1. TOPIC : PANCREAS
(Submitted by Dr. Md Moinul Hoque Chowdhary)
SU24.1 - Describe the clinical features, principles
of investigation, prognosis and management of
pancreatitis
SU24.2 - Describe the clinical features, principles
of investigation, prognosis and management of
pancreatic endocrine tumours
SU24.3 - Describe the principles of investigation
and management of Pancreatic disorders
including pancreatitis and endocrine tumors.
2. ANATOMY
• The name ‘pancreas’ is derived from the Greek
words ‘pan’ (all) and ‘kreas’ (flesh).
• The pancreas is situated in the retroperitoneum.
• The pancreas weighs approximately 80 g and
20cm in length.
• It is divided into a head, neck, body, tail and
uncinate process.
• The head lies within the curve of the duodenum,
overlying the body of the second lumbar vertebra
and the vena cava and extends to the splenic
hilum.
3. • Pancreatic duct system:
1. Main pancreatic duct – Duct of Wirsung
2. Accessory pancreatic duct – Duct of Santorini
• Two components:
1. Exocrine :
- 80–90% is composed of exocrine acinar tissue, which is
organised into lobules.
- Secrete pancreatic juice containing digestive enzymes like
trypsin, chymotrypsin, amylase, lipase, elastase, etc.
2. Endocrine:
- Clusters of endocrine cells, known as islets of Langerhans,
are distributed throughout the pancreas.
-Produce several important hormones like insulin,gulcagon
and somatostatin.
4.
5. PANCREATITIS
• Pancreatitis is inflammation of the pancreatic
parenchyma.
• For clinical purposes, it is divided into –
1. Acute Pancreatitis
2. Chronic Pancreatitis.
6. ACUTE PANCREATITIS
• Acute pancreatitis is defined as an acute condition
presenting with abdominal pain with a threefold or
greater rise in the serum levels of the pancreatic
enzymes amylase or lipase, and/ or characteristic
findings of pancreatic inflammation on contrast-
enhanced CT scan.
• Annual incidence ranges from 5 to 50 per 100 000.
• The disease may occur at any age, with a peak in young
men and older women.
• The underlying mechanism of injury in pancreatitis is
thought to be premature activation of pancreatic
enzymes within the pancreas, leading to a process of
autodigestion.
7. Aetiology : Possible causes of acute pancreatitis
• Gallstones - most common about 50-70%
• Alcoholism
• Post ERCP
• Abdominal trauma
• Following biliary, upper gastrointestinal or cardiothoracic surgery
• Ampullary tumour
• Drugs (corticosteroids, azathioprine, asparaginase, valproic acid, thiazides,
oestrogens)
• Hyperparathyroidism
• Hypercalcaemia
• Pancreas divisum
• Autoimmune pancreatitis
• Hereditary pancreatitis
• Viral infections (mumps, coxsackie B)
• Malnutrition
• Scorpion bite
• Idiopathic
8. Clinical presentation
Symptoms :
1. Pain abdomen is the cardinal symptom.
- severe, constant and refractory to the usual doses of
analgesics.
- usually experienced first in the epigastrium but may be
localised to either upper quadrant or felt diffusely
throughout the abdomen.
- some patients may gain relief by sitting or leaning
forwards.
2. Nausea
3. Repeated vomiting
4. Retching
9. Signs :
1. Appearance may be well or ill with shock,
toxicity and confusion.
2. Tachypnoea
3. Tachycardia
4. SIRS is defined by the presence of two or
more of the following criteria: heart rate
>90/min, core temperature 38 C,
respirations >20/min or pCO2 < 32 mmHg,
and WBC count <4000 or >12000/mm3.
10. 5. Mild icterus can be caused by biliary
obstruction in gallstone pancreatitis.
6. Bleeding into the fascial planes can produce
bluish discolouration of the flanks (Grey
Turner’s sign) or umbilicus (Cullen’s sign).
7. Abdominal examination may reveal distension
due to ileus or more rarely, ascites with
shifting dullness.
8. There is usually muscle guarding in the upper
abdomen, although marked rigidity is unusual.
11. Investigations
Typically, the diagnosis is made on the basis of the clinical
presentation and an elevated serum amylase level - three times
above normal is indicative but not confirmatory.
Causes of raised serum amylase level other than acute pancreatitis :
• Upper gastrointestinal tract perforation
• Mesenteric infarction
• Torsion of an intra-abdominal viscus
• Retroperitoneal haematoma
• Ectopic pregnancy
• Macroamylasaemia
• Renal failure
• Salivary gland inflammation
12. IMAGING
• Ultrasound does not establish a diagnosis but
shows swollen pancreas. USG should be
performed within 24 hours in all patients to
detect gallstones as a potential cause & rule
out acute cholecystitis.
• Contrast-enhanced CT scan is diagnostic.
• Others – EUS, MRCP
13. ASSESSMENT OF SEVERITY
• Atlanta classification of acute pancreatitis (2013) recommends that
patients with acute pancreatitis be stratified into 3 groups :
1. Mild acute pancreatitis:
● no organ failure;
● no local or systemic complications.
2. Moderately severe acute pancreatitis:
● organ failure that resolves within 48 hours (transient organ
failure); and/or
● local or systemic complications without persistent organ failure.
3. Severe acute pancreatitis:
● persistent organ failure (>48 hours);
● single organ failure;
● multiple organ failure
14. • Severity stratification assessments should be
performed in patients at 24 hours, 48 hours and 7 days
after admission.
• The Ranson and Glasgow scoring systems are specific
for acute pancreatitis, and a score of 3 or more at 48
hours indicates a severe attack.
• Several other systems that are used in intensive care
units can also be applied like APACHE, SAPS, SOFA,
MODS and modified Marshall scoring systems.
• Regardless of the system used, persisting organ failure
indicates a severe attack. A serum C-reactive protein
level >150 mg/L at 48 hours after the onset of
symptoms is also an indicator of severity.
15.
16. Management
If after initial assessment a patient is considered
to have a mild attack of pancreatitis, a
conservative approach is indicated :
• Nil by mouth for a brief period
• Intravenous fluid administration
• Analgesics
• Anti-emetics
• Antibiotics are not indicated
• Frequent but non-invasive observation.
17. Management of severe acute pancreatitis :
• Admission to HDU/ICU
• Analgesia
• Aggressive fluid rehydration
• Supplemental oxygen
• Invasive monitoring of vital signs, central venous pressure, urine output, blood
gases
• Frequent monitoring of haematological and biochemical parameters (including
liver and renal function, clotting, serum calcium, blood glucose)
• Nasogastric drainage (only initially)
• Antibiotics if cholangitis suspected; prophylactic antibiotics can be considered
• CT scan essential if organ failure, clinical deterioration or signs of sepsis develop
• ERCP within 72 hours for severe gallstone pancreatitis or signs of cholangitis
• Supportive therapy for organ failure if it develops (inotropes, ventilatory support,
haemofiltration, etc.)
• If nutritional support is required, consider enteral (nasogastric) feeding.
• If the aetiology is gallstones, cholecystectomy is desirable during the same
admission once the patient is fit for surgery.
18.
19. Outcome and Prognosis of acute pancreatitis
• The overall mortality from acute pancreatitis has remained at 10–
15% over the past 20 years.
• There is a clear responsibility before the patient is discharged to
determine the aetiology of the attack of pancreatitis.
• Failure to remove a predisposing factor could lead to a second
attack of pancreatitis, which could be fatal.
• A proportion of patients in the idiopathic group who suffer
repeated attacks may prove to have biliary microlithiasis, which can
be identified only by bile sampling at ERCP or by endoscopic
ultrasound.
• In a patient who has gallstone pancreatitis, the gallbladder and
gallstones should be removed as soon as the patient is fit to
undergo surgery and, preferably, before discharge from hospital.
20. CHRONIC PANCREATITIS
• Chronic pancreatitis is a progressive
inflammatory disease in which there is
irreversible destruction of pancreatic tissue.
• Its clinical course is characterised by severe pain
and, in the later stages, exocrine and endocrine
pancreatic insufficiency.
• The incidence of chronic pancreatitis is 2 to 10
per 100000 population per year.
• Male:female ratio of 4:1.
• Mean age of onset is about 40 years.
21. Aetiology
• High alcohol consumption is the most frequent cause
of chronic pancreatitis.
• Congenital abnormalities such as pancreas divisum and
annular pancreas, if associated with papillary stenosis
are the rare causes.
• Other causes include pancreatic duct obstruction
resulting from stricture formation after trauma, after
acute pancreatitis, or even occlusion of the duct by
pancreatic cancer.
• Hereditary pancreatitis, Cystic Fibrosis, Infantile
malnutrition and a large unexplained idiopathic group.
22. Pathology
• At the onset of the disease when symptoms have developed, the
pancreas may appear normal.
• Later, the pancreas enlarges and becomes hard as a result of
fibrosis.
• The ducts become distorted and dilated with areas of both stricture
formation and ectasia.
• Calcified stones weighing from a few milligrams to 200 mg may
form within the ducts.
• The ducts may become occluded with a gelatinous proteinaceous
fluid and debris, and inflammatory cysts may form.
• Histologically, the lesions affect the lobules, producing ductular
metaplasia and atrophy of acini, hyperplasia of duct epithelium and
interlobular fibrosis.
23. Clinical features
• Pain is the outstanding symptom in the majority of the patients.
• The pain is often dull and gnawing and the site of pain depends to some
extent on the main focus of the disease.
• If the disease is mainly in the head of the pancreas, then epigastric and
right subcostal pain is common, whereas if it is limited to the left side of
the pancreas, left subcostal and back pain are the presenting symptoms.
• Nausea is common during attacks, and vomiting may occur.
• Weight loss is common, because the patient does not feel like eating.
• Analgesic use and abuse is frequent.
• The patient’s lifestyle is gradually destroyed by pain, analgesic
dependence, weight loss and inability to work.
• Loss of exocrine function leads to steatorrhoea in more than 30% of
patients with chronic pancreatitis.
• Loss of endocrine function and the development of diabetes are not
uncommon, and the incidence increases as the disease progresses.
24. Investigations
• Only in the early stages of the disease there will be a
rise in serum amylase.
• CT or MRI scan will show the outline of the gland, the
main area of damage and the possibilities for surgical
correction.
• An MRCP will identify the presence of biliary
obstruction and the state of the pancreatic duct.
• ERCP is the most accurate way of elucidating the
anatomy of the duct and, in conjunction with the
whole organ morphology Shows “chain of lakes
appearance”.
• EUS can also be very useful.
25. Treatment
• Most patients can be managed with medical measures as follows :
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
● Eliminate obstructive factors (duodenum, bile duct, pancreatic duct)
● Escalate analgesia in a stepwise fashion
● Refer to a pain management specialist
● For intractable pain, consider CT/EUS-guided coeliac axis block.
4. Nutritional and pharmacological measures
● Diet: low in fat and high in protein and carbohydrates
● Pancreatic enzyme supplementation with meals
● Correct malabsorption of the fat-soluble vitamins and vitamin B12
● Micronutrient therapy with methionine, vitamins C & E, selenium (may reduce pain and
slow disease progression)
● Steroids (only in autoimmune pancreatitis, for relief of symptoms)
● 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
4. Treat diabetes mellitus.
26. Endoscopic, radiological or surgical
interventions
• Endoscopic pancreatic sphincterotomy: Beneficial in
patients with papillary stenosis and a high sphincter
pressure and pancreatic ductal pressure.
• Endoscopic placement of a stent across the stricture:
The stent should be left in for not more than 4–6
weeks as it will block.
• ERCP : Pancreatic duct stones may be extracted at
ERCP.
• Under EUS guidance pseudocysts may be drained
internally.
• Percutaneous or transgastric drainage of pseudocysts
under ultrasound or CT guidance may be performed.
27. Role of surgery in chronic pancreatitis:
To overcome obstruction and remove mass lesions.
• For mass in the head of the pancreas :
Pancreatoduodenectomy (Whipple procedure), or
Beger procedure (duodenum-preserving resection of
the pancreatic head).
• For duct is markedly dilated:
Longitudinal pancreatojejunostomy (Puestow
procedure), or
Frey procedure.
• Disease limited to the tail Distal pancreatectomy.
• For intractable pain and diffuse disease Total
pancreatectomy and islet auto-transplantation.
28. Prognosis of chronic pancreatitis
• 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.
• In a proportion of patients, the inflammation may gradually
burn out over a period of years, with disappearance of the
pain, leaving only the exocrine and endocrine
insufficiencies.
• Development of pancreatic cancer is a risk in those who
have had the disease for more than 20 years.
• New symptoms or a change in the pattern of symptoms
should be investigated and malignancy excluded.
29. MCQs
1. Which of the following is the most common cause of acute pancreatitis?
a. Alcoholism
b. Gallstones
c. Smoking
d. Viral infection
2. Basic treatment of acute pancreatitis includes early fluid resuscitation, analgesia, and which of the following?
a. Antibiotics
b. Endoscopic retrograde cholangiopancreatography (ERCP)
c. Enteral nutrition
d. Total parenteral nutrition
3. Most common cause of death in early acute pancreatits is
a. Renal failure
b. Cardiac failure
c. Respiratory failure
d. Uncontrolled coagulopathy.
4. Best study for detecting complications of acute and chronic pancreatitis
a. CT scan
b. MRI
d. Doppler ultrasound
e. Laprotomy
5. What is the basic change of chronic pancreatitis?
a) Fibrosing atrophy
b) Ductal atrophy
c) Ductal dilatation
d) Hyperplasia of islets
30. 6. All are indications of elective ERCP with sphincterotomy in acute pancreatitis except:
a. Biliary obstruction
b. Poor candidates for cholecystectomy in biliary pancreatitis
c. Bile duct stones after cholecystectomy
d. Walled off pancreatic necrosis.
7. The feature of chronic pancreatitis with regarding to pancreatic cancer are all except
a. Smooth pancreatic duct dilation with an abrupt interruption
b. Calcification
c. Duct penetrating sign
d. Dilation of bile and pancreatic duct
8. Gold standard investigation for chronic pancreatitis is :
a. MRI
b. ERCP
c. Pancreatic function tests
d. Fecal fat estimation
9. Which of the following is not a feature of acute pancreatitis?
a. Hyperbilirubinemia
b. Hypercalcemia
c. Hyperglycemia
d. Increased serum LDH level
10. Chronic pancreatitis complications include all except:
a. Renal artery stenosis
b. Pseudocyst
c. Splenic vein thrombosis
d. Fistulas
31. PANCREATIC ENDOCRINE TUMOURS
Introduction
• Pancreatic endocrine tumours (PETs) account for 5% of all clinically
detected pancreatic tumours.
• They consist of single or multiple, benign or malignant neoplasms and are
associated in 10–20% of cases with multiple endocrine neoplasia type 1
(MEN 1).
• The endocrine cells of the pancreas are grouped in the islets of
Langerhans, which constitute approximately 1–2% of the mass of the
pancreas.
• There are four main types of cell in the islets of Langerhans, which can be
classified according to their secretions:
1. Beta cells producing insulin (65–80% of the islet cells);
2. Alpha cells producing glucagon (15–20%);
3. Delta cells producing somatostatin (3–10%);
4. Pancreatic polypeptide (PP) cells containing polypeptide (1%).
33. Insulinoma
• Defination: This is an insulin-producing tumour of the pancreas
causing the clinical scenario know as Whipple’s triad, i.e.
1. Symptoms of hypoglycaemia after fasting or exercise,
2. Plasma glucose levels <2.8 mmol/L and
3. Relief of symptoms on intravenous administration of glucose.
• Incidence is 2–4 cases per million population per year.
• Etiology and pathogenesis of insulinomas are unknown.
• No risk factors have been associated with these tumours.
• Prognosis and predictive factors:
1. No markers are available that reliably predict the biological
behaviour of an insulinoma.
2. Approximately 10% are malignant.
3. Insulinomas of <2cm in diameter without significant vascular
invasion or metastases are considered benign.
34. Clinical features:
• Insulinomas are characterised by fasting hypoglycaemia and neuroglycopenic
symptoms.
• The episodic nature of the hypoglycaemic attacks is caused by intermittent insulin
secretion by the tumour.
• This leads to central nervous system symptoms such as diplopia, blurred vision,
confusion, abnormal behaviour and amnesia. Some patients develop loss of
consciousness and coma.
• The release of catecholamines produces symptoms such as sweating, weakness,
hunger, tremor, nausea, anxiety and palpitations.
Biochemical diagnosis :
• A fasting test that may last for up to 72 hours is regarded as the most sensitive
test.
• Usually, insulin, proinsulin, Cpeptide and blood glucose are measured in 1- to 2-
hour intervals to demonstrate inappropriately high secretion of insulin in relation
to blood glucose.
• About 80% of insulinomas are diagnosed by this test, most of them in the first 24
hours.
• Elevated C-peptide levels demonstrate the endogenous secretion of insulin and
exclude factitious hypoglycaemia caused by insulin injection.
35. Medical treatment of insulinoma
• Medical management is reserved only for patients who
are unable or unwilling to undergo surgical treatment
or for unresectable metastatic disease.
• Diazoxide suppresses insulin secretion by direct action
on the beta cells and offers reasonably good control of
hypoglycaemia in approximately 50%of patients.
• When surgical options to treat malignant insulinomas
cannot be applied, chemotherapeutic options include
doxorubicin and streptozotocin.
36. Surgical treatment of insulinoma
INDICATIONS FOR OPERATION:
• After a positive fasting test and exclusion of diffuse abdominal metastases
by ultrasound or CT scan, all patients should be advised to undergo
surgical excision of insulinoma.
PREOPERATIVE LOCALISATION STUDIES :
• Intraoperative exploration of the pancreas is the best method to use for
localisation of insulinoma yet the operating surgeon will need
preoperative localisation.
• Insulinomas are detected in about 65% of cases by endoscopic ultrasound
(EUS), 33% of cases by CT scan and abdominal ultrasound and 15% of
cases by magnetic resonance tomography.
• Intraoperative ultrasound (IOUS) of the pancreas is a vital tool after
mobilisation of the gland.
• For preoperative localisation of an insulinoma, EUS has the highest
sensitivity and should be used if laparoscopic resection is considered.
• If no lesion is identified and one can rely on the biochemical tests for
diagnosis, laparotomy should follow, using IOUS.
37. BENIGN INSULINOMA:
• Surgical cure rates in patients with the biochemical diagnosis of insulinoma range
from 90% to 100%.
• At open surgery an extended Kocher manoeuvre and mobilisation of the head and
then the distal pancreas is performed to explore the whole gland.
• IOUS should then be used to confirm the presence of a tumour, to find non-
palpable lesions and also to identify the relation of the tumour to the pancreatic
duct.
• Tumour enucleation is the technique of choice.
• For superficial tumours, laparoscopic enucleation is undertaken.
• Tumours located deep in the body or tail of the pancreas and those in close
proximity to the pancreatic duct require distal pancreatectomy.
• Postoperatively, blood sugar levels begin to rise in most patients within the first
few hours after removal of the tumour.
• To preserve pancreatic function and reduce the risk of iatrogenic diabetes mellitus,
patients in whom tumour localisation is not successful at operation should not
undergo blind resection.
MALIGNANT INSULINOMA:
• Aggressive attempts at resection are recommended as these tumours are much
less virulent than adenocarcinomas.
38. Gastrinoma (Zollinger–Ellison
syndrome)
• Definition: Zollinger–Ellison syndrome (ZES) is a condition that includes:
(1) fulminating ulcer diathesis in the stomach, duodenum or atypical sites
(2) recurrent ulceration despite ‘adequate’ therapy; and
(3) non-beta islet cell tumours of the pancreas (gastrinoma)
• Incidence is between 0.5 and 4 cases per million population per year.
• More common in males than in females.
• Mean age at the onset of symptoms is 38 years, and the range 7–83 years.
• Etiology and pathogenesis of sporadic gastrinomas are unknown’
• Prognosis and predictive factors:
(1) Progression of gastrinomas is relatively slow with a 5-year survival rate of 65%
and a 10-year survival rate of 51%.
(2) Patients with complete tumour resection have excellent 5- and 10-year survival
rates (90–100%).
(3) Patients with pancreatic tumours have a worse prognosis than those with
primary tumours in the duodenum.
(4) There is no established marker to predict the biological behaviour of
gastrinoma.
39. Clinical and biochemical features:
• Over 90% of patients with gastrinomas have peptic ulcer disease, often
multiple or in unusual sites.
• Diarrhoea is another common symptom, caused by the large volume of
gastric acid secretion.
• Abdominal pain from either peptic ulcer disease or gastro-oesophageal
reflux disease (GORD) remains the most common symptom, occurring in
more than 75% of patients.
Biochemical diagnosis:
• If the patient presents with a gastric pH below 2.5 and a serum gastrin
concentration above 1000pg/mL (normal <100pg/mL) then the diagnosis
of ZES is confirmed.
• Unfortunately, the majority of patients have serum gastrin concentrations
between 100 and 500 pg/mL and in these patients a secretin test should
be performed.
• The secretin test is considered positive if an increase in serum gastrin of
>200pg/ml over the pretreatment value is obtained; this also rules out
other causes of hypergastrinaemia (e.g. atrophic gastritis).
40. Medical treatment of gastrinoma
• In most patients with ZES, gastric hypersecretion
can be treated effectively with proton pump
inhibitors.
• Octreotide can also help to control acid
hypersecretion.
• Systemic chemotherapy is utilised in patients
with diffuse metastatic gastrinomas.
• Streptozotocin in combination with 5-fluorouracil
or doxorubicin is the first-line treatment.
41. Surgical treatment of gastrinoma
INDICATIONS FOR OPERATION:
• Surgical exploration should be performed in all patients without diffuse
metastases, to remove known malignant gastrinomas or benign ones.
PREOPERATIVE LOCALISATION STUDIES:
• Pancreatic gastrinomas are often larger than 1 cm in diameter, whereas
gastrinomas of the duodenum are usually smaller.
• Therefore, it is nearly impossible to identify duodenal gastrinomas by
preoperative imaging.
• Pancreatic gastrinomas are detected by endoscopic ultrasound in about
80–90% of cases, by CT in 39% of cases and by MRI in 46% of cases. In
approximately one-third of patients the results of conventional imaging
studies are negative.
• On the basis of recent studies, either endoscopic ultrasound or CT and
somatostatin receptor scintigraphy (SRS) scan should be performed
preoperatively for staging.
42. PANCREATIC GASTRINOMAS:
• Most pancreatic gastrinomas are solitary, located in the head of the
gland or uncinate process, and can be identified at operation.
• Enucleation with peripancreatic lymph node dissection is the
procedure of choice.
• Rarely, tumours are situated in the body or tail and should be
treated by enucleation or distal resection.
• Even if a tumour is found in the pancreas, duodenotomy is
recommended to detect additional tumours, if the patient has
MEN1.
DUODENAL GASTRINOMAS:
• The duodenum should be opened with a longitudinal incision and
the posterior and anterior walls palpated separately.
• Duodenal tumours smaller than 5mm can be enucleated with the
overlying mucosa; larger tumours are excised with full-thickness
excision of the duodenal wall.
43. Non-functional endocrine pancreatic
tumours (NF-PETs)
• Definition: PETs are clinically classified as non-functioning (NF-PETs)
when they do not cause a clinical syndrome.
• Incidence NF-PETs account for 30–50% of all PETs.
• Most often diagnosed in the fifth to sixth decades of life.
• Pathology: They usually stain positively for chromogranin A and
synaptophysin. The tumours are usually large (>5 cm) and unifocal
except in MEN 1 syndrome.
• Prognosis and predictive factors:
1. About 70% of all NF-PETs are malignant.
2. Overall 5- and 10-year survival rates of 65% and 49% respectively
have been described.
3. When comparing NF-PETs with functioning PETs, the NF-PETs
have a worse prognosis.
44. Clinical features:
• Patients usually present late because of the lack of a
clinical/ hormonal marker of tumour activity.
• Therefore, in contrast to functioning PETs, patients with NF-
PETs present with various non-specific symptoms, including
jaundice, abdominal pain, weight loss and pancreatitis.
• In some cases liver metastases are the first presentation.
Biochemical diagnosis:
• Increased levels of chromogranin A have been reported in
50–80% of NF-PETs
• Level of chromogranin A sometimes correlates with the
tumour burden.
• The combination of elevated chromogranin A and PP
measurements increases the sensitivity of diagnosis from
84% to 96% in NF-PETs.
45. Medical treatment of NF-PETs
• When surgical excision is not possible, chemotherapeutic options include streptozotocin, octreotide and
interferon.
Surgical treatment of NF-PETs
INDICATIONS FOR OPERATION:
• An aggressive surgical approach should be considered in malignant NF-PETs, even in the presence of
distant metastases.
PREOPERATIVE LOCALISATION STUDIES:
• Preoperative ultrasound or CT scan are the procedures of choice as these tumours are relatively large.
• Also, SRS should be performed to differentiate endocrine from non-endocrine pancreatic tumours.
OPERATIVE PROCEDURES:
• The major goal is a potentially curative resection.
• This may require partial pancreaticoduodenectomy as well as the synchronous or metachronous resection
of liver metastases.
• Using an aggressive approach, curative resections are possible in up to 62% of cases and overall 5-year
survival rates of around 65% can be achieved.
• Repeated resections for resectable recurrences or metastases are justified to improve survival.
46. MCQs
1. Most common endocrine tumor of the pancreas is:
a. Insulinoma
b. Gastrinoma
c. Somatostatinoma
d. VIPoma
2. All are true about gastrinoma except:
a. Mostly found in gastrinoma triangle
b. Increases acid production
c. Most common site is pancreas
d. Lymphadenectomy is not required as there is no improvement in survival
3. Best investigation for neuroendocrine tumors of the pancreas:
a. Portal venous sampling
b. CECT
c. EUS
d. SRS
4. Gallstones are associated with which Neuroendocrine tumor:
a. Insulinoma
b. VIPoma
c. Somatostatinoma
d. Glucagonoma
5. Treatment of Zollinger-Ellison syndrome:
a. Total gastrectomy with the removal of the tumor
b. Partial gastrectomy
c. Excision of tumor alone
d. H2 receptor antagonist
47. 6. Not a boundary of gastrinoma triangle:
a. Junction of 2nd and 3rd part of the duodenum
b. Junction of 3rd and 4th part of the duodenum
c. Junction of the head with a body of the pancreas
d. Junction of cystic duct with common bile duct
7. Which is not true regarding insulinoma ?
a. Hypoglycemic attacks
b. Weight loss
c. Usually solitary tumor
d. mostly benign tumor
8. Migratory skin necrosis in a diabetic patient is due to:
a. Somatostatinoma
b. Glucagonoma
c. Insulinoma
d. VIPoma
9. Which is not true about non-functioning NET of the pancreas?
a. most PPomas are benign
b. Slow growing tumors
c. Constitute 30% of all pancreatic NET
d. Prognosis is better than other exocrine tumors
10. Which of the following is not true for Zollinger -Ellison syndrome:
a. recurrent after operation
b. reduced BOA: MAO ratio
c. gastrin-producing tumor
d. Diarrhea may be presenting features
49. Cystic fibrosis
• Inherited as an autosomal recessive condition.
• Incidence of 1:2000 live births
• Cystic fibrosis (CF) develops when there is a mutation
in the CFTR (cystic fibrosis transmembrane
conductance regulator) gene on chromosome 7.
• This gene creates a cell membrane protein that helps
to control the movement of chloride across the cell
membrane.
• CF is a multisystem disorder of exocrine glands that
affects the lungs, intestines, pancreas and liver, and is
characterised by elevated sodium and chloride ion
concentrations in sweat.
50. • Secretions precipitate in the lumen of the pancreatic duct causing
blockage, which results in duct ectasia and fatty replacement of
exocrine acinar tissue.
• Pancreatic exocrine insufficiency leads to fat malabsorption.
Steatorrhoea is usually present from birth, resulting in stools that
are bulky, oily and offensive.
• Outside the newborn period, the earliest clinical signs of CF are
poor growth, poor appetite, rancid greasy stools, abdominal
distension, chronic respiratory disease and finger clubbing.
• Diagnosis can be made by genetic testing (which may be part of
prenatal or newborn screening) and by the sweat test. Levels of
sodium and chloride ions in the sweat above 90 mmol/L confirm
the diagnosis,
• Treatment is aimed at control of the secondary consequences of
the disease.
51. Pancreas divisum
• Pancreas divisum occurs when the embryological ventral and dorsal
parts of the pancreas fail to fuse.
• Incidence ranges from 5% in autopsy series to 10% in some ERCP
and MRCP series.
• Found incidentally in an asymptomatic person does not warrant any
intervention.
• But incidence of pancreas divisum ranges from 25–50% in patients
with recurrent acute pancreatitis, chronic pancreatitis and
pancreatic pain.
• Thus, patients with idiopathic recurrent pancreatitis, pancreas
divisum should be excluded.
• Endoscopic sphincterotomy and stenting of the minor papilla may
relieve the symptoms.
• Surgical intervention can take the form of sphincteroplasty,
pancreatojejunostomy or even resection of the pancreatic head.
52. Annular pancreas
• This occurs as a result of failure of complete rotation of the
ventral pancreatic bud during development, so that a ring
of pancreatic tissue surrounds the second or third part of
the duodenum.
• It is most often seen in association with congenital
duodenal stenosis or atresia and is therefore more
prevalent in children with Down syndrome.
• Duodenal obstruction typically causes vomiting in the
neonate.
• The usual treatment is bypass (duodenoduodenostomy).
• The disease may occur in later life as one of the causes of
pancreatitis, in which case resection of the head of the
pancreas is preferable to lesser procedures.
53. Ectopic pancreas
• Islands of ectopic pancreatic tissue can be found in the
submucosa of:
-- stomach
-- duodenum or small intestine
-- Meckel’s diverticulum
-- gall bladder
-- adjoining the pancrea in the splenic hilum
-- within the liver.
• Ectopic pancreas may also be found in the wall of an
alimentary tract duplication cyst.
54. PSEUDOCYST OF PANCREAS
• A pseudocyst is a collection of amylase-rich fluid enclosed in a well-
defined wall of fibrous or granulation tissue.
• Pseudocysts typically arise –
1. Following 4 weeks or more from the onset of acute pancreatitis.
2. Chronic pancreatitis or
3. After pancreatic trauma.
• A pseudocyst is usually identified on ultrasound or a CT scan
differentiate a pseudocyst from an APFC ( Acute peripancreatic fluid
collection, their wall not matured)
• Occasionally, a cystic neoplasm may be confused with a chronic
pseudocyst. EUS and aspiration of the cyst fluid is very useful in such a
situation.
• The fluid should be sent for measurement of carcinoembryonic antigen
(CEA) levels, amylase levels and cytology. Fluid from a pseudocyst typically
has a low CEA level, and levels above 400 ng/mL are suggestive of a
mucinous neoplasm.
55. • ERCP and MRCP may demonstrate communication of the cyst
with the pancreatic duct system, demonstrate ductal anomalies,
or diagnose chronic pancreatitis and thus help in planning
treatment.
• Pseudocysts will resolve spontaneously in most instances, but
complications can develop like infections, rupture, enlargement,
obstruction and erosion into vessel (hemorrhage).
• Pseudocysts that are thick-walled or large (over 6 cm in
diameter), have lasted for a long time (over 12 weeks), or have
arisen in the context of chronic pancreatitis are less likely to
resolve spontaneously, but these factors are not specific
indications for intervention.
• Therapeutic interventions are advised only if the pseudocyst
causes symptoms, if complications develop, or if a distinction
has to be made between a pseudocyst and a tumour.
56. • Three possible approaches to draining a pseudocyst:
1. Percutaneous
2. Endoscopic
3. Surgical.
• Percutaneous transgastric cystgastrostomy can be done
under imaging guidance, and a double-pigtail drain placed
with one end in the cyst cavity and the other end in the
gastric lumen.
• Endoscopic drainage usually involves puncture of the cyst
through the stomach or duodenal wall under EUS guidance,
and placement of a tube drain with one end in the cyst
cavity and the other end in the gastric lumen.
• Surgical drainage involves internally draining the cyst into
the gastric or jejunal lumen.
57. CARCINOMA OF THE PANCREAS
• Incidence is 10 cases per 100000 population per year.
• More than 85% of pancreatic cancers are ductal
adenocarcinomas.
• The remaining tumours constitute a variety of
pathologies with individual characteristics Cystic
neoplasms.
• Endocrine tumours of the pancreas are rare.
• Tumours arising from the ampulla or from the distal
common bile duct can present as a mass in the head of
the pancreas, and constitute around a third of all
tumours in that area.
58. Risk factors for the development of pancreatic cancer.
• Demographic factors :
- Age (peak incidence 65–75 years)
- Male gender
- Black ethnicity
• Environment/lifestyle :
- Cigarette smoking
• Genetic factors and medical conditions:
- Family history Two first-degree relatives with pancreas
cancer: relative risk increases 18- to 57-fold.
Germline BRCA2 mutations in some rare high-risk families.
- Hereditary pancreatitis (50- to 70-fold increased risk)
- Chronic pancreatitis (5- to 15-fold increased risk)
- Lynch syndrome (HNPCC)
- Ataxia telangiectasia
- Peutz–Jeghers syndrome
- Familial breast–ovarian cancer syndrome
- Familial atypical multiple mole melanoma
- Familial adenomatous polyposis – risk of ampullary/duodenal carcinoma
- Diabetes mellitus
59. Pathology
Ductal adenocarcinomas:
• Arise most commonly in the head of the gland.
• They are solid, scirrhous tumours, characterised by
neoplastic tubular glands within a markedly desmoplastic
fibrous stroma.
• Ductal adenocarcinomas infiltrate locally, typically along
nerve sheaths, along lymphatics and into blood vessels.
• Liver and peritoneal metastases are common.
• Proliferative lesions in the pancreatic ducts can precede
invasive ductal adenocarcinoma. These are termed
pancreatic intraepithelial neoplasia or PanIN, and can
demonstrate a range of structural complexity and cellular
atypia.
60. • Cystic tumours: can be serous or mucinous.
• Serous cystadenomas: are typically found in older
women, and are large aggregations of multiple small cysts,
almost like bubblewrap. They are benign.
• Mucinous tumours: have the potential for malignant
transformation. They include mucinous cystic neoplasms
(MCNs) and intraductal papillary mucinous neoplasms
(IPMNs).
• MCNs seen in perimenopausal women, show up as
multilocular thick-walled cysts in the pancreatic body or
tail, and, histologically, contain an ovarian-type stroma.
• IPMNs more common in the pancreatic head and in
older men, but an IPMN arising from a branch duct can be
difficult to distinguish from an MCN. IPMNs arising within
the main duct are often multifocal and have a greater
tendency to prove malignant
61. Clinical features
• Jaundice secondary to obstruction of the distal bile duct is
the most common symptom.
• Painless, progressive jaundice
• Nausea and epigastric discomfort
• Pruritus
• Dark urine and
• Pale stools with steatorrhoea
• Non-specific symptoms like vague discomfort, anorexia and
weight loss
• Upper abdominal symptoms in a recently diagnosed
diabetic, especially in one above 50 years of age, with no
family history or obesity, should raise suspicion.
62. • Unexplained attack of pancreatitis
• Tumours of the body and tail of the gland often grow
silently and present at an advanced unresectable stage.
• Back pain is a worrying symptom, raising the
possibility of retroperitoneal infiltration.
• On examination, there may be evidence of jaundice,
weight loss, a palpable liver and a palpable gall bladder
(Courvoisier’s law).
• Other signs of intra-abdominal malignancy should be
looked for with care, such as a palpable mass, ascites,
supraclavicular nodes and tumour deposits in the
pelvis; when present, they indicate a grim prognosis.
63. Investigation
• Blood investigations: CBC, LFT, RFT, Coagulation profile, blood sugar, electrolytes.
• ECG & ECHO
• Chest X-ray
• USG abdomen level & cause of obstruction, liver metastasis, ascites.
• CT scan “Pancreatic protocol CT” is the gold standard of investigation to stage
the stage and assess the operability.
Presence of liver or peritoneal metastases, lymph node metastases
distant from the pancreatic head, or encasement of the superior mesenteric,
hepatic or coeliac artery by tumour are clear contraindications to surgical
resection.
• MRI and MR angiography can provide information comparable to CT.
• Endoscopy including endoscopic USG or ERCP if there is diagnostic doubt.
• Diagnostic Laparoscopy
• Biopsy not mandatory.
indicated in cases which are found inoperable by imaging.
indicated when neoadjuvant chemotherapy is planned.
• Tumour markers CA19-9, CEA , CA 125
64. Management
• At the time of presentation, more than 85% of patients
with ductal adenocarcinoma are unsuitable for
resection because the disease is too advanced.
• If imaging shows that the tumour is potentially
resectable, the patient should be considered for
surgical resection as resection is the only chance for a
cure.
• Borderline resectable tumours may benefit from
neoadjuvant therapy and then therapy.
• For those patients who have inoperable disease,
palliative treatment should be offered.
65. PANCREATODUODENECTOMY or
WHIPPLE OPERATION
• Pre-op preparation
1. Prothrombin time should be checked and clotting
abnormalities should be corrected with vitamin K or fresh-
frozen plasma.
2. Hydration should be adequate.
3. Correction of electrolytes.
4. Proper nutrition
• The patient should be aware of the diagnosis, the gravity of the
operation and the risks involved.
• The operation has three distinct phases:
1. Exploration and assessment
2. Resection
3. Reconstruction.
66. Operative Steps:
• A cholecystectomy is performed. The bile duct and hepatic artery are exposed, removing the lymphatic
tissue in this area.
• Exposure of the hepatic artery enables division of the gastroduodenal artery and visualisation of the portal
vein.
• The distal part of the gastric antrum is mobilised. The duodenum and right colon are mobilised from the
retroperitoneal tissues.
• The superior mesenteric vein is exposed inferior to the pancreatic neck.
• Careful dissection into the plane between the vein and the pancreatic substance will reveal whether the
tumour is adherent to the vein. At this juncture, a decision has to be made whether to proceed to the next
phase of resection or not.
• If resection is to be performed, the fourth part of the duodenum is dissected and freed from the ligament
of Treitz so that the upper jejunum can be brought into the supracolic compartment.
• The jejunum is divided 20–30 cm downstream from the duodenojejunal flexure, and the mesentery of the
proximal jejunum is detached.
• The first part of the duodenum is divided. The neck of the pancreas is divided, and then the uncinate
process is separated from the superior mesenteric vein and artery working up towards the upper bile duct,
which is divided, releasing the specimen.
• Retroperitoneal lymph nodes within the operative field are completely removed with the specimen.
• Reconstruction is carried out . The pancreatic stump, the divided bile duct and the duodenal stump are
anastomosed on to the jejunum, in that order; others prefer to create a separate Roux loop of the jejunum
and anastomose the pancreas to that.
• The patients are usually nursed in a high-dependency area for the first 24–48 hours after surgery.
67.
68. ADJUVANT THERAPY
Chemotherapy or chemoradiotherapy:
Regimens are
• 5-fluorouracil (5-FU)
• Gemcitabine
• Gemcitabine with capecitabine
• Most patients with resected ductal adenocarcinoma are now
offered 6 months of adjuvant chemotherapy with gemcitabine
and/or 5-FU.
Chemotherapy for Metastatic pancreas cancer:
Regimens are
• FOLFIRINOX ( Leucovorin, fluorouracil, irinotecan, & oxaliplatin).
• Gemcitabine plus albumin-bound paclitaxel particles (nab-
paclitaxel).
69. Palliation of pancreatic cancer
Relieve jaundice and treat biliary sepsis
● Surgical biliary bypass
● Stent placed at ERCP or percutaneous transhepatic cholangiography
Improve gastric emptying
● Surgical gastroenterostomy
● Duodenal stent
Pain relief
● Stepwise escalation of analgesia
● Coeliac plexus block
● Transthoracic splanchnicectomy
Symptom relief and quality of life
● Encourage normal activities
● Enzyme replacement for steatorrhoea
● Treat diabetes
Consider chemotherapy
70. MCQs
1. All are true about annular pancreas except :
a. They are mostly asymptomatic
b. Has equal incidence in children and adults
c. Treatment of choice is duodenojenostomy
d. Associated with Down syndrome.
2. Sweat chlorides are increased in :
a. Addison’s disease
b. Conn’s disease
c. Cystic fibrosis
d. Phaeochromocytoma
3. 'Double duct' sign is typical of
a. Acute pancreatitis
b. Chronic pancreatitis
c. Pancreatic cancer
d. None
4. Walls of pseudocysts consist of ?
a. Necrotic tissue
b. Granulation tissue
c. Fibrous tissue
d. All of the above
5. The most common site for carcinoma pancreas is:
a. Head
b. Body
c. Tail
d. Neck
71. 6. What is the National Comprehensive Cancer Network (NCCN)-recommended first-line treatment for patients with
metastatic or locally advanced unresectable pancreatic cancer with good performance status?
a. Leucovorin/5-fluorouracil plus oxaliplatin plus irinotecan
b. Gemcitabine
c. Gemcitabine and nab-paclitaxel
d. Gemcitabine, docetaxel and capecitabine
7. The commonest pancreatic tumor is:
a. Ductal adenocarcinoma
b. Cystadenoma
c. Insulinoma
d. Nonislet cell tumor
8. All are true about pancreatic serous cystadenoma except:
a. Increased CEA
b. Honeycomb appearance
c. Lined by a single layer of low cuboidal epithelium
d. Malignancy is rare
9. Which of the following is not a complication of pseudopancreatic cyst?
a. Malignancy
b. Rupture
c. Hemorrhage into cyst
d. Infection
10. All are true about IPMN except:
a. Seen in both small and large ducts
b. Equal incidence in males and females
c. Most common in head
d. Usually diagnosed by octreotide scan
