PANCREATITIS & PANCREATIC PSEUDOCYST

By :- Shweta Achuthan Kutty

•Introduction•History•Aetiology•Pathogenesis•Clinical Features•Complications•Diagnosis•Grading of severity•Management•Differential diagnosis

HEADINGS:

PancreatitisInflammation of the pancreatic parenchyma, which is a retroperitoneal, endocrine and exocrine organ.

Clinical Classification

Pancreatitis

ACUTE Pancreatitis*- (present as emergency)

CHRONIC Pancreatitis- (prolonged-life long-

disorder)**

• Acute Pancreatitis**: inflammatory condition of the pancreas of an acute presentation characterized clinically by abdominal pain and elevated levels of pancreatic enzymes in the blood.

• Chronic Pancreatitis: is a continuing inflammatory disease of the pancreas characterised by irreversible morphological changes typically causing pain and/or permanent loss of function. Can also have an acute on chronic presentation.

Pathological Classification

• Are of two types:• Interstitial oedematous pancreatitis: vast

majority (90-95%)• most often referred to simply as "acute

pancreatitis" or "uncomplicated pancreatitis“• Necrotising pancreatitis: necrosis develops

within the pancreas and/or peripancreatic tissue

Blast from the Past:

• Alexander the Great

• Reginald Huber Fitz – On Acute Pancreatitis

• Eugene Lindsey Opie – Gallstone lodging

• Chiari - Autodigestion

ACUTE PANCREATITIS• DEFINITION: A group of reversible lesions due to inflammation of the pancreas clinically charactersied by abdominal pain and elevated levels of pancreatic enzymes in the blood. It is medical emergency, and requires to be treated as soon as possible.

• GENDER PREDILECTION: Generally M>FIn males more often related to alcoholIn females more often related to biliary tract diseaseIdiopathic pancreatitis no clear gender predilection

• INCIDENCE: Young men and elderly women

• MORTALITY RATE: Mild pancreatitis >1%, Severe cases - 10-30%

• CAUSE OF DEATH: Multi-organ Dysfunction Syndrome

AETIOLOGY• Gall stones - 50 to 70% cases• Alcoholism - 25%• Post ERCP - ***• Abdominal trauma• Post biliary , upper gastrointestinal or cardiothoracic surgery• Ampullary tumour• Drugs like corticosteroids, azathioprine, asparaginase, valproic acid, thiazides, oestrogens

• Hyperparathyroidism• Hypercalcaemia• Pancreas divisum• Autoimmune pancreatitis• Hereditary pancreatitis • Viral Infections – mumps/cockackie B• Malnutrition• Scorpion bite• Idiopathic

PATHOGENESIS : AUTO ACTIVATION AND AUTO DIGESTION

•Two -mild pancreatitis• -severe pancreatitis, •Division is based whether the predominant response to cell injury is inflammation or necrosis, respectively.

•In mild pancreatitis - inflammation and edema of the pancreas •In severe pancreatitis – also features of necrosis and secondary injury to extrapancreatic organs.

•Both types share a common mechanism of abnormal inhibition of secretion of zymogens and inappropriate activation of pancreatic zymogens inside the pancreas, most notably trypsinogen.

CLINICAL FEATURESThe most common symptoms and signs include:

Severe epigastric pain (50% cases) radiating to the back, chest, flanks, and lower abdomen, relieved by leaning forward, that feels worse after eating

Nausea, vomiting, diarrhea and loss of appetiteFever/chills

Hemodynamic instability, including shock- cold clammy extremities, rapid low volume pulse, tachycardia

In severe case may present with tenderness, guarding, rebound tenderness.

Respiratory symptoms: Tachypnoea, respiratory distressHiccups

COMPLICATIONS/SEQUELAE

1) LOCAL: usually develop after first week

• Acute fluid collection• Sterile pancreatic necrosis• Infected pancreatic necrosis• Pancreatic abcess• Pseudocyst• Pancreatic ascites • Pancreatic effusion• Haemorrhage• Portal/Splenic vein thrombosis• Pseudoaneurysm **In the long run, repeated attacks- chronic pancreatitis with irreversible damage

2) SYSTEMIC: more common in the first one week

• Cardiovascular: Shock, arrythmias

• Pulmonary : ARDS

• Renal failure

• Gastrointestinal: Ileus, peritonitis

• Neurological : visual disturbances, confusion, irritability, encephalopathy, coma

• Miscellaneous: Subcutaneous fat necrosis, arthralgia

Others include :

Haematological: DIC

Metabolic: hyperglycaemia, hypocalcaemia, hyperlipidaemia

DIAGNOSISProper history, clinical examination, confirmation by investigations

According to the American College of Gastroenterology's guidelines, there are three criteria that must be present to diagnose acute pancreatitis, including:

•Severe abdominal pain

•Amylase or lipase levels that are three times higher than the upper limit of normal

•"Characteristic" abdominal imaging results

1. Blood

• CBC - neutrophil leucocytosis, thrombocytopenia (DIC)• BUN• Clotting profile- prolonged in DIC• Glucose - hyperglycaemia in severe cases• Electrolytes: Calcium levels -decreased, Potassium levels• ABG – (hypoxemia) , pH (lactic acidosis – shock)• FDP like D-dimer– raised in DIC• Triglycerides• C-reactive protein• IgG4 – autoimmune pancreatitis

INVESTIGATIONS

2. Urine-24h urine ouput-Microscopy: Casts- Urinary amylase-Glycosuria (10% cases)

*Trypsin and its precursor trypsinogen-2 in both the urine and the peritoneal fluid have been evaluated as possible markers for acute pancreatitis (especially post-ERCP pancreatitis) but are not widely used.

*Although not currently in use clinically, polymorphisms in the chemokine monocyte chemotactic protein 1 (MCP-1) gene may also predict severity. This is the first gene identified that plays a role strictly in predicting the severity of disease.

3. Biochemical investigations - Liver function tests: Increased liver enzymes, ALT,ALP, GGT ( gallstones)- Direct bilirubin : Increase in CBD block- Renal function tests: Creatinine, BUN, Urea - Serum amylase: (amylase P): Increased (3-4 times normal diagnostic but not specific)- Serum lipase: Increased- more specific

4. Radiological

•X rays :--Non specific signs – generalised or local ileus (sentinel loop), a colon cut off sign, renal halo sign, calcified gallstones/pancreatic calcifications

USG abdomen:- With in 24 hours- for gallstones, rule out a/c cholecystitis, CBD dilatation diagnosis of vascular complications, i.e. thrombosis, hypoechoic lesions may indicate necrotic change

•CT Abdomen with contrast:- phlegmon(inflammatory mass), pseudocyst or abscess(complications of acute pancreatitis)

CT:typical findings:

-focal or diffuse parenchymal enlargement-calcifications may be seen within the parenchyma-changes in density because of oedema-indistinct pancreatic margins owing to inflammation-surrounding retroperitoneal fat stranding

liquefactive necrosis of pancreatic parenchyma: lack of parenchymal enhancementinfected necrosis

abscess formation : circumscribed fluid collection, little or no necrotic tissues

haemorrhage: high-attenuation fluid in the retroperitoneum or peripancreatic tissues

•MRI :- Contrast-enhanced MR is equivalent to CT in the assessment of pancreatitis.

•ERCP :- Identification and removal of gallstones.

•EUS:- not frequent, used to ultrasonographically visualize pancreas, bile tree, useful for stones, does not have complications of ERCP. More sensitive to pick up microlithiasis and periampullary lesions.

•MRCP:- not frequently used, used for detection of gallstones.

Assessment of Severity

• AIM: to define patients with severe pancreatitis

• Based on history, clinical assessment , investigations - scoring systems – Ranson score, Glasgow scale, APACHE II, BISAP, Balthazar scoring

•Grade severity , provide adequate appropriate treatment/interventions, ward off/better control of another attack

This calculator evaluates the following Clinical Criteria:BUN >25 mg/dL (8.9 mmol/L)Impairment of mental status with a Glasgow coma score <15SIRS (systemic inflammatory response syndrome)Age >60 years oldPleural effusion

Each determinant is given one point

SIRS is defined as 2 or more of the following variables;Fever of more than 38°C (100.4°F) or less than 36°C (96.8°F)Heart rate of more than 90 beats per minuteRespiratory rate of more than 20 breaths per minute or arterial carbon dioxide tension (PaCO2) of less than 32mm HgAbnormal white blood cell count (>12,000/µL or < 4,000/µL or >10% immature [band] forms)

Bedside index of severity in acute pancreatitis (BISAP) score

BISAP Score BISAP Score Observed Mortality0 0.1%1 0.4%2 1.6%3 3.6%4 7.4%5 9.5%

Wu et al, Gut 2008

MANAGEMENTEarly managementManagement of risk factorsManagement of complications

Early Management: aims to provide immediate care and resuscitation

•Admission to HDU/ICU

•Analgesia

•Aggressive fluid rehydration, electrolyte imbalance correction

•Oxygenation

•Monitoring vitals, CVP, urine output, blood gases

• Frequent monitoring : haematological + biochemical parameters- RFT, LFT, clotting profile, serum Calcium, blood sugar levels

• NG drainage

•Antibiotic prophylaxis

• CT scan : essential for organ failure, clinical deterioration or signs or sepsis develops

• 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 feeding using NG tube

SPECIFIC MANAGEMENT OF COMPLICATIONS

1) Acute fluid collection: •Small sterile collections resolve

•large collections- CT/USG guided percutaneous aspiration

2) Sterile/infectious pancreatic necrosis and pancreatic abscesses: A) CT/USG guided wide bore needle aspiration

•Microbiological assessment of pus,

•AB sensitivity- start Abs,

If conservative measures fail especially in very severe cases– B) NECROSECTOMY- thorough removal of necrotic tissues and collections

•Based on clinical symptoms and imaging studies via endoscopy/ midline laparotomy

•Asso high morbidity and mortality

•If tail and body involved – left flank approach

•If gallstones are cause – Cholecystectomy- endoscopic/laparotomy

•After Necrosectomy- more necrotic tissue may form, re-exploration may be needed

C) Management of Post Necrosectomy necrotic tissue:

Closed continuous lavage of Berger: Tube drains are left in and the raw areas flushed

Closed drainage: Incision is closed but cavity is packed with gauze filled Penrose drains and closed suction drains.The Penrose drains are brought out through the flank and slowly pulled out and removed after 7 days.

Open packing: Incision is left open and cavity packed with intention of returning to the OT at regular intervals and repacking until there is a clean granulation cavity.

Closure and relaparotomy: incision is closed with drains with intention of performing a series of planned relaparotomies every 48-72 hours until raw area granulates

3) Pancreatic ascites: Wide bore needle drainage, NG tubing, Octreotide

4) Pancreatic effusion: Imaging guided percutaneous drainage

5) Haemorrhage : Fatal, embolisation and surgery

6) Portal/Splenic vein thrombosis:If Portal HTN – esophageal banding/sclerosing agents,In case of thrombocytosis – antiplatelets like aspirin, clopidogrel, systemic anticoagulation – double edged sword?

DIFFERENTIAL DIAGNOSIS

•Perforated peptic ulcer•Biliary colic-------------•Acute cholecystitis----•Pneumonia----------------•Pleuritic pain--------------•Myocardial infarction---•Oesophageal spasm-----•Perforated viscus•Acute mesentric ischaemia•Acute respiratory distress syndrome

*rule out any cause of acute abdomen

Right upper quadrant pain

Radiation to chest

PANCREATIC PSEUDOCYSTDefinition: Is a collection of amylase rich fluid enclosed in a wall of fibrous or granulation tissue.

Aetiology: after an attack of acute pancreatitis**, in chronic pancreatitis, and post pancreatic trauma

Pathogenesis: Formation >/= 4 weeks from the onset of acute pancreatitis. Thick fibrous capsule – no true epithelial lining. Due to ductal distruption, strictures, calculi, tumours.

Composition: Similar electrolyte concentrations to plasmaHigh concentration of amylase, lipase, and trypsin.

Occurrence: Most common cystic lesions of pancreas, accounting for 75-80% of such massesSingle *, maybe multiple, or loculated

Location: Lesser peritoneal sac in proximity to the pancreasLarge pseudocysts can extend into the paracolic gutters, pelvis, mediastinum, neck or scrotum

CLINICAL FEATURES•Asymptomatic when small•Symptoms

Abdominal pain > 3 weeks (80 – 90%)Nausea / vomitingEarly satietyBloating, indigestion

•Signs:Abdominal fullnessTendernessPalpable mass in the abdomenPeritoneal signs suggesting rupture of the cyst or infectionFeverScleral icterusPleural effusion

COMPLICATIONS/SEQUELAE:Infection: Abscess, systemic sepsis

Rupture: Into gutGI bleeding, internal fistula Into peritoneum Peritonitis

Enlargement: Bowel obstruction, biliary compression, pain

Erosion into vessel: Haemorrhage into the cyst, haemoperitoneum

DIAGNOSISClinically suspicion in case :

• Episode of pancreatitis fails to resolve

• Amylase levels persistantly high

• Persistent abdominal pain • Epigastric mass palpated after pancreatitis

INVESTIGATIONSLabs: Persistently elevated serum amylase

Cyst fluid analysis(EUS+A): Carcinoembryonic antigen (CEA) and CEA-125 (low in pseudocysts and elevated in tumors); fluid viscosity (low in pseudocysts and elevated in tumors); amylase (usually high in pseudocysts and low in tumors)CEA (cystic neoplasm)

Radiological Investigations

•Plain X-ray: Not very useful•Ultrasound TransAbd: 75 -90% sensitive•EUS: helps plan therapy, not useful for Dx•CT : Most accurate (sensitivity 90-100%)•MRI –detection of solid component of cyst and in differentiating between organized necrosis and a pseudocyst

NATURAL HISTORY OF PSEUDOCYST:•~50% resolve spontaneously

•Nearly all <4cm resolve spontaneously

• Those >6cm, >12weeks duration asso c/c pancreatitis persist, necessitate intervention

• Multiple cysts – few spontaneously resolve

MANAGEMENT

If asymptomatic/small – wait for spontaneous resolution

DEFINITIVE TREATMENT DRAINAGEINDICATIONS :

ComplicationsSymptomsConcern about possible malignancy

• 3 approaches to drain a pseudocyst:

Percutaneous

Endoscopic

Surgical**

A) PERCUTANEOUS DRAINAGE:

1) Percutaneous catheter drainage:Done under USG/CT guidance, but has several disadvantages.High recurrence rate, contraindicated In cysts that are communicating with duct lumen- Pancreticocutaneous fistula- and in neoplastic cystsHence not common

2)Percutaneous transgastric cystgastrostomy: radiological guidance Recurrence <15%

B) ENDOSCOPIC DRAINAGE:

1) Under EUS guidance

2) ERCP and Stenting of Ampulla – communicating cyst

C) SURGICAL DRAINAGE: cystogastrostomy

•most preferred, least recurrence rate ( <5%), best for complicated pseudocysts

•Open incision laparotomy or laproscopy (also shows similar rates)

DIFFERENTIAL DIAGNOSIS:

•Acute fluid collections

•Organized necrosis

•Pancreatic abscesses

•Cystic neoplasm

“Never in medical history have so many owed so much to a single

stone”. – Reginald Huber Fitz

The following are the latest terms according to the updated Atlanta classification to describe fluid collections associated with acute pancreatitis:

fluid collections in interstitial oedematous pancreatitisacute peripancreatic fluid collections (APFC): in the first 4 weeks: non-encapsulated peripancreatic fluid collectionspseudocysts: develop after 4 weeks; encapsulated peripancreatic or remote fluid collections

fluid collections in necrotising pancreatitisacute necrotic collections (ANCs): in the first 4 weeks; non-encapsulated heterogeneous non-liquefied materialwalled-off necrosis (WON or WOPN): develop after 4 weeks; encapsulated heterogeneous non-liquefied material

Peritonitis

Signs that are less common, and indicate severe disease, include:Pleural effusions:Grey-Turner's sign (hemorrhagic discoloration of the flanks)Cullen's sign (hemorrhagic discoloration of the umbilicus)

Grünwald signKörte's sign )Kamenchik's signMayo-Robson's sign )Mayo-Robson's point - a point on border of inner 2/3 with the external 1/3 of the line that represents the bisection of the left upper abdominal quadrant, where tenderness on pressure exists in disease of the pancreas. At this point the tail of pancreas is projected on the abdominal wall.