What is the recommended evaluation, tissue sampling, and management approach for periampullary cancer (periamullary carcinoma) based on latest evidence?

Management of Periampullary Carcinoma: Evaluation, Tissue Sampling, and Stagewise Treatment

Periampullary carcinoma requires a systematic approach to evaluation, tissue sampling, and management at specialist centers to optimize outcomes and survival rates.

Initial Diagnostic Evaluation

• Clinical presentation suggesting periampullary cancer should lead without delay to ultrasound of the liver, bile duct, and pancreas as the first-line investigation 1
• When periampullary malignancy is suspected from clinical symptoms and/or ultrasound findings, further imaging with contrast-enhanced CT, MRI/MRCP should be performed to accurately delineate tumor characteristics 2, 1
• CT with arterial and portal phases of contrast enhancement can predict resectability in 80-90% of cases and is the most useful initial test if performed before biliary stenting 2, 3
• MRI with MRCP provides detailed ductal images without risk of ERCP-induced pancreatitis and may clarify diagnostic uncertainty 2, 1
• Endoscopic ultrasound (EUS) is highly sensitive for detecting small tumors and vascular invasion, and should complement staging when available 2, 1
• MD-CT of the chest is recommended to evaluate potential lung metastases 1
• Laparoscopy with laparoscopic ultrasonography may be appropriate in selected cases to detect occult metastases 2, 1

Tissue Sampling Approach

• Attempts should be made to obtain a tissue diagnosis during investigative endoscopic procedures 2, 1
• For patients who will undergo surgery with radical intent, a previous biopsy is not obligatory 1
• EUS-guided biopsy is preferred when tissue sampling is required in ambiguous cases 1
• Failure to obtain histological confirmation does not exclude malignancy and should not delay appropriate surgical treatment in highly suspicious cases 2
• Transperitoneal/percutaneous techniques to obtain tissue diagnosis have limited sensitivity in potentially resectable tumors and should be avoided due to risk of tumor seeding 2, 1
• Tissue diagnosis should be obtained in all patients selected for palliative therapies 2

Management Based on Disease Stage

Resectable Disease (Stage I and some Stage II)

• Radical surgery is the only curative treatment option and should be confined to specialist centers 2, 1
• Pancreaticoduodenectomy (Whipple procedure, with or without pylorus preservation) is the most appropriate resection for tumors of the pancreatic head and ampullary region 2, 4
• Distal pancreatectomy (with splenectomy) is appropriate for localized carcinomas of the body and tail 2
• If a stent is placed prior to surgery, it should be of the plastic type and placed endoscopically; self-expanding metal stents should not be inserted in patients likely to proceed to resection 2, 1
• Percutaneous biliary drainage prior to resection in jaundiced patients does not improve surgical outcome and may increase infection risk 2
• Postoperatively, 6 months of adjuvant chemotherapy (gemcitabine or 5-FU) is recommended 1

Borderline Resectable Disease

• Neoadjuvant chemotherapy or chemoradiotherapy may benefit patients to achieve downsizing of the tumor and potentially convert to resectable status 1
• Patients who develop metastases during neoadjuvant therapy or progress locally are not candidates for secondary surgery 1
• Extended resections involving the portal vein or total pancreatectomy may be required in some cases but do not increase survival when performed routinely 2
• Resection in the presence of preoperative portal vein encasement is rarely justified 2

Locally Advanced Unresectable Disease

• FOLFIRINOX protocol should be considered for patients with good performance status 1
• Adjuvant or neoadjuvant therapies in conjunction with surgery should only be given in the context of clinical trials 2

Metastatic Disease (Stage IV)

• FOLFIRINOX protocol can be considered for patients ≤75 years with good performance status (0 or 1) and normal bilirubin 1
• If chemotherapy is used for palliation, gemcitabine single agent treatment is recommended 2, 1
• Combination of gemcitabine and erlotinib may be considered, with erlotinib continued only if skin rash develops within first 8 weeks 1

Palliative Management

Biliary Obstruction

• Endoscopic stent placement is preferable to trans-hepatic stenting for relief of obstructive jaundice 2, 1
• Metal prostheses should be preferred for patients with life expectancy >3 months 1
• Surgical bypass may be preferred in patients likely to survive more than six months 2

Duodenal Obstruction

• Duodenal obstruction should be treated surgically 2
• Expandable metal stents may be used in some cases of proximal obstruction 1

Pain Management

• Patients should have access to palliative care specialists 2
• Pain relief should be achieved using a progressive analgesic ladder, with opioids for severe pain 2, 1
• Neurolytic celiac plexus block is effective for treatment and prevention of pain 2, 1

Common Pitfalls to Avoid

• Delaying referral to specialist centers reduces resection rates and increases mortality 1
• Using percutaneous biopsy techniques for potentially resectable tumors risks tumor seeding 1
• Inserting self-expanding metal stents in patients who may undergo resection complicates surgery 2, 1
• Routine use of PET scan for staging is not currently recommended 1
• Failure to obtain tissue diagnosis in patients selected for palliative therapy 2