What is the comprehensive approach to diagnosing and managing surgical disorders of the pancreas, including acute and chronic pancreatitis, pancreatic cancer, and cystic neoplasms, considering patient evaluation, laboratory tests, imaging techniques, and surgical interventions?

Surgical Disorders of the Pancreas: A Comprehensive Lecture

I. Acute Pancreatitis

Clinical Recognition and Diagnosis

Acute pancreatitis is diagnosed when any two of the following three criteria are met: abdominal pain consistent with pancreatitis, serum amylase and/or lipase greater than three times the upper limit of normal, and characteristic findings on cross-sectional abdominal imaging 1.

• At admission, obtain serum amylase or lipase, triglyceride levels, calcium levels, and liver chemistries (bilirubin, AST, ALT, alkaline phosphatase) to establish diagnosis and determine etiology 2.
• The etiology should be identifiable in at least 75% of patients through focused history on gallstones, alcohol use, hypertriglyceridemia, hypercalcemia, family history, medications, trauma, and autoimmune diseases 2.
• Abdominal ultrasonography must be obtained at admission to screen for cholelithiasis or choledocholithiasis 2.

Severity Assessment and Imaging

• All patients with severe acute pancreatitis require management in a high dependency or intensive care unit with full monitoring and systems support 3.
• CT should be performed selectively during the initial 72 hours based on clinical features in patients with predicted severe disease, organ failure, or clinical deterioration 2.
• Contrast-enhanced CT performed 72-96 hours after symptom onset assesses the extent of pancreatic necrosis and peripancreatic fluid collections 3.
• Serum C-reactive protein >150 mg/L at 48 hours after disease onset serves as the preferred laboratory adjunct for severity prediction 2.

Management Principles

The cornerstones of management include aggressive intravenous fluid resuscitation, appropriate nutrition, and pain management 1.

• Vigorous fluid resuscitation, supplemental oxygen as required, correction of electrolyte and metabolic abnormalities, and pain control must be provided to all patients 2.
• Nutritional support is indicated in patients likely to remain NPO for more than 7 days, with nasojejunal tube feeding using elemental or semielemental formula preferred over total parenteral nutrition 2.
• Total parenteral nutrition should be reserved for those unable to tolerate enteral nutrition 2.

Gallstone Pancreatitis: Specific Management

Urgent ERCP within 24 hours is mandatory in patients with gallstone pancreatitis who have concomitant cholangitis 2.

• Early ERCP within 72 hours should be performed in those with high suspicion of persistent common bile duct stone (visible stone on imaging, persistently dilated common bile duct, jaundice) 2, 3.
• ERCP must be performed under antibiotic coverage, and endoscopic sphincterotomy is required whether or not stones are found 3.
• For mild gallstone pancreatitis, perform cholecystectomy (laparoscopic preferred) during the same hospital admission or within 2 weeks of discharge to prevent recurrent attacks 3.
• For severe gallstone pancreatitis, delay cholecystectomy until signs of lung injury and systemic disturbance have resolved, typically waiting 4-6 weeks 3.
• In patients unfit for surgery, ERCP and sphincterotomy alone provides adequate long-term therapy 2.

Management of Pancreatic Necrosis

• Sterile necrosis does not usually require therapy 2.
• For patients with persistent symptoms and >30% pancreatic necrosis, or smaller areas with suspected infection, perform image-guided fine needle aspiration for culture 7-14 days after onset 3.
• If infected necrosis is confirmed, complete debridement of all necrotic material is required 3.

Recurrent or Unexplained Pancreatitis

• In patients younger than 40 years with a single episode of unexplained pancreatitis, extensive or invasive evaluation is not recommended 2.
• For recurrent episodes, evaluation with EUS and/or ERCP should be considered, with EUS preferred as the initial test 2.
• CT or EUS should be performed in patients with unexplained pancreatitis who are older than 40 years due to risk of underlying pancreatic malignancy 2.

II. Pancreatic Ductal Adenocarcinoma

Clinical Presentation and Recognition

Painless jaundice in head of pancreas tumors, or persistent back pain with marked rapid weight loss in body/tail tumors, are specific clinical features that should prompt immediate investigation 4.

• Persistent back pain, marked and rapid weight loss, abdominal mass, ascites, and supraclavicular lymphadenopathy usually indicate incurable disease 5.
• New-onset diabetes in adults without predisposing features or family history occurs in up to 10% of patients as the first presentation and should trigger investigation 5, 4.
• Unexplained episodes of acute pancreatitis should prompt investigation for underlying pancreatic cancer 5.

Initial Diagnostic Workup

Obtain a pancreatic protocol CT scan of the chest, abdomen, and pelvis as the primary diagnostic imaging study, combined with baseline CA 19-9 measurement, liver function tests, and family history assessment 4.

• Multiphasic contrast-enhanced CT (including late arterial and portal venous phases) is the first-line imaging modality with >90% positive predictive value for determining unresectability 4.
• Complete blood counts and liver function tests are mandatory baseline laboratories 4.
• Chest CT with contrast is required to assess for metastatic disease 4.
• If jaundice is present from obstructive head tumor, obtain imaging BEFORE biliary drainage or stenting to avoid artifacts 4.

Role of CA 19-9

• CA 19-9 is the most useful tumor marker with 83% sensitivity, but should be used for prognosis and monitoring treatment response rather than screening or initial diagnosis 4.
• Elevated CA 19-9 (>500 IU/ml) indicates worse prognosis after surgery and should prompt consideration of neoadjuvant therapy before surgery 4.
• CA 19-9 is undetectable in patients with Lewis antigen-negative phenotypes (approximately 5-10% of the population) 4.
• CA 19-9 lacks specificity as it can be elevated in benign conditions, particularly cholestasis 4.

Advanced Imaging and Tissue Diagnosis

EUS-guided fine needle aspiration is the single best method for diagnosis and staging of nonmetastatic pancreatic cancer with high accuracy for determining tumor resectability 6, 7.

• EUS should be considered to evaluate small lesions not visible on CT and can complement staging by providing information on vessel invasion and lymph node involvement 4.
• Abdominal MRI with MRCP is recommended when CT is inconclusive, contraindicated, or for evaluating cystic lesions 4.
• ERCP is indicated only if clinical suspicion remains high despite negative CT imaging, or to relieve bile duct obstruction 4.
• Staging laparoscopy should be considered to exclude clinically occult intra-abdominal and lymph node metastases, particularly for left-sided large tumors, high CA 19-9 levels, or when neoadjuvant treatment is considered 5, 4.

Tissue Diagnosis Strategy

For unresectable or metastatic disease, biopsy confirmation is mandatory before initiating systemic therapy, with EUS-guided fine needle aspiration as the preferred method 4.

• Resectable mass on imaging in a surgical candidate can proceed directly to surgery without preoperative biopsy 4.
• Avoid percutaneous biopsy in surgical candidates due to risk of tumor seeding 4.
• If metastatic lesions are present, biopsy these under ultrasound or CT guidance 4.
• Pathological diagnosis should follow WHO classification, with ductal adenocarcinomas constituting 95% of pancreatic epithelial tumors 5, 4.

Resectability Assessment

Resectable tumors must show no evidence of extra-pancreatic disease, direct tumor extension to the celiac axis and superior mesenteric artery, or non-obstructive invasion of the superior mesenteric-portal vein confluence 5.

• Less than 20% of patients have resectable disease at diagnosis 5, 4.
• Evaluation of resectability often requires surgery, preferably staging laparoscopy 5.
• TNM staging system is used, though it does not well reflect tumor resectability 5, 4.

Molecular and Genetic Testing

• KRAS and BRCA testing should be performed for all patients with pancreatic cancer 4.
• For metastatic disease with KRAS wild-type tumors, assess microsatellite instability (MSI) status, NTRK fusion status, and other rare fusions that may be actionable 4.
• BRCA1, BRCA2, or PALB2 mutations indicate potential platinum therapy sensitivity 4.
• Patients with family history or high-risk features should undergo genetic counseling 4.

Tests to Avoid

• PET scan has no role in the diagnosis or routine staging of pancreatic cancer 4.
• Bone scan should not be ordered for routine staging, as only a few patients present with bone involvement at diagnosis 4.

Surgical Management

Complete surgical resection is the only potentially curative treatment available, but five-year overall survival after resection is only 10-20% 5.

• Long-term survival in lymph node positive (N+) tumors is rare 5.
• Stenting or bypass surgery may be required for obstructive jaundice or gastric outlet obstruction 5.
• Optimal symptomatic treatment has a prime role in management 5.

Systemic Therapy

• Gemcitabine has been associated with a small survival benefit compared with bolus 5-fluorouracil 5.

Follow-up and Monitoring

• Due to limited effectiveness of treatments, follow-up after complete resection should be restricted to history and physical examination 5.
• Post-operative surveillance with CA 19-9 every 3 months for 2 years is recommended if preoperatively elevated 4.
• Response evaluation should be symptom-driven rather than based on radiographic tests alone 5.

Special Populations

• Patients at increased inherited risk should be referred to specialist centers offering genetic counseling and appropriate testing 5.
• Secondary screening for pancreatic cancer in high-risk cases should be carried out as part of an investigational program coordinated through specialist centers 5.

III. Cystic Neoplasms of the Pancreas

Diagnostic Approach

• Abdominal MRI is the preferred imaging modality for evaluating cystic lesions 4.
• EUS can provide detailed visualization and allows for cyst fluid aspiration for analysis 2.
• A critical pitfall is misdiagnosing malignant mucinous neoplasms as pseudocysts based solely on sonographic appearance and elevated serum amylase levels 8.

Management Considerations

• For suspicious cystic pancreatic masses, needle aspiration of lesion-contained tissue for amylase, CA19-9, and CEA levels should be performed 8.
• Total pancreatectomy should be considered for univocal mass lesions when malignancy cannot be excluded 8.

IV. Chronic Pancreatitis

Diagnostic Evaluation

• ERCP remains the test of choice for morphological evaluation of chronic pancreatitis 6.
• MRCP offers a noninvasive alternative in selected patients 6.
• EUS can be useful for detecting early chronic pancreatitis 6.
• Secretin-stimulated imaging techniques may provide a noninvasive method of assessing pancreatic exocrine function 6.

Critical Diagnostic Challenge

Chronic pancreatitis can coexist with pancreatic malignancy, making diagnosis extremely challenging 8.

• Diagnosis based solely on imaging or pathological considerations may result in missed malignancy 8.
• Maintain high index of suspicion for malignant transformation in patients with chronic pancreatitis and new or changing symptoms 8.

V. Multidisciplinary Approach

Multidisciplinary consultation should ideally involve expertise from diagnostic imaging, interventional endoscopy, medical oncology, radiation oncology, surgery, and pathology before finalizing treatment decisions 4.