Pancreatic and Periampullary Tumours — Painless Jaundice, Resectability, Whipple Procedure and Ampullary Cancer

The periampullary region is the neighbourhood of the ampulla of Vater, where the common bile duct and the main pancreatic duct join and open into the duodenum. Cancers arising here — from the pancreatic head, the ampulla itself, the distal bile duct or the duodenum — all tend to obstruct the bile duct early and so present with jaundice. They are lumped together because they are operated on with the same procedure, the Whipple operation (pancreaticoduodenectomy), but their outlook differs greatly.

StatPearls stresses that it is important to separate ampullary carcinoma from the other periampullary tumours: pancreatic cancers and cholangiocarcinomas carry a significantly worse prognosis and fewer treatment options than ampullary cancers, even in early disease. This distinction is the core exam point of the whole topic.

Pancreatic ductal adenocarcinoma (PDAC) arises from the duct cells. More than 90% of pancreatic adenocarcinomas are duct cell adenocarcinomas; cystadenocarcinoma and acinar cell carcinoma are the other histological types. Two-thirds arise in the head, one-third in the body and tail. It is the fourth leading cause of cancer death in the United States, and only about 20% are surgically resectable at diagnosis; surgical resection is the only current chance of cure.

The tumour markers associated with pancreatic cancer are CA 19-9 and CEA. At diagnosis, about 52% of patients already have distant metastases and 23% local spread, which explains the poor outcome: StatPearls quotes a 5-year survival of roughly 5–15%.

A head tumour classically produces painless obstructive jaundice (about 50%) from compression of the common bile duct. Other features and their frequency in StatPearls: weight loss (about 90%), abdominal pain (about 75%), anorexia, weakness, pruritus from bile salts, clay-coloured stools and dark urine. A palpable, non-tender, distended gallbladder (Courvoisier sign) points to a malignant distal biliary obstruction. New-onset diabetes and unexplained or recurrent deep vein thrombosis from hypercoagulability can be the first clue to an occult malignancy.

• Labs: raised direct and total bilirubin, raised liver enzymes, sometimes raised amylase and lipase, plus CA 19-9 and CEA.
• Pain is common and severe — pancreatic cancer is one of the most painful malignancies, treated with opioids, antiepileptics and corticosteroids; a pain specialist is part of the team.
• Body and tail tumours produce fewer early signs and are usually found later.

Multidetector CT (MDCT) is the best imaging test to diagnose and stage pancreatic cancer. A pancreatic protocol uses a late arterial (pancreatic) phase 35–50 seconds after contrast to see the parenchyma and a portal venous phase at 60–90 seconds to assess veins and detect liver and distant metastases. MDCT is about 77% accurate in predicting resectability and 93% accurate in predicting unresectability. MRI/MRCP is equally useful for vascular invasion and more sensitive for liver metastases, and is the next step if CT is negative but suspicion is high. Ultrasound is of limited value (bowel gas) but shows biliary dilatation. Endoscopic ultrasound allows FNA; ERCP can place a biliary stent. If a mass is clearly resectable after full work-up, tissue confirmation is not mandatory before excision.

For fit patients, the two principal chemotherapy regimens are FOLFIRINOX (5-fluorouracil, oxaliplatin and irinotecan — very toxic, suited to young fit patients) and gemcitabine plus nab-paclitaxel (protein-bound paclitaxel, lower toxicity, used for older or less fit patients). Typical duration is 4–6 months and these regimens are now used before as well as after surgery. A neoadjuvant-first approach is increasingly adopted in high-volume centres, because many patients never complete adjuvant therapy after a Whipple. Radiotherapy, with chemotherapy, can shrink locally advanced tumours and relieve pain.

Ampullary cancer arises from the ampulla of Vater, the terminal confluence of the distal common bile duct and pancreatic duct. It is rare — about 6% of periampullary tumours — and typically occurs in the 7th decade, earlier in people with hereditary polyposis syndromes or Lynch syndrome, in whom risk may be raised about 200-fold. It arises from a precursor ampullary adenoma and is commonly associated with K-ras mutations. Histologically about 47% are intestinal type and about 24% pancreatobiliary type; the intestinal type behaves better.

The only curative treatment is pancreaticoduodenectomy. Perioperative mortality is below 5% but morbidity is 20–40%, with anastomotic leak and delayed gastric emptying common. About 45% of resected patients develop recurrence, so patients with T2 or higher tumours or positive nodes are considered for adjuvant chemotherapy (gemcitabine or a fluoropyrimidine), sometimes with chemoradiation of about 50.4 Gy. Temporary plastic biliary stents are preferred to metal stents when surgery is planned. Node positivity is the key prognostic factor.

Pancreaticoduodenectomy resects the pancreatic head and uncinate process, duodenum, proximal jejunum, distal bile duct, gallbladder and usually part of the stomach, and then restores bilioenteric continuity. It was first performed by Kausch in Germany and refined by Whipple in the USA. In the pylorus-preserving variant the stomach is retained and the duodenum divided; a duodenojejunostomy replaces the gastrojejunostomy.

SPEN is thought to arise from pluripotent cells of the genital ridge, which would explain the female predominance and expression of sex-hormone receptors. Pseudopapillary structures and pseudorosettes are characteristic, and cercariform cells help distinguish SPEN from a pancreatic neuroendocrine tumour. IPMN with obstructing mucin may present as acute pancreatitis, which is a worrisome feature in the 2024 Kyoto guidelines; see acute pancreatitis.

For an IPMN, the main pancreatic duct diameter separates the types: under 5 mm suggests a branch-duct (BD) lesion with no main-duct involvement; 5 mm or more indicates main-duct or mixed involvement. BD-IPMNs often look like a cluster of grapes on MRI. The 2024 Kyoto guidelines grade the risk features.

EUS with fine-needle aspiration is considered when a cyst has two or more worrisome features, such as size of 3 cm or more, a solid component or a dilated main duct. Surveillance may be stopped for stable cysts under 20 mm after 5 years, depending on life expectancy and preferences.