ENDoscopic Assessment in Acute PANcreatitis Study (ENDOPAN Study)

Acute pancreatitis is one of the most common acute gastrointestinal conditions requiring hospital admission and is associated with a highly variable clinical course. Although most patients develop a mild and self-limiting form of the disease, a clinically important proportion progress to moderately severe or severe acute pancreatitis, with local complications, systemic inflammatory response, organ failure, prolonged hospitalization, need for invasive interventions, and increased mortality. Early identification of patients at risk of an unfavorable course remains a major clinical challenge. Existing prognostic systems and laboratory markers are useful, but they do not fully capture all clinically relevant determinants of disease progression, particularly those related to early upper gastrointestinal mucosal injury, gastric and duodenal involvement, and local inflammatory response in the upper gastrointestinal tract.

The revised Atlanta classification provides a widely accepted framework for the diagnosis and severity assessment of acute pancreatitis. According to this classification, acute pancreatitis is diagnosed when at least two of the following three criteria are present: typical abdominal pain, serum amylase or lipase activity at least three times the upper limit of normal, and imaging findings consistent with acute pancreatitis. Disease severity is classified as mild, moderately severe, or severe. Mild acute pancreatitis is characterized by the absence of organ failure and local or systemic complications. Moderately severe acute pancreatitis is associated with transient organ failure lasting less than 48 hours and/or local or systemic complications without persistent organ failure. Severe acute pancreatitis is defined by persistent organ failure lasting longer than 48 hours, which may involve one or multiple organ systems.

Despite this classification, early prediction of clinical course remains imperfect. Laboratory parameters such as C-reactive protein, white blood cell count, blood urea nitrogen, creatinine, hematocrit, procalcitonin, and biochemical markers of cholestasis may be associated with severity, but their predictive performance varies. Radiological evaluation, particularly contrast-enhanced computed tomography, plays a key role in detecting pancreatic necrosis and local complications; however, early computed tomography may underestimate evolving changes, and the optimal timing for imaging is usually several days after symptom onset or admission. Clinical scores are available, but they can be complex, may require repeated measurements, and may not sufficiently reflect local upper gastrointestinal effects of the disease.

Upper gastrointestinal symptoms are common in acute pancreatitis. Patients frequently present with nausea, vomiting, epigastric pain, feeding intolerance, ileus, gastroesophageal reflux symptoms, or signs of gastric outlet dysfunction. The stomach and duodenum are anatomically close to the pancreas and may be affected by inflammatory edema, local vascular disturbances, impaired motility, stress-related mucosal injury, duodenal compression, and systemic inflammatory changes. Endoscopic abnormalities such as gastritis, duodenitis, erosions, ulcerations, mucosal edema, hemorrhagic lesions, bile reflux, esophagitis, or signs of impaired gastric emptying may therefore reflect both local and systemic consequences of acute pancreatitis. However, early upper gastrointestinal endoscopy is not routinely performed in all patients with acute pancreatitis, and the prognostic significance of early endoscopic mucosal changes remains insufficiently defined.

Preliminary retrospective observations from the study center suggest that upper gastrointestinal mucosal abnormalities are frequent in patients hospitalized with acute pancreatitis and may be associated with disease severity, inflammatory burden, Helicobacter pylori status, and the subsequent clinical course. These observations provide the rationale for a prospective study designed to systematically evaluate early endoscopic findings in a predefined cohort of adult patients with acute pancreatitis. A prospective design will allow standardized timing of endoscopy, uniform collection of clinical and laboratory data, systematic assessment of disease severity, and evaluation of the relationship between mucosal injury and clinically meaningful outcomes.

This study is a prospective observational cohort study conducted in adult patients hospitalized due to acute pancreatitis. The study is designed to assess whether early upper gastrointestinal endoscopic findings are associated with the severity and clinical course of acute pancreatitis. The study will be performed at a single academic clinical center with experience in the diagnosis and treatment of acute pancreatitis and access to surgical, endoscopic, radiological, intensive care, and laboratory facilities. The study does not involve random allocation to treatment groups and does not test an investigational medicinal product or device. All therapeutic decisions will remain at the discretion of the treating physicians and will follow current clinical standards and local institutional protocols. The study intervention consists of protocol-defined diagnostic upper gastrointestinal endoscopy and systematic prospective collection of clinical, laboratory, imaging, microbiological, and outcome data.

The target study population consists of adult patients admitted to the study center with a diagnosis of acute pancreatitis according to the revised Atlanta criteria. Patients will be screened after admission. Eligibility will be confirmed by the study team based on clinical presentation, laboratory results, imaging when available, and safety considerations for endoscopy. Written informed consent will be obtained before enrollment and before any study-specific procedure is performed. The study will include patients with different etiologies of acute pancreatitis, including biliary, alcoholic, hypertriglyceridemic, post-endoscopic retrograde cholangiopancreatography-related, idiopathic, and other less common causes, provided that inclusion and exclusion criteria are met.

The planned sample size is 200 patients. This number was selected to provide a clinically meaningful prospective cohort allowing evaluation of the prevalence and severity of early mucosal abnormalities and their association with disease severity categories and important clinical outcomes. The enrollment period is expected to last approximately two and a half years, depending on the number of eligible patients, consent rate, safety of endoscopy in the early phase of disease, and logistical feasibility. The study start, primary completion, and final completion dates will be reported as anticipated dates and updated as necessary during the conduct of the study.

The primary objective of the study is to evaluate the association between early upper gastrointestinal mucosal abnormalities and the severity of acute pancreatitis according to the revised Atlanta classification. Mucosal abnormalities will be assessed during upper gastrointestinal endoscopy performed within 24 to 48 hours from hospital admission whenever clinically and logistically feasible. Endoscopic findings will be described in a structured manner, including the presence, location, type, and severity of lesions in the esophagus, stomach, and duodenum. Particular attention will be paid to gastric and duodenal mucosal edema, erythema, erosions, ulcerations, hemorrhagic lesions, bile reflux, duodenitis, signs of duodenal compression or narrowing, retained gastric contents, and other abnormalities considered relevant by the endoscopist.

Secondary objectives include assessment of the association between endoscopic findings and transient or persistent organ failure, systemic inflammatory response, local complications of acute pancreatitis, need for intensive care unit admission, need for endoscopic, radiological, or surgical interventions, nutritional tolerance, length of hospital stay, in-hospital mortality, inflammatory marker dynamics, imaging findings, and Helicobacter pylori status when assessed. The study will also explore whether the severity and distribution of upper gastrointestinal mucosal abnormalities add clinically useful information beyond standard laboratory, clinical, and imaging parameters.

Upper gastrointestinal endoscopy will be performed by experienced endoscopists according to local practice and safety standards. The planned timing of the first endoscopy is within 24 to 48 hours from hospital admission. The procedure will be performed only when the patient's clinical condition allows safe examination. Endoscopy will not be performed or will be postponed in patients with hemodynamic instability, severe respiratory compromise, inability to provide informed consent, or any condition judged by the treating physician or investigator to create an unacceptable procedural risk. The decision regarding sedation, monitoring, and procedural precautions will follow institutional standards and individual patient risk assessment. The procedure will be diagnostic. Therapeutic intervention during endoscopy will not be part of the study protocol, but if an urgent clinically indicated intervention is required, it will be performed according to standard medical care and documented.

In patients who develop moderately severe or severe acute pancreatitis, or in patients with clinically significant early endoscopic findings, a follow-up upper gastrointestinal endoscopy may be performed before discharge if it is clinically safe and feasible. The purpose of the follow-up endoscopy is to evaluate the evolution, persistence, improvement, or worsening of mucosal abnormalities during the same hospitalization. The follow-up examination is not mandatory for all participants and will depend on disease severity, clinical condition, consent, and investigator judgment. Reasons for not performing a follow-up endoscopy will be documented when applicable.

Clinical data will be collected prospectively from admission through discharge. Baseline data will include age, sex, body mass index when available, comorbidities, Charlson comorbidity index or individual comorbidity profile, current medications, history of previous acute pancreatitis, history of gallstones or biliary tract disease, alcohol use history when available, smoking status when available, previous endoscopic retrograde cholangiopancreatography, previous abdominal surgery, and other relevant clinical variables. The etiology of acute pancreatitis will be classified according to available clinical, laboratory, imaging, and procedural data. Biliary pancreatitis will be considered in the presence of gallstones, common bile duct stones, biliary sludge, cholestatic laboratory abnormalities, or imaging evidence suggesting biliary obstruction. Alcoholic pancreatitis will be assessed according to clinical history. Hypertriglyceridemic pancreatitis will be identified based on serum triglyceride concentration and clinical context. Post-endoscopic retrograde cholangiopancreatography pancreatitis will be classified according to accepted clinical definitions. Cases without an identifiable cause after standard evaluation will be classified as idiopathic.

Laboratory data will be recorded at baseline and during hospitalization according to clinical availability. These may include serum amylase, lipase, C-reactive protein, white blood cell count, hemoglobin, hematocrit, platelet count, creatinine, urea or blood urea nitrogen, electrolytes, glucose, calcium, bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, albumin, total protein, lactate dehydrogenase, coagulation parameters, triglycerides, arterial blood gas parameters when available, procalcitonin when available, and other clinically relevant markers. The timing of key laboratory values will be documented where possible, with particular attention to admission values and early dynamics during the first days of hospitalization.

Organ failure will be assessed according to the revised Atlanta classification and appropriate clinical scoring components, including respiratory, cardiovascular, and renal failure. Organ failure will be classified as transient if it resolves within 48 hours and persistent if it lasts longer than 48 hours. The need for oxygen therapy, non-invasive ventilation, mechanical ventilation, vasopressor support, renal replacement therapy, intensive care unit admission, or other organ support will be recorded. Systemic complications and exacerbation of pre-existing comorbidities related to acute pancreatitis will also be documented.

Imaging evaluation will be performed according to clinical indications and local standards. Abdominal ultrasound may be used for assessment of gallstones, biliary dilatation, pancreatic morphology when visible, and other abdominal findings. Contrast-enhanced computed tomography will be considered according to current standards, usually when there is diagnostic uncertainty, suspicion of complications, severe disease, failure to improve, or need for interventional planning. If computed tomography is performed, data on pancreatic enlargement, peripancreatic fluid collections, acute necrotic collections, pancreatic or peripancreatic necrosis, walled-off necrosis, pseudocyst, vascular complications, pleural effusion, ascites, and other local complications will be recorded. The timing of computed tomography relative to admission and symptom onset will be documented.

Endoscopic findings will be recorded using a standardized case report form. The esophagus will be assessed for reflux esophagitis, erosions, ulcerations, varices if present, and other abnormalities. The stomach will be assessed in the cardia, fundus, body, incisura, antrum, and pyloric region. Findings such as erythema, edema, erosions, ulcerations, hemorrhagic lesions, petechiae, bile reflux, retained fluid or food, mucosal friability, and signs of impaired gastric motility will be documented. The duodenal bulb and descending duodenum will be assessed for edema, erythema, erosions, ulcerations, hemorrhagic changes, narrowing, extrinsic compression, bile flow, and other abnormalities. The overall severity of mucosal injury will be graded using a predefined descriptive scale in the study documentation, allowing classification into absent, mild, moderate, or severe mucosal abnormalities. Photographic documentation may be obtained according to routine endoscopic practice and local regulations.

Helicobacter pylori status may be assessed during the index endoscopy when clinically appropriate and consistent with the approved protocol. Testing may include rapid urease testing, histology, or other locally available diagnostic methods. The presence or absence of Helicobacter pylori infection will be analyzed in relation to the type and severity of mucosal abnormalities and to clinical outcomes. If Helicobacter pylori testing is not performed in a given patient, the reason may include contraindications to biopsy, technical limitations, patient condition, recent medication use, or investigator judgment.

Nutritional management will follow standard clinical practice. The study will record time to oral intake, tolerance of oral or enteral feeding, need for nasogastric or nasojejunal tube feeding, need for parenteral nutrition, vomiting, gastric retention, ileus, and other manifestations of feeding intolerance. Because upper gastrointestinal mucosal injury and duodenal edema may theoretically influence feeding tolerance and gastric emptying, nutritional outcomes are considered clinically relevant secondary endpoints.

Treatment of acute pancreatitis will not be dictated by the study protocol. Fluid therapy, analgesia, nutritional support, antibiotics, thromboprophylaxis, proton pump inhibitor use, endoscopic retrograde cholangiopancreatography, cholecystectomy, drainage procedures, intensive care management, and other treatments will be provided according to clinical indications and local standards. The study will document relevant treatments and interventions to allow adjustment for potential confounders and descriptive analysis of the clinical course. Proton pump inhibitor therapy, if used, will be recorded as part of standard care rather than as a randomized study intervention. The study does not assign patients to receive or not receive proton pump inhibitors.

The primary outcome measure is the association between early upper gastrointestinal mucosal abnormalities and acute pancreatitis severity according to the revised Atlanta classification during the index hospitalization. For this purpose, endoscopic findings will be categorized and compared across mild, moderately severe, and severe acute pancreatitis. The main analysis will evaluate whether the presence and severity of mucosal abnormalities are associated with a more severe disease category. Additional analyses may evaluate specific endoscopic features, such as duodenal edema, erosive gastroduodenitis, ulcerations, hemorrhagic lesions, retained gastric contents, or severe diffuse mucosal injury, as potential predictors or correlates of unfavorable clinical course.

Secondary outcome measures include organ failure, persistent organ failure, local complications, systemic complications, intensive care unit admission, need for invasive interventions, length of hospital stay, time to feeding tolerance, in-hospital mortality, inflammatory marker levels and dynamics, computed tomography findings, and Helicobacter pylori status. The study may also evaluate composite outcomes such as unfavorable clinical course, defined by development of moderately severe or severe acute pancreatitis, need for intensive care, need for invasive intervention, or death. Definitions of secondary outcomes will be prespecified in the study protocol and statistical analysis plan where applicable.

Safety monitoring will be performed by the principal investigator and the study team. Because the study is observational and does not test an investigational therapeutic intervention, no independent data monitoring committee is planned. Nevertheless, all adverse events related to study procedures, especially upper gastrointestinal endoscopy, will be recorded and evaluated. Potential endoscopy-related adverse events may include aspiration, bleeding, perforation, cardiopulmonary events related to sedation, worsening of clinical status, or other unexpected complications. Serious adverse events will be reported according to local regulations, institutional policies, and requirements of the Bioethics Committee. Endoscopy will only be performed when considered safe by the treating team and the investigator.

The study population may include patients with significant acute illness. Therefore, special attention will be paid to informed consent and procedural safety. Patients will receive information about the study purpose, procedures, potential risks, potential benefits, data collection, confidentiality, voluntary participation, and the right to withdraw. Written informed consent will be obtained before enrollment. If a patient is unable to provide informed consent due to clinical condition, the patient will not be enrolled unless allowed by applicable law, ethics approval, and local institutional policy. Participation in the study will not limit access to standard diagnostic or therapeutic procedures. Refusal to participate will not affect the quality or availability of medical care.

Data will be collected using structured study documentation. Each participant will be assigned a study identifier. Personal data will be protected according to applicable data protection regulations and institutional policies. The study database will include demographic, clinical, laboratory, imaging, endoscopic, treatment, and outcome variables. Access to identifiable data will be limited to authorized members of the study team. Analyses will be performed using coded or pseudonymized data whenever possible. Data quality will be supported by predefined variable definitions, prospective data collection, consistency checks, and review by the principal investigator or designated study personnel.

The statistical analysis will be primarily exploratory and hypothesis-generating, with predefined primary and secondary objectives. Descriptive statistics will be used to summarize baseline characteristics, endoscopic findings, laboratory results, imaging findings, treatments, and outcomes. Continuous variables will be presented as mean with standard deviation or median with interquartile range depending on distribution. Categorical variables will be presented as counts and percentages. Comparisons between groups will be performed using appropriate parametric or non-parametric tests for continuous variables and chi-square or Fisher exact tests for categorical variables. The distribution of endoscopic abnormalities will be compared across acute pancreatitis severity categories.

Regression analyses may be used to evaluate associations between endoscopic findings and clinical outcomes. Ordinal logistic regression may be considered for severity categories according to the revised Atlanta classification. Binary logistic regression may be used for outcomes such as severe acute pancreatitis, persistent organ failure, intensive care unit admission, need for intervention, or in-hospital mortality, depending on the number of events. Linear or generalized linear models may be used for length of stay or other continuous outcomes if appropriate. Multivariable models may adjust for clinically relevant confounders such as age, sex, comorbidity burden, etiology of acute pancreatitis, inflammatory markers, renal function markers, and imaging findings. Given the planned sample size, the number of variables in multivariable models will be limited to avoid overfitting.

The study may also assess whether endoscopic findings provide incremental prognostic information beyond standard clinical and laboratory variables. This may include comparison of models with and without endoscopic variables, evaluation of odds ratios with confidence intervals, and assessment of discrimination or calibration where appropriate. Any predictive analyses will be interpreted cautiously because the study is not primarily designed to validate a definitive prediction model. If the data support development of a preliminary risk model, such a model would require external validation in future studies.

Missing data will be described. The extent and pattern of missing data will be evaluated for key variables. Complete-case analysis may be used for primary analyses when appropriate. Sensitivity analyses may be considered if missing data are substantial and if assumptions allow. Variables not routinely available in all patients will be analyzed descriptively or in subgroup analyses. The timing of endoscopy, timing of laboratory measurements, and timing of imaging will be taken into account in interpretation of results.

Several subgroup analyses may be performed. These may include comparisons by disease etiology, such as biliary versus alcoholic versus other causes; by severity category; by presence or absence of Helicobacter pylori infection; by presence or absence of duodenal involvement; by early versus delayed endoscopy within the allowed time window; and by use or non-use of proton pump inhibitor therapy as part of routine care. Subgroup analyses will be considered exploratory and will be interpreted with caution.

The study has several expected strengths. It is prospective, uses a defined diagnostic framework based on the revised Atlanta criteria, applies early protocol-defined endoscopic assessment, and collects multiple domains of clinical data during the index hospitalization. It focuses on a clinically relevant but insufficiently studied aspect of acute pancreatitis: the potential relationship between early upper gastrointestinal mucosal injury and disease severity. The study may help determine whether endoscopic findings are merely incidental or whether they reflect a biologically and clinically meaningful component of acute pancreatitis progression.

The study also has limitations inherent to its observational design. It cannot prove causality between mucosal abnormalities and disease severity. Endoscopic findings may be influenced by pre-existing gastritis, Helicobacter pylori infection, medication use, alcohol use, stress-related mucosal injury, comorbidities, or the acute systemic inflammatory response. The sickest patients may be unable to undergo early endoscopy, which could introduce selection bias. The study is conducted at a single center, which may limit generalizability. Follow-up endoscopy will not be mandatory in all patients, and its availability may depend on clinical status and logistics. Despite these limitations, the study is expected to provide important prospective data and generate hypotheses for future multicenter studies.

The potential clinical relevance of the study lies in improving understanding of upper gastrointestinal involvement in acute pancreatitis. If early endoscopic abnormalities are associated with more severe disease, persistent organ failure, feeding intolerance, local complications, or prolonged hospitalization, they may serve as additional markers of disease burden. Such findings could support more individualized monitoring, earlier nutritional planning, targeted gastroprotective strategies, or closer follow-up in selected patients. Conversely, if endoscopic abnormalities are frequent but not associated with outcomes, this would also be clinically useful, suggesting that routine early endoscopic assessment should not be used for prognostication in unselected patients.

The study was reviewed and received a positive opinion from the Bioethics Committee of Jan Kochanowski University in Kielce, Collegium Medicum. The committee resolution number is 27/2026, dated May 20, 2026. The study will be conducted in accordance with the approved protocol, applicable ethical principles, local institutional requirements, and relevant regulations concerning medical research, patient safety, and data protection. Any substantial protocol amendments will be submitted for appropriate review and approval before implementation, when required.

In summary, this prospective observational cohort study will evaluate early upper gastrointestinal endoscopic findings in adult patients hospitalized with acute pancreatitis. It will assess the prevalence, type, distribution, and severity of mucosal abnormalities and their relationship with disease severity, organ failure, local and systemic complications, inflammatory response, nutritional tolerance, interventions, length of stay, and mortality. The results may clarify whether early endoscopic mucosal injury has prognostic value in acute pancreatitis and may provide a basis for future studies on gastrointestinal involvement, mucosal protection, and individualized management in this disease.