Do primary research questions exist for a patient with pancreatic disease, such as pancreatic cancer or necrotizing pancreatitis?

Primary Research Questions in Pancreatic Disease

Yes, substantial primary research questions exist for patients with pancreatic disease, particularly in pancreatic cancer and necrotizing pancreatitis, with critical knowledge gaps identified across diagnosis, treatment, and long-term management.

Major Research Gaps in Pancreatic Cancer

Biomarker Development and Tissue Collection

• Robust biorepositories are critically needed to discover predictive and prognostic biomarkers that can guide patient care 1.
• Prospective collection of blood, serum, plasma, and tissue blocks should be mandatory in all phase III trials to enable biomarker interrogation 1.
• Current cooperative groups lack standardized operating procedures for tissue procurement, processing, and quality control across institutions 1.
• Only 5 of 28 institutions surveyed were willing to release tissue blocks without special conditions, creating a major barrier to research 1.

Molecular Targets and Therapeutic Development

• There is an urgent need to identify novel functionally relevant targets through high-throughput screening strategies and validate them in appropriate preclinical models that recapitulate human disease 1.
• Most drugs directed against targets identified in preclinical studies have failed to demonstrate clinically relevant benefit, highlighting the inadequacy of current preclinical models 1.
• The identification of robust prognostic and predictive markers is a top priority to enable patient stratification for specific treatments based on molecular-driven hypotheses 1.

Clinical Trial Design and Patient Enrollment

• Workflow changes are needed in adjuvant trials to require central submission of mandatory research blocks, necessitating patient identification and consent during the preoperative setting rather than post-recovery 1.
• Current adjuvant trials focus on "athletes" who survive surgery and recover quickly, missing the "eligible universe" of real-world patients 1.

Critical Research Gaps in Necrotizing Pancreatitis

Fluid Resuscitation Strategies

• More evidence is needed to determine optimal fluid therapy practice in acute pancreatitis, particularly to quantify benefits and harms of goal-directed therapy versus other approaches 1.
• Current evidence does not support clear benefit of Ringer's lactate compared to normal saline for important outcomes such as organ failure, necrosis, or mortality 1.

Antibiotic Prophylaxis

• High-quality multicenter RCTs are required to determine whether prophylactic antibiotics have a role in specific groups of patients with predicted severe acute pancreatitis and necrotizing pancreatitis 1.
• Current evidence does not support routine use of prophylactic antibiotics in predicted severe acute pancreatitis 1.

Timing of ERCP

• The appropriate timing of ERCP in patients with predicted severe biliary pancreatitis with persistent biliary obstruction needs clarification in future studies 1.

Research Gaps in Chronic Pancreatitis

Type 3c Diabetes Management

• Type 3c diabetes (pancreatogenic diabetes) represents a substantial research gap requiring immediate attention regarding the nature of the disease and dietary management 1.
• In a study of 30 patients surviving severe acute pancreatitis, 48% had undiagnosed endocrine insufficiency (30% diabetes, 17% impaired glucose tolerance), with only a minority showing exclusively pancreatogenic etiology 1.
• Most patients demonstrated insulin resistance consistent with type 2 diabetes rather than purely pancreatic origin, highlighting the complexity of this condition 1.

Sarcopenia and Muscle Depletion

• Research is needed on the prevalence and impact of sarcopenia in chronic pancreatitis, along with intervention studies to prevent or reduce muscle depletion 1.

Nutritional Interventions

• Intervention studies are needed on the effectiveness and safety of nutrient supplementation in chronic pancreatitis 1.
• Dietary intake, nutritional requirements, and dietary intervention studies require investigation 1.

Osteoporosis Prevention and Treatment

• Research is needed on dietary and pharmacological strategies for prevention and treatment of osteoporosis in chronic pancreatitis patients 1.

Microbiome and Inflammation

• Medium-term efforts should focus on understanding the potential relationship between the microbiome and inflammation in chronic pancreatitis 1.
• Exploration of therapeutic agents that may modulate the disease process and improve outcomes is warranted 1.

Long-term Outcome Research Priorities

Alcohol and Tobacco Cessation

• Future research should focus on the impact of alcohol and tobacco cessation interventions on endpoints such as recurrent acute pancreatitis, progression to chronic pancreatitis and pancreatic cancer, quality of life, healthcare utilization, and mortality 1.

Severity Prediction Tools

• There is a dearth of high-quality evidence measuring the actual clinical impacts of using any particular severity prediction tool in acute pancreatitis 1.

Common Pitfalls in Current Research

• Lack of standardization across cooperative groups in tissue procurement and biospecimen distribution creates inefficiency and duplication of effort 1.
• Inadequate preclinical models that fail to recapitulate human pancreatic cancer lead to therapeutic failures in clinical trials 1.
• Failure to collect tissue prospectively from all eligible patients, particularly in the adjuvant setting, limits biomarker discovery 1.
• Insufficient focus on real-world patient populations rather than highly selected trial participants limits generalizability of findings 1.