University of

Leicester

The pancreas “The shape and size of a kipper”

Ashley Dennison

University of Leicester

Exploring the Science of Digestion Birmingham Town hall

Tuesday 6th December,2016

University of

Leicester

History of the pancreas

• The pancreas was first identified by a Greek anatomist Herophilus in 335–280 BC

• Another Greek anatomist and physician Ruphos of Ephesus in the late 1st century AD gave the pancreas its name.

• Etymologically, the term "pancreas“ is a modern Latin adaptation of the Greek πάγκρεας, πᾶν "all", "whole", and κρέας "flesh", originally meaning sweetbread although literally meaning all-flesh, presumably because of its fleshy consistency

University of

Leicester

The pancreas is essential

• Pancreatic tissue is present in all vertebrates

• Can be up to three pancreas’s but fused into one in humans

• Sometimes no discrete pancreas with tissue distributed in the mesentery of the bowel and other organs such as the liver and spleen

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Leicester

Studies on the pancreas

• The study of the pancreas began on March 2, 1642, when a German émigré, Johann Georg Wirsüng, discovered the pancreatic duct in the San Francisco Monastery in Padua, Italy. Wirsüng was murdered by a student the year after the discovery.

• 1671 Regnier de Graaf investigated the physiological functions of the pancreas by examining the juice in dogs

University of

Leicester

Where is the pancreas

• Shape and size of a kipper with a head, neck, body and tail

• At the back of the upper abdomen • Six inch's long weighing 60-100g • Draped over the blood vessels at the

back of the abdomen • Has a duct like the backbone of a kipper • Connected to the first part of the bowel

after the stomach, the duodenum

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Leicester

Anatomy of the pancreas

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Leicester

Under the microscope

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Leicester

Function remained a mystery

• The digestive enzymes, (amylase, lipase, trypsin, etc), secreted by the pancreas into the intestine, were discovered in the mid to late 19th century.

• In 1889 Oscar Minkowski discovered that removing the pancreas from a dog caused it to become diabetic.

• In 1921 insulin was discovered by Frederick Banting and Charles Best

• Beginning in 1898 surgeons started to operate on the pancreas Codivilla (1898) and Halsted (1898), Kausch (1909), Hirschel (1913), Tenani (1918), and Whipple (1934-1940) who performed the first successful one-stage resection of a cancer of the pancreas in New York City on March 6, 1940.

University of

Leicester

Main functions of the pancreas

• Digestion of food by producing enzymes (exocrine) such as lipase, protease and amylase

• Blood sugar control and metabolism (endocrine) by hormones (insulin, glucagon, somatostatin and pancreatic polypeptide).

• Control of the function of the bowel

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Leicester

What can go wrong

• Tumours

Cancer

Other tumours

• Inflammation

Acute

Chronic

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Leicester

Pancreas cancer

• Common disease – 9,000 per year in UK; 5th commonest fatal cancer

• 85-90% inoperable at presentation

• Only 20% of the remainder cured by surgery

• 97% will die of the disease

• 8,500 deaths per year

Incidence approximates to mortality

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Leicester

Signs and symptoms

• Painless jaundice

Pale stools (clay coloured) and

dark (tea coloured) urine

• Back pain (depends on the position of the tumour)

• Weight loss

University of

Leicester

Outlook of pancreas cancer

• Locally advanced cancer: median

survival without treatment about 6

months

• Disseminated disease: median

survival without treatment ~3

months

• With standard chemotherapy

(gemcitabine) 18% survive one year;

2% without.

• Results have not improved significantly for 30 years

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Leicester

Other pancreas tumours

Neuroendocrine tumours (NET’s)

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Leicester

“Acute pancreatitis is an acute inflammatory process of the pancreas with variable involvement of other regional tissues or remote organ systems”

In 1925 Sir Berkeley Moynihan wrote “acute pancreatitis is the most terrible of all calamities that occur in connection with the abdominal viscera. The suddenness of its onset, the illimitable agony which accompanies it and the mortality attendant upon it render it the most formidable of catastrophes.”

Acute Pancreatitis

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Leicester

Causes of acute pancreatitis

• Gallstones

• Alcohol

• Trauma

• High lipids and calcium

• Infection

• Drugs

• Cancer

• Pregnancy

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Leicester

Intracellular oedema

Cell membrane destruction

Causes cell damage

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Leicester

“There have been sharp increases in the incidence of acute pancreatitis over the last 30 years in the UK and other European or western countries. These include studies in Croatia, Denmark, Finland, Germany, Ireland, Norway, Sweden, the Netherlands, and the USA”

“From 1999-2010 the incidence of acute pancreatitis was 30.0 per 100 000 population overall, mortality was 6.4% at 60 days. Incidence increased significantly from 27.6 per 100 000 in 1999 to 36.4 in 2010 (average annual increase = 2.7% per year).”

Incidence in the UK

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Leicester

• Mild attack in 80-90% but severe in 10-20% • Overall mortality 6-8% but 25-40% when severe • Recurrent episode within 3 years in 16.5-25% • Mortality has steadily fallen over the last 30 years • Pancreatic necrosis in 10-20% • Infected pancreatic necrosis 20-30% (of patients with

necrosis)

Effects of acute pancreatitis

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Leicester

In an American study; “The estimated total cost for acute pancreatitis admissions was $2.2B at a mean cost per hospitalization of $9870 and a mean cost per hospital day of $1670. Costs per hospitalization were higher in urban hospitals, teaching hospitals, and for patients older than 65 years, based on a longer length of stay.”

In a European study; “The overall hospital cost and cost for loss of production was per person in mean €5,100 for mild acute pancreatitis and €28,200 for severe acute pancreatitis. The costs for treating AP during the two-year-long study period were on average €9,762 per patient. Extrapolated to a national perspective, the annual financial burden for AP in Sweden would be €38,500,000; corresponding to €4,100,000 per million inhabitants”

Acute pancreatitis is very expensive

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Leicester

Chronic pancreatitis

Chronic pancreatitis (CP) is an inflammatory disease that causes

progressive damage to the pancreatic parenchyma with irreversible

morphological changes and fibrotic replacement of the gland

• In the UK ~50% caused by alcohol

• ~50% idiopathic (unknown)

• Small number due to genetic causes

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Leicester

Chronic pancreatitis damage

Normal pancreas Chronic pancreatitis

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Leicester

Symptoms of chronic pancreatitis

• Severe unremitting abdominal pain

• Back pain

• Malabsorption (loose motions due to steatorrhoea; offensive smell)

• Weight loss

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Leicester

Conclusions

• The pancreas is a complex organ

• Prone to a number of problems

• Pancreas cancer has a very poor outlook

• Pancreatitis, both acute and chronic, is potentially fatal and very costly