 disease; CBC and comprehensive chemistry; EUS if no evidence of M1 or unresectable disease; endoscopic resection (ER) is recommended for accurate staging of early-stage cancers (Tis, T1a, or T1b) and may also be therapeutic; bronchoscopy if the tumor is at or above the carina with no evidence of M1; biopsy of metastatic disease as clinically indicated; assign Siewert category; nutritional assessment and counseling; smoking-cessation counseling; screen for family history. BIOMARKERS: universal MSI (PCR/NGS) or MMR (IHC) testing AND universal PD-L1 testing in ALL newly diagnosed patients; HER2 and CLDN18.2 testing if advanced/metastatic adenocarcinoma is documented or suspected; NGS should be considered. Multidisciplinary evaluation is recommended for stage I-IVA (locoregional) disease (ESOPH-E). ENDOSCOPIC THERAPY (ESOPH-A): the goal of endoscopic therapy (EMR, ESD, and/or ablation) is complete removal or eradication of early-stage disease, pTis, pT1a, and SELECTED superficial pT1b without LVI, plus the pre-neoplastic Barrett's segment. Tis/HGD must first be fully characterized for nodularity, lateral spread and multifocality, with EUS to rule out nodal metastases in select higher-risk cases. Areas of nodularity or ulceration must be RESECTED, not ablated. Completely flat lesions ≤2 cm (squamous HGD/Tis, and BE with flat HGD) should be treated by ER because it gives more accurate histologic assessment; flat lesions >2 cm can be treated by ER but with greater complication risk, and may be treated by ablation alone (data for ablation-alone in squamous HGD are very limited). Lesions pathologically limited to lamina propria/muscularis mucosae (pT1a) or superficial submucosa (pT1b), in the absence of nodal metastases, LVI, or poor differentiation, can be treated with full ER, HOWEVER a thorough patient-and-surgeon discussion of esophagectomy versus the risk of concurrent nodal disease should be undertaken, especially for larger tumors or deeper invasion. Ablation of residual Barrett's should follow ER; complete BE eradication may also be achieved by widefield EMR or ESD at the initial intervention when needed to resect superficial tumor or nodularity ≤2 cm. For SCC, the level of evidence for ablation after ER is LOW; additional ablation may be needed only for multifocal HGD/CIS elsewhere, and may not be needed for completely excised lesions. Endoscopic therapy is 'PREFERRED' for limited early-stage disease: Tis and T1a, ≤2 cm, well or moderately differentiated. Esophagectomy is indicated for extensive carcinoma in situ (pTis/HGD), pT1a, or superficial pT1b, especially nodular disease not adequately controlled endoscopically. PRIMARY TREATMENT, MEDICALLY FIT PATIENTS, ADENOCARCINOMA (ESOPH-13): cT1b-cT2, N0 LOW-RISK (<3 cm, well differentiated) → esophagectomy. cT2 N0 HIGH-RISK (LVI, ≥3 cm, or poorly differentiated), cT1b-cT2 N+, or cT3-cT4a any N → perioperative systemic therapy is PREFERRED (FLOT: 5-FU 2600 mg/m2 IV over 24 h day 1, leucovorin 200 mg/m2, oxaliplatin 85 mg/m2, docetaxel 50 mg/m2, every 14 days, 4 cycles pre- and 4 cycles postoperatively; or FLOT + durvalumab 1500 mg for PD-L1 CPS ≥1 or TAP ≥1%, category 1 for EGJ, category 2A for esophageal adenocarcinoma; note MATTERHORN showed no EFS advantage for durvalumab in diffuse-type disease), QUALIFIER: perioperative therapy is preferred for patients medically fit and with access to frequent toxicity evaluation; preoperative chemoradiation for planned esophagectomy remains an option and may be considered for borderline-resectable patients or patients who are not FLOT candidates (perioperative FOLFOX/CAPOX is another alternative). Consider neoadjuvant or perioperative immune checkpoint inhibitor if the tumor is MSI-H/dMMR (in multidisciplinary consultation; the role of surgery after complete response is unclear). Definitive chemoradiation for patients who are medically unfit/inoperable for surgery or who decline surgery. cT4b → definitive chemoradiation, or chemotherapy alone with invasion of trachea, great vessels, vertebral body, or heart. SQUAMOUS CELL CARCINOMA (ESOPH-2): cT1b-cT2, N0 LOW-RISK (<3 cm, well differentiated) → esophagectomy (non-cervical esophagus). cT2 N0 high-risk (LVI, ≥3 cm, poorly differentiated), cT1b-cT2 N+, or cT3-cT4a any N → PREOPERATIVE CHEMORADIATION is preferred (or definitive chemoradiation). cT4b → definitive chemoradiation, or chemotherapy alone for trachea/great-vessel/vertebral/cardiac invasion. NCCN states explicitly: 'Preoperative chemoradiation is preferred for esophageal SCC.' Preoperative RT dose 41.4-50.4 Gy at 1.8-2.0 Gy/day (23-28 fractions); preferred concurrent regimens include weekly paclitaxel 50 mg/m2 + carboplatin AUC 2 (CROSS, category 1) and fluorouracil + oxaliplatin (category 1). POSTOPERATIVE (ESOPH-F): nivolumab is the preferred postoperative regimen ONLY after PREOPERATIVE CHEMORADIATION with R0 resection and residual pathologic disease (category 1), 240 mg IV every 14 days for 16 weeks, then 480 mg IV every 28 days, maximum treatment duration 1 year. PALLIATION (ESOPH-A/H): esophageal dilation with balloons or bougies for temporary relief of malignant or treatment-related obstruction (avoid overdilation, perforation risk); long-term dysphagia palliation by endoscopic tumor ablation (Nd:YAG laser, PDT, cryoablation) or expandable metal/plastic stents; feeding gastrostomy or jejunostomy for anorexia/dysphagia/malnutrition, but placement of a GASTROSTOMY preoperatively may compromise the gastric vasculature and interfere with gastric-conduit reconstruction and SHOULD BE AVOIDED (feeding jejunostomy is generally preferred for postoperative nutritional support; multidisciplinary expertise is recommended before percutaneous gastrostomy).

Perform individual gastric risk assessment and staging of precancerous conditions at first-time gastroscopy, irrespective of the patient's country of origin. Use high quality endoscopy with virtual chromoendoscopy (VCE), after proper training, for screening, diagnosis and staging of atrophy and intestinal metaplasia and after endoscopic therapy; VCE guides the biopsy site, with random biopsies taken only when there are no endoscopically suspected changes. Take biopsies from at least two topographic sites, 2 from the antrum/incisura and 2 from the corpus, VCE-guided, in two separate, clearly labeled vials; an additional incisura biopsy is optional, not required. Stage with validated endoscopic classifications of atrophy (e.g. Kimura-Takemoto) or intestinal metaplasia (e.g. EGGIM) to stratify gastric cancer risk (suggestion, weaker than the biopsy recommendation). Follow up patients with extensive endoscopic changes (Kimura C3+ or EGGIM 5+) OR an advanced histological stage that reaches OLGA/OLGIM III/IV, severe atrophy or intestinal metaplasia and/or significant changes in both antrum and corpus rising to stage III/IV, not any intestinal metaplasia or any antrum-plus-corpus involvement on its own, with high quality endoscopy every 3 years, irrespective of country of origin (strong recommendation, moderate quality). Propose NO surveillance for patients with mild to moderate atrophy or intestinal metaplasia restricted to the antrum, in the absence of endoscopic signs of extensive lesions or other risk factors (family history of gastric cancer, incomplete intestinal metaplasia, persistent H. pylori infection), the guideline states this group constitutes most individuals found in clinical practice. Eradicate H. pylori in all patients with precancerous conditions and after endoscopic or surgical therapy. Discontinue or do not start gastric cancer screening or surveillance in asymptomatic individuals over 80, and weigh comorbidities when planning treatment of superficial lesions. Advise smoking cessation; low-dose daily aspirin may be considered for gastric cancer prevention only in selected individuals already at high cardiovascular risk. For visible neoplasia, use ESD for differentiated lesions clinically staged as dysplastic (low or high grade) or intramucosal carcinoma (any size if not ulcerated, or ≤30 mm if ulcerated), with EMR an alternative for Paris 0-IIa lesions ≤10 mm with low likelihood of malignancy. At the population level, endoscopic screening is suggested every 2-3 years in high-risk regions (age-standardized rate >20 per 100,000 person-years), every 5 years in intermediate-risk regions (ASR 10-20) only if cost-effectiveness has been proven, and not at all in low-risk regions (ASR <10).

Evaluate for achalasia any patient with dysphagia to solids and liquids, regurgitation, or chest pain, and specifically consider it in patients presumed to have GERD who do not respond to acid suppression (strong recommendation, very low quality). Diagnose with high-resolution manometry using esophageal pressure topography rather than conventional line tracings (strong, high). Subtype by Chicago Classification (I, II, III), this is a conditional recommendation (low quality): subtyping may inform prognosis and treatment choice, with type II having the most favorable outcomes and type III requiring a longer/tailored myotomy; ACG does not make subtyping mandatory for diagnosis. Always perform upper endoscopy in suspected achalasia to exclude pseudoachalasia from an obstructing mass; use cross-sectional imaging and/or endoscopic ultrasound in difficult cases (ACG states this as narrative guidance, not a numbered recommendation, and specifies no biopsy protocol). FLIP is described as complementary, useful in patients who cannot tolerate manometry and as an arbiter in difficult cases where manometry fails to diagnose achalasia despite high clinical suspicion, not as a required confirmatory test. TREATMENT: pneumatic dilation is superior to medical therapy for symptom relief and esophageal emptying (strong, very low). PD and laparoscopic Heller myotomy are both effective and equivalent short- and long-term for patients who are candidates for definitive therapy (strong, high). POEM and LHM give comparable symptomatic improvement (strong, moderate). POEM and PD give comparable symptomatic improvement in type I or II (conditional, low). For type III, tailored POEM or LHM is recommended as a more efficacious disruptive LES therapy than PD (strong, moderate), ACG does NOT single out POEM over LHM for type III. When surgical myotomy is performed, add fundoplication: myotomy with fundoplication is superior to myotomy alone for controlling distal esophageal acid exposure (strong, moderate), using either Dor or Toupet (conditional, moderate). Botulinum toxin injection is first-line therapy for patients unfit for definitive therapy (strong, moderate), and prior botulinum toxin does not significantly compromise subsequent myotomy performance or outcomes (strong, low). POEM carries a higher incidence of GERD than LHM with fundoplication or PD (strong, moderate). Do not place stents for long-term dysphagia (strong, low). Reserve esophagectomy for surgically fit patients with megaesophagus who have failed other interventions (strong, low), and consider Heller myotomy before esophagectomy in patients who failed PD and POEM when the anatomy is conducive and there is evidence of incomplete myotomy (strong, very low). FOLLOW-UP: use timed barium esophagram as the first-line test to evaluate continued or recurrent symptoms after definitive therapy (strong, very low); the Eckardt score alone or HRM alone should not be used to define treatment failure. Do not obtain routine gastrografin esophagram after dilation, reserve it for clinical suspicion of perforation (strong, low). RETREATMENT: PD is appropriate and safe after failed surgical myotomy or POEM (strong, moderate), and POEM is safe in patients who previously underwent PD or LHM (strong, low). SURVEILLANCE: ACG recommends AGAINST routine endoscopic surveillance for esophageal carcinoma in patients with achalasia (strong, low), although risk is elevated (~1 cancer per 300 patient-years), absolute numbers are low, an estimated >400 endoscopies would be needed to detect one cancer, and surveillance has not demonstrated improved survival.