Pancreas
It weighs 80 g, it is an endocrine (islets of Langerhans with different cell types : B cells: producing insulin, A: producing glucagon, D: producing stomatostatin) & exocrine gland(80-90%). It is a soft, lobulated organ that lies retroperitoneally in transpyloric plane. It is divided into : 1. Head : Disc shaped, lying within the concavity of duodenum. Part of it extends behind the superior mesenteric vessels (uncinate process) 2. Neck : The constricted portion. It lies in front of beginning of portal vein, & the origin of superior mesenteric artery from aorta. 3. Body : Runs upwards & to the left 4. Tail : Passes forward in lienorenal ligament & comes in contact with the hilus of spleen (injury to pancreas with pancreatitis may occur after splenectomy). The main pancreatic duct begins in the tail & runs the length of the gland.Relation :
Anteriorly : Lesser sac ( inflammation or damage to pancreas may result in effusion of fluid into this space with formation of pseudocysts ), stomach, attachment of transverse mesocolon, & transverse colon.
Posteriorly : Bile duct (because of the intimate relation of the head of pancreas to the bile duct, cancer of head of pancreas often causes obstructive jaundice), portal vein, splenic vein, IVC, aorta, origin of superior mesenteric artery, left psoas, left suprarenal gland, left kidney, & hilus of spleen.
Blood supply : 1. Splenic artery : Arises from the celiac trunk 2. Superior pancreaticoduodenal artery : Arises from gastroduodenal artery 3. Inferior pancreaticoduodenal artery : Arises from superior mesenteric artery Corresponding veins drain into the portal vein
Lymphatic drainage :Drainage to lymph nods along the arteries that supply the gland, then to celiac lymph nods & superior mesenteric lymph nods
Nerve supply : Parasympathetic : From the vagus nerve.
Sympathetic : From celiac plexus
Investigations :
1-Estimation of pancreatic enzymes in body fluids eg. S. amylase : Increased in pancreatic damage (pancreatitis) within a few hours & declines over the next 4-8 days.It increased in other conditions like:upper GIT perforation, mesenteric infarction, tortion of an intra-abdominal viscus, retroperitoneal haematoma, ectopic pregnancy, renal failure, salivary gland inflammation.2-Pancreatic function tests : By assessing pancreatic exocrine function (secretion) in response to a standardised stimulation.
3-Imaging investigations :
a-Abdominal ultrasonography : It is the initial investigation of choice in patients with jaundice.
b-Computerised tomography (CT)
c-Magnetic resonance imaging (MRI) , Magnetic resonance cholangiography & pancreatography (MRCP)
d-Endoscopic retrograde cholangiopancreatography (ERCP): It is replaced by MRCP as it is non-invasive & less exspensive.
e-Endoscopic ultrasound : (EUS) :Can identify small tumours that may not show up well in CT or MRI & transgastric or transduodenal fine needle aspiration biopsy under EUS can be performed.
Congenital anomalies
1-Cystic fibrosis : It is an autosomal recessive, affects the lungs, intestine, pancreas, & liver, characterised by elevated concentration of sodium & chloride ions in sweat. Organ damage is due to blockage of the narrow passages by thickened secretions. When affects the pancreas, exocrine insufficiency causes steatorrhoea which present from birth & results in bulky, oily, & offensive stool.
2-Annular pancreas : A ring of pancreatic tissue surrounds the second or third part of the duodenum causes duodenal obstruction with vomiting in the neonate. Treatment is bypass dudenodudenostomy
3-Ectopic pancreas : Pancreatic tissues found in the submucosa of stomach, duodenum, small intestine (Meckelsdiverticulum), gall bladder, hilum of the spleen, & within the liver.
4-Congenital cystic disease of pancreas : May be associated with congenital disease of kidney & liver.
Pancreatic injuries
External injuries : It is often associated with injuries to other organs, especially the liver, spleen & duodenum. Blunt trauma may crush the body of the pancreas against the vertebral column. Pancreatic injuries may range from contusion or laceration of parenchyma without duct disruption to major parenchymal destruction with duct disruption (sometimes complete transaction) & rarely massive destruction of pancreatic head. Pancreatic duct disruption is the most important factor that determine the treatment.
Blunt pancreatic trauma usually present with epigastric pain. Serum amylase usually increased. CT scan demonstrates the damage & if there is doubt about duct disruption an urgent ERCP or MRCP may be needed.
Treatment : Conservative, by i.v. fluid, nothing by mouth, & antibiotic. Operation is indicated when there is duct disruption, when the patient is haemodynamically unstable, or presence of peritonitis. An urgent surgical exploration is needed in penetrating injuries, especially if the patient is unstable or associated with other organs injuries. For minor parenchymal injuries, haemostasis & closed drainage is adequate. If the gland is transected in the body or tail distal pancreatectomy with or without splenectomy is needed. If the damage is confined to the head, haemostasis & external drainage is effective. If there is severe injury to the head & duodenum, pancreaticodudenectomy may be needed.
Prognosis: Death may happen due to severe blood loss from other organs injuries. Pancreatic fistula may occur. Duct strictures may occur leading to recurrent episodes of pancreatitis treatment is resection of the tail of the pancreas up to the site of duct disruption. Pancreatic pseudocyst may develop (treated by percutaneous aspiration), but if it is associated with complete disruption of the pancreas then distal resection or pancreatojejunostomy with Roux-en-Y loop must be done.
2-Iatrogenic injuries: a- Injury to the tail of pancreas during splenectomy leading to pancreatic fistula. b- Injury to the accessory pancreatic duct during Billroth ІІ gastrectomy. c-Enucleation of islet cell tumours of the pancreas can result in fistula.
Pancreatic fistula
Usually follows operative trauma to the pancreas or as a complication of pancreatitis. It may be externally to the skin or internally to bowel. Measurement of the amylase content of the fluid will determine its nature. Investigation of the cause of the fistula is required to treat the underlying cause (frequently the cause is related to obstruction within the pancreatic duct which is treated by the insertion of the stent or catheter endoscopically into the pancreatic duct. Correction of fluid & electrolyte imbalances, protection of the skin, adequate drainage, parenteral or nasojejunal feeding, octreotide may be useful to suppress pancreatic secretion.Pancreatitis :
Inflammation of the pancreatic parenchyma, caused by premature activation of pancreatic enzymes within the pancreas that leads to autodigestion. It is caused by injury of the acinar cell (impairs the secretion of zymogen granules) or duct epithelium (delays enzymatic secretion). Inflammation can lead to pancreatic oedema, haemorrhage, & necrosis. Inflammatory mediators released into the circulation lead to systemic complications (haemodynamic instability, bacteraemia due to translocation of gut flora, acute respiratory distress syndrome ARDS, pleural effusion, GI haemorrhage, renal failure, & disseminated intravascular coagulation DIC. It could be acute or chronic.
Acute pancreatitis
Acute pancreatitis is defined as an acute condition presenting with abdominal pain and is usually associated with raised pancreatic enzyme levels in the blood or urine as a result of pancreatic inflammation. Acute pancreatitis may recur. It may be mild or severe. Mild acute pancreatitis characterised by interstitial oedema of pancreas & minimal pancreatic dysfunction. Severe acute pancreatitis characterised by pancreatic necrosis, severe systemic inflammatory response & often multi-organ failure, with mortality of 20-50%. One third of deaths occur in the early phase of the attack, from multiple organ failure. After first week of onset deaths are due to septic complications.
Etiology:
The two major causes of acute pancreatitis are biliary calculi and alcohol abuse. 1- Biliary calculi (in 50-70% of patients). When the bile & pancreatic ducts have a common channel, biliary calculi may cause obstruction with reflux of bile or activated pancreatic enzymes into the pancreatic duct. 2- Alcohol abuse (in 25% of patients). 3- Post ERCP (1-3%). 4-Abdominal trauma. 5- Following biliary, upper gastrointestinal or cardiothoracic surgery 6- Ampullary tumour. 7- Hyperparathyroidism. 8- Hypercalcemia. 9- Viral infection (mumps). 11- Drugs (corticosteroids, azathioprine , oestrogens, thiazides). 12- Hereditary (with high risk of developing pancreatic cancer). 13-Autoimmune. 14- Idiopathic. 15- Malnutrition. 16- Scorpion bite.
Patient presented with upper abdominal pain (usually severe in the epigastrium or either upper quadrant or diffuse throughout the abdomen, with radiation to the back in 50% of patients), which is refractory to the usual doses of analgesics, but may gain relief by sitting or leaning forwards. Nausea, vomiting, retching, & hiccoughs (due to gastric dilatation or irritation of diaphragm). Clinical examination : a patient may look well, or gravely ill with profound shock, toxicity & confusion. Hypotension, tachycardia, tachypnoea, temperature (normal, subnormal or increased if inflammation or cholangitis develop). Bluish discolouration of the flanks (Grey Turners sign) or umbilicus (Cullens sign: first described in ruptured ectopic pregnancy) due to bleeding into the fascial plains may be present, but neither sign is pathognomonic. Small ,red, tender nodules on the skin of the legs may be present (due to subcutaneous fat necrosis). Abdominal examination may reveal distension (due to ileus), ascites, epigastric mass (due to inflammation), muscle guarding in the upper abdomen. Pleural effusion is present in 10-20%.
Investigations :
The diagnosis is made on the basis of clinical presentation & an elevated serum amylase (3-4 times above normal is indicative of the disease, it is not pathognomonic. A normal serum amylase cannot exclude acute pancreatitis). Serum lipase provides more sensitive & specific test than amylase. Imaging : 1- Plain erect chest & abdominal radiographs shows generalized or local ileus (sentinel loop), a colon cut-off sign & a renal halo sign, calcified gallstones or pancreatic calcification. Chest radiograph may show a pleural effusion, a diffuse alveolar interstitial shadowing (suggest acute respiratory distress syndrome). 2- abdominal US does not establish diagnosis of acute pancreatitis. It may show swollen pancreas, gallstones, dilated common bile duct. 3- Contrast enhanced CT scan : is the best single imaging investigation. 4- Cross-sectional MRI. 5- Endoscopic US . 6- MRCP . 7- ERCP: In patients with severe acute gallstone pancreatitis & signs of biliary obstruction & cholangitis an urgent ERCP should be done.
Assessment of severity : Various scoring systems have been introduced, such as Ranson & Glasgow scoring systems. In both systems pancreatitis is classified as severe when 3 or more of the following factors are present : 1- Age > 55years. 2- WBC count > 15 -16 109/L 3- Blood glucose > 10 mmol /L (no history of diabetes). 4- 4 4-LDH > 600 - 700 units /L 5- 5-5- Blood urea > 16 mmol /L (no response to IV fluid). 6- 6-Arterial oxygen saturation PaO2 < 60 mmHg. 7- 7-Serum calcium < 2 mmol /L 8- Base deficit > 4 mmol /L 9- Fluid sequestration > 6 litres. 10- Serum albumin < 32 g /L.
Occasionally the diagnosis is only made at laparotomy, with finding of widespread fat necrosis of omentum (caused by splitting of fat by the liberated lipase into glycerol & fatty acids with combination of free fatty acids with calcium & blood- stained peritoneal fluid).
Management of acute pancritits :
It is important to reach the diagnosis of acute pancrititis (should be differentiated from all cases of upper abdominal pain like perforated viscus, cholecystitis, hepatitis, intestinal obstruction, myocardial infarction, pneumonia) from history, clinical examination, and investigations. All cases should be admitted to the hospital. Mild pancreatitis should be treated conservatively with intravenous fluid administration, analgesics, anti-emetics & frequent observation. If there is deterioration CT scanning is necessary and treated accordingly. Severe pancreatitis : Patients should be admitted to intensive care or high-dependency unit. Adequate analgesia, aggressive fluid resuscitation. Frequent measurement of vital signs, urine output & central venous pressure. Supplemental oxygen should be administered with serial blood gas analysis. The haematocrit, clotting profile, blood glucose, serum calcium & magnesium should be monitored. A naso-gastric tube is inserted only if the patient is vomiting or for nutritional support (enteral nutrition). Prophylactic antibiotics (IV cefuroxime or ciprofloxacin plus metronidazole) should not exceed 14 days, additional antibiotics should be according to culture & sensitivity tests. Urgent ERCP should be carried out within 72 hours if gallstones are the cause, presence of jaundice, cholangitis, or a dilated common bile duct, where sphincteretomy with removal of stone could be done or a biliary stent placed to drain the duct. Patients with systemic complications should be managed by multidisciplinary team. When there is organ failure, appropriate supportive therapies may include inotropic support for haemodynamic instability, haemofiltration in the event of renal failure, ventilatory support for respiratory failure, & correction of coagulopathies (including DIC).
Local complications :may occur which should be managed conservatively, & when this fails the surgical interference should be carried out. 1- Acute fluid collection : It is sterile fluid located in or near the pancreas, usually resolve. If fluid collection is large & causes pressure symptoms, it should be aspirated percutaneously under US or CT guidance, or transgastric drainage under EUS. 2- Sterile & infected pancritic necrosis :It is diffuse or local area of non-viable parenchyma), a CT scan should be performed & a needle passed into the area under CT guidance, if the aspirate is purulent, percutaneous drainage of the infected fluid should be carried out with the widest bore tube, & the aspirate should be sent for microbiological assessment with appropriate antibiotic therapy. If the sepsis worsen despite this, then pancreatic necrosectomy should be considered (which carries a high morbidity & mortality). Sterile necrotic material should not be drained or interfered with. 3- Pancreatic abscess : It is a circumscribed intra-abdominal collection of pus, usually in proximity to the pancreas, may be infected acute fluid collection or infected pseudocyst. Treatment is by antibiotic, & percutaneous drainage with the widest drain under imaging guidance, with supportive care. Vey occasionally open drainage is needed. 4- Pancreatic ascites : It is a chronic, generalized, peritoneal, enzyme-rich effusion usually associated with pancreatic duct disruption. Paracentesis will reveal turbid fluid with a high amylase level. Treatment consists of percutaneous drainage with the widest drain under imaging guidance, parenteral or naso-jejunal feeding, administration of octreotide, an ERCP may demonstrate the duct disruption & allow placement of a pancreatic stent. 5- Pancreatic effusion :It is an encapsulated collection of fluid in the pleural cavity. It may be associated with pancreatic ascites or communicated with an intra-abdominal collection. Treatment is percutaneous drainage under imaging guidance. 6- Haemorrhage :This may happen in the gut, retroperitoneum, or peritoneal cavity. Treatment is by embolization or surgery. 7- Portal or splenic vein thrombosis : A marked rise of platelet count raises suspicion. Treatment is conservative, use of aspirin or other antiplatelet drugs, if manifestations of portal hypertension develop they should be treated accordingly. 8- Pseudocyst : It is a collection of amylase rich fluid enclosed in a wall of fibrous or granulation tissue. It typically follows acute pancreatitis, but can develop in chronic pancreatitis or after pancreatic trauma. It needs 4 weeks or more after the onset of acute pancreatitis to develop. It may be confused with cystic neoplasm, in such situation it should be aspirated under EUS guidance & fluid sent for measurement of serum amylase & carcinoembryonic antigen (CEA) levels & cytology. Most pseudocysts resolve spontaneously. Surgery (internal drainage of the cyst into the gastric or jejunal lumen) is needed only for distinction from a tumour, when pseudocyst causes symptoms (pain), or develops complications (infection, abscess, rupture, bleeding, internal fistula, pressure effects like jaundice from biliary compression & bowel obstruction, erosion into a vessel).
Chronic pancreatitis
Chronic pancreatitis is a chronic inflammatory disease in which there is irreversible progressive destruction of pancreatic tissue. Its clinical course is characterised by severe pain and, in the later stages, exocrine and endocrine pancreatic insufficiency. In the early stages of its evolution, it is frequently complicated by attacks of acute pancreatitis, which are responsible for the recurrent pain that may be the only clinical symptom. The pancreas enlarges & becomes hard as a result of fibrosis , the ducts become distorted & dilated with areas of stricture & ectasia, & calcified stones may form within the ducts. It occurs more frequently in men (male to female ratio is 4 : 1).
Etiology :
High alcohol consumption is the most frequent cause (60-70% of cases).
2-duct obstruction result from stricture formation after trauma, acute pancreatitis, or occlusion of the duct by pancreatic cancer. 3-Hereditary pancreatitis : The importance of hereditary pancreatitis and pancreatitis occurring at a young age is that there is a markedly increased risk of developing pancreatic cancer, particularly if the patient smokes tobacco. 4-Hyperlipidaemia & hypercalcaemia 5- Idiopathic chronic pancratitis 6-Autoimmune pancreatitis
Clinical presentation :
Patient usually presented with upper abdominal pain (often dull & gnawing, but may be severe). Epigastric or right subcostal pain ( when the disease is mainly in the head of pancreas). Left subcostal & back pain ( if the disease is in the left side of the pancreas). Radiation the shoulders (usually the left) may occur. Nausea & vomiting may happen. Weight loss is common & inability to work. Patient may be presented with steatorrhoea, diabetes or with complications (like those that occur in acute pancreatitis). Analgesic use and abuse is frequent. The patients lifestyle is gradually destroyed by pain, analgesic dependence, weight loss and inability to work
Investgations :
Tests of pancreatic function confirms the presence of pancreatic insufficiency or that more than 70% of the gland has been destroyed.
Abdominal X-ray shows calcification.
CT or MRI scan will show the outline of the gland, the main area of damage and the possibilities for surgical correction (a normal-looking pancreas on CT or MRI does not rule out chronic pancreatitis). (Calcification is seen very well on CT but not on MRI)
MRCP will show the state of pancreatic duct. ERCP is the most accurate way of elucidating the anatomy of the duct EUS is very useful. Sonographic findings characteristic of chronic pancreatitis include the presence of stones, visible side branches, cysts, lobularity, an irregular main pancreatic duct, hyperechoic foci and strands, dilation of the main pancreatic duct and hyperechoic margins of the main pancreatic duct. The presence of four or more of these features is highly suggestive of chronic pancreatitis.
Treatment :
Most patients can be managed with medical measures.1- Treat the addiction
Help the patient to stop alcohol consumption and tobacco smoking
Involve a dependency counsellor or a psychologist
2- Alleviate abdominal pain
a- Eliminate obstructive factors (duodenum, bile duct, pancreatic duct)
b- Escalate analgesia in a stepwise fashion
c- Refer to a pain management specialist
For intractable pain, consider CT/EUS-guided coeliac axis block
3- Nutritional and digestive measures
Diet: low in fat and high in protein and carbohydrates
Pancreatic enzyme supplementation with meals
Correct malabsorption of the fat-soluble vitamins (A, D, E, K) and vitamin B12
Medium-chain triglycerides in patients with severe fat malabsorption (they are directly absorbed by the small intestine without the need for digestion)
Reducing gastric secretions may help
Treat diabetes mellitus
Endoscopic, radiological, or surgical intervention are indicated mainly to relieve obstruction of the pancreatic duct (relieve pain), bile duct, or duodenum, or in dealing with complications (pseudocyst, abscess, fistula, ascites, variceal haemorrhage). Endoscopic pancreatic sphincterotomy may be beneficial in papillary stenosis & high pancreatic duct pressure. Patient with pancreatic duct stricture may benefit from placement of a stent across the stricture. Pancreatic duct stones may be extracted at ERCP & sometimes may be combined with extracorporeal shock wave lithotripsy. Pseudocyst may be drained internally under EUS guidance. Percutaneous or transgastric drainage of pseudocysts under US or CT guidance may be performed.
Surgery is done for removal of a mass lesion in head by doing pancreatoduodenectomy or duodenum preserving resection of pancreatic head (Beger procedure). Also surgery is done to overcome obstruction, if the duct is markedly dilated then a longitudinal pancreatojejunostomy can be useful. Rarely the disease is limited to the tail then distal pancreatectomy could be done. Total pancreatectomy & islet autotransplantation has been reported in selected patients.
Prognosis :
Chronic pancreatitis is a difficult condition to manage. Patients often suffer a gradual decline in their professional, social and personal lives. The pain may abate after a surgical or percutaneous intervention, but tends to return over a period of time. Development of pancreatic cancer is a risk in those who have had the disease for more than 20 years.
CARCINOMA OF THE PANCREAS
More than 85% of pancreatic cancer are ductal adenocarcinomas. It arises most commonly in the head of pancreas. It is solid, scirrhous tumour, infiltrates locally along nerve sheaths, lymphatics, & into blood vessels. It metastasizes to liver & peritoneal cavity. Cystic tumours of the pancreas may be serous or mucinous. Adenocarcinoma of ampulla of Vater often presents early with biliary obstruction (more favourable than pancreatic ductal adenocarcinoma). Other malignant neoplasms can arise at the ampulla such as carcinoid tumours & high grade neuroendocrine carcinomas.
Clinical features :
Usually patients present with painless jaundice (secondary to obstruction of the distal bile duct) which may be associated with nausea & epigastric discomfort. Pruritus,dark urine, & pale stools with steatorrhoea accompany jaundice. In the absence of jaundice, symptoms are often non-specific, namely vague discomfort, anorexia & weight loss. Upper abdominal discomfort in a recently diagnosed diabetic, especially in one above 50 years of age, with no family history or obesity, should raise suspicion. Patients may be presented with unexplained attack of pancreatitis. Tumour of the body & tail of the pancreas may be silent (asymptomatic). Later patients may be presented at an advanced unresectable stage. Backache may raise the possibility of retroperitoneal infiltration.
Clinical exam: There may be evidence of jaundice, weight loss, palpable liver, & palpable gall bladder (Courvoisier law). Signs of intra-abdominal malignancy such as palpable mass, ascites, supraclavicular lymph nodes & tumour deposits in the pelvis (indicate grim prognosis).
Investigations :
In a jaundiced patient, the usual blood tests & abdominal US should be performed. If there is a genuine suspicion of a tumour in the head of pancreas, the preferred test is a contrast- enhanced CT scan. MRI and MR angiography can provide information. ERCP & biliary stenting should be carried out if there is any suggestion of cholangitis. It relieves the jaundice and can also provide a brush cytology or biopsy specimen to confirm the diagnosis
EUS is useful if CT fails to demonstrate the tumour. Transduodenal or transgastric FNA or Trucut biopsy performed under EUS guidance. Diagnostic laparoscopy with laparoscopic ultrasonography. The tumour marker CA19-9 (is not highly specific or sensitive) is useful in identifying recurrence.
Management :
More than 85% of patients presented at too advanced stage (unsuitable for resection), so palliative treatment should be offered. If imaging shows that the tumour is potentially resectable, the patient should be considered for surgical resection. Tumours of ampulla should, if at all possible be resected. Surgical resection : The standard resection for a tumour of pancreatic head or the ampulla is a pylorus-preserving pancreatoduodenectomy. Total pancreatoduodenectomy is done when dealing with multifocal tumour, or body & tail are too inflammed or too friable to achieve save anastomosis with the bowel. Distal pancreatectomy with splenectomy is the standard for the tumours of the body & tail. Palliation: If unresectable disease is found at laparotomy, the surgeon should do choledochoenterostomy & a gastroenterostomy (to relieve jaundice & duodenal obstruction) (cholecystojejunostomy is easier to perform but the bile should drain through the cystic duct which is narrow). A coeliac plexus block can be administered. If unresectable disease is found on imaging, jaundice is relieved by stenting at ERCP. If the patient is unsuitable candidate for ERCP, a percutaneous transhepatic stent can be placed. Surgical bypass (gastrojejunostomy) or duodenal stent should be done for those with duodenal obstruction. Pain relief by analgesics, ceoliac plexus block, or transthoracic splanchnicectomy. Symptoms relief & quality of life by encouraging normal activities, enzymes replacement for steatorrhoea, & treatment of diabetes.
If no operative procedure is undertaken, EUS-guided or percutaneous biopsy of the tumour should be performed before consideration of chemotherapy or chemoradiation.