What is the comprehensive illness script for a patient diagnosed with pancreatic cancer?

Illness Script for Pancreatic Cancer

Epidemiology and Risk Factors

Pancreatic cancer is projected to become the second-leading cause of cancer-related mortality by 2030, with incidence increasing by 0.5% to 1.0% annually. 1

• Cigarette smoking is the strongest modifiable risk factor 2
• Adult-onset diabetes (less than 2 years' duration) without predisposing features or family history should raise suspicion 2, 3
• Chronic pancreatitis and unexplained acute pancreatitis in patients over 50 years increase risk 2, 3
• Hereditary pancreatitis and familial pancreatic cancer syndromes confer elevated risk 2
• Familial adenomatous polyposis increases risk of periampullary cancers 2

Pathophysiology

• Ductal adenocarcinoma accounts for 95% of pancreatic epithelial tumors 3
• Most present at locally advanced stages with vascular invasion and lymph node metastases 2
• Only 10-20% of patients have resectable disease at diagnosis 3, 1
• Approximately 50-55% present with metastatic disease at diagnosis 1

Clinical Presentation

Symptoms Suggesting Potentially Curable Disease

• Obstructive jaundice (most common presenting symptom for head lesions) 2
• Unexplained weight loss 2
• Unexplained upper abdominal or back pain 2
• Unexplained steatorrhea 2
• New-onset diabetes in patients over 50 without family history, obesity, or steroid use 2, 3
• "Idiopathic" acute pancreatitis in patients over 50 years 2

Symptoms Indicating Advanced/Incurable Disease

The presence of persistent back pain, marked and rapid weight loss, abdominal mass, ascites, and supraclavicular lymphadenopathy usually indicates an incurable situation. 2, 3

• Persistent back pain 2, 3
• Marked and rapid weight loss 2, 3
• Palpable abdominal mass 2, 3
• Ascites 2, 3
• Supraclavicular lymphadenopathy 2, 3

Diagnostic Workup

Initial Evaluation

Clinical presentation suggesting pancreatic cancer should lead without delay to ultrasound of the liver, bile duct, and pancreas. 2, 3, 4

• Abdominal ultrasound as first-line imaging 2, 3, 4
• Blood counts and liver enzymes in initial workup 3
• CA 19-9 level (in absence of jaundice) 2
• Chest x-ray to evaluate for intrathoracic metastases 2

Definitive Staging

When pancreatic malignancy is suspected, multiphase CT scan of the abdomen and pelvis using a pancreatic protocol or MRI should be performed to assess anatomic relationships and detect metastases. 2, 4

• Pancreatic protocol CT or MRI with MRCP accurately delineates tumor size, infiltration, and metastatic disease 2, 3, 4
• Endoscopic ultrasound (EUS) may be used for supplemental staging and to facilitate biopsy 2, 4
• Laparoscopy with laparoscopic ultrasonography may be appropriate in selected cases to exclude occult metastases 2, 3
• PET scan has no role in diagnosis of pancreatic cancer 4

Tissue Diagnosis

• Attempts should be made to obtain tissue diagnosis during endoscopic procedures 2, 3
• EUS-guided biopsy is preferred when tissue diagnosis is needed 4
• Percutaneous biopsy should be avoided in potentially resectable tumors due to limited sensitivity and risk of tumor seeding 2, 4
• Failure to obtain histological confirmation does not exclude malignancy and should not delay appropriate surgical treatment 2, 3

Staging and Resectability Assessment

Resectable Disease (10-15% at presentation)

• No radiographic interface between primary tumor and mesenteric vasculature on high-definition imaging 2
• No evidence of extra-pancreatic disease 3
• No direct tumor extension to celiac axis or superior mesenteric artery 3
• No non-obstructive invasion of superior mesenteric-portal vein confluence 3

Borderline Resectable Disease

• Localized disease involving major vascular structures 1
• Radiographic findings suspicious but not diagnostic for extrapancreatic disease 2

Locally Advanced Unresectable Disease (30-35% at presentation)

• Too much cancer tissue in nearby blood vessels or spread beyond pancreas preventing complete surgical removal 2
• No distant organ metastases 2

Metastatic Disease (50-55% at presentation)

• Spread to distant organs identified 2, 1

Treatment Approach

Resectable Disease

Primary surgical resection followed by 6 months of adjuvant chemotherapy is the standard approach for resectable pancreatic cancer. 2, 3

• Pancreaticoduodenectomy (with or without pylorus preservation) for head tumors 4
• Distal pancreatectomy with splenectomy for body/tail tumors 4
• Adjuvant chemotherapy with gemcitabine and capecitabine doublet is preferred; alternatively gemcitabine or fluorouracil plus folinic acid monotherapy 2
• Adjuvant FOLFIRINOX provides median overall survival of 54.4 months versus 35 months for gemcitabine (HR 0.64, p=0.003) 1
• Adjuvant treatment should be initiated within 8 weeks of surgical resection 2
• Five-year overall survival after resection is only 10-20% 3

Borderline Resectable Disease

• Neoadjuvant chemotherapy or chemoradiotherapy to achieve tumor downsizing 4
• Re-evaluation for surgery after neoadjuvant therapy 4

Locally Advanced Unresectable Disease

• FOLFIRINOX is recommended for patients with ECOG PS 0-1, favorable comorbidity profile, and access to infusion pump services 2
• Median OS with FOLFIRINOX is 11.1 months versus 6.8 months with gemcitabine (HR 0.57, p<0.001) 2

Metastatic Disease

For metastatic pancreatic cancer, multiagent chemotherapy regimens provide survival benefit of 2-6 months compared with single-agent gemcitabine. 1

• FOLFIRINOX for patients ≤75 years with ECOG PS 0-1 and bilirubin ≤1.5 ULN 4
• Gemcitabine plus nab-paclitaxel as alternative regimen 1
• Nanoliposomal irinotecan plus fluorouracil as subsequent-line therapy 1
• Olaparib maintenance therapy for the 5-7% of patients with BRCA germline variants after platinum-based therapy improves progression-free survival 1

Palliative Care and Symptom Management

Biliary Obstruction

Endoscopic stent placement is preferable to trans-hepatic stenting for relief of obstructive jaundice. 2

• Self-expanding metal stents are preferred for patients with life expectancy >3 months 2, 4
• Plastic stents can be considered for patients expected to survive <3 months 2
• Surgical bypass may be preferred in patients likely to survive more than 6 months 2

Pain Management

Patients with severe pain must receive opioids, with morphine generally being the drug of choice. 2, 4

• Oral route is preferred in routine practice 2
• Percutaneous or EUS-guided celiac plexus blockade can be considered for patients with poor opioid tolerance, with analgesic response rates of 50-90% 2, 4
• Early neurolytic sympathectomy leads to better pain control, less opioid consumption, and better quality of life 2
• Hypofractionated radiotherapy may improve pain control and reduce analgesic consumption 2, 4

Gastric Outlet/Duodenal Obstruction

• Duodenal obstruction should be treated surgically 2, 4
• Endoscopic duodenal stenting is successful in majority of patients with median stent patency of 6 months 2

Nutritional Support

• Pancrelipase replacement with meals for exocrine pancreatic insufficiency improves digestion and nutrient absorption 2
• Consultation with nutritionist/dietician is recommended 2

Other Complications

• Ascites: Intermittent paracentesis for symptom relief; spironolactone as diuretic; long-term drainage catheter if reaccumulation requires frequent (>weekly) paracentesis 2
• Depression and anxiety: All patients benefit from discussion of psychosocial concerns; antidepressants or anxiolytics may be warranted 2

Multidisciplinary Care Requirements

Multidisciplinary collaboration to formulate treatment and care plans should be the standard of care for patients with pancreatic cancer. 2

• Goals of care discussion including advance directives with patient and caregivers 2
• Baseline performance status and comorbidity profile evaluation 2
• Referral to high-volume pancreatic cancer treatment center if feasible, as this may lead to changes in therapeutic recommendations 2
• Every patient should be offered information about clinical trials in all lines of treatment 2
• Comprehensive germline testing should be performed for all patients 1
• Integrated supportive care is recommended 1

Follow-up After Resection

• CA19.9 assessment every 3 months for 2 years if elevated preoperatively 2, 4
• Abdominal CT scan every 6 months 2, 4
• Follow-up should be designed to avoid emotional stress and economic burden, as there is no advantage in earlier detection of recurrences 2, 4

Common Pitfalls

• Delaying ultrasound when clinical presentation suggests pancreatic cancer reduces time to diagnosis 2, 3
• Using percutaneous biopsy in potentially resectable tumors risks tumor seeding 2, 4
• Inserting self-expanding metal stents in patients who may undergo resection complicates surgery 4
• Failing to refer to specialist centers reduces resection rates and increases mortality 2, 4
• Not obtaining comprehensive germline testing misses opportunities for targeted therapy in BRCA-mutated disease 1
• Delaying palliative care integration increases symptom burden and reduces quality of life 2