embryology of pancreas - surg.szote.u-szeged.hu · • general fluid resuscitation: plasma,...
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Surgery of the pancreas
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EMBRYOLOGY OF PANCREAS
EMBRYOGENESIS:
Pancreas is formed by fusion of dorsal and ventral segments (7th week)
Origin: endodermal hepatic and ventral mesenteric bud (4th week)
Ductal system: duct of dorsal pancreas – SANTORINI
duct of ventral pancreas – WIRSUNG
Anomalies: agenesis, ectopia, annular pancreas, pancreas divisum
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Agenesis: rare, and being associated with multiple anomalies
Ectopic pancreas: 5% of autopsies
Site: stomach, duodenum, small intestine
Symptoms: peptic ulcer (gastrin release), pyloric obstruction (inflammation), haemorrhage
Treatment: local excision
Annular pancreas: Origin: fixation of free end of ventral pancreas --encirclement of duodenum – obstruction
Symptoms: colicky abdominal pain, duodenal ulcer, vomit
Treatment: bypass procedure: gastroenterostomy
Pancreas divisum: Failure of fusion of ductal system
Symptoms: epigastric pain, recurrent pancreatitis
Treatment: pancreatic head resection, sphincteroplasty of minor papilla
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ANATOMY
Retroperitoneal organ, 15-20 cm length, 80-90 G weight.
Four parts of pancreas:
head (uncinate process), neck, body, tail
Blood supply:
Pancreato-duodenal arteries, Splenic artery
Mesenteric superior -, Splenic vein, Portal vein
Lymphatic drainage is diffuse, complex (celiac and mesenteric nodes)
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PHYSIOLOGY
Pancreas consist of exocrine and endocrine functions.
Endocrine functions: islets of Langerhans (1-2 M): insulin , glucagon, somatostatine
Exocrine functions: acinar cells: enzymes for digestion: amylase, lipase, trypsin etc.
Pancreatic juice: 1-2 l/day, Ph 7.6-8.3, clear, contains water, electrolytes and protein
Laboratory examinations: amylase, lipase, stool elastase, blood glucose, hormones determinations; stimulate pancreatic secretion (effect of secretin, cholelcystokinin)
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DIAGNOSTIC EXAMINATIONS
Abdominal X-ray (calcifications, „sentinel loop”)
Sonography, endosonography
CT, MRI, MRCP
Endoscopic retrograde cholangio-pancreatography (ERCP)
Angiography (selective)
PTC, PTD
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ACUTE PANCTREATITIS
Definition: Acute pancreatitis is a clinical syndrome of
epigastric pain, associated with fever, tachycardia,
ileus, haemorrhage and shock.
Pancreatitis is a nonbacterial inflammation on the
pancreas.
Base of pathologic manifestations: obstruction and/or
stimulated secretion results in extravasations of
activated pancreatic enzymes and in production of
vasoactive polypeptides. The presence of these
agents accounts for local and systemic
manifestations of the disease.
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Pathology of acute pancreatitis
Marseille definition 1984:
mild form: interstitial oedema, focal necrosis
severe form: extensive necrosis, haemorrhage,
suppuration
Atlanta definition 1992:
1. mild and severe acute pancreatitis
2. sterile and infected necrotizing pancreatitis
3. post acute pseudocyst
4. pancreatic abscess
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ETIOLOGIES OF ACUTE PANCREATITIS
1. Biliary tract disease (gallstone, common-channel)
2. Alcohol ingestion (1.-2.: cc. 90%)
3. Hyperlipidemy
4. Trauma (external, operative, ERCP, EST)
5. Hypocalcemy
6. Vascular (hypotension, embolism, vasculitis)
7. Pancreatic duct obstruction (tumour, pancreas divisum)
8. Drugs
9. Viral infection
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CLINICAL PRESENTATION AND
DIAGNOSIS
No characteristic clinical picture, the symptoms depend on the
severity of the attack.
Symptoms: midepigastric pain, back pain, vomiting,
tachycardia, dyspnoe, fever, jaundice, hypotension, shock
Physical examination: abdominal distension, epigastric
tenderness, discoloration in the flank (Gray-Turner’s sign)
or around the umbilicus (Cullen’s sign)
The base of DIAGNOSIS: anamnesis, clinical presentation,
laboratory determinations, radiographic findings
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DIAGNOSIS OF ACUTE PANCREATITIS
Laboratory test:
• Serum, urine amylase
• Serum lipase
• Serum elastase
• WBS
• Serum Ca
• Blood gases
• C-reactive protein (CRP)
• Procalcitonin (PCT)
• Il-6
Radiographic procedures:
• Plain chest X-ray
• Plain abdominal X-ray („sentinel loop”)
• ultrasonography
• Fine needle aspiration (FNA)
• CT
• MRI
• ERCP
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DISORDERS ASSOCIATED WITH
HYPERAMYLASAEMIA
Intra-abdominal:
• Biliary tract disease
• Perforated peptic ulcer
• Intestinal obstruction
• Peritonitis
• Acute appendicitis
• Mesenteric infarction
• Ruptured aortic aneurysm
Extra-abdominal:
• Salivary gland disorders
• Renal failure
• Cerebral trauma
• Severe burns
• Myocardial infarction
• Drugs
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PROGNOSIS
Nearly 90% of the patients with mild, self-limited illness,
mortality rate is 0-3%. 10 to 15% of the patients develop a
severe from with complications, mortality rate is 35-40%.
Prediction of severity:
• Ranson’s score
• APACHE II score
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Ranson's prognostic signs help predict the
prognosis of acute pancreatitis.
Five of Ranson's signs can be documented at admission:
• Age > 55 yr
• Plasma glucose > 200 mg/% (> 11.1 mmol/L)
• Serum LDH > 350 IU/L
• Serum GOT > 250 UL
• WBC count > 16,000/μL
The rest of Ranson's signs are determined within 48 h of admission:
• Hcrt decrease > 10%
• BUN increase > 5 mg/% (> 1.78 mmol/L)
• Serum Ca < 8 mg/% (< 2 mmol/L)
• PaO2 < 60 mm Hg (< 7.98 kPa)
• Base deficit > 4 mEq/L (> 4 mmol/L)
• Estimated fluid sequestration > 6 L
Mortality increases with the number of positive signs: if < 3 signs are positive, the mortality rate is < 5%; if ≥ 3 are positive, mortality is 15 to 20%.
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COMPLICATIONS OF ACUTE
PANCREATITIS
Systemic (early)
• Shock
• ARDS
• Renal insufficiency
• Gastrointestinal bleeding
• DIC
• Multiple organ failure (MOF)
Localised (late)
• Infected pancreatic necrosis (IPN)
• Abscesses
• Pseudocyst
• Disruption of pancreatic duct (pancreatic ascites)
• Disruption of arterial pseudoanaurism
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TREATMENT
Acute pancreatitis is not a surgical disease, therefore the
immediate treatment is nonoperative (!)
if gallstone are present: ERCP, EST, stone extraction is
indicated, in afraid state laparoscopic cholecystectomy must
be performed.
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BASIC THERAPY
1. Relief of pain: iv. procaine, epidural anaesthesia
2. Supportive care: (deficits of circulating blood volume, „internal burn”)
• general fluid resuscitation: plasma, electrolyte solution, dextran
• cardio-respiratory support
• administration of calcium
• nutritional support: TPN, jejunal feeding
• fasting, nasogastric suction, antacid, proton pump antagonist
3. Inhibition of excess cytokine production (pentoxifylline)
4. Antibiotics: prophylaxis in severe form (imipenem)
5. Indication of surgery: uncertainty of clinical diagnosis;progressive clinical status despite adequate therapy
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COMPLICATIONS OF NECROTIZING
PANCREATITIS
1. Infected pancreatic necrosis: a serious and life threatening
complication following secondary infection of necrotic
pancreatic, peripancreatic and retroparitoneal tissue.
Source of infection: large bowel, infected bile
Bacteria: enteric bacteria, Candida
Diagnosis: clinical and laboratory manifestation of sepsis,
palpable abdominal mass, sonography (?) CT scan, PCT,
FNA, bacteriological examinations
Treatment: Surgery: débridement, necrosectomy, widespread
continuous washing drainage
supportive therapy
adequate antibiotic
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“THERE IS NO GOOD
MEDICINE
AGAINST BAD SURGERY “
J. Goris
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COMPLICATIONS OF ACUTE
PANCREATITIS
Systemic (early)
• Shock
• ARDS
• Renal insufficiency
• Gastrointestinal bleeding
• DIC
• Multiple organ failure (MOF)
Localised (late)
• Infected pancreatic necrosis (IPN)
• Abscesses
• Pseudocyst
• Disruption of pancreatic duct (pancreatic ascites)
• Disruption of arterial pseudoanaurism
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2. Abscess: localized infection of necrotic pancreas or
retroperitoneal area; or infected pseudocyst
Diagnosis: septic condition, palpable mass
sonography, CT scan
Treatment: adequate drainage (internal, external)
antibiotics
3. Pancreatic ascites: disruption of pancreatic duct or
perforation of pseudocyst
Diagnosis: laboratory examination: high amylase level in the
ascites fluid, increased protein content
ERCP
Treatment: internal drainage (Wirsungo-jejunostomy)
pancreatic resection
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4. Rupture of arterial pseudoaneurism: a serious complication
following pancreatic pseudocyst formation
Localization: gastroduodenal, pancreaticoduodenal or splenic
arteries
Symptoms: anaemia, shock, severe pain, haemosaccus
Diagnosis: sonography (Doppler), CT scan, angiography
Treatment: angiographic occlusion, in afroid state internal
drainage or resection
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5. Pseudocyst: encapsulated collection of necrotic tissue, old
blood, and secretion from the pancreas (no true capsule!)
Diagnosis: clinical findings, sonography, CT scan
Complications: (depending on the size and location) jaundice,
gastrodoudenal obstruction, rupture, infection,
haemorrhage
Treatment: internal drainage (open abdomen, or laparoscopic
surgery, endoscopic stent implantation)
resection operations
percutaneous aspiration and drainage (?)
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CHRONIC PANCREATITIS
Definition: a progressive, obstructive process, with cellular
infiltration, fibrosis, necrosis and calcification with loss of
functioning exocrine and endocrine tissue
Etiology: alcoholism (70%!)
gallstones
hyperlipidemy
idiopathic
Types: 1. obstructive
2. calcificated
3. fibrosis
4. mixed
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Clinical findings: chronic abdominal pain, weight loss, steatorrhea (exocrine insufficiency), diabetes mellitus (endocrine insufficiency), duodenal obstruction, jaundice
Diagnosis: evocative testing (ATT, Lund’s test, stool elastase)
glucose tolerance test
sonography, CT scan
ERCP, MRCP
Treatment: avoidance and treatment of etiologic factors (especially alcohol), stent implantation (?)
Surgery: drainage operation: sphincteroplasty, Wirsungo-jejeunostomy, Wirsungo-gastrostomy
resection operation: PPPD, DPPHR, DOPPHR, distal resection, subtotal pancreatectomy (?) and implantation of pancreatic islets
Postoperative supportive therapy: diet, pancreatin, no alkohol (!)
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Epidemiology
● Incidence rate: 12-15/100.000/year
● Incidence has tripled in the past 80 years
● Fourth leading cause of cancer death
● Accounts for 6% cancer death
● Increase with age
● Male>female, black>white
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Precursors of ductal adenocarcinoma
PanIN: pancreatic intraepithelial neoplasia
• PanIN 1A - flat hyperplasia
• PanIN 1B - ductal papillary hyperplasia
• PanIN 2 - ductal papillary hyperplasia with
atypia
• PanIN 3 - severe dysplasia or in situ carcinoma
IPMT: intraductal papillary mucinous
tumorsBiankin AV et al: Pathology 5: 14-24, 2003
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Pancreatic cancer – risk factors
Epidemiologic Associations:
● Diabetes mellitus: 1,5x, 9-year
● Chronic pancreatitis: 15x, 20-year
● Cystic fibrosis
● Hereditary pancreatitis: 50x
● Peutz-Jeghers sy.: 100x
● Familial Atypical Mole-Malignant Melanoma: 15x
● Hereditary breast and ovarian cancer sy.
● HNPCC
● Familial clusters: variable risk
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Pathology
94% - adenocarcinoma
95% - ductal cell (ERCP!)
70% - pancreatic head (icterus)
20% - pancreatic body
10% - pancreatic tail
5% - acinar cell
5% - islet cell carcinoma
1% - others (cystadenocc., sarcoma, carcinoid,
lymphoma etc.)
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Symptoms
● Non specific, insidious (lack of appetite, weakness)
● In advanced stage (90% inoperable)
● Abdominal pain
● Belt-like
● Eating, supine position worsens
● Jaundice, pruritus, Courvoisier sign
● Weight loss
● Migratory thrombophlebitis
● Nausea, vomiting, early satiety
● Diarrhoea, anorexia, splenomegaly
● IGT, diabetes mellitus
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Diagnosis – imaging procedures
1. Detection
2. Staging
3. Confirmation
Non-invasive:
● US
● CT, (MDCT)
● MRI, MRCP
Invasive:
● ERCP, IUS
● EUS
● Laparoscopy
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Abdominal CT
„gold standard” in detection and
staging
Contrast-enhanced, helical CT
MDCT 3D reconstruction
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ERCP: diagnosis + palliation
● 95 % ductal origin
● Indication:
● obstr. icterus
● neg. CT
● diff. dg. (CP – PC)
● Diagnosis
● brush cytology
● biopsy
● Endotherapy
● plastic stent
● self expandable wallstent
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TREATMENT OF CANCER OF
THE PANCREAS
• Explorative laparotomy (laparoscopy!)
• Duodeno-pancreatectomia (Whipple) +
lymph node dissection
• Pylorus preserving pancreatic head resection
+ lymph node dissection
• Distal pancreatic resection + splenectomy
• Total pancreatectomy (?)
• Palliation: choledocho-duodenostomy, -
jejunostomy; GEA
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Prognosis
● 5-year survival: 3-5%. Silent killer.
● complete surgical resection – possible in only
15-25% of patients – offers the only potential
for cure
● The prognosis depends on the early diagnosis!
● After curative resection - 5-year survival:
pancreatic head: 10-20%. cc <2 cm: 20%, cc
>2cm: 10%; ampulla Vateri: 40-45%
● Not suitable for surgery – survival: 4-6 months
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Pancreatic cancer
Can an earlier diagnosis be made?
Back pain + weight loss → gastroenterologist
Newly diagnosed diabetes (old, non obese) →
abdominal US/CT
Jaundice in pts. over 40 → biliary obstruction
Acute pancreatitis with unknown etiology →
CT/MRCP or ERCP