Acute Pancreatitis Question And Answers
Pancreas
Pancreatitis:
Table of Contents
Acute Pancreatitis:
Question 1. Discuss the etiology, clinical features, investigations, diagnosis, complications and management of acute pancreatitis.
Answer:
Acute Pancreatitis Definition: Acute pancreatitis is best defined clinically by a patient presenting with two of the three criteria listed.
Read And Learn More: General Medicine Questions and Answers
Criteria for diagnosis of acute pancreatitis:
- Symptoms: Epigastric pain, consistent with the disease.
- Laboratory findings: Serum amylase or lipase is three times greater than the upper limit of normal.
- Radiologic imaging: Findings consistent with the diagnosis, by either computed tomography (CT) or magnetic resonance imaging (MRI).
Classification of Acute Pancreatitis:
Atlanta classification of acute pancreatitis:
- Interstitial edematous acute pancreatitis: Characterized by acute inflammation of the pancreatic parenchyma and peripancreatic tissues, but without tissue necrosis.
- Necrotizing acute pancreatitis: Characterized by inflammation associated with pancreatic parenchymal necrosis and/or peripancreatic necrosis.
Classification of acute pancreatitis according to the severity:
- Mild acute pancreatitis: Not associated with organ failure and local or systemic complications.
- Moderately severe acute pancreatitis: No organ failure or transient organ failure (<48 hours) and/or local complications.
- Severe acute pancreatitis: Persistent organ failure (>48 hours) that may involve one or multiple organs.
Acute Pancreatitis Etiology:
Mnemonic for causes of pancreatitis:
I GET SMASHED:
- Idiopathic
- Gallstones
- Ethanol
- Trauma
- Steroid
- Mumps
- Autoimmune
- Scorpion bite
- Hyperlipidemia
- ERCP
- Drugs
Question 2. Describe the etiology of acute pancreatitis.
Answer:
Causes of acute pancreatitis:
Acute Pancreatitis Pathogenesis:
- Autodigestion of the pancreatic substance is a currently accepted pathogenic theory of acute pancreatitis.
- According to this theory, acute pancreatitis develops as a consequence of premature and exaggerated activation of proteolytic enzymes within the pancreas itself (e.g. trypsinogen, chymotrypsinogen, proelastase, and lipolytic enzymes such as phospholipase A2).
Activation of pancreatic enzymes:
Activation of trypsin: One of the proenzyme is trypsinogen, which is prematurely activated to trypsin. It is an important triggering event.
Actions of trypsin are:
- Activates other proenzymes: Trypsin converts many proenzymes into active forms (such as proelastase and pro phospholipase). Activated enzymes elastase (from proelastase) and phospholipase (pro phospholipase) can damage the elastic fibers of blood vessels and degrade fat cells.
- Activation of kinin, clotting, and complement system: Trypsin acts on the kinin system and converts prekallikrein to its activated form kallikrein. This in turn can activate the Hageman factor (factor XII), the clotting and complement systems.
- The severity of acute pancreatitis depends on the balance of two opposite sets of forces, namely the activity of released proteolytic enzymes and antiproteolytic factors.
- The latter consists of an intracellular pancreatic trypsin inhibitor protein and circulatingb2-macroglobulin, a1-antitrypsin, and C1-esterase inhibitors.
Acute Pancreatitis Clinical Features:
Question 3. Write a short note on the signs and symptoms of acute pancreatitis.
Answer:
Acute Pancreatitis Symptoms:
- Abdominal pain: It is the cardinal and major symptom of acute pancreatitis.
- Its characteristics are:
- Location: Upper abdominal pain usually located in the epigastric and periumbilical region more on the left or right side, depending on the portion of the pancreas is involved.
- Onset: Sudden onset and gradually increases in severity.
- Nature: Constant, steady, intense (over 15–60 minutes)/dull and boring.
- Pain is relieved by sitting or leaning forward (Mohammedan prayer sign) due to shifting forward of abdominal contents and taking pressure off from the inflamed pancreas.
- When the retroperitoneum is involved, pain often radiates to the upper back as well as to the chest, flanks, and lower abdomen.
- 5–10% of patients with acute severe pancreatitis may have painless disease and have unexplained hypotension
- Other symptoms: These include anorexia, nausea, and vomiting. Acute pancreatitis may present as acute abdomen as a medical emergency.
- Its characteristics are:
Acute Pancreatitis Signs:
- Early stages:
- Distressed and anxious patient.
- Marked epigastric tenderness and abdominal distension (due to gastric and intestinal hypomotility). In the early stages, rebound tenderness and guarding are absent because the inflammation is mainly in the retroperitoneal region.
- Tachypnea due to ARDS, atelectasis and pleural effusion.
- In patients with gallstones, jaundice may develop due to compression of the intrapancreatic portion of the common bile duct caused by edema of the head of the pancreas.
- Severe disease:
- Low-grade fever, tachycardia, and hypotension are common.
- Shock with oliguria may develop due to:
- Hypovolemia is secondary to the exudation of blood and plasma into the retroperitoneal space.
- Vasodilation and increased vascular permeability are produced due to the increased formation and release of kinin peptides.
- Systemic effects of proteolytic and lipolytic enzymes released from the pancreas into the circulation.
- Abdominal examination may show tenderness with guarding as well as diminished or absent bowel sounds (when paralytic ileus develops).
- Respiratory system: Lungs findings include basal rales, atelectasis, and pleural effusion.
- Skin: Erythematous skin nodules due to focal subcutaneous fat necrosis may be seen.
- Purtscher retinopathy: Ischemic injury to the retina may be visible on fundus examination.
- Cutaneous ecchymoses:
- Cullen’s sign: Faint bluish discoloration (bruising) around the umbilicus due to hemoperitoneum. It may be also found in association with ruptured ectopic pregnancy, ruptured aortic aneurysm, ruptured spleen and hepatocellular carcinoma, blunt abdominal trauma, and spontaneous bleeding secondary to coagulopathy.
- Grey Turner’s sign: Blue-red-purple or green-brown discoloration of the flanks due to tissue catabolism of hemoglobin.
- Fox’s sign: Bluish discoloration over the inguinal ligament.
Laboratory Investigations:
Question 4. Write a short note on the diagnosis and treatment of acute pancreatitis.
(or)
Write a short note on investigation (including biochemical evaluation) in acute pancreatitis.
Answer:
Acute Pancreatitis Blood:
The diagnosis of acute pancreatitis is usually established by the finding of a raised level of serum amylase and lipase and ultrasound or CT evidence of pancreatic swelling.
1. Serum amylase:
- Levels markedly (three times the upper limit of normal) raised within 6–12 hours and then declined to normal within 3–5 days.
- Persistently elevated serum amylase levels indicate the development of complications such as pancreatic abscess or pseudocyst formation.
- Amylase levels may be spuriously normal in 20% of patients with alcoholic pancreatitis and 50% of patients with hypertriglyceridemia.
- Peritoneal amylase is massively raised in pancreatic ascites.
- Serum amylase concentrations are also elevated in other conditions like perforated bowel, salivary gland obstruction/ infection, ruptured ectopic pregnancy, renal failure, mesenteric infarction macroamylasemia, etc.
2. Urinary amylase: Levels may be diagnostic because they remain elevated over a longer period of time.
3. Serum lipase:
- Preferable to amylase for diagnosis as it remains elevated for a longer period of time (8–14 days) than levels of serum amylase. It has greater diagnostic accuracy and is a more useful indicator of acute pancreatitis.
- Rises within 4–8 hours of the onset of symptoms, peak at 24 hours.
- Marked elevation of lipase in pleural or peritoneal fluid (> 5000 IU/dL) suggests acute pancreatitis.
4. C-reactive protein level: It is useful in assessing the severity and prognosis of acute pancreatitis.
5. Other blood investigations:
- Low Hb: Indicates prolonged hematemesis/melena, and internal hemorrhage.
- Leukocytosis: Moderate to severe acute pancreatitis usually shows leukocytosis.
- Low platelets: DIC
- Hyperglycemia and glycosuria: It occurs in 10% of cases. Possibly due to hyperglucagonemia, associated with relative hypoinsulinemia.
- Hypocalcemia: It is due to the precipitation of calcium soaps in necrotic fat. Persistent hypocalcemia is a poor prognostic sign.
- Other baseline investigations: These include urea and electrolytes, liver biochemistry, (raised bilirubin, AST/ALT/ LDH, ALP, GGTP-gallstone pancreatitis) LDH, triglycerides, and arterial blood gases.
Acute Pancreatitis Radiology:
The enlarged inflamed pancreas may be directly visualized by radiography.
- Plain X-ray (X-ray of abdomen and chest): Useful for excluding other causes of acute abdominal pain (e.g. gastroduodenal perforation or obstruction). A supine abdominal X-ray may reveal gallstones or pancreatic calcification. Nonspecific signs like ‘colon cut-off sign’, and ‘sentinel loop sign’ can be seen.
- Abdominal ultrasound scan: Used as a screening test to evaluate gallbladder and biliary tree (to identify gallstones, biliary obstruction or pseudocyst formation). It may show pancreatic swelling, necrosis, and peripancreatic fluid collections. However, the pancreas may not be visualized because of the gas-filled loops of the bowel.
- CT scan of abdomen: May show swollen pancreas (phlegmon), pseudocyst, or pancreatic abscess. Helpful in assessing the severity, the risk of morbidity and mortality, and the complications of acute pancreatitis.
- Contrast-enhanced CT scanning: Should be performed after 72 hours of the onset of symptoms to know the extent of pancreatic necrosis. Necrotizing pancreatitis shows decreased pancreatic enhancement on CT, following intravenous injection of contrast material. It can detect complications such as fluid collection, abscess formation, pseudocyst, and involvement of the colon, blood vessels, and other adjacent structures by the inflammatory process. The presence of gas within necrotic material suggests infection and possible abscess formation.
- MRI abdomen and magnetic resonance cholangiopancreatography (MRCP):
- Its uses are:
- For assessing the degree of pancreatic damage/necrosis.
- To identify gallstones within the biliary tree.
- To differentiate between fluid and solid inflammatory masses.
- Endoscopic retrograde cholangiopancreatography (ERCP): Used for removing bile duct stones in a few selected cases of gallstone-related pancreatitis and for sphincterotomy/stent placement.
Determining the Severity of Acute Pancreatitis:
- Course of acute pancreatitis: The majority of cases of acute pancreatitis are mild and run a short, self-limiting course. About 25% develop a more complicated course and in about 10% this may be life-threatening.
- The best scoring system available is: the Ranson scoring system
- The modified Glasgow or the Imrie criteria consists of 8 parameters and requires a 48-hour period of observation and scores 3 or more it indicating severe pancreatitis.
- Acute physiology and chronic health evaluation (APACHE) II score: It is based on common physiological and laboratory values, adjusted for age and the presence or absence of a number of other chronic health problems (>8 predicts severe disease).
- Bedside index for severity in acute pancreatitis (BISAP), also uses the first letter of each parameter for 1 point.
- The BISAP score provides a single point for 5 parameters: blood urea nitrogen (BUN) greater than 25 mg/dL, impaired mental status, systemic inflammatory response syndrome, age greater than 60, and/or the presence of a pleural effusion, for a possible total of 5 points.
- A BISAP score greater than 3 is associated with a seven- to twelve-fold increase in developing organ failure.
- The computed tomography (CT) grading system of Balthazar and the CT severity index (CTSI) is presented in Table 12.3 (added score >5 indicates severe pancreatitis).
Apart from the above scoring systems, individual laboratory tests have been suggested to establish severity.
These include methemalbumin, alpha-2 macroglobulin, alpha-1 antitrypsin, C3 and C4 levels, phospholipase A2, C-reactive protein, trypsinogen-activated peptide (TAP) and granulocytic elastase.
Modified Glasgow criteria:
- P – PaO
- 2 <8 kPa
- A – Age >55-year-old
- N – Neutrophilia: WBC >15 × 109/L
- C – Calcium <2 mmol/L
- R – Renal function, urea >16 mmol/L
- E – Enzymes: LDH >600 IU/L; AST >200 IU/L
- A – Albumin <32 g/L (serum)
- S – Sugar: Blood glucose >10 mmol/L
Computed tomography (CT) grading system of Balthazar and CT severity index (CTSI):
Differential Diagnosis of Acute Pancreatitis:
Complications of Acute Pancreatitis:
Question 5. Write a short note on complications of acute pancreatitis.
Answer:
Local (Pancreatic) Complications:
- Acute peripancreatic fluid collections (APFC) do not have a well-defined wall and usually remain asymptomatic.
- Pancreatic pseudocyst: It represents a localized peripancreatic collection of pancreatic juice and debris usually developing in the lesser sac following inflammatory rupture of the pancreatic duct. It may be palpable in the upper abdomen four to six weeks after the onset of symptoms.
- Small pseudocysts are common and resolve as the pancreatitis recovers, but those larger than 6 cm can persist causing
abdominal pain and may compress or erode surrounding structures. - Pancreatic necrosis (sterile or infected): Necrosis may result in an acute necrotic collection (ANC) that contains a
a variable amount of fluid and necrosis or walled-off necrosis (WON), which consists of a mature, encapsulated collection. - Pancreatic abscess: Localized collection of pus close to the pancreas and containing little or no pancreatic necrotic tissue.
- Pancreatic ascites: May develop due to leakage of fluid from a disrupted pancreatic duct into the peritoneal cavity.
Systemic complications are listed:
Complications of acute pancreatitis:
Question 6. Write a short note on the treatment of acute pancreatitis.
Answer:
Acute Pancreatitis Management/Treatment:
Steps involved:
Acute Pancreatitis General supportive care:
In about 85–90% of patients, acute pancreatitis is self-limited and subsides spontaneously. The initial management of acute pancreatitis is similar, irrespective of the cause.
- Intravenous (IV) fluids: 5 to 10 mL/kg per hour of isotonic crystalloid solution to maintain normal intravascular volume. There may be a large amount of fluid loss during the early phase of acute pancreatitis.
- Feeding:
- Nil orally initially only in severe pancreatitis.
- In the absence of ileus, nausea, or vomiting, oral feeding can be initiated early (within 24 hours) as tolerated.
- Total parenteral nutrition may be associated with a high risk of infection.
- Nasogastric/nasojejunal administration of feed is possible in most of the patients followed by gradual oral intake.
- Analgesia for pain: Tramadol or other opiates (hydroxy morphine, fentanyl, meperidine) are the drugs for pain control. Morphine and diamorphine are avoided, because they may exacerbate pancreatic ductular hypertension by causing contraction of the sphincter of Oddi.
- Nasogastric suction/aspiration: Indications include
- Continuation Of Pain
- Presence Of Protracted Vomiting
- Obstruction was observed on a plain X-ray abdomen. It prevents abdominal distension and vomiting and the risk of aspiration pneumonia.
- Prophylactic antibiotics: Prophylactic antibiotics are not recommended in patients with acute pancreatitis. Carbapenems
(imipenem or meropenem) or ceftazidime/cefuroxime used only for infected pancreatic necrosis. - Other drugs: Proton-pump inhibitors, glucagon, octreotide, pentoxifylline, and aprotinin (protease inhibitor).
- Anticoagulation with a low molecular weight heparin for prevention of deep vein thrombosis (DVT).
- Management of acute pancreatitis.
- Indications for surgery.
- Endoscopic retrograde cholangiopancreatography (ERCP) is indicated within the first 36–48 hours in severe pancreatitis associated with gallstone obstruction (particularly when complicated by cholangitis or jaundice).
- A small percentage of patients develop multiorgan failure (reflecting the extent of pancreatic necrosis) and all severe cases should be managed in a high-dependency or intensive care unit.
- Detection and treatment of complications
- Treatment of the underlying cause (e.g. gallstones, hypercalcemia, hypertriglyceridemia).
Indications for surgery in acute pancreatitis:
- Infected pancreatic necrosis (pancreatic abscess).
- Complications: Most patients with complications such as acute peripancreatic fluid collections and/or pseudocysts do not require surgical interventions unless they become infected or cause compression of other organs.
- Cholecystectomy: It should be carried out in gallstone-related pancreatitis as soon as feasible (within 2 weeks after the resolution of the acute episode). This will prevent
potentially fatal/recurrent episode of pancreatitis.
Chronic Pancreatitis:
Question 7. Write a short essay/note on chronic pancreatitis.
Answer:
- Chronic pancreatitis is defined as chronic inflammation of the pancreas presenting as recurrent pain, characterized by the presence of inflammation, fibrosis, and loss of acinar and islet cells. The pancreas shows irreversible damage to the exocrine pancreas in the form of fibrosis causing exocrine deficiency (malabsorption). In the late stages, there may be destruction of endocrine parenchyma producing endocrine deficiency (diabetes mellitus).
Chronic Pancreatitis Etiology:
Question 8. Write a short essay/note on the causes and complications of chronic pancreatitis.
Answer:
Chronic Pancreatitis Pathogenesis:
Repeated attacks of acute pancreatitis may lead to chronic pancreatitis. Four models have been suggested that are responsible for the development of chronic pancreatitis.
- Obstruction theory: Some etiological agents cause increased protein concentrations and precipitation of these proteins; forming ductal plugs in pancreatic juice. The ductal plugs may calcify to form calculi which further obstruct the pancreatic ducts.
- Necrosis-fibrosis theory: The inflammation and scarring resulting from bouts of acute pancreatitis cause obstruction and stasis within the duct. It may subsequently form stones in the duct.
- Toxic-metabolic theory: Toxins such as alcohol and its metabolites can cause direct toxic damage to acinar cells, and eventually fibrosis.
- Oxidative stress theory: The pancreas is exposed to ‘oxidative stress’ either through systemic circulation or through reflux of bile into the pancreatic duct. It also results in recurrent inflammation, tissue damage and fibrosis, and the activation of lysosomes and proenzymes.
Causes of chronic pancreatitis: TIGAR-O classification system:
Clinical Features:
Question 9. Discuss the clinical features of chronic calcific pancreatitis.
Answer:
- Predominantly affects middle-aged alcoholic men. In southern India, severe chronic calcific pancreatitis may develop in nonalcoholics, probably as a result of malnutrition and cassava consumption.
- Abdominal pain: Due to increased pressure within the pancreatic ducts and direct involvement of pancreatic and peripancreatic nerves by the inflammatory process. Pain is variable in location, severity, and frequency.
- May be continuous or intermittent.
- May be referred to back.
- Pain is often increased by eating of heavy meals. This may lead to a fear of eating with consequent weight loss.
- No uniform relationship between pain and alcohol. Pain may be either exacerbated by alcohol excess or may be relieved by drinking alcohol.
- It is partially relieved on stooping and bending forward (Mohammedan prayer sign).
- Features of maldigestion/malabsorption: Manifested as chronic diarrhea, steatorrhea, weight loss, fatigue.
- Diabetes mellitus [pancreatogenic (type 3c) diabetes] develops in about 30% of patients.
- In late stages, mechanical obstruction of the common bile duct due to fibrosed head of the pancreas can produce jaundice.
Chronic calcific pancreatitis Physical Examination:
Thin, malnourished patient with tenderness in the epigastric region.
Chronic calcific pancreatitis Investigations:
- Serum amylase and lipase: These may be elevated but in advanced disease, they are usually normal.
- Plain X-ray of the abdomen: May show diffuse calcifications in the pancreatic area (in ~30%) and usually indicate significant damage to the pancreas.
- Transabdominal ultrasound scan: Used for initial assessment.
- Contrast-enhanced spiral CT scan: Useful for a more detailed assessment. It may show pancreatic calcification, dilated pancreatic duct, pancreatic atrophy, and dilatation/stricture of bile duct.
- Endoscopic retrograde cholangiopancreatography (ERCP) is the gold standard for accurate diagnosis and demonstrates pancreatic ducts.
- MRI with MRCP: Provides a direct view of the pancreatic duct and detects more subtle abnormalities of the pancreatic duct. MRI and MRCP are now the diagnostic procedures of choice.
- Endoscopic ultrasonography (EUS): It is useful for specifically assessing complications of chronic pancreatitis including pseudocyst formation and possible development of malignancy.
- Pancreatic exocrine function tests:
- Secretin/cholecystokinin (CCK) stimulation test: Collection of pure pancreatic juice after secretin/CCK injection (gold standard but invasive and seldom used).
- Fecal chymotrypsin or elastase level: Abnormal in the majority of moderate to severe chronic pancreatitis.
- 24-hour fecal fat, the Lundh test meal, oral glucose tolerance test, and pancreolauryl or PABA test.
- Gene mutation analysis: In cases where the etiology is not known. Common mutations include PRSS1, SPINK-1, and CFTR encoding genes.
Complications of Chronic Pancreatitis:
Pseudocyst formation, bile duct or duodenal obstruction, pancreatic ascites or pleural effusion, splenic vein thrombosis, pseudoaneurysms, osteopenia, osteoporosis, and, pancreatic cancer are the complications of chronic pancreatitis.
Chronic calcific pancreatitis Treatment:
- Long-term abstinence of alcohol in patients with alcohol-related chronic pancreatitis may benefit. Smoking cessation prevents progression.
- Treatment of abdominal pain: About 60% of patients will become pain-free after about 6–10 years.
- Opioids (tramadol) or non-steroidal anti-inflammatory drugs (NSAIDs): Tricyclic antidepressants (e.g. amitriptyline) and membrane stabilizing agents (e.g. pregabalin) may also be used for chronic pain.
- Intractable pain may be treated by celiac axis nerve block.
- Surgery includes pancreatectomy and pancretojejunostomy performed for unremitting pain.
- Endoscopic therapy is useful in painful chronic pancreatitis to drain pancreatic ducts in patients with obstructed ducts and treatment of complications (e.g. pseudocysts and bile duct obstruction with jaundice).
- Steatorrhea:
- The steatorrhea seen in pancreatic insufficiency may be high, with up to 30 mmol of fat lost/24 h. This is treated with pancreatic enzyme supplements particularly lipase, 80,000–1,00,000 units before each meal.
- An acid suppressor (H 2-receptor antagonist or proton pump inhibitor) to prevent inactivation of pancreatic enzymes by gastric acid.
- A diet rich in medium-chain triglycerides which do not require lipase for digestion may be given.
- Vitamin D supplementation (calcifediol)
- Treatment of diabetes: With insulin.
Fibrocalcific/Tropical Pancreatitis:
Question 10. Describe the features of tropical pancreatitis.
Answer:
- Juvenile form of chronic calcific pancreatitis and is not related to alcohol intake.
- Almost exclusively observed in tropical countries. In India, it is more common in southern states namely Kerala and Tamil Nadu.
Fibrocalcific/Tropical Pancreatitis Etiology:
The exact etiology is not known and possible risk factors:
Risk factors for tropical pancreatitis:
- Malnutrition
- Infections, e.g. coxsackie and viral hepatitis
- Oxidant stress
- A diet rich in cassava, tapioca (contains cyanogenic glycosides)
- Familial.
Fibrocalcific/Tropical Pancreatitis Clinical Features:
- Age and gender: Young males.
- Course: Accelerated course.
- Symptoms: Recurrent abdominal pain, typically in an epigastric area with radiation to the back. Pain precipitated by heavy meals. Pancreatic exocrine deficiency presents with steatorrhea and malabsorption and endocrine deficiency presents with diabetes mellitus. Even without insulin ketosis is uncommon and frequent episodes of hypoglycemia with insulin are observed.
- Signs: Malnutrition, enlarged parotid glands, abdominal distention, and a peculiar cyanotic hue of the lips.
Fibrocalcific/Tropical Pancreatitis Investigations:
- Plain X-ray and ultrasound of abdomen: Shows multiple, large intraductal calculi.
- Blood: Sugar, serum amylase, lipids, and calcium need to be checked.
Fibrocalcific/Tropical Pancreatitis Treatment:
- Similar to chronic pancreatitis described earlier.
- Insulin for diabetes requires a careful watch for hypoglycemia.
Differences between Alcoholic Pancreatitis and Tropical:
Pancreatitis:
Question 11. How will you differentiate tropical pancreatitis from alcoholic pancreatitis?
Answer:
Autoimmune Pancreatitis (AIP)/Autoimmune Chronic Pancreatitis (ACP):
Autoimmune pancreatitis is a distinct chronic inflammatory and sclerosing disease of the pancreas.
- Subtypes:
- Type 1—IgG4-related disorder: It is one of the IgG4-related disorders characterized by a raised serum IgG4 level. Other IgG4-related disorders are autoimmune cholangitis, Riedel’s thyroiditis, aortitis, and tubulointerstitial nephritis. Microscopically, IgG4-related disorders show dense lymphoplasmacytic infiltration with many IgG4-positive plasma cells, mild to moderate infiltration by eosinophils, and obliterative phlebitis in some organs, e.g. pancreas.
- Type 2—idiopathic duct-centric pancreatitis or AIP with a granulocytic epithelial lesion.
- Age and gender: It is more common in men (2:1) and usually manifests in middle age (>85% above the age of 50 years).
- Clinical presentation: It presents with abdominal pain, weight loss, or painless obstructive jaundice (due to obstruction of the intrapancreatic bile duct), without acute attacks of pancreatitis. Other symptoms include vomiting and glucose intolerance.
- Association with other autoimmune disease: AIP may also develop in association with other autoimmune disorders. These disorders include Sjögren’s syndrome, primary sclerosing cholangitis (PSC), inflammatory bowel disease, and retroperitoneal fibrosis (most commonly presenting as hydronephrosis due to entrapment of the ureter).
- Laboratory findings: Elevated serum immunoglobulins (IgG or IgG4), and the presence of other autoantibodies including those directed towards nuclear and smooth muscle antigens.
- Imaging: It shows diffuse enlargement of the pancreas, narrowing of the pancreatic duct, and stricturing of the lower bile duct. The Mayo Clinic HISORt criteria for the diagnosis of autoimmune pancreatitis.
Alcoholic pancreatitis Treatment: Glucocorticoid therapy usually produces rather dramatic improvement with rapid resolution of both symptoms and radiographic abnormalities. This is the hallmark of autoimmune pancreatitis. Some patients require azathioprine.
Pancreatic Cancer:
- Pancreatic cancer is the fifth most common cause of cancer death in the Western World.
- Age and gender: Its incidence increases with age and the majority occur in the elderly over the age of 60. Males are affected twice as often as females.
Alcoholic pancreatitis Etiology:
- Risk factors:
- The most important environmental factor is cigarette smoking
- The second most modifiable risk factor is obesity
- Excess intake of alcohol, high fat, and protein diet, excessive intake of coffee and tea consumption, and chronic calcific pancreatitis
- DM is associated with a 40% ↑ risk of pancreatic cancer.
- Genetic predisposition: About 5 to 10% of patients with pancreatic cancer have a family history of the disease. FAM (familial atypical multiple mole melanoma syndromes), HNPCC (hereditary nonpolyposis colorectal cancer syndrome), hereditary pancreatitis, MEN, Lynch syndrome, and Peutz-Jeghers syndrome have an increased risk of pancreatic cancer.
- Mutational activation of oncogenes, predominantly KRAS, and inactivation of tumor suppressor genes such as TP53 (70%), p16/CDKN2A (98%), and SMAD4 (55%) are commonly associated.
Alcoholic pancreatitis Pathology:
- Ductal adenocarcinoma accounts for 85–90% of pancreatic tumors. Cystic neoplasms represent 10%–15% of cystic lesions of the pancreas. 5% are endocrine tumors. Only 2% of tumors of the exocrine pancreas are benign.
- Location: About 60–70% of these tumors are localized in the head of the gland, 5–10% in the body, and 10–15% in the tail.
- Spread: Local spread, lymphatic spread as well as hematogenous spread occurs rapidly.
Alcoholic pancreatitis Clinical Features:
Alcoholic pancreatitis Symptoms:
- Central abdominal pain: Pain is a common symptom and is usually incessant and gnawing, epigastric, radiates from the upper abdomen to the back, increasing on lying down and relieved by sitting up or bending forward. Pain is primarily due to invasion of the celiac or superior mesenteric arterial plexus.
- Others: Loss of weight and cachexia.
- Symptoms depend upon the site of the tumor.
- Carcinoma of the head of the pancreas: They present early because the obstruction to the common bile duct by the tumor produces obstructive jaundice present in >50% of patients (due to obstruction of bile flow), often with severe pruritus (secondary to cholestasis). Other symptoms include clay-colored stools with or without melena or silver stools. Obstruction of the pancreatic duct may cause episodes of pancreatitis.
- Less common symptoms include those of diabetes and pancreatitis.
- Carcinoma of the body and tail of the pancreas: May be silent till quite large and widely disseminated.
Alcoholic pancreatitis Physical Signs:
- General: Pallor, jaundice, and weight loss may be present. Scratch marks and erythema ab igne is seen.
- Abdominal mass: A mass may be felt in the epigastrium; the liver may be enlarged (hepatomegaly) due to biliary obstruction or secondary involvement (hepatic metastasis).
- Courvoisier’s law: A distended nontender gallbladder may be palpable in a jaundiced patient due to distal biliary obstruction by pancreatic cancer.
- Due to the spread of the tumor:
- With peritoneal involvement and ascites, shifting dullness and fluid thrill can be elicited. On per rectal examination, nodules (Blumer’s shelf) or peritoneal fluid may be felt.
- Involvement of the left supraclavicular node (Virchow’s node) and umbilicus (Sister Mary Joseph’s node) indicates advanced carcinoma.
- Other presenting physical signs: Migratory thrombophlebitis—recurrent venous thrombosis (Trousseau sign), diabetes, polyarthritis, paraneoplastic syndromes (Cushing syndrome), skin nodules (secondary to localized fat necrosis and
associated inflammation) and hypercalcemia may be seen in some cases.
Alcoholic pancreatitis Investigations:
- Blood: It may show anemia. Liver function tests may show features of obstructive jaundice with elevated alkaline phosphatase. Urobilinogen is absent in urine whereas bile salts and bile pigments are evident. Occult blood may be present in stool.
- Radiology: Barium meal shows a widening of the ‘C’ loop (pad sign) and reverses the ‘3’ sign in periampullary carcinoma. Hypotonic duodenography reveals a ‘rose thorn’ appearance. Endoscopic retrograde cholangiography increases the diagnostic yield; USG and CT scans are helpful in localizing the tumor.
- Ultrasound, contrast CT, and ERCP yield in localization of the tumor, assessing the spread as well as operability, guided biopsy/ cytology helps to confirm the diagnosis.
- ERCP: A “double-duct sign,” representing strictures in biliary and pancreatic ducts, is classically found in many patients. Tissue sampling can also be obtained during ERCP.
- Endoscopic ultrasonography is the most accurate test for the detection of pancreatic cancer.
- Tumor markers: Carcinoembryonic antigen (CEA) and CA-19-9 [high sensitivity (80%) but a high false-positive rate].
Alcoholic pancreatitis Prognosis:
Overall survival is about 3–5%, with a median survival of 6–10 months for locally advanced cancer and 3–5 months for those with metastases.
Alcoholic pancreatitis Treatment:
- Surgical resection: It is the only method of effecting cure. Resectable tumors in the head and periampullary region are removed by Whipple’s pancreaticoduodenectomy or its modifications.
- Chemotherapy: For inoperable cases chemotherapy with gemcitabine, capecitabine, paclitaxel, cisplatin, docetaxel, oxaliplatin, irinotecan, 5-fluorouracil, mitomycin, streptozotocin and high-dose methotrexate, alone or in combination, may be beneficial. Tyrosine kinase inhibitors of EGFR (e.g. erlotinib) and monoclonal antibodies cetuximab is under trials.
- FOLFIRINOX is a chemotherapy regimen for the treatment of advanced pancreatic cancer (FOL folinic acid (leucovorin), F fluorouracil (5-FU), IRIN irinotecan, OX oxaliplatin)
- Radiotherapy may be supportive.
- Palliative treatment:
- Pain: Palliation for pain may be achieved with either analgesic nerve blocks (coeliac axis block/neurolysis, percutaneous cordotomy) or with duct drainage (pancreatic gastric anastomosis).
- Jaundice can be relieved by choledochojejunostomy or percutaneous/endoscopic stenting—endoprostheses (elderly and with very advanced disease).
Endocrine Tumors Of Pancreas/Pancreatic Neuroendocrine Tumors (Pnets):
- Endocrine tumors of the pancreas (ETP) are classified as functioning or nonfunctioning according to the type and level of their hormonal secretion.
- Among functioning ETP, insulinomas (50%) and gastrinomas (30%) are the most frequent; tumors secreting vasoactive intestinal peptide (VIPomas), glucagon (glucagonomas), and somatostatin (somatostatinomas) are much rarer (5–10%).
These secreting growth-hormone-releasing factor (GHRH), adrenocorticotropic hormone (ACTH) or corticotropin-releasing factor (CRF), and parathyroid hormone-related peptide (PTHrp) are anecdotal. - Conversely, at least 15% of ETPs are nonfunctioning or secrete non-clinically active peptides such as human pancreatic polypeptides (PPomas).
Insulinoma (Beta Cell Tumor):
- Most common of endocrine tumors; 10% are malignant and produce pronounced hypoglycemia.
Alcoholic pancreatitis Clinical Features:
- Higher incidence in women.
Whipple’s triad:
- Attack of hypoglycemia (mental confusion, weakness, fatigue and convulsions) while fasting. Neuroglycopenic symptoms (anxiety, nervousness, dizziness, and confusion) may develop during fasting. In some psychoses, seizures related to hypoglycemia and weight gain are seen.
- Blood sugar <50 mg/dL during an attack.
- Relief of symptoms by administration of glucose.
Alcoholic pancreatitis Diagnosis:
Fasting blood levels of insulin and glucose:
- Inappropriately elevated serum level of insulin (>54 u/mL) for the level of glucose establishes the diagnosis.
- Blood insulin-to-glucose ratio of >0.4 is diagnostic.
- A blood fasting C-peptide level of >1.7 mg/mL is a good indicator.
- Proinsulin level is elevated and is used as a tumor marker.
- Suppression and stimulation (tolbutamide, calcium, glucagon) tests may be performed.
Alcoholic Pancreatitis Radiology:
- Selective angiography is the best investigation, with few false positive results.
- USG is positive in 20–40% of cases.
- CT with intravenous contrast shows a dense blush.
- MRI: Bright spots are seen on T2 weighted images. In the presence of somatostatin receptors, an octreotide scan may be useful. Portal venous sampling has 75% accuracy.
- Calcium angiography: It can determine the location of insulinoma whereas endoscopic USG has 80% positivity.
Gastrinoma (Delta Cell Tumor):
(Synonym: Zollinger-Ellison syndrome):
- The second most common islet cell tumor (0.1–0.4/million population/year), but with MEN I it is the most common functional pancreatic neoplasm; 20% of ZES have MEN I.
Treatment of Insulinoma:
- Aim: To localize and remove the tumor safely.
- Hypoglycemia can be managed medically (by using diazoxide, octreotide, and lanreotide).
- Surgery:
- If the tumor is small and in the head: Removed by enucleation.
- If in the body or tail: Remove it either by enucleation or by distal (subtotal) pancreatectomy.
- If the tumor is malignant and is operable: Resection.
- For metastasis (liver, adjacent lymph nodes):
- Hepatic artery embolization, RFA, and cryoablation or radioembolization.
- Streptozotocin, chlorozocin, 5-FU, either alone or in combination.
Question 12. Write a short essay/note on the etiology, clinical features, and treatment of Zollinger-Ellison syndrome.
Answer:
Zollinger-Ellison syndrome Pathology:
- Sites: The most common sites of gastrinoma are duodenum (50-88% in sporadic ZES, 70-100% in MEN1 ZES), pancreas (only 25%, and rarely in gastric antrum).
- Effects: It produces excessive gastrin.
- Characteristics:
- Often solitary and malignant.
- When occur as part of MEN I, they are multiple and less malignant.
- Duodenal gastrinomas are less malignant than pancreatic tumors. They are slow-growing even in the presence of metastasis.
Gastrinoma Triangle of Passaro:
- Junction between the cystic duct and common bile duct
- The junction between the 2nd and 3rd parts of the duodenum
- The junction between the neck and body of the pancreas 60–90% of gastrinomas arise within this triangle
Zollinger-Ellison syndrome Clinical Features:
- More frequent in middle-aged men. With MEN I, the symptoms occur earlier (3rd decade).
- Zollinger-Ellison syndrome is characterized by hyperacidity and non-healing ulcers (gastric, duodenal, jejunal, or in atypical locations). Epigastric pain with duodenal ulcer is seen in 90% of cases; 1/3rd have diarrhea, and weight loss is common (40% of cases). Esophagitis, dysphagia (30%), stricture, and perforation may occur.
Zollinger-Ellison syndrome Diagnosis:
- ZES: About 30–40% do not have evidence of peptic ulcer disease and 40% have duodenal instead of pancreatic tumor.
- Gastric acid hypersecretion (basal acid output >15 mEq/L) and elevated fasting gastrin (> 100 pg/mL) are suggestive. Provocative tests using secretin, calcium, or gastrin may be used. Gastric pH <2 and fasting serum gastrin level > 1000 pg/ mL is diagnostic.
- Immunohistochemistry: Demonstration of gastrin in neoplastic cells by immunoperoxidase is confirmatory.
- Tumor localization: Using ultrasound, CT scan, and endoscopic USG.
- Selective angiography is best for primary and metastatic gastrinomas (40–60% accuracy) and with secretin stimulation, the accuracy increases to 70%.
- Portal venous sampling for gastrin.
Zollinger-Ellison syndrome Treatment:
Zollinger-Ellison syndrome Medical:
- Control acid secretion using H2 blockers. Dose: 2 grams ranitidine, 0.3 g famotidine or 80 mg omeprazole/pantoprazole per day. Parenteral ranitidine may be used.
Zollinger-Ellison syndrome Surgery:
- Accurately identification of duodenal or pancreatic tumor by inspection, palpation, and if needed by intraoperative USG or transillumination duodenotomy.
- Surgical management
- Excision, gastrectomy, and enucleation are based on tumor size, number, and location.
- Patients with MEN I having gastrinoma:
- Surgery is not indicated.
- Four-gland parathyroidectomy with autografts is the initial procedure of choice to control hyperparathyroidism. Gastric acid hypersecretion is controlled as in sporadic gastrinoma (mentioned above).
- If liver metastasis is present and resectable: Resection.
- Chemotherapy: Doxorubicin, 5-FU, and streptozotocin show a 40% response. Interferon and octreotide may also be used.
Glucagonoma (Alpha Cell Tumor): Rare a-cell tumor.
Glucagonoma Clinical Features:
- Functional tumors: They produce the glucagonoma syndrome comprising abnormal glucose tolerance test, normocytic normochromic anemia, necrolytic migratory erythema (pathognomonic), red tongue, angular stomatitis, weight loss, the tendency to develop infection and depression.
- Elevated fasting plasma glucagon >500 pg/mL is diagnostic.
Glucagonoma Treatment: Preoperative control of diabetes, treatment of venous thrombosis, and correction of nutritional status with total parenteral nutrition. Surgical resection is done after localizing the tumor.
Somatostatinoma (Delta Cell Tumor):
Rare malignant D cell tumors of the pancreas and 30% occur in the duodenum and small bowel. They affect both sexes equally, with an approximate age of 50 years. They cause diabetes mellitus, gallstones, and diarrhea/steatorrhea.
Glucagonoma Diagnosis: High fasting serum somatostatin levels.
Glucagonoma Treatment: Octreotide therapy may be tried and the tumor surgically resected after localization. Cholecystectomy may be required for cholelithiasis.
VIPoma (WDHA Syndrome; Verner-Morrison Syndrome; Pancreatic Cholera):
- Endocrine pancreatic tumor-producing vasoactive intestinal polypeptide (VIP).
- Symptoms: Severe secretory diarrhea secondary to the stimulation of adenyl cyclase within the enterocyte (VernerMorrison syndrome). Large-volume diarrhea (>3 L/day), hypokalemia, and hypo- or achlorhydria form part of the syndrome; hence the term Watery Diarrhea, Hypokalemia, Achlorhydria (WDHA) syndrome.
Glucagonoma Diagnosis: Presence of severe secretory diarrhea, detection of elevated fasting levels of plasma VIP (>250 pg/mL), and localization of pancreatic islet cell tumor.
Glucagonoma Treatment:
- Correction of dehydration, hypokalemia, and other metabolic abnormalities.
- Octreotide may be tried for symptomatic relief.
- Surgical removal of the tumor.
- For unresectable and metastatic tumors chemotherapy with 5-FU and streptozotocin. Interferon has also been used. Palliative debulking for incurable and metastatic tumors.
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