Pancreas HU/echogenicity = liver, but with age/fat infiltration becomes echogenic/hypodense.
Fatty lesions include diffuse/focal fatty infiltration or lipoma. Fatty infiltraiton from aging, obesity, pancreatic atrophy (CF, chronic pancreatitis). May have focal fatty sparing (esp head, uncinate process) mimicing a mass.
The exocrine pancreas consists of acini, forming ducts. Ductal cells produce bicarbonate to neutralise stomach chyme (semifluid partly digested food expelled from the stomach with pH~2), stimulated by the hormone secretin (made by S cells in the duodenum). Acinar cells are stimulated by cholecystokinin (CCK, produced by duodenum), inhibited by somatostatin. Acini synthesize and secrete proteases (trypsinogen, chymotrypsinogen), peptidases (carboxypeptidase), elastases, pancreatic lipase, cholesterol esterase, phospholipase, nucleases, and pancreatic amylase. Apart from amylase and lipase, these are all inactive proenymes, requiring activtion by trypsin in the duodenal lumen.
The endocrine pancreas consists of islets of Langerhans, with β (insulin), α (glucagon), Î´ (somatostatin, suppresses insulin and glucagon release), PP (pancreatic polypeptide, self-regulates pancreatic secretion, hepatic glycogen levels and GI secretions), D1 (vasoactive intestinal polypeptide VIP, induces glycogenlysis, stimulates GI secretion), and enterochromaffin (serotonin) cells.
Band-like ring of pacreatic tissue encircling D2.
Some ectopic pancreatic tissue in 2% of the population; including stomach, duodenum, jejunum, Meckel diverticulum, ileum. May cause pain or rarely mucosal bleeding. 2% of islet cell neoplasms arise this ectopic tissue.
3-10% of population, failed fusion of foetal dorsal and ventral pancreatic primordia. Body, tail and most of head drain via duct of Santorini to the more proximal minor sphincter. The uncinate process and some of the head drain via duct of Wirsung to papilla of Vater.
Reversible inflammation causing disruption of small ducts and leakage of pancreatic secretions with inappropriate activation of trypsinogen and autodigestion. Duct obstruction causes oedema, impaired blood flow and ischaemia. Pancreas lacks a capsule, so enzymes digest fascial layers spreading across compartments. Necrosis of fat by lipolytic enzymes (chalky, pale), proteolytic destruction of pancreatic parenchyma, oedema and acute inflammation, destruction of blood vessels with haemorrhage. Focal/diffuse enlargement, oedema (low HU, hypoechoic) indistinct margins, fat stranding. Focal pancreatitis more common in the head. Serum amylase rises in 1st 24hrs, lipase within 72-96hrs. Causes include:
- Alcohol (most chronic pancreatitis) – M>F. Chronic ingestion -> secretion of protein-rich pancreatic fluid -> inspissated protein plugs causing obstruction of small ducts. Alcohol also transiently increases exocrine secretion and contraction of sphincter of Oddi, direct toxic effects of pancreatic acinar cells.
- Gallstones (50%, most acute pancreatitis) – 5% of patients with gallstones develop pancreatitis, F>M. Occasionally from biliary sludge.
- Metabolic – Hypercalcaemia, hyperlipidaemia, malnutrition.
- Trauma – Blunt trauma, surgery, ERCP.
- Ischaemia – Shock, vascular thrombosis, embolism, vasculitis.
- Penetrating ulcer
- Malignancy – Adenocarcinoma, lymphoma.
- Drugs – Steroids, tetracycline, frusemide, azathioprine, oestrogens etc.
- Infection – Viral (mumps, hepatitis, infectious mononucleosis, AIDS), parasites (ascariasis, clonorchis).
- Structural – Choledochocoele, pancreatic divism.
- Idiopathic (20%)
- Hereditary pancreatitis (10-20%) – Recurrent severe pancreatitis usually starting in childhood. Most from mutation in trypsinogen gene (PRSS1, AD) causing premature activation of proenzymes, serine protease inhibitor Kazal type 1 (SPINK1, AR).
- Collections of enzyme-rich pancreatic juices:
- Acute – Anywhere in abdomen or into chest, spontaneously resolve in 50%.
- Pseudocyst – Collections of necrotic-haemorrhagic material rich in pancreatic enzymes developing after 4 weeks, 50% spontaneously resolve, others require drainage/surgery. Most develop after acute pancreatitis in setting of chronic alcoholic pancreatitis. Round/oval, fibrous capsule (not lined by epithelium), common septations and loculations.
- Necrotising pancreatitis (liquefactive necrosis) – Lack of enhancement, often multifocal. Significantly increased morbidity/mortality.
- Abscess – Thick indistinct wall, may have gas, debris. Confirmed with aspiration/biopsy, requires drainage.
- Haemorrhage – Erosion into vessels. Dense blood in retroperitoneum.
- Ascites – Pancreatic secretions in peritoneum.
- Pseudoaneurysm – Autodigestion of arterial walls, lined by fibrous tissue, maintaining communication with parent artery.
Recurrent and prolonged acute pancreatitis causing irreversible atrophy, fibrosis, impaired exocrine and endocrine functions. Destruction of acini with relative sparing of islets of Langerhans until late (causing diabetes mellitus). May cause pancreatic exocrine insufficiency with malabsorption. Variable increased risk of pancreatic cancer (40% in hereditary pancreatitis). 70% from alcohol, 20% long standing obstruction (esp biliary stones), others from tropical pancreatitis (?aetiology, Africa and Asia), hereditary, CFTR mutations (esp CF), autoimmune pancreatitis, 40% idiopathic. Dilated pancreatic duct (80%) usually in beaded pattern, pancreatic atrophy, parenchymal calcification of small ductal plugs (40-50%, esp alcohol; stippled to coarse), intrapancreatic and extrapancreatic collections, focal enlargement (pseudotumour, benign inflammation and fibrosis), dilated biliary duct (from fibrosis or inflammatory mass in head), fascial thickening.
(Lymphoplasmacytic sclerosing pancreatitis). Increased IgG4-producing plasma cells with inflammatory infiltrate, venulitis. Diffuse pancreatic duct narrowing and capsule around pancreas causing it to be sausage-shaped. May be associated with sclerosing cholangitis, pseudotumours in other organs (esp kidneys). Very sensitive to steroids.
Almost all are ductal adenocarcinomas. Poor prognosis, usually unresectable. Develop from precursor pancreatic intraepithelial neoplasias (PanINs). 80% 60-80yo, blacks > whites. Increased risk with smoking, fatty diet, chronic pancreatitis, diabetes mellitus (may also be a sign of carcinoma), alcohol, FHx, BRCA2, Peutz-Jeghers, HNPCC, hereditary pancreatitis, familial melanoma.
60% from head (tend to present earlier due to duct obstruction), 15% body, 5% tail, 20% diffuse. Hypodense/hypoechoic mass distorting pancreatic contour, biliary and pancreatic duct obstruction (in 50%) with jaundice in most, atrophy of distal pancreatic tissue. Very rarely calcifies (cf chronic pancreatitis, neuroendocrine tumours).Metastases to LN, liver, peritoneum. Common perineural spread.
Tumours are classified as resectable, borderline resectable or locally advanced/unresectable disease. The adjacent SMA/SMV is encased (unresectable) if >180deg contact; abutment if if </= 180deg. Unresectable if there is SMA encasement (>180deg) or contour irregularity (tear-drop deformity, calibre change), IVC abutment, coeliac axis abutment (any contact with head, >180 encasement in body/tail), unreconstructibile SMV/PV occlusion. Borderline resectable if GDA encased, SMA abutment (</=180deg), distorted/narrowed/occluded SMV or PV (with suitable vessel proximal and distal).
Important to mention presence of venous thrombosis (tumoural or bland), extend of contact of common hepatic artery, extent of SMA/SMV contact to 1st branch, stranding contacting vessels (may be tumour, scarring or inflammation), arterial variants.
May be duodenal, biliary duct or pancreatic in origin.
Pancreatic Endocrine Neoplasms
(Islet cell tumours, neuroendocrine tumour). 2% of pancreatic neoplasms, adults, anywhere along length of pancreas or immediate peripancreatic tissues. May be single or multiple. Hypervascular, hypoechoic, low-T1, high T2. May have cystic degeneration, haemorrhage, fibrosis, calcification. Intraoperative US helps identify position during surgery. Difficult to predict malignancy even on histology, except if there are metastases, vascular invasion or local infiltration. 90% of insulinomas are benign, 60-90% of the other tumours are malignant.
- Functional tumours tend to present when small <40mm. Some tumours are multihormonal tumours.
- Insulinoma (β-cell, most common) – 80% have hypoglycaemia esp with fasting or exercise. Usually <20mm. Only 10% malignant.
- Gastrinoma – 90% have Zollinger-Ellison syndrome of gastric hypersecretion (causing diarrhoea) and peptic ulcers. May arise anywhere in the gastrinoma triangle (duodenum and peripancreatic tissues). 60% are malignant. 25% have MEN1, more likely multifocal.
- Glucagonoma (α-cell) – Most peri/post-menopausal women. Mild DM, painful glossitis, skin rash, anaemia. 80% are malignant. Coarse calcification, heterogeneous with cystic degeneration and necrosis, local and vascular invasion, metastases.
- Somatostatinoma (Î´-cell) – DM, steatorrhea, cholelithiasis, hypochlorhydia.
- VIPoma (D1 cells) – WDHA syndrome of watery diarrhoea, hypokalaemia, achlorrhydia; may also be seen in neural crest tumours (neuroblastoma, ganglioneuroblastoma, ganglioneuroma, pheochromocytoma).
- Pancreatic carcinoid (enterochromaffin cell) – Produce serotonin, very rare.
- Nonfunctional tumours present when large (60-200mm), 80% are malignant. PP cells (pancreatic polypeptide) tumours, despite being functional are asymptomatic.
Most are RCC or bronchogenic carcinoma. Solitary well-defined heterogeneous enhancement, diffuse heterogeneous enlargement, or multiple nodules. Low T1, high T2 (apart from melanoma high T1 due to melanin).
Direct extension from retroperitoneum, or rarely primary. Homogeneous, hypodense (may appear cystic), limited enhancement. Well-defined mass or diffusely infiltrating enlarging/replacing pancreas.
DDx duodenal diverticula. Most are pseudocysts with only 10% neoplastic.
True Pancreatic Cysts
Lined by uniform cuboidal epithelium and contains clear fluid. ?Anomalous development of ducts. Seen in 10% of ADPKD, 30% of vHL (also at risk of islet cell tumours, microcystic adenomas), some with CF. Solitary sporadic cysts rare. Well-defined, usually thin-walled, unilocular, up to 50mm.
Serous Cystadenoma (25%)
(Glycogen-rich cystadenoma). Benign cystic tumour, lining cuboidal epithelial cells rich in glycogen. 80% >60yo, F:M 2:1. Increased risk with vHL. Microcystic adenomas have innumerable small 1-20mm cysts, may appear solid. Macrocystic serous cystadenomas (10%) have uni/bi-locular cysts >20mm, indistinguishable from mucinous cystic tumours. Central stellate fibrous scar which may calcify (characterstic), well-defined, vascular with marked enhancement of septations in honeycomb appearance.
Mucinous Cystic Neoplasm
(Macrocystic adenoma, mucinous cystadenoma/cystadenocarcinoma). 80% in women, peak middle-aged. 20-300mm mucin-filled cyst lined by columnar epithelium and thick fibrous capsule. Multilocular or unilocular, usually body or tail, <6 separate cysts. May have peripheral egg-shell type calcification. 1/3 harbour invasive adenocarcinoma malignancy, requiring complete excision for evaluation. Liver metastases tend to be cystic.
Intraductal Papillary Mucinous Neoplasm (IPMN)
(Intraductal papillary mucinous tumour IPMT). M>F. Tumour with excessive mucin production causing marked dilatation of pancreatic duct and ductules, mucin pours into duodenum via ampulla. 15% are multifocal. Main duct IPMN dilates entire main pancreatic duct, may see the papillary tumour in the duct, atrophic rim of parenchyma, bulging papilla of Vater with mucin. Branch duct IPMN has focal small 10-20mm interconnecting cysts, most commonly uncinate process or head, adjacent parenchymal atrophy which becomes a capsule.
Solid Pseudopapillary Neoplasm
Uncommon, most young women, benign. Large, well-defined mass with solid and cystic components filled with haemorrhagic debris. Most are cured by resection.
Group of metabolic diseases with hyperglycaemia, from defect in insulin secretion and/or insulin action. Insulin secretion is stimulated by glucose and acts to increase transport into striated muscle (including myocardium, for storage as glycogen) and to a lesser extent adipocytes (for storage as lipid) and brain.
- Type 1 diabetes (5-10%) – Autoimmune destruction of β-cells of the islets of Langerhan. Most diagnosed <20yo. 90-95% have defect on the HLA locus of chromosome 6 (cf 40% of normals). ?Association with viruses including mumps, rubella, coxsackie B, CMV.
- Type 2 diabetes (90-95%) – Combination of peripheral resistance to insulin and β-cell dysfunction impairing insulin secretion. Most patients are overweight.
- Monogenic forms – Mutations causing defect in β-cell function or insulin receptor.
- Secondary to exocrine pancreatic defects – Chronic pancreatitis, pancreatectomy, trauma, neoplasia, cystic fibrosis, haemachromatosis.
- Endocrinopathies – Acromegaly, Cushing syndrome, hyperthyroidism, pheochromocytoma, glucagonoma.
- Infections – CMV, coxsackie B, congenital rubella.
- Genetic syndrome – Down syndrome, Kleinfelter syndrome, Turner syndrome, Prader-Willi syndrome.
- Gestational diabetes
Complications are from combinations of advanced gycation of end products (AGEs; nonenzymatic glycation inducing inflammation, ROS, procoagulant and proliferation of vascular smooth muscle, bind to collagen to reduce vascular elasticity), activation or protein kinase C (causing neovascularity, vasoconstriction, profibrogenic, inflammation), and intracellular hypergycaemia (prone to oxidative stress).
- Macrovascular disease – Medium and large muscular artery accelerated atherosclerosis and hyaline arteriosclerosis. Increasesd risk of MI, CVA, gangrene.
- Microvascular disease – Capillary dysfunction and diffuse thickening of basement membranes. Causes retinopathy, nephropathy and neuropathy.